Journal of Personalized Medicine

13 pages, 617 KiB

Open AccessEditor’s ChoiceReview

Advancing Patient Care: How Artificial Intelligence Is Transforming Healthcare

by Diana Gina Poalelungi, Carmina Liana Musat, Ana Fulga, Marius Neagu, Anca Iulia Neagu, Alin Ionut Piraianu and Iuliu Fulga

J. Pers. Med. 2023, 13(8), 1214; https://doi.org/10.3390/jpm13081214 - 31 Jul 2023

Cited by 64 | Viewed by 17405

Abstract

Artificial Intelligence (AI) has emerged as a transformative technology with immense potential in the field of medicine. By leveraging machine learning and deep learning, AI can assist in diagnosis, treatment selection, and patient monitoring, enabling more accurate and efficient healthcare delivery. The widespread [...] Read more.

Artificial Intelligence (AI) has emerged as a transformative technology with immense potential in the field of medicine. By leveraging machine learning and deep learning, AI can assist in diagnosis, treatment selection, and patient monitoring, enabling more accurate and efficient healthcare delivery. The widespread implementation of AI in healthcare has the role to revolutionize patients’ outcomes and transform the way healthcare is practiced, leading to improved accessibility, affordability, and quality of care. This article explores the diverse applications and reviews the current state of AI adoption in healthcare. It concludes by emphasizing the need for collaboration between physicians and technology experts to harness the full potential of AI. Full article

(This article belongs to the Special Issue Patient-Centered Care for Chronic Diseases)

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30 pages, 1377 KiB

Open AccessEditor’s ChoiceReview

Contemporary Biomarkers for Renal Transplantation: A Narrative Overview

by Dorin Novacescu, Silviu Constantin Latcu, Razvan Bardan, Liviu Daminescu and Alin Adrian Cumpanas

J. Pers. Med. 2023, 13(8), 1216; https://doi.org/10.3390/jpm13081216 - 31 Jul 2023

Cited by 7 | Viewed by 3018

Abstract

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to [...] Read more.

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies. Full article

(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)

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16 pages, 1400 KiB

Open AccessEditor’s ChoiceReview

Immune Biomarkers in Triple-Negative Breast Cancer: Improving the Predictivity of Current Testing Methods

by Francesca Maria Porta, Elham Sajjadi, Konstantinos Venetis, Chiara Frascarelli, Giulia Cursano, Elena Guerini-Rocco, Nicola Fusco and Mariia Ivanova

J. Pers. Med. 2023, 13(7), 1176; https://doi.org/10.3390/jpm13071176 - 23 Jul 2023

Cited by 15 | Viewed by 4924

Abstract

Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards [...] Read more.

Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards biomarker-based approaches for TNBC, with a particular emphasis on the tumor immune landscape. Immune biomarkers in TNBC are now a subject of great interest due to the presence of tumor-infiltrating lymphocytes (TILs) in these tumors. This characteristic often coincides with the presence of PD-L1 expression on both neoplastic cells and immune cells within the tumor microenvironment. Furthermore, a subset of TNBC harbor mismatch repair deficient (dMMR) TNBC, which is frequently accompanied by microsatellite instability (MSI). All of these immune biomarkers hold actionable potential for guiding patient selection in immunotherapy. To fully capitalize on these opportunities, the identification of additional or complementary biomarkers and the implementation of highly customized testing strategies are of paramount importance in TNBC. In this regard, this article aims to provide an overview of the current state of the art in immune-related biomarkers for TNBC. Specifically, it focuses on the various testing methodologies available and sheds light on the immediate future perspectives for patient selection. By delving into the advancements made in understanding the immune landscape of TNBC, this study aims to contribute to the growing body of knowledge in the field. The ultimate goal is to pave the way for the development of more personalized testing strategies, ultimately improving outcomes for TNBC patients. Full article

(This article belongs to the Special Issue Cancer Biomarkers and Therapy)

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16 pages, 1131 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Factors Associated with Poor Asthma Control in Adults with Severe Eosinophilic Asthma

by Clara Padró-Casas, María Basagaña, María Luisa Rivera-Ortún, Ignasi García-Olivé, Carlos Pollan-Guisasola, Aina Teniente-Serra, Eva Martínez-Cáceres, José-Tomás Navarro, Jorge Abad-Capa, Antoni Rosell, Albert Roger and Carlos Martínez-Rivera

J. Pers. Med. 2023, 13(7), 1173; https://doi.org/10.3390/jpm13071173 - 22 Jul 2023

Cited by 5 | Viewed by 1640

Abstract

A study was conducted in 98 adult patients diagnosed with severe eosinophilic asthma (73.5% women, mean age 47.2 years) and followed prospectively for 1 year. The aim of the study was to characterize this population and to identify factors associated with poor prognosis [...] Read more.

A study was conducted in 98 adult patients diagnosed with severe eosinophilic asthma (73.5% women, mean age 47.2 years) and followed prospectively for 1 year. The aim of the study was to characterize this population and to identify factors associated with poor prognosis at 1 year of follow-up. At the initial visit, uncontrolled severe asthma was diagnosed in 87.7% of patients. Allergic sensitization was observed in 81.7% (polysensitization in 17.3%), with clinically significant allergic asthma in 45%. The mean percentage of sputum eosinophils was 4.7% (standard deviation(SD) 6.3%) and the mean (SD) blood eosinophil count 467 (225) cells/µL. Almost half of the patients (48.3%) had sputum eosinophilia (>3% eosinophils). Sputum eosinophils correlated significantly with peripheral eosinophilia (p = 0.004) and, to a lesser extent, with fractional exhaled nitric oxide (FeNO) (p = 0.04). After 1 year, 48 patients (49%) had uncontrolled asthma in all visits, and 50 (51%) had controlled asthma in some visits. Airway obstruction (FEV₁ < 80% predicted) was the main reason for uncontrolled asthma. In the multivariate analysis, an obstructive pattern (odds ratio (OR) 7.45, 95% confidence interval (CI) 2.41–23.03, p < 0.0001) and the patient’s age (OR 1.045, 95% CI 1.005–1.086, p = 0.026) were independent predictors of poor asthma control. In adult-onset and long-standing asthma, serum interleukin (IL) IL-17 was higher in the uncontrolled asthma group. This study contributes to characterizing patients with severe eosinophilic asthma in real-world clinical practice. Full article

(This article belongs to the Section Mechanisms of Diseases)

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17 pages, 3434 KiB

Open AccessEditor’s ChoiceArticle

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure

by Silvia Spoto, Josepmaria Argemi, Roberta Di Costanzo, Juan Josè Gavira Gomez, Nahikari Salterain Gonzales, Stefania Basili, Roberto Cangemi, Antonio Abbate, Luciana Locorriere, Francesco Masini, Giulia Testorio, Rodolfo Calarco, Giulia Battifoglia, Fabio Mangiacapra, Marta Fogolari, Sebastiano Costantino and Silvia Angeletti

J. Pers. Med. 2023, 13(7), 1155; https://doi.org/10.3390/jpm13071155 - 18 Jul 2023

Cited by 10 | Viewed by 2579

Abstract

Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in [...] Read more.

Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. Aim and Methods: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Results: Levels of MR-proADM (median: 2.07; (25th–75th percentiles: 1.40–3.02) vs. 1.11 (0.83–1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691–11,874) vs. 271 (89–931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13–7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42–30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05–9.91; p = 0.041). Conclusion: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy. Full article

(This article belongs to the Section Disease Biomarker)

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14 pages, 2568 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Glissonean Pedicle Isolation Focusing on the Laennec’s Capsule for Minimally Invasive Anatomical Liver Resection

by Mamoru Morimoto, Yoichi Matsuo, Keisuke Nonoyama, Yuki Denda, Hiromichi Murase, Tomokatsu Kato, Hiroyuki Imafuji, Kenta Saito and Shuji Takiguchi

J. Pers. Med. 2023, 13(7), 1154; https://doi.org/10.3390/jpm13071154 - 18 Jul 2023

Cited by 8 | Viewed by 3855

Abstract

Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec’s capsule covering the liver parenchyma [...] Read more.

Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec’s capsule covering the liver parenchyma is essential for safe and precise GPI. The purpose of this study was to verify identification of the Laennec’s capsule, to confirm the validity of GPI in minimally invasive surgery, and to demonstrate the value of GPI focusing on the Laennec’s capsule using a robotic system that has been developed in recent years. Methods: We used a cadaveric model to simulate the Glissonean pedicle and the surrounding liver parenchyma for pathologic verification of the layers. We performed 60 LALRs and 39 robotic anatomical liver resections (RALRs) using an extrahepatic Glissonean approach, from April 2020 to April 2023, and verified the layers of the specimens removed during LALR and RALR based on pathologic examination. In addition, the surgical outcomes of LALR and RALR were compared. Results: Histologic examination facilitated by Elastica van Gieson staining revealed the presence of Laennec’s capsule covering the liver parenchyma in a cadaveric model. Similar findings were obtained following LALR and RALR, thus confirming that the gap between the Glissonean pedicle and the Laennec’s capsule can be dissected without injury to the parenchyma. The mean GPI time was 32.9 and 27.2 min in LALR and RALR, respectively. The mean blood loss was 289.7 and 131.6 mL in LALR and RALR, respectively. There was no significant difference in the incidence of Clavien–Dindo grade ≥III complications between the two groups. Conclusions: Laennec’s capsule is the most important anatomical landmark in performing a safe and successful extrahepatic GPI. Based on this concept, it is possible for LALR and RALR to develop GPI focusing on the Laennec’s capsule. Furthermore, a robotic system has the potential to increase the safety and decrease the difficulty of this challenging procedure. Full article

(This article belongs to the Special Issue Minimally Invasive Liver Resection)

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Graphical abstract

23 pages, 924 KiB

Open AccessEditor’s ChoiceReview

Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments

by Rui Sousa Martins, Tito Teles Jesus, Luís Cardoso, Paula Soares and João Vinagre

J. Pers. Med. 2023, 13(7), 1132; https://doi.org/10.3390/jpm13071132 - 13 Jul 2023

Cited by 6 | Viewed by 2626

Abstract

Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common [...] Read more.

Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common oncogenic events. MTC can be resistant to cytotoxic chemotherapy, and multitarget kinase inhibitors (MKIs) have been considered a treatment option. They act by inhibiting the activities of specific tyrosine kinase receptors involved in tumor growth and angiogenesis. Several tyrosine kinase inhibitors are approved in the treatment of advanced MTC, including vandetanib and cabozantinib. However, due to the significant number of adverse events, debatable efficiency and resistance, there is a need for novel RET-specific TKIs. Newer RET-specific TKIs are expected to overcome previous limitations and improve patient outcomes. Herein, we aim to review MTC signaling pathways, the most recent options for treatment and the applications for personalized medicine. Full article

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13 pages, 615 KiB

Open AccessEditor’s ChoiceReview

Impact of Colorectal Cancer Sidedness and Location on Therapy and Clinical Outcomes: Role of Blood-Based Biopsy for Personalized Treatment

by Sasha Waldstein, Marianne Spengler, Iryna V. Pinchuk and Nelson S. Yee

J. Pers. Med. 2023, 13(7), 1114; https://doi.org/10.3390/jpm13071114 - 10 Jul 2023

Cited by 7 | Viewed by 3083

Abstract

Colorectal cancer is one of the most common malignant diseases in the United States and worldwide, and it remains among the top three causes of cancer-related death. A new understanding of molecular characteristics has changed the profile of colorectal cancer and its treatment. [...] Read more.

Colorectal cancer is one of the most common malignant diseases in the United States and worldwide, and it remains among the top three causes of cancer-related death. A new understanding of molecular characteristics has changed the profile of colorectal cancer and its treatment. Even controlling for known mutational differences, tumor side of origin has emerged as an independent prognostic factor, and one that impacts response to therapy. Left- and right-sided colon cancers differ in a number of key ways, including histology, mutational profile, carcinogenesis pathways, and microbiomes. Moreover, the frequency of certain molecular features gradually changes from the ascending colon to rectum. These, as well as features yet to be identified, are likely responsible for the ongoing role of tumor sidedness and colorectal subsites in treatment response and prognosis. Along with tumor molecular profiling, blood-based biopsy enables the identification of targetable mutations and predictive biomarkers of treatment response. With the application of known tumor characteristics including sidedness and subsites as well as the utilization of blood-based biopsy, along with the development of biomarkers and targeted therapies, the field of colorectal cancer continues to evolve towards the personalized management of a heterogeneous cancer. Full article

(This article belongs to the Special Issue Personalized Diagnosis, Treatment, and Prognosis of Gastrointestinal Oncology)

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12 pages, 1507 KiB

Open AccessEditor’s ChoiceArticle

Controlling Nutritional Status (CONUT) Score as a Predictive Marker in Hospitalized Frail Elderly Patients

by Aurelio Lo Buglio, Francesco Bellanti, Cristiano Capurso and Gianluigi Vendemiale

J. Pers. Med. 2023, 13(7), 1119; https://doi.org/10.3390/jpm13071119 - 10 Jul 2023

Cited by 8 | Viewed by 2268

Abstract

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to detect altered nutritional status as well as to predict clinical adverse outcomes in specific populations. No data are available in frail patients. This study aims to investigate the predictive role [...] Read more.

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to detect altered nutritional status as well as to predict clinical adverse outcomes in specific populations. No data are available in frail patients. This study aims to investigate the predictive role of the CONUT score on mortality and length of stay (LOS) in frail patients admitted to an Internal Medicine Department. We consecutively enrolled 246 patients aged 65 years or older, divided into two groups based on frailty status. The two groups were further divided according to low (<5) or high (≥5) CONUT score. Length of stay (LOS) was higher in frail patients than not-frail patients, as well as in the frail group with high CONUT scores compared to the frail group with low CONUT scores. Multiple linear regression showed an increase of 2.1 days for each additional point to the CONUT score. In-hospital mortality was higher in frail compared to not-frail patients, but it did not differ between frail patients with high CONUT scores and frail patients with low CONUT scores. An analysis of the survival curve for 30-day mortality showed a higher mortality rate for frail/high-CONUT-score patients as compared to the not-frail/low-CONUT-score group. The CONUT score shows high prognostic value for higher LOS—but not mortality—in the clinical setting of internal medicine departments for old frail patients. Full article

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14 pages, 2202 KiB

Open AccessEditor’s ChoiceArticle

Using Anatomy-Based Fitting to Reduce Frequency-to-Place Mismatch in Experienced Bilateral Cochlear Implant Users: A Promising Concept

by Anja Kurz, David Herrmann, Rudolf Hagen and Kristen Rak

J. Pers. Med. 2023, 13(7), 1109; https://doi.org/10.3390/jpm13071109 - 8 Jul 2023

Cited by 16 | Viewed by 3039

Abstract

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, [...] Read more.

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, which were determined via post-operative high-resolution flat panel volume computer tomography and clinical fitting software. The outcome measures were speech understanding in quiet and noise and self-perceived sound quality with the CBF map and with the ABF map. Participants were 10 experienced bilateral CI users. The ABF map provided better speech understanding in quiet and noisy environments compared to the CBF map. Additionally, two approaches of reducing the frequency-to-place mismatch revealed that participants are more likely to accept the ABF map if their electrode array is inserted deep enough to stimulate the apical region of their cochlea. This suggests an Angular Insertion Depth of the most apical contact of around 720°–620°. Participants had better speech understanding in quiet and noise with the ABF map. The maps’ self-perceived sound quality was similar. ABF mapping may be an effective tool for compensating the frequency-to-place mismatch in experienced bilateral CI users. Full article

(This article belongs to the Special Issue Personalized Medicine in Otolaryngology: Special Topic Otology)

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16 pages, 2711 KiB

Open AccessEditor’s ChoiceArticle

A Statistical Approach to Assess the Robustness of Radiomics Features in the Discrimination of Mammographic Lesions

by Alfonso Maria Ponsiglione, Francesca Angelone, Francesco Amato and Mario Sansone

J. Pers. Med. 2023, 13(7), 1104; https://doi.org/10.3390/jpm13071104 - 7 Jul 2023

Cited by 9 | Viewed by 1907

Abstract

Despite mammography (MG) being among the most widespread techniques in breast cancer screening, tumour detection and classification remain challenging tasks due to the high morphological variability of the lesions. The extraction of radiomics features has proved to be a promising approach in MG. [...] Read more.

Despite mammography (MG) being among the most widespread techniques in breast cancer screening, tumour detection and classification remain challenging tasks due to the high morphological variability of the lesions. The extraction of radiomics features has proved to be a promising approach in MG. However, radiomics features can suffer from dependency on factors such as acquisition protocol, segmentation accuracy, feature extraction and engineering methods, which prevent the implementation of robust and clinically reliable radiomics workflow in MG. In this study, the variability and robustness of radiomics features is investigated as a function of lesion segmentation in MG images from a public database. A statistical analysis is carried out to assess feature variability and a radiomics robustness score is introduced based on the significance of the statistical tests performed. The obtained results indicate that variability is observable not only as a function of the abnormality type (calcification and masses), but also among feature categories (first-order and second-order), image view (craniocaudal and medial lateral oblique), and the type of lesions (benign and malignant). Furthermore, through the proposed approach, it is possible to identify those radiomics characteristics with a higher discriminative power between benign and malignant lesions and a lower dependency on segmentation, thus suggesting the most appropriate choice of robust features to be used as inputs to automated classification algorithms. Full article

(This article belongs to the Special Issue Precision Medicine in Radiomics and Radiogenomics)

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18 pages, 1584 KiB

Open AccessEditor’s ChoiceSystematic Review

Comparison of a Peripheral Nerve Block versus Spinal Anesthesia in Foot or Ankle Surgery: A Systematic Review and Meta-Analysis with a Trial Sequential Analysis

by Myeongjong Lee, Cheol Lee, Junsung Lim, Hyungtae Kim, Yoo-Shin Choi and Hyun Kang

J. Pers. Med. 2023, 13(7), 1096; https://doi.org/10.3390/jpm13071096 - 4 Jul 2023

Cited by 6 | Viewed by 2639

Abstract

Background: This systematic review and meta-analysis with trial sequential analysis (TSA) aimed to compare perioperative outcomes of peripheral nerve blocks (PNBs) and spinal anesthesia (SA) in elective foot and ankle surgery. Methods: The study protocol was registered in PROSPERO (CRD42021229597). Researchers independently searched [...] Read more.

Background: This systematic review and meta-analysis with trial sequential analysis (TSA) aimed to compare perioperative outcomes of peripheral nerve blocks (PNBs) and spinal anesthesia (SA) in elective foot and ankle surgery. Methods: The study protocol was registered in PROSPERO (CRD42021229597). Researchers independently searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs). Results: Analysis of nine RCTs (n = 802; 399 PNBs, 403 SA) revealed significantly shorter block performance times (WMD: 7.470; 95% CI 6.072 to 8.868), the onset of sensory (WMD: 7.483; 95% CI 2.837 to 12.130) and motor blocks (WMD: 9.071; 95% CI 4.049 to 14.094), durations of sensory (WMD: 458.53; 95% CI 328.296 to 588.765) and motor blocks (WMD: 247.416; 95% CI 95.625 to 399.208), and significantly higher postoperative analgesic requirements (SMD: −1.091; 95% CI −1.634 to −0.549) in the SA group. Additionally, systolic blood pressure (SBP) at 30 min (WMD: 13.950; 95% CI 4.603 to 23.298) was lower in the SA group. Conclusions: The SA demonstrated shorter block performance time, faster onset and shorter duration of sensory and motor blocks, higher postoperative analgesic requirements, and lower SBP at 30 min compared to PNBs in elective foot and ankle surgery. Full article

(This article belongs to the Section Evidence Based Medicine)

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12 pages, 955 KiB

Open AccessEditor’s ChoiceArticle

Patient’s Scar Satisfaction after Conventional Thyroidectomy for Differentiated Thyroid Cancer

by Massimo Campagnoli, Valeria Dell’Era, Maria Silvia Rosa, Fabiola Negri, Eric Malgrati, Massimiliano Garzaro and Paolo Aluffi Valletti

J. Pers. Med. 2023, 13(7), 1066; https://doi.org/10.3390/jpm13071066 - 29 Jun 2023

Cited by 10 | Viewed by 1854

Abstract

Differentiated thyroid carcinoma (DTC) is the most frequent endocrine neoplasm. Its treatment is based on surgery with consequent impact on patients’ quality of life (QoL) and aesthetic implication. The aim of the present study is to assess scar satisfaction in patients affected by [...] Read more.

