Category: Nevin Manimala

Pediatr Rheumatol Online J. 2024 Dec 28;22(1):111. doi: 10.1186/s12969-024-01053-4.

ABSTRACT

BACKGROUND: Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis.

METHODS: A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently.

RESULTS: A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914-11.420, p = 0.067) and 3.923 (95CI: 1.13-13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02-29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26-36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic.

CONCLUSION: Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.

PMID:39732702 | DOI:10.1186/s12969-024-01053-4

BioData Min. 2024 Dec 28;17(1):61. doi: 10.1186/s13040-024-00413-w.

ABSTRACT

BACKGROUND: Epistasis, the phenomenon where the effect of one gene (or variant) is masked or modified by one or more other genes, significantly contributes to the phenotypic variance of complex traits. Traditionally, epistasis has been modeled using the Cartesian epistatic model, a multiplicative approach based on standard statistical regression. However, a recent study investigating epistasis in obesity-related traits has identified potential limitations of the Cartesian epistatic model, revealing that it likely only detects a fraction of the genetic interactions occurring in natural systems. In contrast, the exclusive-or (XOR) epistatic model has shown promise in detecting a broader range of epistatic interactions and revealing more biologically relevant functions associated with interacting variants. To investigate whether the XOR epistatic model also forms distinct network structures compared to the Cartesian model, we applied network science to examine genetic interactions underlying body mass index (BMI) in rats (Rattus norvegicus).

RESULTS: Our comparative analysis of XOR and Cartesian epistatic models in rats reveals distinct topological characteristics. The XOR model exhibits enhanced sensitivity to epistatic interactions between the network communities found in the Cartesian epistatic network, facilitating the identification of novel trait-related biological functions via community-based enrichment analysis. Additionally, the XOR network features triangle network motifs, indicative of higher-order epistatic interactions. This research also evaluates the impact of linkage disequilibrium (LD)-based edge pruning on network-based epistasis analysis, finding that LD-based edge pruning may lead to increased network fragmentation, which may hinder the effectiveness of network analysis for the investigation of epistasis. We confirmed through network permutation analysis that most XOR and Cartesian epistatic networks derived from the data display distinct structural properties compared to randomly shuffled networks.

CONCLUSIONS: Collectively, these findings highlight the XOR model’s ability to uncover meaningful biological associations and higher-order epistasis derived from lower-order network topologies. The introduction of community-based enrichment analysis and motif-based epistatic discovery emphasize network science as a critical approach for advancing epistasis research and understanding complex genetic architectures.

PMID:39732697 | DOI:10.1186/s13040-024-00413-w

Trials. 2024 Dec 28;25(1):853. doi: 10.1186/s13063-024-08688-4.

ABSTRACT

BACKGROUND: Intermediate-high risk pulmonary embolism (PE) carries a significant risk of hemodynamic deterioration or death. Treatment should balance efficacy in reducing clot burden with the risk of complications, particularly bleeding. Previous studies on high-dose, short-term thrombolysis with alteplase (rtPA) showed a reduced risk of hemodynamic deterioration but no change in mortality and increased bleeding complications. Catheter-based techniques, including ultrasound-assisted thrombolysis (USAT), and low-dose thrombolysis may offer reasonable efficacy with lower risk. However, studies comparing these methods have been few. This trial aims to address this gap by randomizing patients to three treatment modalities.

METHODS: Multicenter, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE, excluding those with absolute contraindications to thrombolysis. Patients are eligible for inclusion if they are > 18 years of age, have had symptoms < 14 days, and are able to give informed consent. Patients are allocated 1:1:1 into three treatment strategies: (1) unfractionated heparin (UFH)/low molecular weight heparin (LMWH), (2) UFH/LMWH + 20 mg rtPA/6 h intravenously (IV), or (3) UFH + 20 mg rtPA/6 h via USAT. Co-primary outcomes include reduction in clot burden as assessed by refined Miller score from pre-treatment to follow-up (48-96 h) computed tomography pulmonary angiogram (CTPA) comparing low-dose rtPA (± USAT) groups to UFH/LMWH group (p < 0.01, N = 210) and reduction in refined Miller score on follow-up CT angiography comparing low-dose rtPA by USAT to intravenous rtPA, p < 0.04, N = 140). Secondary outcomes comprise bleeding complications, duration of index admission, FiO₂, blood pressure, respiratory and heart rate at the time of follow-up CT angiography, mortality in the three groups, incidence of tricuspid regurgitation pressure gradient < 40 mmHg at 3 months follow-up echocardiography, 6-min walk test at 3 months comparing the three groups, and health-related quality of life at 3 months follow-up comparing the three groups.

