Journal of Personalized Medicine最新文献

{"title":"High Ocular Disease Burden and Increased Referral Needs in Patients with Chronic Kidney Disease: A Step Toward Personalized Care.","authors":"Yulia Liem, Pavitra Thyagarajan, Miao Li Chee, Cynthia Ciwei Lim, Boon Wee Teo, Charumathi Sabanayagam","doi":"10.3390/jpm15050204","DOIUrl":"10.3390/jpm15050204","url":null,"abstract":"<p><p><b>Background/Objectives:</b> To evaluate the prevalence of eye diseases in patients with confirmed chronic kidney disease (CKD) and their referral patterns to ophthalmologists, with the aim of informing personalized screening and referral strategies. <b>Methods:</b> This study involved 528 CKD patients from a tertiary hospital's outpatient renal clinics in Singapore, with CKD defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Retinal photographs from each dilated eye were graded for the presence of diabetic retinopathy (DR) and other eye diseases by professional graders. Patients with significant eye conditions were referred to ophthalmologists based on severity and urgency, categorized as urgent (same day or within 24 h), semi-urgent (within 1-2 weeks), fast-track (within 1-3 months), or annual referrals. <b>Results:</b> More than half of the CKD patients (53.7%) had some form of eye disease; 20% were diagnosed with DR, and 29% required fast-track referrals. Of the 251 patients with diabetes, 67% adhered to annual follow-ups; however, despite this regular monitoring, over half required fast-track referrals for severe eye conditions. Among the 167 non-diabetic CKD patients, nearly a third (31%) were on follow-up, with 7.8% requiring fast-track referrals. Notably, 11% of those not on follow-up also needed fast-track referrals. Seven non-diabetic and ten diabetic patients required urgent referral due to critical conditions such as pseudo-holes, impending occlusions, and disc swelling. <b>Conclusions:</b> These findings underscore the high prevalence and severe nature of eye diseases in CKD patients, even those who are under regular annual follow-up. Integrating systematic eye screening into CKD care supports personalized medicine by enabling early detection and tailored interventions, ultimately improving both visual and overall patient outcomes.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes in the Treatment of Pertrochanteric Femur Fractures: A Retrospective Cohort Study.","authors":"Cesare Donadono, Domenico Tigani, Andrea Assenza, Davide Censoni, Francesco Pesce, Giuseppe Melucci","doi":"10.3390/jpm15050202","DOIUrl":"10.3390/jpm15050202","url":null,"abstract":"<p><p><b>Background:</b> Pertrochanteric fractures of the proximal femur present a common challenge for traumatologists, with intramedullary nailing emerging as the preferred treatment. Complication rates are around 20%, including screw jamming, refractures, implant breakage, or medial migration, with cut-out being the most common. A tip-apex distance (TAD) of >25 mm and incorrect cephalic screw position are predictive factors for cut-out. This study assesses outcomes using the Elos intramedullary nail, based on the experience of the Department of Orthopedics and Traumatology at Ospedale Maggiore in Bologna. <b>Methods:</b> We conducted a retrospective cohort study of 344 patients treated with the Elos intramedullary nail for pertrochanteric femoral fractures from 1 January 2017 to 31 December 2022. The Elos^®-Intrauma nail was implanted using the standard technique. Initial X-rays classified fractures according to the AO-OTA classification, and postoperative X-rays confirmed the cephalic screw's placement per Cleveland's regions. Patients were divided into two groups: optimal cephalic screw position (positions 5-8-9) and other positions. We evaluated TAD, calcar-referred TAD (CalTAD), and postoperative reduction quality using Chang's criteria. The incidence of cut-out and other complications were assessed in connection with these measurements. <b>Results:</b> Among the 344 patients, 227 (65.9%) had the screw in positions 5-8-9, while 117 (34.1%) had it in other positions. The median TAD was 19.47 ± 6.26 mm (range 3.96-46.6), with TAD ≤ 25 mm in 265 patients (77%). The median CalTAD was 22.37 ± 5.65 mm (range 8.75-45.3), with CalTAD ≤ 25 mm in 231 patients (67.1%). According to Chang's criteria, 8 cases (2.3%) had poor reduction, 139 cases (40.4%) had acceptable reduction, and 197 cases (57.3%) had excellent reduction. Cut-out occurred in four cases (1.19%). Multivariate analysis revealed only poor reduction and TAD > 25 mm as independent predictors of cut-out (<i>p</i> < 0.05), while cephalic screw position, CalTAD, and fracture type did not impact cut-out incidence. <b>Conclusions:</b> This study indicates that optimal TAD and quality of reduction are crucial for minimizing cut-out risks. The Elos intramedullary nail shows favorable outcomes with a low cut-out incidence when these parameters are met. Emphasis should be placed on achieving a TAD ≤ 25 mm and excellent reduction quality to reduce complications.