Journal of Personalized Medicine

10 pages, 240 KiB

Open AccessBrief Report

Attitudes of Neurologists Toward Serum Neurofilament Light-Chain Testing in the Management of Relapsing–Remitting Multiple Sclerosis with Cognitive Impairment

by José M. García-Domínguez, Jorge Maurino, José E. Meca-Lallana, Lamberto Landete, Virginia Meca-Lallana, Elena García-Arcelay, Eduardo Agüera-Morales, Ana B. Caminero, Sergio Martínez-Yélamos, Luis Querol, Nicolas Medrano, Rocío Gómez-Ballesteros, Luisa M. Villar, Enric Monreal and Gustavo Saposnik

J. Pers. Med. 2025, 15(2), 69; https://doi.org/10.3390/jpm15020069 - 14 Feb 2025

Abstract

Background: Cognitive impairment has an impact upon the function and quality of life of patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression and are also associated with impaired cognitive performance. This study aimed to assess the attitudes of [...] Read more.

Background: Cognitive impairment has an impact upon the function and quality of life of patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression and are also associated with impaired cognitive performance. This study aimed to assess the attitudes of neurologists toward sNfL testing as regards making therapeutic decisions in clinically and radiologically stable patients experiencing cognitive decline. Methods: A web-based observational study was conducted among neurologists caring for patients with MS. The role of sNfL in therapeutic decisions was assessed through a simulated case scenario describing a 31-year-old woman with relapsing–remitting MS for four years on glatiramer acetate. Her partner reported increased distractibility and difficulties in organizing daily activities over the past 18 months. There was no history of new relapses, and a follow-up brain MRI scan showed no new lesions. Her performance in the Symbol Digit Modalities Test decreased by 8 points from the previous year, with 46 correct answers. The patient had an sNfL level of 21 pg/mL, with no other identified factors that could have altered this value. The participants were tasked with deciding to either escalate treatment or to continue the current treatment and schedule the patient for reassessment in 6–12 months (defined as decisions misaligned with emerging evidence [DMEE]). Multivariate regression analysis was conducted to determine factors associated with DMEE. Results: One hundred and sixteen neurologists participated in the study. Almost 50% of the participants (n = 57) opted not to escalate treatment despite high sNfL levels. This was more common among neurologists not fully dedicated to MS care (60.5% vs. 43.6%). The multivariate analysis showed that being a neurologist not fully dedicated to MS (odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.01–5.50; p = 0.04) and having a poor perception of sNfL benefits (OR = 1.02, 95% CI 1.00–1.04; p = 0.01) were associated with DMEE. Conclusions: Neurologists’ lack of full dedication to MS care and limited perception of sNfL’s clinical utility were key factors associated with suboptimal therapeutic decisions in a simulated case of cognitive decline with elevated sNfL. These findings underscore the need for increased education on the role of sNfL to improve evidence-based decision-making in MS management. Full article

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

11 pages, 862 KiB

Open AccessArticle

A Personalized Approach to Adhesion Prevention in Single-Port Access Laparoscopic Surgery: A Randomized Prospective Study Evaluating the Efficacy of Adhesion Barriers and Patient-Specific Risk Factors

by Seongyun Lim, Joseph Noh, Junhyeong Seo, Youngeun Chung and Taejoong Kim

J. Pers. Med. 2025, 15(2), 68; https://doi.org/10.3390/jpm15020068 - 12 Feb 2025

Abstract

Abstract: Background/Objectives: Single-port access (SPA) laparoscopic surgery has gained popularity due to its cosmetic benefits and reduced postoperative pain. However, concerns persist regarding the increased risk of adhesions due to the larger umbilical incision. This study aims to contribute to personalized [...] Read more.

