Search Results (5,962)

Background/Objectives: Diabetes is major metabolic disorder and rapidly increasing public health problem globally. The greatest way to reduce diabetic complications is adequate knowledge about the condition. Hence, the primary objectives of this study were to evaluate the psychometric properties of the Simplified Diabetes Knowledge Test—Arabic version (SDKT-A) among Iraqi insulin-dependent diabetic patients. Additionally, the secondary objectives were to assess the associated independent variables and the risk of atherosclerosis and cardiovascular risk event by using atherogenic indices and lipid ratios with the SDKT-A. Methods: A cross-sectional, descriptive study was conducted in primary healthcare clinics. The SDKT was translated into Arabic using forward–backward translation, reconciliation, and pilot testing. Thereafter, psychometric properties of the SDKT-A were evaluated depending on different criteria. Atherogenic indices of Castelli risk indices I and II (CRI-I and II), triglyceride/HDL ratio, non-HDL-C ratio, atherogenic coefficient (AC), and triglyceride–total cholesterol–body weight index (TCBI) were calculated using specific formulas. Results: The SDKT-A questionnaire showed acceptable readability and validity. Cronbach’s alpha test (95% confidence interval) was 0.662 (0.59–0.73). The Pearson correlation coefficient of reliability for test–retest was found to be 0.659. The item difficulty index for most items was between 0.237 and 0.877. The point biserial correlation values ranged from 0.028 to 0.535 with Ferguson’s sigma value equal to 0.962. The content validation results showed a significant content validity ratio (CVR) value for most of the questions, ranging from 0.8 to 1. The content validity index (CVI) value for SDKT-A was found to be 0.98, which showed good agreement between experts. In addition, the exploratory factor analysis with promax rotation identified four domains for the final 20 items of the SDKT-A that explained 41.83% of the scale total variance. The mean score of the SDKT-A was 11.09 ± 3.40. The total score of the SDKT-A was positively and significantly correlated with education level (r = 0.322, p < 0.01). In addition, the total scores of the SDKT-A were negatively and significantly correlated with glycemic control, age, CRI-I, CRI-II, triglyceride/HDL ratio, AC, non-HDL-C ratio, and TCBI. Furthermore, the glycemic control (HbA1c) was positively and significantly correlated with the preventive measures factor (r = 0.175, p < 0.05), and were negatively and significantly correlated with the lifestyle and modification factor (r = −0.169, p < 0.05), diet and monitoring factor (r = −0.158, p < 0.05), and awareness factor (r = −0.149, p < 0.05). Conclusions: This study showed acceptable psychometric properties for the SDKT-A, with low levels of knowledge of diabetic disease in the sample population. Finally, comprehensive and interactive educational programs regarding lifestyle and modification, diet, and monitoring and awareness in primary healthcare centers in Iraq are warranted. Full article

Background: Sentinel lymph node (SLN) biopsy has emerged as a cornerstone in melanoma staging, offering targeted evaluation of regional lymphatic spread and guiding therapeutic decision-making. Traditionally, SLN mapping relies on lymphoscintigraphy using technetium-99m (Tc-99m) radiocolloid, but in recent years, indocyanine green (ICG) fluorescence imaging has emerged as a promising alternative. The aim of this review is to evaluate the diagnostic accuracy of ICG–near-infrared (NIR) imaging compared to standard Tc-99m lymphoscintigraphy in SLN biopsy (SLNB). Methods: A systematic review and meta-analysis were conducted, including 12 studies. The primary outcome was the false-negative rate; secondary outcomes included the total number of sentinel lymph nodes (SLNs) identified by ICG–NIR imaging and Tc-99m lymphoscintigraphy, the number of metastatic SLNs detected by each method, and the number of patients with metastatic disease. The statistical analysis for dichotomous variables was performed using the “Odds Ratio” (O.R.) calculated with the Mantel–Haenszel method. For continuous variables, the analysis utilized the “Mean Difference” calculated by the inverse variance method. All data are presented with a 95% confidence interval (CI). Results: ICG was associated with a significantly higher number of SLNs identified compared to Tc-99m (O.R.: 0.41, 95% CI: 0.34–0.49; p < 0.00001), while no significant differences were found in the detection of metastatic nodes, either as a proportion of total SLNs (O.R.: 1.04, 95% CI: 0.86–1.25; p = 0.68) or relative to total positive nodes (O.R.: 0.36, 95% CI: 0.16–0.81; p = 0.01). No statistically significant differences between the two techniques were found in the detection of metastatic patients (OR: 0.80, 95% CI: 0.31–2.03, p = 0.33) and in the total number of false-negative patients missed (risk difference (RD): 0.03, 95% CI: −0.04 to 0.09, p = 0.93). Conclusions: While ICG identifies a higher number of SLNs compared to Tc-99m, its ability to detect metastatic involvement is comparable between the two modalities. No significant differences were observed in the proportion of metastatic SLNs, the total number of positive nodes detected, the number of metastatic patients identified, and the false-negative rate. Given its favorable profile, ICG could represent a reliable alternative or adjunct to Tc-99 in SLNB. However, prospective studies are warranted to validate its standalone diagnostic role. Full article