Differentiated thyroid carcinoma (DTC) is the most frequent endocrine neoplasm. Its treatment is based on surgery with consequent impact on patients’ quality of life (QoL) and aesthetic implication. The aim of the present study is to assess scar satisfaction in patients affected by DTC who underwent total or partial thyroidectomy. A comparison was also made between scar satisfaction with different subcuticular suture. Validated questionnaires have been employed during a 3-month follow-up: Patient and Observer Scar Assessment Scale (POSAS) and the Patient Scar Assessment Questionnaire (PSAQ). Eventually, the impact of thyroid cancer on QoL of patients was performed in the studied population employing the Thyroid-related patient-reported outcome questionnaire (ThyPRO) and European Organisation for Research Additionally, Treatment of Cancer—Quality of Life questionnaire-C30 (EORTC QLQ-C30). It was conducted in a single center observational study considering 74 patients respecting inclusion criteria. Overall scar satisfaction was found to improve during follow-up, reaching the best scores at 3 months from surgery. Subcuticular suture does not seem to influence the scar satisfaction. In our study male patients seem to be more satisfied, on the other hand age does not seem to influence satisfaction. Overall, the ThyPRO questionnaire and EORTC QLQ-C30 scores did not statistically differ between preoperative and postoperative suggesting a small impact of DTC in QoL. Full article

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

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12 pages, 1038 KiB

Open AccessEditor’s ChoiceArticle

Hybrid Value-Aware Transformer Architecture for Joint Learning from Longitudinal and Non-Longitudinal Clinical Data

by Yijun Shao, Yan Cheng, Stuart J. Nelson, Peter Kokkinos, Edward Y. Zamrini, Ali Ahmed and Qing Zeng-Treitler

J. Pers. Med. 2023, 13(7), 1070; https://doi.org/10.3390/jpm13071070 - 29 Jun 2023

Cited by 8 | Viewed by 2878

Abstract

Transformer is the latest deep neural network (DNN) architecture for sequence data learning, which has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and [...] Read more.

Transformer is the latest deep neural network (DNN) architecture for sequence data learning, which has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and natural language data, clinical data presents unique complexities that make adapting Transformer to this domain challenging. To address this issue, we have designed a new Transformer-based DNN architecture, referred to as Hybrid Value-Aware Transformer (HVAT), which can jointly learn from longitudinal and non-longitudinal clinical data. HVAT is unique in the ability to learn from the numerical values associated with clinical codes/concepts such as labs, and in the use of a flexible longitudinal data representation called clinical tokens. We have also trained a prototype HVAT model on a case-control dataset, achieving high performance in predicting Alzheimer’s disease and related dementias as the patient outcome. The results demonstrate the potential of HVAT for broader clinical data-learning tasks. Full article

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16 pages, 3510 KiB

Open AccessEditor’s ChoiceArticle

ATR-FTIR Spectroscopy with Chemometrics for Analysis of Saliva Samples Obtained in a Lung-Cancer-Screening Programme: Application of Swabs as a Paradigm for High Throughput in a Clinical Setting

by Francis L. Martin, Andrew W. Dickinson, Tarek Saba, Thomas Bongers, Maneesh N. Singh and Danielle Bury

J. Pers. Med. 2023, 13(7), 1039; https://doi.org/10.3390/jpm13071039 - 25 Jun 2023

Cited by 8 | Viewed by 2451

Abstract

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab “dip” test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot [...] Read more.

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab “dip” test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot study, a total of 211 saliva samples (n = 170 benign, 41 designated cancer-positive) were randomly taken during the course of this prospective lung-cancer-screening programme. The samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. An exploratory analysis using principal component analysis (PCA,) with or without linear discriminant analysis (LDA), was then undertaken. Three pairwise comparisons were undertaken including: (1) benign vs. cancer following swab analysis; (2) benign vs. cancer following swab analysis with the subtraction of dry swab spectra; and (3) benign vs. cancer following swab analysis with the subtraction of wet swab spectra. Consistent and remarkably similar patterns of clustering for the benign control vs. cancer categories, irrespective of whether the swab plus saliva sample was analysed or whether there was a subtraction of wet or dry swab spectra, was observed. In each case, MANOVA demonstrated that this segregation of categories is highly significant. A k-NN (using three nearest neighbours) machine-learning algorithm also showed that the specificity (90%) and sensitivity (75%) are consistent for each pairwise comparison. In detailed analyses, the swab as a substrate did not alter the level of spectral discrimination between benign control vs. cancer saliva samples. These results demonstrate a novel swab “dip” test using saliva as a biofluid that is highly applicable to be rolled out into a larger lung-cancer-screening programme. Full article

(This article belongs to the Special Issue Clinical Applications of Biospectroscopy and Imaging)

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13 pages, 1115 KiB

Open AccessEditor’s ChoiceArticle

Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial

by Rebecca Daly, Kate Hetherington, Emily Hazell, Bethany R. Wadling, Vanessa Tyrrell, Katherine M. Tucker, Glenn M. Marshall, David S. Ziegler, Loretta M. S. Lau, Toby N. Trahair, Tracey A. O’Brien, Kiri Collins, Andrew J. Gifford, Michelle Haber, Mark Pinese, David Malkin, Mark J. Cowley, Jonathan Karpelowsky, Donna Drew, Chris Jacobs and Claire E. Wakefield Show full author list Hide full author list

J. Pers. Med. 2023, 13(7), 1033; https://doi.org/10.3390/jpm13071033 - 23 Jun 2023

Cited by 8 | Viewed by 4219

Abstract

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia’s first [...] Read more.

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia’s first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care. Full article

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12 pages, 236 KiB

Open AccessEditor’s ChoiceArticle

Parents’ Perspectives on the Utility of Genomic Sequencing in the Neonatal Intensive Care Unit

by Amy A. Lemke, Michelle L. Thompson, Emily C. Gimpel, Katelyn C. McNamara, Carla A. Rich, Candice R. Finnila, Meagan E. Cochran, James M. J. Lawlor, Kelly M. East, Kevin M. Bowling, Donald R. Latner, Susan M. Hiatt, Michelle D. Amaral, Whitley V. Kelley, Veronica Greve, David E. Gray, Stephanie A. Felker, Hannah Meddaugh, Ashley Cannon, Amanda Luedecke, Kelly E. Jackson, Laura G. Hendon, Hillary M. Janani, Marla Johnston, Lee Ann Merin, Sarah L. Deans, Carly Tuura, Trent Hughes, Heather Williams, Kelly Laborde, Matthew B. Neu, Jessica Patrick-Esteve, Anna C. E. Hurst, Brian M. Kirmse, Renate Savich, Steven B. Spedale, Sara J. Knight, Gregory S. Barsh, Bruce R. Korf, Gregory M. Cooper and Kyle B. Brothers Show full author list Hide full author list

J. Pers. Med. 2023, 13(7), 1026; https://doi.org/10.3390/jpm13071026 - 21 Jun 2023

Cited by 8 | Viewed by 1949

Abstract

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: [...] Read more.

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child’s sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. Results: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child’s future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent–infant bonding, and reported variable impact on their feelings of guilt. Conclusion: Parents reported that GS during the neonatal period was useful because it provided a “backbone” for their child’s care. Parents did not consistently endorse negative impacts like interference with parent–infant bonding. Full article

14 pages, 4026 KiB

Open AccessEditor’s ChoiceArticle

Impact of REAC Regenerative Endogenous Bioelectrical Cell Reprogramming on MCF7 Breast Cancer Cells

by Vania Fontani, Sara Cruciani, Sara Santaniello, Salvatore Rinaldi and Margherita Maioli

J. Pers. Med. 2023, 13(6), 1019; https://doi.org/10.3390/jpm13061019 - 20 Jun 2023

Cited by 7 | Viewed by 2539

Abstract

Human breast adenocarcinoma is a form of cancer which has the tendency to metastasize to other tissues, including bones, lungs, brain, and liver. Several chemotherapeutic drugs are used to treat breast tumors. Their combination is used to simultaneously target different mechanisms involved in [...] Read more.

