Journal of Personalized Medicine

16 pages, 2552 KiB

Open AccessArticle

Yeast-Produced Human Recombinant Lysosomal β-Hexosaminidase Efficiently Rescues GM2 Ganglioside Accumulation in Tay–Sachs Disease

by Orhan Kerim Inci, Andrés Felipe Leal, Nurselin Ates, Diego A. Súarez, Angela Johana Espejo-Mojica, Carlos Javier Alméciga-Diaz and Volkan Seyrantepe

J. Pers. Med. 2025, 15(5), 196; https://doi.org/10.3390/jpm15050196 (registering DOI) - 10 May 2025

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Abstract

Background: Tay–Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder characterized by the accumulation of GM2 ganglioside due to mutations in the HEXA gene, which encodes the α-subunit of β-Hexosaminidase A. This accumulation leads to significant neuropathological effects and premature death in [...] Read more.

Background: Tay–Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder characterized by the accumulation of GM2 ganglioside due to mutations in the HEXA gene, which encodes the α-subunit of β-Hexosaminidase A. This accumulation leads to significant neuropathological effects and premature death in affected individuals. No effective treatments exist, but enzyme replacement therapies are under investigation. In our previous work, we demonstrated the internalization and efficacy of human recombinant lysosomal β-hexosaminidase A (rhHex-A), produced in the methylotrophic yeast Pichia pastoris, in reducing lipids and lysosomal mass levels in fibroblasts and neural stem cells derived from patient-induced pluripotent stem cells (iPSCs). In this study, we further evaluated the potential of rhHex-A to prevent GM2 accumulation using fibroblast and neuroglia cells from a TSD patient alongside a relevant mouse model. Methods: Fibroblasts and neuroglial cell lines derived from a murine model and TSD patients were treated with 100 nM rhHexA for 72 h. After treatment, cells were stained by anti-GM2 (targeting GM2 ganglioside; KM966) and anti-LAMP1 (lysosomal-associated membrane protein 1) colocalization staining and incubated with 50 nM LysoTracker Red DND-99 to label lysosomes. In addition, GM2AP and HEXB expression were analyzed to assess whether rhHex-A treatment affected the levels of enzymes involved in GM2 ganglioside degradation. Results: Immunofluorescence staining for LysoTracker and colocalization studies of GM2 and Lamp1 indicated reduced lysosomal mass and GM2 levels. Notably, rhHex-A treatment also affected the expression of the HEXB gene, which is involved in GM2 ganglioside metabolism, highlighting a potential regulatory interaction within the metabolic pathway. Conclusions: Here, we report that rhHex-A produced in yeast can efficiently degrade GM2 ganglioside and rescue lysosomal accumulation in TSD cells. Full article

(This article belongs to the Special Issue Inborn Errors of Metabolism: From Pathomechanisms to Treatment)

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25 pages, 1626 KiB

Open AccessSystematic Review

Methodologies for the Emulation of Biomarker-Guided Trials Using Observational Data: A Systematic Review

by Faye D. Baldwin, Rukun K. S. Khalaf, Ruwanthi Kolamunnage-Dona and Andrea L. Jorgensen

J. Pers. Med. 2025, 15(5), 195; https://doi.org/10.3390/jpm15050195 - 10 May 2025

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Abstract

Background: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment [...] Read more.

Background: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment and/or determine eligibility, are often unfeasible in practice due to sample size requirements or ethical concerns. Here, we undertake a systematic review of methodologies used in target trial emulations, comparing treatment effectiveness, critically appraising them, and considering their applicability to the emulation of biomarker-guided trials. Methods: A comprehensive search strategy was developed to identify studies reporting on methods for target trial emulation comparing the effectiveness of treatments using observational data, and applied to the following bibliographic databases: PubMed, Scopus, Web of Science, and Ovid MEDLINE. A narrative description of methods identified in the review was undertaken alongside a critique of their relative strengths and limitations. Results: We identified a total of 59 papers: 47 emulating a target trial (‘application’ studies), and 12 detailing methods to emulate a target trial (‘methods’ studies). A total of 25 papers were identified as emulating a biomarker-guided trial (42%). While all papers reported methods to adjust for baseline confounding, 40% of application papers did not specify methods to adjust for time-varying confounding. Conclusions: This systematic review has identified a range of methods used to control for baseline, time-varying, and residual/unmeasured confounding within target trial emulation and provides a guide for researchers interested in emulation of biomarker-guided trials. Full article

(This article belongs to the Section Disease Biomarker)

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17 pages, 2456 KiB

Open AccessArticle

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

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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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10 pages, 571 KiB

Open AccessArticle

Study on the Epidemiological Characteristics, Treatment Patterns, and Factors Influencing the Timeliness of Treatment in Head and Neck Squamous Cell Carcinoma (HNSCC) in Stages III and IV: Experience of a Mexican Hospital

by Victor Manuel Oyervides Juarez, Daneli Ruiz Sanchez, Alejandro De Leon Cruz, Luis Angel Ceceñas Falcon, Marco Mendez Saenz, Carlos Alfredo Gomez de la Cruz, Mario Alberto Campos Coy, Juan Manuel Sánchez Castillo, Oscar Vidal Gutierrez, Joaquin Manzo Merino, Silvia Peralonso Bombin, Yuridia Evangelina Rodríguez Rosales, Gabriela Lugo Martinez, Jimena Maria Iglesias, Sebastian Medina Gonzalez and Claudia Catalina Beltran Rodriguez

J. Pers. Med. 2025, 15(5), 193; https://doi.org/10.3390/jpm15050193 - 9 May 2025

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Abstract

Objective: In Mexico, head and neck cancers pose a significant health burden. GLOBOCAN reported approximately 3183 new cases and 1636 deaths in 2020. Despite being the sixth leading cause of cancer incidence and mortality worldwide, data on epidemiology and treatment patterns in Mexico [...] Read more.

Objective: In Mexico, head and neck cancers pose a significant health burden. GLOBOCAN reported approximately 3183 new cases and 1636 deaths in 2020. Despite being the sixth leading cause of cancer incidence and mortality worldwide, data on epidemiology and treatment patterns in Mexico remain limited. This study aimed to characterize the profile, clinical features, and management of patients with Stage III–IVB head and neck squamous cell carcinoma (HNSCC) in a real-world setting. Methods: We retrospectively analyzed a database of 187 patients with Stage III, IVA, or IVB HNSCC treated at the University Hospital Dr. José Eleuterio González. Demographics, disease characteristics, and treatment patterns were summarized as frequencies and percentages. Exploratory endpoints included clinical outcomes and recurrence types. Results: The cohort was 82.9% male (n = 155). The most frequent tumor sites were the oral cavity (36.9%) and larynx (36.9%), with 55% (n = 103) diagnosed at stage IVA. Of 75 cases tested for p16, 35.3% (n = 36) were positive. The median time from symptom onset to diagnosis was 166.5 days (95% CI: 123.4–197.8) and from diagnosis to treatment 42 days (95% CI: 31.6–50.4). Initial treatments included surgery (36.4%), chemoradiotherapy (24.6%), induction chemotherapy (19.8%), supportive care (11.2%), and radiotherapy (8%). Locoregional control was achieved in 42.8% of patients, with an overall recurrence rate of 2.8%. Conclusions: This study provides real-world insights into the epidemiology and management of locally advanced HNSCC in Mexico, outlining the patient journey from initial symptoms to treatment and underscoring the need for more individualized therapeutic strategies based on molecular profiling and clinical characteristics. Full article

(This article belongs to the Section Epidemiology)

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16 pages, 1030 KiB

Open AccessSystematic Review

Three in a Bed: Can Partner Support Improve CPAP Adherence? A Systematic Review and Intervention Recommendations

by Giada Rapelli, Carola Caloni, Francesca Cattaneo, Marco Redaelli, Roberto Cattivelli, Giulia Landi, Eliana Tossani, Silvana Grandi, Gianluca Castelnuovo and Giada Pietrabissa

J. Pers. Med. 2025, 15(5), 192; https://doi.org/10.3390/jpm15050192 - 8 May 2025

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Abstract

Background/Objectives: Continuous positive airway pressure (CPAP) is the standard approach for treating obstructive sleep apnea syndrome (OSAS), but patient adherence is often low due to various influencing factors. Recently, researchers have increasingly begun to explore the influence of partner support on adherence [...] Read more.

