Search Results (2,557)

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of ischemic heart disease (IHD). Some discrepancies exist between cardiological and nephrological guidelines regarding the extent of diagnostic procedures in CKD patients who are candidates for kidney transplantation. The aim of this study was to assess the cardiac status of these patients after cardiological checkup. Methods: The present study included all kidney transplant candidates referred to the Regional Qualification Center between January 2021 and February 2024. We characterized the group of patients in whom IHD was diagnosed during the cardiological checkup. Results: Among 346 patients, IHD was newly identified in 44 (12.7%) subjects. These patients were significantly older [median 62.9 (51.9–65.4) vs. 47.2 (36.8–57.9) years; p < 0.001], had longer dialysis vintage [median 20 (12.5–42) vs. 14 (6–31) months; p < 0.05] and were more frequently diabetic (29.6 vs. 16.9%, p < 0.05) than the rest of the study cohort. Of note, they were also characterized by significantly more frequent manifestation of atherosclerosis lesions visualized using routine imaging methods (i.e., chest X-ray and abdominal aorta and iliac artery visualization). The stepwise logistic regression analysis revealed that age [OR 1.05 (1.02–1.09); p <0.01] and the ad hoc atherosclerotic score [OR 1.88 (1.27–2.77); p < 0.001] independently predicted the diagnosis of IHD during the cardiological qualification of potential kidney transplant candidates. Conclusions: During the cardiological examination, IHD was diagnosed in a substantial number of kidney transplant candidates. The presence of atherosclerotic lesions detected by routine noninvasive vascular system imaging methods may suggest the need for extending IHD diagnostics even in relatively young patients without clinical symptoms. Full article

Soluble B-cell maturation antigen (sBCMA), generated by shedding of the plasma-cell receptor BCMA/TNFRSF17, is a circulating marker of plasma-cell burden in multiple myeloma (MM). We investigated whether early sBCMA kinetics capture treatment-induced changes in disease biology and predict subsequent Quality of Response (QoR) beyond free light chain (FLC)-based measures. In this prospective longitudinal study, 100 patients with newly diagnosed or relapsed MM starting treatment were evaluated at baseline, 1 month, and 6 months. sBCMA, involved FLC (iFLC), and involved-to-uninvolved FLC ratio (rFLC) were measured, and a 6-month response was assigned according to International Myeloma Working Group criteria. All biomarkers decreased significantly after treatment initiation (p < 0.0001). Across disease-status cohorts, sBCMA, but not iFLC or rFLC, differed at baseline and showed significantly different 1-month percentage reductions. Larger early decreases in sBCMA, iFLC, and rFLC were associated with deeper 6-month responses. In ordinal logistic regression including the three biomarkers dichotomized by a 50% reduction threshold at 1 month, only sBCMA remained independently associated with QoR; patients with <50% sBCMA reduction had higher odds of worse 6-month response (OR 5.44, 95% CI 1.58–18.76; p = 0.007). These findings support early sBCMA kinetics as a biologically informative marker for short-term response monitoring in MM. Full article

Background: The addition of CD-38 monoclonal antibody daratumumab (DARA) to front-line therapy for newly diagnosed multiple myeloma (NDMM) has improved outcomes. The real-world (RW) adoption of treatments remains inconsistent. We aimed to evaluate the adoption of DARA regimens in the treatment of NDMM. Methods: We conducted a retrospective study at a multi-site academic–community healthcare system from August 2020–September 2023. Patients (n = 414) were ≥18 years with NDMM upon initiating front-line therapy. Results: The median age was 69; most were male (60.6%, n = 251), white (69.1%, n = 286), and non-Hispanic (89.6%, n = 371). At diagnosis, 52.2% (n = 216) had R-ISS stage II, and the performance status was preserved, with 69.3% (n = 287) having ECOG 0–1. The adoption of DARA-based induction was incomplete (53.9%, n = 223) and was higher at the academic myeloma center than the community sites (63.9% vs. 47.7%; p = 0.001). At three months after treatment initiation, patients receiving DARA-based induction achieved deeper responses than those treated without DARA. The distribution of IMWG responses favored the DARA group, with a higher proportion attaining VGPR or better (65.0% [n = 145] vs. 51.3% [n = 98]). Conclusions: DARA-based regimens for NDMM were underutilized and notably less common at community sites. Coordinated implementation strategies at the provider and community levels may narrow adoption gaps and translate trial-proven benefits into routine practice. Full article