Human breast adenocarcinoma is a form of cancer which has the tendency to metastasize to other tissues, including bones, lungs, brain, and liver. Several chemotherapeutic drugs are used to treat breast tumors. Their combination is used to simultaneously target different mechanisms involved in cell replication. Radio electric asymmetric conveyer (REAC) technology is an innovative technology, used both in vitro and in vivo, to induce cell reprogramming and counteract senescence processes. Within this context, we treated MCF-7 cells with a regenerative (RGN) REAC treatment for a period ranging between 3 and 7 days. We then analyzed cell viability by trypan blue assays and gene and protein expression by real time-qPCR and confocal microscope, respectively. We also detected the levels of the main proteins involved in tumor progression, DKK1 and SFRP1, by ELISA and cell senescence by β-galactosidase tests. Our results showed the ability of REAC RGN to counteract MCF-7 proliferation, probably inducing autophagy via the upregulation of Beclin-1 and LC3-I, and the modulation of specific tumorigenic biomarkers, such as DKK1 and SPFR1. Our results could suggest the application of the REAC RGN in future in vivo experiments, as an aid for the therapeutic strategies usually applied for breast cancer treatment. Full article

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21 pages, 350 KiB

Open AccessEditor’s ChoiceReview

A Critical Review of the Prognostic and Predictive Implications of KRAS and STK11 Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer

by Peter Manolakos and Linda D. Ward

J. Pers. Med. 2023, 13(6), 1010; https://doi.org/10.3390/jpm13061010 - 18 Jun 2023

Cited by 12 | Viewed by 3751

Abstract

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be [...] Read more.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent KRAS and STK11 mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of KRAS mutations, STK11 mutations, or KRAS/STK11 co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, KRAS mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. KRAS mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that STK11 mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, KRAS/STK11 co-mutations may predict primary resistance to ICI. Prospective KRAS/STK11-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published KRAS analyses are retrospective and hypothesis-generating in nature. Full article

15 pages, 706 KiB

Open AccessEditor’s ChoiceArticle

Serum and Bronchoalveolar Lavage Fluid Levels of Cytokines in Patients with Lung Cancer and Chronic Lung Disease: A Prospective Comparative Study

by Patricia Hogea, Emanuela Tudorache, Ovidiu Fira-Mladinescu, Monica Marc, Diana Velescu, Diana Manolescu, Felix Bratosin, Ovidiu Rosca, Adelina Mavrea and Cristian Oancea

J. Pers. Med. 2023, 13(6), 998; https://doi.org/10.3390/jpm13060998 - 14 Jun 2023

Cited by 5 | Viewed by 2063

Abstract

The role of chronic inflammation in the initiation and progression of carcinogenesis has been well-established in previous studies, particularly in the stages of malignant conversion, invasion, and metastasis. This study aimed to explore the potential correlation between the levels of cytokines in serum [...] Read more.

The role of chronic inflammation in the initiation and progression of carcinogenesis has been well-established in previous studies, particularly in the stages of malignant conversion, invasion, and metastasis. This study aimed to explore the potential correlation between the levels of cytokines in serum and bronchoalveolar lavage fluid (BALF) by comparing their levels between patients with lung cancer and those with benign lung diseases. The study measured the concentration of IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-12p70, in venous blood and BALF of a total of 33 patients with lung cancer and 33 patients with benign lung diseases. Significant differences were found between the two groups in various clinical parameters. The cytokine levels were significantly higher among patients with malignant disease, while the BALF analysis revealed higher cytokine levels compared with serum analysis. It was discovered that the levels of cancer-specific cytokines in the lavage fluid increased significantly sooner and were present at a greater concentration than those in the peripheral blood. After one month of treatment, the serum markers decreased significantly but slower in the lavage fluid. The differences between serum and BALF markers remained significant. It was observed that the highest correlation was among IL-6 (serum) and IL-6 (lavage), with a coefficient of 0.774 (p-value < 0.001), and IL-1 (serum) and IL-1β (lavage), with a coefficient value of 0.610 (p-value < 0.001). Other significant correlations among serum and lavage cytokines were observed between IL-6 (lavage) and IL-1 (serum) (rho = 0.631, p-value < 0.001) and CRP (rho = 0.428, p-value = 0.001), respectively. This study revealed significant differences and correlations in clinical parameters, serum markers, and BALF inflammatory markers between patients with lung cancer and those with benign lung pathologies. The results highlight the importance of understanding the inflammatory profiles of these conditions and could contribute to the development of targeted therapies or diagnostic approaches in the future. Further research is needed to validate these findings, explore their implications for clinical practice, and determine the diagnostic and prognostic value of these cytokines for lung cancer. Full article

(This article belongs to the Special Issue Respiratory Health and Chronic Disease Management)

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14 pages, 1800 KiB

Open AccessEditor’s ChoiceArticle

MGMT Promoter Methylation: Prognostication beyond Treatment Response

by Keyoumars Ashkan, Asfand Baig Mirza, Christos Soumpasis, Christoforos Syrris, Dimitrios Kalaitzoglou, Chaitanya Sharma, Zachariah Joseph James, Abbas Khizar Khoja, Razna Ahmed, Amisha Vastani, James Bartram, Kazumi Chia, Omar Al-Salihi, Angela Swampilai, Lucy Brazil, Ross Laxton, Zita Reisz, Istvan Bodi, Andrew King, Richard Gullan, Francesco Vergani, Ranjeev Bhangoo, Safa Al-Sarraj and Jose Pedro Lavrador Show full author list Hide full author list

J. Pers. Med. 2023, 13(6), 999; https://doi.org/10.3390/jpm13060999 - 14 Jun 2023

Cited by 7 | Viewed by 3247

Abstract

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, [...] Read more.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively. Full article

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

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24 pages, 5334 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Interleukin-6 with Other Markers in Diagnosis of Ovarian Cancer

by Magdalena Bizoń, Zofia Awiżeń-Panufnik and Włodzimierz Sawicki

J. Pers. Med. 2023, 13(6), 980; https://doi.org/10.3390/jpm13060980 - 11 Jun 2023

Cited by 5 | Viewed by 1935

Abstract

The lack of specific symptoms in ovarian cancer delays onset of the diagnostic process. Hence, most cases are recognized in late stages of the disease. The aim of this study was to confirm the role of Il-6 compared to other markers in diagnosis [...] Read more.

The lack of specific symptoms in ovarian cancer delays onset of the diagnostic process. Hence, most cases are recognized in late stages of the disease. The aim of this study was to confirm the role of Il-6 compared to other markers in diagnosis and survival in ovarian cancer. The database was collected from 13 January 2021 to 15 February 2023. In total, 101 patients with pelvic tumors with a mean age of 57.86 ± 16.39 participated in the study. In every case, CA125, HE4, CEA, CA19-9, Il-6, C-reactive protein and procalcitonin measurements were taken. Patients with ovarian borderline tumor and metastatic ovarian tumors were excluded from further analysis. Statistically significant correlations were found between diagnosis of ovarian cancer and levels of CA125, HE4, CRP, PCT and Il-6. Comparison of Il-6 with other markers revealed that longer overall survival correlated with lower values of Il-6. In the case of a higher concentration of Il-6, OS and PFS were shorter. Sensitivity and specificity of Il-6 in diagnosis of ovarian cancer were 46.8% and 77.8%, respectively, while for CA125, CRP and PCT were 76.6% and 63%; 68% and 57.5%; 36% and 77%, respectively. More investigations are needed to identify the most specific and sensitive marker for ovarian cancer. Full article

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14 pages, 335 KiB

Open AccessEditor’s ChoiceArticle

Sex- and Gender-Specific Drug Abuse Dynamics: The Need for Tailored Therapeutic Approaches

by Susanna Marinelli, Giuseppe Basile, Roberto Manfredini and Simona Zaami

J. Pers. Med. 2023, 13(6), 965; https://doi.org/10.3390/jpm13060965 - 8 Jun 2023

Cited by 6 | Viewed by 4022

Abstract

Sex and gender have been gaining ever greater attention due to their associated risks, dynamics, patterns and protective factors underlying substance abuse and addiction. Such differentiations and the clarification of complexities thereof take on even greater relevance in light of drug abuse scope [...] Read more.

Sex and gender have been gaining ever greater attention due to their associated risks, dynamics, patterns and protective factors underlying substance abuse and addiction. Such differentiations and the clarification of complexities thereof take on even greater relevance in light of drug abuse scope worldwide. According to the 2022 World Drug Report released by the United Nations Office on Drugs and Crime (UNODC), in 2020 an estimated 284 million people worldwide aged 15–64 had used a drug within the last 12 months. The authors have set out to shed a light on determinants and contributing factors of drug abuse based on sex and gender and outline policy and medicolegal remarks aimed at delineating sex- and gender-based approaches towards drug abuse therapeutic interventions that are both therapeutically and ethically/legally viable and grounded in an evidence-based set of standards. Neurobiological data suggest that estrogen may facilitate drug taking by interacting with reward- and stress-related systems. In animal research, the administration of estrogen increases drug taking and facilitates the acquisition, escalation, and reinstatement of cocaine-seeking behavior. From a medicolegal perspective, it is of utmost importance to take into account the whole picture constituting each patient profile, which certainly includes gender factors and contributors, when outlining a therapeutic approach. Failure to do so could lead to negligence-based malpractice allegations, in light of the scientific findings representing best practices with which clinicians need to comply when caring for SUD patients. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

31 pages, 1401 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Spectrum of Extraglandular Manifestations in Primary Sjögren’s Syndrome

by Ancuta Mihai, Constantin Caruntu, Ciprian Jurcut, Florin Cristian Blajut, Mihnea Casian, Daniela Opris-Belinski, Ruxandra Ionescu and Ana Caruntu

J. Pers. Med. 2023, 13(6), 961; https://doi.org/10.3390/jpm13060961 - 7 Jun 2023

Cited by 12 | Viewed by 5499

Abstract

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of [...] Read more.

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of knowledge in this complex domain of extraglandular extension in pSS need to be overcome in order to increase the diagnostic accuracy of EGMs in pSS. The timely identification of EGMs, as early as from subclinical stages, can be facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on the diagnostic criteria for the wide range of extraglandular involvement in pSS, which associates important underdiagnosing of EGMs, subsequent undertreatment and progression to severe organ dysfunction in these patients. This review article presents the most recent basic and clinical science research conducted to investigate pathogenic mechanisms leading to EGMs in pSS patients. In addition, it presents the current diagnostic and treatment recommendations and the trends for future therapeutic strategies based on personalized treatment, as well as the latest research in the field of diagnostic and prognostic biomarkers for extraglandular involvement in pSS. Full article

(This article belongs to the Special Issue The Challenges and Therapeutic Prospects in Autoimmune Diseases)

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13 pages, 2279 KiB

Open AccessEditor’s ChoiceArticle

Perception of Pathologists in Poland of Artificial Intelligence and Machine Learning in Medical Diagnosis—A Cross-Sectional Study

by Alhassan Ali Ahmed, Agnieszka Brychcy, Mohamed Abouzid, Martin Witt and Elżbieta Kaczmarek

J. Pers. Med. 2023, 13(6), 962; https://doi.org/10.3390/jpm13060962 - 7 Jun 2023

Cited by 4 | Viewed by 2562

Abstract

Background: In the past vicennium, several artificial intelligence (AI) and machine learning (ML) models have been developed to assist in medical diagnosis, decision making, and design of treatment protocols. The number of active pathologists in Poland is low, prolonging tumor patients’ diagnosis and [...] Read more.

