Journal of Personalized Medicine

26 pages, 2477 KB

Open AccessEditor’s ChoiceReview

Deciphering Breast Tumor Heterogeneity Through Patient-Derived Organoids and Circulating Tumor Cells

by Benedetta Policastro, Nikoline Nissen and Carla L. Alves

J. Pers. Med. 2025, 15(7), 271; https://doi.org/10.3390/jpm15070271 - 25 Jun 2025

Cited by 7 | Viewed by 3666

Breast cancer is a highly heterogeneous disease, with tumors capable of adapting to shifting conditions, making the development of effective personalized therapies particularly challenging. Patient-derived models, such as patient-derived organoids (PDOs) and circulating tumor cell (CTC) cultures, have emerged as powerful tools for [...] Read more.

Breast cancer is a highly heterogeneous disease, with tumors capable of adapting to shifting conditions, making the development of effective personalized therapies particularly challenging. Patient-derived models, such as patient-derived organoids (PDOs) and circulating tumor cell (CTC) cultures, have emerged as powerful tools for investigating intra- and inter-tumor heterogeneity. These models largely retain the genetic, phenotypic, and microenvironmental features of the original tumors, providing valuable insights into disease progression, drug response, and resistance mechanisms. Furthermore, by enabling tumors’ spatiotemporal molecular profiling, PDOs and CTCs offer a dynamic approach to assess treatment efficacy over time. However, to fully capture the complexity of breast cancer heterogeneity, it is required to develop models from multiple tumor and blood samples collected throughout the course of treatment. This review explores the potential of integrating PDOs and CTC models to better understand intra-tumor heterogeneity while addressing key challenges in developing patient-derived models that accurately recapitulate patients’ tumors to advance personalized care. The integration of PDOs and CTCs could represent a paradigm shift in the personalized management of metastatic breast cancer. Full article

(This article belongs to the Section Disease Biomarkers)

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20 pages, 729 KB

Open AccessEditor’s ChoiceSystematic Review

Can Radiomics Predict Pathologic Complete Response After Neoadjuvant Chemoradiotherapy for Rectal Cancer? A Systematic Review and Meta-Analysis of Diagnostic-Accuracy Studies

by Fotios Seretis, Antonia Panagaki, Stavroula Tzamouri, Tania Triantafyllou, Charikleia Triantopoulou and Dimitrios Theodorou

J. Pers. Med. 2025, 15(6), 244; https://doi.org/10.3390/jpm15060244 - 10 Jun 2025

Cited by 6 | Viewed by 3594

Abstract

Background: The rectal cancer treatment paradigm is rapidly changing with the advent of total neoadjuvant therapy and non-operative management approaches in responders. A good clinical response to neoadjuvant treatment documented by magnetic resonance imaging, endoscopy and clinical examination corresponds, to a large extent, [...] Read more.

Background: The rectal cancer treatment paradigm is rapidly changing with the advent of total neoadjuvant therapy and non-operative management approaches in responders. A good clinical response to neoadjuvant treatment documented by magnetic resonance imaging, endoscopy and clinical examination corresponds, to a large extent, to a pathologic complete response, as assessed in surgical specimens. Methods: We undertook a systematic review and meta-analysis on the MRI-based omics approach to predicting pathologic complete responses. Results: A total of 29 studies with relevant data available reporting on a total of 4486 patients were eligible for meta-analysis. The calculated values for the area under the curve in receiver operator curves of diagnostic accuracy for radiomics-only and radiomics-combined-with-clinical-data models were 0.80 and 0.88, respectively, for studies incorporating baseline imaging data only. The value for studies using delta radiomic data was 0.86, and those for studies using data from the post-neoadjuvant setting were 0.75 and 0.83, respectively, for the radiomics-only and radiomics-combined-with-clinical-data models. Conclusions: Radiomics-based prediction models for pathologic complete response assessment might further enable individualized treatment decisions to be made in patients with rectal cancer. Full article

(This article belongs to the Special Issue Novel Biomarkers in the Diagnostics of Cancer)

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21 pages, 661 KB

Open AccessEditor’s ChoiceArticle

Clinical Pharmacogenetics: Results After Implementation of Preemptive Tests in Daily Routine

by Xando Díaz-Villamarín, María Martínez-Pérez, María Teresa Nieto-Sánchez, Emilio Fernández-Varón, Alicia Torres-García, Isabel Blancas, José Cabeza-Barrera and Rocío Morón

J. Pers. Med. 2025, 15(6), 245; https://doi.org/10.3390/jpm15060245 - 10 Jun 2025

Cited by 5 | Viewed by 3474

Abstract

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug–gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., [...] Read more.

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug–gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., single-gene vs. multi-gene panels), or how to translate genotypes into actionable therapeutic recommendations. Methods: We describe the implementation of PGx in real daily clinical routine at a single institution to guide other centers. We analyze the drug–gene interactions and genetic variants included in our program based on allelic, genotypic, and phenotypic frequencies, resulting therapeutic recommendations. Linkage disequilibrium and haplotype analyses are also performed. Results and Conclusions: PGx testing was primarily requested by the oncology department. Not all variants included in typical panels had clinical utility in our setting. We do not recommend testing CYP2C19*17 prior to clopidogrel prescription, as it does not translate into a dosing recommendation. TPMT*3B may be considered just to confirm TPMT*3A due to its linkage with TPMT*3C. Similarly, we do not recommend the routine testing of CYP2C9*2 prior to siponimod prescription, as it does not inform therapeutic decisions according to the current drug label. Full article

(This article belongs to the Section Pharmacogenetics)

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14 pages, 3509 KB

Open AccessEditor’s ChoiceArticle

Enhancing the Outcomes of Temporalis Fascia Tympanoplasty Using Autologous Platelet-Rich Plasma and Gel: A Randomized Controlled Trial

by Nejc Steiner, Domen Vozel, Nina Bozanic Urbancic, Kaja Troha, Andraz Lazar, Veronika Kralj-Iglic and Saba Battelino

J. Pers. Med. 2025, 15(6), 233; https://doi.org/10.3390/jpm15060233 - 4 Jun 2025

Cited by 4 | Viewed by 3281

Abstract

Objectives: This study aimed to investigate the impact of platelet-rich plasma (PRP) and platelet-rich gel (PRG) on tympanic membrane closure rates, hearing improvement, and quality of life following tympanoplasty. Methods: Seventy-two patients with chronic tympanic membrane perforations were enrolled in a double-blinded, randomized [...] Read more.

Objectives: This study aimed to investigate the impact of platelet-rich plasma (PRP) and platelet-rich gel (PRG) on tympanic membrane closure rates, hearing improvement, and quality of life following tympanoplasty. Methods: Seventy-two patients with chronic tympanic membrane perforations were enrolled in a double-blinded, randomized controlled trial at a single tertiary referral center. All patients underwent tympanoplasty using a temporalis fascia graft and were randomly assigned to one of two groups: one group received standard tympanoplasty alone, while the other received intraoperative application of autologous PRP and PRG, in addition to the standard procedure. Results: The PRP group demonstrated a significantly higher rate of complete tympanic membrane closure compared to the control group (32/36; 88.9% vs. 24/36; 66.7%; p < 0.05). Bone conduction hearing remained unchanged in both groups, while air conduction hearing improved significantly from pre- to post-treatment in each group. However, the difference in air conduction improvement between the PRP group and the control group was not statistically significant (PRP group: Mdn = −8.25; control group: Mdn = −12.20; U = 618; z = −0.54; p = 0.30). Quality of life improved in both the PRP and control groups; however, the difference between the groups was not statistically significant (PRP group: 10.44 ± 10.46; control group: 10.47 ± 8.22; 95% CI [−4.45; 4.40]; t(66) = −0.01; p = 0.16). Conclusions: Our findings suggest that intraoperative application of autologous PRP and PRG may improve tympanoplasty outcomes, particularly in cases with lower expected success rates or when performing minimally invasive transcanal procedures under local anesthesia. However, variability in PRP preparation, application methods, and graft materials across studies limits direct comparisons. Standardized protocols and further controlled studies are necessary to clarify PRP’s clinical value in tympanoplasty. Full article

(This article belongs to the Special Issue Personalized Medicine in Otolaryngology: Novel Prognostic Markers)

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15 pages, 3292 KB

Open AccessEditor’s ChoiceArticle

Pericapsular Nerve Group (PENG) Associated with Lateral Femoral Cutaneous Nerve (LFCN) Block Versus Fascia Iliaca Compartment Block (FICB) for Total Hip Replacement Surgery: Double-Blind Randomized Controlled Trial

by Francesco Vetrone, Stefano Marelli, Andrea Galimberti, Michele Umbrello, Miriam Gotti, Angelo Pezzi and Alessandro Girombelli

J. Pers. Med. 2025, 15(6), 230; https://doi.org/10.3390/jpm15060230 - 3 Jun 2025

Cited by 9 | Viewed by 3991

Abstract

Background: Total hip arthroplasty (THA) improves the quality of life by alleviating pain and restoring function. The optimal pain control with minimal muscle weakness is paramount for early rehabilitation and for reducing complications. Although PROSPECT and ICAROS guidelines recommend the Fascia Iliaca Compartment [...] Read more.

Background: Total hip arthroplasty (THA) improves the quality of life by alleviating pain and restoring function. The optimal pain control with minimal muscle weakness is paramount for early rehabilitation and for reducing complications. Although PROSPECT and ICAROS guidelines recommend the Fascia Iliaca Compartment Block (FICB), it is associated with insufficient pain relief and a prolonged quadriceps motor block. The association of the PENG (Pericapsular Nerve Group) with LFCN (lateral femoral cutaneous nerve) blocks may address these limitations, provide improved motor-sparing pain control, and offer a more tailored approach that enhances both an early postoperative recovery and patient satisfaction. Methods: A randomized controlled trial (November 2023–July 2024) compared the PENG + LFCN to the FICB in patients undergoing elective THAs under spinal anesthesia. The primary outcome was quadriceps weakness at 6 h post-block. Secondary outcomes included the degree of hip flexion and pain scores at 6, 24, and 48 h post-block, opioid consumption, and time to ambulation. Results: Fifty-eight patients were randomized (twenty-nine per group). The PENG + LFCN group achieved a significantly greater muscle strength (MRC: 4 [4; 4] vs. 3 [3; 4], p < 0.0001) and better hip flexion at all measured moments (6 h: 45° [37; 60] vs. 30° [25; 43], 24h: 59° [49; 66] vs. 47° [36; 50], 48 h: 62° [55; 70] vs. 50° [40; 55], all p < 0.0001). Resting pain was lower in the PENG + LFCN group (0 [0; 1], 0 [0; 2], and 0 [0; 1] vs. 2 [0; 3], 1 [0; 3], 1 [0; 3]), as was the dynamic pain during movement (1 [0; 2], 2 [2; 4], and 2 [1; 2] vs. 3 [2; 5], 3 [2; 4], and 3 [1; 3]; all p < 0.001), along with a lower total opioid consumption (0 [0; 0] vs. 7.5 [7.5; 22.5] MME, p < 0.001). Conclusions: The PENG + LFCN block outperformed the FICB in muscle strength, hip flexion, pain control, and opioid use, suggesting it may be a more effective option for THAs. Full article

(This article belongs to the Special Issue Anesthesiology and Pain Management in Clinical Medicine)

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10 pages, 241 KB

Open AccessEditor’s ChoiceReview

Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach

by Andrea Paradisi, Maria Mannino, Francesco Brunetti, Enrico Bocchino, Alessandro Di Stefani and Ketty Peris

J. Pers. Med. 2025, 15(6), 226; https://doi.org/10.3390/jpm15060226 - 1 Jun 2025

Cited by 5 | Viewed by 4901

Abstract

Background/Objectives: Systemic therapy with hedgehog pathway inhibitors (HHIs) and anti-programmed cell death protein 1 (PD-1) antibodies represent the first- and second-line treatment options for advanced basal cell carcinoma (aBCC), respectively. A shift in the treatment paradigms toward the neoadjuvant approach is gaining increasing [...] Read more.

Background/Objectives: Systemic therapy with hedgehog pathway inhibitors (HHIs) and anti-programmed cell death protein 1 (PD-1) antibodies represent the first- and second-line treatment options for advanced basal cell carcinoma (aBCC), respectively. A shift in the treatment paradigms toward the neoadjuvant approach is gaining increasing interest in aBCC management, whereby prior systemic therapy followed by surgery is likely to yield more favorable outcomes. The aim of this narrative review is to summarize the current evidence on systemic treatment options and the neoadjuvant approach for aBCC management. Methods: We performed a non-systematic review of the literature based on PubMed as search engine. Results: The pivotal phase II trials ERIVANCE and BOLT investigated the efficacy and safety profile of vismodegib and sonidegib, respectively, with reported objective response rates (ORRs) of 60.3% and 56% in laBCC patients, respectively. The pivotal phase II trial NCT03132636 investigated the efficacy and safety profile of cemiplimab in patients who progressed or were intolerant to prior HHI therapy, with an ORR of 32.1% in laBCC patients. Real-life studies confirmed the effectiveness and safety profile of HHI and anti-PD-1 immunotherapy. Several phase I/II clinical trials are currently investigating HHIs and immune-checkpoint inhibitors in the neoadjuvant setting followed by surgery for aBCC patients, with the aim of providing more favorable treatment outcomes, especially when upfront surgery would result in functional and/or aesthetic sequelae. Conclusions: Advanced BCC treatment is challenging, and the neoadjuvant approach followed by surgery is expected to reduce surgical complexity, increase tissue preservation, and improve patients’ satisfaction. Full article

(This article belongs to the Special Issue Dermatology: Molecular Mechanisms, Diagnosis and Therapeutic Targets)

26 pages, 9374 KB

Open AccessEditor’s ChoiceReview

Right Ventricular Strain by Echocardiography: Current Clinical Applications and Future Directions for Mechanics Assessment of the Forgotten Ventricle

by Mahmoud Abdelnabi, Ramzi Ibrahim, Hoang Nhat Pham, Bobbi Jo Heon, George Bcharah, Girish Pathangey, Milagros Pereyra Pietri, Juan M. Farina, Ian C. Chang, Reza Arsanjani and Chadi Ayoub

J. Pers. Med. 2025, 15(6), 224; https://doi.org/10.3390/jpm15060224 - 30 May 2025

Cited by 5 | Viewed by 10703

Abstract

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV [...] Read more.

