Search Results (43,311)

Background: Adverse pregnancy outcomes such as preeclampsia (PE), preterm birth, low birth weight (LBW), small for gestational age (SGA), and stillbirth are major contributors to maternal and neonatal morbidity and mortality. Elevated maternal homocysteine (Hcy) levels, influenced by genetic, dietary, and lifestyle factors, have been increasingly associated with placental dysfunction and adverse pregnancy outcomes. This review aims to evaluate the link between hyperhomocysteinemia and pregnancy complications to inform clinical practice. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Central Library was conducted up to December 2024. Observational studies assessing maternal Hcy levels in relation to pregnancy complications were included. Heterogeneity was measured using the I² statistic, and a random-effects model using the DerSimonian–Laird method was applied to account for study variability. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. Elevated maternal Hcy was significantly associated with: PE (OR: 2.49; 95% CI: 1.41–4.40; I² = 96.03%; n = 9), preterm birth (OR: 4.01; 95% CI: 1.84–8.72; I² = 91.08%; n = 6), fetal loss (OR: 1.76; 95% CI: 1.22–2.52; I² = 41.47%; n = 6), SGA (OR: 1.69; 95% CI: 1.35–2.11; I² = 0.00%; n = 3), and LBW (OR: 2.46; 95% CI: 1.37–4.43; I² = 77.71%; n = 3). Conclusions: This review highlights a significant association between elevated maternal Hcy levels and various pregnancy complications. However, given the substantial heterogeneity and reliance on observational evidence, these findings should be interpreted with caution. Future well-designed prospective cohort studies with standardized definitions of hyperhomocysteinemia, consistent timing of exposure assessment across pregnancy trimesters, and adjustment for key confounders are needed to better clarify these associations and underlying mechanisms. Full article

Background: The early detection of prostate and testicular tumors remains challenging as standard diagnostic tools often lack sensitivity and produce ambiguous results. Seminal fluid is a biologically rich medium that closely reflects the state of male reproductive tissues and has therefore emerged as a promising source of non-invasive molecular biomarkers. Objective: This study aimed to critically evaluate the evidence regarding cell-free DNA, RNA, proteins and metabolites in seminal fluid, and to assess their potential for improving the early detection of male reproductive cancers. Methods: A systematic review was performed according to PRISMA guidelines. Comprehensive searches of the PubMed and Scopus databases were conducted to identify original clinical studies analyzing molecular biomarkers in seminal fluid from patients with prostate or testicular tumors. For each study, data were extracted on biomarker types, cohort characteristics, analytical methods and diagnostic performance. Results: Forty-two eligible studies were included, covering multiple biomarker classes. Most were observational, single-center investigations classified as level 3b evidence. Across the different types of biomarkers, seminal fluid was associated with tumor-associated molecular changes. Alterations in the concentration, fragmentation and methylation patterns of cell-free DNA (e.g., GSTP1, RARβ2, LGALS3 and OCT3/4) distinguished malignant from benign conditions with sensitivities of up to 80–100%. RNA-based markers, including microRNAs, small non-coding RNAs, and tRNA fragments, showed improved performance in several studies, with multimarker models achieving areas under the curve (AUCs) of 0.85–0.93. Proteomic analyses identified high-specificity candidates such as TGM4, AMACR, PROS1 and DKK3. Metabolomic profiling further strengthened the diagnostic potential; reduced seminal citrate outperformed prostate-specific antigen (AUC 0.748 vs. 0.548), and reproducible shifts in amino acid and lipid profiles were observed in testicular tumors. However, substantial heterogeneity in study design, patient selection, and analytical platforms was observed. Risk of bias varied, and large prospective validation cohorts were lacking. Conclusions: Current evidence suggests that seminal fluid contains molecular signals associated with tumors that could be used for diagnosis. However, the available data are predominantly exploratory and methodologically heterogeneous. Before seminal fluid-based biomarkers can be considered for routine clinical implementation, robust prospective studies with standardized protocols are required. Full article

