Journal of Personalized Medicine

13 pages, 245 KiB

Open AccessArticle

Precision Oncology in Clinical Practice: Two Years of Comprehensive Genomic Profiling in Croatia

by Dora Čerina Pavlinović, Jelena Šuto Pavičić, Antonela Njavro, Nikša Librenjak, Ilijan Tomaš, Robert Šeparović, Stjepko Pleština, Žarko Bajić, Natalija Dedić Plavetić and Eduard Vrdoljak

J. Pers. Med. 2025, 15(2), 59; https://doi.org/10.3390/jpm15020059 - 31 Jan 2025

Abstract

Background: The widespread adoption of precision medicine in routine cancer care remains a critical challenge, even as advanced technologies expand and personalized therapies demonstrate remarkable success in certain cancer types. While breakthrough innovations in targeted treatments have revolutionized outcomes for specific cancers, translating [...] Read more.

Background: The widespread adoption of precision medicine in routine cancer care remains a critical challenge, even as advanced technologies expand and personalized therapies demonstrate remarkable success in certain cancer types. While breakthrough innovations in targeted treatments have revolutionized outcomes for specific cancers, translating these scientific advances into standard clinical practice continues to be an evolving and complex endeavor. Croatia has a nationwide project of precision oncology through the comprehensive genomic profiling (CGP) analysis. Since collecting and analyzing real-world data is crucial for clinical research and defining the value of CGP in precision oncology, we aimed to present the data from everyday clinical practice given the opportunities and challenges we faced. Methods: This was a retrospective observational study conducted at the national level in all patients whose tumor samples were subjected to CGP between 1 January 2020 and 31 December 2021. Results: In total, 481 patients with CGP results were included in this study. Gastrointestinal and reproductive malignancies were the most common, accounting for 29.1% and 28.9% of all tested tumors, respectively. Specifically, colorectal tumors made up 19.1% of cases, while uterine tumors represented 11.2%. At least one clinically relevant genomic alteration was found in 76.7% of patients, with the KRAS mutation (27.2%) being the most common. During the two-year study period, 26,709 individuals lost their lives to cancer in Croatia. Combining this with the CGP selection criteria valid at the time, there was an estimated population of approximately 13,350 potentially eligible patients for the CGP analysis, meaning that only 3.6% of potentially eligible patients were tested. Conclusions: The analysis identified clinically actionable genomic alterations in approximately 80% of the evaluated patients, suggesting they could be candidates for targeted therapeutic interventions. The adoption of CGP remains limited, with estimates indicating that under 5% of metastatic cancer patients received testing in the initial two-year implementation period, despite established national insurance coverage guidelines. This low utilization rate suggests a significant gap in access to genomic testing, leaving many eligible cancer patients without the potential benefits of this diagnostic approach. Full article

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

17 pages, 4177 KiB

Open AccessArticle

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

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

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

Abstract

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

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

\approx 0.85

, AUPRC:

\approx 0.52

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

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

23 pages, 1309 KiB

Open AccessSystematic Review

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

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

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

Abstract

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

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

(This article belongs to the Section Mechanisms of Diseases)

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10 pages, 293 KiB

Open AccessArticle

The Significance of Renal Impairment in Children with Eating Disorders

by Avisha Meleika Hamilton and Michael Eisenhut

J. Pers. Med. 2025, 15(2), 56; https://doi.org/10.3390/jpm15020056 - 29 Jan 2025

Abstract

Background: Eating disorders have previously been associated with renal impairment. Low muscle mass reduces serum creatinine used for the calculation of the estimated glomerular filtration rate (eGFR), leading to overestimation of renal function. To solve this problem, the development of a tool to [...] Read more.

Background: Eating disorders have previously been associated with renal impairment. Low muscle mass reduces serum creatinine used for the calculation of the estimated glomerular filtration rate (eGFR), leading to overestimation of renal function. To solve this problem, the development of a tool to detect renal impairment in individual patients with a specific muscle mass is required to individualize risk assessment for further management. The objectives of our study were as follows: To investigate the percentage drop in creatinine (pdCr) during rehydration as a new indicator of renal dysfunction not dependent on muscle mass and to investigate a correlation between cardiovascular function and fluid management with renal function. Methods: In a 5-year retrospective cohort study of all consecutive children admitted because of an eating disorder, renal function expressed as eGFR on admission and as pdCr between admission and the lowest creatinine level was analysed in relation to cardiovascular parameters and fluid management. Results: We included 29 patients. The mean age was 13.4 years. A pdCr after admission was noted in 26/29 (89.7%). The eGFR was <90 in 15 (65%) and improved to >90 in 13/15 (86.6%). In patients with a fluid management plan, there was a median of 18.6% for those with pdCr and 6.4% (p = 0.02) for those without. Renal dysfunction was not related to cardiovascular parameters. Conclusions: The majority of patients with an eating disorder had renal impairment. PdCr was more sensitive in the detection of renal impairment in individual patients compared to eGFR. Full article