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological Features of Non-Small Cell Lung Carcinoma with NRAS Mutation.","authors":"Andrea Ambrosini-Spaltro, Claudia Rengucci, Laura Capelli, Elisa Chiadini, Chiara Bennati, Angelo Delmonte, Silvia Vecchiarelli, Francesco Limarzi, Sofia Nosseir, Graziana Gallo, Mirca Valli, Paola Ulivi, Daniele Calistri","doi":"10.3390/jpm15050199","DOIUrl":"10.3390/jpm15050199","url":null,"abstract":"<p><p><b>(1) Background</b>: NRAS mutations affect fewer than 1% of lung adenocarcinomas. The aim of this study was to describe the clinicopathological features of lung carcinomas with NRAS mutations. <b>(2) Methods</b>: A series of NRAS-mutated lung carcinomas was collected from a molecular diagnostic unit (from four hospitals). The cases were analyzed with next-generation sequencing. A log-rank test for overall survival (OS) was calculated. <b>(3) Results</b>: NRAS mutations were detected in 14/1948 samples (0.72%) of non-small-cell lung carcinomas from 13 patients (8 males, 5 females). NRAS mutations involved codon 61 in the majority (9/13, 69.2%) of cases. The other NRAS mutations affected codon 12 (2/13, 15.4%), codon 13 (1/13, 7.7%), and codon 142 (1/13, 7.7%). In 7/13 cases, co-alterations in additional genes were also present. Pleomorphic/sarcomatoid features were identified in 3/13 (23.1%) cases, in 2/8 (25.0%) histological specimens, and in 2/5 (40.0%) surgical specimens, respectively. Follow-up data were available in 11/13 cases, with 6 patients deceased. By a log-rank test, patients with NRAS mutations in codon 61 had a better outcome (estimated mean of 32.6 ± 7.1 months) compared to those with other NRAS mutations (estimated mean of 8.7 ± 4.4 months), with a significant difference (<i>p</i> = 0.048 for OS). <b>(4) Conclusions</b>: Lung carcinomas with NRAS mutation may display pleomorphic or sarcomatoid features. Mutations in codon 61 showed a more favorable prognosis than those in other codons.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trans-Oral Robotic Surgery (TORS) and Postoperative Hemorrhage: An Analysis of Risk Factors.","authors":"Andrea Migliorelli, Elia Biancoli, Marianna Manuelli, Alberto Caranti, Andrea Ciorba, Chiara Bianchini, Giuseppe Meccariello, Claudio Vicini","doi":"10.3390/jpm15050201","DOIUrl":"10.3390/jpm15050201","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Postoperative hemorrhage is the most common complication after Trans-Oral Robotic Surgery (TORS) described in the literature. The aim of this study is to assess the presence of any risk factors that may impact postoperative bleeding. <b>Methods</b>: This was a retrospective study based on the analysis of patient data. Patients undergoing TORS procedures at the ENT Unit of Forlì Hospital from 2008 to 2022 for OSA (obstructive sleep apnea) or oncological disease and with a minimum follow-up of 30 days were included. The comorbidities analyzed were perioperative anticoagulant/antiplatelet therapy and clinicopathological features concerning the pathology. Total bleeding and severe bleeding (which required management in the operating room) were included. <b>Results</b>: A total of 414 patients (106 oncological TORS and 308 OSA TORS patients) were included. Post-TORS bleeding occurred in 47 cases (11.3%) and severe bleeding in 18 cases (4.3%). The pathology (oncology vs. OSA) treated with TORS did not represent a risk factor (<i>p</i> = 0.466). Antiplatelet intake represented an important risk factor (<i>p</i> = 0.002). Postoperative hemorrhage for oncological TORS occurred in 11.3% patients; of these, 6.6% had severe bleeding. Artery ligation during neck dissection prevented the risk of severe bleeding (<i>p</i> < 0.001). In TORS for OSA, postoperative hemorrhage was found in 11.4% cases, of which 3.6% were major bleeding. Neither the degree of OSA nor the association with other concurrent procedures were risk factors for postoperative bleeding in this study. <b>Conclusions</b>: Patients taking perioperative antiplatelet therapy have an almost 5-fold increased risk of developing postoperative bleeding. The pathology (oncology vs. OSA) does not influence the risk of bleeding. Prophylactic arterial ligation during neck dissection significantly decreases the risk of severe bleeding.