Background: Older adults hospitalized with acute heart failure frequently present with multimorbidity, frailty, and reduced physiological reserve. This makes accurate prognostic assessment particularly challenging in internal medicine. Traditional heart failure risk models often fail to capture this multidimensional vulnerability. The PROFUND index, developed to estimate medium-term mortality in multimorbid patients, and serum albumin, an established biomarker of nutritional and inflammatory status, may provide complementary prognostic information. This formed the aim of the present study. This study’s objective is to evaluate the individual and combined prognostic value of the PROFUND index and serum albumin for one-year mortality in patients admitted with AHF. Methods: We conducted a prospective, multicenter cohort study within the PROFUNDIC registry. We included consecutive adults hospitalized with AHF or decompensated chronic heart failure who met European Society of Cardiology diagnostic criteria and had NT-proBNP levels >1500 pg/mL. PROFUND scores were obtained at admission, and hypoalbuminaemia was dichotomized as ≤3.5 g/dL. The primary outcome was one-year mortality, analyzed using Kaplan–Meier survival estimates, Cox proportional hazards models, and time-dependent ROC curves. Results: Among 544 included patients (mean age 85 years; 60% women), high PROFUND scores (>7) were present in 39% and hypoalbuminaemia in 55%. Both variables independently predicted one-year mortality, with the highest risk observed in patients presenting both high PROFUND scores (HR 2.26; 95% CI 1.66–3.09; p < 0.001) and hypoalbuminaemia (HR 1.70; 95% CI 1.18–2.46; p = 0.0046). The combined use of these markers modestly improved discriminatory performance compared with the PROFUND index alone (HR 2.83; 95% CI 1.72–4.64; p < 0.000). Conclusions: These findings suggest that integrating clinical complexity, assessed by the PROFUND index, with serum albumin provides a simple and clinically meaningful approach to early risk stratification in very elderly multimorbid patients treated in internal medicine wards. Full article

Background/Objectives: Oocyte donation (OD) pregnancies involve complete maternal–fetal genetic disparity and are associated with increased placental dysfunction and adverse perinatal outcomes. However, a unified histopathological framework to characterize alloimmune-mediated placental injury in OD gestations is lacking. This study evaluates immune and vascular alterations in OD triplet placentas and proposes a structured scoring system, the Placental Allograft Rejection-like Score (PARS), to quantify immunovascular dysregulation. Methods: This retrospective study included all OD triplet pregnancies with placental examination performed during 24 years at a tertiary referral center. Maternal, obstetric, fetal, neonatal, and pathological variables were analyzed at the pregnancy level. Histological and immunohistochemical features previously shown to differ between OD and non-OD pregnancies were grouped into six domains: innate immunity, adaptive immunity, checkpoint regulation, vascular remodeling, complement activation, and trophoblastic behavior. Binary thresholds, immunoreactive scores or established morphological cut-offs, were applied to construct a 20-point score classified into three grades. Results: Forty-five OD triplet pregnancies were analyzed. Intra-pregnancy concordance for PARS components was high, with intraclass correlation coefficient ≥0.70 in 87.3% pregnancies. Increasing PARS grades demonstrated a clear clinical gradient. Grade 3 pregnancies had significantly lower birthweight, higher rates of prematurity (<34 weeks), and increased fetal growth restriction. Placental weight decreased progressively with higher PARS. Histologically, grade 3 placentas showed significantly increased accelerated villous maturation and intervillous fibrin deposition. Conclusions: PARS integrates immune and vascular placental lesions into a structured and reproducible framework that correlates with clinically relevant perinatal outcomes and may support future clinical risk stratification, although further validation in larger, multicenter prospective cohorts is required. Full article