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV longitudinal strain (RVLS) in clinical practice. RVLS provides a more sensitive indicator of subtle myocardial dysfunction than conventional parameters for RV function assessment (i.e., tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction), with utility for the risk stratification and surveillance of conditions affecting the right heart. However, accurate interpretation of RVLS requires a comprehensive understanding of RV mechanics, pathology, and loading conditions across various cardiovascular conditions, as well as the effects of image quality and technical aspects of image acquisition and tracking in RV strain measurements. This review provides an updated overview of current practical guidelines for RV strain analysis, current clinical applications, and future directions for its potential use in clinical practice. Full article

(This article belongs to the Special Issue New Advances in Techniques and Personalized Medicine in Cardiology)

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19 pages, 696 KB

Open AccessEditor’s ChoiceReview

PRP Therapy for Stress Urinary Incontinence and Pelvic Organ Prolapse: A New Frontier in Personalized Treatment?

by Anna Pitsillidi, Laura Vona, Stefano Bettocchi, Sven Schiermeier and Günter Karl Noé

J. Pers. Med. 2025, 15(6), 214; https://doi.org/10.3390/jpm15060214 - 22 May 2025

Cited by 6 | Viewed by 6790

Abstract

Background: Pelvic organ prolapse (POP) and stress incontinence (SUI) are very common medical conditions, affecting women’s quality of life worldwide. Current surgical and conservative therapies often yield variable outcomes and carry risks of complications or recurrence. Platelet-rich plasma (PRP) has emerged as a [...] Read more.

Background: Pelvic organ prolapse (POP) and stress incontinence (SUI) are very common medical conditions, affecting women’s quality of life worldwide. Current surgical and conservative therapies often yield variable outcomes and carry risks of complications or recurrence. Platelet-rich plasma (PRP) has emerged as a promising regenerative approach in various medical disciplines. Its application in urogynecology remains relatively new and emerging. The objective of this study was to review and consolidate existing evidence regarding the application of PRP injections for treating POP and/or SUI. Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR). The search strategy included MEDLINE (PubMed), Web of Science, and Scopus databases, covering articles published up to February 2025, with no restrictions on publication date. Results: We included in our review a total of 13 manuscripts and 320 patients at the end of the screening process. A total of ten SUI studies, comprising 273 patients, and three POP studies, involving 47 patients, satisfied all the review criteria. Both clinical entities reported high subjective improvement following PRP treatment. Moreover, PRP appeared to have no significant adverse effects. Conclusions: Our scoping review suggests that PRP may have potential benefits in the treatment of POP and SUI. Nevertheless, the current evidence on its application in this area remains limited. Therefore, well-designed, large-scale randomized controlled trials (RCTs) with extended follow-up periods are urgently needed, in the era of personalized medicine. Full article

(This article belongs to the Special Issue Precision Medicine in Gynecological Endoscopy: From Personalized Diagnosis to Tailored Surgical Interventions)

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19 pages, 649 KB

Open AccessEditor’s ChoiceReview

Interstitial Lung Diseases and Lung Cancer: A Review on Similarities, Common Pathogenesis and Therapeutic Approach

by Gioele Castelli, Elisabetta Cocconcelli, Giuliana Grimaudo, Irene Di Leo, Serena Bellani, Giordano Fiorentù, Giacomo Giulianelli, Nicol Bernardinello, Elisabetta Balestro and Paolo Spagnolo

J. Pers. Med. 2025, 15(5), 213; https://doi.org/10.3390/jpm15050213 - 21 May 2025

Cited by 5 | Viewed by 6502

Abstract

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that [...] Read more.

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that worsen patients’ prognosis. This growth of malignant cells on a fibrotic background has also been called scar-cinoma. For this reason, not only an early diagnosis but also personalized decisions on the best treatment approach should be considered for each patient in a multidisciplinary discussion, since in some cases chemotherapy or surgery could be detrimental for patients with pulmonary fibrosis. LC and lung fibrosis may share common pathogenetic mechanisms like an altered healing process in response to repeated tissue damage from environmental exposure in genetically susceptible individuals. Smoking history and air pollution together with mutations in telomere and surfactant protein genes lead to the production of cytokines and nitro derivatives in the microenvironment that facilitate the carcinomatous transformation during fibrogenesis. The evolution of LC therapy and the implementation of immunotherapy acting on targetable immune checkpoints have raised interest in evaluating ILD-LC actionable mutations. The main pathogenetic mechanisms, clinical presentations and treatment implications are presented in this review. Full article

(This article belongs to the Special Issue Pathology and Molecular Diagnostics in the Personalized Treatment of Lung Diseases)

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17 pages, 2456 KB

Open AccessEditor’s ChoiceArticle

The Accuracy of ChatGPT-4o in Interpreting Chest and Abdominal X-Ray Images

by Pietro G. Lacaita, Malik Galijasevic, Michael Swoboda, Leonhard Gruber, Yannick Scharll, Fabian Barbieri, Gerlig Widmann and Gudrun M. Feuchtner

J. Pers. Med. 2025, 15(5), 194; https://doi.org/10.3390/jpm15050194 - 10 May 2025

Cited by 17 | Viewed by 8141

Abstract

Background/Objectives: Large language models (LLMs), such as ChatGPT, have emerged as potential clinical support tools to enhance precision in personalized patient care, but their reliability in radiological image interpretation remains uncertain. The primary aim of our study was to evaluate the diagnostic accuracy [...] Read more.

Background/Objectives: Large language models (LLMs), such as ChatGPT, have emerged as potential clinical support tools to enhance precision in personalized patient care, but their reliability in radiological image interpretation remains uncertain. The primary aim of our study was to evaluate the diagnostic accuracy of ChatGPT-4o in interpreting chest X-rays (CXRs) and abdominal X-rays (AXRs) by comparing its performance to expert radiology findings, whilst secondary aims were diagnostic confidence and patient safety. Methods: A total of 500 X-rays, including 257 CXR (51.4%) and 243 AXR (48.5%), were analyzed. Diagnoses made by ChatGPT-4o were compared to expert interpretations. Confidence scores (1–4) were assigned and responses were evaluated for patient safety. Results: ChatGPT-4o correctly identified 345 of 500 (69%) pathologies (95% CI: 64.81–72.9). For AXRs 175 of 243 (72.02%) pathologies were correctly diagnosed (95% CI: 66.06–77.28), while for CXRs 170 of 257 (66.15%) were accurate (95% CI: 60.16–71.66). The highest detection rates among CXRs were observed for pulmonary edema, tumor, pneumonia, pleural effusion, cardiomegaly, and emphysema, and lower rates were observed for pneumothorax, rib fractures, and enlarged mediastinum. AXR performance was highest for intestinal obstruction and foreign bodies, and weaker for pneumoperitoneum, renal calculi, and diverticulitis. Confidence scores were higher for AXRs (mean 3.45 ± 1.1) than CXRs (mean 2.48 ± 1.45). All responses (100%) were considered to be safe for the patient. Interobserver agreement was high (kappa = 0.920), and reliability (second prompt) was moderate (kappa = 0.750). Conclusions: ChatGPT-4o demonstrated moderate accuracy for the interpretation of X-rays, being higher for AXRs compared to CXRs. Improvements are required for its use as efficient clinical support tool. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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11 pages, 3510 KB

Open AccessEditor’s ChoiceArticle

Antibiotic-Mixed Cement Filling for Chronic Osteomyelitis

by Seung-Hwan Park, Young Rak Choi, Inyong Jeong and Ho Seong Lee

J. Pers. Med. 2025, 15(5), 187; https://doi.org/10.3390/jpm15050187 - 6 May 2025

Cited by 8 | Viewed by 3554

Abstract

Background/Objectives: Traditional treatment for chronic osteomyelitis is temporary implantation of antibiotic-impregnated cement beads, followed by bone grafting after the infection is controlled. In this way, a staged operation is needed, and undergoing repetitive general anesthesia is a burden. Moreover, damage to the soft [...] Read more.

Background/Objectives: Traditional treatment for chronic osteomyelitis is temporary implantation of antibiotic-impregnated cement beads, followed by bone grafting after the infection is controlled. In this way, a staged operation is needed, and undergoing repetitive general anesthesia is a burden. Moreover, damage to the soft tissue at the surgical site due to several incisions is a concern. This study was conducted to investigate the outcomes of one-stage antibiotic-mixed cement blocks, instead of beads, used as a primary salvage procedure to treat chronic osteomyelitis of the foot, ankle, and lower leg. Methods: Twenty patients with chronic osteomyelitis of the leg and foot were included. They underwent complete debridement of the infected bone, and antibiotic-mixed cement fillings were placed into the defected bone space. Full-weight-bearing activities were allowed immediately after surgery. Results: For 16 of the 18 patients, infection was controlled after one-time surgery. Repeat antibiotic cement-filling surgery was necessary for two patients. Two-staged surgery with continuous irrigation and cement filling was necessary for one large tibial lesion. Conversion into arthrodesis of the metatarsophalangeal joint was necessary for metatarsal head infection. Conclusions: One-stage surgery with complete debridement and antibiotic-mixed cement filling is a simple and effective procedure for treating intractable chronic osteomyelitis, which makes full-weight-bearing walking possible immediately after surgery. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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13 pages, 1104 KB

Open AccessEditor’s ChoiceReview

Temporary Mechanical Support in Cardiogenic Shock Secondary to Heart Failure: An Evolving Paradigm

by Nandini Nair, Dongping Du and Balakrishnan Mahesh

J. Pers. Med. 2025, 15(5), 184; https://doi.org/10.3390/jpm15050184 - 2 May 2025

Cited by 3 | Viewed by 2784

Abstract

Cardiogenic shock can be defined as a state of circulatory collapse resulting in hypoperfusion and end-organ dysfunction. It carries a large burden of mortality, but management strategies are driven by expert consensus rather than adequately powered randomized clinical trials. The goal of this [...] Read more.

Cardiogenic shock can be defined as a state of circulatory collapse resulting in hypoperfusion and end-organ dysfunction. It carries a large burden of mortality, but management strategies are driven by expert consensus rather than adequately powered randomized clinical trials. The goal of this review is to highlight the differences in presentation and outcomes in cardiogenic shock depending on the etiology, such as acute myocardial infarction (AMI) versus acute-on-chronic heart failure (HF), gender-based differences in treatment strategies and outcomes and the need for more precise risk stratification and modeling to improve the efficiency of treatment delivery in a personalized fashion. PubMed and Google Scholar were used to search the literature for this qualitative review. The differences in gender and etiology of cardiogenic shock are not consistent in all studies in the exiting literature. There is a need for identification of novel risk factors that define the different phenotypes that present with similar hemodynamic and biomarker profiles. There is an urgent need to devise a methodology to understand and differentiate the different cardiogenic shock phenotypes and their trajectories. Better risk prediction models should be generated to help deliver well-tailored treatment, paving the way to the efficient delivery of personalized medicine. Full article

(This article belongs to the Special Issue New Perspectives of Critical Care Medicine)

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13 pages, 601 KB

Open AccessEditor’s ChoiceArticle

The Association of Assisted Reproductive Technology with Placental and Umbilical Abnormalities

by Antonios Siargkas, Ioannis Tsakiridis, Sonia Giouleka, Petya Chaveeva, Maria Mar Gil, Walter Plasencia, Catalina De Paco Matallana, Efstratios M. Kolibianakis and Themistoklis Dagklis

J. Pers. Med. 2025, 15(5), 176; https://doi.org/10.3390/jpm15050176 - 27 Apr 2025

Cited by 6 | Viewed by 3553

Abstract

Objective: Global utilization of assisted reproductive technology (ART) is increasing; however, it is associated with adverse perinatal outcomes. Placental and umbilical cord abnormalities contribute significantly to these negative outcomes. However, it remains unclear whether ART independently increases the risk of such abnormalities. This [...] Read more.

Objective: Global utilization of assisted reproductive technology (ART) is increasing; however, it is associated with adverse perinatal outcomes. Placental and umbilical cord abnormalities contribute significantly to these negative outcomes. However, it remains unclear whether ART independently increases the risk of such abnormalities. This study aimed to investigate the association between ART and key umbilico-placental abnormalities, after adjustment for confounders. Methods: In this retrospective cohort study, singleton pregnancies receiving routine antenatal care (January 2015 to June 2024) at the 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece, were analyzed. Pregnancies conceived via ART were compared to those conceived spontaneously. To investigate placental and cord anomalies, this study employed multiple logistic regression. This approach adjusted for various confounders, including maternal age, BMI, parity, smoking status, history of previous cesarean section, diabetes mellitus, and thyroid disease. Results: This study included a total of 13,854 singleton pregnancies, of which 647 were conceived via ART. ART was significantly associated with an increased risk of placenta previa (aOR 1.99, 95% CI 1.10–3.61), low-lying placenta (aOR 1.71, 95% CI 1.38–2.11), bilobate placenta (aOR 2.81, 95% CI 1.92–4.11), single umbilical artery (aOR 2.62, 95% CI 1.022–6.715), marginal (aOR 1.63, 95% CI 1.32–2.01) and velamentous cord insertion (aOR 3.13, 95% CI 1.98–4.95), and vasa previa (aOR 5.51, 95% CI 1.28–23.76). Conclusions: ART-conceived pregnancies appear to carry a higher risk for certain placental and umbilical cord abnormalities, potentially contributing to adverse perinatal outcomes. Further studies are required to investigate the pathophysiology underlying these associations. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Maternal Fetal Medicine)

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20 pages, 679 KB

Open AccessEditor’s ChoiceReview

Beyond Biomarkers: Machine Learning-Driven Multiomics for Personalized Medicine in Gastric Cancer

by Dongheng Ma, Canfeng Fan, Tomoya Sano, Kyoka Kawabata, Hinano Nishikubo, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Tasuku Matsuoka and Masakazu Yashiro

J. Pers. Med. 2025, 15(5), 166; https://doi.org/10.3390/jpm15050166 - 24 Apr 2025

Cited by 27 | Viewed by 5783

Abstract

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with most cases diagnosed at advanced stages. Traditional biomarkers provide only partial insights into GC’s heterogeneity. Recent advances in machine learning (ML)-driven multiomics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, [...] Read more.