Abstract: Background/Objectives: Single-port access (SPA) laparoscopic surgery has gained popularity due to its cosmetic benefits and reduced postoperative pain. However, concerns persist regarding the increased risk of adhesions due to the larger umbilical incision. This study aims to contribute to personalized medicine by evaluating the effectiveness of applying an anti-adhesive agent (Guardix SG^®, HanmiPharmaceutical Co., Ltd., Seoul, Korea) at the umbilical incision and identifying patient-specific risk factors for adhesion formation in SPA laparoscopic surgeries. Methods: In this randomized prospective study, 55 female patients with benign gynecological conditions were enrolled. Participants were randomly assigned to either an intervention group, which received the anti-adhesive agent at both the surgical and umbilical sites, or a control group, which received it only at the surgical site. Participants returned for outpatient visits 1–3 months post-surgery to assess incision site complications, including adhesions. Results: The overall adhesion rate was 10.9%, with 13.3% in the control group and 8% in the intervention group, though the difference was not statistically significant (p = 0.678). Infection rates were 6.7% in the control group and 4% in the intervention group; however, there was no significant difference in complications. Logistic regression identified pre-existing adhesions as a significant risk factor (p = 0.0379; OR = 6.909). Conclusions: Although the adhesion barrier showed a trend toward reducing umbilical adhesions, the difference was not statistically significant. The application of the adhesion barrier did not influence incision site complications, confirming its safety. Our findings highlight the need for personalized approaches to adhesion prevention, considering individual patient characteristics and risk factors. Further larger studies are necessary to explore adhesion prevention in a more personalized manner for individual patients in this context. Full article

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

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12 pages, 1035 KiB

Open AccessArticle

Is CK7 a Prognostic Marker in Pulmonary LCNEC? Evidence from a Limited Cohort Study

by Hruy Menghesha, Donatas Zalepugas, Amina Camo, Georg Schlachtenberger, Konstantinos Grapatsas, Andres Amorin Estremadoyro, Fabian Doerr, Matthias Heldwein, Alexander Quaas, Servet Bölükbas, Gerardus Bennink, Joachim Schmidt and Khosro Hekmat

J. Pers. Med. 2025, 15(2), 67; https://doi.org/10.3390/jpm15020067 - 12 Feb 2025

Abstract

Objectives: While the treatment of non-small-cell lung carcinoma has improved rapidly, the treatment of pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains underdeveloped. The use of immunohistochemistry allows for accurate risk stratification. With our study, we investigated the outcome of patients with pulmonary LCNEC and [...] Read more.

Objectives: While the treatment of non-small-cell lung carcinoma has improved rapidly, the treatment of pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains underdeveloped. The use of immunohistochemistry allows for accurate risk stratification. With our study, we investigated the outcome of patients with pulmonary LCNEC and analyzed whether CK7 correlates with long-term survival. Methods: We retrospectively collected the monocentric data of patients which underwent anatomical resection for lung cancer between January 2012 and December 2020. Patients that did not show pulmonary LCNEC or adenocarcinoma, had a positive resection margin, or underwent neoadjuvant therapy were excluded. The long-term survival rate of the LCNEC and adenocarcinoma groups were compared before and after propensity score matching. Furthermore, we performed survival analyses for a subgroup of LCNEC distinguished by CK7 expression, followed by Cox regression analyses. Results: A total of 466 patients were integrated for further analysis. The mean age was 65.3 ± 9.6 years. There were no significant differences between both groups regarding age, gender, or comorbidities. In terms of the UICC stage, the groups were equally distributed. Mean survival in the LCNEC group was significantly worse than in the adenocarcinoma group (LCENC: 36.4 ± 7.5 months; adenocarcinoma: 80.7 ± 8.1 months; p-value = 0.001). The mean survival rate was 19.23 ± 4.8 months in the CK7 expression group and 57.01 ± 8.5 months in the group without expression, which reached statistical significance (p-value = 0.019). Conclusions: Our study suggests that pulmonary LCNEC has a significantly worse prognosis than pulmonary adenocarcinoma. CK7 expression seems to be correlated with a worse outcome for the long-term survival rate of patients suffering from highly malignant pulmonary LCNEC. Full article

(This article belongs to the Special Issue Personalized Treatments in Thoracic Oncology Surgery)

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13 pages, 535 KiB

Open AccessSystematic Review

Treatments of Interest in Male Breast Cancer: An Umbrella Review

by Stefano Spinaci, Luca Arecco, Agnese Anedda, Lucia Martino, Emma Firpo, Matteo Ghilli, Matteo Lambertini and Giulia Ferrarazzo

J. Pers. Med. 2025, 15(2), 66; https://doi.org/10.3390/jpm15020066 - 11 Feb 2025

Abstract

Background: Male breast cancer (MaBC) is a rare disease and due to its rarity and the lack of specific protocols for its management, treatment algorithms are extrapolated from female breast cancer (FBC). To optimize MaBC treatment, we conceived an umbrella review with the [...] Read more.