Background: Liver biopsy remains the gold standard for staging chronic hepatitis B (CHB), yet it is invasive, costly, and associated with potential complications. There is a critical need for non-invasive, cost-effective biomarkers to monitor disease progression. This study aimed to evaluate the correlation between the Prognostic Nutritional Index (PNI) and Systemic Immune–Inflammatory Index (SII) with histological fibrosis stages and the Histological Activity Index (HAI) in patients with CHB. Methods: This retrospective study analyzed 274 patients diagnosed with CHB (HBsAg positivity > 6 months) who underwent liver biopsy at the University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital between February 2016 and February 2022. Histopathological findings were staged using the Ishak fibrosis score and HAI. PNI and SII were calculated from peripheral blood parameters. Statistical discrimination power was assessed using Area Under the Receiver Operating Characteristic (AUROC) curves. Results: The cohort comprised 119 females (43.4%) and 155 males (56.6%), with a mean age of 45.25 ± 11.2 years. Mean values were 55.83 ± 5.33 for PNI and 494.37 ± 336.86 for SII. Fibrosis distribution showed 56.2% at stages F0–F1 and 43.8% at ≥F2. For fibrosis staging, SII demonstrated statistically significant but limited predictive ability for Ishak scores ≥F2, while PNI was significant for identifying advanced fibrosis (≥F4) (p < 0.05). SII showed moderate diagnostic performance for severe inflammation (HAI ≥12; AUROC = 0.848), although this finding should be interpreted cautiously. For lower HAI thresholds (≥6), both PNI and SII demonstrated poor discriminative ability (AUROC 0.5–0.6). Conclusions: Both indices were associated with histological parameters but showed limited overall diagnostic performance. SII appeared relatively better; however, this was descriptively observed without formal statistical comparison. These markers may provide complementary information but should not be used as standalone diagnostic tools. Full article

Background/Objectives: Immune aging has been associated with survival outcomes in patients with lung adenocarcinoma (LUAD), but its relevance within the tumor microenvironment (TME) remains unclear. Methods: Clinical, RNA-sequencing, and somatic mutation data from the TCGA LUAD cohort were analyzed. Immune aging score within the TME was quantified using a predefined blood-driven 121-gene immune aging signature (IAS-121), and patients were categorized into the lowest versus the highest IAS-121 tertiles. Immune cell composition in the TME was inferred using xCell. Overall survival (OS) was evaluated using Kaplan–Meier analysis, Cox proportional hazards models adjusted for age, sex, tumor stage, smoking status, and EGFR mutation status, and restricted cubic spline analysis to examine the dose–response relationship between IAS-121 and mortality risk. Sensitivity analyses comparing the highest versus lowest quartiles or higher than median versus lower than median of IAS-121 were performed. Two independent LUAD cohorts (GSE68465 and GSE50081) were employed for validation. Results: A total of 518 patients with LUAD from the TCGA cohort were analyzed. Restricted cubic spline analysis showed a linear association between IAS-121 and OS. Patients in the highest IAS-121 tertile showed significantly better survival than those in the lowest tertile in both the TCGA cohort (p < 0.001) and the external validation cohorts (p = 0.003). In multivariable-adjusted Cox models, the lowest IAS-121 tertile was associated with worse survival in TCGA (adjusted HR 1.87, 95% CI 1.20–2.92) and in the pooled external cohorts (adjusted HR 1.57, 95% CI 1.02–2.43). Subgroup analyses showed generally consistent associations across clinical strata. Tumors with higher IAS-121 exhibited lower CD8⁺ and CD4⁺ naïve T-cell enrichment but higher neutrophil infiltration. Conclusions: Immune aging within TME is associated with poorer survival in LUAD. Given this study is hypothesis-generating, further investigations integrating tissue- and blood-based measures of immune aging are warranted to clarify its clinical and biological implications. Full article

