Prospective Case-control Study Research Articles

Role of Artificial intelligence model in prediction of low back pain using T2 weighted MRI of Lumbar spine

Background Low back pain (LBP), the primary cause of disability, is the most common musculoskeletal disorder globally and the primary cause of disability. Magnetic resonance imaging (MRI) studies are inconclusive and less sensitive for identifying and classifying patients with LBP. Hence, this study aimed to investigate the role of artificial intelligence (AI) models in the prediction of LBP using T2 weighted MRI image of the lumbar spine. Methods This was a prospective case-control study. A total of 200 MRI patients (100 cases and controls each) referred for lumbar spine and whole spine screening were included. The scans were performed using 3.0 Tesla MRI (United Imaging Healthcare). T2 weighted images of the lumbar spine were segmented to extract radiomic features. Machine learning (ML) models, such as random forest, decision tree, logistic regression, K-nearest neighbors, adaboost, and deep learning methods (DL), such as ResNet and GoogleNet, were used, and performance measures were calculated. Results Our study showed that Random forest and AdaBoost are the most reliable ML models for predicting LBP. Random forest showed high performance with area under curve (AUC) values from 0.83 to 0.88 across all lumbar vertebrae and L2-L3, L3-L4, and L4-L5 intervertebral discs (IVDs), with AUCs of 0.88 the highest at L5-S1 IVD (0.92). Adaboost demonstrated high performance at the L2-L5 vertebrae with AUC values of 0.82 to 0.90, with the highest AUC (0.97) at the L5-S1 IVD. Among the DL models, GoogleNet outperformed the other models at 30 epochs with an accuracy of 0.85, followed by ResNet 18 (30 epochs) with an accuracy of 0.84. Conclusion The study demonstrated that ML and DL models can effectively predict LBP from MRI T2 weighted image of the lumbar spine. ML and DL models could also enhance the diagnostic accuracy of LBP, potentially leading to better patient management and outcomes.

Association between neutrophil-to-lymphocyte ratio and motor subtypes in idiopathic Parkinson's disease: a prospective observational study.

Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1βand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1β in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1β plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1β was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1β showed better performance in identifying the AR motor subtype. NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD.

Prospective In Vivo Confocal Microscopy of the Central Cornea in Terrien Marginal Degeneration.

To analyze central corneal in vivo confocal microscopy (IVCM) in Terrien marginal degeneration (TMD). An observational prospective case-control study. Ten Finnish patients with TMD from a tertiary referral center were compared with 10 age- and sex-matched healthy volunteers. Seven patients had bilateral TMD. Age, anterior segment optical coherence tomography, extent of thinning in clock hours, grade of microdots, and stage of TMD were analyzed. According to Süveges and Wang classification, the median stage of TMD was 2 (range, 2-3) and 2 (range, 2-6), respectively. Twelve (71%) of 17 eyes with clinical TMD showed corneal thinning at all clock hours. The median age at the time of examination was 70 years (range, 28-81), and the median time from diagnosis 8.8 years (range, 6.0-15.2). By IVCM, the epithelium, subepithelial nerve plexus, and endothelium were intact in all eyes. The anterior stroma showed bilateral hyperreflective dots in the central cornea beneath the subepithelial nerve plexus in all eyes, and larger patches were detected in the posterior stroma anterior to Descemet membrane; both were invisible by anterior segment optical coherence tomography. As compared with controls, the grade of anterior microdots increased faster with age before the age of 65, and that of posterior stromal patches was higher. Two patients additionally had bilateral hyperreflective needle-like deposits in the anterior and midstroma. By IVCM, TMD is characterized regardless of clinical laterality by bilateral microdots in the central corneal stroma. They might be a supporting diagnostic criterion and alone could suggest subclinical disease.

Evaluation of Anterior and Middle Brain Structures With Cerebrovascular Flow in Fetuses With Fetal Growth Restriction: A Prospective Study.