Background: Male breast cancer (MaBC) is a rare disease and due to its rarity and the lack of specific protocols for its management, treatment algorithms are extrapolated from female breast cancer (FBC). To optimize MaBC treatment, we conceived an umbrella review with the aim of supplying an evidence-based summary of systematic reviews published about this topic in the last twenty years. Methods: This umbrella review was performed according to a predefined protocol (PROSPERO number CRD42024574299). We performed a literature search of the PubMed and Cochrane Libraries databases and we considered systematic reviews on MaBC treatment published from 2004 to 2024. We evaluated relevant treatments in the management of MaBC, including surgery, radiotherapy, and systemic treatments. We conducted the quality assessment according to A MeaSurement Tool to Assess systematic Reviews version 2 (AMSTAR-2), and the description of the main findings of eligible articles. Results: Seven systematic reviews were selected and the main findings were compiled. Breast-conserving surgery is a reasonable treatment approach and, in selected cases, equivalent in terms of safety and survival outcomes compared to mastectomy. Sentinel lymph node biopsy represents a successful surgical practice with similar accuracy compared to female cases. Adjuvant radiotherapy improves overall survival in MaBC patients following partial mastectomy and after radical mastectomy, in case of involved nodes. Finally, Tamoxifen is associated with an improvement of survival outcomes; aromatase inhibitor and gonadotrophin-releasing hormone should be used only in case of contraindications to tamoxifen. Conclusions: Further research and improved guidelines for MaBC treatment should consider these evidence-based data. Full article

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

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19 pages, 330 KiB

Open AccessReview

Occlusion and Biomechanical Risk Factors in Implant-Supported Full-Arch Fixed Dental Prostheses—Narrative Review

by Andrea Berzaghi, Tiziano Testori, Riccardo Scaini and Sergio Bortolini

J. Pers. Med. 2025, 15(2), 65; https://doi.org/10.3390/jpm15020065 - 7 Feb 2025

Abstract

The biophysiological differences between teeth and dental implants and the issue of occlusal overload, although controversial, form the basis for the management of occlusion in implant-supported full-arch fixed dental prostheses (ISFAFDPs). Although there is currently a lack of scientific evidence on occlusal management, [...] Read more.

The biophysiological differences between teeth and dental implants and the issue of occlusal overload, although controversial, form the basis for the management of occlusion in implant-supported full-arch fixed dental prostheses (ISFAFDPs). Although there is currently a lack of scientific evidence on occlusal management, it is clear that the favorable prognosis of ISFAFDPs is linked to a correct understanding of the biomechanical principles involved. In the design of ISFAFDPs, the lack of proprioceptive feedback requires special attention to biomechanical factors: minimizing overloading complications and providing biomechanical stability are among the main goals of the occlusion. In ISFAFDPs, the occlusion must be decided on the basis of several factors that influence the loads on prosthesis and implants: each case must be evaluated individually and requires a personalized occlusion. The main aim of this narrative review is to provide an overview of the occlusal principles and materials that can be used in ISFAFDPs based on the data currently available in the literature. Practical clinical recommendations for the occlusion management of ISFAFDPs and a biomechanical risk score index to personalize implant-prosthetic treatment are proposed. Full article

(This article belongs to the Special Issue Personalized Medicine in Dental and Oral Health)

10 pages, 333 KiB

Open AccessArticle

Efficacy and Safety of Omalizumab and Dupilumab in Pediatric Patients with Skin Diseases: An Observational Study

by Francesca Galletta, Ludovica Rizzuti, Stefano Passanisi, Emanuela Rosa, Lucia Caminiti and Sara Manti

J. Pers. Med. 2025, 15(2), 64; https://doi.org/10.3390/jpm15020064 - 7 Feb 2025

Abstract

Background: Chronic spontaneous urticaria (CSU) and moderate-to-severe atopic dermatitis (AD) are significant challenges in pediatric populations, negatively impacting quality of life (QoL). Biologic therapies, including omalizumab and dupilumab, showed considerable promise for patients unresponsive to conventional treatments. This study evaluated the real-life efficacy [...] Read more.