Objective: To investigate the relationship between cardiovascular risk factors and the progression of motor and non-motor symptoms in Parkinson’s disease (PD). Methods: We used data from the Parkinson’s Progression Markers Initiative (PPMI) cohort with a follow-up duration of >5 years. Baseline assessments included genetic analysis, brain MRI, cardiovascular risk factors, and overall cardiovascular disease (CVD) risk. Motor symptoms and non-motor symptoms of PD were evaluated using the Movement Disorders Society revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and sub-scores, Hoehn–Yahr stage, and Montreal Cognitive Assessment (MoCA). Statistical analyses comprised univariate and multivariate linear regression and stratified analysis. Results: A total of 169 newly diagnosed PD patients and 78 healthy controls (HCs) were included. At baseline, no significant differences in cardiovascular risk factors or overall CVD risk were observed between PD patients and HCs. Hypertension (β = 6.748, p = 0.040) and hyperlipidemia (β = 8.316, p = 0.005) were associated with faster motor progression. ApoE genotype was correlated with motor progression (β = 7.593, p = 0.007). PD patients with a moderate-to-low CVD risk (<20%) had milder axial motor symptoms (3.0 [IQR, 4.0] vs. 4.0 [IQR, 5.0], p = 0.048) and lower MDS-UPDRS Part I total scores (7.0 [IQR, 6.25] vs. 9.0 [IQR, 7.0], p = 0.039) at last follow-up compared to high-CVD-risk (≥20%) patients. Overall CVD risk was negatively correlated with total MoCA score at last follow-up (β = −0.208, p< 0.001). Conclusions: Cardiovascular risk factors accelerate the progression of motor and non-motor symptoms in PD, suggesting that management of modifiable CVD risk factors may represent a promising target to delay the progression of PD. Full article

Bone resorption secondary to stress shielding is a leading cause of hip implant failure, primarily due to the stiffness mismatch between the femur and the prosthesis. Although anatomical stem designs generally provide improved load transfer, Dorr type C femurs often require straight stems to ensure adequate primary stability. This work presents a systematic approach to designing a straight, additively manufactured porous titanium hip stem aimed at minimizing stress shielding. The lattice architecture is customized to replicate the mechanical properties of bone based on patient-specific femoral CT scans. The performance of the resulting porous implant is numerically assessed under simplified physiological gait loading conditions. The implant behavior is evaluated through a homogenization strategy to model the lattice structure, significantly reducing the computational effort and making the methodology easily replicable. Compared to its full counterpart, the porous design achieves a significant reduction in predicted bone loss, suggesting that the proposed framework is a promising proof of concept for patient-specific implants. While further experimental validation and larger cohort studies are required, these findings highlight the potential of mechanically tunable porous structures to mitigate the stress shielding phenomenon in anatomical conditions such as Dorr type C femurs, which require straight stems. Full article

Background/Objectives: Zinc deficiency has been associated with increased cancer-related mortality, yet its prognostic relevance in patients with breast cancer and comorbid diabetes remains unclear. This study evaluated the association between zinc deficiency and adverse 5-year clinical outcomes in this population. Methods: This retrospective cohort study used the TriNetX database to identify women aged ≥20 years with breast cancer and type 2 diabetes who had recorded serum zinc levels within 3 months before the index date during the period from 1 January 2013 to 4 April 2026. Patients were categorized into zinc-deficiency, normal-zinc, or high-zinc groups. Outcomes included all-cause mortality, hospitalization, intensive care unit admission, and emergency department visits at the 1-, 3-, and 5-year follow-ups. Cox proportional hazards regression models were applied after 1:1 propensity score matching across 12 demographic and clinical variables. Results: Among 648 eligible patients, 282 had zinc deficiency, 311 had normal zinc levels, and 55 had high zinc levels. After matching, 218 remained in each of the zinc-deficient and control groups. Zinc deficiency was associated with higher all-cause mortality at 1 year (hazard ratio [HR], 2.45; 95% CI, 1.41, 4.28), 3 years (hazard ratio [HR], 2.09; 95% CI, 1.34, 3.28), and 5 years (HR, 1.92; 95% CI, 1.27, 2.92), as well as increased risks of emergency department visits, hospitalization, and ICU admission across follow-up periods. No significant differences were observed between the high-zinc and zinc-normal groups, possibly due to limited sample size. Subgroup analyses identified several exploratory subgroup-specific associations. Conclusions: Zinc deficiency was associated with poorer clinical outcomes in women with breast cancer and type 2 diabetes. However, because low serum zinc may also reflect malnutrition, systemic inflammation, frailty, or disease burden, these findings should be interpreted as hypothesis-generating rather than causal. Full article

