Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma.

BACKGROUND: Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases. METHODS: In this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline. RESULTS: In patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). The mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001). Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.).

Lung function decline is mitigated following liver transplantation in people with cystic fibrosis: A retrospective cohort study.

There is paucity of literature on the health outcomes following liver transplantation (LT) in people with cystic fibrosis (pwCF). We aim to evaluate changes in lung function following LT in pwCF. We performed a retrospective cohort study of pwCF who underwent LT between 1987 and 2019 in the United States and Canada. Simultaneous lung-liver transplants and individuals who had lung transplant prior to LT were excluded. We analyzed pre-LT and post-LT percent predicted forced expiratory volume in 1 second, body mass index, rates of pulmonary exacerbation, and post-LT overall survival. A total of 402 LT recipients were included. The median age of transplant was 14.9 years and 69.7% of the transplants were performed in children less than 18 years old. The rate of decline in percent predicted forced expiratory volume in 1 second was attenuated after LT from -2.2% to -0.7% predicted per year with a difference of 1.5% predicted per year (95% CI, 0.8, 2.2; p < 0.001). Following LT, the rate of decline in body mass index was reduced, and there were fewer pulmonary exacerbations (0.6 pre vs. 0.4 post; rate ratio 0.7, p < 0.01). The median survival time post-transplant was 13.9 years and the overall probability of survival at 5 years was 77.6%. Those with higher lung function pre-LT had a lower risk of death post-LT, and those with genotypes other than F508 deletion had worse survival. LT in pwCF occurs most often in children and adolescents and is associated with a slower rate of decline in lung function and nutritional status, and a reduction in pulmonary exacerbations.

Assessing the inter-observer and intra-observer reliability of radiographic measurements for size-specific dose estimates.

BACKGROUND: Calculating size-specific dose estimates (SSDEs) requires measurement of the patient's anteroposterior (AP) and lateral thickness based on computed tomography (CT) images. However, these measurements can be subject to variation due to inter-observer and intra-observer differences. This study aimed to investigate the impact of these variations on the accuracy of the calculated SSDE. METHODS: Four radiographers with 1-10 years of experience were invited to measure the AP and lateral thickness on 30 chest, abdomen, and pelvic CT images. The images were sourced from an internet-based database and anonymized for analysis. The observers were trained to perform the measurements using MicroDicom software and asked to repeat the measurements 1 week later. The study was approved by the institutional review board at Taibah University, and written informed consent was obtained from the observers. Statistical analyses were performed using Python libraries Pingouin (version 0.5.3), Seaborn (version 0.12.2), and Matplotlib (version 3.7.1). RESULTS: The study revealed excellent inter-observer agreement for the calculated effective diameter and AP thickness measurements, with Intraclass correlation coefficients (ICC) values of 0.95 and 0.96, respectively. The agreement for lateral thickness measurements was lower, with an ICC value of 0.89. The second round of measurements yielded nearly the same levels of inter-observer agreement, with ICC values of 0.97 for the effective diameter, 1.0 for AP thickness, and 0.88 for lateral thickness. When the consistency of the observer was examined, excellent consistency was found for the calculated effective diameter, with ICC values ranging from 0.91 to 1.0 for all observers. This was observed despite the lower consistency in the lateral thickness measurements, which had ICC values ranging from 0.78 to 1.0. CONCLUSIONS: The study's findings suggest that the measurements required for calculating SSDEs are robust to inter-observer and intra-observer differences. This is important for the clinical use of SSDEs to set diagnostic reference levels for CT scans.