Background: In the past vicennium, several artificial intelligence (AI) and machine learning (ML) models have been developed to assist in medical diagnosis, decision making, and design of treatment protocols. The number of active pathologists in Poland is low, prolonging tumor patients’ diagnosis and treatment journey. Hence, applying AI and ML may aid in this process. Therefore, our study aims to investigate the knowledge of using AI and ML methods in the clinical field in pathologists in Poland. To our knowledge, no similar study has been conducted. Methods: We conducted a cross-sectional study targeting pathologists in Poland from June to July 2022. The questionnaire included self-reported information on AI or ML knowledge, experience, specialization, personal thoughts, and level of agreement with different aspects of AI and ML in medical diagnosis. Data were analyzed using IBM^® SPSS^® Statistics v.26, PQStat Software v.1.8.2.238, and RStudio Build 351. Results: Overall, 68 pathologists in Poland participated in our study. Their average age and years of experience were 38.92 ± 8.88 and 12.78 ± 9.48 years, respectively. Approximately 42% used AI or ML methods, which showed a significant difference in the knowledge gap between those who never used it (OR = 17.9, 95% CI = 3.57–89.79, p < 0.001). Additionally, users of AI had higher odds of reporting satisfaction with the speed of AI in the medical diagnosis process (OR = 4.66, 95% CI = 1.05–20.78, p = 0.043). Finally, significant differences (p = 0.003) were observed in determining the liability for legal issues used by AI and ML methods. Conclusion: Most pathologists in this study did not use AI or ML models, highlighting the importance of increasing awareness and educational programs regarding applying AI and ML in medical diagnosis. Full article

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

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14 pages, 4701 KiB

Open AccessEditor’s ChoiceArticle

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18

by Lara Sánchez-Trujillo, Oscar Fraile-Martinez, Cielo García-Montero, Luis M. García-Puente, Luis G. Guijarro, Diego De Leon-Oliva, Diego Liviu Boaru, David Gardón-Alburquerque, María del Val Toledo Lobo, Mar Royuela, Ignacio García-Tuñón, Antonio Rios-Parra, Juan A. De León-Luis, Coral Bravo, Melchor Álvarez-Mon, Julia Bujan, Miguel A. Saez, Natalio García-Honduvilla and Miguel A. Ortega

J. Pers. Med. 2023, 13(6), 956; https://doi.org/10.3390/jpm13060956 - 5 Jun 2023

Cited by 5 | Viewed by 2170

Abstract

Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially [...] Read more.

Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers—Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10—in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings. Full article

(This article belongs to the Section Mechanisms of Diseases)

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17 pages, 937 KiB

Open AccessEditor’s ChoiceReview

Shear Wave Dispersion in Chronic Liver Disease: From Physical Principles to Clinical Usefulness

by Matteo Garcovich, Mattia Paratore, Maria Elena Ainora, Laura Riccardi, Maurizio Pompili, Antonio Gasbarrini and Maria Assunta Zocco

J. Pers. Med. 2023, 13(6), 945; https://doi.org/10.3390/jpm13060945 - 2 Jun 2023

Cited by 10 | Viewed by 2633

Abstract

The development of new applications in ultrasound (US) imaging in recent years has strengthened the role of this imaging technique in the management of different pathologies, particularly in the setting of liver disease. Improved B-mode imaging (3D and 4D), contrast-enhanced US (CEUS) and [...] Read more.

The development of new applications in ultrasound (US) imaging in recent years has strengthened the role of this imaging technique in the management of different pathologies, particularly in the setting of liver disease. Improved B-mode imaging (3D and 4D), contrast-enhanced US (CEUS) and especially US-based elastography techniques have created the concept of multiparametric ultrasound (MP-US), a term borrowed from radiological sectional imaging. Among the new elastography techniques, shear wave dispersion is a newly developed imaging technology which enables the assessment of the shear waves’ dispersion slope. The analysis of the dispersion qualities of shear waves might be indirectly related to the tissue viscosity, thus providing biomechanical information concerning the pathologic state of the liver such as necroinflammation. Some of the most recent US devices have been embedded with software that evaluate the dispersion of shear waves/liver viscosity. In this review, the feasibility and the clinical applications of liver viscosity are reviewed based on the preliminary findings of both animal and human studies. Full article

(This article belongs to the Special Issue Towards Personalized Medicine for Chronic Liver Disease)

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15 pages, 893 KiB

Open AccessEditor’s ChoiceReview

Enhancing Radiotherapy Workflow for Head and Neck Cancer with Artificial Intelligence: A Systematic Review

by Ciro Franzese, Damiano Dei, Nicola Lambri, Maria Ausilia Teriaca, Marco Badalamenti, Leonardo Crespi, Stefano Tomatis, Daniele Loiacono, Pietro Mancosu and Marta Scorsetti

J. Pers. Med. 2023, 13(6), 946; https://doi.org/10.3390/jpm13060946 - 2 Jun 2023

Cited by 9 | Viewed by 2822

Abstract

Background: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the [...] Read more.

Background: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the HNC RT process. Methods: The PubMed database was queried, and a total of 168 articles (2016–2022) were screened by a group of experts in radiation oncology. The group selected 62 articles, which were subdivided into three categories, representing the whole RT workflow: (i) target and OAR contouring, (ii) planning, and (iii) delivery. Results: The majority of the selected studies focused on the OARs segmentation process. Overall, the performance of AI models was evaluated using standard metrics, while limited research was found on how the introduction of AI could impact clinical outcomes. Additionally, papers usually lacked information about the confidence level associated with the predictions made by the AI models. Conclusions: AI represents a promising tool to automate the RT workflow for the complex field of HNC treatment. To ensure that the development of AI technologies in RT is effectively aligned with clinical needs, we suggest conducting future studies within interdisciplinary groups, including clinicians and computer scientists. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Radiation Oncology)

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16 pages, 6824 KiB

Open AccessEditor’s ChoiceArticle

Uterine Artery Embolization for the Treatment of Symptomatic Uterine Fibroids of Different Sizes: A Single Center Experience

by Alberta Cappelli, Cristina Mosconi, Maria Adriana Cocozza, Nicolò Brandi, Laura Bartalena, Francesco Modestino, Maria Cristina Galaverni, Giulio Vara, Alexandro Paccapelo, Gloria Pizzoli, Gioia Villa, Renato Seracchioli and Matteo Renzulli

J. Pers. Med. 2023, 13(6), 906; https://doi.org/10.3390/jpm13060906 - 28 May 2023

Cited by 11 | Viewed by 2860

Abstract

The present study aimed to evaluate the clinical and radiological 1-year outcomes of uterine artery embolization (UAE) performed in a selected population of women with symptomatic myomas and who do not wish to conceive. Between January 2004 and January 2018, a total of [...] Read more.

The present study aimed to evaluate the clinical and radiological 1-year outcomes of uterine artery embolization (UAE) performed in a selected population of women with symptomatic myomas and who do not wish to conceive. Between January 2004 and January 2018, a total of 62 patients with pre-menopausal status and with no wish to conceive in the future underwent UAE for the treatment of symptomatic fibroids. All the patients underwent magnetic resonance imaging (MRI) and/or transvaginal ultrasonography (TV-US) before and after the procedure at 1-year follow-up. Clinical and radiological parameters were recorded, stratifying the population into 3 groups according to the size of the dominant myoma (group 1: <50 mm; group 2: ≥50 and ≤80 mm; group 3: >80 mm). Mean fibroid diameter was significantly reduced (42.6% ± 21.6%) at 1-year follow-up, with excellent improvements in terms of both symptoms and quality of life. No significant difference was observed regarding baseline dimension and the number of myomas. No major complications were reported (2.5%). The present study confirms the safety and efficacy of UAE in the treatment of symptomatic fibroids in pre-menopausal women with no desire to conceive. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology and Women's Health)

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13 pages, 1316 KiB

Open AccessEditor’s ChoiceReview

Ophthalmic Manifestations in Fabry Disease: Updated Review

by Gloria Gambini, Luca Scartozzi, Federico Giannuzzi, Matteo Mario Carlà, Francesco Boselli, Tomaso Caporossi, Umberto De Vico, Antonio Baldascino and Stanislao Rizzo

J. Pers. Med. 2023, 13(6), 904; https://doi.org/10.3390/jpm13060904 - 27 May 2023

Cited by 7 | Viewed by 3572

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular [...] Read more.

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular abnormalities, corneal epithelial opacities (cornea verticillata), lens opacities, and retinal vascular abnormalities. Although a severe vision impairment is rare, these abnormalities are diagnostic indicators and prognostics for severity. Cornea verticillata is the most common ophthalmic feature in both hemizygous men and heterozygous females. Vessel tortuosity has been linked to a faster disease progression and may be useful in predicting systemic involvement. New technologies such as optical coherence tomography angiography (OCTA) are useful for monitoring retinal microvasculature alterations in FD patients. Along with OCTA, corneal topographic analysis, confocal microscopy, and electro-functional examinations, contributed to the recognition of ocular abnormalities and have been correlated with systemic involvement. We offer an update regarding FD ocular manifestations, focusing on findings derived from the most recent imaging modalities, to optimize the management of this pathology. Full article

(This article belongs to the Special Issue Update and Perspectives on Corneal Diseases)

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32 pages, 10714 KiB

Open AccessEditor’s ChoiceArticle

Using EfficientNet-B7 (CNN), Variational Auto Encoder (VAE) and Siamese Twins’ Networks to Evaluate Human Exercises as Super Objects in a TSSCI Images

by Yoram Segal, Ofer Hadar and Lenka Lhotska

J. Pers. Med. 2023, 13(5), 874; https://doi.org/10.3390/jpm13050874 - 22 May 2023

Cited by 8 | Viewed by 3510

Abstract

In this article, we introduce a new approach to human movement by defining the movement as a static super object represented by a single two-dimensional image. The described method is applicable in remote healthcare applications, such as physiotherapeutic exercises. It allows researchers to [...] Read more.