Background/Objectives: Individuals with alcohol use disorder (AUD) and tobacco use disorder (TUD) are at increased risk for severe COVID-19 outcomes. However, real-world evidence on vaccine effectiveness (VE) in these populations remains limited, particularly in low- and middle-income countries. This study aimed to evaluate the effectiveness of three or more COVID-19 vaccine doses against mortality in hospitalized patients with AUD and TUD in Brazil. Methods: This retrospective cohort study used data from the SIVEP Gripe database, a national surveillance system of hospitalized COVID-19 cases in Brazil. The study included adults aged ≥18 years with confirmed SARS-CoV 2 infection between February 2020 and June 2025. The intervention was defined as receipt of three or more vaccine doses (fully vaccinated) versus no doses (unvaccinated). Propensity score matching was performed separately for AUD and TUD cohorts. Vaccine effectiveness was estimated using McNemar’s test for paired samples, and the average treatment effect (ATE) and number needed to vaccinate (NNV) were calculated. Results: Among 2,184,723 hospitalized patients, 12,115 had AUD and 45,679 had TUD. After matching, VE against mortality was 42% (95% CI: 27.5–53.5) in the AUD group and 52.6% (95% CI: 46.5–58.1) in the TUD group, compared to 58.5% and 58.9% in their respective non-exposed counterparts. The ATE was consistent across groups (approximately −0.12), and the NNV to prevent one death was 8 (95% CI: 6–15 for AUD; 7–12 for TUD). Conclusions: Although VE was attenuated in individuals with AUD and TUD compared to the general population, the absolute benefit of vaccination remained substantial. Full article

Background: Wireless capsule endoscopy is widely used for diagnosing gastrointestinal diseases, but manual interpretation of capsule videos is time-consuming and can vary between clinicians. Artificial intelligence has been increasingly studied to support capsule analysis and reduce clinical workload. This systematic literature review and meta-analysis summarizes current evidence on artificial intelligence methods applied to wireless capsule endoscopy, with a focus on diagnostic performance, validation strategies, and clinical readiness. Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and Google Scholar. Original journal articles were included based on predefined eligibility criteria. The reviewed studies addressed multiple artificial intelligence tasks, including detection, classification, segmentation, and localization of gastrointestinal abnormalities. Results: A total of 72 studies were included. Meta-analysis using random effects models showed high pooled diagnostic performance across clinical indications and gastrointestinal tract locations, with the strongest results reported for bleeding and vascular lesions and more variable performance for inflammatory bowel disease and mixed abnormality categories. The review also identified important clinical and technical barriers that may limit reliability and slow clinical adoption. These included limited external validation, small patient cohorts, retrospective study designs, and inconsistent reporting and evaluation practices. Conclusions: Artificial intelligence methods show strong potential to support wireless capsule endoscopy interpretation. Based on the findings, we propose practical recommendations to improve study design and validation. If these recommendations are applied, future studies may report more robust and reliable results, supporting better translation into clinical workflows. Full article