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications. Variant/divergent features may coexist with conventional high-grade urothelial carcinoma (HGUC) or present with 100% variant morphology. In urinary tract cytology (UTC), urothelial carcinoma can display divergent differentiation, such as squamous, glandular, or small cell carcinoma differentiation. The use of cell block preparations and immunohistochemistry with available residual urine can enhance diagnostic accuracy. On the other hand, identifying urothelial carcinoma variants, including nested, micropapillary, and plasmacytoid subtypes, poses significant challenges in UTC. Many cases of these variants are only detected retrospectively after variant histology has been established from resection specimens. Moreover, some variants exhibit features inconsistent with the diagnostic criteria for HGUC according to the Paris System for Reporting Urinary Tract Cytology. Nevertheless, the rarity of pure variant morphology and the occurrence of some false negatives for these variant cases are essential to maintain the specificity of UTC overall. This review covers the histology, cytomorphology, and important clinical aspects observed in urothelial carcinoma exhibiting divergent differentiation and various urothelial carcinoma variants detected in UTC.

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin.

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

A Comparison of Systematic, Targeted and Combined Biopsy Using Machine Learning for Prediction of Prostate Cancer Risk: A Multi-Center Study.

OBJECTIVES: To construct a new prognostic prediction model for detecting Prostate Cancer (PCa) patients using Machine Learning (ML) techniques and to compare those models across systematic and target biopsy detection techniques. METHODS: The records of the two main hospitals in Riyadh, Saudi Arabia, were analyzed for data on diagnosed PCa from 2019 - 2023. Four ML algorithms were utilized for the prediction and classification of PCa. RESULTS: 528 patients with prostate-specific antigen (PSA) greater than 3.5 ng/mL who had undergone transrectal ultrasound-guided prostate biopsy (TRUS) were evaluated. The total number of confirmed PCa cases was 234. Age, prostate volume, PSA, Body Mass Index (BMI), multiparametric Magnetic Resonance Imaging (mpMRI) score, number of regions of interest detected in MRI, and the diameter of the largest size lesion were significantly associated with PCa. Random Forest (RF) and XG Boost (XGB) (ML algorithms) accurately predicted PCa. Yet, their performance for classification and prediction of PCa was higher and more accurate for cases detected by targeted and combined biopsy (systematic and targeted together) compared to systematic biopsy alone. F1, the Area Under the Curve (AUC), and the accuracy of XGB and RF models for targeted biopsy and combined biopsy ranged from 0.94 - 0.97 compared to the AUC of systematic biopsy for RF and XGB algorithms, respectively. CONCLUSIONS: The Random Forest (RF) model generated and presented an excellent prediction capability for the risk of PCa detected by targeted and combined biopsy compared to systematic biopsy alone. ML models can prevent missed PCa diagnoses by serving as a screening tool.

Correlation between impulse oscillometry with bronchodilator reversibility in asthmatic population in a tertiary referral centre.

INTRODUCTION: Spirometry is considered as a 'gold standard' for diagnosis of asthma. Impulse oscillometry (IOS) is an alternative diagnostic tool which requires less cooperation by the participants. We performed a study to determine the correlation of IOS with bronchodilator reversibility from spirometry in asthmatic participants. We studied the correlation between forced expiratory flow (FEF25%-75%) and differences between the resistance at 5Hz and 20Hz (R5-R20) in small airway disease (SAD) and the proportion of SAD diagnosed using IOS. MATERIALS AND METHODS: This was a cross-sectional study involving 82 asthmatic participants in Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia (UKM) conducted between December 2020 till January 2022. Participants performed pre- and post-bronchodilator IOS and spirometry within the same day. Correlation between spirometry and IOS parameters and FEF25%-75% with IOS were determined and analysed. RESULTS: The change of forced expiratory volume in 1 second (FEV1) was statistically correlated with a change of R5 in IOS. A decrement of 14.5% in R5 can be correlated with positive bronchodilator response (BDR) with a sensitivity of 63.9% and specificity of 60.9%, p=0.007. Pre-bronchodilator FEF25%-75% correlated with all parameters of SAD in IOS, e.g., R5-R20, reactance at 5Hz (X5) and area of reactance (AX), p < 0.05. IOS detection for SAD is higher compared to FEF25%-75% in the BDR negative group (91.3% vs 58.7%). CONCLUSION: IOS detected both bronchodilator reversibility and SAD hence can be considered as an alternative tool to spirometry for diagnosis of asthma in adults. IOS detected SAD more than FEF25%-75%, especially in BDR-negative group.