Background: Chronic spontaneous urticaria (CSU) and moderate-to-severe atopic dermatitis (AD) are significant challenges in pediatric populations, negatively impacting quality of life (QoL). Biologic therapies, including omalizumab and dupilumab, showed considerable promise for patients unresponsive to conventional treatments. This study evaluated the real-life efficacy and safety of these biologics in pediatric CSU and AD patients. Methods: A retrospective, monocentric study was conducted enrolling pediatric patients (aged 6–18 years) followed at the “G. Martino” Hospital, University of Messina. This study included patients with CSU unresponsive to antihistamines and those with moderate-to-severe AD refractory to topical therapies. Disease severity and treatment efficacy were evaluated using the Urticaria Activity Score 7 (UAS7) for CSU, the Eczema Area and Severity Index (EASI) for AD, and QoL metrics, including the Dermatology Life Quality Index (DLQI) and numerical rating scales, for pruritus (p-NRS) and sleep (s-NRS), at baseline, 16 weeks, and 52 weeks. Safety was assessed through the monitoring of reported adverse events (AEs). Results: Omalizumab significantly reduced UAS7 scores by 71.9% at 16 weeks and 75.3% at 52 weeks (p < 0.001), with concurrent improvements in c-DLQI. Dupilumab reduced the EASI score by 75.3%, p-NRS by 40%, and s-NRS by 52.9% over 52 weeks, with c-DLQI improving by 72.6%. No severe AEs were observed; mild reactions included injection-site erythema and respiratory symptoms. Conclusions: Omalizumab and dupilumab demonstrated significant efficacy in reducing disease severity and improving QoL in pediatric patients with CSU and AD. Moreover, their safety profile underscores their potential as essential treatments for these conditions. Full article

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

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11 pages, 913 KiB

Open AccessArticle

Artificial Intelligence-Driven Analysis of Telehealth Effectiveness in Youth Mental Health Services: Insights from SAMHSA Data

by Masab Mansoor and Kashif Ansari

J. Pers. Med. 2025, 15(2), 63; https://doi.org/10.3390/jpm15020063 - 7 Feb 2025

Abstract

Background: The rapid adoption of telehealth services for youth mental health care necessitates a comprehensive evaluation of its effectiveness. This study aimed to analyze the impact of telehealth on youth mental health outcomes using artificial intelligence techniques applied to large-scale public health [...] Read more.

Background: The rapid adoption of telehealth services for youth mental health care necessitates a comprehensive evaluation of its effectiveness. This study aimed to analyze the impact of telehealth on youth mental health outcomes using artificial intelligence techniques applied to large-scale public health data. Methods: We conducted an AI-driven analysis of data from the National Survey on Drug Use and Health (NSDUH) and other SAMHSA datasets. Machine learning techniques, including random forest models, K-means clustering, and time series analysis, were employed to evaluate telehealth adoption patterns, predictors of effectiveness, and comparative outcomes with traditional in-person care. Natural language processing was used to analyze sentiment in user feedback. Results: Telehealth adoption among youth increased significantly, with usage rising from 2.3 sessions per year in 2019 to 8.7 in 2022. Telehealth showed comparable effectiveness to in-person care for depressive disorders and superior effectiveness for anxiety disorders. Session frequency, age, and prior diagnosis were identified as key predictors of telehealth effectiveness. Four distinct user clusters were identified, with socioeconomic status and home environment strongly associated with positive outcomes. States with favorable reimbursement policies saw a 15% greater increase in youth telehealth utilization and 7% greater improvement in mental health outcomes. Conclusions: Telehealth demonstrates significant potential in improving access to and effectiveness of mental health services for youth. However, addressing technological barriers and socioeconomic disparities is crucial to maximize its benefits. Full article