Carcinomas of the pancreas and bile duct remain highly lethal malignancies, with surgical resection representing the only potentially curative treatment. Despite improvements in perioperative mortality, postoperative complications remain frequent and negatively affect long-term outcomes. Recent evidence suggests that the pancreas and bile ducts harbor distinct microbial communities, challenging the traditional concept of sterility in these environments. However, their composition and clinical relevance remain incompletely understood. This study aimed to characterize microbiome profiles across different anatomical sites in patients undergoing pancreatic surgery, evaluate the impact of preoperative biliary stenting, and assess associations between prevalent bacterial species and postoperative outcomes. A total of 224 samples (bile, pancreatic fluid, duodenal tissue, tumor tissue, and healthy pancreatic tissue) from 58 patients with pancreatic cancer, bile duct cancer, chronic pancreatitis, or healthy pancreas were analyzed using 16S rRNA gene sequencing. Microbial diversity was assessed using the Shannon index for alpha diversity and nMDS with PERMANOVA for beta diversity. Distinct microbial profiles were identified across body sites, with significant beta-diversity differences between duodenal, bile, and pancreatic fluid samples and between duodenal and pancreatic fluid samples from the same patient. Preoperative biliary stenting significantly influenced microbial composition. Enterococcus faecalis was associated with a reduced risk of severe postoperative complications (Clavien–Dindo ≥ III). Overall, microbial composition varies across anatomical sites and disease entities, and specific bacteria may influence surgical outcomes, warranting further investigation in larger cohorts. Full article

Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value. Full article

Background: We present a retrospective radiographic analysis showcasing the ability to correct hallux valgus using the Lapidus arthrodesis without focused frontal plane rotation of the first metatarsal. Methods: A total of 33 feet in 30 patients who had undergone Lapidus arthrodesis for the treatment of hallux abducto valgus deformity from 1 August 2015 to 31 December 2020 were identified. The median age of the cohort was 55.4 years (range, 33–78 years), 23 were female (76.7%), three (10%) underwent bilateral Lapidus arthrodesis, and the median duration of follow-up was 15.9 months (range, 5–72 months). Results: The median (minimum, maximum) preoperative first intermetatarsal angle was 16° (13°, 28°), and at final follow-up it was 5° (0°, 6°) (p < 0.001). The median (minimum, maximum) preoperative hallux abductus angle was 37° (26°, 51°), and at final follow-up it was 8.5° (0°, 22.5°) (p < 0.001). The median (minimum, maximum) preoperative tibial sesamoid position was 6 (4, 7), and at final follow-up it was 3 (2, 5) (p = 0.001). Conclusions: We found the radiographic first metatarsal lateral round sign to be ambiguous. Qualitative comparison of the results of this investigation with prior studies describing outcomes following Lapidus arthrodesis with focused frontal plane rotation of the first metatarsal suggests that similar outcomes can be achieved without employment of a decisive frontal plane rotation of the first metatarsal. Our findings lead us to believe that correction of substantial hallux abducto valgus deformities can be accomplished using the Lapidus procedure combined with lateral release of the first metatarsophalangeal joint without focused derotation of the first metatarsal. Full article

Background: Scabies is a highly contagious ectoparasitic skin infection that is considered a global public health problem. Treatment primarily focuses on mite eradication, but an inflammatory phase may persist despite successful therapy, known as post-scabietic pruritus (PSP). This study aimed to investigate the clinical features, duration, and severity of PSP in patients with persistent symptoms despite successful treatment. Methods: This cross-sectional descriptive study included 43 adult patients with dermoscopically documented scabies resolution, who reported pruritus persisting for more than 28 days. Demographic and clinical data, including clinical characteristics, treatment history, and pruritus severity assessed by the Visual Analogue Scale (VAS), were collected via structured questionnaires. Results: PSP persisted for 30–365 days, and 48.8% of patients experienced pruritus longer than 45 days. Pruritus severity in 72.1% of patients was reported as a VAS score ≥8. Nodular lesions were observed in 55.8% of patients. Sixteen patients (37.2%) had an atopic background, and nine patients (20.9%) reported a house dust mite (HDM) allergy. Heat, hot baths, and sweating were the most frequent aggravating factors. Despite persistent symptoms, 44.2% of patients reported not receiving any specific treatment after mite eradication. Conclusions: PSP can be prolonged and severe. Nodular lesions may be more frequent than previously reported. Eradication of the mite is the first step, and treatment is not complete until the post-treatment inflammatory phase is controlled. Full article