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

12 pages, 607 KiB

Open AccessArticle

Associations of Clinical Presentation of Coeliac Disease with Comorbidities and Complications: A Retrospective Single-Centre Analysis

by Judit Bajor, Zsófia Vereczkei, Réka Bencs, Enikő Nagy, Míra Zsófia Peresztegi, Ivett Hegedűs, Nelli Farkas, András Tárnok, Nóra Szigeti and Zsolt Szakács

J. Pers. Med. 2025, 15(2), 55; https://doi.org/10.3390/jpm15020055 (registering DOI) - 29 Jan 2025

Abstract

Background: The clinical presentation of coeliac disease (CD) is various and may influence disease course. We aimed to investigate the associations of clinical presentation with comorbidities and disease complications in a cohort of Hungarian coeliac patients. Methods: In this retrospective study, data of [...] Read more.

Background: The clinical presentation of coeliac disease (CD) is various and may influence disease course. We aimed to investigate the associations of clinical presentation with comorbidities and disease complications in a cohort of Hungarian coeliac patients. Methods: In this retrospective study, data of consecutive CD patients were analysed. Clinical presentation (classical vs. non-classical), extraintestinal manifestations and comorbidities (anaemia, metabolic bone disease, dermatitis herpetiformis, IgA deficiency, chromosomal abnormalities, autoimmune diseases and malignancy) were assessed. Student’s t-test (for age at diagnosis) and the Chi-squared test or Fisher’s exact test (for categorical variables) were applied as analyses. Results: A total of 738 patients were included. In classical vs. non-classical comparisons, classical presentation was significantly associated with metabolic bone disease (59 vs. 36%, respectively, p < 0.001), anaemia (47 vs. 38%, respectively, p = 0.027) and malignancy (6 vs. 2%, respectively, p = 0.006); however, autoimmune diseases and dermatitis herpetiformis were more common with non-classical presentation (23 vs. 31%, p = 0.02, and 5 vs. 16%, p = 0.014, respectively). Conclusions: Our findings confirm that clinical presentation is associated with certain comorbidities and complications in CD. More personalised follow-up may be recommended based on clinical presentation. Full article

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

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16 pages, 853 KiB

Open AccessSystematic Review

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

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

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

Abstract

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

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

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

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18 pages, 4913 KiB

Open AccessArticle

Endoscopic transfacet Decompression for Severe Lumbar Spinal Stenosis: A Technical Note, Illustrative Clinical Series, and Surgeon Survey Regarding Post-Decompression Instability

by Kai-Uwe Lewandrowski, Álvaro Dowling, Choll Kim, Brian Kwon, John Ongulade, Kenyu Ito, Paulo Sergio Terxeira de Carvalho and Morgan P. Lorio

J. Pers. Med. 2025, 15(2), 53; https://doi.org/10.3390/jpm15020053 - 28 Jan 2025

Abstract

Background: Lumbar spinal stenosis (LSS) remains a predominant cause of debilitating back and leg pain, affecting many aging populations. Traditional decompression surgeries can be invasive and pose significant risks and recovery time. This study elucidates the techniques and preliminary outcomes of endoscopic [...] Read more.