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with most cases diagnosed at advanced stages. Traditional biomarkers provide only partial insights into GC’s heterogeneity. Recent advances in machine learning (ML)-driven multiomics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, pathomics, and radiomics, have facilitated a deeper understanding of GC by integrating molecular and imaging data. In this review, we summarize the current landscape of ML-based multiomics integration for GC, highlighting its role in precision diagnosis, prognosis prediction, and biomarker discovery for achieving personalized medicine. Full article

(This article belongs to the Special Issue The Intersection of Multi-Omics Data and Machine Learning in Medicine)

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13 pages, 1544 KB

Open AccessEditor’s ChoiceArticle

Multimodal Performance of GPT-4 in Complex Ophthalmology Cases

by David Mikhail, Daniel Milad, Fares Antaki, Jason Milad, Andrew Farah, Thomas Khairy, Jonathan El-Khoury, Kenan Bachour, Andrei-Alexandru Szigiato, Taylor Nayman, Guillaume A. Mullie and Renaud Duval

J. Pers. Med. 2025, 15(4), 160; https://doi.org/10.3390/jpm15040160 - 21 Apr 2025

Cited by 11 | Viewed by 2269

Abstract

Objectives: The integration of multimodal capabilities into GPT-4 represents a transformative leap for artificial intelligence in ophthalmology, yet its utility in scenarios requiring advanced reasoning remains underexplored. This study evaluates GPT-4’s multimodal performance on open-ended diagnostic and next-step reasoning tasks in complex ophthalmology [...] Read more.

Objectives: The integration of multimodal capabilities into GPT-4 represents a transformative leap for artificial intelligence in ophthalmology, yet its utility in scenarios requiring advanced reasoning remains underexplored. This study evaluates GPT-4’s multimodal performance on open-ended diagnostic and next-step reasoning tasks in complex ophthalmology cases, comparing it against human expertise. Methods: GPT-4 was assessed across three study arms: (1) text-based case details with figure descriptions, (2) cases with text and accompanying ophthalmic figures, and (3) cases with figures only (no figure descriptions). We compared GPT-4’s diagnostic and next-step accuracy across arms and benchmarked its performance against three board-certified ophthalmologists. Results: GPT-4 achieved 38.4% (95% CI [33.9%, 43.1%]) diagnostic accuracy and 57.8% (95% CI [52.8%, 62.2%]) next-step accuracy when prompted with figures without descriptions. Diagnostic accuracy declined significantly compared to text-only prompts (p = 0.007), though the next-step performance was similar (p = 0.140). Adding figure descriptions restored diagnostic accuracy (49.3%) to near parity with text-only prompts (p = 0.684). Using figures without descriptions, GPT-4’s diagnostic accuracy was comparable to two ophthalmologists (p = 0.30, p = 0.41) but fell short of the highest-performing ophthalmologist (p = 0.0004). For next-step accuracy, GPT-4 was similar to one ophthalmologist (p = 0.22) but underperformed relative to the other two (p = 0.0015, p = 0.0017). Conclusions: GPT-4’s diagnostic performance diminishes when relying solely on ophthalmic images without textual context, highlighting limitations in its current multimodal capabilities. Despite this, GPT-4 demonstrated comparable performance to at least one ophthalmologist on both diagnostic and next-step reasoning tasks, emphasizing its potential as an assistive tool. Future research should refine multimodal prompts and explore iterative or sequential prompting strategies to optimize AI-driven interpretation of complex ophthalmic datasets. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Ophthalmology—2nd Edition)

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17 pages, 889 KB

Open AccessEditor’s ChoiceArticle

Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience)

by Marco Di Nicola, Maria Pepe, Giacomo d’Andrea, Ilaria Marcelli, Mauro Pettorruso, Ileana Andriola, Stefano Barlati, Matteo Carminati, Carlo Ignazio Cattaneo, Massimo Clerici, Domenico De Berardis, Sergio De Filippis, Bernardo Dell’Osso, Giorgio Di Lorenzo, Giuseppe Maina, Mirko Manchia, Matteo Marcatili, Vassilis Martiadis, Cinzia Niolu, Antonino Petralia, Gianluca Rosso, Gianluca Serafini, Maria Salvina Signorelli, Tommaso Vannucchi, Matteo Vismara, Raffaella Zanardi, Antonio Vita, Gabriele Sani, Giovanni Martinotti and REAL-ESKperience Study Group Show full author list Hide full author list

J. Pers. Med. 2025, 15(4), 161; https://doi.org/10.3390/jpm15040161 - 21 Apr 2025

Cited by 21 | Viewed by 5556

Abstract

Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients’ perspective on this treatment are limited. This multicentric [...] Read more.

Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients’ perspective on this treatment are limited. This multicentric Italian study explored experiences with ESK-NS in TRD patients, focusing on perceived therapeutic effects and overall satisfaction. Methods. A self-report survey was administered to 236 outpatients with TRD (55.1% females, 54.1 ± 14.1 years) treated with ESK-NS for at least three consecutive months within standard clinical care. Based on satisfaction levels, participants were classified as “unsatisfied” (10.2%), “partially satisfied” (19.1%), “satisfied” (44.4%), or “very satisfied” (26.3%), and compared for sociodemographic, clinical characteristics, and feedback on perceived benefits. Artificial intelligence (OpenAI) served to categorize responses to an open-ended question. Results. Enhanced quality of life was reported by 88.4% of participants. Significant differences emerged in earliest self-perceived benefits, most relevant effects, and impact on global functioning across groups. Specifically, “very satisfied” patients described the following: early improvements in depressed mood, suicidal thoughts, and restlessness; decreased suicidal thoughts among the most significant effects; and functional gains across all domains. OpenAI identified experiences of personal growth and rediscovery and a desire for tailored settings and approaches as recurring topics. Conclusions. Most patients reported a positive perception of ESK-NS treatment. The most satisfied participants highlighted significant benefits to depressed mood, suicidal thoughts, and overall functioning. Patient-reported experiences offer insights into different psychopathological dimensions, including functional outcomes and quality of life. Integrating these perspectives into clinical practice might assist treatment personalization, improving patients’ adherence and satisfaction. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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12 pages, 519 KB

Open AccessEditor’s ChoiceArticle

Effect of Flecainide in Idiopathic Premature Ventricular Contractions and the Induced Cardiomyopathy—UNIFLECA: A Single Arm, Non-Randomized Trial: Review of the Literature and Initial Results

by Sotirios Kotoulas, Dimitrios Tsiachris, Michail Botis, Athanasios Kordalis, Dimitrios Varvarousis, Georgios Leventopoulos, Eleftherios Kallergis, Ioannis Doundoulakis, Leonidas E. Poulimenos and Konstantinos Tsioufis

J. Pers. Med. 2025, 15(4), 132; https://doi.org/10.3390/jpm15040132 - 29 Mar 2025

Cited by 6 | Viewed by 8680

Abstract

Background/Objectives: Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend flecainide for PVCs originating from the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study, aiming to assess the [...] Read more.

Background/Objectives: Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend flecainide for PVCs originating from the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study, aiming to assess the efficacy and safety of flecainide in PVC burden reduction in adults, irrespective of PVC origin, focusing secondarily on symptom relief and improvement of left ventricular ejection fraction (LVEF) in patients suffering from PVC-induced cardiomyopathy. Methods: Participants were adults with frequent PVCs, defined as PVC burden > 5%, confirmed by two 24 h Holter recordings taken at least one month apart, who denied catheter ablation treatment. Patients who were deemed ineligible for catheter ablation were also included. A total of 50 patients were screened and 35 were administered Flecainide, with dosage adjustment based on follow-up Holter results and QRS increases. Changes in PVC burden, LVEF, symptomatic status, along with treatment adherence, were evaluated. Results: In adults with frequent PVCs, flecainide led to a significant reduction in PVC burden, with a mean decrease of 76.2% in the first month, and 63.1% of patients achieving a PVC burden reduction greater than 80%. Conclusions: UNIFLECA contributes to the understanding of how personalized, non-interventional therapeutic modalities can be employed to manage PVCs, especially for patients unwilling to have or ineligible for ablation procedures. Full article

(This article belongs to the Special Issue The Challenges and Therapeutic Prospects in Cardiovascular Disease)

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17 pages, 3545 KB

Open AccessEditor’s ChoiceArticle

Artificial Intelligence Detection of Occlusive Myocardial Infarction from Electrocardiograms Interpreted as “Normal” by Conventional Algorithms

by Shifa R. Karim, Hans C. Helseth, Peter O. Baker, Gabriel A. Keller, H. Pendell Meyers, Robert Herman and Stephen W. Smith

J. Pers. Med. 2025, 15(4), 130; https://doi.org/10.3390/jpm15040130 - 28 Mar 2025

Cited by 13 | Viewed by 5905

Abstract

Background: Some authors advocate that ECGs with conventional computer algorithm (CCA) interpretations of “normal” need not be immediately reviewed. However, such ECGs may actually manifest findings of acute coronary occlusion myocardial infarction (OMI). We sought to determine if such cases can be [...] Read more.

Background: Some authors advocate that ECGs with conventional computer algorithm (CCA) interpretations of “normal” need not be immediately reviewed. However, such ECGs may actually manifest findings of acute coronary occlusion myocardial infarction (OMI). We sought to determine if such cases can be detected by artificial intelligence (AI). Methods: We studied a retrospective series (2014–2024) of cases with ≥1 pre-angiography ECGs with a proven OMI outcome with a CCA ECG interpretation of “normal”. The OMI outcome was defined as (1) the diagnosis of acute type I MI, (2) an angiographic culprit with intervention, and (3) one of the following, (a) TIMI-0-2 flow, or (b) TIMI-3 or unknown flow, with high peak troponin or new wall abnormality. Each ECG as retrospectively interpreted by the PMcardio OMI AI ECG model. The primary analysis was the performance of AI in diagnosing "OMI" among these CCA “normal” ECGs. Results: Forty-two patients with OMI met the inclusion criteria. The first ECG was interpreted as “normal” by the CCA in 88% of cases; AI interpreted 81% as OMI and 86% as abnormal. Of the 78 total ECGs interpreted by the CCA, 73% were diagnosed as “normal”. Of this 73%, AI identified 81% as abnormal and 72% as OMI. Conclusion: The Conventional Computer Algorithm may interpret an ECG manifesting OMI as “normal”. AI not only recognized these as abnormal, but in 81% of patients, correctly recognized OMI on the first ECG and recognized 72% of all the CCA “normal” ECGs as OMI. It was rare for AI to diagnose a normal ECG for any OMI patient. Full article

(This article belongs to the Section Personalized Medical Care)

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15 pages, 247 KB

Open AccessEditor’s ChoiceReview

The Role of Dual-Energy CT in Differentiating Adrenal Adenomas from Metastases: A Comprehensive Narrative Review

by Francesco Tiralongo, Cristina Mosconi, Pietro Valerio Foti, Aldo Eugenio Calogero, Sandro La Vignera, Corrado Ini’, Davide Giuseppe Castiglione, Emanuele David, Stefania Tamburrini, Sebastiano Barbarino, Stefano Palmucci and Antonio Basile

J. Pers. Med. 2025, 15(4), 131; https://doi.org/10.3390/jpm15040131 - 28 Mar 2025

Cited by 5 | Viewed by 2839

Abstract

Dual-energy CT (DECT) has emerged as a novel imaging modality that offers a multiparametric approach for noninvasive adrenal lesion characterization. This narrative review examines recent advances in DECT—including virtual non-contrast imaging, iodine density quantification, spectral curve analysis, and material density mapping—for differentiating benign [...] Read more.

Dual-energy CT (DECT) has emerged as a novel imaging modality that offers a multiparametric approach for noninvasive adrenal lesion characterization. This narrative review examines recent advances in DECT—including virtual non-contrast imaging, iodine density quantification, spectral curve analysis, and material density mapping—for differentiating benign adrenal adenomas from metastases. Conventional CT techniques rely primarily on unenhanced attenuation measurements and contrast washout kinetics; however, these methods may be limited in evaluating lipid-poor adenomas, and in cases where imaging features overlap with metastatic lesions. Although virtual non-contrast imaging with DECT tends to overestimate attenuation relative to true non-contrast scans, the recalibration of diagnostic thresholds and integration with complementary parameters, such as the iodine density-to-virtual non-contrast attenuation ratio, can significantly enhance sensitivity and specificity. Additional parameters, including fat fraction analysis and the evaluation of attenuation changes across energy spectra, further refine tissue characterization by quantifying intracellular lipid content and vascularity. Material density analysis has demonstrated near-perfect diagnostic accuracy in select studies. By tailoring imaging evaluation to the unique spectral and compositional features of each adrenal lesion, DECT contributes to a more personalized diagnostic approach. This individualization allows for better differentiation between benign and malignant findings, potentially avoiding unnecessary interventions and enabling more targeted clinical management. Despite these promising developments, challenges remain regarding the standardization of acquisition protocols, optimization of diagnostic thresholds, and minimization of interobserver variability. Emerging radiomics and machine learning applications may further automate lesion classification and improve diagnostic accuracy. Thus, DECT holds considerable potential to improve diagnostic confidence, reduce radiation exposure, and streamline the management of patients with adrenal incidentalomas, although further multicenter validation is warranted. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

31 pages, 1617 KB

Open AccessEditor’s ChoiceReview

The Role of the Gut–Biliary–Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications

by Mario Romeo, Marcello Dallio, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Giuseppina Martinelli, Pierluigi Federico, Simone Olivieri, Patrizia Iodice and Alessandro Federico

J. Pers. Med. 2025, 15(4), 124; https://doi.org/10.3390/jpm15040124 - 24 Mar 2025

Cited by 13 | Viewed by 2363

Abstract

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut–liver [...] Read more.