(1) Background: Coronary artery disease (CAD) frequently coexists with thoracic aortic disease and may increase the risk of adverse outcomes after thoracic endovascular aortic repair (TEVAR). Whether routine preoperative coronary angiography (CAG) improves outcomes remains unclear. (2) Methods: We retrospectively analyzed 177 patients undergoing elective TEVAR between 2015 and 2025 with a median follow-up of 4.9 years. Two analyses were performed: patients who underwent preoperative CAG versus those who did not, and patients with versus without CAD. Survival was assessed using Kaplan–Meier analysis and overlap-weighted Cox regression. (3) Results: Preoperative CAG was performed in 94 patients (53.1%) and identified newly diagnosed or progressive CAD in 42 (44.7%). Overall, 24 patients (13.6%) underwent coronary revascularization before TEVAR. Patients with CAD were older and had a greater comorbidity burden. Despite these differences, preoperative CAG was not associated with differences in in-hospital mortality (2.1% vs. 6.0%, p = 0.159), major adverse cardiovascular events (11.3% vs. 9.0%, p = 0.754), or long-term survival (log-rank p = 0.10). Patients with CAD showed higher unadjusted long-term mortality than those without CAD (31.7% vs. 17.5%; log-rank p = 0.003). However, after overlap weighting, CAD was no longer significantly associated with mortality (adjusted HR 1.4, 95% CI 0.71–2.8). Among patients with angiographically verified coronary disease, preoperative revascularization before TEVAR was not associated with improved long-term survival (HR 2.20, 95% CI 0.69–6.98). (4) Conclusions: Preoperative CAG detects clinically relevant, often unrecognized CAD in a substantial proportion of TEVAR candidates and enables revascularization before surgery. Despite a higher coronary burden, patients who underwent CAG had outcomes comparable to those who did not, and the crude long-term survival disadvantage of CAD was largely explained by the accompanying systemic atherosclerotic burden. Routine preoperative coronary assessment appears justified in elective TEVAR. Full article

Background: Here, we propose a novel predictive scoring system incorporating age and the systemic inflammation response index (SIRI), which is calculated using neutrophil, monocyte, and lymphocyte counts, for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). Methods: The study included 55 consecutive patients with sufficient blood test data and follow-up at our institution between November 2006 and May 2022. Age and SIRI were identified as prognostic factors and incorporated into a predictive multivariate Cox proportional hazards model. A scoring system of 0–2 points was created, with 1 point each assigned to age ≥ 65 years and high SIRI score (≥1.43 × 10⁹/L). We subsequently validated the predictive scoring system in an independent external validation cohort. Results: Patients with 0, 1, and 2 points were assigned to groups 1, 2, and 3, respectively. The median overall survival (OS) was 35.9 months in the entire training cohort and 57.8, 37.2, and 16.1 months in groups 1, 2, and 3, respectively. The three groups showed significant differences in median OS (p < 0.001), with lower scores corresponding to longer survival times. The performance of our new scoring system was significant in the training cohort and in the external validation cohort. Conclusion: Our new scoring system incorporating age and SIRI may serve as a preliminary prognostic model for predicting OS in patients with PCNSL. This score may be beneficial for disease risk stratification and clinical decision-making in the future. Full article