Hemopatch® as a primary dural sealant in cranial neurosurgery: Technical note and a retrospective study.

OBJECTIVES: To determine the effectiveness and safety of Hemopatch® as a primary dural sealant in preventing CSF leakage following cranial surgery. Cerebrospinal fluid (CSF) leaks occur in cranial operations and are associated with significant patient burden and expense. The use of Hemopatch® as a dural sealant in cranial neurosurgical procedures is described and analyzed in this study. METHODS: Data were retrospectively collected from all patients who underwent a craniotomy for various neurosurgical indications where Hemopatch® was used as the primary dural sealant between June 2017 and June 2022. Infection and CSF leak were the main indicators evaluated after surgery. RESULTS: A total of 119 consecutive patients met our inclusion criteria. The median was age 41.5 years, and 52.5% were female. The mean follow-up period was 2.3 years (7 months to 6 years). There were 110 (92.44%) supratentorial and 9 (7.56%) infratentorial craniotomies. Postoperative CSF leak was reported in 2 patients (1.68%), one in each cohort. Postoperative infection occurred in one patient (0.84%). CONCLUSION: The results suggest that using Hemopatch® as a dural sealant in cranial surgery is effective and safe. After supra-/infratentorial craniotomies, the rate of postoperative adverse events in our sample was within the range of known surgical revision rates. Future randomized clinical studies are required to confirm our encouraging findings.

Assessment of clinician adherence to Fingolimod instructions and its effect on patient safety.

OBJECTIVES: To assess clinicians' adherence to fingolimod's effective use according to the prescribed recommendations to reduce safety risk, identify the consequences, and highlight areas for improvement to policy makers for the benefit of both patient and care-giver. METHODS: A retrospective observational study conducted at a tertiary hospital targeting multiple sclerosis patients on fingolimod from January 2017 to December 2021. The physicians' adherence to the manufacturer's instructions was assessed and categorized into good, moderate, and poor based on adherence to fingolimod instructions and monitoring measures. Four monitoring measures were assessed: bradycardia observation, ophthalmic examination, liver enzymes, and infections. In addition, the impact of adherence on patient safety was also assessed. RESULTS: A total of 140 patients were included. Seventy-twopatients (51.4%) had physician with poor adherence (followed only one instruction or none). Sixty-five patients (46.4%) had 2-3 manufacture recommendations where physician's adherence was moderate. Three patients (2.10%) had all manufacturer's recommendations. In terms of fingolimod complications, 18 patients found to have bradycardia after the first does, macular oedema and infections was reported in 4 patients, and the elevation in hepatic enzymes was reported in 6 patients. Poor physician's adherence has resulted in treatment incompleteness and highest fingolimod discontinuation or switching to other treatment options. CONCLUSION: Adherence to fingolimod instructions was poor among physicians which resulted in highest drug switching or discontinuing rate.

Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier.

Changes to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of multiple sclerosis (MS) brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. These pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the lymphotoxin-α (LTα) and interferon-γ (IFNγ) genes. We show that tumour necrosis factor (TNF), IFNγ, and glutamate can provoke paranodal elongation in cerebellar slice cultures, which could be reversed by an N-methyl-D-aspartate (NMDA) receptor blocker. When these changes were inserted into a computational model to simulate axonal conduction, a rapid decrease in velocity was observed, reaching conduction failure in small diameter axons. We suggest that glial cells activated by pro-inflammatory cytokines can produce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and conduction deficits.

A Comparative Analysis of Marginal Adaptation Values between Lithium Disilicate Glass Ceramics and Zirconia-Reinforced Lithium Silicate Endocrowns: A Systematic Review of In Vitro Studies.