To investigate the adaptation of the anterior cerebral artery (ACA) in fetuses with fetal growth restriction (FGR) and assess if forebrain and midbrain structures are affected by vascular adaptations. A prospective case-control study involving normally developed fetuses and those with late-onset FGR (estimated fetal weight < 3rd percentile and/or abdominal circumference < 3rd percentile). Doppler indices of the middle cerebral artery (MCA), ACA and umbilical artery (UA) were determined between 32 + 0 and 37 + 0 weeks. Neurosonography assessed the depth of the insula, the sylvian fissure, and the antero-posterior diameter of the frontal lobes (FAPD). The cerebral-placental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were lower in FGR cases. ACA PI percentile values were significantly lower in the FGR group (p = 0.020). Sylvian fissure depth was significantly lower in FGR fetuses. The ACA may be the first cranial vascular structure affected in fetuses with FGR. This may be related to the impact on postnatal cognitive functions in FGR patients. NCT06215690.

Comparison of a Scheimpflug imaging with other screening indices in diagnosing keratoconus and keratoconus suspect

Keratoconus (KC) is an irreversible blinding eye disease; therefore, early screening of KC suspects (KCS) is crucial for protecting patients’ quality of life. Scheimpflug imaging is a commonly used screening device in clinical practice. We aimed to evaluate the diagnostic ability of a Scheimpflug imaging device (Scansys) for KC and KCS and compared it with other Scheimpflug-based devices (Pentacam and Corvis ST). This prospective case-control study included 107 normal eyes, 72 KCS, and 57 KC. Scansys screening index Keratoconus probability (KCP) showed excellent performance in diagnosing KC at a cutoff value of 16.4 (area under the receiver operating characteristic [AUROC] = 1.000), with 100% sensitivity and 98.11% specificity. KCP had a better KCS diagnostic ability at a cutoff value of 8.9 (AUROC = 0.813) than Corvis biomechanical index (CBI, AUROC = 0.764), reaching 67.61% sensitivity and 85.85% specificity. Pentacam screening index Belin/Ambrósio enhanced ectasia display deviation (BAD-D) showed the best performance with 92.96% sensitivity and 89.62% specificity at a cutoff value of 1.525 (AUROC = 0.970) in diagnosing KCS. Scansys provides accurate KCP parameters in diagnosing KC; however, the efficiency of diagnosing KCS should be further optimized.

Copeptin as an inflammatory marker in diagnosis and prognosis of neonatal sepsis

BackgroundCopeptin is an immediate biomarker of individual stress response; many life-threatening diseases are causing a high elevation of its concentration in plasma, such as myocardial infarction and cardiovascular shock. Moreover, copeptin is a promising marker in sepsis. We aimed to evaluate copeptin as a diagnostic and prognostic marker in neonatal sepsis for the early initiation of appropriate therapy and the prediction of mortality. A prospective case-control study involved 237 neonates (165 cases had neonatal sepsis, and 72 served as controls). Cases were admitted to the neonatal intensive care unit (NICU) and followed up for symptoms and signs of sepsis confirmed by laboratory data: complete blood count (CBC), c-reactive protein (CRP), and cultures. Serum copeptin level by the enzyme-linked immunosorbent assay (ELISA) was measured for all included neonates. We observed that the copeptin level was significantly higher in cases than control (3.51 ± 1.4, 1.61 ± 0.51 pmol/liter, respectively). The cut-off value of copeptin at which we can discriminate between cases and controls was above 2.065 pmol/liter. Among cases, copeptin was higher in early-onset sepsis (EOS) than late-onset sepsis (LOS) neonates, and there was a significant correlation between its level and all the following: age at admission, birth weight, gestational age, history of perinatal asphyxia, maternal chorioamnionitis, and premature rupture of membrane (PROM). Also, copeptin was strongly associated with CRP level and the poor prognosis of patients. Copeptin can predict the death of cases at a cut-off value above 2.995 pmol/liter.ConclusionSerum copeptin level can be used as a diagnostic and prognostic marker in neonatal sepsis.