Background: Lumbar spinal stenosis (LSS) remains a predominant cause of debilitating back and leg pain, affecting many aging populations. Traditional decompression surgeries can be invasive and pose significant risks and recovery time. This study elucidates the techniques and preliminary outcomes of endoscopic transfacet decompression in treating severe LSS. Methods: A retrospective review was performed on 65 patients with severe LSS who underwent endoscopic transfacet decompression. The patient outcomes were analyzed using the VAS for leg pain and the modified Macnab criteria. Pre-operative and post-operative scores were compared, and any complications were analyzed. An online survey was administered to 868 surgeons using Likert-scale ratings to evaluate surgeons’ experience with endoscopic decompression in patients with painful spondylolisthesis. The survey responses were analyzed using descriptive statistics and Polytomous Rasch analysis to evaluate surgeon endorsement. Results: The study included 65 patients, of which 29 (44.6%) were female and 36 (55.4%) were male, with a mean age of 65.79 ranging from 38 to 84 years. The available mean post-operative follow-up period was 31.44 months, ranging from 24 to 39 months. The VAS score for leg pain reduced significantly from pre-operative 7.54 ± 1.67 to 2.20 ± 1.45 by 5.34 ± 2.03 (p < 0.001) with a large effect size (Cohen’s d = 2.626). At the final follow-up, functional Macnab outcomes were reported as excellent by 20 (30.8%), good by 37 (56.9%), fair by 5 (7.7%), and poor by 3 (4.6%) of patients. There were no incidental durotomies, nerve root injuries, wound complications, or instances of post-operative instability. Only five patients (7.7%) developed post-operative dysesthesia. Incomplete decompression led to fair and poor outcomes in 8 (12.3%) patients. No revision surgeries were performed. post-operative instability was not observed. The surgeon survey corroborated these observations, where the polytomous Rasch analysis showed consensus on the effectiveness of the percutaneous endoscopic decompression of low-grade spondylolisthesis. Differential item functioning (DIF) analysis showed no significant bias in item responses between orthopaedic and neurosurgeons. Conclusions: The endoscopic transfacet decompression technique delineated herein showcased excellent Macnab outcomes in managing severe LSS, with a combined success rate of 87.7%. Patients also experienced a statistically significant reduction in leg pain. Dysesthesia rates were lower than with the transforaminal approach, likely because of limited exiting and traversing nerve root manipulation. This technique might represent a viable, less invasive alternative to open microsurgical dissection and decompression for patients with severe LSS, where fusion may be required. This approach was found to be highly accepted among endoscopic spine surgeons. Full article

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

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11 pages, 3320 KiB

Open AccessArticle

The Orientation of the Prosthetic Trochlear Angle Is Predictable in Kinematically Aligned Total Knee Arthroplasty

by Giorgio Cacciola, Daniele Vezza, Alessandro Massè and Luigi Sabatini

J. Pers. Med. 2025, 15(2), 52; https://doi.org/10.3390/jpm15020052 - 28 Jan 2025

Abstract

Abstract: Objective: This study aimed to predict the orientation of the prosthetic trochlear angle (PTA) relative to the quadriceps line of force (QLF) in kinematically aligned total knee arthroplasty (KA-TKA) by using preoperative radiographic parameters. Methods: This study included 144 patients [...] Read more.

Abstract: Objective: This study aimed to predict the orientation of the prosthetic trochlear angle (PTA) relative to the quadriceps line of force (QLF) in kinematically aligned total knee arthroplasty (KA-TKA) by using preoperative radiographic parameters. Methods: This study included 144 patients who underwent KA-TKA with a femoral component designed for mechanical alignment (MA_DFC), with a PTA of 6°. Radiographic parameters, including the lateral distal femoral angle (LDFA) and the QLF^FMA (quadriceps line of force–femoral mechanical axis angle), were measured pre- and postoperatively. We developed and validated a formula to predict PTA orientation based on these values: “X = QLF^FMA−(PTA−(90°−LDFA))”, where values of x > 0° predict a lateral PTA orientation, while x < 0° predicts a medial PTA. Results: The formula accurately predicted PTA orientation in 100% of the cases, with a difference between the predicted and actual PTA values of <0.5° in 75% of the cases. Patients with an LDFA < 86° and lower QLF^FMA values were identified as at risk for medial PTA orientation, which can affect patellar tracking. Conclusions: Our formula offers a reliable preoperative tool for predicting PTA orientation in KA-TKA, aiding in component selection and alignment strategies to improve patellofemoral function and patient outcomes. Full article

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

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22 pages, 297 KiB

Open AccessReview

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

by Laura Sun and Jason T. Romancik

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

Abstract

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

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

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

18 pages, 712 KiB

Open AccessReview

Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy

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

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

Abstract

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

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

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

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28 pages, 1220 KiB

Open AccessReview

Precision Medicine in Myeloid Neoplasia: Challenges and Opportunities

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

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

Abstract

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

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

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

16 pages, 2640 KiB

Open AccessArticle

Psychopathological Influences on Surgical and Clinical Outcomes in Lumbar Disk Herniation: Prediction Models and Literature Analysis

by Gianluca Galieri, Vittorio Orlando, Edoardo Mazzucchi, Fabrizio Pignotti, Davide Cusumano, Paola Bazzu, Sofia Mantini, Roberto Altieri, Manlio Barbarisi, Alessandro Olivi, Giovanni Sabatino and Giuseppe La Rocca

J. Pers. Med. 2025, 15(2), 48; https://doi.org/10.3390/jpm15020048 - 26 Jan 2025

Abstract

Background/Objectives: Lumbar disk herniation (LDH) significantly affects quality of life due to lower back and radiating leg pain. Surgical intervention, such as discectomy, is effective for symptom relief when conservative measures fail; however, psychological factors like anxiety, depression, and maladaptive coping strategies [...] Read more.