This systematic review aimed to identify and analyze in vitro studies on the marginal adaptation values of computer-aided-design/computer-aided-manufacturing (CAD/CAM) and heat-pressed lithium disilicate glass ceramics and zirconia-reinforced lithium silicates and endocrown restorations. A full literature search was conducted in Web of Science, PubMed/Medline, EMBASE, Scopus, Cochrane Library, Google Scholar, and ProQuest electronic databases. The following keywords: endocrown [(marginal adaption) or (marginal fit) or internal fitting)], endocrown [(molar(s)) or (premolar(s) or (posterior teeth) or (maxillary arch) or (mandibular arch)] and ceramic materials as [(lithium disilicate glass ceramic CAD/CAM) or (zirconia) or (heat-press)] were used. Articles were manually searched utilizing their reference lists. Study selection was restricted or limited to the time of publication but not to the type of tested teeth or ceramic material, endocrown design, system of endocrown construction, abutment scanning, and system of the marginal adaption measurement. A total of 17 in vitro studies published between 2016 and 2023 were included in this systemic review. Less than half of the studies were published during 2023. Most studies used lithium disilicate glass ceramic and zirconia-reinforced lithium silicate all-ceramic materials by CAD/CAM or heat-press systems. Marginal adaptation, or marginal gap, was almost equal in the 2 materials, while it was slightly or marginally higher in the heat-press than in the CAD/CAM system. All-ceramic lithium disilicate glass ceramic and/or zirconia endocrowns fabricated for posterior teeth in both arches using CAD/CAM or heat-press had recorded marginal adaptation values within an acceptable range.

Perioperative Levels of Troponin and BNP and the Outcome after Coronary Artery Bypass Grafting.

BACKGROUND: The independent predictive values of troponin I (cTnI) and B-type natriuretic peptide (BNP) after coronary artery bypass grafting (CABG) have been reported in several studies. However, adjustment only has been limited to preoperative risk factors. AIM: This study was conducted to assess the independent values of postoperative cTnI and BNP to predict the outcome after CABG with adjustment for preoperative risk estimates and postoperative complications and to report risk stratification gains, when considering the European System for Cardiac Operative Risk Evaluation (EuroSCORE) combined with postoperative biomarkers. METHODS: This retrospective cohort study included 282 consecutive patients undergoing CABG between January 2018 and December 2021. We evaluated the preoperative and postoperative cTnI and BNP, EuroSCORE, and postoperative complications. The composite endpoint was death or cardiac-related adverse events. RESULTS: The AUROC for postoperative cTnI was significantly higher than that of BNP (0.777 vs. 0.625, p = 0.041). The optimal cut-off values to predict the composite outcome were >4830 (pg/mL) and >6.95 (ng/mL) for BNP and cTnI, respectively. Adjustment for relevant and significant perioperative factors showed that postoperative BNP and cTnI had a high discriminatory power (C-index = 0.773 and 0.895, respectively) for predicting major adverse events. CONCLUSIONS: Postoperative BNP and cTnI are independent predictors of death or major adverse events, following CABG, and can add to the predictive power of EuroSCORE II.

Recognition of Differentially Expressed Molecular Signatures and Pathways Associated with COVID-19 Poor Prognosis in Glioblastoma Patients.

Glioblastoma (GBM) is a type of brain cancer that is typically very aggressive and difficult to treat. Glioblastoma cases have been reported to have increased during COVID-19. The mechanisms underlying this comorbidity, including genomic interactions, tumor differentiation, immune responses, and host defense, are not completely explained. Therefore, we intended to investigate the differentially expressed shared genes and therapeutic agents which are significant for these conditions by using in silico approaches. Gene expression datasets of GSE68848, GSE169158, and GSE4290 studies were collected and analyzed to identify the DEGs between the diseased and the control samples. Then, the ontology of the genes and the metabolic pathway enrichment analysis were carried out for the classified samples based on expression values. Protein-protein interactions (PPI) map were performed by STRING and fine-tuned by Cytoscape to screen the enriched gene module. In addition, the connectivity map was used for the prediction of potential drugs. As a result, 154 overexpressed and 234 under-expressed genes were identified as common DEGs. These genes were found to be significantly enriched in the pathways involved in viral diseases, NOD-like receptor signaling pathway, the cGMP-PKG signaling pathway, growth hormone synthesis, secretion, and action, the immune system, interferon signaling, and the neuronal system. STAT1, CXCL10, and SAMDL were screened out as the top 03 out of the top 10 most critical genes among the DEGs from the PPI network. AZD-8055, methotrexate, and ruxolitinib were predicted to be the possible agents for the treatment. The current study identified significant key genes, common metabolic signaling networks, and therapeutic agents to improve our perception of the common mechanisms of GBM-COVID-19.