Background: Cardiovascular comorbidities are major determinants of poor outcomes among patients admitted with COVID-19. However, the prognostic role of arterial hypertension alone remains uncertain. Little is known about the cumulative impact of concomitant hypertension and heart failure. This study assessed whether the combined burden of arterial hypertension and pre-existing heart failure identifies a high-risk phenotype for adverse in-hospital outcomes among COVID-19 patients. Methods: In this retrospective, real-world cohort study, 395 consecutive adults hospitalized with confirmed COVID-19 at a single infectious diseases center between March 2020 and December 2024 were included. We categorized patients into three cardiovascular phenotype groups: no hypertension or heart failure (n = 23), hypertension without heart failure (n = 193), and concomitant hypertension and heart failure (n = 178). The primary outcome was in-hospital all-cause mortality, while ICU admission served as a secondary outcome, invasive mechanical ventilation, and length of hospital stay. Multivariable logistic regression included age, sex, BMI, diabetes mellitus, and vaccination status to evaluate independent associations between the cardiovascular risk group and outcomes. Results: Overall in-hospital mortality was 7.3% (29/395). Mortality increased stepwise across the cardiovascular risk groups: 8.7% in patients without hypertension or heart failure, 3.1% in those with hypertension only, and 11.8% in patients with concomitant hypertension and heart failure (p = 0.004). In adjusted analyses, concomitant hypertension and heart failure were linked to higher adjusted odds of in-hospital death than no cardiovascular disease (odds ratio, 3.49; 95% confidence interval, 1.46–8.35). Isolated hypertension was not significantly associated with mortality. ICU admission and length of hospital stay also increased with cumulative cardiovascular burden. Patients with combined hypertension and heart failure showed more pronounced inflammatory and renal abnormalities at admission. Conclusions: Among hospitalized COVID-19 patients, the coexistence of arterial hypertension and heart failure identifies a vulnerable cardiovascular phenotype associated with higher in-hospital mortality and resource use than either no cardiovascular disease or hypertension alone. These findings support evaluating cardiovascular comorbidities cumulatively rather than in isolation. These findings are exploratory and require external validation in independent, larger multicentre cohorts. Findings may support careful use for short-term risk stratification and closer monitoring strategies during COVID-19 hospitalization. Full article

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are often used in hypertensive patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, binds the ACE2 receptor on the cell surface. This study aimed to identify the risk factors influencing COVID-19 infection in hypertensive patients. Methods: This is a part of a single-center, retrospective, observational study investigating patients ≥ 20 years old at Kenwakai Hospital (Nagano, Japan). COVID-19 was diagnosed by polymerase chain reaction. All patients received antihypertensive drugs. Results: Among 316 patients (mean age, 75.0 ± 13.4 years; men, 55.1%), COVID-19 was diagnosed in 39 (12.3%). Multiple logistic regression analysis after adjustment for age, sex, and smoking status identified increased serum creatinine (Scr) as a significant risk factor for COVID-19 (odds ratio [OR] 1.10; 95% confidence interval [CI] 1.00–1.20; p = 0.046). Conversely, lower serum chloride was associated with COVID-19 (OR 0.92; 95% CI 0.85–0.99; p = 0.047). There was no significant association between COVID-19 and the use of ACEIs and ARBs. Conclusions: Scr was independently associated with COVID-19 risk, whereas ACEI/ARB use was not associated with COVID-19 risk in Japanese hypertensive patients, suggesting that these users need not discontinue or change their treatment. The study population included a very high proportion of patients with advanced chronic kidney disease, which makes the cohort substantially different from the general hypertensive population. However, our results can help guide targeted treatment strategies, improving patient outcomes in healthcare settings. Full article

