Journal of Personalized Medicine最新文献

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Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and affects male patients more often than women. Prior studies, however, suggested that women are diagnosed later and at advanced stages of the disease, present with more pronounced symptoms, and experience worse outcomes. Objectives: To investigate sex-specific differences in clinical, laboratory, and comprehensive imaging characteristics in a contemporary cohort of HCM patients from a tertiary referral center in Austria. Methods: We retrospectively analyzed 321 HCM patients enrolled in a prospective registry (2018-2024). All patients underwent a comprehensive baseline evaluation, including medical history, laboratory assessment, transthoracic echocardiography, and cardiac magnetic resonance imaging. Results: At diagnosis, women were significantly older (62 vs. 53 years, p < 0.001) and presented with more advanced functional class (NYHA ≥ II: 80% vs. 49%, p < 0.001). Six-minute walking distance was lower and obstructive HCM was more prevalent in women (425 vs. 505 m, p < 0.001, and 55% vs. 32%, p < 0.001, respectively). Echocardiographic assessment revealed higher diastolic filling pressures (E/E' 18 vs. 10, p < 0.001), larger indexed atrial volumes (29.5 vs. 26.6 mL/m², p < 0.001), a higher left ventricular ejection fraction (70% vs. 62%, p < 0.001), and a larger indexed interventricular septal thickness in women (10.2 vs. 9.3 mm/m², p = 0.004). Moreover, serum levels of NT-proBNP were significantly higher in women (760 vs. 338 pg/L, p < 0.001). Conclusions: Female patients with HCM were diagnosed at an older age, presented with more advanced symptoms, had higher rates of obstructive physiology, and a phenotype characterized by diastolic dysfunction and elevated biomarkers, closely resembling heart failure with preserved ejection fraction. Recognizing these sex-specific disparities is crucial in improving diagnostic awareness and individualized therapeutic management.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the intra- and extrahepatic bile ducts, and is often associated with inflammatory bowel disease (IBD) [...].

Oral infections in neutropenic patients are an underestimated but likely fatal cause of infectious complications, with clinical manifestations often diminished or absent due to immune deficiency. The evaluation and management of these infections requires a personalized multidisciplinary strategy, including prevention through pre-therapy dental assessment, individualized oral hygiene protocols, and rapid treatment of dental lesions. Antimicrobial strategies should be adapted not only to the local resistance profile and individual risk, with a priority on antibiotic stewardship and rapid de-escalation when possible, but also to individual patterns of colonization and comorbidities. Dental procedures can be performed without risk in neutropenic patients with a low complication rate, but further studies are key to stratifying risk. Future research directions include the application of artificial intelligence for infectious risk stratification, the use of salivary or microbiome biomarkers for early detection, and the development of innovative technologies for targeted antimicrobial delivery. This narrative review aims to provide an overview of the common clinical manifestations in neutropenic patients and also the potential progression of dental infections into sepsis in this category of patients.

Background: MiRNAs have emerged as minimally invasive biomarkers with considerable potential for the early detection of oral squamous cell carcinoma (OSCC). Although numerous studies have evaluated circulating miRNAs across different biofluids, the comparative diagnostic performance of saliva-, serum-, and plasma-derived miRNAs has not been systematically clarified. Methods: A meta-analysis was performed by screening PubMed, MEDLINE, Scopus, CINAHL, and related databases. Nineteen eligible studies evaluating miRNA-based assays in saliva, serum, or plasma were included. A random-effects bivariate model was used to calculate pooled sensitivity, specificity, and area under the HSROC curve. Meta-regression using log diagnostic odds ratio (lnDOR) examined whether biofluid type significantly influenced diagnostic performance. Results: Salivary miRNAs showed a pooled sensitivity of 0.76 (95% CI: 0.68-0.82; I² = 84.69%), specificity of 0.79 (95% CI: 0.70-0.85; I² = 70.41%), and an AUC of 0.84 (95% CI: 0.80-0.87). Plasma miRNAs produced comparable results with a pooled sensitivity of 0.77 (95% CI: 0.61-0.88; I² = 90.45%), specificity of 0.79 (95% CI: 0.63-0.89; I² = 80.20%), and an AUC of 0.85 (95% CI: 0.81-0.89). Serum-derived miRNAs demonstrated the highest accuracy with a pooled sensitivity of 0.82 (95% CI: 0.70-0.90; I² = 76.92%), specificity of 0.88 (95% CI: 0.75-0.95; I² = 74.87%), and an AUC of 0.91 (95% CI: 0.89-0.94). Despite serum's numerically superior performance, meta-regression revealed no significant matrix effect (Wald χ² = 0.20, p = 0.903). Conclusions: Although serum-derived miRNAs performed best overall, biofluid type was not a statistically significant determinant of diagnostic performance.