Design, Synthesis, In Silico and POM Studies for the Identification of the Pharmacophore Sites of Benzylidene Derivatives.

Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6-O-benzylidene-α-d-glucopyranoside (MBG) derivatives (2-7). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4, 5, 6 and 7. The compounds with the most significant antifungal efficacy were 4, 5, 6 and 7. Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure-activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH3(CH2)10CO-), cinnamoyl-(C6H5CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1δ-----O2δ-) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

Oral microbiota analyses of paediatric Saudi population reveals signatures of dental caries.

BACKGROUND: Oral microbiome sequencing has revealed key links between microbiome dysfunction and dental caries. However, these efforts have largely focused on Western populations, with few studies on the Middle Eastern communities. The current study aimed to identify the composition and abundance of the oral microbiota in saliva samples of children with different caries levels using machine learning approaches. METHODS: Oral microbiota composition and abundance were identified in 250 Saudi participants with high dental caries and 150 with low dental caries using 16 S rRNA sequencing on a NextSeq 2000 SP flow cell (Illumina, CA) using 250 bp paired-end reads, and attempted to build a classifier using random forest models to assist in the early detection of caries. RESULTS: The ADONIS test results indicate that there was no significant association between sex and Bray-Curtis dissimilarity (p ~ 0.93), but there was a significant association with dental caries status (p ~ 0.001). Using an alpha level of 0.05, five differentially abundant operational taxonomic units (OTUs) were identified between males and females as the main effect along with four differentially abundant OTUs between high and low dental caries. The mean metrics for the optimal hyperparameter combination using the model with only differentially abundant OTUs were: Accuracy (0.701); Matthew's correlation coefficient (0.0509); AUC (0.517) and F1 score (0.821) while the mean metrics for random forest model using all OTUs were:0.675; 0.054; 0.611 and 0.796 respectively. CONCLUSION: The assessment of oral microbiota samples in a representative Saudi Arabian population for high and low metrics of dental caries yields signatures of abundances and diversity.

Bartter Syndrome: A Systematic Review of Case Reports and Case Series.

Background and Objectives: Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods: Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ. Subsequently, the information was extracted in order to characterize the clinical presentation, laboratory results, treatment options, and follow-up of the patients with BS. Results: Overall, 118 patients, 48 case reports, and 9 case series (n = 70) were identified. Out of these, the majority of patients were male (n = 68). A total of 21 patients were born from consanguineous marriages. Most cases were reported from Asia (73.72%) and Europe (15.25%). In total, 100 BS patients displayed the genetic variants, with most of these being reported as Type III (n = 59), followed by Type II (n = 19), Type I (n = 14), Type IV (n = 7), and only 1 as Type V. The most common symptoms included polyuria, polydipsia, vomiting, and dehydration. Some of the commonly used treatments were indomethacin, potassium chloride supplements, and spironolactone. The length of the follow-up time varied from 1 month to 14 years. Conclusions: Our systematic review was able to summarize the clinical characteristics, presentation, and treatment plans of BS patients. The findings from this review can be effectively applied in the diagnosis and patient management of individuals with BS, rendering it a valuable resource for nephrologists in their routine clinical practice.

An overview of structure-based activity outcomes of pyran derivatives against Alzheimer's disease.