New Marker in the Umbilical Cord Blood of Fetuses with Fetal Growth Restriction: Serum Sortilin-1 Level

Objective: To determine the role of sortilin in the pathogenesis of fetal growth restriction (FGR) by examining serum sortilin levels in fetal cord blood. Methods: This prospective case-control study was conducted at Ankara Etlik City Hospital between July 2023 and January 2024. Group 1 included 44 pregnant women with late FGR; Group 2 included 44 healthy pregnant women as controls. Results: Umbilical cord blood sortilin levels were significantly higher in the FGR group [2.96 (2.43–4.01)] compared to the control group [2.12 (1.74–3.18)] (p = 0.001). Sortilin levels negatively correlated with APGAR scores at 1 min (r=-0.281, p = 0.008) and 5 min (r=-0.292, p = 0.006). A sortilin threshold of 2.58 ng/ml predicted composite adverse neonatal outcomes with 66.7% sensitivity, 53.1% specificity, and an AUC of 0.652 (95% CI: 0.529–0.775, p = 0.031). Conclusion: This study showed that sortilin levels, which are indicators of oxidation, were higher in the cord blood of newborns with late FGR.

Cardiopulmonary exercise testing following acute pulmonary embolism: Systematic review and pooled analysis of global studies.

Recent reports have revealed a substantial morbidity burden associated with "post-PE syndrome" (PPES). Cardiopulmonary exercise testing (CPET) has shown promise in better characterizing these patients. In this systematic review and pooled analysis, we aim to use CPET data from PE survivors to understand PPES better. A literature search was conducted in PubMed, EMBASE, and Cochrane for studies reporting CPET results in post-PE patients without known pulmonary hypertension published before August 1, 2023. Studies were independently reviewed by two authors. CPET findings were subcategorized into (1) exercise capacity (percent predicted pVO2 and pVO2) and (2) ventilatory efficiency (VE/VCO2 slope and VD/VT). We identified 14 studies (n = 804), 9 prospective observational studies, 4 prospective case-control studies, and 1 randomized trial. Pooled analysis demonstrated a weighted mean percent predicted pVO2 of 76.09 ± 20.21% (n = 184), with no difference between patients tested <6 months (n = 76, 81.69±26.06%) compared to ≥6 months post-acute PE (n = 88, 82.55 ± 21.47%; p = 0.817). No difference was seen in pVO2 in those tested <6 months (n = 76, 1.67 ± 0.51 L/min) compared to ≥6 months post-acute PE occurrence (n = 144, 1.75 ± 0.57 L/min; p = 0.306). The weighted mean VE/VCO2 slope was 32.72 ± 6.02 (n = 244), with a significant difference noted between those tested <6 months (n = 91, 36.52 ± 6.64) compared to ≥6 months post-acute PE (n = 191, 31.99 ± 5.7; p < 0.001). In conclusion, this study, which was limited by small sample sizes and few multicenter studies, found no significant difference in exercise capacity between individuals tested <6 months versus ≥6 months after acute PE. However, ventilatory efficiency was significantly improved in patients undergoing CPET ≥ 6 months compared to those <6 months from the index PE.

Impact of Pemphigus on Sleep Quality: A Prospective Observational Single-Center Case-Control Study.