Background/Objectives: Individual responses to CFTR modulators vary widely among people with cystic fibrosis (pwCF), underscoring the need for functional approaches that provide biological context alongside genotype-based therapy selection. Nasal epithelial cultures provide an individual-specific model for theratyping, but most studies rely on freshly isolated cells, restricting repeated testing and long-term sample use. In this study, we tested whether CFTR modulator responses measured in biobanked nasal cells were associated with real-world clinical outcomes. Methods: Cryopreserved nasal epithelial cells from 23 pwCF were differentiated at the air-liquid interface and assessed for CFTR modulator-responsive ion transport using Ussing chambers. In vitro responses were correlated with 6-month changes in sweat chloride concentration (SCC), FEV₁, and BMI. Results: Cryopreserved cultures retained donor-specific CFTR modulator responsiveness. Modulator-induced forskolin/IBMX-stimulated currents correlated with changes in SCC (R = -0.512). CFTR inhibitor-sensitive currents correlated with FEV₁ (R = 0.564). Associations between forskolin/IBMX-stimulated currents and FEV₁ were positive but did not reach statistical significance using two-tailed analysis. BMI changes showed no significant association. Conclusions: Biobanked nasal epithelial cultures preserve clinically relevant CFTR modulator responses at the cohort level, supporting their use as functional assays for population-level assessment in cystic fibrosis. This cryopreservation-based strategy enables repeated testing and may expand access to theratyping beyond freshly obtained samples.

Background/Objectives: Fluoroscopy-guided procedures are widely used across surgical and interventional specialties but expose operators to ionizing radiation with associated stochastic and deterministic effects. The aim is to characterize occupational radiation exposure, evaluate the effectiveness of shielding strategies, assess long-term cancer risks, and identify compliance patterns. Methods: This structured narrative review summarizes evidence on operator dose, shielding effectiveness, compliance with protective practices, and long-term cancer risk. A search of PubMed, Scopus, Embase, and Web of Science (limited to January 2000-March 2024) identified 62 records; 27 full texts were reviewed, and 16 studies met the inclusion criteria. Results: Across studies, unshielded chest exposure averaged 0.08-0.11 mSv per procedure, and eye exposure averaged 0.04-0.05 mSv. Lead aprons reduced exposure by about 90% at 0.25 mm and 99% at 0.5 mm, thyroid collars reduced neck dose by 60-70%, and lead glasses reduced ocular dose 2.5-4.5-fold. Compliance with aprons and thyroid collars was high, whereas lead glasses and lower-body shielding were inconsistently used. Limited epidemiologic data suggested a higher cancer burden in exposed surgeons, and Biologic Effects of Ionizing Radiation (BEIR) VII-based modeling projected increased lifetime risks of solid cancers in chronically exposed operators. Conclusions: Protective equipment substantially reduces operator dose, but exposure variability and inconsistent shielding practices persist and justify standardized monitoring, stronger enforcement of radiation safety protocols, and longitudinal studies.

Residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remain a complex diagnostic and therapeutic challenge. Although NAC has significantly improved pathologic complete response (pCR) rates and transformed surgical approaches, the persistence or evolution of microcalcifications may not accurately reflect residual disease. This discrepancy complicates radiologic interpretation, impacts surgical decision-making, and may lead to overtreatment or unnecessary mastectomies. This review synthesizes current evidence on the radiologic-pathologic correlation of post-NAC microcalcifications, their prognostic value, and their relevance to guiding surgical management in contemporary precision oncology. A narrative review of the literature was performed, focusing on imaging evolution after NAC, pathologic correlations, predictive and prognostic implications, and the role of microcalcifications in defining optimal surgical strategies, ranging from breast-conserving surgery to mastectomy. Emerging contributions from digital breast tomosynthesis, contrast-enhanced mammography (CEM), Magnetic Resonance (MR) and radiomics are also examined. Studies consistently demonstrate that residual microcalcifications are often poor predictors of viable tumor tissue after NAC. Up to half of cases with persistent calcifications may reflect minimal or absent residual invasive cancer, whereas calcifications may also persist in areas of treatment-induced necrosis or fibrosis. Reliance on calcifications alone may therefore lead to unnecessary extensive resections. Conversely, specific morphologic patterns, especially fine pleomorphic or branching calcifications, are more strongly associated with residual malignancy. Advanced imaging and radiomics show promise in improving predictive accuracy. Residual microcalcifications after NAC should not be interpreted as a direct surrogate of residual disease. A multimodal assessment integrating imaging evolution, tumor biology, and treatment response is essential to optimize surgical planning and avoid overtreatment. Precision surgery in the NAC era increasingly requires individualized decision-making supported by advanced imaging and robust radiologic-pathologic correlation.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in screening and therapeutic strategies, early detection and individualized treatment remain major challenges. In recent years, an expanding repertoire of biomarkers has emerged, spanning genomic, transcriptomic, proteomic, and metabolomic signatures. Epigenetic features, such as DNA methylation panels, as well as non-coding RNAs and the gut microbiome, hold potential not only for improving early diagnosis but also for refining prognosis and predicting therapeutic responses within the framework of precision oncology. This narrative review provides an updated, integrative overview of CRC diagnostic, prognostic, and predictive biomarkers. We distinguish established markers already in clinical practice, such as RAS and BRAF mutations, HER2 amplification, microsatellite instability/mismatch repair deficiency (MSI/dMMR), and widely investigated molecular alterations including TP53 mutations and immune-checkpoint-related markers, from novel biomarkers with growing translational potential. We also discuss the implementation challenges of these biomarkers in clinical practice, including issues related to validation, standardization, and cost-effectiveness, as well as the multi-modal approach for the development of composite diagnostic panels.

Background/Objectives: Bipolar disorder (BD) is increasingly recognized as a multisystem condition in which metabolic abnormalities, particularly insulin resistance (IR), may be linked to illness severity and neuroprogression. Despite growing evidence linking IR to adverse clinical outcomes, the data is heterogeneous and preliminary, and its specific association in hospitalized patients with BD remains underexplored. Methods: This cross-sectional study included 86 inpatients with a primary diagnosis with BD at the IRCCS Ospedale Policlinico San Martino, Genoa, Italy, between July 2023 and January 2024. Sociodemographic, clinical, and metabolic characteristics were systematically investigated. IR was defined as a HOMA-IR index ≥ 2.5. Results: Twenty-eight patients met criteria for IR. Insulin resistant patients showed a significantly longer illness duration, more frequent residual symptoms, and higher rates of ≥5 lifetime psychiatric hospitalizations. They also exhibited greater polypharmacy (≥4 psychotropics at discharge) and daily alcohol use. Furthermore, the IR subgroup was significantly associated with higher body mass index and triglycerides, lower HDL cholesterol and physical activity levels. Conclusions: Our findings indicate that IR is associated with markers of greater illness burden in BD. While these results are consistent with emerging hypotheses on metabolic dysfunction in BD, longitudinal studies are required to clarify temporal and causal relationships. These associations suggest that IR may represent a clinically relevant component of BD rather than a secondary metabolic consequence. Routine metabolic screening and the preferential use of metabolically neutral agents may improve long-term outcomes and align with the emerging paradigm of precision psychiatry.