Background/Objectives: Continuous positive airway pressure (CPAP) is the standard approach for treating obstructive sleep apnea syndrome (OSAS), but patient adherence is often low due to various influencing factors. Recently, researchers have increasingly begun to explore the influence of partner support on adherence to CPAP therapy. This systematic review seeks to consolidate current evidence regarding the impact of partner support on CPAP adherence in individuals with OSAS. Methods: A comprehensive literature search was carried out across PubMed, Scopus, Medline, PsycINFO, and Web of Science databases under PRISMA guidelines. Stringent inclusion criteria were used, and at least two independent reviewers screened all studies. The mixed methods appraisal tool (MMAT) was used to assess selected articles for quality. Data relevant to the review’s objectives were extracted and presented through narrative synthesis. The review protocol was preregistered (Prospero CRD420251016574). Results: Nine studies met the inclusion criteria. Findings highlighted the significant influence of adherence to CPAP. Partner support, relationship quality, and collaborative efforts emerged as facilitators of adherence, with partnered individuals exhibiting higher adherence to CPAP use. However, barriers such as anxiety, interruption in intimacy, and conflict in relationships were also identified. Conclusions: To the best of our knowledge, this is the first systematic review to synthesize evidence on the partner’s role in CPAP adherence and inform clinicians on the importance of providing personalized care based on biopsychosocial characteristics of patients; for example, assessing the partner support in the management of the illness. Furthermore, the findings emphasize the need for further research—particularly randomized controlled trials and dyadic designs—to deepen understanding of how partner dynamics influence effects of CPAP treatment. Full article

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

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11 pages, 811 KiB

Open AccessArticle

From Consultation to Collaboration: A Patient-Centered Approach to Shingles Pain and Postherpetic Neuralgia Management

by Yin-Tse Wu, Hsuan-Chih Lao, Sheng-Chin Kao, Ying-Chun Lin, Ying-Wei Yang, Ying-Hsin Li and Yi-Jun Chen

J. Pers. Med. 2025, 15(5), 191; https://doi.org/10.3390/jpm15050191 - 8 May 2025

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Abstract

Background/Objectives: Herpes zoster (shingles), caused by reactivation of the varicella zoster virus, often leads to acute pain that may progress to postherpetic neuralgia (PHN). Current evidence is insufficient to determine the optimal interventional treatment for these conditions. This study aimed to evaluate [...] Read more.

Background/Objectives: Herpes zoster (shingles), caused by reactivation of the varicella zoster virus, often leads to acute pain that may progress to postherpetic neuralgia (PHN). Current evidence is insufficient to determine the optimal interventional treatment for these conditions. This study aimed to evaluate the effectiveness of shared decision-making (SDM) forms developed by MacKay Memorial Hospital (MMH) in reducing patient anxiety and improving personalized care. Method: Between 1 August 2022 and 30 August 2024, we retrospectively reviewed SDM records of patients with shingles pain and PHN who were referred to the pain clinic for interventional treatment due to unresolved pain. The SDM forms were developed, reviewed, and authorized by the MMH Committee of Medical Quality and Safety. We analyzed the chosen interventions, anxiety levels, pain intensity, and patient preferences regarding treatment selection. Results: A total of 51 individuals (36 with shingles pain, 15 with PHN) were included in this cohort study. Most patients with acute or chronic zoster pain opted for subcutaneous steroid injections. Anxiety scores significantly decreased following SDM intervention, from 5.0 (IQR: 3.5–5.0) to 3.0 (IQR: 2.0–3.0) in shingles patients and from 5.0 (IQR: 4.0–5.0) to 2.0 (IQR: 2.0–3.0) in PHN patients. Pain intensity, measured using the numerical rating scale (NRS), also improved markedly after interventional pain management, with scores reducing from 8.0 (IQR: 6.0–9.0) to 3.0 (IQR: 1.0–6.5) in shingles patients and from 5.0 (IQR: 4.0–8.0) to 2.0 (IQR: 1.0–3.0) in PHN patients. Shingles patients expressed greater concern about the risks of interventional therapy complications, whereas PHN patients prioritized cost, complication rates, treatment frequency, and continuity of care. Additionally, SDM forms received high scores for promoting patient participation and knowledge, indicating that they improved their understanding of their condition and treatment options. Conclusions: SDM significantly improved patient comprehension, reduced anxiety, facilitated informed treatment decisions, and strengthened doctor–patient communication for those with shingles pain and PHN. Full article

(This article belongs to the Special Issue How to Undertake Personalized Assessments and Cures for Pain)

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12 pages, 744 KiB

Open AccessReview

Tissue Preservation and Access: Modern Innovation in Biobanking Moving Forwards a Personalized Treatment

by Chiara Tessari, Saima Jalil Imran, Nukhba Akbar and Gino Gerosa

J. Pers. Med. 2025, 15(5), 190; https://doi.org/10.3390/jpm15050190 - 7 May 2025

Viewed by 58

Abstract

Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal [...] Read more.

Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal therapeutic approach that is still not fully resolved. There are multiple ways to preserve heart tissue grafts, and the choice of method is solely dependent upon the nature and complexity of the tissue and the length of storage. The conventional cold storage method provides the base to nearly all of the preservation protocols for short- and long-term storage. Short-term storage methods frequently rely on designing preserving solutions to protect the graft against warm and cold ischemia at the temperature above freezing point. As ice-nucleation is the major notorious phenomenon during graft preservation, the modern era of research is focusing on developing ice-free preservation techniques, termed vitrification. However, despite the promising outcomes of vitrification, there are several recognized hurdles required to be overcome to build a biobank of heart grafts for an extended period of time. Besides tissue deterioration due to extreme cold temperature, there is another extreme phenomenon of tissue rejection mainly caused by the presence of cellular antigens. The modern approach of decellularization has the potential to minimize the chances of tissue rejection by removing the cells and providing a structural support and sustained biochemical signal via keeping the extracellular matrix of the graft intact. In conclusion, both nano-warming and decellularization are the leading approaches that have great potential to store the graft tissue in its optimal form via keeping its viability safe for a longer time and extending its applicability. This review article outlines a variety of approaches for the preservation and bioengineering of tissue to fulfill the need for the availability of on-shelf long-lasting grafts both in clinical and laboratory setups. Full article

(This article belongs to the Special Issue Updates on Heart Valve Diseases: Personalized Treatment and Management)

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12 pages, 2852 KiB

Open AccessArticle

Real-Life Treatment Intervals and Morphological Outcomes Following the Switch to Faricimab Therapy in Neovascular Age-Related Macular Degeneration

by Katrin Löw, Vasilena Sitnilska, Yuhe Tang, Jeany Q. Lammert, Tim U. Krohne and Lebriz Altay

J. Pers. Med. 2025, 15(5), 189; https://doi.org/10.3390/jpm15050189 - 6 May 2025

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Abstract

Objectives: To evaluate the efficacy of faricimab in patients with neovascular age-related macular degeneration (nAMD) that did not respond to other VEGF inhibitors. Methods: This retrospective study included the eyes of patients diagnosed with nAMD who had been switched to faricimab [...] Read more.