Pemphigus, an autoimmune disorder, significantly impacts the quality of life for those affected. This study examined the sleep quality in patients with pemphigus, a domain for which the existing literature provides limited data without a focused analysis. A total of 156 individuals, 52 in the case and 104 in the control group, completed several questionnaires (Pittsburgh Sleep Quality Index [PSQI], General Health Questionnaire-12 [GHQ-12], and ABQOL [Autoimmune Bullous Disease Quality of Life]). Disease severity was evaluated using the Pemphigus disease area index (PDAI index). The case group exhibited significantly higher levels of psychological distress, reflected in GHQ-12 scores (P = 0.00), and notably poorer sleep quality compared to controls across various parameters (sleep latency [SL], disturbances [SDi], medication [SM], daytime sleep dysfunction [DSD]), and the global PSQI score (GS)] (P = 0.00)). Significant correlations were observed between PDAI scores and sleep duration (SDu) (P = 0.01), SM (P=0.03), SL (P =0.03), and GS (P=0.00). An association was found between the equivalent steroid intake and SDu (P=0.00) as well as GS (P=0.02). No statistically significant correlation emerged between disease duration and PSQI scores. Our findings indicated a correlation between poor sleep quality and cutaneous rather than mucosal manifestations (p=0.01). Pemphigus affects sleep quality. Severe disease showed heightened SDi, correlating with higher steroid doses, and in the chronic phase, the impact seems to have been more influenced by the pro-inflammatory stage of the disease. Patients with cutaneous pemphigus exhibited reduced sleep quality compared to those with oral pemphigus. Understanding that pemphigus worsens sleep quality can be beneficial for the holistic management of individuals with this condition.

Urinary Free Glycosaminoglycans Identify Adults at High Risk of Developing Early-stage High-grade Bladder Cancer

Background and objectiveScreening for bladder cancer (BCa) could reduce mortality via early detection of early-stage high-grade (Ta/T1 N0 M0 grade 2–3) disease. Noninvasive biomarkers could aid in screening, but current markers lack the specificity required. The urinary free glycosaminoglycan profile (GAGome) is a promising biomarker for early detection of BCa metabolism. MethodsIn a prospective case-control development study, we included patients with BCa or no evidence of disease (NED) and measured the urinary GAGome. We then developed a score to predict the probability of BCa using GAGome features that correlated with BCa versus NED according to Bayesian regression. Next, in a retrospective, population-based, case-control study, we included adults from the Lifelines Cohort Study who were presumed healthy at baseline. All cases with BCa confirmed in the cancer registry by the 2-yr or 6-yr study visit were matched to randomly selected control subjects. We developed a reference logistic regression model using age and sex to predict BCa at 7 yr after baseline. We then added the GAGome score to the model and assessed model improvement using the likelihood ratio test. We dichotomized outputs for the reference model and saturated model (reference + GAGome score) into high-risk versus low-risk categories using a 99% specificity cutoff and estimated the sensitivity for association with BCa at 7 yr. Key findings and limitationsWe prospectively included 51 individuals with BCa and 38 with NED and observed alterations in three GAGome features compatible with BCa. We developed a score that discriminated BCa with an area under the receiver operating characteristic curve of 0.77 (95% confidence interval [CI] 0.67–0.87). We retrospectively selected a cohort of 1088 presumed healthy adults (median age 48 yr, 56% females), of whom 48 had developed BCa by 7 yr after baseline (median time to diagnosis 1.4 yr). The GAGome score was an independent predictor of BCa at 7 yr when added to the reference model (p < 0.001). The sensitivity for BCa at 7 yr for high-risk subjects was 31% (95% CI 20–43%) using the saturated model and 17% (95% CI 4.7–29%) using the reference model at 99% specificity (95% CI 98–99%). Conclusions and clinical implicationsThe urinary free GAGome is specifically altered in BCa and can be used for noninvasive identification of adults at high risk of developing BCa, independent of age and sex. This information could be useful for the design of risk-stratified targeted screening programs for BCa. Patient summaryWe tested whether measurement of a class of sugars called glycosaminoglycans (GAGs) in urine could be used for early detection of bladder cancer. Our results show that GAG levels in urine can distinguish people at high risk of developing bladder cancer within 7 years, even if they are healthy at the time of the urine sampling.

