Journal of Personalized Medicine最新文献

Gestational diabetes mellitus (GDM) has witnessed a persistent rise in the prevalence over the past few decades, imposing a substantial burden on global health and economies. GDM exerts both short-term and long-term effects on neuropsychiatric systems of the mothers and their progeny. This review catalogs the neurodevelopmental and neuropsychiatric disorders in GDM women and their offspring and summarizes the possible relationships as well as the underlying mechanisms, which would enhance our understanding of the neuropsychiatric disorders related to GDM, offering information on personalized strategies for patients.

Thromboprophylaxis in hospitalized patients is a critical component of care aimed at preventing venous thromboembolism (VTE), a common and potentially fatal complication during hospitalization. The risk of VTE varies substantially across patient populations, influenced by the type of illness, including both surgical procedures and medical comorbidities, and requires individualized assessment. At the same time, the implementation of pharmacological thromboprophylaxis must carefully balance the risk of thrombosis against the potential for bleeding. Commonly used risk assessment models, such as the Padua and IMPROVE scores, can help clinicians stratify patients according to their individual risk of VTE and bleeding complications. The aim of the present review is to provide a structured synthesis of the current evidence on thromboprophylaxis strategies in hospitalized patients, critically appraise the performance and applicability of existing VTE and bleeding risk models and highlight how these tools can guide a tailored illness-specific approach to prophylactic decision-making. Where relevant, the review also outlines practical, risk-adapted algorithms to optimize thromboprophylaxis across diverse clinical settings.

Growth Differentiation Factor-15 (GDF-15) is a stress-responsive cytokine belonging to the Transforming Growth Factor-beta (TGF-β) superfamily. Initially identified as macrophage inhibitory cytokine-1 (MIC-1), GDF-15 is expressed in various tissues and markedly upregulated under pathological conditions involving inflammation, oxidative stress, and tissue injury. Notably, GDF-15 upregulation has been associated with several cardiovascular events, such as heart failure, atrial fibrillation, atherosclerosis, coronary artery disease, and stroke. Furthermore, it has been observed that GDF-15, either alone or in combination with other cardiac biomarkers, can provide valuable complementary information enhancing risk assessment, early detection of cardiovascular events, and prediction of adverse outcomes. GDF-15 can be measured in various body fluids, using different methods. Immunoassays are widely employed and offer good sensitivity and reproducibility; however, variability between methods and potential interference from genetic variants highlight the need for standardization. This review summarizes current insights into GDF-15, with emphasis on its quantification methods, biological functions in cardiovascular diseases, and its emerging role as a diagnostic and prognostic biomarker.

Purpose: Candida bloodstream infections remain a major global health challenge, with mortality rates approaching 40%. Beyond classical immunocompromised status, recent evidence highlights additional risk factors, including iatrogenic immunosuppression, advanced age, prolonged hospitalization, exposure to broad-spectrum antibiotics, and total parenteral nutrition. While Candida albicans (C. albicans) remains the most common species in Europe and the USA, non-albicans species, particularly Nakaseomyces glabratus (N. glabratus), Candida tropicalis (C. tropicalis), and Candida parapsilosis (C. parapsilosis), are emerging worldwide. Methods: This retrospective observational cohort study was conducted at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in Salerno, Italy, from January 2015 to December 2024. It included all patients with at least one positive blood culture for Candida species. Demographic data, hospital ward of admission, and antifungal susceptibility profiles were collected and analyzed using SPSS software (IBM SPSS Statistics for Mac, version 30 (IBM Corp., Armonk, NY, USA)). Results: The incidence rate is 48.7 new isolates per one thousand patient-days, with a trend of increasing episodes over time among a total of 364 patients. Most cases occurred in medical wards (59.5%), where patients were older (median age 76 (17). C. albicans accounted for 57.9% of isolates, and a significant association was found between species distribution and hospital unit (p < 0.05). Resistance to fluconazole, voriconazole, and amphotericin B increased among C. albicans, with similar trends in N. glabratus and C. parapsilosis. Conclusions: This large single-center cohort highlights both the persistent dominance of C. albicans and the worrisome rise in resistance among C. parapsilosis. Given the aging patient population and increasing antifungal resistance, local epidemiological data are crucial to guide empirical therapy. Our findings underscore the need for multidisciplinary antifungal stewardship programs to optimize personalized treatment strategies and contain the emergence of resistant strains.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that causes progressive renal failure, nephrolithiasis, and nephrocalcinosis in children. It is characterized by hepatic overproduction of oxalate. Conventional management, which involves combined liver-kidney transplantation, vitamin B6 supplementation, and intense hydration, does not address the underlying metabolic defect for most patients and it generally provides only supportive care. The first approved disease-modifying treatment for pediatric PH1 is Lumasiran, a small interfering RNA (siRNA) therapeutic. By specifically inhibiting the hepatic glycolate oxidase mRNA, Lumasiran lowers the production of oxalate at its origin. Along with fewer kidney stone events and stabilization of nephrocalcinosis, clinical trials (ILLUMINATE-A/B/C) showed significant decreases in urinary oxalate excretion. The most frequently reported adverse event is mild injection-site reactions, which are generally well tolerated. The molecular mechanism, pharmacokinetics, and clinical effectiveness of Lumasiran in children with PH1 are compiled in this review. We go over possible long-term safety concerns, the impact of early intervention on renal outcomes, and the function of siRNA therapies in pediatric precision medicine. Furthermore, we highlight Lumasiran's importance as a model for targeted treatment in uncommon pediatric kidney diseases by considering it in the larger context of RNAi-based therapies. A paradigm shift in pediatric nephrology is signaled by Lumasiran, which changes the therapeutic approach from supportive care to precision, targeted medicine. Further research and empirical data will clarify its long-term advantages, the best ways to treat it, and the possible use of siRNA technologies for other genetic renal disorders.