Objectives: To evaluate the efficacy of faricimab in patients with neovascular age-related macular degeneration (nAMD) that did not respond to other VEGF inhibitors. Methods: This retrospective study included the eyes of patients diagnosed with nAMD who had been switched to faricimab treatment due to the persistence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), despite monthly anti-VEGF treatment with aflibercept, bevacizumab, or ranibizumab using the treat and extend regimen, and who had received at least three faricimab injections following the switch. Best-corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) analysis were performed at each visit, and the OCT results were graded by two independent readers. Results: We included 41 eyes of 39 patients (21 male, 18 female) with a mean age of 80.5 ± 8.1 years. The median duration of anti-VEGF treatment prior to the switch to faricimab was 5.0 years, with a median of 53 injections. Complete resolution of IRF and SRF was observed after the first dose of faricimab in 12 eyes (29.3%) and after the third dose in 15 eyes (36.6%). Twenty-eight eyes reached a follow-up time after a switch of at least 12 months, with a median of 10 faricimab injections. Of these 28 eyes, 10 eyes (35.7%) exhibited complete IRF/SRF resolution; treatment intervals were extended beyond 4 weeks in 21 eyes (80.7%), and 8 eyes (28.6%) presented complete IRF/SRF resolution under extended treatment intervals at month 12. Central retinal thickness after 12 months was reduced from a median of 368.0 µm to 297.5 µm (p < 0.001), and the BCVA remained stable (p = 0.057). No adverse events were reported throughout the entire treatment period. Conclusions: In nAMD patients with poor anti-VEGF treatment response, complete and fast fluid resolution and the extension of treatment intervals can be reached by switching to faricimab, even after years of prior unsuccessful therapy. Full article

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

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3 pages, 321 KiB

Open AccessCorrection

Correction: Zieliński, G.; Gawda, P. Analysis of the Use of Sample Size and Effect Size Calculations in a Temporomandibular Disorders Randomised Controlled Trial—Short Narrative Review. J. Pers. Med. 2024, 14, 655

by Grzegorz Zieliński and Piotr Gawda

J. Pers. Med. 2025, 15(5), 188; https://doi.org/10.3390/jpm15050188 - 6 May 2025

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Abstract

In the original publication [...] Full article

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11 pages, 3510 KiB

Open AccessArticle

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

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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 Clinical Medicine, Cell, and Organism Physiology)

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9 pages, 722 KiB

Open AccessArticle

Accuracy of Patient-Specific Osteosynthesis in Bimaxillary Surgery: Comparative Feasibility Analysis of Four- and Two-Miniplate Fixation

by Hylke van der Wel, Haye Glas, Johan Jansma and Rutger Schepers

J. Pers. Med. 2025, 15(5), 186; https://doi.org/10.3390/jpm15050186 - 4 May 2025

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Abstract

Background/Objectives: Patient-specific osteosynthesis (PSO) plates, in combination with virtual surgical planning (VSP), have significantly improved the accuracy of orthognathic surgery. This study aimed to compare the surgical accuracy of two-plate versus four-plate fixation methods in Le Fort I osteotomies using PSO. Methods [...] Read more.

Background/Objectives: Patient-specific osteosynthesis (PSO) plates, in combination with virtual surgical planning (VSP), have significantly improved the accuracy of orthognathic surgery. This study aimed to compare the surgical accuracy of two-plate versus four-plate fixation methods in Le Fort I osteotomies using PSO. Methods: A retrospective cohort study was conducted on 21 patients who underwent maxilla-first bimaxillary surgery at a single centre in 2024. Eight patients received two-plate fixation, while thirteen received four-plate fixation. All surgeries were planned using VSP. Postoperative cone beam computed tomography scans were used to assess the accuracy of maxillary positioning by comparing the planned versus achieved outcomes in terms of translation and rotation. Results: Both fixation methods yielded comparable results in maxillary positioning, with no significant differences observed between the two groups regarding translational or rotational deviations. The two-plate PSO approach demonstrated practical benefits, including reduced material usage and the potential for smaller surgical incisions, without compromising surgical accuracy. Conclusions: Two-plate PSO fixation is a viable alternative to the traditional four-plate method for Le Fort I osteotomies, offering similar accuracy with potential procedural advantages. While these findings support broader clinical adoption, further research is warranted to confirm the results in larger cohorts and to investigate biomechanical considerations. Full article

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

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15 pages, 5739 KiB

Open AccessArticle

Prevalence of Actionable Exposures to Pharmacogenetic Medications Among Solid Organ Transplant Recipients in a Population-Scale Biobank

by Alaa Radwan, Kimberly M. Deininger, Amrut V. Ambardekar, Heather D. Anderson, Nicholas Rafaels, Laura M. Saba, The Colorado Center for Personalized Medicine and Christina L. Aquilante

J. Pers. Med. 2025, 15(5), 185; https://doi.org/10.3390/jpm15050185 - 2 May 2025

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Abstract

Background/Objectives: Solid organ transplant (SOT) recipients are exposed to multiple medications, many of which have pharmacogenetic (PGx) prescribing recommendations. This study leveraged data from a population-scale biobank and an enterprise data warehouse to determine the prevalence of actionable exposures to PGx medications [...] Read more.

Background/Objectives: Solid organ transplant (SOT) recipients are exposed to multiple medications, many of which have pharmacogenetic (PGx) prescribing recommendations. This study leveraged data from a population-scale biobank and an enterprise data warehouse to determine the prevalence of actionable exposures to PGx medications among kidney, heart, and lung transplant recipients during the first six months post-transplant. Methods: We conducted a retrospective analysis of adult SOT patients with genetic data available from the Colorado Center for Personalized Medicine (CCPM) biobank and clinical data from Health Data Compass (HDC). We evaluated 29 variants in 13 pharmacogenes and 42 Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B medications (i.e., sufficient evidence to recommend at least one prescribing action based on genetics). The primary outcome was actionable exposure to a PGx medication (i.e., actionable phenotype and a prescription for an affected PGx medication). Results: The study included 358 patients. All patients were prescribed at least one PGx medication, and 49.4% had at least one actionable exposure to a PGx medication during the first six months post-transplant. The frequency of actionable exposure was highest for tacrolimus (15.4%), followed by proton pump inhibitors (PPIs) (15.1%) and statins (12.8%). Statin actionable exposures significantly differed by transplant type, likely due to variations in prescribing patterns and actionable phenotypes for individual statins. Conclusions: Our findings highlight the potential clinical utility of PGx testing among SOT patients. Further studies are needed to address the impact on clinical outcomes and the optimal timing of PGx testing in the SOT population. Full article

(This article belongs to the Section Pharmacogenetics)

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13 pages, 1104 KiB

Open AccessReview

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

Viewed by 375

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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11 pages, 627 KiB

Open AccessSystematic Review

Endoscopic Sinus Surgery in Frontal Sinus Inverted Papilloma: A Systematic Review

by Maxime Fieux, Valentin Favier, Andre Sousa Machado, Mikail Nourredine, Caroline Giroudon, Florent Carsuzaa, Paresh P. Naik and the yo-IFOS Group

J. Pers. Med. 2025, 15(5), 183; https://doi.org/10.3390/jpm15050183 - 2 May 2025

Viewed by 226

Abstract

Background: Frontal sinus inverted papilloma (IP) is a particularly rare form of IP and its management is challenging, with a high rate of recurrence. Objectives: Our aim was to evaluate the recurrence rate of frontal sinus IP after surgery and compare [...] Read more.