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut–liver axis and gut–biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools. Full article

(This article belongs to the Section Mechanisms of Diseases)

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13 pages, 1097 KB

Open AccessEditor’s ChoiceReview

Advances in Basivertebral Nerve Ablation for Chronic Low Back Pain: A Narrative Review

by Sujeivan Mahendram and Paul J. Christo

J. Pers. Med. 2025, 15(3), 119; https://doi.org/10.3390/jpm15030119 - 19 Mar 2025

Cited by 3 | Viewed by 7590

Abstract

Chronic low back pain has traditionally been thought to stem from intervertebral disc degeneration. However, emerging evidence over the last few decades has revealed other contributing sources. One such etiology of chronic non-radiating axial low back pain has been attributed to vertebral end [...] Read more.

Chronic low back pain has traditionally been thought to stem from intervertebral disc degeneration. However, emerging evidence over the last few decades has revealed other contributing sources. One such etiology of chronic non-radiating axial low back pain has been attributed to vertebral end plate disruption and degeneration, leading to basivertebral nerve-mediated nociception. These degenerative events, described as Modic changes on MRI, provide a means of diagnosis and offer personalized treatment options, like minimally invasive radiofrequency ablation, to help address this source of low back pain. This review focuses on recent advancements, rationale, efficacy, and safety profile intraosseous basivertebral nerve ablation in the treatment of vertebrogenic back pain, and discusses current knowledge gaps that may help guide future research in the field. Full article

(This article belongs to the Special Issue Towards Precision Anesthesia and Pain Management)

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10 pages, 932 KB

Open AccessEditor’s ChoiceArticle

Impact of Surgical Timing, Fasciotomy, and External Fixation on Infection Risk in Tibial Plateau Fractures

by Salvatore Risitano, Antonio Rea, Giorgia Garofalo, Francesco Onorato, Ahmed Elzeiny, Stefano Artiaco, Marcello Capella, Pier Francesco Indelli and Alessandro Massè

J. Pers. Med. 2025, 15(3), 108; https://doi.org/10.3390/jpm15030108 - 11 Mar 2025

Cited by 11 | Viewed by 3566

Abstract

Background/Objectives: Tibial plateau fractures (TPFs) are commonly associated with complex patterns requiring advanced surgical strategies. High-energy trauma often results in severe soft tissue damage, complicating surgical outcomes. Despite advancements in soft tissue management, postoperative complications such as surgical site infections (SSIs) remain [...] Read more.

Background/Objectives: Tibial plateau fractures (TPFs) are commonly associated with complex patterns requiring advanced surgical strategies. High-energy trauma often results in severe soft tissue damage, complicating surgical outcomes. Despite advancements in soft tissue management, postoperative complications such as surgical site infections (SSIs) remain prevalent, with rates ranging from 9.9% to 30%. This study aims to analyze risk factors and surgical approaches influencing acute SSIs following TPF fixation. Methods: A retrospective analysis was conducted on 365 patients treated for TPFs with open or arthroscopy-assisted reduction and internal fixation (ORIF/ARIF) at a single center between January 2018 and December 2023. Inclusion criteria encompassed fractures classified by the Schatzker system and definitive management through ORIF/ARIF. Exclusion criteria included non-tibial plateau fractures, polytrauma, multiligament injuries and associated femoral fractures. Patient demographics, fracture patterns, surgical interventions, and postoperative complications were reviewed. Statistical analysis was performed using chi-square and ANOVA tests, with significance set at p < 0.05. Results: The final cohort included 364 patients (mean age: 45.4 ± 17.4 years; 59.2% male). High-energy fractures (Schatzker IV–VI) accounted for 47.7%, with 6.86% being open fractures. The mean interval to surgery was 14.9 ± 20.6 days. Superficial infections occurred in 21 cases (5.8%), predominantly at external fixator pin sites, while 15 cases (4.1%) involved deep infections. A statistically significant correlation was observed between SSIs and preoperative fasciotomy (p < 0.0001), damage control orthopedic protocols (p < 0.0001), and delays in definitive treatment of 10–30 days (p < 0.0001). No significant associations were found between infection rates and fracture type, dual surgical approaches, or the use of arthroscopy. Conclusions: External fixation, preoperative fasciotomy, and delayed definitive treatment are independent risk factors for SSIs following TPF fixation. High-energy injuries and soft tissue damage exacerbate infection risk. A personalized surgical approach, based on minimally invasive techniques and optimized surgical timing may mitigate these complications and significantly improve clinical outcomes in TPFs. Full article

(This article belongs to the Special Issue Computer-Assisted Diagnosis and Personalized Treatment of Fracture)

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17 pages, 1366 KB

Open AccessEditor’s ChoiceReview

The Uncommon Phenomenon of Short QT Syndrome: A Scoping Review of the Literature

by Aristi Boulmpou, Andreas Giannopoulos, Christodoulos Papadopoulos, Georgios Giannopoulos, Ioannis Papagiannis, Georgios Zormpas, Anastasia Keivanidou, Liana Fidani and Vassilios Vassilikos

J. Pers. Med. 2025, 15(3), 105; https://doi.org/10.3390/jpm15030105 - 8 Mar 2025

Cited by 6 | Viewed by 8013

Abstract

Background: Short QT syndrome (SQTS) is a rare inheritable channelopathy characterized by a shortened corrected QT interval on an electrocardiogram and a significant risk of atrial and ventricular arrhythmias, potentially leading to sudden cardiac death. Despite advancements in our understanding of SQTS, knowledge [...] Read more.

Background: Short QT syndrome (SQTS) is a rare inheritable channelopathy characterized by a shortened corrected QT interval on an electrocardiogram and a significant risk of atrial and ventricular arrhythmias, potentially leading to sudden cardiac death. Despite advancements in our understanding of SQTS, knowledge gaps persist due to its extreme rarity. This scoping review aims to summarize the available knowledge on its clinical presentations, genetic mutations, and management strategies, while identifying areas for further investigation. Methods: This scoping review was conducted across the PubMed, Scopus, and Cochrane databases and identified relevant case reports, case series, and available studies on SQTS. We focused on articles that reported clinical outcomes, genetic mutations, diagnostic criteria, and management strategies, while excluding studies on the secondary causes of short QT intervals. Results: SQTS is present across a wide age range, from asymptomatic individuals to those experiencing syncope, palpitations, or sudden cardiac arrest. Common genetic mutations include KCNQ1, KCNH2, and KCNJ2. Management strategies vary, with some patients receiving implantable cardioverter defibrillators for secondary prevention and others treated pharmacologically, primarily with hydroquinidine. Our findings highlight the rarity and clinical variability of SQTS, underscoring the need for optimized diagnostic criteria and individualized management strategies. Conclusions: This review emphasizes the need for continued research to better understand the genetic basis of SQTS, optimize diagnostic tools, and improve treatment approaches. Large-scale studies and the integration of genetic and clinical data are critical to addressing the gaps in SQTS management and improving outcomes for patients with this potentially life-threatening arrhythmic disorder. Full article

(This article belongs to the Special Issue Molecular and Technological Advances in the Diagnosis and Therapy of Cardiovascular Diseases)

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13 pages, 2416 KB

Open AccessEditor’s ChoiceReview

Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome

by Dimitra Mougiou, Georgia Gioula, Lemonia Skoura, Cleo Anastassopoulou and Melania Kachrimanidou

J. Pers. Med. 2025, 15(3), 94; https://doi.org/10.3390/jpm15030094 - 28 Feb 2025

Cited by 16 | Viewed by 6426

Abstract

Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and [...] Read more.

Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection’s symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI. Full article

(This article belongs to the Special Issue Personalized Medicine in Infectious Diseases)

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21 pages, 1633 KB

Open AccessEditor’s ChoiceReview

Precision Surgery for Glioblastomas

by Stephen J. Price, Jasmine G. Hughes, Swati Jain, Caroline Kelly, Ioana Sederias, Francesca M. Cozzi, Jawad Fares, Yonghao Li, Jasmine C. Kennedy, Roxanne Mayrand, Queenie Hoi Wing Wong, Yizhou Wan and Chao Li

J. Pers. Med. 2025, 15(3), 96; https://doi.org/10.3390/jpm15030096 - 28 Feb 2025

Cited by 4 | Viewed by 5194

Abstract

Glioblastomas are the most common primary malignant brain tumor. Most of the recent improvements their treatment are due to improvements in surgery. Although many would consider surgery as the most personalized treatment, the variation in resection between surgeons suggests there remains a need [...] Read more.

Glioblastomas are the most common primary malignant brain tumor. Most of the recent improvements their treatment are due to improvements in surgery. Although many would consider surgery as the most personalized treatment, the variation in resection between surgeons suggests there remains a need for objective measures to determine the best surgical treatment for individualizing therapy for glioblastoma. We propose applying a personalized medicine approach to improve outcomes for patients. We suggest looking at personalizing preoperative preparation, improving the resection target by understanding what needs removing and what ca not be removed, and better patient selection with personalized rehabilitation plans for all patients. Full article

(This article belongs to the Special Issue Precision Medicine in Neurooncology and Neurosurgery for the 21st Century, 2nd Edition)

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10 pages, 5487 KB

Open AccessEditor’s ChoiceArticle

Testing the Reliability of ChatGPT Assistance for Surgical Choices in Challenging Glaucoma Cases

by Matteo Mario Carlà, Gloria Gambini, Federico Giannuzzi, Francesco Boselli, Laura De Luca and Stanislao Rizzo

J. Pers. Med. 2025, 15(3), 97; https://doi.org/10.3390/jpm15030097 - 28 Feb 2025

Cited by 7 | Viewed by 1583

Abstract

Background: This study’s aim is to assess ChatGPT’s capability to analyze detailed case descriptions in glaucomatous patients and suggest the best possible surgical treatment. Methods: We conducted a retrospective analysis of 60 medical records of surgical glaucoma cases, divided into “ordinary” cases ( [...] Read more.

Background: This study’s aim is to assess ChatGPT’s capability to analyze detailed case descriptions in glaucomatous patients and suggest the best possible surgical treatment. Methods: We conducted a retrospective analysis of 60 medical records of surgical glaucoma cases, divided into “ordinary” cases (n = 40) and “challenging” cases (n = 20). We entered every case description into ChatGPT-3.5’s interface and inquired “What kind of surgery would you perform?”. The frequency of accurate surgical choices made by ChatGPT, compared to those reported in patients’ files, was reported. Furthermore, we assessed the level of agreement with three senior glaucoma surgeons, asked to analyze the same 60 cases and outline their surgical choices. Results: Overall, ChatGPT surgical choices were consistent with those reported in patients’ files in 47/60 cases (78%). When comparing ChatGPT choices with the three glaucoma specialists, levels of agreement were 75%, 70%, and 83%, respectively. In ordinary cases, we did not report any significant differences when comparing ChatGPT answers with those of the three glaucoma specialists, when both of them were matched with patients’ files (p > 0.05 for all). ChatGPT’s performances were lower in “challenging” cases: when compared to patients’ files, the accuracy was 13/20 (65%); when compared to glaucoma specialists, the level of agreement was 50%, 40%, and 70%, respectively. Conclusion: In ordinary conditions, ChatGPT was able to propose coherent personalized treatment plans, and its performance was comparable to that of skilled glaucoma specialists but showed its limitations in the evaluation of more complex cases. Full article

(This article belongs to the Special Issue Advances in Personalized Diagnosis and Treatment of Ophthalmic Diseases)

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13 pages, 2007 KB

Open AccessEditor’s ChoiceArticle

Comparison of Outcomes Between Functionally and Mechanically Aligned Total Knee Arthroplasty: Analysis of Parallelism to the Ground and Weight-Bearing Position of the Knee Using Hip-to-Calcaneus Radiographs

by Hongyeol Yang, Chanjin Park, Jaehyeok Cheon, Jaeyeon Hwang and Jongkeun Seon

J. Pers. Med. 2025, 15(3), 91; https://doi.org/10.3390/jpm15030091 - 27 Feb 2025

Cited by 6 | Viewed by 2856

Abstract

Background: The objective of this study was to compare the outcomes between patients undergoing mechanically aligned conventional total knee arthroplasty (MA-CTKA) and functionally aligned robotic-arm-assisted TKA (FA-RTKA). Methods: We reviewed a prospectively collected database of consecutive patients who underwent primary total knee arthroplasty [...] Read more.