Background/Objectives: Recurrence after curative gastrectomy for gastric cancer remains common, and treatment options are limited. In selected patients with isolated locoregional relapse, salvage re-gastrectomy may provide durable disease control. This study compared outcomes of salvage re-gastrectomy and chemotherapy for isolated locoregional recurrence. Methods: We reviewed 500 consecutive gastrectomies performed between 2010 and 2024. In total, 66 patients (12.8%) developed isolated locoregional recurrence after previous R0 resection: 25 underwent salvage re-gastrectomy, and 41 received chemotherapy. Propensity-score matching (intended 1:2) was used to balance clinical and pathologic variables, yielding 42 patients (17 surgery, 25 chemotherapy). The primary endpoint was overall survival (OS) from recurrence diagnosis; secondary endpoints included perioperative outcomes and patterns of treatment failure. Results: There were no 30-, 60-, or 90-day deaths after salvage re-gastrectomy. Overall mortality was lower in the surgical group (41.2%) compared with chemotherapy (80.0%; p = 0.010). Salvage re-gastrectomy was independently associated with better OS (HR 0.15, 95% CI 0.02–0.87, and p = 0.035). A longer disease-free interval correlated strongly with survival (ρ = 0.80 and p < 0.001). Surgical patients experienced fewer local (0% vs. 52%) and peritoneal (0% vs. 20%) recurrences. Conclusions: For carefully selected patients with late, isolated locoregional recurrence, salvage re-gastrectomy is feasible and associated with longer survival and improved local control compared with chemotherapy alone. Larger prospective studies are warranted. Full article

Background/Objectives: Considering the excretion pathways and administered gadolinium dose, our institution has developed a tailored gadolinium-based contrast agents (GBCAs) administration protocol for patients with renal impairment to facilitate more rapid elimination and minimal retention of gadolinium. This study aims to evaluate the 8-year clinical outcomes and safety of this institutional protocol. Methods: This single-center retrospective study included patients with renal impairment who underwent GBCA-enhanced MRI between January 2015 and December 2022. The protocol recommended specific GBCAs and adjusted doses based on chronic kidney disease (CKD) stage and serum bilirubin levels: gadoxetate disodium was used for normal serum bilirubin level due to its dual excretion pathway, while macrocyclic agents were used for those with elevated serum bilirubin levels. During the follow-up period, occurrence of nephrogenic systemic fibrosis (NSF) and evidence of gadolinium deposition in brain tissues were evaluated. Results: A total of 288 patients (age, 64.6 ± 11.7 years; male, 64.9%) underwent 716 GBCA-enhanced MRI examinations in accordance with the institutional protocol. The cohort included 62 patients with CKD stage 4 and 131 patients with CKD stage 5 or undergoing hemodialysis. In patients with CKD stage 4 and 5 and those undergoing hemodialysis, 597 examinations were performed using gadoxetate disodium, and 119 used macrocyclic agents. No cases of NSF or gadolinium deposition in brain tissues were identified over mean follow-up intervals of 27.5 and 27.8 months, respectively. Conclusions: The tailored GBCA administration protocol, considering the excretion pathways and administered gadolinium dose, appears to be safe with respect to NSF for patients with renal impairment, and no evidence of brain gadolinium deposition was observed in the evaluated subset of patients. Full article

Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD. Full article

Background: Electrocardiography (ECG) represents an important noninvasive screening tool for heart disease in preparticipation screening of competitive athletes. However, interpretation of pediatric ECG based on age-specific reference values remains challenging, due to considerable variation among studies, influenced by population characteristics and documentation methodology. The variability of normal values in key pediatric ECG features regarding left ventricular hypertrophy (LVH), QTc prolongation and pre-excitation detection seem to have a significant impact on the efficacy of pediatric ECG as a preparticipation screening tool. Aims and Scope of the Study: This review aims to compare contemporary pediatric ECG reference ranges for key ECG features relevant to LVH, QTc, PR and QRS duration and highlight physiological and methodological sources of observed variability. Methods: A review of the current literature was conducted using common biomedical databases for studies reporting certain quantitative ECG reference values in healthy children from infancy through adolescence regarding the above selected key features. Reported values were summarized descriptively, with emphasis on developmental trends and methodological differences among studies affecting ECG values. Results: Across 16 pediatric studies, ECG parameters demonstrated consistent age-dependent developmental patterns, despite variability in absolute values. R-wave amplitudes in left precordial leads increased from infancy through early childhood and remained stable in older children, whereas S-wave amplitudes in right precordial leads showed greater variation between studies. PR intervals and QRS duration increased progressively with age across all datasets, while QTc values remained relatively stable throughout childhood and adolescence, with minimal sex-related differences. Variability in reported reference ranges was most pronounced for amplitude-based—compared to interval duration—parameters, and was influenced by differences in population characteristics, ECG acquisition techniques, and measurement methodology. Conclusions: This review summarizes contemporary ECG reference data in healthy children for the early detection of LVH, pre-excitation and QT prolongation, which are the main objectives of ECG screening in young athletes. Full article