Background: Frontal sinus inverted papilloma (IP) is a particularly rare form of IP and its management is challenging, with a high rate of recurrence. Objectives: Our aim was to evaluate the recurrence rate of frontal sinus IP after surgery and compare this rate according to the surgical modality (purely endoscopic sinus surgery vs. a combined/open approach). Design: A systematic review without meta-analysis conducted by a working group of the Young Otolaryngologists of the International Federation of Otorhinolaryngological Societies (yo-IFOS). Data Sources and Methods: A systematic analysis of the literature was performed and reported following the criteria laid down in the SWiM guidelines. The review was registered on Prospero, a dedicated software was used for screening (Covidence), and R (v.4.2.2) was used for statistical analysis. Eligible articles were studies reporting at least five cases of frontal sinus IP surgically treated. Results: A total of 2925 studies were identified based on the MeSH equation, and 39 studies were included (n = 642 patients). Among the studies included, the recurrence rate was 18.4% (118/642) with a mean time to recurrence of 25.6 (±11.7) months. The difference between surgical modalities was not statistically significant in terms of recurrence rate (14.7% vs. 16.5%; p = 0.675). Conclusions: The recurrence rate of frontal sinus IP is not different between surgical modalities. However, it does not reduce the need for a tailored therapeutic strategy, as other factors also need to be considered (time to recurrence, complications, quality of life) when choosing the most appropriate approach. Full article

(This article belongs to the Special Issue Personalized Medicine for Otolaryngology (ENT))

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10 pages, 715 KiB

Open AccessArticle

Association of MMP-8 -799C/T Polymorphism with Peri-Implantitis: A Cross-Sectional Study

by Ioannis Fragkioudakis, Christine Kottaridi, Aikaterini-Elisavet Doufexi, Konstantinos Papadimitriou, Leonidas Batas and Dimitra Sakellari

J. Pers. Med. 2025, 15(5), 182; https://doi.org/10.3390/jpm15050182 - 1 May 2025

Viewed by 191

Abstract

Purpose: This study explored the relationship between matrix metalloproteinase−8 (MMP−8) gene polymorphisms (−799C/T, −381A/G, and +17C/G) and peri-implantitis, examining clinical parameters including the probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Methods: This cross-sectional study involved 120 [...] Read more.

Purpose: This study explored the relationship between matrix metalloproteinase−8 (MMP−8) gene polymorphisms (−799C/T, −381A/G, and +17C/G) and peri-implantitis, examining clinical parameters including the probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Methods: This cross-sectional study involved 120 participants categorized into peri-implantitis and healthy implant groups according to the 2018 classification criteria for periodontal and peri-implant diseases. Saliva samples were analyzed for MMP−8 polymorphisms using polymerase chain reaction (PCR) and Sanger sequencing. Statistical analyses were conducted to evaluate genotype- and allele-specific risks and their associations with clinical parameters. Results: Among the 95 samples analyzed, the −799C/T polymorphism was significantly associated with peri-implantitis, with T allele carriers having a higher diagnosis rate (odds ratio: 3.04, p = 0.010). Although T allele carriers exhibited higher mean values for the probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP), these differences were not statistically significant across genotypes. No associations were found between the −381A/G and +17C/G polymorphisms and peri-implantitis clinical parameters. Conclusions: The −799C/T polymorphism, specifically the T allele, is strongly linked to peri-implantitis, indicating its potential as a genetic marker for disease susceptibility. Further research is required to investigate the role of MMP-8 polymorphisms in peri-implant diseases and to advance the development of personalized diagnostic tools. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 3596 KiB

Open AccessArticle

Central Nervous System Metastases from Primary Lung Carcinoma: Significance of RNA Fusion Testing and Early Versus Late Metastases

by Michelle Garlin Politis, Mahesh Mansukhani, Benjamin O. Herzberg, Lanyi N. Chen, Mark Stoopler, Maelle Saliba, Markus Siegelin, Zhe Zhu, Joshua Sonett, Brian S. Henick, Simon K. Cheng, Swarnali Acharyya, Catherine A. Shu, Michael L. Miller, Benjamin Izar, Helen Fernandes, Susan Hsiao and Anjali Saqi

J. Pers. Med. 2025, 15(5), 181; https://doi.org/10.3390/jpm15050181 - 1 May 2025

Viewed by 191

Abstract

Background/Objectives: While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance [...] Read more.

Background/Objectives: While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA–reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. Methods: We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA–reflex RNA next-generation sequencing (NGS). The DNA NGS panel included the driver mutations EGFR, BRAF, KRAS, MET, and ERBB2. RNA NGS included ALK, RET, ROS1, and MET. Additionally, mutational profiles were examined between those with early versus late CNS metastases. Results: Of the 58 patients, 44 (75.9%) had mutations or alterations, including 34 identified by DNA NGS [EGFR (n = 17; 50.0%), KRAS (n = 15; 44.1%), MET (n = 2; 5.9%)] and 10/24 by RNA NGS [ALK (n = 7; 70%), MET (n = 2; 20%), ROS1 (n = 1; 10%)]. Of all patients, 32 (55%) presented with early and 26 (45%) with late CNS metastases. Although patients with early metastases had worse survival compared to those with late metastases (p < 0.001), there were no statistically significant differences in the mutational profiles between the two cohorts. Conclusions: A significant proportion of CNS metastases without driver mutations identified by DNA NGS had targetable alterations identified by RNA NGS (10/24, 41.7%). In summary, a combined DNA with reflex RNA fusion testing approach plays a significant role in detecting and potentially managing CNS metastases. Comprehensive prospective studies are essential to elucidate the differences between early and late CNS metastases. Full article

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

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16 pages, 251 KiB

Open AccessArticle

Personalized Care in Advance Care Planning with Cancer and Chronic Progressive Diseases Using the Go Wish Game

by Sara Alquati, Marta Perin, Simona Sacchi, Ludovica De Panfilis and Silvia Tanzi

J. Pers. Med. 2025, 15(5), 180; https://doi.org/10.3390/jpm15050180 - 30 Apr 2025

Viewed by 225

Abstract

Background: The Go Wish Game (GWG) is a card game designed to ease Advance Care Planning (ACP) discussions. It helps patients to consider their values and priorities, and to share them with families and healthcare professionals (HPs). Despite a general appreciation of the [...] Read more.