Assessment of salivary and serum leptin in tobacco smokers and oral squamous cell carcinoma-A case-control study

ObjectivesOral squamous cell carcinoma (OSCC) is the most common head and neck malignancy and tobacco-related cancers account for a significant portion of all oral cancers. Cancer patients often suffer from cachexia, which contributes significantly to mortality. Leptin is a protein released by adipocytes identified to play an important role in obesity and inflammation. The present study aimed to quantify and compare salivary and serum leptin in tobacco smokers and OSCC. Materials and MethodsThe present prospective case-control study enrolled 42 subjects divided equally among OSCC and tobacco smokers without oral lesions (TS). Both saliva and blood were collected from each subject and leptin levels were determined using enzyme-linked immunosorbent assay. The data obtained were analysed using Mann Whitney U, Kruskal Wallis, Friedman, and Spearman correlation tests (p < 0.05). ResultsA significant reduction in both salivary and serum leptin levels in OSCC was observed (p < 0.001, 0.002 respectively). In addition, significant reductions in weight and body mass index were also observed during follow-ups at 3, 6, and 9 months (p < 0.001 for both). ConclusionsReduced salivary and serum leptin levels in OSCC proved that it is an important diagnostic marker, with non-invasive saliva measurement being more patient-friendly. Future multicentric studies with higher samples in OSCC subgroups are warranted. Clinical RelevanceLeptin reduction in oral squamous cell carcinoma proved to be an important diagnostic marker. Non-invasive salivary techniques could be employed in mass screening programmes. The significant correlation between leptin and BMI also shed insight into the overall well-being of the patient.

Metabolomics of basal tears in amyotrophic lateral sclerosis: a cross-sectional study

PurposeAmyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes. MethodsA single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed. ResultsTwenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p>0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid). ConclusionThis study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.

Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance

BackgroundChildren with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors.MethodCMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors.ResultsCardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1–2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (β = −0.425, P = 0.019) and LVRI (β = −0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (β = 0.429, P = 0.022). In the CKD stage 3–5 group, higher in systolic blood pressure (SBP) (β = 0.464, P = 0.005) and PCR (β = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3–5 group with hypertension than those without.ConclusionCardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3–5. Strict BP control may help reverse or prevent remodeling.

Stress Assessment in Parents of Children With Autism Spectrum Disorder: A Prospective Case-Control Study

Stress Assessment in Parents of Children With Autism Spectrum Disorder: A Prospective Case-Control Study

Investigating soluble CD40 ligand as a prognostic factor among acute coronary syndromes patients: A multi-center prospective case-control study.

Soluble CD40 ligand (sCD40L) is a protein that plays a crucial role in the inflammatory response associated with the development and progression of acute coronary syndrome (ACS). Recent studies have suggested that sCD40L may be a useful prognostic factor for ACS, but the data are conflicting. This study aimed to investigate the potential of sCD40L as a prognostic marker among ACS patients and provide valuable insights for clinical practice. To our knowledge, this is the first study of its type in the Arabic World. A multi-center prospective case-control study was conducted in Damascus, Syria, involving 158 participants with different ACS subtypes (STEMI, NSTEMI, UA) and a control group of healthy individuals. Sociodemographic data, medical history, and sCD40L levels were collected. The predictive ability of sCD40L for ACS, STEMI, NSTEMI, and UA was assessed using receiver operating characteristic (ROC) curves. Statistical analysis was performed using IBM SPSS version 25. The study included 58 STEMI, 33 NSTEMI, 36 UA patients, and 30 healthy individuals. The mean age of participants was 55 years (SD 10.7 years). Analysis of sCD40L levels revealed significantly higher concentrations in ACS patients compared to the control group (P < .001). ROC curve analysis demonstrated that sCD40L had a significant predictive ability for ACS, STEMI, and NSTEMI (P < .05), while its predictive value for UA was not statistically significant. This study provides evidence supporting the potential of sCD40L as a prognostic factor in ACS. The elevated levels of sCD40L observed in these subtypes indicate its potential usefulness in risk stratification and predicting adverse cardiovascular events. Further investigations are warranted to establish standardized sCD40L cutoff values and evaluate its clinical implications in the management of ACS patients.

T cell responses and clinical symptoms among infants with congenital cytomegalovirus infection.