(This article belongs to the Special Issue Ehealth, Telemedicine, and AI in the Precision Medicine Era)

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16 pages, 3868 KiB

Open AccessArticle

BDNF/BDNF-AS Gene Polymorphisms Modulate Treatment Response and Remission in Bipolar Disorder: A Randomized Clinical Trial

by Anton Shkundin, Heather E. Wheeler, James Sinacore and Angelos Halaris

J. Pers. Med. 2025, 15(2), 62; https://doi.org/10.3390/jpm15020062 - 7 Feb 2025

Abstract

Background: Bipolar disorder (BD) is a chronic condition associated with treatment resistance, cognitive decline, structural brain changes, and an approximately 13-year reduction in life expectancy compared to the general population. Depression in BD substantially impairs quality of life, while neuroinflammation and excitotoxicity are [...] Read more.

Background: Bipolar disorder (BD) is a chronic condition associated with treatment resistance, cognitive decline, structural brain changes, and an approximately 13-year reduction in life expectancy compared to the general population. Depression in BD substantially impairs quality of life, while neuroinflammation and excitotoxicity are thought to contribute to the recurrence of mood episodes and disease progression. Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal growth and function, with its dysregulation being linked to various psychiatric disorders. This study is an extension of a previously published clinical trial and was conducted to assess the effects of three BDNF and BDNF-AS gene polymorphisms (rs1519480, rs6265, and rs10835210) on treatment outcomes and serum BDNF levels in patients with treatment-resistant bipolar disorder depression (TRBDD) over an eight-week period. Methods: This study included 41 participants from a previously conducted randomized clinical trial, all of whom had available BDNF serum samples and genotype data. The participants, aged 21 to 65, were diagnosed with bipolar disorder, and treatment-resistant depression was assessed using the Maudsley Staging Method. Participants were randomly assigned to receive either escitalopram plus a placebo (ESC+PBO) or escitalopram plus celecoxib (ESC+CBX) over an 8-week period. Statistical analyses included a mixed ANOVA and chi-square tests to compare the minor allele carrier status of three SNPs with treatment response and remission rates. Results: Non-carriers of the rs6265 A allele (p = 0.005) and carriers of the rs10835210 A allele (p = 0.007) showed a significantly higher response to treatment with adjunctive celecoxib compared to escitalopram alone. Additionally, remission rates after adjunctive celecoxib were significantly higher in both carriers and non-carriers across all three SNPs compared to escitalopram alone. However, remission rates were notably higher in non-carriers of the rs1519480 G allele and rs10835210 A allele, as well as in carriers of the rs6265 A allele. Conclusions: This study suggests that genetic variations in BDNF and BDNF-AS genes significantly influence treatment response to and remission with escitalopram and celecoxib in bipolar disorder. Full article

(This article belongs to the Section Omics/Informatics)

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11 pages, 638 KiB

Open AccessArticle

Expanding the Genetic and Clinical Spectrum of Hereditary Transthyretin Amyloidosis: The Glu61Ala Variant

by Christian Messina, Salvatore Gulizia, Federica Scalia, Eugenia Borgione, Francesco Cappello, Filippo Brighina and Vincenzo Di Stefano

J. Pers. Med. 2025, 15(2), 61; https://doi.org/10.3390/jpm15020061 - 6 Feb 2025

Abstract

Introduction. Hereditary transthyretin amyloidosis (hATTR) is a rare disorder with a largely variable worldwide prevalence, and it is caused by autosomal dominant mutations in the transthyretin (TTR) gene, leading to cardiological, neurological, or mixed phenotypes. Apart from the Glu89Gln, Phe64Leu, and [...] Read more.