Background: The Go Wish Game (GWG) is a card game designed to ease Advance Care Planning (ACP) discussions. It helps patients to consider their values and priorities, and to share them with families and healthcare professionals (HPs). Despite a general appreciation of the GWG, mechanisms related to its implementation have been poorly investigated. Objective: to determine optimal strategies for integration of the GWG into clinical practice and to investigate the experiences of a Palliative Care Unit (PCU) trained in the use of the GWG. Methods: We performed a descriptive qualitative study. Data were collected through a focus group (FG) and we followed the thematic analysis. The PCU’s team described their experience using the GWG focusing on 15 patients (9 oncological, 6 non-oncological) patients, managed by the PCU. Results: Our data revealed five main themes, along with their subthemes: (1) personalizing the GWG proposal; (2) the role of the caregiver; (3) organizational aspects; (4) meaning of the GWG in clinical practice, and (5) dealing with patient’s priorities. Comparison of real-life cases has led to the identification of specific facilitators and barriers that can hinder or promote the use of the GWG for personalized medicine. Conclusions: Findings suggest that certain aspects still require attention in GWG implementation, particularly regarding the training and competencies (communicative, relational, ethical) of the healthcare professionals, and the process leading to the proposal of the GWG to the patient. Full article

(This article belongs to the Special Issue New Insights into Personalized Care in Advance Care Planning)

24 pages, 2869 KiB

Open AccessSystematic Review

Comparison of Depression in Hemodialysis, Peritoneal Dialysis, and Kidney Transplant Patients: A Systematic Review with Meta-Analysis

by Gloria M. Zaragoza-Fernández, José C. De La Flor, Verónica Fernández Abreu, Elisa Iglesias Castellano, Laura Rodríguez-Barbero Requena and Rafael Fernández Castillo

J. Pers. Med. 2025, 15(5), 179; https://doi.org/10.3390/jpm15050179 - 28 Apr 2025

Viewed by 381

Abstract

Background: Depression is a common comorbidity in patients with chronic kidney disease undergoing renal replacement therapy. This meta-analysis compares depression prevalence across hemodialysis, peritoneal dialysis, and kidney transplantation, considering mean age, treatment duration, comorbidities (diabetes and hypertension), and measurement instruments. Methods: A systematic [...] Read more.

Background: Depression is a common comorbidity in patients with chronic kidney disease undergoing renal replacement therapy. This meta-analysis compares depression prevalence across hemodialysis, peritoneal dialysis, and kidney transplantation, considering mean age, treatment duration, comorbidities (diabetes and hypertension), and measurement instruments. Methods: A systematic review and meta-analysis of 16 studies involving 26,301 participants was conducted in accordance with PRISMA guidelines and registered in PROSPERO. It analyzed observational studies (2000–2024) on depression in patients receiving hemodialysis, peritoneal dialysis, or kidney transplantation. Data extraction included sample size, mean age, treatment duration, comorbidities, and measurement instruments. Random-effects models calculated the standardized mean differences and pooled prevalence estimates. Heterogeneity (Cochran’s Q, I²) and publication bias (Egger’s test) were assessed. Results: Depression prevalence was 35.56% (95% CI: 34.2–37.0%) in hemodialysis, 35.09% (95% CI: 33.5–36.7%) in peritoneal dialysis, and 25.33% (95% CI: 24.0–26.6%) in kidney transplant recipients. No significant differences were found between hemodialysis and peritoneal dialysis. Mean age, treatment duration, comorbidities, and measurement instruments were not significantly associated with depression prevalence. Conclusions: Kidney transplantation is linked to a lower depression prevalence than dialysis, while no significant differences exist between hemodialysis and peritoneal dialysis. These findings highlight the need to ensure timely transplantation access and enhance psychological support for dialysis patients. Further research should explore psychosocial factors and targeted interventions to improve mental health in this population. Full article

(This article belongs to the Special Issue Kidney Disease: From Basic Research to Clinical Practice)

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12 pages, 631 KiB

Open AccessReview

A Scoping Review of Precision Medicine in Breast Reconstruction (2011–2025)

by Zain Aryanpour, Alec S. McCranie, Jason W. Yu, Julian Winocour, Katie G. Egan, David Mathes and Christodoulos Kaoutzanis

J. Pers. Med. 2025, 15(5), 178; https://doi.org/10.3390/jpm15050178 - 28 Apr 2025

Viewed by 218

Abstract

Background: Personalization of medical care is a significant topic of interest. Precision medicine denotes customized medical treatments based on individual genetic, molecular, and/or biomarker data. We conducted a scoping review to identify studies exploring precision medicine in breast reconstruction. Objectives: (1) To map [...] Read more.

Background: Personalization of medical care is a significant topic of interest. Precision medicine denotes customized medical treatments based on individual genetic, molecular, and/or biomarker data. We conducted a scoping review to identify studies exploring precision medicine in breast reconstruction. Objectives: (1) To map the existing literature, (2) to identify key concepts, and (3) to discuss current and future clinical implications of precision medicine in breast reconstruction. Eligibility criteria: Indexed journal articles (primary research studies) relating to precision medicine in breast reconstruction written in the English language. Sources of evidence: Medline (via Pubmed), Web of Science, and the Cochrane Library. Charting methods: Data charting of selected studies was performed independently by two reviewers using Microsoft Excel. Any discrepancies in data charting were addressed through inter-reviewer discussion and/or expert review. Results: Of 321 initial records, 9 studies that were published between 2011 and 2025 were included in the final review. Eight studies focused predominantly on genomics, and one study focused predominantly on targeted therapies. Genomic-based studies were frequently implemented to evaluate patient risk and inform clinical decision-making, while targeted therapies were used to optimize reconstructive outcomes through cell-based therapies. Conclusions: There is a limited but emerging body of literature on precision medicine in breast reconstruction. Genomic data are the driving force of precision medicine in breast reconstruction, and multiple potential avenues exist to achieve translational applications in the short-term period. Future efforts should focus on translating known genomic data into real-time clinical applications and investing in precision-based research for targeted therapies and regenerative medicine in breast reconstruction. Full article

(This article belongs to the Special Issue Precision Medicine in Plastic Surgery and Reconstruction)

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33 pages, 718 KiB

Open AccessReview

Proteomics in Diagnostic Evaluation and Treatment of Breast Cancer: A Scoping Review

by Menelaos Zafrakas, Ioannis Gavalas, Panayiota Papasozomenou, Christos Emmanouilides and Maria Chatzidimitriou

J. Pers. Med. 2025, 15(5), 177; https://doi.org/10.3390/jpm15050177 - 27 Apr 2025

Viewed by 370

Abstract

Objectives: The aim of this scoping review was to delineate the current role and possible applications of proteomics in personalized breast cancer diagnostic evaluation and treatment. Methods: A comprehensive search in PubMed/MEDLINE and Scopus/EMBASE was conducted, according to the PRISMA–ScR guidelines. Inclusion criteria: [...] Read more.