Background: At the onset of Type 1 Diabetes (T1D), international guidelines recommend initiating subcutaneous insulin therapy within a wide dosage range (0.5-1 IU/kg/day), as insulin requirement (IR) varies greatly based on several factors, including age, pubertal status, and the presence of diabetic ketoacidosis (DKA). In clinical practice, some individuals require higher-than-expected IR, leading to prolonged hospitalization. This study aimed to identify predictive factors for elevated IR at T1D onset. Methods: We conducted a retrospective observational study including 218 children and adolescents diagnosed with T1D between January 2010 and September 2020. Clinical and laboratory parameters were collected. IR was defined as the highest daily subcutaneous insulin dose (IU/kg/day) during hospitalization, after resolution of DKA. Results: As expected, DKA severity and HbA1c levels were associated with increased IR. However, the strongest independent predictor in the multivariate model was serum triglyceride level (β = 0.27, p < 0.001), with an adjusted R² of 0.37. No evidence of multicollinearity was detected, and ROC analysis yielded an AUC of approximately 0.70. Conclusions: Hypertriglyceridemia at T1D onset is independently associated with higher IR, regardless of DKA severity. Early recognition of this marker could help optimize insulin dosing, improve metabolic stabilization, and potentially shorten hospital stays.

Background/Objectives: The hypothalamic-pituitary-testis axis is known to be dysregulated in patients with hematological malignancies. However, data on the association between the type of hematological malignancies and semen quality are discordant. In the era of personalized medicine, identifying disease-specific patterns of reproductive impairment is crucial to optimize fertility preservation strategies. While patients with leukemia often show a clear deterioration in semen quality, studies on Hodgkin and non-Hodgkin lymphomas have shown that spermatogenesis is not always compromised. Indeed, some patients may present normospermia before treatment. This study aimed to assess semen parameters in males affected by hematological malignancies compared with a non-cancer population and to explore implications for individualized fertility preservation counseling. Methods: We performed a retrospective monocentric study including all patients affected by hematological malignancies who underwent fertility preservation at the Maternal and Child Department, Gynecology and Obstetrics, Oncofertility Unit, Federico II of Naples, from January 2017 through December 2024. In total, 247 patients with hematological malignancies and 63 non-cancer males undergoing in vitro fertilization for female tubal factor, selected as a control group, were included in the analysis. Sperm parameters (semen volume, sperm concentration, motility, and morphology) were first compared between the hematological malignancy group and the control group, and then among hematological malignancies classified as Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and leukemia (L). Results: Overall, according to World Health Organization (WHO, 2021) criteria, semen parameters of patients with hematological malignancies were at the 25th percentile, except for motility, which was below the 5th percentile. Significant differences were observed in sperm concentration/mL, total sperm number, and percentage of total sperm motility between the hematological malignancy group and the control group (p = 0.0004; p = 0.0003; p < 0.0001). Based on disease classification, 158 patients had Hodgkin lymphoma, 54 had non-Hodgkin lymphoma, and 35 had leukemia. Significant differences in concentration/mL and total sperm number were found between the Hodgkin lymphoma group and the control group (p = 0.003; p = 0.001). The percentage of total sperm motility was significantly decreased in all subtypes of hematological malignancies compared with controls, especially in the leukemia group (HL p = 0.001; NHL p = 0.004; L p < 0.001). Conclusions: These findings highlight significant impairment of semen quality, particularly motility, reinforcing the role of personalized medicine in tailoring fertility preservation strategies according to malignancy subtype and baseline reproductive risk.