Background/Objectives: Chromosomal microarray analysis (CMA) is an essential tool in modern cytogenetics for detecting copy number alterations and copy-neutral loss of heterozygosity (CN-LOH). As optical genome mapping (OGM) emerges as a potential replacement for traditional cytogenetic methods, the extent to which CMA remains necessary in routine diagnostic workflows remains to be elucidated. Methods: We retrospectively reviewed 53 primary neoplastic cases, selected from a larger cohort of 327 hematologic malignancy specimens, in which CMA identified one or more CN-LOH events. Event size, genomic content, and correlation with next-generation sequencing (NGS) findings were assessed. A separate cohort of newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) was analyzed to evaluate disease-specific CN-LOH frequency. Results: Nearly half of CN-LOH events detected were <25 Mb, below the current detection threshold of OGM inferred from published benchmarks and validated workflows. Many encompassed clinically relevant genes, including FLT3, JAK2, TET2, TP53, and RUNX1. Additionally, two-thirds of cases harbored pathogenic or likely pathogenic variants by NGS within the corresponding CN-LOH regions, further underscoring the clinical value of detecting these copy-neutral events. In contrast, CN-LOH was uncommon in B-ALL, and most alterations identified by CMA would be detectable by OGM. Many of these patients also harbored complex structural rearrangements that required multiple conventional assays for full characterization; these could be resolved by OGM in a single analysis. Conclusions: Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types. Full article

Background/Objectives: To evaluate the diagnostic potential of apparent diffusion coefficient (ADC) values for classifying lymph nodes as benign or malignant in breast cancer patients undergoing [¹⁸F]FDG-PET/MRI staging. Methods: Mean ADC values and short-axis diameters (±standard deviation) of 199 thoracic lymph nodes in 113 newly diagnosed breast cancer patients were retrospectively analyzed. All patients underwent [¹⁸F]FDG-PET/MRI staging, between July 2017 and June 2021. A node-by-node comparison was performed with respect to pathological node status. Nodal FDG uptake in whole-body [¹⁸F]FDG-PET/MRI served as reference standard for nodal malignancy. Group comparison using Mann–Whitney U test, receiver operating characteristic curve (ROC) analysis and diagnostic performance were calculated. p values below 0.05 were defined as statistically significant. Confidence intervals (CI; 95%) were calculated. Results: Ninety-three lymph nodes were FDG-negative while 106 lymph nodes were FDG-positive. FDG-negative lymph nodes had significantly lower short-axis diameters ((5.1 ± 1.5 mm versus 12.3 ± 5.3 mm); p < 0.01; U: 405.50; Z: −11.24). ADC values were significantly lower in FDG-positive lymph nodes (0.72 ± 0.14 × 10⁻³ mm²/s) than in FDG-negative lymph nodes ((1.18 ± 0.18 × 10⁻³ mm²/s); p < 0.01; U: 173.00; Z: −11.80). ROC analysis and Youden’s index revealed an ADC cut-off of 0.95 × 10⁻³ mm²/s (AUC: 0.98; p < 0.01; 95% CI: 0.96–1.01). According to the calculated cut-off, sensitivity, specificity, and accuracy of ADC values for differentiating FDG-negative from FDG-positive lymph nodes were 98%, 97% and 97%, respectively. Conclusions: ADC values derived from MRI were significantly associated with FDG uptake in this retrospective cohort and may serve as a complementary imaging biomarker for lymph node characterization. Full article

Background: Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder occurring during the pubertal growth spurt, and prior studies have demonstrated regional seasonal variation in presentation volume. The relationship between seasonality, socioeconomic deprivation, and disease severity remains incompletely characterized. This study investigated whether SCFE presentation volume demonstrates seasonal variation and whether seasonality is associated with socioeconomic deprivation, body mass index (BMI), and radiographic severity. Methods: We retrospectively reviewed children newly diagnosed with SCFE at a single institution in Wisconsin (USA) between January 2012 and March 2024. Variables included age, sex, race, Area Deprivation Index (ADI), BMI, month of symptom onset, Southwick slip angle, stability, chronicity, and symptom duration. Presentation volume was analyzed using 3-month rolling averages and sinusoidal regression with 12-month periodicity. Associations among ADI, BMI, and slip angle were assessed using linear regression and Spearman’s correlation. Results: In total, 122 of 160 patients met the inclusion criteria. SCFE presentation volume demonstrated significant seasonality (p < 0.05). Lower-volume months were associated with higher neighborhood deprivation and greater radiographic severity (p < 0.05). ADI correlated with slip angle (r = 0.29, p < 0.05) and BMI (r = 0.33, p < 0.05), whereas BMI was not significantly associated with slip angle. Chronic slips demonstrated greater slip angles than acute presentations (p < 0.05). Conclusions: SCFE presentation volume in Wisconsin follows a significant seasonal pattern, and social determinants of health may influence the timing of presentation and disease severity. Full article