BACKGROUNDCongenital cytomegalovirus (cCMV) infection can cause developmental impairment and sensorineural hearing loss (SNHL). To determine the relationship between immune responses to cCMV infection and neurologic sequelae, T cell responses were compared for their connection to clinical symptoms at birth and neurodevelopmental outcomes.METHODSThirty cCMV-infected and 15 uninfected infants were enrolled in a single-center prospective observational case-control study. T cell pp65-specific cytokine responses; CD57, CD28, and PD-1 expression; and memory subsets were compared.RESULTSInfected neonates (73% symptomatic at birth) lacked pp65-specific cytokine-secreting T cells, with elevated frequencies of CD57+, CD28-, and PD-1+CD8+ T cells and effector memory subsets. Though frequencies overlapped between cCMV symptom groups, asymptomatic infants had higher frequencies of CD57+PD-1+CD8+ T cells. Neonates with subsequent developmental delay lacked detectable CMV-specific T cell responses, with patterns resembling those of uninfected infants. Two children with progressive SNHL had high frequencies of PD-1+CD8+ T cells over the first year compared with children without progressive SNHL.CONCLUSIONSimilar to published reports, neonatal viral antigen-specific cytokine-secreting T cell responses were not detected, but overall patterns indicate that globally differentiated memory CD8+ T cell populations were induced by cCMV infection, with higher frequencies of terminally differentiated PD-1+CD8+ T cells potentially associated with asymptomatic infection. In this cohort, a lack of in utero T cell differentiation was associated with developmental delay, and high frequencies of PD-1+CD8+ T cells persisted only in children with progressive SNHL. Further work is needed to define the specificity of these T cells and their mechanistic connection to these outcomes.FUNDINGThis study was funded through an intramural research award at Nationwide Children's Hospital, the Pediatric Infectious Disease Society Fellowship Award funded by Stanley and Susan Plotkin and Sanofi Pasteur, the Abigail Wexner Research Institute at Nationwide Children's Hospital, and the Pichichero Family Foundation Vaccines for Children Initiative Research Award from the Pediatric Infectious Diseases Society Foundation.

Dietary Determinants of Metabolic and Gut Microbial Health in Patients with Inflammatory Bowel Disease

Background: Diet has been linked to gut dysbiosis and the onset, course, and response to treatment of patients with IBD and metabolic disease. Methods: This single-centre prospective case-control study investigated the relationship between dietary intake, metabolic profile, and stool microbial composition in 57 individuals with IBD in clinical remission and 24 healthy individuals (HC). Participants’ baseline anthropometric measurements, serum metabolic parameters, lipid profiles, and oral and stool samples for microbiota testing were collected. Their dietary intake and physical activity were documented. A partially corrected correlation was performed to examine the associations between variables and p-values adjusted for multiple comparisons using the Benjamini–Hochberg equation (adj-p). Results: In participants with IBD, the intake of saturated fat correlated positively, and the intake of dietary fibre correlated negatively with anthropometric indices (saturated fat and BMI: r = 0.37, adj-p = 0.04, fibre and BMI: r = −0.45, adj-p = 0.01). Higher anthropometric indices were associated with poorer glucose control and a less favourable serum lipid profile (BMI and insulin: r = 0.48, p &lt; 0.01, WHR and triglycerides: r = 0.57, p &lt; 0.01). The stool microbiota of participants in the IBD group was less diverse and more similar to their oral microbiota than was observed in the HC group (Mann–Whitney U test p = 0.03). Within the IBD group, a higher intake of added sugar and processed meat and a higher serum insulin level was associated with lower stool microbial alpha diversity (processed meat intake and Shannon’s diversity: r = −0.43, adj-p = 0.02; added sugar and Shannon’s diversity: r = −0.39, adj-p = 0.03; insulin and Shannon’s diversity: r = −0.45, adj-p = 0.02). Neither the dietary intake nor stool microbial composition correlated with the risk of disease flaring. Conclusions: Our findings suggest that dietary intake is associated with the metabolic health and gut microbial composition of IBD patients.

A study of the relationship between circulating cytokines (interleukin-2 receptor and tumor necrosis factor receptor 2) and risk of B-cell non-hodgkin lymphoma.