In this article, we introduce a new approach to human movement by defining the movement as a static super object represented by a single two-dimensional image. The described method is applicable in remote healthcare applications, such as physiotherapeutic exercises. It allows researchers to label and describe the entire exercise as a standalone object, isolated from the reference video. This approach allows us to perform various tasks, including detecting similar movements in a video, measuring and comparing movements, generating new similar movements, and defining choreography by controlling specific parameters in the human body skeleton. As a result of the presented approach, we can eliminate the need to label images manually, disregard the problem of finding the start and the end of an exercise, overcome synchronization issues between movements, and perform any deep learning network-based operation that processes super objects in images in general. As part of this article, we will demonstrate two application use cases: one illustrates how to verify and score a fitness exercise. In contrast, the other illustrates how to generate similar movements in the human skeleton space by addressing the challenge of supplying sufficient training data for deep learning applications (DL). A variational auto encoder (VAE) simulator and an EfficientNet-B7 classifier architecture embedded within a Siamese twin neural network are presented in this paper in order to demonstrate the two use cases. These use cases demonstrate the versatility of our innovative concept in measuring, categorizing, inferring human behavior, and generating gestures for other researchers. Full article

(This article belongs to the Special Issue Selected Papers from the pHealth 2022 Conference, Oslo, Norway, 8–10 November 2022)

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17 pages, 1629 KiB

Open AccessEditor’s ChoiceArticle

Radiomics in Breast Imaging: Future Development

by Alessandra Panico, Gianluca Gatta, Antonio Salvia, Graziella Di Grezia, Noemi Fico and Vincenzo Cuccurullo

J. Pers. Med. 2023, 13(5), 862; https://doi.org/10.3390/jpm13050862 - 20 May 2023

Cited by 6 | Viewed by 2424

Abstract

Breast cancer is the most common and most commonly diagnosed non-skin cancer in women. There are several risk factors related to habits and heredity, and screening is essential to reduce the incidence of mortality. Thanks to screening and increased awareness among women, most [...] Read more.

Breast cancer is the most common and most commonly diagnosed non-skin cancer in women. There are several risk factors related to habits and heredity, and screening is essential to reduce the incidence of mortality. Thanks to screening and increased awareness among women, most breast cancers are diagnosed at an early stage, increasing the chances of cure and survival. Regular screening is essential. Mammography is currently the gold standard for breast cancer diagnosis. In mammography, we can encounter problems with the sensitivity of the instrument; in fact, in the case of a high density of glands, the ability to detect small masses is reduced. In fact, in some cases, the lesion may not be particularly evident, it may be hidden, and it is possible to incur false negatives as partial details that may escape the radiologist’s eye. The problem is, therefore, substantial, and it makes sense to look for techniques that can increase the quality of diagnosis. In recent years, innovative techniques based on artificial intelligence have been used in this regard, which are able to see where the human eye cannot reach. In this paper, we can see the application of radiomics in mammography. Full article

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

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17 pages, 1194 KiB

Open AccessEditor’s ChoiceReview

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas

by Grace Hey, Rohan Rao, Ashley Carter, Akshay Reddy, Daisy Valle, Anjali Patel, Drashti Patel, Brandon Lucke-Wold, Daniel Pomeranz Krummel and Soma Sengupta

J. Pers. Med. 2023, 13(5), 853; https://doi.org/10.3390/jpm13050853 - 19 May 2023

Cited by 6 | Viewed by 4035

Abstract

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can [...] Read more.

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas. Full article

(This article belongs to the Section Mechanisms of Diseases)

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13 pages, 1747 KiB

Open AccessEditor’s ChoiceReview

Predicting Hospital Ward Admission from the Emergency Department: A Systematic Review

by Nekane Larburu, Laiene Azkue and Jon Kerexeta

J. Pers. Med. 2023, 13(5), 849; https://doi.org/10.3390/jpm13050849 - 18 May 2023

Cited by 8 | Viewed by 3002

Abstract

Background: The emergency department (ED) is often overburdened, due to the high influx of patients and limited availability of attending physicians. This situation highlights the need for improvement in the management of, and assistance provided in the ED. A key point for this [...] Read more.

Background: The emergency department (ED) is often overburdened, due to the high influx of patients and limited availability of attending physicians. This situation highlights the need for improvement in the management of, and assistance provided in the ED. A key point for this purpose is the identification of patients with the highest risk, which can be achieved using machine learning predictive models. The objective of this study is to conduct a systematic review of predictive models used to detect ward admissions from the ED. The main targets of this review are the best predictive algorithms, their predictive capacity, the studies’ quality, and the predictor variables. Methods: This review is based on PRISMA methodology. The information has been searched in PubMed, Scopus and Google Scholar databases. Quality assessment has been performed using the QUIPS tool. Results: Through the advanced search, a total of 367 articles were found, of which 14 were of interest that met the inclusion criteria. Logistic regression is the most used predictive model, achieving AUC values between 0.75–0.92. The two most used variables are the age and ED triage category. Conclusions: artificial intelligence models can contribute to improving the quality of care in the ED and reducing the burden on healthcare systems. Full article

(This article belongs to the Collection Advances of Emergency and Intensive Care)

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19 pages, 359 KiB

Open AccessEditor’s ChoiceReview

Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review

by Martin M. Schumacher and Jacopo Santambrogio

J. Pers. Med. 2023, 13(5), 837; https://doi.org/10.3390/jpm13050837 - 16 May 2023

Cited by 10 | Viewed by 5079

Abstract

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing [...] Read more.

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing melancholic depression, reporting a diagnostic sensitivity of 67% and a specificity of 95%. While this study generated much enthusiasm and high expectations in the field of biological psychiatry, subsequent studies produced equivocal results, leading to the test being rejected by the American Psychiatric Association. The scientific reasons leading to the rise and fall of the DST are assessed in this review, suggestions are provided as to how the original test can be improved, and its potential applications in clinical psychiatry are discussed. An improved, standardized, and validated version of the DST would be a biologically meaningful and useful biomarker in psychiatry, providing a tool for clinicians caring for depressed patients in the areas of diagnosis, treatment, and prognosis, and predicting the risk of suicide. Additionally, such a test could be a crucial part in the generation of biologically homogenous patient cohorts, necessary for the successful development of new psychotropic medications. Full article

(This article belongs to the Special Issue Biomarkers in Psychiatric Disorders)

12 pages, 299 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Precision Medicine in Fatty Liver Disease/Non-Alcoholic Fatty Liver Disease

by Laura Valenzuela-Vallejo, Despina Sanoudou and Christos S. Mantzoros

J. Pers. Med. 2023, 13(5), 830; https://doi.org/10.3390/jpm13050830 - 14 May 2023

Cited by 16 | Viewed by 4105

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most commonly present in the context of metabolic syndrome and obesity, but not uncommonly, may also be present without metabolic abnormalities and in subjects with normal body mass index. Therefore, a more specific pathophysiology-based subcategorization of fatty liver disease (FLD) is needed to better understand, diagnose, and treat patients with FLD. A precision medicine approach for FLD is expected to improve patient care, decrease long-term disease outcomes, and develop better-targeted, more effective treatments. We present herein a precision medicine approach for FLD based on our recently proposed subcategorization, which includes the metabolic-associated FLD (MAFLD) (i.e., obesity-associated FLD (OAFLD), sarcopenia-associated FLD (SAFLD, and lipodystrophy-associated FLD (LAFLD)), genetics-associated FLD (GAFLD), FLD of multiple/unknown causes (XAFLD), and combined causes of FLD (CAFLD) as well as advanced stage fibrotic FLD (FAFLD) and end-stage FLD (ESFLD) subcategories. These and other related advances, as a whole, are expected to enable not only improved patient care, quality of life, and long-term disease outcomes, but also a considerable reduction in healthcare system costs associated with FLD, along with more options for better-targeted, more effective treatments in the near future. Full article

(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)

13 pages, 672 KiB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of Axiostat^® Hemostatic Dressing in Aiding Manual Compression Closure of the Femoral Arterial Access Site in Patients Undergoing Endovascular Treatments: A Preliminary Clinical Experience in Two Centers

by Roberto Minici, Raffaele Serra, Claudio Maglia, Giuseppe Guzzardi, Marco Spinetta, Federico Fontana, Massimo Venturini and Domenico Laganà

J. Pers. Med. 2023, 13(5), 812; https://doi.org/10.3390/jpm13050812 - 11 May 2023

Cited by 10 | Viewed by 3261

Abstract

Background: Hemostasis of the femoral arterial access site by manual compression or a vascular closure device is critical to the safe completion of any endovascular procedure. Previous investigations evaluated the hemostatic efficacy at the radial access site of some chitosan-based hemostatic pads. This [...] Read more.

Background: Hemostasis of the femoral arterial access site by manual compression or a vascular closure device is critical to the safe completion of any endovascular procedure. Previous investigations evaluated the hemostatic efficacy at the radial access site of some chitosan-based hemostatic pads. This study aims to assess the efficacy and safety of a new chitosan-based hemostatic dressing, namely Axiostat^®, in aiding manual compression closure of the femoral arterial access site in patients undergoing endovascular treatments. Furthermore, the outcomes were compared with evidence on manual compression alone and vascular closure devices. Methods: This investigation is a two-center retrospective analysis of 120 consecutive patients who had undergone, from July 2022 to February 2023, manual compression closure of the femoral arterial access site aided by the Axiostat^® hemostatic dressing. Endovascular procedures performed with introducer sheaths ranging from 4 Fr to 8 Fr were evaluated. Results: Primary technical success was achieved in 110 (91.7%) patients, with adequate hemostasis obtained in all cases of prolonged manual compression requirements. The mean time-to-hemostasis and time-to-ambulation were 8.9 (±3.9) and 462 (±199) minutes, respectively. Clinical success was achieved in 113 (94.2%) patients, with bleeding-related complications noted in 7 (5.8%) patients. Conclusions: Manual compression aided by the Axiostat^® hemostatic dressing is effective and safe in achieving hemostasis of the femoral arterial access site in patients undergoing endovascular treatment with a 4–8 Fr introducer sheath. Full article

(This article belongs to the Special Issue Vascular Repair and Remodeling in Health and Disease)

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16 pages, 472 KiB

Open AccessEditor’s ChoiceArticle

Association between Periodontitis Extent, Severity, and Progression Rate with Systemic Diseases and Smoking: A Retrospective Study

by Georgios S. Chatzopoulos, Ziou Jiang, Nicholas Marka and Larry F. Wolff

J. Pers. Med. 2023, 13(5), 814; https://doi.org/10.3390/jpm13050814 - 11 May 2023

Cited by 9 | Viewed by 3153

Abstract

Background: The aim of this study was to analyze the relationship between extent, severity (stage), and rate of progression (grade) of periodontitis with systemic diseases as well as smoking using a large database. Methods: Patients’ records identified in the BigMouth Dental Data Repository [...] Read more.