Preclinical studies and data from other cancers suggest that inhibition of the Hedgehog (Hh) pathway also has antiproliferative effects on glioma cells. A key component of this pathway is the Smoothened (SMO) protein, which is expressed in high-grade gliomas. Itraconazole (ITRA), a widely used antifungal agent, inhibits SMO, the PI3K/AKT/mTOR pathway, and the VEGF/VEGFR-2 axis—both of which are critical for GBM progression and angiogenesis. This protocol describes a prospective, single-center, dose-escalation phase I study with the classical 3 + 3 design in order to determine the MTD of ITRA. The study enrolls patients with a newly histologically confirmed diagnosis of GBM, without previous treatment except surgery. They will be treated with standard RT schedule (60 Gy in 30 fractions) with concurrent TMZ 75 mg/m² and ITRA 2 × 100 mg, 200 mg, or 300 mg daily. The primary endpoint is to determine the MTD of ITRA given concurrently with RT + TMZ. Secondary endpoints include safety and tolerability of ITRA, overall survival (OS), progression-free survival (PFS), overall objective response rate, use of corticosteroids, treatment compliance, and health-related quality of life (EORTC QLQ-C30 and BN20). Participants will be monitored for one week post-treatment. All relevant statistics will be primarily descriptive. Full article

Background/Objectives: Peripheral biomarkers for autism spectrum disorder (ASD) have shown mixed results in previous studies. In this study, complete blood count-derived immune-inflammatory markers, iron and micronutrient levels, and thyroid function were compared between drug-naïve preschoolers newly diagnosed with ASD and healthy controls. Additionally, the relationships between these markers, symptom severity, and developmental skills were examined. Methods: This retrospective case–control study included 62 children with ASD (aged 24–72 months) and 61 age-matched healthy controls. Symptom severity, behavioral traits, and developmental status were assessed using the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Denver II Developmental Screening Test (DDST), respectively. Composite inflammatory indices were calculated from hemogram data. Statistical analyses incorporated Holm–Bonferroni corrections for multiple comparisons and sex-stratified exploratory analyses of conditional associations using 95% bootstrap confidence intervals based on 5000 resamples. Results: Children with ASD demonstrated significantly lower mean corpuscular volume (MCV; d = 0.66, adj. p = 0.019), lower mean platelet volume (MPV; d = 0.58, adj. p = 0.034), and higher absolute lymphocyte counts (LYMPH; d = 1.10, adj. p = 0.019). Initial group differences in ferritin, serum iron, and transferrin saturation did not survive adjustment (adj. p > 0.05). Composite inflammatory indices were not significantly associated with clinical or developmental scores. Higher CARS and ABC scores correlated with lower personal–social and language scores on the DDST (p < 0.01). Furthermore, exploratory sex-stratified, conditional association analyses suggested preliminary basophil- and lymphocyte-related patterns in girls; however, these findings are strictly hypothesis-generating due to the small female sample size (n = 12). Conclusions: Newly diagnosed, drug-naïve preschoolers with ASD showed a distinct baseline blood profile, including lower MCV and MPV and higher lymphocyte counts. Clinical challenges were most evident in personal–social and language domains. While the primary diagnostic value of routine hemograms in this context appears limited, the exploratory sex-stratified basophil- and lymphocyte-related patterns require validation in adequately powered future cohorts. Full article