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Preliminary Urinalysis to Decision Support: Machine Learning for UTI Prediction in Real-World Laboratory Data.","authors":"Athanasia Sergounioti, Dimitrios Rigas, Vassilios Zoitopoulos, Dimitrios Kalles","doi":"10.3390/jpm15050200","DOIUrl":"10.3390/jpm15050200","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Urinary tract infections (UTIs) are frequently diagnosed empirically, often leading to overtreatment and rising antimicrobial resistance. This study aimed to develop and evaluate machine learning (ML) models that predict urine culture outcomes using routine urinalysis and demographic data, supporting more targeted empirical antibiotic use. <b>Methods</b>: A real-world dataset comprising 8065 urinalysis records from a hospital laboratory was used to train five ensemble ML models, including random forest, XGBoost (eXtreme gradient boosting), extra trees, voting classifier, and stacking classifier. Models were developed using 10-fold stratified cross-validation and assessed via clinically relevant metrics including specificity, sensitivity, likelihood ratios, and diagnostic odds ratios (DORs). To enhance screening utility, threshold optimization was applied to the best-performing model (XGBoost) using the Youden index. <b>Results</b>: XGBoost and random forest demonstrated the most balanced diagnostic profiles (AUROC: 0.819 and 0.791, respectively), with DORs exceeding 21. The voting and stacking classifiers achieved the highest specificity (>95%) and positive likelihood ratios (>10) but exhibited lower sensitivity. Feature importance analysis identified positive nitrites, white blood cell count, and specific gravity as key predictors. Threshold tuning of XGBoost improved sensitivity from 70.2% to 87.9% and reduced false negatives by 82%, with an associated NPV of 96.4%. The adjusted model reduced overtreatment by 56% compared to empirical prescribing. <b>Conclusions</b>: ML models based on structured urinalysis and demographic data can support clinical decision-making for UTIs. While high-specificity models may reduce unnecessary antibiotic use, sensitivity trade-offs must be considered. Threshold-optimized XGBoost offers a clinically adaptable tool for empirical treatment decisions by improving sensitivity and reducing overtreatment, thus supporting the more personalized and judicious use of antibiotics.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shoulder Tendinopathy Induced by Statins: A Case Report and Systematic Review.","authors":"Nicola Manocchio, Carmelo Pirri, Andrea Sorbino, Laura Giordani, Giulia Vita, Concetta Ljoka, Calogero Foti","doi":"10.3390/jpm15050198","DOIUrl":"10.3390/jpm15050198","url":null,"abstract":"<p><p><b>Background:</b> Statins are essential for managing cholesterol levels but can induce musculoskeletal side effects, including tendinopathy of the shoulder. Rotator Cuff Disease (RCD) is one of the most common shoulder tendinopathy. The aim of the present study is to report a clinical case of statin-induce RCD after performing a systematic review on the subject. <b>Materials and Methods:</b> We performed a systematic review of the literature and report the case of a 49-year-old man with statin-induced RCD treated with a personalized individual rehabilitation project (IRP) (steroid and HA injections, mesotherapy, and therapeutic exercise) to investigate the relationship between statins and shoulder tendinopathy. The review followed PRISMA guidelines (2020 version), searching PubMed, Web of Science, and SCOPUS. <b>Results:</b> Out of a total of 217 articles, three cohort studies were suitable for our review. Conflicting evidence emerged regarding the association between statins and shoulder tendinopathy from the included papers. The case report describes a patient who experienced RCD after increasing atorvastatin dosage, with symptoms improving after dose reduction and a multimodal personalized IRP. <b>Conclusions:</b> Statins may contribute to tendon injury by altering the extracellular matrix and cell membrane integrity. While tendinopathy and statin relation is still under discussion, clinicians should monitor patients for tendinopathy and consider switching to alternative treatments in case symptoms arise. The case report demonstrated the successful management of statin-induced RCD with a multimodal personalized IRP. Further research is needed to clarify the relationship between statins and shoulder tendinopathy. Early diagnosis and appropriate personalized management are crucial for optimizing patient outcomes.