Background: The objective of this study was to compare the outcomes between patients undergoing mechanically aligned conventional total knee arthroplasty (MA-CTKA) and functionally aligned robotic-arm-assisted TKA (FA-RTKA). Methods: We reviewed a prospectively collected database of consecutive patients who underwent primary total knee arthroplasty (TKA) for knee osteoarthritis between June 2022 and May 2023. Patients were divided into two groups—MA-CTKA (n = 50) and FA-RTKA (n = 50)—based on the introduction of a robotic-arm-assisted system during the study period. The hip–knee–ankle (HKA) angle, joint line orientation angle (JLOA) relative to the floor, and weight-bearing line (WBL) ratio were evaluated using full-length standing hip-to-calcaneus radiographs to compare the conventional mechanical axis (MA) and the ground mechanical axis (GA) passing through the knee joint between the groups. Clinical outcomes were also compared between the two groups. Results: There were no significant differences in the postoperative HKA angle between the groups, due to discrepancies in the targeted alignment strategies (FA-RTKA: 2.0° vs. MA-CTKA: 0.5°; p = 0.001). The postoperative JLOA in the FA-RTKA group was more parallel to the floor, whereas the MA-CTKA group showed a downward angulation toward the lateral side (0.6° vs. −2.7°; p < 0.001). In the FA-RTKA group, the GA passed through a neutral position when accounting for the calcaneus, while the MA-CTKA group showed a more lateral GA position (48.8% vs. 53.8%; p = 0.001). No significant differences in clinical outcomes were shown between the FA-RTKA and MA-CTKA groups, with the FA-RTKA group demonstrating higher Forgotten Joint Scores and a greater range of motion (all p < 0.05). Conclusions: Functionally aligned TKA demonstrated improved joint line parallelism to the floor and more neutral weight-bearing alignment in the GA compared to mechanically aligned TKA. These findings indicate a more balanced load distribution across the knee, which may contribute to the superior clinical outcomes observed in the functionally aligned group. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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23 pages, 1360 KB

Open AccessEditor’s ChoiceSystematic Review

Executive Functions Training Improves Language Abilities in Aphasia Rehabilitation: A Systematic Review

by Laura Culicetto, Desirèe Latella, Viviana Lo Buono, Fabio Orecchio, Anna Maria Murdaca, Angelo Quartarone and Silvia Marino

J. Pers. Med. 2025, 15(3), 92; https://doi.org/10.3390/jpm15030092 - 27 Feb 2025

Cited by 6 | Viewed by 8118

Abstract

Background/Objectives: In recent years, the popularity of non-verbal cognitive training for aphasia has increased. Building on evidence that language abilities engage brain areas involved in executive functions (EFs) processing, this review aims to analyze the utility of EFs training alone or combined [...] Read more.

Background/Objectives: In recent years, the popularity of non-verbal cognitive training for aphasia has increased. Building on evidence that language abilities engage brain areas involved in executive functions (EFs) processing, this review aims to analyze the utility of EFs training alone or combined with traditional rehabilitation approaches to improve language abilities in aphasia. Methods: Systematic searches were performed in four databases evaluating studies focusing on the effects of EFs training in language rehabilitation, yielding 185 studies. After reading the full text of the selected studies and applying predefined inclusion criteria, nine studies were included based on pertinence and relevance to the topic. This systematic review has been registered in the Prospective Register of Systematic Reviews (PROSPERO 2024) with the number CRD42024519087. Results: The results of the analyzed studies indicate that various EFs training methods, such as computer-assisted executive control training, Cognitive Flexibility in Aphasia Therapy (CFAT), and the Dr. Neuronowski^® program, as well as the combination of transcranial direct current stimulation (tDCS) with EFs training, can lead to improvements in language abilities in people with aphasia. Additionally, EFs training often results in specific effects on treated functions like working memory (near transfer effects) and untreated ones such as spoken sentence comprehension (far transfer effects). Conclusions: Despite the heterogeneity of the treatments and the small simple size of the studies analyzed, preliminary results are promising. Future research should further explore the effectiveness and specific contribution of EFs training to improving language functions in aphasia. Full article

(This article belongs to the Special Issue The Applications of Non-Invasive Brain Stimulation in Neuropsychiatric Research and Treatment)

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18 pages, 441 KB

Open AccessEditor’s ChoiceReview

A Personalized, Risk-Based Approach to Active Surveillance for Prostate Cancer with Takeaways from Broader Oncology Practices: A Mixed Methods Review

by Jeroen J. Lodder, Sebastiaan Remmers, Roderick C. N. van den Bergh, Arnoud W. Postema, Pim J. van Leeuwen and Monique J. Roobol

J. Pers. Med. 2025, 15(3), 84; https://doi.org/10.3390/jpm15030084 - 25 Feb 2025

Cited by 4 | Viewed by 4575

Abstract

Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a [...] Read more.

Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a systematic review and a narrative review. The systematic review was conducted according to the Preferred Reporting Items for Systematic rviews and Meta-Analyses (PRISMA) guidelines, with searches performed in the Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Only studies evaluating personalized, risk-based AS programs for PCa were included. The narrative review focused on AS approaches in other solid tumors (thyroid, breast, kidney, and bladder cancer) to contextualize the findings and highlight lessons learned. Results: After screening 3137 articles, 9 were suitable for inclusion, describing the following four unique risk-based AS tools: PRIAS, Johns Hopkins, Canary PASS, and STRATCANS. These models were developed using data from men with low-risk (Grade Group 1) disease, with little to no magnetic resonance imaging (MRI) data. They used patient information such as (repeated) prostate-specific antigen (PSA) measurements and biopsy results to predict the risk of upgrading at the next biopsy or at radical prostatectomy, or to assign a patient to a pre-defined risk category with a corresponding pre-defined follow-up (FU) regimen. Performance was moderate across models, with the area under the curve/concordance index values ranging from 0.58 to 0.85 and calibration was generally good. The PRIAS, Canary PASS, and STRATCANS models demonstrated the benefits of less burdensome biopsies, clinic visits, and MRIs during FU when used, compared to current one-size-fits-all practices. Although little is known about risk-based AS in thyroid, breast, kidney, and bladder cancer, learning from their current practices could further refine patient selection, streamline monitoring protocols, and address adoption barriers, improving AS’s overall effectiveness in PCa management. Conclusions: Personalized, risk-based AS models allow for a reduction in the FU burden for men at low risk of progression while maintaining sensitive FU visits for those at higher risk. The comparatively limited evidence and practice of risk-based AS in other cancer types highlight the advanced state of AS in PCa. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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17 pages, 4178 KB

Open AccessEditor’s ChoiceArticle

Towards Trustworthy AI in Healthcare: Epistemic Uncertainty Estimation for Clinical Decision Support

by Adrian Lindenmeyer, Malte Blattmann, Stefan Franke, Thomas Neumuth and Daniel Schneider

J. Pers. Med. 2025, 15(2), 58; https://doi.org/10.3390/jpm15020058 - 31 Jan 2025

Cited by 13 | Viewed by 4958

Abstract

Introduction: Widespread adoption of AI for medical decision-making is still hindered due to ethical and safety-related concerns. For AI-based decision support systems in healthcare settings, it is paramount to be reliable and trustworthy. Common deep learning approaches, however, have the tendency towards overconfidence [...] Read more.

Introduction: Widespread adoption of AI for medical decision-making is still hindered due to ethical and safety-related concerns. For AI-based decision support systems in healthcare settings, it is paramount to be reliable and trustworthy. Common deep learning approaches, however, have the tendency towards overconfidence when faced with unfamiliar or changing conditions. Inappropriate extrapolation beyond well-supported scenarios may have dire consequences highlighting the importance of the reliable estimation of local knowledge uncertainty and its communication to the end user. Materials and Methods: While neural network ensembles (ENNs) have been heralded as a potential solution to these issues for many years, deep learning methods, specifically modeling the amount of knowledge, promise more principled and reliable behavior. This study compares their reliability in clinical applications. We centered our analysis on experiments with low-dimensional toy datasets and the exemplary case study of mortality prediction for intensive care unit hospitalizations using Electronic Health Records (EHRs) from the MIMIC3 study. For predictions on the EHR time series, Encoder-Only Transformer models were employed. Knowledge uncertainty estimation is achieved with both ensemble and Spectral Normalized Neural Gaussian Process (SNGP) variants of the common Transformer model. We designed two datasets to test their reliability in detecting token level and more subtle discrepancies both for toy datasets and an EHR dataset. Results: While both SNGP and ENN model variants achieve similar prediction performance (AUROC:

\approx 0.85

, AUPRC:

\approx 0.52

for in-hospital mortality prediction from a selected MIMIC3 benchmark), the former demonstrates improved capabilities to quantify knowledge uncertainty for individual samples/patients. Discussion/Conclusions: Methods including a knowledge model, such as SNGP, offer superior uncertainty estimation compared to traditional stochastic deep learning, leading to more trustworthy and safe clinical decision support. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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23 pages, 1309 KB

Open AccessEditor’s ChoiceSystematic Review

Mineralocorticoid Receptor Antagonists and Cognitive Outcomes in Cardiovascular Disease and Beyond: A Systematic Review

by Paola Pastena, Gabriele Campagnoli, Ali Reza Rahmani and Andreas P. Kalogeropoulos

J. Pers. Med. 2025, 15(2), 57; https://doi.org/10.3390/jpm15020057 - 30 Jan 2025

Cited by 7 | Viewed by 6201

Abstract

Background/Objectives: Cognitive impairment is a debilitating comorbidity affecting diverse patient populations, yet the cognitive effects of therapies like mineralocorticoid receptor antagonists (MRAs) remain underexplored. Preclinical evidence suggests that MRAs, particularly spironolactone, may reduce cognitive decline by modulating aldosterone-dependent pathways and targeting hippocampal receptors. [...] Read more.

Background/Objectives: Cognitive impairment is a debilitating comorbidity affecting diverse patient populations, yet the cognitive effects of therapies like mineralocorticoid receptor antagonists (MRAs) remain underexplored. Preclinical evidence suggests that MRAs, particularly spironolactone, may reduce cognitive decline by modulating aldosterone-dependent pathways and targeting hippocampal receptors. However, evidence in humans is fragmented, and no systematic review has consolidated these findings. This review evaluates the cognitive effects of MRAs, synthesizes current data, and identifies research gaps. Methods: A literature search using terms related to MRAs and cognitive outcomes was performed in PubMed and Web of Science from 1979 to 2023. A total of 143 articles were identified and 85 were screened after removing duplicates. Ultimately, 44 studies were included and were classified based on study design and population focus (preclinical, healthy controls, patients with psychiatric disorders, and cardiovascular patients). Results: Spironolactone demonstrated mixed effects on cognition. In healthy participants, it improved spatial memory under stress and prevented stress-related suppression of medial temporal activity, but impaired working memory and selective attention. In patients with psychiatric conditions, spironolactone reduced cognitive empathy deficits in major depressive disorder and improved working memory in bipolar I disorder. In cardiovascular patients, spironolactone improved cognitive scores and hippocampal memory but had no effect on non-hippocampal memory. Conclusions: Spironolactone exhibits potential cognitive benefits across diverse populations. However, its effects on cognition are mixed, highlighting the need for further research to understand its mechanisms and therapeutic potential, particularly in patients with heart failure and other related conditions. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 853 KB

Open AccessEditor’s ChoiceSystematic Review

Enhanced Lymph Node Detection in Colon Cancer Using Indocyanine Green Fluorescence: A Systematic Review of Studies from 2020 Onwards

by Roxana Loriana Negrut, Adrian Cote, Bogdan Feder, Florian Dorel Bodog and Adrian Marius Maghiar

J. Pers. Med. 2025, 15(2), 54; https://doi.org/10.3390/jpm15020054 - 29 Jan 2025

Cited by 6 | Viewed by 3951

Abstract

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for [...] Read more.

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for enhancing lymph node visualization during surgical intervention. The high rates of local recurrence in colon cancer patients require innovative methods to improve lymphatic mapping and lymph node dissection. This review evaluates the clinical utility and efficacy of ICG imaging in enhancing lymph node accuracy in colon cancer surgery. Materials and methods: A systematic search was conducted in October 2024 (last day of consulting the database was 16 November) across Web of Science, Scopus, and PubMed to identify studies published from 2020 onwards focusing on the use of indocyanine green in colon cancer surgeries. The search terms used were “indocyanine green”, “ICG”, “fluorescent imaging”, “near-infrared imaging”, “colon cancer”, “colorectal cancer”, “colon carcinoma”,” colon neoplasms”, “surgery”, “surgical procedure”, “surgical resection”, surgical precision”. The search followed PRISMA guidelines. The records underwent a two-phase independent screening process conducted by the authors, first based on the title and abstract, followed by full record evaluation. Articles were excluded following certain exclusion criteria: non-human studies; restricted access publications; other publication type than article (review, meta-analysis, questionnaire-based study, case report, etc.), studies focusing on other diseases or studies that focused on the surgical treatment of metastasis from colon cancer; foreign language (non-English); no data of interest for the current review; studies that focused on rectal cancer and that grouped rectal and colon cancer. Data extraction involved both quantitative and qualitative data, such as detection rates, sensitivity, specificity, and other surgical outcomes. Risk of bias was assessed using ROBINS-I, J Joanna Briggs Institute (JBI) Critical Appraisal Checklist, and the Newcastle–Ottawa Scale, depending on study type. The study was not preregistered in PROSPERO. However, to ensure methodological rigor and transparency, it was retrospectively registered in Open Science Framework (OSF). Results: From the 3300 records initially identified, 9 studies were included in this review. Detection rates varied from 55% to 100%, with the highest rate reported in robot-assisted surgeries. The studies showed an improved lymph node detection and lymphatic flow accuracy using ICG fluorescence. Discussion: ICG fluorescence demonstrated substantial benefits, improving staging accuracy and potentially reducing recurrence rates by guiding the lymphadenectomy. The variability observed in detection rates is largely attributed to differences in ICG administration, cancer stage, and surgical approaches. Conclusions: ICG-guided surgery for colon cancer represents a promising advancement, enhancing lymph node detection and staging accuracy. Large-scale randomized trials are essential to establish standardized protocols and validate the efficacy in improving surgical outcomes. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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22 pages, 297 KB

Open AccessEditor’s ChoiceReview

The Development and Application of Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma

by Laura Sun and Jason T. Romancik

J. Pers. Med. 2025, 15(2), 51; https://doi.org/10.3390/jpm15020051 - 28 Jan 2025

Cited by 13 | Viewed by 5783

Abstract

T-cell-engaging bispecific antibodies (BsAbs) are monoclonal antibodies that redirect the cytotoxic activity of T-cells to target malignant neoplasms. B-cell non-Hodgkin lymphoma (B-NHL) is a heterogenous group of aggressive and indolent malignancies with significant therapeutic challenges due to high relapse rates and limited options [...] Read more.