Objectives: The aim of this scoping review was to delineate the current role and possible applications of proteomics in personalized breast cancer diagnostic evaluation and treatment. Methods: A comprehensive search in PubMed/MEDLINE and Scopus/EMBASE was conducted, according to the PRISMA–ScR guidelines. Inclusion criteria: proteomic studies of specimens from breast cancer patients, clinically relevant studies and clinical studies. Exclusion criteria: in silico, in vitro and studies in animal models, review articles, case reports, case series, comments, editorials, and articles in language other than English. The study protocol was registered in the Open Science Framework. Results: In total, 1093 records were identified, 170 papers were retrieved and 140 studies were selected for data extraction. Data analysis and synthesis of evidence showed that most proteomic analyses were conducted in breast tumor specimens (n = 77), followed by blood samples (n = 48), and less frequently in other biologic material taken from breast cancer patients (n = 19). The most commonly used methods were liquid chromatography–tandem mass spectrometry (LC–MS/MS), followed by Matrix-assisted laser desorption/ionization-time of flight (MALDI–TOF), Surface-Enhanced Laser Desorption/Ionization Time-of-Flight (SELDI–TOF) and Reverse Phase Protein Arrays (RPPA). Conclusions: The present review provides a thorough map of the published literature reporting clinically relevant results yielded from proteomic studies in various biological samples from different subgroups of breast cancer patients. This analysis shows that, although proteomic methods are not currently used in everyday practice to guide clinical decision-making, nevertheless numerous proteins identified by proteomics could be used as biomarkers for personalized diagnostic evaluation and treatment of breast cancer patients. Full article

(This article belongs to the Special Issue Breast Cancer: Current Trends and Future Challenges in Evaluation and Treatment)

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13 pages, 601 KiB

Open AccessArticle

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

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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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22 pages, 332 KiB

Open AccessReview

Personalized Medical Approach in Gastrointestinal Surgical Oncology: Current Trends and Future Perspectives

by Dae Hoon Kim

J. Pers. Med. 2025, 15(5), 175; https://doi.org/10.3390/jpm15050175 - 27 Apr 2025

Viewed by 290

Abstract

Advances in artificial intelligence (AI), multi-omic profiling, and sophisticated imaging technologies have significantly advanced personalized medicine in gastrointestinal surgical oncology. These technological innovations enable precise patient stratification, tailored surgical strategies, and individualized therapeutic approaches, thereby significantly enhancing clinical outcomes. Despite remarkable progress, challenges [...] Read more.

Advances in artificial intelligence (AI), multi-omic profiling, and sophisticated imaging technologies have significantly advanced personalized medicine in gastrointestinal surgical oncology. These technological innovations enable precise patient stratification, tailored surgical strategies, and individualized therapeutic approaches, thereby significantly enhancing clinical outcomes. Despite remarkable progress, challenges persist, including the standardization and integration of diverse data types, ethical concerns regarding patient privacy, and rigorous clinical validation of predictive models. Addressing these challenges requires establishing international standards for data interoperability, such as Fast Healthcare Interoperability Resources, and adopting advanced security methods, such as homomorphic encryption, to facilitate secure multi-institutional data sharing. Moreover, ensuring model transparency and explainability through techniques such as explainable AI is critical for fostering trust among clinicians and patients. The successful integration of these advanced technologies necessitates strong multidisciplinary collaboration among surgeons, radiologists, geneticists, pathologists, and oncologists. Ultimately, the continued development and effective implementation of these personalized medical strategies complemented by human expertise promise a transformative shift toward patient-centered care, improving long-term outcomes for patients with gastrointestinal cancer. Full article

(This article belongs to the Special Issue Personalized Medicine in Gastrointestinal Surgical Oncology)

13 pages, 1543 KiB

Open AccessReview

Personalized Surgical Approach for Nonunion of the Second Metatarsal Fracture and Post-Traumatic Metatarsalgia: A Case Report and Literature Review

by Roberto Bevoni, Elena Artioli, Marco Di Ponte, Silvio Caravelli and Massimiliano Mosca

J. Pers. Med. 2025, 15(5), 174; https://doi.org/10.3390/jpm15050174 - 27 Apr 2025

Viewed by 192

Abstract

Nonunion of the second metatarsal presents a significant clinical challenge, often leading to pain, functional impairment, and deformity. Various treatment strategies have been described in the literature, tailored to the patient’s specific characteristics. To provide a comprehensive overview of the available therapeutic options, [...] Read more.

Nonunion of the second metatarsal presents a significant clinical challenge, often leading to pain, functional impairment, and deformity. Various treatment strategies have been described in the literature, tailored to the patient’s specific characteristics. To provide a comprehensive overview of the available therapeutic options, a literature review was conducted. In this context, this article aims to present an innovative and personalized surgical technique for patients with nonunion and an altered metatarsal formula following a proximal shaft fracture of the second metatarsal. This technique enables the simultaneous consolidation of the nonunion and restoration of metatarsal alignment, with favorable clinical, functional, and radiological outcomes observed over a three-year follow-up period. Full article

(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)

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11 pages, 1035 KiB

Open AccessArticle

Short-Term Changes in Tear Film Stability and Tear Volume Following the Application of Various DED Management Options in a Healthy Young Population

by Belén Sabucedo-Villamarin, Jacobo Garcia-Queiruga, Laura Cacabelos-Torres, Maria J. Giraldez, Eva Yebra-Pimentel and Hugo Pena-Verdeal

J. Pers. Med. 2025, 15(5), 173; https://doi.org/10.3390/jpm15050173 - 27 Apr 2025

Viewed by 304

Abstract

Background: To determine short-term changes in tear film volume and stability after various treatments for dry eye disease in healthy participants. Methods: 36 healthy participants aged from 18 to 35 years were recruited for a single-session examination and randomly assigned to one of [...] Read more.

Background: To determine short-term changes in tear film volume and stability after various treatments for dry eye disease in healthy participants. Methods: 36 healthy participants aged from 18 to 35 years were recruited for a single-session examination and randomly assigned to one of three treatment groups (1:1:1 treatment, 1:1 eye): Group 1 (artificial tears ‘Comfort Drops’), Group 2 (eyelid wipes ‘Systane Lid Wipes’), and Group 3 (ocular bath ‘Acuaiss’). Tear Meniscus Height (TMH) was assessed at baseline, 2, 5, 10, 15, and 20 min, and Non-Invasive Break-Up Time (NIBUT) at baseline, 2, 10, and 20 min, all using the OCULUS Keratograph 5M by one examiner. Results: Of the initially recruited participants, 35 were analyzed; one was excluded for reflex tearing. Group 1 (n = 12) showed a significant TMH increase at 2 min compared to 10 and 20 min (Friedman, p = 0.004; Bonferroni, p ≤ 0.028). Group 3 (n = 12) showed a significant increase at 2 and 5 min compared to baseline and decrease at 10 min against 2 and 5 min (Friedman, p < 0.001; Bonferroni, p ≤ 0.034). Group 2 (n = 11) showed no significant changes over time (Friedman, p = 0.108). NIBUT showed no significant differences at any time-point in any group (Friedman, p ≥ 0.231). Basal TMH differed between groups (ANOVA, p = 0.048), but post hoc analysis found no significance (Bonferroni, all p ≥ 0.088). No significant differences in TMH at other time-points (Kruskal–Wallis/ANOVA, p ≥ 0.265) or in NIBUT between groups (Kruskal–Wallis/ANOVA, p = 0.108) were found. Conclusions: In healthy participants, artificial tears and ocular baths temporarily increase TMH, while eyelid wipes do not. Neither has an immediate impact on NIBUT. Full article

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

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37 pages, 2066 KiB

Open AccessReview

Redefining Non-Motor Symptoms in Parkinson’s Disease

by Laura Peña-Zelayeta, Karen M. Delgado-Minjares, Marcos M. Villegas-Rojas, Karen León-Arcia, Alberto Santiago-Balmaseda, Jesús Andrade-Guerrero, Isaac Pérez-Segura, Emmanuel Ortega-Robles, Luis O. Soto-Rojas and Oscar Arias-Carrión

J. Pers. Med. 2025, 15(5), 172; https://doi.org/10.3390/jpm15050172 - 26 Apr 2025

Viewed by 430

Abstract

Parkinson’s disease involves widespread neurodegeneration that extends far beyond the basal ganglia, giving rise to a diverse range of non-motor symptoms that frequently emerge before motor onset. These include autonomic dysfunction, cognitive decline, neuropsychiatric disturbances, sleep-related disorders, and sensory deficits. Here, we synthesize [...] Read more.