Background/Objectives: Lumbar disk herniation (LDH) significantly affects quality of life due to lower back and radiating leg pain. Surgical intervention, such as discectomy, is effective for symptom relief when conservative measures fail; however, psychological factors like anxiety, depression, and maladaptive coping strategies may negatively impact surgical outcomes. This study aims to assess the role of preoperative psychological evaluations in predicting postoperative recovery and to identify key psychological and functional predictors of surgical success. Methods: A prospective study was conducted on 888 patients undergoing microdiscectomy for LDH at Mater Olbia Hospital between December 2020 and December 2023. Preoperative evaluations included the Visual Analog Scale, Symptom Checklist 90-R, Oswestry Disability Index, and Short Form 36. Logistic regression models and ROC curve analysis were used to identify significant predictors of outcomes and evaluate model accuracy. Results: Preoperative pain levels and emotional well-being emerged as the strongest determinants of postoperative improvement in the Oswestry Disability Index. The predictive model demonstrated high specificity (90.2%) in identifying patients likely to benefit from surgery. Clinically significant improvements were achieved by 69% of patients, highlighting the importance of psychological and functional assessments. Conclusions: Preoperative psychological assessment is critical in predicting outcomes of lumbar disk herniation surgery. Addressing psychological factors preoperatively enhances recovery, supports personalized treatment planning, and improves patient education. These findings advocate for an integrated care model that considers both physical and psychological health, optimizing surgical outcomes and patient satisfaction. Full article

(This article belongs to the Special Issue Orthopedic Trauma: New Perspectives and Innovative Techniques)

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12 pages, 979 KiB

Open AccessArticle

Mid-Regional Pro-Adrenomedullin Is Associated with Adverse Cardiovascular Outcomes After Cardiac Surgery

by Ulrike Baumer, Niema Kazem, Andreas Hammer, Felix Hofer, Eva Steinacher, Lorenz Koller, Daniel Zimpfer, Martin Andreas, Barbara Steinlechner, Christian Hengstenberg, Alexander Niessner and Patrick Sulzgruber

J. Pers. Med. 2025, 15(2), 47; https://doi.org/10.3390/jpm15020047 - 26 Jan 2025

Abstract

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that [...] Read more.

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization. Full article

(This article belongs to the Section Disease Biomarker)

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17 pages, 1526 KiB

Open AccessArticle

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

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

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

Abstract

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

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

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

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12 pages, 1034 KiB

Open AccessArticle

Urinary Bladder Acute Inflammations and Nephritis of the Renal Pelvis: Diagnosis Using Fine-Tuned Large Language Models

by Mohammad Khaleel Sallam Ma’aitah, Abdulkader Helwan and Abdelrahman Radwan

J. Pers. Med. 2025, 15(2), 45; https://doi.org/10.3390/jpm15020045 - 24 Jan 2025

Abstract

Background: Large language models (LLMs) have seen a significant boost recently in the field of natural language processing (NLP) due to their capabilities in analyzing words. These autoregressive models prove robust in classification tasks where texts need to be analyzed and classified. Objectives: [...] Read more.

Background: Large language models (LLMs) have seen a significant boost recently in the field of natural language processing (NLP) due to their capabilities in analyzing words. These autoregressive models prove robust in classification tasks where texts need to be analyzed and classified. Objectives: In this paper, we explore the power of base LLMs such as Generative Pre-trained Transformer 2 (GPT-2), Bidirectional Encoder Representations from Transformers (BERT), Distill-BERT, and TinyBERT in diagnosing acute inflammations of the urinary bladder and nephritis of the renal pelvis. Materials and Methods: the LLMs were trained and tested using supervised fine-tuning (SFT) on a dataset of 120 examples that include symptoms that may indicate the occurrence of these two conditions. Results: By employing a supervised fine-tuning method and carefully crafted prompts to present the data, we demonstrate the feasibility of using minimal training data to achieve a reasonable diagnostic, with overall testing accuracies of 100%, 100%, 94%, and 79%, for GPT-2, BERT, Distill-BERT, and TinyBERT, respectively. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Personalized Medicine: Diagnosis and Treatment)

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12 pages, 3314 KiB

Open AccessArticle

The Use of the Great Toe Pulp Free Flap in Dystrophic Fingertips

by Alessandro Crosio, Mauro Magnani, Simona Odella, Matilde Cacianti, Francesco Maria Locatelli and Pierluigi Tos

J. Pers. Med. 2025, 15(2), 44; https://doi.org/10.3390/jpm15020044 - 23 Jan 2025

Abstract

Background: Lesions of the digital apices are common, and several treatment strategies can be considered for them. Among these, the free great toe pulp flap can be used. Methods: This is a retrospective report in which five patients undergoing hallux free [...] Read more.