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Stop Mitral Valve Transcatheter Edge-to-Edge Repair and Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Mitral Regurgitation: A Systematic Review and Meta-Analysis.","authors":"Konstantinos Pamporis, Dimitrios Tsiachris, Konstantinos Grigoriou, Paschalis Karakasis, Ioannis Doundoulakis, Panagiotis Theofilis, Panagiotis Kouvatsos, Athanasios Saplaouras, Athanasios Kordalis, Aikaterini-Eleftheria Karanikola, Panagiotis Antonios Goutis, Konstantinos Tsioufis","doi":"10.3390/jpm15050197","DOIUrl":"10.3390/jpm15050197","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patients with atrial fibrillation and mitral regurgitation (MR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) often have concomitant indications for left atrial appendage occlusion (LAAO), mandating a more personalized treatment approach. This study aimed to examine the effectiveness and safety of combining M-TEER/LAAO in one procedure. <b>Methods</b>: MEDLINE (PubMed), Scopus, and Cochrane were searched through 21 March 2025 for studies examining M-TEER/LAAO with or without control (M-TEER only). Double-independent study selection, extraction, and quality assessments were performed. Frequentist random-effects models were used to calculate mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). <b>Results</b>: Seven studies (223 participants) were included. For M-TEER/LAAO, the mean procedural time was 101.6 min (95% CI = [85.06, 118.13]), the mean radiation time was 29.97 min (95% CI = [23.85, 36.09]), the mean length of stay was 5.21 days (95% CI = [3.31, 7.12]), procedural success was achieved in 89.5% of cases (95% CI = [73.4, 96.3], and post-procedure MR > 2+ occurred in 14.8% of cases (95% CI = [3.6, 44.5]). Compared to M-TEER only, patients with M-TEER/LAAO had similar procedural (RR = 0.91, 95% CI = [0.71, 1.17]) and technical success (RR = 1, 95% CI = [0.94, 1.06]) with a similar risk of acute kidney injury (RR = 1, 95% CI = [0.07, 15.12]), bleeding (RR = 0.40, 95% CI = [0.01, 18.06]), and all-cause death (RR = 0.59, 95% CI = [0.22, 1.54]). M-TEER/LAAO was non-significantly associated with in-hospital death (RR = 3, 95% CI = [0.13, 70.23]), stroke (RR = 3, 95% CI = [0.13, 70.23]), and vascular complications (RR = 1.55, 95% CI = [0.43, 5.59]) compared to M-TEER only. Most patients (34.2%, 95% CI = [2.8, 90.4]) received dual antiplatelet therapy at discharge, followed by anticoagulation only (20.2%, 95% CI = [7.5, 44.3]). <b>Conclusions</b>: M-TEER/LAAO can be combined into a single procedure with good peri-procedural outcomes. Safety was also satisfactory; however, some concerns may arise regarding in-hospital death, stroke, and vascular complications. Further research is needed to explore the effectiveness and safety of this combined strategy and elucidate the risk-benefit profile of this personalized treatment approach.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodologies for the Emulation of Biomarker-Guided Trials Using Observational Data: A Systematic Review.","authors":"Faye D Baldwin, Rukun K S Khalaf, Ruwanthi Kolamunnage-Dona, Andrea L Jorgensen","doi":"10.3390/jpm15050195","DOIUrl":"10.3390/jpm15050195","url":null,"abstract":"<p><p><b>Background</b>: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment and/or determine eligibility, are often unfeasible in practice due to sample size requirements or ethical concerns. Here, we undertake a systematic review of methodologies used in target trial emulations, comparing treatment effectiveness, critically appraising them, and considering their applicability to the emulation of biomarker-guided trials. <b>Methods</b>: A comprehensive search strategy was developed to identify studies reporting on methods for target trial emulation comparing the effectiveness of treatments using observational data, and applied to the following bibliographic databases: PubMed, Scopus, Web of Science, and Ovid MEDLINE. A narrative description of methods identified in the review was undertaken alongside a critique of their relative strengths and limitations. <b>Results</b>: We identified a total of 59 papers: 47 emulating a target trial ('application' studies), and 12 detailing methods to emulate a target trial ('methods' studies). A total of 25 papers were identified as emulating a biomarker-guided trial (42%). While all papers reported methods to adjust for baseline confounding, 40% of application papers did not specify methods to adjust for time-varying confounding. <b>Conclusions</b>: This systematic review has identified a range of methods used to control for baseline, time-varying, and residual/unmeasured confounding within target trial emulation and provides a guide for researchers interested in emulation of biomarker-guided trials.