Background/Objectives: To evaluate the long-term effects of eosinophilic esophagitis (EoE) on the nutritional status and growth of children. Methods: We performed a retrospective cohort study to assess longitudinal growth patterns (height and BMI z-scores) in pediatric patients (<18 years) newly diagnosed with EoE and followed for at least one year. Nutritional status was classified using BMI-based criteria from the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition and the World Health Organization. Results: Among 50 patients, 20% presented with impaired nutritional status at diagnosis, including 12% with moderate malnutrition (BMI z-score < −2) and 8% with obesity (BMI z-score > +2). After a mean follow-up of 24.5 months, the prevalence of moderate malnutrition decreased to 6%, whereas obesity increased to 12%. Height z-scores remained largely stable over the follow-up period. Conclusions: EoE affects children across the full BMI spectrum. Long-term follow-up highlights the importance of monitoring nutritional status in all pediatric patients with EoE, given the risks of both malnutrition and obesity during disease management. Full article

Background/Objectives: The rising global burden of type 2 diabetes mellitus (T2DM) demands multifaceted and more effective treatment strategies beyond monotherapy to achieve optimal metabolic control. The study aimed to evaluate the integrated effects of SGLT2 inhibitors and metformin in newly diagnosed T2DM patients on biochemical parameters, clinical outcomes and hormonal changes. Methods: This prospective longitudinal study was conducted at the Department of Biochemistry, Baqai Medical University, in collaboration with the Baqai Institute of Diabetology and Endocrinology. A total of 120 newly diagnosed T2DM patients were enrolled and stratified into three groups (n = 40): Group 1 (SGLT2 inhibitors only), Group 2 (SGLT2 inhibitors + metformin), and Group 3 (metformin only). Patients were followed for six months with data collection at baseline, at 3 months and 6 months. Anthropometric indices (weight, BMI, waist and hip circumferences, WHR), biochemical markers (FBS, HbA1c, lipid profile, uric acid, serum creatinine, HOMA-IR), and hormonal levels (insulin, glucagon) were assessed at baseline, first follow-up, and second follow-up. ANOVA, post hoc, Bonferroni and Tukey’s tests were applied; p-value < 0.05 was considered significant. Results: The findings indicate that Group 2 showed the greatest improvement in anthropometric parameters, particularly waist and hip circumferences (p < 0.01). Group 3 demonstrated the most significant improvement in glycemic indices and lipid profile (p < 0.01). HOMA-IR significantly decreased in Group 3 from baseline to the first follow-up (p < 0.01). While insulin levels remain insignificantly different among all groups. Glucagon levels declined significantly from baseline to the second follow-up in all groups, with a more pronounced decrease in Group 3 (p < 0.01). Serum creatinine and uric acid levels showed significant reductions from baseline to the second follow-up in Group 1 and Group 2 (p < 0.05). However, given the observational design, these associations should not be interpreted as causal evidence of renoprotection. Conclusions: Within the limitations of this observational study, early differences among treatment regimens were observed, though metabolic outcomes became statistically comparable across groups by six months. These hypothesis-generating findings suggest potential benefits of early combination therapy that require confirmation in randomized controlled trials. Given the substantial within-group variability and non-randomized design, no definitive conclusions about therapeutic associations can be drawn from these data. Full article

Introduction: Subcortical motor mapping thresholds are routinely used during glioblastoma resection to reduce the risk of permanent neurological injury, but their association with survival is not well established. We evaluated whether the final subcortical motor mapping threshold recorded at the end of resection is associated with overall survival (OS) in patients undergoing mapping-guided resection of motor-eloquent glioblastoma, including exploratory evaluation by residual fluorescence adjacent to the motor pathway. Methods: We performed a retrospective single-center cohort study of consecutive adults with newly diagnosed IDH-wild-type glioblastoma (2018–2024) who underwent motor mapping-guided resection with a documented final subcortical stimulation threshold and received adjuvant oncological therapy. The prespecified exposure was stimulation threshold ≤ 5 mA versus >5 mA. OS was analyzed using Kaplan–Meier estimates and Cox regression. To reduce overfitting, the primary adjusted Cox model included stimulation threshold, age, and temozolomide exposure; a fully adjusted model including age, sex, extent of resection, radiotherapy regimen, and temozolomide was established for sensitivity analysis. Because proportional hazards assumptions were not fully satisfied, restricted mean survival time (RMST) differences were also estimated at prespecified horizons. Results: Among 36 patients, stimulation threshold ≤ 5 mA was associated with shorter OS compared with >5 mA (log-rank p = 0.001). In the primary adjusted Cox model, stimulation threshold > 5 mA remained associated with lower mortality risk (HR 0.35, 95% CI 0.15–0.82, p = 0.016); results were directionally consistent in the fully adjusted model (HR 0.24, 95% CI 0.089–0.643, p = 0.0046). RMST analyses favored the >5 mA group at 12, 18, and 24 months. In exploratory analyses, the association appeared most evident in patients without residual fluorescence adjacent to the motor pathway. Conclusions: Lower final subcortical stimulation thresholds were associated with shorter overall survival after mapping-guided resection of motor-eloquent glioblastoma. These findings suggest that the final intraoperative stimulation threshold was associated with overall survival in adjusted exploratory models and may provide prognostic information in addition to its established role in surgical safety; however, prospective validation in larger cohorts is warranted. Full article