Background: Lesions of the digital apices are common, and several treatment strategies can be considered for them. Among these, the free great toe pulp flap can be used. Methods: This is a retrospective report in which five patients undergoing hallux free flap surgery for loss of pulpal substance at the level of the hand were evaluated. They were re-evaluated by using both clinical testing to assess sensitivity and the use of questionnaires to estimate function. Results: None of the performed flaps failed. The mean follow-up was 36 months (range 16–66 months). With SW-MF, the mean value was 3.734 compared to 2.986 for the same contralateral finger. The S2-PD test attested a mean value of 6.8 mm (range 6–8 mm) in contrast to the contralateral finger, which showed a mean result of 3.2 mm (range 3–5 mm), while the D-2PD indicated lower values for both the operated finger, with a mean value of 6.4 mm (range 4–8 mm), and the healthy finger. Conclusions: When a dystrophic fingertip results from an inappropriate acute management, the GTP flap appears to be an excellent strategy to restore the specialized tissue of finger pulp and to bring supple tissue to the correct PIP flexion contracture or the small first web space contracture. It is mostly required for thumb and radial fingers’ reconstruction, especially in young patients or those who need high functional demands and/or present an extensive loss of substance that cannot be resolved with local flaps. Full article

(This article belongs to the Special Issue Surgical Innovation and Advancement in Limb Extremities)

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14 pages, 1355 KiB

Open AccessArticle

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

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

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

Abstract

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

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

(This article belongs to the Section Molecular Targeted Therapy)

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12 pages, 3420 KiB

Open AccessArticle

Implementation and Feasibility of Mechanomyography in Minimally Invasive Spine Surgery

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

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

Abstract

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

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

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

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14 pages, 1207 KiB

Open AccessArticle

Meningeal Metastasis from Naso-Ethmoidal Malignancies: Pathogenesis, Risk Factors, and Prognostic Impact

by Remo Accorona, Isabelle Dohin, Davide Mattavelli, Marco Ferrari, Marco Ravanelli, Vittorio Rampinelli, Davide Farina, Piero Nicolai, Cesare Piazza and Alberto Schreiber

J. Pers. Med. 2025, 15(2), 41; https://doi.org/10.3390/jpm15020041 - 22 Jan 2025

Abstract

Introduction: Meningeal metastasis (MM) from naso-ethmoidal malignancies (NEMs) is rare, its metastatic route is still debated, and its prognostic impact remains unclear. Our aim is to analyze a retrospective series of NEMs with non-contiguous MM to study the possible route of spread and [...] Read more.

Introduction: Meningeal metastasis (MM) from naso-ethmoidal malignancies (NEMs) is rare, its metastatic route is still debated, and its prognostic impact remains unclear. Our aim is to analyze a retrospective series of NEMs with non-contiguous MM to study the possible route of spread and the prognostic value of MM. Materials and methods: The institutional database of SNC treated at the University of Brescia between 1995 and 2021 was reviewed. Clinical–pathological data were collected, and survivals were estimated with Kaplan–Meier. Univariate and multivariate logistic regression analysis were run to identify predictors of MM. Results: Among 296 patients, 17 experienced non-contiguous MM, all located along the dura. Intestinal-type adenocarcinoma (10/17) and olfactory neuroblastoma (3/17) were the most frequent histologies. At univariate analysis, brain edema (p < 0.0001), resection (p = 0.026) or invasion (p = 0.006) of brain parenchyma, and local (p = 0.0004) and nodal (p = 0.021) recurrence were predictors of MM. At multivariate analysis, local recurrence was confirmed as an independent factor (odds ratio: 11.88, p = 0.0005). Dural surgical resection was not a risk factor. The five-year disease-specific survival was longer in patients with exclusive MM compared with patients with distant metastasis at other sites (64.3% vs. 30.1% p = 0.046). Conclusions: Dural venous shunt is the most likely pathway of spread of MM. Local recurrence is the only independent risk factor. Exclusive MM has a better prognosis than extrameningeal metastasis. Full article

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

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