Introduction. Hereditary transthyretin amyloidosis (hATTR) is a rare disorder with a largely variable worldwide prevalence, and it is caused by autosomal dominant mutations in the transthyretin (TTR) gene, leading to cardiological, neurological, or mixed phenotypes. Apart from the Glu89Gln, Phe64Leu, and Thr49Ala variants, recently, other mutations of TTR gene have been reported in Sicily (His90Asn, Val122Ile, Ser77Phe, Val20Ala). With this paper, we describe a novel mutation in the TTR gene, the Glu61Ala variant, which had been previously reported in only one case with a cardiac phenotype, and the clinical findings surrounding it. Materials and Methods. One individual affected by chronic idiopathic polyneuropathy and a major red flag for hATTR underwent genetic testing to look for mutations in the TTR gene. Then, his relatives were subjected to the same test. We assessed the anamnestic profile and conducted general and neurological examination, blood tests, nerve conduction studies (NCS), electrocardiogram, and Sudoscan for each patient. Written informed consent was acquired for every patient. Results. Among 7 patients screened, 5 patients carried the Glu61Ala variant (71%). The mean age was 64.6 ± 10.2 years, whereas the mean age at onset was 59.4 ± 7.9 years. In our study, three patients (60%) showed a mixed phenotype, whereas two of them (40%) showed a neurological phenotype. Discussion. The Glu61Ala variant was reported only in one case with a cardiological phenotype, but our patients showed both neurological and cardiological involvement. Further studies are needed to improve knowledge of this genetic variant. Full article

(This article belongs to the Special Issue Role of Genetic Tools in Diagnosis and Personalized Treatment for Neurological Diseases)

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9 pages, 762 KiB

Open AccessProtocol

The Design and Feasibility of Optimal Treatment for Coronary Drug-Eluting Stent In-Stent Restenosis (OPEN-ISR)—A Prospective, Randomised, Multicentre Clinical Trial

by Péter Márton Kulyassa, Balázs Tamás Németh, István Hizoh, Laura Krisztina Jankó, Zoltán Ruzsa, Zoltán Jambrik, Brúnó Bánk Balázs, Dávid Becker, Béla Merkely and István Ferenc Édes

J. Pers. Med. 2025, 15(2), 60; https://doi.org/10.3390/jpm15020060 - 2 Feb 2025

Abstract

Introduction: Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is a cornerstone of the management of ischemic heart disease. However, in-stent restenosis (ISR) remains a significant clinical challenge, occurring in approximately 5–10% of patients undergoing PCI. This study is designed to compare the [...] Read more.

Introduction: Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is a cornerstone of the management of ischemic heart disease. However, in-stent restenosis (ISR) remains a significant clinical challenge, occurring in approximately 5–10% of patients undergoing PCI. This study is designed to compare the efficacy and safety of the primary therapeutic approaches for DES-ISR, specifically drug-coated balloons (DCBs)—paclitaxel-coated balloons (PCBs) and sirolimus-coated balloons (SCBs)—with a new-generation everolimus-eluting stent (EES), contributing to the evolving field of personalized medicine. Methods and Analysis: This prospective, multicentre, randomised, non-inferiority trial aims to enroll 150 patients with DES-ISR, who will be randomised into one of the following: SCB, PCB, or EES. The primary endpoint comparing DCB and EES is late lumen loss (LLL) at 6 months, as measured by quantitative coronary angiography (QCA). Secondary endpoints comparing the three arms include a device-oriented composite endpoint, intraluminal gain, optical coherence tomography (OCT) measured LLL, and correlations between LLL and quantitative flow ratio (QFR). The primary endpoint will be analysed using a non-inferiority design, with a margin set at 0.25 mm, for which the sample size was calculated. Statistical analysis of the primary endpoint will be conducted on an intention-to-treat basis with a one-tailed Mann–Whitney U test with a significance level of 95. Secondary endpoints will be analysed via superiority testing using ANOVA, the Kruskal–Wallis test, logistic regression, or Fisher’s exact test, as appropriate. Ethics and Dissemination: The study protocol has been approved by the Medical Devices Department of the Hungarian National Institute of Pharmacy and Nutrition, ensuring compliance with ethical standards as outlined in the Declaration of Helsinki. All investigators declare no conflicts of interest related to this study. The trial is registered in ClinicalTrials.gov under the ID: NCT04862052. Full article

(This article belongs to the Special Issue Complex and High-Risk Coronary Interventional Procedures)

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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, 4178 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)

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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, 694 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)

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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 - 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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Graphical abstract

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)

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