Pyran is a heterocyclic group containing oxygen that possesses a variety of pharmacological effects. Pyran is also one of the most prevalent structural subunits in natural products, such as xanthones, coumarins, flavonoids, benzopyrans, etc. Additionally demonstrating the neuroprotective properties of pyrans is the fact that this heterocycle has recently attracted the attention of scientists worldwide. Alzheimer's Disease (AD) treatment and diagnosis are two of the most critical research objectives worldwide. Increased amounts of extracellular senile plaques, intracellular neurofibrillary tangles, and a progressive shutdown of cholinergic basal forebrain neuron transmission are often related with cognitive impairment. This review highlights the various pyran scaffolds of natural and synthetic origin that are effective in the treatment of AD. For better understanding synthetic compounds are categorized as different types of pyran derivatives like chromene, flavone, xanthone, xanthene, etc. The discussion encompasses both the structure-activity correlations of these compounds as well as their activity against AD. Because of the intriguing actions that were uncovered by these pyran-based scaffolds, there is no question that they are at the forefront of the search for potential medication candidates that could treat Alzheimer's disease.

Predictive risk factors for pneumothorax following fluoroscopic-guided transbronchial lung biopsy.

INTRODUCTION: Fluoroscopic-guided transbronchial lung biopsy (FG-TBLB) is routinely performed via bronchoscopy to diagnose focal peripheral lesions and diffuse lung disease. Identifying the risk factors of FG-TBLB-related pneumothorax can assist the operator in taking pre-emptive measures to prepare for this potential complication. MATERIALS AND METHODS: We retrospectively analysed data from 157 patients who underwent FG-TBLB, with the primary outcome being procedure-related pneumothorax. We assessed several risk factors for pneumothorax following FG-TBLB: patient characteristics, location of biopsy, number of biopsies and computed tomography pattern. Univariate and multivariate logistic regression analyses were performed. RESULTS: One-hundred fifty-seven patients were included [mean (SD) age 57.9 (16.2) years; 60.5% male]. The most common location for FG-TBLB was the right upper lobe (n=45, 28.7%). The mean (SD) number of biopsy samples was 6.7 (2.1). Radiographic evidence of pneumothorax was reported in 12 (7.6%) patients, with 11 of those requiring intercostal chest tube intervention (mean air leak time: 5.7 days and 1 had persistent air leak requiring autologous blood patch pleurodesis. None experienced pneumothorax recurrence. Female gender and upper lobe location of the biopsy were identified as predisposing factors for pneumothorax. In the multivariable analysis, upper lobe biopsies were associated with a higher risk of pneumothorax (OR 0.120; 95% CI 0.015-0.963; p = 0.046). CONCLUSION: The overall rate of pneumothorax is low. We recognise the increased risk of pneumothorax associated with upper lobe biopsy. These findings suggest that clinicians should exercise caution when performing FGTBLB in this region and consider alternative biopsy locations whenever feasible. We suggest adequate planning and preparation should be implemented to minimise the risk of pneumothorax following FG-TBLB.

Post COVID-19 Guillain-Barre syndrome presents as sensory dominant neuropathy with reversible conduction failure.

Guillain-Barré syndrome (GBS) has several clinical variants. The sensory presentations of GBS are atypical but well-recognized. We report a patient who presented with predominantly sensory symptoms associated with reversible conduction failure (RCF). RCF is a well-defined neurophysiological abnormality noted mainly in axonal GBS and may be misinterpreted as evidence of demyelination. A 25-year-old woman presented 2 weeks after a coronavirus 2019 infection with acute sensory symptoms, distal allodynia, mild weakness, and mild hyporeflexia in her upper limbs. A nerve conduction study (NCS) showed delayed motor distal latencies, and lumbar puncture confirmed cytoalbuminologic dissociation. After excluding other etiologies, she was diagnosed with GBS, treated with an IV immunoglobulin course, and showed remarkable recovery. Results of a repeat NCS were consistent with RCF and confirmed the presence of axonal GBS. Increased awareness of sensory GBS and RCF is expected to improve the diagnosis and management of atypical GBS presentations.