T-cell-engaging bispecific antibodies (BsAbs) are monoclonal antibodies that redirect the cytotoxic activity of T-cells to target malignant neoplasms. B-cell non-Hodgkin lymphoma (B-NHL) is a heterogenous group of aggressive and indolent malignancies with significant therapeutic challenges due to high relapse rates and limited options for relapsed/refractory disease. BsAbs function by simultaneously binding to CD3 on endogenous T-cells and a tumor-associated antigen, creating an immunologic synapse which results in the death of the target cell. The widespread T-cell activation that occurs with BsAb administration can result in cytokine release syndrome and neurological adverse events. Mosunetuzumab, epcoritamab, and glofitamab are CD20-targeting BsAbs that have demonstrated promising single-agent activity in both indolent and aggressive B-NHL. BsAbs are now being evaluated in combination with other anti-lymphoma agents and in earlier lines of treatment, and the results of ongoing clinical trials involving these agents have the potential to reshape the treatment landscape for B-NHL. In this review, we describe the structural features, clinical data, and toxicity profile associated with the BsAbs currently used to treat B-NHL and then discuss ongoing studies and future directions for this exciting new class of therapeutic agents. Full article

(This article belongs to the Special Issue Precision Medicine for Hematological Malignancies)

18 pages, 713 KB

Open AccessEditor’s ChoiceReview

Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy

by Taranatee Khan, Manojavan Nagarajan, Irene Kang, Chunjing Wu and Medhi Wangpaichitr

J. Pers. Med. 2025, 15(2), 50; https://doi.org/10.3390/jpm15020050 - 27 Jan 2025

Cited by 17 | Viewed by 6577

Abstract

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis to oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also [...] Read more.

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis to oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also contribute to immune evasion through mechanisms such as reactive oxygen species (ROS) generation and the upregulation of immune checkpoint molecules like PD-L1. This review explores the potential of targeting metabolic weaknesses in drug-resistant cancers to enhance therapeutic efficacy. Key metabolic pathways involved in resistance, including glycolysis, glutamine metabolism, and the kynurenine pathway, are discussed. The combination of metabolic inhibitors with immune checkpoint inhibitors (ICIs), particularly anti-PD-1/PD-L1 therapies, represents a promising approach to overcoming both metabolic and immune evasion mechanisms. Clinical trials combining metabolic and immune therapies have shown early promise, but further research is needed to optimize treatment combinations and identify biomarkers for patient selection. In conclusion, targeting cancer metabolism in combination with immune checkpoint blockade offers a novel approach to overcoming drug resistance, providing a potential pathway to improved outcomes in cancer therapy. Future directions include personalized treatments based on tumor metabolic profiles and expanding research to other tumor types. Full article

(This article belongs to the Special Issue Exploiting Metabolic Weaknesses: A Novel Approach to Overcome Drug Resistance in Cancer Therapy)

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17 pages, 1527 KB

Open AccessEditor’s ChoiceArticle

Impact of Whole-Body Cryotherapy on Pain, Sleep Quality, Functional Status, and Quality of Life in Multiple Sclerosis: A Comparative Study with Follow-Up

by Ewa Zielińska-Nowak, Anna Lipert, Łukasz Kikowski and Elżbieta Miller

J. Pers. Med. 2025, 15(2), 46; https://doi.org/10.3390/jpm15020046 - 26 Jan 2025

Cited by 6 | Viewed by 9403

Abstract

Background/Objectives: Whole-body cryotherapy (WBC) is widely recognized for its analgesic and anti-inflammatory effects. Despite growing interest in its therapeutic potential, the impact of WBC on functional performance, pain perception, sleep quality, and quality of life among individuals with multiple sclerosis (MS) remains underexplored. [...] Read more.

Background/Objectives: Whole-body cryotherapy (WBC) is widely recognized for its analgesic and anti-inflammatory effects. Despite growing interest in its therapeutic potential, the impact of WBC on functional performance, pain perception, sleep quality, and quality of life among individuals with multiple sclerosis (MS) remains underexplored. This study aimed to assess the effects of a 10-session WBC protocol on functional and psychological parameters in patients with MS and compare them with individuals without neurological disorders. Methods: A total of 73 participants divided into two groups, non-neurological individuals (non-MS, n = 43) and patients with MS (MS, n = 30), underwent 10 WBC sessions (−120 °C to −130 °C) over 2 weeks. Assessments included the Numerical Rating Scale (NRS), 30-Second Chair Stand Test (30CST), Timed Up and Go (TUG) test, and Pittsburgh Sleep Quality Index, with the WHOQOL-BREF conducted pre-treatment, post-treatment, and at a 10-day follow-up. Results: In the MS group, significant improvements were observed post-treatment in the NRS, 30CST, WHOQOL-1, and PSQI. However, only the CST and WHOQOL-3 maintained improvements during follow-up. In the non-MS group, statistically significant improvements were observed post-treatment across most parameters, except for the NRS and WHOQOL-3, with most effects diminishing by the follow-up. No deterioration in any assessed parameters was observed in either group. Conclusions: WBC demonstrates potential benefits for managing MS symptoms, particularly pain and sleep quality, with no observed deterioration in parameters and some effects emerging only during follow-ups, underscoring its safety and the need for further research on long-term outcomes. Full article

(This article belongs to the Special Issue Cold Perspectives: Advancements and Applications of Cryotherapy in Clinical Settings)

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24 pages, 1484 KB

Open AccessEditor’s ChoiceReview

Precision Medicine in Myeloid Neoplasia: Challenges and Opportunities

by Michael J. Hochman, Joshua P. Muniz and Nikolaos Papadantonakis

J. Pers. Med. 2025, 15(2), 49; https://doi.org/10.3390/jpm15020049 - 26 Jan 2025

Cited by 4 | Viewed by 3450

Abstract

High-risk myeloid neoplasms encompass a group of hematologic malignancies known to cause significant cytopenias, which are accompanied by the risk of end-organ damage. They tend to have an aggressive clinical course and limit life expectancy in the absence of effective treatments. The adoption [...] Read more.

High-risk myeloid neoplasms encompass a group of hematologic malignancies known to cause significant cytopenias, which are accompanied by the risk of end-organ damage. They tend to have an aggressive clinical course and limit life expectancy in the absence of effective treatments. The adoption of precision medicine approaches has been limited by substantive diversity in somatic mutations, limited fraction of patients with targetable genetic lesions, and the prolonged turnaround times of pertinent genetic tests. Efforts to incorporate targeted agents into first-line treatment, rapidly determine pre-treatment molecular or cytogenetic aberrations, and evaluate functional vulnerabilities ex vivo hold promise for advancing the use of precision medicine in these malignancies. Given the relative accessibility of malignant cells from blood and bone marrow, precision medicine strategies hold great potential to shape future standard-of-care approaches to patients with high-risk myeloid malignancies. This review aims to summarize the development of the targeted therapies currently available to treat these blood cancers, most notably acute myeloid leukemia, and also evaluate future opportunities and challenges related to the integration of personalized approaches. Full article

(This article belongs to the Special Issue Precision Medicine for Hematological Malignancies)

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12 pages, 3420 KB

Open AccessEditor’s ChoiceArticle

Implementation and Feasibility of Mechanomyography in Minimally Invasive Spine Surgery

by Fabian Sommer, Ibrahim Hussain, Noah Willett, Mousa K. Hamad, Chibuikem A. Ikwuegbuenyi, Rodrigo Navarro-Ramirez, Sertac Kirnaz, Lynn McGrath, Jacob Goldberg, Amanda Ng, Catherine Mykolajtchuk, Sam Haber, Vincent Sullivan, Pravesh S. Gadjradj and Roger Härtl

J. Pers. Med. 2025, 15(2), 42; https://doi.org/10.3390/jpm15020042 - 23 Jan 2025

Cited by 8 | Viewed by 2930

Abstract

Background: Mechanomyography (MMG) is a neurodiagnostic technique with a documented ability to evaluate the compression of nerve roots. Its utility in degenerative spine surgery is unknown. Objective: To assess the utility of intraoperative MMG during cervical posterior foraminotomy, minimally invasive transforaminal [...] Read more.

Background: Mechanomyography (MMG) is a neurodiagnostic technique with a documented ability to evaluate the compression of nerve roots. Its utility in degenerative spine surgery is unknown. Objective: To assess the utility of intraoperative MMG during cervical posterior foraminotomy, minimally invasive transforaminal interbody fusion (MIS-TLIF), and tubular lumbar far lateral discectomy. Methods: A prospective feasibility study was conducted during which MMG was applied during three procedures. Adhesive accelerometers were placed on two muscle groups per procedure. Stimulus threshold in mA was recorded before and after the decompression of the nerve root. Differences in stimulation thresholds were correlated with operative findings. Results: In total, 22 patients were included in this study; 5 patients underwent cervical foraminotomies, 3 underwent MIS-TLIFs, and 14 underwent tubular far lateral discectomies. For the foraminotomies, all cases showed a reduction in stimulation threshold (mean of 3.4 mA) after decompression. For MIS-TLIF cases, there was a limited reduction in the stimulation threshold after decompression (mean 1.7 mA). For far lateral discectomy, there was a mean reduction of 4.3 mA in the stimulation threshold following decompression. Conclusions: MMG is a method that may provide intraoperative feedback on the decompression of nerve roots. In the context of MIS-TLIF, MMG showed a limited decrease in stimulus threshold. This may be due to the identification of the nerve occurring after decompression is already underway. For cervical foraminotomies and far lateral discectomies, MMG showed promising results in determining adequate decompression of the nerve root. Full article

(This article belongs to the Special Issue Clinical Research of Minimally Invasive Spine Surgery)

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14 pages, 1355 KB

Open AccessEditor’s ChoiceArticle

Dupilumab Effectiveness in Patients with Severe Allergic Asthma Non-Responsive to Omalizumab

by Diego Bagnasco, Benedetta Bondi, Luisa Brussino, Stefania Nicola, Paolo Cameli, Angelica Tiotiu, Giuseppe Guida, Chiara Gollinucci, Dina Visca, Antonio Spanevello, Laura Pini, Marco Caminati, Gianenrico Senna, Cristiano Caruso, Rikki Frank Canevari, Melania Bertolini, Sara Fedele, Marcello Mincarini, Giorgio Walter Canonica, Fulvio Braido and on behalf of the SANI group Show full author list Hide full author list

J. Pers. Med. 2025, 15(2), 43; https://doi.org/10.3390/jpm15020043 - 23 Jan 2025

Cited by 9 | Viewed by 5506

Abstract

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab [...] Read more.

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab in patients with severe allergic asthma, non-responsive to omalizumab, according to the maintenance of their oral corticosteroid (OCS) dose, an exacerbation rate decrease, or poor control of the disease, despite optimized treatment. Methods: A retrospective analysis of data from severe asthma clinics was performed, observing the efficacy of the switch to dupilumab in patients who experienced a failed treatment with omalizumab. Results: Forty-two patients were included. Dupilumab proved to be effective in patients who experienced a failed omalizumab treatment, with a significant reduction in the exacerbation number and OCS use. Furthermore, remission of the disease, according to the Severe Asthma Network of Italy (SANI) criteria, was achieved in 35 patients, with complete remission in 19 (45%) and partial remission in 16 (38%). The analysis of the predictors of the success of dupilumab therapy in achieving clinical remission, through univariate analysis of the data at baseline, showed that complete remission was more easily reached in patients with concomitant aspirin (ASA) intolerance or in those with nasal polyposis. Conclusions: Dupilumab is an effective drug for the treatment of patients with severe asthma with an allergic component, with better benefits in patients with an ASA intolerance or nasal polyposis. Full article

(This article belongs to the Section Molecular Targeted Therapy)

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15 pages, 5044 KB

Open AccessEditor’s ChoiceReview

Navigating the Uncertainty of B3 Breast Lesions: Diagnostic Challenges and Evolving Management Strategies

by Sabatino D’Archi, Beatrice Carnassale, Alejandro Martin Sanchez, Cristina Accetta, Paolo Belli, Flavia De Lauretis, Enrico Di Guglielmo, Alba Di Leone, Antonio Franco, Stefano Magno, Francesca Moschella, Maria Natale, Lorenzo Scardina, Marta Silenzi, Riccardo Masetti and Gianluca Franceschini

J. Pers. Med. 2025, 15(1), 36; https://doi.org/10.3390/jpm15010036 - 18 Jan 2025

Cited by 5 | Viewed by 7030

Abstract

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia [...] Read more.

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia (FEA), radial scars (RSs), lobular neoplasia (LN), and phyllodes tumors (PTs), occupy a “grey zone” between benign and malignant pathologies, making their management complex and often controversial. This article explores the diagnostic difficulties associated with B3 lesions, focusing on the limitations of current imaging techniques, including mammography, ultrasound, and magnetic resonance imaging (MRI), as well as the challenges in histopathological interpretation. Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are widely used for diagnosis, but both methods have inherent limitations, including sampling errors and the inability to determine malignancy in some cases definitively. The therapeutic approach to B3 lesions is nuanced, with treatment decisions strongly influenced by factors such as the lesion size, radiological findings, histopathological characteristics, and patient factors. While some lesions can be safely monitored with watchful waiting, others may require vacuum-assisted excision (VAE) or surgical excision to rule out malignancy. The decision-making process is further complicated by the discordance between the BI-RADS score and biopsy results, as well as the presence of additional risk factors, such as microcalcifications. This review provides an in-depth analysis of the current diagnostic challenges and treatment strategies for B3 lesions, emphasizing the importance of a multidisciplinary approach to management. By synthesizing the most recent research, this article aims to provide clinicians with a clearer understanding of the complexities involved in diagnosing and treating B3 breast lesions while highlighting areas for future research, such as artificial intelligence and genomics, to improve the diagnostic accuracy and patient outcomes. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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66 pages, 1373 KB

Open AccessEditor’s ChoiceReview

Concussion and the Autonomic, Immune, and Endocrine Systems: An Introduction to the Field and a Treatment Framework for Persisting Symptoms

by Jon L. Pertab, Tricia L. Merkley, Holly Winiarski, Kelly M. J. Cramond and Alex J. Cramond

J. Pers. Med. 2025, 15(1), 33; https://doi.org/10.3390/jpm15010033 - 17 Jan 2025

Cited by 8 | Viewed by 13338

Abstract

A significant proportion of patients who sustain a concussion/mild traumatic brain injury endorse persisting, lingering symptoms. The symptoms associated with concussion are nonspecific, and many other medical conditions present with similar symptoms. Medical conditions that overlap symptomatically with concussion include anxiety, depression, insomnia, [...] Read more.