Bortezomib is a 26S proteasome inhibitor used to treat multiple myeloma and systemic amyloidosis. While effective in prolonging survival, bortezomib has been increasingly associated with cardiovascular adverse events (CVAEs), including cardiac failure and arrhythmias, yet a comprehensive post-marketing cardiac safety profile remains incompletely defined. We analyzed cardiovascular adverse events reported between May 2003 and May 2025 using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) via the OpenVigil 2.1 platform. Disproportionality analysis was performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Among over 9 million drug-related adverse events in FAERS, 552 cardiac events were linked to bortezomib. Several cardiac outcomes, including atrial flutter, left ventricular dysfunction, cardiac failure, cardiomyopathy, atrial fibrillation, right ventricular failure, myocarditis, and supraventricular tachycardia, demonstrated elevated disproportionality signals. Separately, cardiac amyloidosis exhibited the highest disproportionality signal (ROR: 35.58; 95% CI: 28.16–44.95), a finding that reflects underlying disease severity rather than treatment-emergent cardiotoxicity. Cardiac failure accounted for the greatest number of hospitalizations (301) and deaths (208), followed by atrial fibrillation and cardiac amyloidosis. Older adults (≥65 years) and patients with amyloidosis or multiple myeloma were the most vulnerable populations. Overall, bortezomib was associated with serious cardiac adverse events, particularly cardiac failure and atrial arrhythmias, underscoring the need for routine cardiovascular risk assessment and proactive monitoring in high-risk patients. Full article

Background: ExPEC9V is a 9-valent vaccine candidate designed to prevent invasive Escherichia coli disease, a life-threatening condition occurring when extraintestinal pathogenic E. coli (ExPEC) invade sterile sites. We evaluated immunogenicity and safety when ExPEC9V was co-administered with high-dose (HD) quadrivalent seasonal influenza vaccine. Methods: This Phase 3, double-blind, placebo-controlled study (NCT06134804) randomized 959 adults (≥65 years) to receive co-administration of ExPEC9V and HD quadrivalent seasonal influenza vaccine (CoAd) or each vaccine alone, 29 days apart (Control). Co-primary objectives were non-inferiority of co-administration versus separate administration following predefined criteria based on influenza strain-specific hemagglutination inhibition (HAI) antibody titers and ExPEC9V O-serotype binding antibody levels (multiplex electrochemiluminescence-based immunoassay), 29 days post vaccination. Reactogenicity and safety were assessed. Results: Co-administration of ExPEC9V with HD influenza vaccine demonstrated non-inferiority (upper bound of 2-sided 95% confidence interval [CI] < 1.5 for HAI geometric mean ratio [Control/CoAd]) for all influenza strains. Non-inferiority for ExPEC9V O-serotype antibody levels was not demonstrated (upper bound 95% CI > 1.5). One of nine serotypes met the non-inferiority criterion; eight did not, with four narrowly failing to meet the non-inferiority criterion. ExPEC9V immunogenicity was similar regardless of urinary tract infection history. ExPEC9V was safe and well tolerated, with no serious adverse events related to ExPEC9V. Reactogenicity rate was higher with co-administration. Conclusions: Co-administration of ExPEC9V with HD influenza vaccine met non-inferiority criteria of humoral immune responses for influenza antigens, but not for ExPEC9V O-serotype antigens. ExPEC9V, administered alone or with HD influenza vaccine, was safe and well tolerated, with an acceptable reactogenicity profile. Full article