DISCUSSION: We hypothesize that in patients with intermediate-high risk PE (1) administration of 20 mg rtPA leads to a greater reduction in clot burden compared to heparins and (2) administration of 20 mg rtPA via USAT results in a greater reduction in clot burden compared to 20 mg rtPA intravenous.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04088292. Registered in September 2019 (retrospectively registered).

PMID:39732696 | DOI:10.1186/s13063-024-08688-4

BMC Nutr. 2024 Dec 28;10(1):165. doi: 10.1186/s40795-024-00976-1.

ABSTRACT

BACKGROUND: Experimental and clinical studies have suggested that symbiotics might effectively manage type 2 diabetes mellitus (T2DM) by modulating the intestinal microbiota. However, these studies’ limited sources, small sample sizes, and varied study designs have led to inconsistent outcomes regarding glycaemic control. This study aimed to investigate the effects of symbiotics on the anthropometric measures, glycaemic control, and lipid profiles of patients with T2DM.

METHODS: A double-blind, placebo-controlled, parallel clinical trial was conducted at two diabetes outpatient clinics. The main researcher and participants were blinded to the capsule content throughout the study. Sixty-six patients with T2DM aged 30-75 years were randomly allocated, using even and odd numbers, into two equal groups. These groups received either symbiotic capsules containing 200 million colony-forming units plus fructo-oligosaccharide or a placebo for 12 weeks. The primary objective was a decrement in glycated haemoglobin [HbA1c]. The patients’ anthropometric measures, fasting blood sugar, high-density lipoprotein [HDL], low-density lipoprotein [LDL], total serum cholesterol and serum triglyceride levels were also assessed at baseline and after 12 weeks of intervention. Non-parametric tests were used for statistical analyses.

RESULTS: Within-group analysis revealed significant decreases in body mass index (BMI) and waist circumference (P = 0.005 and 0.023, respectively) and a significant increase in HDL levels in the symbiotic group (P = 0.04). HbA1c levels significantly increased in the placebo group (P = 0.016) but were not significantly reduced in the symbiotic group. The between-group analysis revealed significantly lower fasting blood sugar (FBS) levels in the symbiotic group, and higher in the placebo group (P = 0.02). No significant changes existed in total serum cholesterol, LDL, and triglyceride levels in either the symbiotic or placebo group.

CONCLUSIONS: Symbiotics improve BMI, waist circumference, HDL, and FBS levels and prevent the worsening of HbA1c levels in patients with T2DM. Our preliminary results indicate the potential benefits of symbiotics in patients with T2DM, which may lead to better diabetes control. However, this evidence requires further assessment in larger trials.

TRIAL REGISTRATION: The trial was registered retrospectively at the International Standard Registered Clinical/Social Study Number Registry (ISRCTN34652973) on 05/01/2024.

PMID:39732694 | DOI:10.1186/s40795-024-00976-1

BMC Pediatr. 2024 Dec 28;24(1):842. doi: 10.1186/s12887-024-05340-7.

ABSTRACT

BACKGROUND: Despite progress made towards SDG 3, sub-Saharan Africa lags behind the rest of the world, accounting for over 50% of global neonatal deaths. The increased number of hospital births in the region has not reciprocated the reduction in neonatal mortality rates. Sick newborns face uncertain journeys from peripheral facilities to specialized centres arriving in suboptimal conditions, which impacts their outcomes, due partly to the scarcity of dedicated neonatal transport services.

METHODS: This was a 2-arm nonrandomized controlled cluster study of preterm and low-birth-weight neonates transferred from eight peripheral sites to a tertiary neonatal unit via conventional methods or the KMC (August 2022-April 2023).

RESULTS: A total of 77 (mother-baby pairs) were recruited, 34 in the KMC group and 43 in the conventional arm. Most (60%) were transported by taxis/private cars. Overall mortality was 20.8%. No untoward event was recorded for neonates transported by KMC, with marginally better temperatures on arrival. Although the observed differences were not statistically significant given that this was not the primary aim, the findings add to evidence that KMC transport may not be more life-threatening than the current practice of transporting newborns in the caregiver’s arms. KMC transport has the added advantage of ensuring non-separation of the small and sick child from its mother from birth and improved temperatures upon arrival.

CONCLUSION: KMC transport for preterm and Low birth weight infants using available transport in Sub-Saharan Africa is feasible. Local large-scale randomized trials are needed to gather more evidence for policy direction needed to inform a scale-up of this low-cost intervention.

TRIAL REGISTRATION: ISRCTN98748162. Retrospectively registered 02.09.2024.

PMID:39732693 | DOI:10.1186/s12887-024-05340-7

Head Face Med. 2024 Dec 28;20(1):72. doi: 10.1186/s13005-024-00476-4.