Background: The aim of this study was to analyze the relationship between extent, severity (stage), and rate of progression (grade) of periodontitis with systemic diseases as well as smoking using a large database. Methods: Patients’ records identified in the BigMouth Dental Data Repository with a periodontal diagnosis based on the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions were evaluated. Patients were further categorized based on extent, severity, and rate of progression. Data were extracted from patients’ electronic health records including demographic characteristics, dental procedural codes, and self-reported medical conditions, as well as the number of missing teeth. Results: A total of 2069 complete records were ultimately included in the analysis. Males were more likely to have generalized periodontitis and stage III or IV periodontitis. Older individuals were more likely diagnosed with grade B and stage III or IV periodontitis. Individuals with generalized disease, grade C, and stage IV demonstrated a significantly higher number of missing teeth. Higher numbers of tooth loss reported during supportive periodontal treatment were noted in generalized disease and stage IV periodontitis. Multiple sclerosis and smoking were significantly associated with grade C periodontitis. Conclusions: Within the limitations of this retrospective study that utilized the BigMouth dental data repository, smokers were significantly associated with rapid progression of periodontitis (grade C). Gender, age, number of missing teeth, and number of tooth loss during supportive periodontal treatment were associated with disease characteristics. Full article

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15 pages, 3406 KiB

Open AccessEditor’s ChoiceArticle

Non-Surgical Transversal Dentoalveolar Compensation with Completely Customized Lingual Appliances versus Surgically Assisted Rapid Palatal Expansion in Adults—Tipping or Translation in Posterior Crossbite Correction?

by Jonas Q. Schmid, Elena Gerberding, Ariane Hohoff, Johannes Kleinheinz, Thomas Stamm and Claudius Middelberg

J. Pers. Med. 2023, 13(5), 807; https://doi.org/10.3390/jpm13050807 - 9 May 2023

Cited by 6 | Viewed by 2159

Abstract

The aim of this study was to investigate buccolingual tooth movements (tipping/translation) in surgical and nonsurgical posterior crossbite correction. A total of 43 patients (f/m 19/24; mean age 27.6 ± 9.5 years) treated with surgically assisted rapid palatal expansion (SARPE) and 38 patients [...] Read more.

The aim of this study was to investigate buccolingual tooth movements (tipping/translation) in surgical and nonsurgical posterior crossbite correction. A total of 43 patients (f/m 19/24; mean age 27.6 ± 9.5 years) treated with surgically assisted rapid palatal expansion (SARPE) and 38 patients (f/m 25/13; mean age 30.4 ± 12.9 years) treated with dentoalveolar compensation using completely customized lingual appliances (DC-CCLA) were retrospectively included. Inclination was measured on digital models at canines (C), second premolars (P2), first molars (M1), and second molars (M2) before (T₀) and after (T₁) crossbite correction. There was no statistically significant difference (p > 0.05) in absolute buccolingual inclination change between both groups, except for the upper C (p < 0.05), which were more tipped in the surgical group. Translation, i.e., bodily tooth movements that cannot be explained by pure uncontrolled tipping, could be observed with SARPE in the maxilla and with DC-CCLA in both jaws. Dentoalveolar transversal compensation with completely customized lingual appliances does not cause greater buccolingual tipping compared to SARPE. Full article

(This article belongs to the Special Issue Recent Advances in Dental Practice)

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16 pages, 340 KiB

Open AccessEditor’s ChoiceReview

Lung and Gut Microbiome in COPD

by Efstathios Karakasidis, Ourania S. Kotsiou and Konstantinos I. Gourgoulianis

J. Pers. Med. 2023, 13(5), 804; https://doi.org/10.3390/jpm13050804 - 8 May 2023

Cited by 13 | Viewed by 3997

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung [...] Read more.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung and gut microbiomes in COPD pathophysiology. A systematic search of the PubMed database for relevant articles submitted up to June 2022 was performed. We examined the association between the lung and gut microbiome dysbiosis, reflected in bronchoalveolar lavage (BAL), lung tissue, sputum, and feces samples, and the pathogenesis and progression of COPD. It is evident that the lung and gut microbiomes affect each other and both play a vital role in the pathogenesis of COPD. However, more research needs to be carried out to find the exact associations between microbiome diversity and COPD pathophysiology and exacerbation genesis. Another field that research should focus on is the impact of treatment interventions targeting the human microbiome in preventing COPD genesis and progression. Full article

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

13 pages, 323 KiB

Open AccessEditor’s ChoiceArticle

Epigenetic Signatures in Hypertension

by Gerardo Alfonso Perez and Victor Delgado Martinez

J. Pers. Med. 2023, 13(5), 787; https://doi.org/10.3390/jpm13050787 - 1 May 2023

Cited by 7 | Viewed by 2153

Abstract

Clear epigenetic signatures were found in hypertensive and pre-hypertensive patients using DNA methylation data and neural networks in a classification algorithm. It is shown how by selecting an appropriate subset of CpGs it is possible to achieve a mean accuracy classification of 86% [...] Read more.

Clear epigenetic signatures were found in hypertensive and pre-hypertensive patients using DNA methylation data and neural networks in a classification algorithm. It is shown how by selecting an appropriate subset of CpGs it is possible to achieve a mean accuracy classification of 86% for distinguishing control and hypertensive (and pre-hypertensive) patients using only 2239 CpGs. Furthermore, it is also possible to obtain a statistically comparable model achieving an 83% mean accuracy using only 22 CpGs. Both of these approaches represent a substantial improvement over using the entire amount of available CpGs, which resulted in the neural network not generating accurate classifications. An optimization approach is followed to select the CpGs to be used as the base for a model distinguishing between hypertensive and pre-hypertensive individuals. It is shown that it is possible to find methylation signatures using machine learning techniques, which can be applied to distinguish between control (healthy) individuals, pre-hypertensive individuals and hypertensive individuals, illustrating an associated epigenetic impact. Identifying epigenetic signatures might lead to more targeted treatments for patients in the future. Full article

(This article belongs to the Special Issue Cardiovascular Disease Risk Stratification in the Era of Machine Learning and Personalized Medicine)

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14 pages, 636 KiB

Open AccessEditor’s ChoiceArticle

Avatar Intervention for Cannabis Use Disorder in Individuals with Severe Mental Disorders: A Pilot Study

by Sabrina Giguère, Stéphane Potvin, Mélissa Beaudoin, Laura Dellazizzo, Charles-Édouard Giguère, Alexandra Furtos, Karine Gilbert, Kingsada Phraxayavong and Alexandre Dumais

J. Pers. Med. 2023, 13(5), 766; https://doi.org/10.3390/jpm13050766 - 29 Apr 2023

Cited by 6 | Viewed by 2901

Abstract

Cannabis use disorder (CUD) is a complex issue, even more so when it is comorbid with a severe mental disorder (SMD). Available interventions are at best slightly effective, and their effects are not maintained over time. Therefore, the integration of virtual reality (VR) [...] Read more.

Cannabis use disorder (CUD) is a complex issue, even more so when it is comorbid with a severe mental disorder (SMD). Available interventions are at best slightly effective, and their effects are not maintained over time. Therefore, the integration of virtual reality (VR) may increase efficacy; however, it has not yet been investigated in the treatment of CUD. A novel approach, avatar intervention for CUD, uses existing therapeutic techniques from other recommended therapies (e.g., cognitive behavioral methods, motivational interviewing) and allows participants to practice them in real-time. During immersive sessions, participants are invited to interact with an avatar representing a significant person related to their drug use. This pilot clinical trial aimed to evaluate the short-term efficacity of avatar intervention for CUD on 19 participants with a dual diagnosis of SMD and CUD. Results showed a significant moderate reduction in the quantity of cannabis use (Cohen’s d = 0.611, p = 0.004), which was confirmed via urinary quantification of cannabis use. Overall, this unique intervention shows promising results. Longer-term results, as well as comparison with classical interventions in a larger sample, are warranted through a future single-blind randomized controlled trial. Full article

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

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19 pages, 893 KiB

Open AccessEditor’s ChoiceReview

CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier

by Revathi Gnanasekaran, Justin Aickareth, Majd Hawwar, Nickolas Sanchez, Jacob Croft and Jun Zhang

J. Pers. Med. 2023, 13(5), 751; https://doi.org/10.3390/jpm13050751 - 28 Apr 2023

Cited by 5 | Viewed by 3076

Abstract

Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) [...] Read more.

Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood–brain barrier (BBB) permeability. Within the NVU, tight junctions (TJs) and adherens junctions (AJs) between endothelial cells play a critical role in regulating the permeability of the BBB. Disruptions to these junctions can compromise the BBB, potentially leading to a hemorrhagic stroke. Understanding the molecular signaling cascades that regulate BBB permeability through EC junctions is, therefore, essential. New research has demonstrated that steroids, including estrogens (ESTs), glucocorticoids (GCs), and metabolites/derivatives of progesterone (PRGs), have multifaceted effects on blood–brain barrier (BBB) permeability by regulating the expression of tight junctions (TJs) and adherens junctions (AJs). They also have anti-inflammatory effects on blood vessels. PRGs, in particular, have been found to play a significant role in maintaining BBB integrity. PRGs act through a combination of its classic and non-classic PRG receptors (nPR/mPR), which are part of a signaling network known as the CCM signaling complex (CSC). This network couples both nPR and mPR in the CmPn/CmP pathway in endothelial cells (ECs). Full article

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16 pages, 2362 KiB

Open AccessEditor’s ChoiceArticle

A New Detection Method of Oral and Oropharyngeal Squamous Cell Carcinoma Based on Multivariate Analysis of Surface Enhanced Raman Spectra of Salivary Exosomes

by Cosmin Ioan Faur, Cristian Dinu, Valentin Toma, Anca Jurj, Radu Mărginean, Anca Onaciu, Rareș Călin Roman, Carina Culic, Magdalena Chirilă, Horațiu Rotar, Alexandra Fălămaș, Gabriela Fabiola Știufiuc, Mihaela Hedeșiu, Oana Almășan and Rares Ionuț Știufiuc

J. Pers. Med. 2023, 13(5), 762; https://doi.org/10.3390/jpm13050762 - 28 Apr 2023

Cited by 13 | Viewed by 2973

Abstract

Raman spectroscopy recently proved a tremendous capacity to identify disease-specific markers in various (bio)samples being a non-invasive, rapid, and reliable method for cancer detection. In this study, we first aimed to record vibrational spectra of salivary exosomes isolated from oral and oropharyngeal squamous [...] Read more.

Raman spectroscopy recently proved a tremendous capacity to identify disease-specific markers in various (bio)samples being a non-invasive, rapid, and reliable method for cancer detection. In this study, we first aimed to record vibrational spectra of salivary exosomes isolated from oral and oropharyngeal squamous cell carcinoma patients and healthy controls using surface enhancement Raman spectroscopy (SERS). Then, we assessed this method’s capacity to discriminate between malignant and non-malignant samples by means of principal component–linear discriminant analysis (PC-LDA) and we used area under the receiver operating characteristics with illustration as the area under the curve to measure the power of salivary exosomes SERS spectra analysis to identify cancer presence. The vibrational spectra were collected on a solid plasmonic substrate developed in our group, synthesized using tangential flow filtered and concentrated silver nanoparticles, capable of generating very reproducible spectra for a whole range of bioanalytes. SERS examination identified interesting variations in the vibrational bands assigned to thiocyanate, proteins, and nucleic acids between the saliva of cancer and control groups. Chemometric analysis indicated discrimination sensitivity between the two groups up to 79.3%. The sensitivity is influenced by the spectral interval used for the multivariate analysis, being lower (75.9%) when the full-range spectra were used. Full article

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20 pages, 890 KiB

Open AccessEditor’s ChoiceReview

Review of Endometrial Receptivity Array: A Personalized Approach to Embryo Transfer and Its Clinical Applications

by Sarah C. Rubin, Mawerdi Abdulkadir, Joshua Lewis, Aleksandr Harutyunyan, Rahim Hirani and Cara L. Grimes

J. Pers. Med. 2023, 13(5), 749; https://doi.org/10.3390/jpm13050749 - 27 Apr 2023

Cited by 17 | Viewed by 6796

Abstract

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an [...] Read more.

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an embryo. In 2011, the endometrial receptivity array (ERA) was first published as a tool to determine when the endometrium is most receptive to an embryo, commonly referred to as the “window of implantation” (WOI). The ERA uses molecular arrays to assess proliferation and differentiation in the endometrium and screens for inflammatory markers. Unlike PGT-A, there has been dissent within the field concerning the efficacy of the ERA. Many studies that contest the success of the ERA found that it did not improve pregnancy outcomes in patients with an already-good prognosis. Alternatively, studies that utilized the ERA in patients with repeated implantation failure (RIF) and transfer of known euploid embryos demonstrated improved outcomes. This review aims to describe the ERA as a novel technique, review the various settings that the ERA may be used in, such as natural frozen embryo transfer (nFET) and hormone replacement therapy frozen embryo transfer (HRT-FET), and provide a summary of the recent clinical data for embryo transfers in patients with RIF utilizing the ERA. Full article

(This article belongs to the Special Issue Precision Medicine in Reproductive Health)

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14 pages, 2087 KiB

Open AccessEditor’s ChoiceReview

The Role of Cold Atmospheric Plasma in Wound Healing Processes in Critically Ill Patients

by Tatiana Bolgeo, Antonio Maconi, Menada Gardalini, Denise Gatti, Roberta Di Matteo, Marco Lapidari, Yaroslava Longhitano, Gabriele Savioli, Andrea Piccioni and Christian Zanza

J. Pers. Med. 2023, 13(5), 736; https://doi.org/10.3390/jpm13050736 - 26 Apr 2023

Cited by 23 | Viewed by 6351

Abstract

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been [...] Read more.

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been proposed as a viable option for many biological and medical applications, given its capacity to reduce wound bacterial contamination and promote wound healing. The aim of this narrative review is to describe how CAP works and its operating mechanisms, as well as reporting its possible applications in critical care settings. The success of CAP in the treatment of wounds, in particular, bedsores or pressure sores, presents an innovative path in the prevention of nosocomial infections and an opportunity of reducing the negative implications of these diseases for the NHS. This narrative review of the literature was conducted following the ‘Scale for the Assessment of Narrative Review Articles’ (SANRA) methodology. Previous literature highlights three biological effects of plasma: inactivation of a wide range of microorganisms, including those that are multi-drug-resistant; increased cell proliferation and angiogenesis with a shorter period of plasma treatment; and apoptosis stimulation with a longer and more intensive treatment. CAP is effective in many areas of the medical field, with no significant adverse effects on healthy cells. However, its use can produce potentially serious side effects and should, therefore, be used under expert supervision and in appropriate doses. Full article

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12 pages, 296 KiB

Open AccessEditor’s ChoiceReview

Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System

by Cristina Dettori, Francesca Ronca, Marco Scalese and Federica Saponaro

J. Pers. Med. 2023, 13(5), 714; https://doi.org/10.3390/jpm13050714 - 24 Apr 2023

Cited by 10 | Viewed by 3775

Abstract

Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such [...] Read more.

Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such as the Central Nervous System (CNS). In humans, PTH-related peptides are Parathyroid Hormone (PTH), PTH-like hormones (PTHrP and PTHLH), and tuberoinfundibular peptide of 39 (TIP39 or PTH2). With different affinities, these ligands can bind parathyroid receptor type 1 (PTH1R) and type 2 (PTH2R), which are part of the type II G-protein-coupled-receptors (GPCRs) family. The PTH/PTHrP/PTH1R system has been found to be expressed in many areas of the brain (hippocampus, amygdala, hypothalamus, caudate nucleus, corpus callosum, subthalamic nucleus, thalamus, substantia nigra, cerebellum), and literature data suggest the system exercises a protective action against neuroinflammation and neurodegeneration, with positive effects on memory and hyperalgesia. TIP39 is a small peptide belonging to the PTH-related family with a high affinity for PTH2R in the CNS. The TIP39/PTH2R system has been proposed to mediate many regulatory and functional roles in the brain and to modulate auditory, nociceptive, and sexual maturation functions. This review aims to summarize the knowledge of PTH-related peptides distribution and functions in the CNS and to highlight the gaps that still need to be filled. Full article

15 pages, 987 KiB

Open AccessEditor’s ChoiceReview

Modulation of Ferroptosis by microRNAs in Human Cancer

by Irena Velkova, Martina Pasino, Zumama Khalid, Paola Menichini, Emanuele Martorana, Alberto Izzotti and Alessandra Pulliero

J. Pers. Med. 2023, 13(5), 719; https://doi.org/10.3390/jpm13050719 - 24 Apr 2023

Cited by 13 | Viewed by 2817

Abstract

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation [...] Read more.

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a “hallmark” of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects. Full article

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

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20 pages, 1875 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Impact of Hypothermic Oxygenated Machine Perfusion on Hepatocellular Carcinoma Recurrence after Liver Transplantation

by Federica Rigo, Nicola De Stefano, Damiano Patrono, Victor De Donato, Ludovico Campi, Diana Turturica, Teresa Doria, Veronica Sciannameo, Paola Berchialla, Francesco Tandoi and Renato Romagnoli

J. Pers. Med. 2023, 13(5), 703; https://doi.org/10.3390/jpm13050703 - 22 Apr 2023

Cited by 9 | Viewed by 2021

Abstract

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective [...] Read more.

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). Results: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. Conclusions: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC. Full article

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19 pages, 811 KiB

Open AccessEditor’s ChoiceSystematic Review

Investigating the Role of Maintenance TMS Protocols for Major Depression: Systematic Review and Future Perspectives for Personalized Interventions

by Giacomo d’Andrea, Gianluca Mancusi, Maria Chiara Santovito, Carlotta Marrangone, Fabrizio Martino, Mario Santorelli, Andrea Miuli, Francesco Di Carlo, Maria Salvina Signorelli, Massimo Clerici, Mauro Pettorruso and Giovanni Martinotti

J. Pers. Med. 2023, 13(4), 697; https://doi.org/10.3390/jpm13040697 - 21 Apr 2023

Cited by 25 | Viewed by 5557

Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance [...] Read more.

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and TRD patients who have received acute treatment. A literature search was conducted following the PRISMA guidelines of 2015 on PubMed, Scopus, and Web of Science databases for publications up to March 2022. Fourteen articles were included. High protocol heterogeneity was observed. Most studies highlighted significant efficacy of maintenance protocols in decreasing relapse risk, suggesting that administering two or fewer stimulations per month is ineffective in sustaining an antidepressant effect or in reducing the risk of relapse in responder patients. The risk of relapse was most pronounced after five months from the acute treatment. Maintenance TMS appears to be a resourceful strategy to maintain acute antidepressant treatment effects, significantly reducing relapse risk. The ease of administering and the ability to monitor treatment adherence should be considered when evaluating the future use of maintenance TMS protocols. Further studies are needed to clarify the clinical relevance of overlapping acute TMS effects with maintenance protocols and to evaluate their long-term effectiveness. Full article

(This article belongs to the Special Issue Biomarkers in Psychiatric Disorders)

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