Introduction: Subungual squamous cell carcinoma is a rare malignancy of the nail unit that is frequently misdiagnosed as benign nail disease, leading to prolonged diagnostic delays and sometimes invasive spread. Objective: To synthesize the dermoscopic features of histologically confirmed subungual squamous cell carcinoma and to compare patterns between invasive and in situ disease. Methods: We performed a systematic review and meta-analysis (PROSPERO CRD42023470387) following PRISMA and MOOSE guidance. PubMed, Scopus and Cochrane CENTRAL were searched. Extracted data included study design, lesion counts, histologic subtype and specific dermoscopic signs. Random-effects meta-analysis (DerSimonian–Laird with Freeman–Tukey transformation) produced pooled prevalences with 95% confidence intervals. Between-study heterogeneity was assessed with Cochran’s Q and I². We used subgroup and meta-regression analyses to explore the influence of histologic subtype, sample size and publication year. When the data allowed, diagnostic odds ratios were calculated versus common benign mimickers. Results: Twenty studies comprising 121 lesions (96 invasive, 25 in situ) were included. In invasive lesions, the most common dermoscopic findings were subungual hyperkeratosis (pooled prevalence 89%; 95% CI 78–97; I² = 0%), onycholysis (85%; 75–93; I² = 28%), irregular borders (72%; 50–90; I² = 42%), and splinter hemorrhages (52%; 40–65; I² = 36%). In situ lesions more often presented with melanonychia (89%) and showed lower rates of hyperkeratosis (50%). Meta-regression identified histologic subtype as a significant predictor of feature prevalence (p < 0.01). Key comparative performance estimates included a diagnostic odds ratio of 12.6 (95% CI 8.3–19.1) for polymorphous vessels distinguishing squamous cell carcinoma from warts and 6.8 (95% CI 3.2–14.5) for hyperkeratosis versus onychomycosis. Conclusions: Dermoscopy reliably identifies features, particularly hyperkeratosis, onycholysis, irregular margins and hemorrhagic spots, that are common in invasive subungual squamous cell carcinoma; in situ disease more commonly presents with pigmentary changes. Recognition of these signs should lower the threshold for biopsy of suspicious single-digit nail lesions and may facilitate earlier diagnosis and treatment. Full article

Background: Proton pump inhibitors (PPIs) are commonly used to manage acid-related gastrointestinal conditions. Nevertheless, growing attention has been paid to their long-term safety, especially their possible link to dementia and Alzheimer’s disease (AD). Prior research has yielded inconsistent findings, underscoring the need for a comprehensive and current evaluation. Methods: A systematic search was conducted across PubMed, Embase (Ovid), and the Cochrane Library to identify relevant publications up to May 28, 2025, without language restrictions. Two investigators independently extracted study information and evaluated methodological quality as well as potential sources of bias. Eligible studies were observational in design and investigated the association between proton pump inhibitor (PPI) exposure and the risk of developing dementia compared with non-use. For the quantitative synthesis, pooled risk ratios (RRs) and corresponding confidence intervals were generated using a random-effects approach. Study Results: Eighteen studies, encompassing more than 6.3 million participants, met the inclusion criteria. The pooled estimate showed no statistically significant association between PPI use and overall dementia risk (RR = 1.14, 95% CI 0.98–1.33; I² = 99%). However, significant heterogeneity and variable risk of bias—particularly due to confounding, exposure misclassification, and immortal time bias—limit certainty in these findings. Subgroup analyses revealed significantly elevated risks among individuals aged ≥65 years (RR = 1.21, 95% CI 1.01–1.46) and in studies from Asia (RR = 1.31, 95% CI 1.12–1.52) and Europe (RR = 1.32, 95% CI 1.10–1.59), suggesting possible population- or context-specific vulnerability. Conclusions: Our findings reveal a lack of consistent evidence supporting a link between PPI use and dementia risk, primarily due to significant heterogeneity among existing studies. While no robust overall association was demonstrated, significant subgroup signals in older adults and specific regions suggest that clinical uncertainty remains. Rather than indicating a direct causal risk, these results underscore the importance of prescribing stewardship. Clinicians should focus on appropriate prescribing, ensuring long-term PPI therapy is reserved for patients with a clear therapeutic justification and utilized for the shortest effective duration. Full article