Background and Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as potential biomarkers in type 2 diabetes mellitus and its complications. This pilot exploratory study aimed to identify circulating miRNAs with differential expression in plasma from patients with newly diagnosed type 2 diabetes mellitus compared to age- and sex-matched healthy controls. Materials and Methods: Peripheral venous blood samples were collected from diabetic patients (n = 24) and controls (n = 12). Due to the exploratory nature of the study and limited sample material, samples were pooled within each group prior to plasma separation. Total RNA, including miRNAs, was extracted from plasma and analyzed using a high-throughput qPCR panel. Two normalization methods were applied to assess miRNA expression, and overlapping results were used for downstream analysis. Fold regulation was calculated using the 2^(−ΔCt) method. Results: A total of 33 and 42 miRNAs were identified as differentially expressed using the first and second normalization methods, respectively. Fourteen miRNAs were consistently downregulated across both methods. Several of these miRNAs, including hsa-miR-26a-5p, hsa-miR-146a-5p, hsa-miR-186-5p, hsa-miR-19a-3p, and hsa-miR-652-3p, have been previously associated with glucose metabolism, inflammation, and diabetic complications, such as retinopathy, neuropathy, and endothelial dysfunction. The pooling strategy enabled an efficient exploratory assessment of miRNA expression patterns while reducing inter-individual variability. Conclusions: This exploratory pilot study identifies a panel of circulating miRNAs with altered expression in pooled plasma samples from patients with newly diagnosed type 2 diabetes mellitus. These findings provide preliminary insights that warrant further validation in larger, individual-level studies to assess their diagnostic and prognostic potential. Full article

Background: Eosinophilic infiltration is frequently observed in ulcerative colitis (UC), but its impact on disease course remains incompletely understood. This study aimed to assess eosinophilic infiltration of the colonic mucosa in patients with newly diagnosed UC and to investigate its association with the achievement of clinical remission during the first year of follow-up. Methods: A retrospective study was conducted in patients with newly diagnosed UC. Patients were stratified into two groups according to clinical outcome during the first year of follow-up: clinical remission (n = 30) and non-remission (n = 30). Clinical and laboratory data were extracted from an integrated medical information system database. Archived colonic mucosal biopsy specimens were independently evaluated by two pathologists. Mean eosinophil density across five high-power fields and peak eosinophil count were assessed. Results: In primary biopsy specimens, the median eosinophil density was 19 (11 to 27) cells in the clinical remission group and 33 (23 to 51) cells in the non-remission group. Logistic regression analysis showed that an increased eosinophil count (OR 6.48; 95% CI 1.76 to 23.88; p = 0.005) and the presence of extraintestinal manifestations (OR 5.78; 95% CI 1.17 to 28.6; p = 0.031) were associated with failure to achieve clinical remission during the first year of treatment. Conclusions: In adult patients with ulcerative colitis, a higher density of eosinophils in the colonic mucosa at the time of initial diagnosis is associated with failure to achieve clinical remission during the first year of treatment. These results should be considered hypothesis-generating and require confirmation in larger prospective studies to further clarify the potential prognostic significance of tissue eosinophilia in ulcerative colitis. Full article