Parkinson’s disease involves widespread neurodegeneration that extends far beyond the basal ganglia, giving rise to a diverse range of non-motor symptoms that frequently emerge before motor onset. These include autonomic dysfunction, cognitive decline, neuropsychiatric disturbances, sleep-related disorders, and sensory deficits. Here, we synthesize current evidence on the anatomical, neurochemical, and network-level mechanisms that drive these symptoms, and we examine how they shape disease progression and clinical heterogeneity. We highlight the limitations of dopamine-centric models and advocate for a framework that treats non-motor symptoms as the disorder’s primary, mechanistically distinct features. We also discuss how emerging technologies—such as multi-omic profiling, artificial intelligence, and network neuroscience—enable earlier identification, stratification of non-motor phenotypes, and the development of precision-based therapeutic strategies. Recognizing non-motor symptoms as central to Parkinson’s disease redefines how the disorder should be diagnosed, studied, and treated. Full article

(This article belongs to the Special Issue Neurodegenerative Diseases: Molecular Pathology and Personalized Treatment)

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15 pages, 976 KiB

Open AccessArticle

Oxidative Stress Biomarkers as Preclinical Markers of Mild Cognitive Impairment: The Impact of Age and Sex

by Stavroula Ioannidou, Magda Tsolaki, Argyrios Ginoudis, Androniki Tamvakis, Anthoula Tsolaki, Kali Makedou and Evgenia Lymperaki

J. Pers. Med. 2025, 15(5), 171; https://doi.org/10.3390/jpm15050171 - 26 Apr 2025

Viewed by 287

Abstract

Background: Reactive oxygen species (ROS) are involved in the pathophysiology of neurodegeneration and cognitive decline, indicating the potential use of oxidative stress biomarkers for early diagnosis. Mild cognitive impairment (MCI) is defined as a cognitive decline beyond normal aging, without significant impact on [...] Read more.

Background: Reactive oxygen species (ROS) are involved in the pathophysiology of neurodegeneration and cognitive decline, indicating the potential use of oxidative stress biomarkers for early diagnosis. Mild cognitive impairment (MCI) is defined as a cognitive decline beyond normal aging, without significant impact on daily functioning, and is considered an important stage of early detection of neurodegeneration. This study aimed to investigate serum and cerebrospinal fluid (CSF) levels of oxidative stress biomarkers, total ROS and malondialdehyde (MDA) in patients with MCI to evaluate their utility in the early diagnosis of Alzheimer’s disease (AD). Levels of oxidative stress biomarkers were also assessed according to age and sex, as well as their correlation with the established CSF biomarkers, including amyloid-beta (Aβ40, Aβ42 and Aβ42/Aβ40 ratio), phosphorylated tau protein (p-tau) and total tau (t-tau). Methods: A total of 114 adults were divided into three groups: MCI (A−) patients with a normal CSF Aβ42/Aβ40 ratio (n = 38), MCI (A+) patients with an abnormal Aβ42/Aβ40 ratio (n = 38) and healthy cognitive function individuals with a normal Aβ42/Aβ40 ratio (n = 38). Established CSF biomarkers were conducted using an automated immunochemical method, while total ROS levels were measured by fluorometry and MDA levels were determined by competitive inhibition enzyme immunoassay. Results: A statistically significant difference was observed in CSF MDA levels (p < 0.05) and serum ROS levels (p < 0.05) between the study groups. Sex analysis revealed significantly higher levels of CSF MDA levels in the MCI (A+) males’ group (p < 0.05). In terms of age categorization, serum MDA levels were markedly higher in the MCI (A+) group of older patients (p < 0.01). Conclusions: These findings highlight the importance of individualized approaches, including investigation of oxidative stress biomarkers profile to prevent and manage individuals in the early stages of MCI, considering demographic factors. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Therapy in Diseases)

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10 pages, 1773 KiB

Open AccessArticle

Clinical and Surgical Insights into Zuska Disease: A Retrospective Analysis

by Letizia Cuniolo, Raquel Diaz, Francesca Pitto, Federica Murelli, Chiara Cornacchia, Francesca Depaoli, Marco Gipponi, Cecilia Margarino, Chiara Boccardo, Simonetta Franchelli, Marianna Pesce, Franco De Cian and Piero Fregatti

J. Pers. Med. 2025, 15(5), 170; https://doi.org/10.3390/jpm15050170 - 25 Apr 2025

Viewed by 226

Abstract

Background/Objectives: Zuska disease is a rare inflammatory condition of the mammary gland, characterized by recurrent non-puerperal abscesses in the periareolar region, often complicated by fistula formation. It predominantly affects women who smoke, particularly perimenopausal women. This study aims to investigate the clinical features, [...] Read more.

Background/Objectives: Zuska disease is a rare inflammatory condition of the mammary gland, characterized by recurrent non-puerperal abscesses in the periareolar region, often complicated by fistula formation. It predominantly affects women who smoke, particularly perimenopausal women. This study aims to investigate the clinical features, treatment outcomes, and recurrence rates of Zuska disease in a cohort of patients. Methods: We conducted a retrospective analysis of 19 patients diagnosed with Zuska disease and treated at the Breast Surgery Clinic of San Martino Policlinic Hospital between January 2021 and June 2024. Data were collected on demographics, clinical presentation, imaging findings, surgical interventions, intraoperative cultures, and postoperative outcomes. The types of surgeries performed, antibiotic therapy regimens, and histological findings were recorded. Results: The mean age of the patients was 43.8 years. The most common presentation was a painful breast mass without fistula formation (12 patients), signs of a past abscess with negative preoperative ultrasound findings (five patients), and abscesses with fistulas (two patients). Intraoperative cultures revealed a range of bacterial species. Recurrence occurred in five patients (26%), and reoperation was required in three cases. All patients were free of symptoms at follow-up, with an average recurrence time of 13.6 months. Conclusions: Zuska disease presents significant treatment challenges due to its recurrent nature. While surgical interventions, such as abscess drainage and ductal excision, are effective, recurrence remains common, particularly in patients with risk factors like smoking. A personalized therapeutic approach, tailored to each patient’s clinical profile, is essential to improving long-term outcomes. Early diagnosis, timely surgical management, and lifestyle modifications play a crucial role in reducing recurrence. Future studies should focus on optimizing treatment protocols and developing individualized strategies for managing comorbidities. Full article

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

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12 pages, 12885 KiB

Open AccessArticle

The Prognostic Impact of the Tumor Immune Microenvironment in Synovial Sarcoma: An Immunohistochemical Analysis Using Digital Pathology and Conventional Interpretation

by Emilio Medina-Ceballos, Francisco Giner, Isidro Machado, Begoña Heras-Morán, Mónica Espino, Samuel Navarro and Antonio Llombart-Bosch

J. Pers. Med. 2025, 15(5), 169; https://doi.org/10.3390/jpm15050169 - 25 Apr 2025

Viewed by 230

Abstract

Background and Objectives: Innate and adaptive immune responses serve a crucial role in neoplasms. The interaction of immune cells with the neoplastic tissue influences tumor behavior, resulting in either pro-tumorigenic or anti-tumorigenic effects. However, the prognostic significance of the tumor immune microenvironment (TIME) [...] Read more.