A significant proportion of patients who sustain a concussion/mild traumatic brain injury endorse persisting, lingering symptoms. The symptoms associated with concussion are nonspecific, and many other medical conditions present with similar symptoms. Medical conditions that overlap symptomatically with concussion include anxiety, depression, insomnia, chronic pain, chronic fatigue, fibromyalgia, and cervical strain injuries. One of the factors that may account for these similarities is that these conditions all present with disturbances in the optimal functioning of the autonomic nervous system and its intricate interactions with the endocrine system and immune system—the three primary regulatory systems in the body. When clinicians are working with patients presenting with persisting symptoms after concussion, evidence-based treatment options drawn from the literature are limited. We present a framework for the assessment and treatment of persisting symptoms following concussion based on the available evidence (treatment trials), neuroanatomical principles (research into the physiology of concussion), and clinical judgment. We review the research supporting the premise that behavioral interventions designed to stabilize and optimize regulatory systems in the body following injury have the potential to reduce symptoms and improve functioning in patients. Foundational concussion rehabilitation strategies in the areas of sleep stabilization, fatigue management, physical exercise, nutrition, relaxation protocols, and behavioral activation are outlined along with practical strategies for implementing intervention modules with patients. Full article

(This article belongs to the Special Issue Clinical Advances in Traumatic Brain Injury and Concussion)

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13 pages, 1208 KB

Open AccessEditor’s ChoiceArticle

Robotic Versus Sternotomy, Thoracotomy and Video-Thoracoscopy Approaches for Thymoma Resection: A Comparative Analysis of Short-Term Results

by Beatrice Trabalza Marinucci, Matteo Tiracorrendo, Camilla Vanni, Fabiana Messa, Giorgia Piccioni, Alessandra Siciliani, Silvia Fiorelli, Mohsen Ibrahim, Erino A. Rendina and Antonio D’Andrilli

J. Pers. Med. 2025, 15(1), 34; https://doi.org/10.3390/jpm15010034 - 17 Jan 2025

Cited by 7 | Viewed by 2946

Abstract

OBJECTIVE. The optimal surgical approach for thymoma resection is still an object of debate. The increasing experience in robotic-assisted thoracic surgery (RATS) has led to the progressive affirmation of this technique as a valid alternative to Sternotomy, Thoracotomy and Video-Assisted Thoracic Surgery [...] Read more.

OBJECTIVE. The optimal surgical approach for thymoma resection is still an object of debate. The increasing experience in robotic-assisted thoracic surgery (RATS) has led to the progressive affirmation of this technique as a valid alternative to Sternotomy, Thoracotomy and Video-Assisted Thoracic Surgery (VATS) in this setting. The present study aims to compare the post-operative and short-term results of RATS Thymectomy for thymoma with those of other main surgical approaches (sternotomy, thoracotomy and VATS) from a high-volume single center. METHODS. Between May 2021 and September 2023, 40 consecutive patients underwent RATS Thymectomy for stage I to limited-stage III thymoma in our center. Three homogenous groups of patients who received thymoma resection through main alternative approaches (sternotomy, thoracotomy, VATS) over the last 5 years, were identified in order to perform a comparative analysis. Data including surgery duration, associated resections, conversion rate, overall morbidity, tumor size, radicality of resection, post-operative pain, length of hospital stay and cosmetic results were retrospectively collected and compared between the RATS and each control group. RESULTS. Mean tumor size was higher in the sternotomy group, but not significantly. The mean operative time of RATS interventions was significantly lower than that of sternotomy and VATS. It was significantly shorter compared to thoracotomy if excluding docking-undocking time. A higher rate of associated adjacent structures resection was reported in the sternotomy group (p = 0.005). Conversion rate was significantly higher in the VATS group (p = 0.026) compared to RATS. Post-operative pain at 24 and 48 h was significantly lower in the RATS group compared to the others. Improved cosmetics results were reported after RATS compared to sternotomy (p = 0.0001) and thoracotomy (p = 0.001) groups, with a trend towards better results compared to VATS (p = 0.05). Length of hospital stay was shorter in the RATS group with a significant difference vs. the sternotomy group (p < 0.001). CONCLUSIONS. These results from a single center confirm the safety and efficacy of RATS for the treatment of limited stage thymoma. An advantage in terms of operative outcomes, post-operative pain, cosmetic results and hospital stay was observed if compared to the alternative approaches. The short-term oncologic outcome was excellent based on the high complete resection rate of the tumor. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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15 pages, 1149 KB

Open AccessEditor’s ChoiceArticle

A Mediation Appraisal of Neuropathic-like Symptoms, Pain Catastrophizing, and Central Sensitization-Related Signs in Adults with Knee Osteoarthritis—A Cross-Sectional Study

by Fausto Salaffi, Marina Carotti, Sonia Farah, Carlo Ciccullo, Antonio Pompilio Gigante, Francesca Bandinelli and Marco Di Carlo

J. Pers. Med. 2025, 15(1), 22; https://doi.org/10.3390/jpm15010022 - 10 Jan 2025

Cited by 11 | Viewed by 3313

Abstract

Objective. To investigate the relationships among neuropathic pain (NP), pain catastrophizing (PC), and central sensitization (CS) in relation to functional status and radiological damage in patients with knee osteoarthritis (OA). Methods. This cross-sectional study included knee OA patients derived from an observational cohort. [...] Read more.

Objective. To investigate the relationships among neuropathic pain (NP), pain catastrophizing (PC), and central sensitization (CS) in relation to functional status and radiological damage in patients with knee osteoarthritis (OA). Methods. This cross-sectional study included knee OA patients derived from an observational cohort. The Spearman correlation test was used to analyze the relationship between the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the PainDetect Questionnaire (PDQ), Central Sensitization Inventory (CSI), and Pain Catastrophizing Scale (PCS). The Kruskal–Wallis test was employed to compare WOMAC scores according to CSI categories. A multivariate analysis was conducted to identify predictors of functional ability, with the WOMAC score as the dependent variable and the independent variables including pain-related indices such as PCS, PDQ, and CSI, along with Kellgren–Lawrence (K-L) grading and demographic characteristics. Results. This study included 149 patients (76.5% female; mean age 71.5 years; mean duration of pain 8.1 years). In total, 23.5% exhibited NP, 30.9% showed PC, and 33.6% had CS. Higher mean values of WOMAC were correlated with CSI categories (p < 0.0001). WOMAC showed a significant relationship with CSI (rho = 0.791; p < 0.0001), PDQ (rho = 0.766; p < 0.0001), and PCS (rho = 0.536; p < 0.0001). In the multiple regression analysis, WOMAC was independently associated with CSI (p < 0.0001), PDQ (p < 0.0001), and PC (p = 0.0001). No association was observed between the K-L grading and the other variables. Conclusions. A reduced functional capacity in patients with knee OA is correlated with the presence of NP, PC and CS, without being significantly associated with radiological damage. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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13 pages, 265 KB

Open AccessEditor’s ChoiceArticle

Prostatic Artery Embolization in Elderly Comorbid Patients with Benign Prostatic Hyperplasia: Safety, Efficacy, and Predictive Factors of Clinical Failure

by Federico Zorzi, Giulio Rossin, Michelangelo Digregorio, Simone Lavecchia, Andrea Piasentin, Fabio Traunero, Carmelo Morreale, Michele Rizzo, Tommaso Cai, Carlo Trombetta, Alessandro Zucchi and Giovanni Liguori

J. Pers. Med. 2025, 15(1), 23; https://doi.org/10.3390/jpm15010023 - 10 Jan 2025

Cited by 8 | Viewed by 4377

Abstract

Background: This study aims to evaluate the safety and efficacy of prostatic artery embolization (PAE) in elderly, multimorbid patients with benign prostatic hyperplasia (BPH). Additionally, it seeks to identify technical and clinical factors that predict clinical failure at the mid-term follow-up. Methods [...] Read more.

Background: This study aims to evaluate the safety and efficacy of prostatic artery embolization (PAE) in elderly, multimorbid patients with benign prostatic hyperplasia (BPH). Additionally, it seeks to identify technical and clinical factors that predict clinical failure at the mid-term follow-up. Methods: We analyzed the clinical records of 175 consecutive patients who underwent PAE. Technical success was defined as achieving embolization on at least one side. Safety was assessed using the Clavien–Dindo classification. The pre-procedural international prostate symptom score (IPSS), quality of life (QoL) score, prostate volume (PV), prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), and post-void residual urine (PVR) were compared with values assessed at the follow-up evaluation. Clinical failure was defined as no improvement or worsening of lower urinary tract symptoms (LUTS) based on the IPSS at the follow-up evaluation. Univariate and multivariate regression models were applied to identify predictors of clinical failure. Results: 158 patients met the inclusion criteria. The median age was 74 years (68, 79), with a median ASA score of 2 (2, 3) and a Charlson comorbidity index (CCI) of 5 (4, 7). Follow-up assessments were carried out at a median of 12 months (0, 1). IPSS decreased by −5 points (−8, 0), QoL by −1 point (−1, 0), PV by −19 cc (−26, −8), PVR by −45 cc (−25 to −80), and PSA by −1.1 ng/mL (−2.5, −0.2) (p < 0.01); while Qmax improved by 4 mL/s (2, 6) (p < 0.01). A total of 44 patients (30.3%) experienced clinical failure, which was significantly correlated with unilateral embolization (p < 0.01). Multivariate regression analysis indicated that higher CCI, elevated PVR, and the use of larger microspheres were associated with poorer clinical outcomes, with odds ratios of 2.17 (95% CI: 1.4–3.38), 1.02 (95% CI: 1.01–1.03), and 26.83 (95% CI: 4.81–149.8), respectively (p < 0.01). Conclusions: PAE is a safe and effective treatment for elderly multimorbid patients with BPH. Comprehensive pre-procedural clinical assessment, incorporating the CCI and PVR, is essential to optimize treatment outcomes. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Urological Diseases)

21 pages, 702 KB

Open AccessEditor’s ChoiceReview

The Role of Artificial Intelligence and Emerging Technologies in Advancing Total Hip Arthroplasty

by Luca Andriollo, Aurelio Picchi, Giulio Iademarco, Andrea Fidanza, Loris Perticarini, Stefano Marco Paolo Rossi, Giandomenico Logroscino and Francesco Benazzo

J. Pers. Med. 2025, 15(1), 21; https://doi.org/10.3390/jpm15010021 - 9 Jan 2025

Cited by 37 | Viewed by 8385

Abstract

Total hip arthroplasty (THA) is a widely performed surgical procedure that has evolved significantly due to advancements in artificial intelligence (AI) and robotics. As demand for THA grows, reliable tools are essential to enhance diagnosis, preoperative planning, surgical precision, and postoperative rehabilitation. AI [...] Read more.

Total hip arthroplasty (THA) is a widely performed surgical procedure that has evolved significantly due to advancements in artificial intelligence (AI) and robotics. As demand for THA grows, reliable tools are essential to enhance diagnosis, preoperative planning, surgical precision, and postoperative rehabilitation. AI applications in orthopedic surgery offer innovative solutions, including automated hip osteoarthritis (OA) diagnosis, precise implant positioning, and personalized risk stratification, thereby improving patient outcomes. Deep learning models have transformed OA severity grading and implant identification by automating traditionally manual processes with high accuracy. Additionally, AI-powered systems optimize preoperative planning by predicting the hip joint center and identifying complications using multimodal data. Robotic-assisted THA enhances surgical precision with real-time feedback, reducing complications such as dislocations and leg length discrepancies while accelerating recovery. Despite these advancements, barriers such as cost, accessibility, and the steep learning curve for surgeons hinder widespread adoption. Postoperative rehabilitation benefits from technologies like virtual and augmented reality and telemedicine, which enhance patient engagement and adherence. However, limitations, particularly among elderly populations with lower adaptability to technology, underscore the need for user-friendly platforms. To ensure comprehensiveness, a structured literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included “artificial intelligence”, “machine learning”, “robotics”, and “total hip arthroplasty”. Inclusion criteria emphasized peer-reviewed studies published in English within the last decade focusing on technological advancements and clinical outcomes. This review evaluates AI and robotics’ role in THA, highlighting opportunities and challenges and emphasizing further research and real-world validation to integrate these technologies into clinical practice effectively. Full article

(This article belongs to the Special Issue Artificial Intelligence for Personalized Medicine: Bridging Innovative Technologies and Patient-Centric Care)

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16 pages, 3367 KB

Open AccessEditor’s ChoiceArticle

Patient-Specific Variability in Interleukin-6 and Myeloperoxidase Responses in Osteoarthritis: Insights from Synthetic Data and Clustering Analysis

by Laura Jane Coleman, John L. Byrne, Stuart Edwards and Rosemary O’Hara

J. Pers. Med. 2025, 15(1), 17; https://doi.org/10.3390/jpm15010017 - 4 Jan 2025

Cited by 5 | Viewed by 1869

Abstract

Objectives: This study investigated the inflammatory responses of fibroblast-like synoviocytes (FLS) isolated from osteoarthritis (OA) patients, stimulated with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both experimental and synthetic data were utilised to investigate the variability in IL-6 and myeloperoxidase (MPO) production and its implications [...] Read more.