Background: Congenital anomalies are influenced by genetic and environmental factors. While interventions including folic acid supplementation have reduced neural tube defects, data on modifiable socio-demographic risk factors remain limited. Aim: This study aimed to assess variation in the prevalence of selected congenital anomalies across the United States according to socio-demographic factors. Methods: A population-based analysis was conducted using CDC-WONDER natality data from 2016 to 2023. Included anomalies were anencephaly, spina bifida, cyanotic heart disease, diaphragmatic hernia, omphalocele, gastroschisis, limb reduction, cleft lip/palate, Down syndrome, chromosomal disorders, and hypospadias. Associations with maternal age, BMI, race, tobacco use, diabetes, and fertility treatments were analyzed. Prevalence rates were calculated per 1000 live births. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Joinpoint regression was used to assess annual percent changes (APCs), with p < 0.05 considered significant. Results: Among 3,482,944 singleton live births in 2023, the overall prevalence of the selected congenital anomalies was 3.3 per 1000. Compared to Caucasian mothers, risk was lower in Asian (RR 0.57; 95% CI: 0.52–0.63) and Black (RR 0.81; 95% CI: 0.76–0.85) infants and higher in American Indian/Alaska Native infants. Significant risk factors included pre-pregnancy diabetes (RR 2.41; 95% CI: 2.16–2.69), maternal age > 45 (RR 2.95; 95% CI: 2.36–3.69), and tobacco use (RR 1.78; 95% CI: 1.64–1.94). A significant decline in prevalence was observed from 2016 to 2023 (APC: –0.6%; 95% CI: –1.1 to –0.2; p = 0.006). Conclusions: Significant disparities and modifiable maternal risk factors were associated with the prevalence of selected congenital anomalies in the U.S. from 2016 to 2023. A modest statistically significant decline in overall prevalence was observed during the study period, supporting the importance of continued national surveillance and targeted preconception and prenatal interventions to reduce risk and address inequities. Full article

Background: Sickle cell disease (SCD) is a prevalent hereditary hemoglobinopathy associated with substantial morbidity, particularly in regions with limited access to advanced laboratory diagnostics. Conventional diagnostic workflows, including manual peripheral blood smear examination and biochemical or molecular assays, are resource-intensive, time-consuming, and subject to observer variability. Recent advances in artificial intelligence (AI) enable automated analysis of blood smear images and offer a scalable alternative for SCD screening. Methods: This study presents a controlled benchmark of CNNs, Vision Transformers, hierarchical Transformers, and hybrid CNN–Transformer architectures for image-level SCD classification using a publicly available peripheral blood smear dataset. Eleven ImageNet-pretrained models were fine-tuned under identical conditions using an explicit leakage-safe evaluation protocol, incorporating duplicate-aware, group-based data splitting and repeated splits to assess robustness. Performance was evaluated using accuracy and macro-averaged precision, recall, and F1-score, complemented by bootstrap confidence intervals, paired statistical testing, error-type analysis, and explainable AI (XAI). Results: Across repeated group-aware splits, CNN-based and hybrid architectures demonstrated more stable and consistently higher performance than transformer-only models. MaxViT-Tiny and DenseNet121 ranked highest overall, while pure ViTs showed reduced effectiveness under data-constrained conditions. Error analysis revealed a dominance of false-positive predictions, reflecting intrinsic morphological ambiguity in challenging samples. XAI visualizations suggest that CNNs focus on localized red blood cell morphology, whereas hybrid models integrate both local and contextual cues. Conclusions: Under limited-data conditions, convolutional inductive bias remains critical for robust blood-smear-based SCD classification. CNN and hybrid CNN–Transformer models offer interpretable and reliable performance, supporting their potential role as decision-support tools in screening-oriented research settings. Full article

Tuberculosis (TB) remains a leading cause of infectious-disease-related morbidity and mortality worldwide, including in low-incidence, high-income countries, where cases increasingly cluster among vulnerable populations. In these settings, persistent diagnostic and treatment delays, rather than a lack of therapeutic options, drive preventable morbidity, ongoing transmission, and inappropriate antimicrobial use. We argue that TB antimicrobial stewardship must extend beyond treatment adherence and resistance containment to encompass the entire diagnostic continuum. Emerging evidence demonstrating a substantial burden of subclinical and asymptomatic TB challenges symptom-based diagnostic paradigms and reveals an underrecognized “asymptomatic delay”, during which radiologic or microbiologic disease is present but undetected. Failure to identify TB during this interval represents a critical stewardship failure, perpetuating empirical broad-spectrum antibiotic exposure while allowing disease progression and transmission. We review diagnostic challenges across the early clinical spectrum of pulmonary and extrapulmonary TB in low-incidence settings, with particular emphasis on migrants and other high-risk populations disproportionately affected by structural and healthcare system barriers. We propose a stewardship-oriented framework integrating targeted screening, enhanced clinical vigilance, front-loaded and parallel diagnostic pathways, and early referral to specialized TB centers. Explicit incorporation of asymptomatic delay into TB diagnostic frameworks can strengthen system accountability, reduce inappropriate antibiotic use, improve patient outcomes, and accelerate progress toward TB elimination in high-income, low-incidence countries. Full article