ABSTRACT

Growth-differentiation factor 15 (GDF-15) is a cytokine involved in cellular stress responses and inflammation. This meta-analysis evaluates the association between circulating GDF-15 levels and functional outcomes in patients with acute ischemic stroke (AIS). A comprehensive search of Medline, Web of Science, Embase, Wanfang, and CNKI was conducted up to July 15, 2024. Observational studies with longitudinal follow-up that measured GDF-15 levels within 24 h of stroke onset and reported functional outcomes, defined as a modified Rankin Scale (mRS) score of ≥ 2, were included. Odds ratios (OR) with 95% confidence intervals (CI) were used to quantify associations. Heterogeneity was evaluated using I² statistics, and a random-effects model was used to pool the results by incorporating the influence of heterogeneity. Ten studies involving 4,231 patients were included. The pooled OR indicated that high circulating GDF-15 levels were associated with a significantly higher risk of poor functional outcomes at 3 months (OR: 2.60, 95% CI: 1.95 to 3.46, p < 0.001). Sensitivity analyses by excluding one study at a time did not significantly change the results. Subgroup analyses revealed stronger associations in studies with GDF-15 cutoff values < 1200 ng/L as compared to ≥ 1200 ng/L, and in those defining poor outcomes as mRS ≥ 3 as compared to those ≥ 2. In conclusion, elevated circulating GDF-15 levels are associated with worse functional outcomes following AIS. These findings support the potential use of GDF-15 as a prognostic biomarker in stroke patients. Further research is warranted to confirm these results and explore clinical applications.

PMID:39732689 | DOI:10.1186/s13005-024-00476-4

Arthritis Res Ther. 2024 Dec 28;26(1):230. doi: 10.1186/s13075-024-03464-w.

ABSTRACT

OBJECTIVE: To investigate differences in arterial involvement patterns on ¹⁸F-FDG PET-CT between predominant cranial and isolated extracranial phenotypes of giant cell arteritis (GCA).

METHODS: A retrospective review of ¹⁸F-FDG PET-CT findings was conducted on 140 patients with confirmed GCA. The patients were divided into two groups: the cranial group, which presented craniofacial ischemic symptoms either at diagnosis or during follow-up, and the isolated extracranial group which never exhibited such manifestations.

RESULTS: Of the 140 patients (90 women), 99 (71%) were considered to have a predominantly cranial phenotype, while 41 (29%) had isolated extracranial GCA. Patients with the extracranial phenotype were younger (p = 0.001), had lower TAB positivity (25%), and experienced longer diagnostic delays (p = 0.004). Polymyalgia rheumatica was more common in the extracranial group (p = 0.029), which also showed fewer constitutional symptoms, milder increases in acute phase reactants, and more frequent limb claudication and aortic complications, although these differences were not statistically significant. When comparing arterial involvement on ¹⁸F-FDG PET-CT, we observed statistically significant differences. The extracranial phenotype showed greater involvement across all segments of the thoracic aorta (p = 0.001), as well as in the abdominal aorta (p = 0.005), subclavian (p = 0.021), iliac (p = 0.004), and femoral arteries (p = 0.025). In contrast, the cranial phenotype exhibited a higher frequency of vertebral artery involvement (p < 0.001).

CONCLUSION: Significant differences in arterial involvement patterns on ¹⁸F-FDG PET-CT were observed between phenotypes. These findings may explain atypical symptoms such as inflammatory lower back pain or limb claudication and the increased risk of aortic complications in extracranial GCA.

PMID:39732686 | DOI:10.1186/s13075-024-03464-w

BMC Med Inform Decis Mak. 2024 Dec 28;24(1):410. doi: 10.1186/s12911-024-02835-2.

ABSTRACT

BACKGROUND: High triglyceride (TG) affects and is affected of other hematological factors. The determination of serum fasted triglycerides concentrations, as part of a lipid profile, is crucial key point in hematological factors and significantly affect various systemic diseases. This study was carried out to assess the potential relation between the concentration of TG and hematological factors.

METHOD: Our sample size was 9704 participants beginning in 2007 and ending in 2020 aged between 35 and 65 years, sourced from the MASHAD cohort (northeastern Iran). Machine learning methodologies, specifically logistic regression, decision tree, and random forest algorithms, were utilized for data analysis in the investigation of individuals with normal and high TG levels.

RESULTS: The highest Gini score belongs to RLR (Red cell distribution width/Lymphocyte) (236.10), RPR (Red cell distribution width/Platelets) (215.78), and PHR (Platelets/high-density lipoprotein) (273.66). We also found that factors such as age are statistically associated with the level of TG in women probably due to the drop in menopausal estrogen. RF model showed to have higher accuracy in predicting the TG level in both males and females.

CONCLUSION: Our model assessed the association between serum TG with several hematological factors like RLR, RPR, and PHR. Other hematological factors also have been reported to be related to the TG level. As these results give us new insights into the association of TG on various hematological factors and their possible interactions with each other. future studies are needed to provide sufficient data for the mechanism and the pathophysiology of the findings.