Objectives: This study investigated the inflammatory responses of fibroblast-like synoviocytes (FLS) isolated from osteoarthritis (OA) patients, stimulated with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both experimental and synthetic data were utilised to investigate the variability in IL-6 and myeloperoxidase (MPO) production and its implications for OA pathogenesis. Methods: Synovial biopsies were obtained from OA patients undergoing joint replacement surgery. FLS were isolated, cultured, and stimulated with varying concentrations of LPS and IL-6. The production of IL-6 and MPO was measured using enzyme-linked immunosorbent assays (ELISA). Synthetic data generation techniques expanded the dataset to support comprehensive statistical analyses. Results: The patterns of inflammatory responses revealed distinct patient subgroups, highlighting individual variability. The integration of synthetic data with experimental observations validated their reliability and demonstrated dose-dependent differences in IL-6 and MPO production across patients. Conclusions: The results highlighted the importance of patient-specific factors in OA inflammation and demonstrated the utility of combining experimental and synthetic data to model individual variability. The results support the development of personalised treatment strategies in OA. Future research should include larger patient datasets and an exploration of molecular mechanisms underlying these responses. Full article

(This article belongs to the Section Mechanisms of Diseases)

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13 pages, 2186 KB

Open AccessEditor’s ChoiceArticle

Stroke-SCORE: Personalizing Acute Ischemic Stroke Treatment to Improve Patient Outcomes

by Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák and László Szapáry

J. Pers. Med. 2025, 15(1), 18; https://doi.org/10.3390/jpm15010018 - 4 Jan 2025

Cited by 5 | Viewed by 4474

Abstract

Background/Objectives: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Despite advances in interventions such as thrombolysis (TL) and mechanical thrombectomy (MT), current treatment protocols remain largely standardized, focusing on general eligibility rather than individual patient characteristics. To [...] Read more.

Background/Objectives: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Despite advances in interventions such as thrombolysis (TL) and mechanical thrombectomy (MT), current treatment protocols remain largely standardized, focusing on general eligibility rather than individual patient characteristics. To address this gap, we introduce the Stroke-SCORE (Simplified Clinical Outcome Risk Evaluation), a predictive tool designed to personalize AIS management by providing data-driven, individualized recommendations to optimize treatment strategies and improve patient outcomes. Methods: The Stroke-SCORE was derived using retrospective data from 793 AIS patients admitted to the University of Pécs (February 2023–September 2024). Logistic regression analysis identified age, National Institutes of Health Stroke Scale (NIHSS) score at admission, and pre-morbid modified Rankin Scale (pre-mRS) score as key predictors of unfavorable outcomes at 90 days (defined as modified Rankin Scale [mRS] score > 2). Based on these predictors, a simplified risk score was developed to stratify patients into low-, moderate-, and high-risk groups, guiding treatment decisions on TL, MT, combination therapy (TL + MT), or standard care (SC). Internal validation was performed to assess the model’s predictive performance via receiver operating characteristic (ROC) analysis and isotonic regression calibration with bootstrapping. Results: The Stroke-SCORE was moderately positively correlated with a 90-day mRS score > 2 (odds ratio [OR] = 0.70, 95% confidence interval [CI]: 0.58–0.83, p < 0.001), with an area under the curve (AUC) of 0.86, a sensitivity and specificity of 79% and 81%, respectively, and an overall accuracy of 80%. Simulations indicated that personalized treatment guided by the Stroke-SCORE significantly reduced unfavorable outcomes. Conclusions: The Stroke-SCORE demonstrates strong predictive performance as a practical, data-driven approach for personalizing AIS treatment decisions. In the future, external, multicenter prospective validation is needed to confirm its applicability in real-world settings. Full article

(This article belongs to the Topic Diagnosis and Management of Acute Ischemic Stroke)

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12 pages, 1624 KB

Open AccessEditor’s ChoiceArticle

Expression of Tissue Remodeling- and Inflammation-Related Factors During the Wound-Healing Process in Humans

by Dimitrios Vardakostas, Athanasios Moustogiannis, Zoe Garoufalia, Elli Karatza, Anastassios Philippou, Gregory Kouraklis, Michael Koutsilieris and Dimitrios Mantas

J. Pers. Med. 2025, 15(1), 14; https://doi.org/10.3390/jpm15010014 - 2 Jan 2025

Cited by 22 | Viewed by 7917

Abstract

Background/Objectives: There is a growing interest in the research of wound healing mechanisms worldwide. Particular attention has been paid to the expression of tissue remodeling- and inflammation-related factors. Herein, we investigate the expression patterns of TGF-β1, IL-6, TNF-a, uPA, uPA receptors, MMP-2, [...] Read more.

Background/Objectives: There is a growing interest in the research of wound healing mechanisms worldwide. Particular attention has been paid to the expression of tissue remodeling- and inflammation-related factors. Herein, we investigate the expression patterns of TGF-β1, IL-6, TNF-a, uPA, uPA receptors, MMP-2, and MMP-9 through the four phases of the normal wound-healing process in humans. Methods: Twenty-two individuals presenting with a first episode of pilonidal sinus underwent surgical excision and the wound was left to heal by secondary intention. Sequential biopsies were collected on day 0 (operation), day 2 (inflammatory phase), day 9 (proliferative phase), and day 14 (tissue remodeling phase). The expression levels of the proteins were evaluated using reverse transcription–quantitative PCR. Statistical analyses were performed using GraphPad Prism software. One-way analysis of variance (ANOVA) with Dunn’s Multiple Comparison post hoc test was used. Results: The results showed statistically significant differences in the expressions of the factors during wound healing (p < 0.05). TGF-b1 increased on days 2 and 9. TNF-a increased on day 2 and then decreased on day 9. Il-6 was increased on day 2 and decreased on days 9 and 14. uPa mRNA increased up to day 9 but its receptor exhibited high expression throughout the observation time. Finally, MMP-2 mRNA expression increased on day 2 and declined on days 9 and 14, while MMP-9 was highly expressed until the 14th postoperative day. Conclusions: Each factor investigated in this study has an important and distinct role in the normal wound repair procedure. Further investigation is required to evaluate the tissue-specific regulation of these factors and their potential use as therapeutic targets or prognostic biomarkers in wound healing. Full article

(This article belongs to the Special Issue Clinical and Experimental Surgery in Personalized Molecular Medicine)

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21 pages, 2284 KB

Open AccessEditor’s ChoiceSystematic Review

Survival Outcomes in Sinonasal Mucosal Melanoma: Systematic Review and Meta-Analysis

by María Jesús Rojas-Lechuga, Sara Jubés, Manuel Molina-García, Rui Milton Patricio da Silva-Júnior, Claudio Sampieri, Cristóbal Langdon, Juan Ramón Gras-Cabrerizo, Manuel Bernal-Sprekelsen, Susana Puig and Isam Alobid

J. Pers. Med. 2024, 14(12), 1120; https://doi.org/10.3390/jpm14121120 - 26 Nov 2024

Cited by 17 | Viewed by 4145

Abstract

Background/Objectives: Sinonasal mucosal melanomas (SNMMs) are rare and aggressive malignancies with poor survival outcomes. Our systematic review and meta-analysis aim to evaluate overall survival (OS) rates in patients with SNMM; Methods: We conducted a systematic search, following PRISMA guidelines across PubMed, [...] Read more.

Background/Objectives: Sinonasal mucosal melanomas (SNMMs) are rare and aggressive malignancies with poor survival outcomes. Our systematic review and meta-analysis aim to evaluate overall survival (OS) rates in patients with SNMM; Methods: We conducted a systematic search, following PRISMA guidelines across PubMed, Web of Science (WOS), and citation searching for studies reporting survival and prognosis outcomes for SNMMs. Inclusion criteria included studies with 5-year OS rates. Studies were excluded if they included tumor sites other than the paranasal sinuses or nasal cavity, were published in languages other than English and Spanish, or had a sample size of fewer than 15 patients. Two reviewers independently screened studies, extracted data, and assessed study quality using the Joanna Briggs Institute (JBI) critical appraisal checklist. Analyses of survival probabilities were conducted. Meta-analyses were performed using a random-effects model. PROSPERO ID CRD42024565137; Results: A total of 515 articles were identified after removing duplicates, and 99 reports were assessed for eligibility. Of these, 35 studies were included in the meta-analysis, encompassing a total of 2383 SNMM patients, of whom 1192 (50%) were female, with a weighted mean age of 65.4 years (SD = 5.4). Fifteen studies were from Europe (42.9%), six (17.1%) were from America, eleven (31.4%) were from Asia, two (5.7%) were from Australia, and one (2.9%) combined European, United Kingdom, and American populations. The 5-year OS was 34.8 [95% CI = 30.6–39.5], with the highest OS in America at 40.5 [95% CI = 34.1–48.1], followed by Europe at 36.6 [95% CI = 30.6–43.7], Australia at 32.3 [95% CI = 12.5–83.8], and Asia at 28.1 [95% CI = 19.5–40.7]. The age-standardized incidence rate (ASIR) for SNMM ranges was between 0.07 and 0.14 per 100,000 persons/year, with a slightly higher incidence in women than in men; Conclusions: This meta-analysis, one of the largest to date on SNMM, confirms the aggressive nature of this melanoma subtype with poor survival outcomes. Despite geographic differences in survival rates, the overall 5-year survival remains low, highlighting the urgent need for improved treatment strategies and more research to improve patient outcomes. Full article

(This article belongs to the Special Issue Sinonasal and Skull Base Pathologies: Personalized Management Based on Radiological and Biological Fingerprint)

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18 pages, 584 KB

Open AccessEditor’s ChoiceSystematic Review

Diabetes Awareness Campaigns to Prevent Ketoacidosis at the Diagnosis of Type 1 Diabetes: Efficacy on Multiple Outcomes and Predictors of Success: A Systematic Review

by Elisa Minerba, Evelina Maines, Nadia Quaglia, Ludovica Fedi, Stefania Fanti, Alessandro Fierro and Enza Mozzillo

J. Pers. Med. 2024, 14(12), 1115; https://doi.org/10.3390/jpm14121115 - 21 Nov 2024

Cited by 13 | Viewed by 3233

Abstract

Background/Objectives: In Italy, the incidence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is still very high (35.7–39.6%), especially in youths. We aimed to determine the efficacy of awareness campaigns to prevent DKA on multiple outcomes and identify success predictors. [...] Read more.

Background/Objectives: In Italy, the incidence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is still very high (35.7–39.6%), especially in youths. We aimed to determine the efficacy of awareness campaigns to prevent DKA on multiple outcomes and identify success predictors. Methods: We searched electronic databases (Pubmed, Cochrane, and Web of Science) for studies published between 1 August 1990 and 1 August 2024. The review included studies that focused on children under 18 years old, and outcomes were measured by comparing before and after implementing the campaigns in the same area and between areas where interventions took place or not. Results: Of 236 records identified, 15 were eligible for analysis. After campaign implementation, the pooled DKA reduction resulted between 1% and 65.5%, based on the characteristics of the campaigns. A decrease in the rate of acute complications, such as cerebral edema, was reported. Hemoglobin A1c (HbA1c) at onset showed a mean reduction of 0.7–5.1%; C-peptide increased in patients without DKA at diagnosis, and length of hospitalization decreased. Campaign costs were lower than the costs of treating subjects with DKA. Conclusions: This review demonstrated that DKA awareness campaigns effectively reduce DKA incidence and improve other parameters, such as acute complications, HbA1c and C-peptide levels, length of hospitalization, and costs, among youths with T1D. To be effective, campaigns must follow specific principles of target population, modality, and minimal duration, as reported in this review. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives, 2nd Edition)

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17 pages, 1531 KB

Open AccessEditor’s ChoiceReview

Digital Twins’ Advancements and Applications in Healthcare, Towards Precision Medicine

by Konstantinos Papachristou, Paraskevi F. Katsakiori, Panagiotis Papadimitroulas, Lidia Strigari and George C. Kagadis

J. Pers. Med. 2024, 14(11), 1101; https://doi.org/10.3390/jpm14111101 - 11 Nov 2024

Cited by 113 | Viewed by 12586

Abstract

This review examines the significant influence of Digital Twins (DTs) and their variant, Digital Human Twins (DHTs), on the healthcare field. DTs represent virtual replicas that encapsulate both medical and physiological characteristics—such as tissues, organs, and biokinetic data—of patients. These virtual models facilitate [...] Read more.

This review examines the significant influence of Digital Twins (DTs) and their variant, Digital Human Twins (DHTs), on the healthcare field. DTs represent virtual replicas that encapsulate both medical and physiological characteristics—such as tissues, organs, and biokinetic data—of patients. These virtual models facilitate a deeper understanding of disease progression and enhance the customization and optimization of treatment plans by modeling complex interactions between genetic factors and environmental influences. By establishing dynamic, bidirectional connections between the DTs of physical objects and their digital counterparts, these technologies enable real-time data exchange, thereby transforming electronic health records. Leveraging the increasing availability of extensive historical datasets from clinical trials and real-world sources, AI models can now generate comprehensive predictions of future health outcomes for specific patients in the form of AI-generated DTs. Such models can also offer insights into potential diagnoses, disease progression, and treatment responses. This remarkable progression in healthcare paves the way for precision medicine and personalized health, allowing for high-level individualized medical interventions and therapies. However, the integration of DTs into healthcare faces several challenges, including data security, accessibility, bias, and quality. Addressing these obstacles is crucial to realizing the full potential of DHTs, heralding a new era of personalized, precise, and accurate medicine. Full article

(This article belongs to the Section Pharmacogenetics)

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