Background and Objectives: Innate and adaptive immune responses serve a crucial role in neoplasms. The interaction of immune cells with the neoplastic tissue influences tumor behavior, resulting in either pro-tumorigenic or anti-tumorigenic effects. However, the prognostic significance of the tumor immune microenvironment (TIME) in synovial sarcoma (SS) remains poorly studied. This study aimed to analyze the TIME of SS to determine its impact on the prognosis by examining the intratumoral lymphocytic and macrophagic infiltrate and its potential correlation with survival and recurrence. Methods: We conducted a retrospective observational study of 49 fusion-confirmed SS cases collected from two different institutions. We obtained clinical and follow-up data, and SSs were histologically classified according to WHO criteria. Immunohistochemical analysis, including of CD163, CD68, CD3, CD8, and CD20, was conducted in tissue microarrays using an analog scale. We examined the whole-slide tissue for the 23 cases with sufficient material available and then assessed the positive area by scanning the slides and analyzing the images using QuPath (0.4.4, Belfast, Northern Ireland) to calculate the positive area in an immune hotspot. We correlated the expression of these markers with clinical outcomes. A log-rank test and Kaplan–Meyer curves were used as appropriate (significance: p ≤ 0.05). Results: The most frequent morphological subtype was monophasic (59.6%), followed by biphasic (26.9%) and undifferentiated (7%). The mean disease specific survival (DSS) was 55.3 months, with a median of 33 months. The median overall survival (OS) was 50 months (range: 2–336 months). Both evaluation methods showed a good correlation for all antibodies, with Chi-square values of p < 0.05. All cases showed variable amounts of CD163-positive macrophages. The cases that showed a higher density of CD163-positive macrophages in whole-slide images subjected to digital analysis demonstrated an improved OS and DSS on Kaplan–Meier curves. Cases with lower CD8 and CD3 positivity showed a tendency toward faster progression and a slightly worse prognosis. Conclusions: The tumor immune microenvironment in sarcomas is a complex system that requires further investigation to fully understand its impact on tumorigenesis and patient clinical outcomes. Our results demonstrate that a higher amount of intratumoral CD163-positive macrophage infiltrate is associated with an increased OS and DSS. Our findings show that digital pathology is more precise than subjective quantitative analysis. Full article

(This article belongs to the Special Issue Molecular Pathology in Cancer Research)

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19 pages, 1235 KiB

Open AccessArticle

Validation of Binocular Vision and Ocular Surface Assessment Tools in Digital Eye Strain Syndrome: The DESIROUS Study

by Maria João Barata, Pedro Aguiar, Andrzej Grzybowski, Carla Lança and André Moreira-Rosário

J. Pers. Med. 2025, 15(5), 168; https://doi.org/10.3390/jpm15050168 - 25 Apr 2025

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Abstract

Background: To understand if binocular vision disorders are associated with Digital Eye Strain Syndrome (DESS), a study protocol is needed to ensure consistency across observational studies. This study aims to test the feasibility of a protocol to assess DESS, screen time, binocular [...] Read more.

Background: To understand if binocular vision disorders are associated with Digital Eye Strain Syndrome (DESS), a study protocol is needed to ensure consistency across observational studies. This study aims to test the feasibility of a protocol to assess DESS, screen time, binocular vision, and dry eye. Methods: DESIROUS is an observational cross-sectional study among Polytechnic students at the Lisbon School of Health Technology, Portugal. The protocol includes three questionnaires (Computer Vision Syndrome Questionnaire [CVS-Q], Convergence Insufficiency Symptom Survey [CISS], and Dry Eye Questionnaire version 5 [DEQ-5]), an assessment of visual acuity and binocular vision (cover test for near and distance, stereopsis, near point convergence (NPC), near point accommodation (NPA), accommodative facility, vergence), and the ocular surface break-up tear (BUT) test. The questionnaires were validated using Cronbach’s alpha. Interobserver variability for BUT was assessed using Cohen’s Kappa, Intraclass Correlation Coefficient (ICC), and Bland–Altman analysis involving three observers (A, B, and C), compared against an expert as the gold standard. Results: A total of 18 students were included in the validation phase (mean age: 21.50 ± 0.62 years; females: 77.8%). The internal consistency of the CVS-Q (α = 0.773) and the CISS (α = 0.756) was considered good, while the DEQ-5 showed a reasonable internal consistency (α = 0.594). Observer A had the highest agreement with the gold standard (Cohen’s Kappa = 0.710 and p < 0.001; ICC = 0.924, p < 0.001). Conclusions: We provide a protocol to assess binocular vision and the ocular surface, with an emphasis on objective measures while integrating other assessment approaches. Further studies are necessary to validate this protocol, potentially incorporating new measures to enhance its validity across different populations. Full article

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

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Open AccessArticle

Semi-Supervised Learning for Predicting Multiple Sclerosis

by Sotiris Kotsiantis, Georgia Melagraki, Vassilios Verykios, Aikaterini Sakagianni and John Matsoukas

J. Pers. Med. 2025, 15(5), 167; https://doi.org/10.3390/jpm15050167 - 24 Apr 2025

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Abstract

Background: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system with a propensity to inflict severe neurological disability. Accurate and early prediction of MS progression is extremely crucial for its management and treatment. Methods: In this paper, [...] Read more.

Background: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system with a propensity to inflict severe neurological disability. Accurate and early prediction of MS progression is extremely crucial for its management and treatment. Methods: In this paper, we compare a number of self-labeled semi-supervised learning methods used to predict MS from labeled and unlabeled medical data. Specifically, we compare the performance of Self-Training, SETRED, Co-Training, Co-Training by Committee, Democratic Co-Learning, RASCO, RelRASCO, CoForest, and TriTraining in different labeled ratios. The data contain clinical, imaging, and demographic features, allowing for a detailed comparison of each method’s predictive ability. Results and Conclusions: The experimental results demonstrate that several self-labeling semi-supervised learning (SSL) algorithms perform competitively in the task of Multiple Sclerosis (MS) prediction, even when trained on as little as 30–40% of the labeled data. Notably, Co-Training by Committee, CoForest, and TriTraining consistently deliver high performance across all metrics (accuracy, F1-score, and MCC). Full article

(This article belongs to the Special Issue Novel Applications of Artificial Intelligence in Personalized Medicine)

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J. Pers. Med., Volume 15, Issue 5 (May 2025) – 35 articles

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