Mature B-cell non-Hodgkin lymphoma (B-NHL) occurs due to uncontrolled B-lymphocyte clonal expansion. Cytokines can directly stimulate B-cell proliferation and prevent B-cell apoptosis. Dysregulation of cytokines may play an important role in the development of B-NHL by enhancing chromosomal translocation, which is the hallmark of B-NHL. Both interleukin 2 and tumor necrosis factor-α are proinflammatory cytokines and play important roles in the growth, differentiation, and apoptosis of B cells.We conducted a prospective case-control study applied to 50 patients with B-NHL at Kasr Al Aini Hospital, Cairo University, and 50 age- and sex-matched controls. Clinical, laboratory and imaging data were collected. In all patients and controls, sIL-2R and sTNF-R2 levels were measured by enzyme-linked immunosorbent assay (ELISA). The Spearman correlation test was used to evaluate the correlation between the studied cytokines and clinical, laboratory and imaging findings. Sensitivity analysis was conducted to detect the cutoff values of the studied cytokines.Serum levels of sIL-2R and sTNF-R2 were significantly higher in patients than in controls. Additionally, their levels were significantly higher in aggressive types and advanced stages of lymphoma. Also, the studied cytokines were significantly correlated with different clinical and laboratory parameters of lymphoma. The level of sIL-2R and sTNF-R2 were closely related to the type of lymphoma (P value ˂ 0.001 and 0.012, respectively), further it was also associated with the natural history of lymphoma (aggressive vs. indolent) (P value ˂0.001 and 0.04 respectively).We concluded that Pretreatment levels of sIL-2R and sTNF-R2 may play a role in the natural history and prognosis of lymphoma. They may be used as a prognostic factor for B-NHL patients and may also help with treatment decisions.

Correlation between Overweight, Obesity, Gestational Diabetes Mellitus, Adipokines (Adipolin and Adiponectin), and Adverse Pregnancy Outcomes: A Pilot Study.

Background: The prevalence of overweight (OW), obesity (OB), and gestational diabetes mellitus (GDM) has been increasing worldwide in recent years. Adipolin is a new adipokine with reduced circulating levels in obesity and type 2 diabetes mellitus (T2DM). Objectives: Our prospective case-control study aimed to evaluate the maternal serum levels of adipolin and adiponectin, metabolic parameters, and anthropometric characteristics at the time of oral glucose tolerance test (OGTT) in pregnant women with a pre-pregnancy body mass index (BMI) ≥ 25 Kg/m2 and correlate them with newborn adipolin, adiponectin levels, and anthropometric characteristics of the newborns, and secondly to evaluate pregnancy outcomes. Material and Methods: After the OGTT results, we had 44 OW/OB pregnant women with GDM, 30 OW/OB pregnant women without GDM, and 92 lean healthy (LH) pregnant women. Data were analyzed by ANOVA and correlation tests, with a p-value < 0.05 considered significant. Results: We found no differences between adipolin values of the OW/OB pregnant women with GDM and the LH group (p > 0.99), OW/OB without GDM and the LH group (p = 0.56), and between OW/OB groups (p = 0.57). OW/OB pregnant women with GDM had a higher rate of gestational hypertension compared with the LH group (p < 0.0001). Newborns from OW/OB pregnant women with GDM were more frequently diagnosed with jaundice (p = 0.02), and they required more frequent admission to the neonatal intensive care unit (NICU) for treatment of respiratory distress (p = 0.01) compared with newborns from LH mothers. Conclusions: Our study revealed that the serum levels of adipolin in the second trimester among the group of OW/OB pregnant women with GDM, matched for age and BMI with OW/OB pregnant women without GDM, were not significantly different. This suggests that adipolin may not play an essential role in the occurrence of GDM in these patients. Despite good glycemic control during pregnancy, OW/OB pregnant women with GDM and their newborns tend to have more complications (gestational hypertension, jaundice, NICU admission) than LH pregnant women and their newborns, highlighting the importance of weight control before pregnancy.