Background: Systemic inflammation is an essential factor in the formation of the tumor microenvironment and has an impact on patient response to immune checkpoint inhibitors. Although there is a growing interest in biomarkers of inflammation, there is a gap in understanding their predictive value for response to nivolumab in clinical practice. The objective of this research was to design and assess a multi-algorithmic machine learning (ML) model based on regular systemic inflammation measurements to forecast the response of treatment to nivolumab. Methods: An analysis of a retrospective real-world cohort of 177 nivolumab-treated patients was performed. Baseline inflammatory biomarkers, such as neutrophils, lymphocytes, platelets, CRP, LDH, albumin, and derived indices (NLR, PLR, SII), were derived. After preprocessing, 5 ML models (Logistic Regression, Random Forest, Gradient Boosting, Support Vector Machine, and Neural Network) were trained and tested on a 70/30 stratified split. Accuracy, AUC, precision, recall, F1-score, and Brier score were used to evaluate predictive performance. The interpretability of the model was analyzed based on feature-importance ranking and SHAP. Results: Gradient Boosting performed best in terms of discriminative (AUC = 0.816), whereas Support Vector Machine performed best on overall predictive profile (accuracy = 0.833; F1 = 0.909; recall = 1.00; and Brier Score = 0.134) performance. CRP and LDH became the most common predictors of all models, and then neutrophils and platelets. SHAP analysis has verified that high CRP and LDH were strong predictors that forced the prediction to non-response, whereas higher lymphocyte levels were weak predictors that increased the response probability prediction. Conclusions: Machine learning models based on common inflammatory systemic markers give useful predictive information about nivolumab response. Their discriminative ability is moderate, but the high performance of SVM and Gradient Boosting pays attention to the opportunities of inflammation-based ML tools in making personalized decisions regarding immunotherapy. A combination of clinical, radiomic, and molecular biomarkers in the future can increase predictive capabilities and clinical use.

Background/Objectives: Female tubal factor infertility is a major clinical challenge. While surgical repair of the fallopian tubes remains the traditional standard, biological fibrin sealants have been proposed to reduce tissue trauma and improve reproductive outcomes. Methods: We conducted database searches of PubMed/MEDLINE, EMBASE and Google Scholar until 31 August 2025, using the keywords "tubal anastomosis", "tubal reanastomosis," "tubal reanastomosis", "uterine horn anastomosis", "fibrin glue", "fibrin sealant", "biological sealant", "tissue adhesive", "rabbit", "rat" and "sterilization reversal." Reference lists of retrieved articles have been examined to find studies which tested end-to-end tubal (or small-animal uterine horn) anastomosis through biological adhesives with or without additional components to evaluate patency success, fertility results and adhesion formation. Results: Thirteen studies met the inclusion criteria (eleven animal; two human). Rat and rabbit models demonstrated that fibrin sealants with intraluminal splints and one-to-two anchoring sutures produced results comparable to microsutures for patency (tubal patency rates of 75-100%) and pregnancy success (pregnancy rates of 60-83%) while reducing surgical time and decreasing peritubal adhesions. The success rates of the procedures depended on the anastomosis locations. Isthmic-isthmic anastomosis produced better results than ampullary repairs which tended to fail or develop stenosis. Fibrin sealant-only repairs without splinting were associated with lower patency (almost 60%) despite acceptable histologic healing. Human data showed similar pregnancy rates (intrauterine pregnancy in about 40-50% of women) and tubal patency but no consistent decrease in adhesions. Ectopic pregnancy rates ranged from 9 to 11%. Conclusions: Fibrin sealants are useful adjuncts to microsurgical tubal repair, but they should not replace the basic repair procedures. The effectiveness of this procedure is dependent on three critical factors: precise segment alignment, proper use of splints and stents, and selection of segments with comparable caliber. In a personalized-medicine framework, fibrin-assisted reanastomosis may offer a tailored option for selected women who desire natural pregnancy. Modern standardized research is required to define indications and analyze how the adaptation of fibrin sealants in minimally invasive procedures affect reproductive outcomes, ectopic pregnancy rates, and adhesion development.

Background: A subset of patients with T1-T2 oesophageal cancer are not candidates for surgery or chemotherapy and have a poor prognosis due to limited treatment options. This study evaluated the combination of external beam radiotherapy (EBRT) and endo-oesophageal brachytherapy (EBT) as a curative treatment in these patients, with cause-specific survival (CSS) and local recurrence-free survival (LRFS) as the primary endpoints. Methods: This was a single-centre retrospective analysis of 11 patients with T1-T2 oesophageal cancer treated between 2005 and 2024 with combined EBRT and EBT schedules. Clinical data, treatment schedules, outcomes, and complications were obtained from patient medical records and follow-up documentation. Descriptive statistics and Kaplan-Meier survival analysis were used. Results: The median follow-up was 22 months (2-61 months). CSS rates were 79.5% at 2 years, 66% at 3 years, and 30% at 5 years. LRFS rates were 74.1%, 59%, and 39%, respectively. One severe toxicity (grade ≥ 3) was observed. The most frequent mild toxicities were oesophageal mucositis (18.2%) and ulceration (18.2%). Conclusions: EBT in combination with EBRT seems to be a feasible and well-tolerated treatment with curative intent for inoperable T1-T2 oesophageal cancer patients, offering favourable survival outcomes in a population with limited therapeutic alternatives.