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast-Produced Human Recombinant Lysosomal β-Hexosaminidase Efficiently Rescues GM2 Ganglioside Accumulation in Tay-Sachs Disease.","authors":"Orhan Kerim Inci, Andrés Felipe Leal, Nurselin Ates, Diego A Súarez, Angela Johana Espejo-Mojica, Carlos Javier Alméciga-Diaz, Volkan Seyrantepe","doi":"10.3390/jpm15050196","DOIUrl":"10.3390/jpm15050196","url":null,"abstract":"<p><p><b>Background:</b> Tay-Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder characterized by the accumulation of GM2 ganglioside due to mutations in the <i>HEXA</i> gene, which encodes the α-subunit of β-Hexosaminidase A. This accumulation leads to significant neuropathological effects and premature death in affected individuals. No effective treatments exist, but enzyme replacement therapies are under investigation. In our previous work, we demonstrated the internalization and efficacy of human recombinant lysosomal β-hexosaminidase A (rhHex-A), produced in the methylotrophic yeast <i>Pichia pastoris</i>, in reducing lipids and lysosomal mass levels in fibroblasts and neural stem cells derived from patient-induced pluripotent stem cells (iPSCs). In this study, we further evaluated the potential of rhHex-A to prevent GM2 accumulation using fibroblast and neuroglia cells from a TSD patient alongside a relevant mouse model. <b>Methods:</b> Fibroblasts and neuroglial cell lines derived from a murine model and TSD patients were treated with 100 nM rhHexA for 72 h. After treatment, cells were stained by anti-GM2 (targeting GM2 ganglioside; KM966) and anti-LAMP1 (lysosomal-associated membrane protein 1) colocalization staining and incubated with 50 nM LysoTracker Red DND-99 to label lysosomes. In addition, <i>GM2AP</i> and <i>HEXB</i> expression were analyzed to assess whether rhHex-A treatment affected the levels of enzymes involved in GM2 ganglioside degradation. <b>Results:</b> Immunofluorescence staining for LysoTracker and colocalization studies of GM2 and Lamp1 indicated reduced lysosomal mass and GM2 levels. Notably, rhHex-A treatment also affected the expression of the <i>HEXB</i> gene, which is involved in GM2 ganglioside metabolism, highlighting a potential regulatory interaction within the metabolic pathway. <b>Conclusions:</b> Here, we report that rhHex-A produced in yeast can efficiently degrade GM2 ganglioside and rescue lysosomal accumulation in TSD cells.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Accuracy of ChatGPT-4o in Interpreting Chest and Abdominal X-Ray Images.","authors":"Pietro G Lacaita, Malik Galijasevic, Michael Swoboda, Leonhard Gruber, Yannick Scharll, Fabian Barbieri, Gerlig Widmann, Gudrun M Feuchtner","doi":"10.3390/jpm15050194","DOIUrl":"10.3390/jpm15050194","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Large language models (LLMs), such as ChatGPT, have emerged as potential clinical support tools to enhance precision in personalized patient care, but their reliability in radiological image interpretation remains uncertain. The primary aim of our study was to evaluate the diagnostic accuracy of ChatGPT-4o in interpreting chest X-rays (CXRs) and abdominal X-rays (AXRs) by comparing its performance to expert radiology findings, whilst secondary aims were diagnostic confidence and patient safety. <b>Methods</b>: A total of 500 X-rays, including 257 CXR (51.4%) and 243 AXR (48.5%), were analyzed. Diagnoses made by ChatGPT-4o were compared to expert interpretations. Confidence scores (1-4) were assigned and responses were evaluated for patient safety. <b>Results:</b> ChatGPT-4o correctly identified 345 of 500 (69%) pathologies (95% CI: 64.81-72.9). For AXRs 175 of 243 (72.02%) pathologies were correctly diagnosed (95% CI: 66.06-77.28), while for CXRs 170 of 257 (66.15%) were accurate (95% CI: 60.16-71.66). The highest detection rates among CXRs were observed for pulmonary edema, tumor, pneumonia, pleural effusion, cardiomegaly, and emphysema, and lower rates were observed for pneumothorax, rib fractures, and enlarged mediastinum. AXR performance was highest for intestinal obstruction and foreign bodies, and weaker for pneumoperitoneum, renal calculi, and diverticulitis. Confidence scores were higher for AXRs (mean 3.45 ± 1.1) than CXRs (mean 2.48 ± 1.45). All responses (100%) were considered to be safe for the patient. Interobserver agreement was high (kappa = 0.920), and reliability (second prompt) was moderate (kappa = 0.750). <b>Conclusions:</b> ChatGPT-4o demonstrated moderate accuracy for the interpretation of X-rays, being higher for AXRs compared to CXRs. Improvements are required for its use as efficient clinical support tool.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}