PMID:39732685 | DOI:10.1186/s12911-024-02835-2

BMC Oral Health. 2024 Dec 28;24(1):1565. doi: 10.1186/s12903-024-05357-5.

ABSTRACT

BACKGROUND: Endodontic emergencies, often presented as acute pain or swelling, constitute a substantial challenge in dental practice. While effective management emphasizes prompt intervention, antibiotics are typically indicated only when systemic signs and symptoms are present. There is limited research exists on evaluating the knowledge and clinical approach of dental practitioners in managing endodontic emergencies from our region of the world. Therefore, this study aims to evaluate dentists’ knowledge, attitude, and practices regarding clinical management and the prescription of antibiotics in endodontic emergency cases.

MATERIALS AND METHODS: A web-based questionnaire was distributed to working dentists in secondary and tertiary care hospitals and clinics. Eligible participants included dental practitioners, postgraduate trainees, and consultants. The questionnaire included demographic information and inquiries about endodontic emergency treatment approaches, antibiotic prescribing habits, and awareness of guidelines. Statistical analysis was performed Stata software version 17 (StataCorp, College Station, Texas, USA), employing a χ2 test.

RESULTS: Of the 527 dentists approached, 409 completed the survey (response rate: 77.6%). The majority of respondents were female (68%) and general dental practitioners (60.32%) with up to 5 years of experience (80.93%). Survey findings highlighted varied treatment approaches, favoring root canal treatment in multiple visits for cases of both irreversible pulpitis (73.59%) as well as with necrotic pulps/periapical lesions (79.95%). Similarly, 45.48% and 37.9% of the respondents favored pulpectomy combined with analgesics and antibiotics in managing irreversible pulpitis and acute apical periodontitis respectively. Moreover, antibiotics were frequently prescribed for acute apical abscess, with amoxicillin-clavulanate being the most common choice (83.6%). Most practitioners (69%) recommended a minimum of 5-day antibiotic course.

CONCLUSIONS: This study highlights Pakistani dentists’ preferences in managing endodontic emergencies and prescribing antibiotics. Despite awareness of guidelines and the consequences of overuse, there’s a tendency towards antibiotic overprescription, indicating a need for educational interventions to promote rational antibiotic use and mitigate antibiotic resistance.

PMID:39732678 | DOI:10.1186/s12903-024-05357-5

BMC Geriatr. 2024 Dec 28;24(1):1044. doi: 10.1186/s12877-024-05586-x.

ABSTRACT

BACKGROUND: Fall prevention programmes are essential interventions in societies with aging populations. This study assessed the fall rate and other health outcomes, as well as the cost-effectiveness of a home-based fall prevention programme for community-dwelling older people. In a single home visit, trained physical or occupational therapists performed fall risk assessments, eliminated environmental risk factors, and provided tailored exercises.

METHODS: A prospective, longitudinal observational study was performed with participants of a fall prevention programme who agreed to be followed-up over one year. Baseline data included self-reported falls one month and one year before the intervention. Participants were monitored through bi-monthly telephone calls, assessing their number of falls, fear of falling (using the Falls Efficacy Scale-International (FES-I), quality of life (using the EuroQuol-5 Dimensions-5 Levels, EQ-5D-5L), and physical activity (in minutes per week). Statistical analysis of the data used a Generalized Estimating Equations (GEE) Poisson-Modell for number of falls and a Linear Mixed Model (LMM) for fear of falling, quality of life and physical activity. In addition, health insurance claims data were used to compare the number of medically treated falls in the year before and after the intervention, as well as the related healthcare spending. Cost-effectiveness of the programme versus usual care was estimated as cost per prevented medically treated fall.

RESULTS: Overall, 639 person-years of observation time were analyzed. Participants had a mean age of 81.8 years (+/- 5.2) and 59% were female. On average, the fall rate decreased from 1.35 to 1.02 per person-year, or -23.9% (95%CI from -35.92 to -9.67), fear of falling decreased by -1.27 points (95%CI from -1.50 to -1.05), quality of life improved by -0.88 points (95%CI from -1.09 to -0.68), and physical activity increased by 9.87 min per day (95%CI from 5.65 to 14.09). Analysis of claims data showed a 48.0% reduction (95%CI from 30.5% to 61.0%) in medically treated falls. The average cost per prevented medically treated fall was estimated at approximately 1,353 USD, with a 50% probability of the intervention being cost saving.

CONCLUSIONS: This fall prevention programme with a single home visit was found to be effective and cost effective. Health policies should establish such a model as a reimbursed standard care to assist in combatting the increasing burden of falls on individuals and societies.

PMID:39732675 | DOI:10.1186/s12877-024-05586-x