Histopathological response to chemotherapy and survival of mucinous type gastric cancer.

BACKGROUND: Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. METHODS: Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). RESULTS: In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). CONCLUSION: Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

Hyaluronic acid and urology: a systematic review and meta-analysis.

INTRODUCTION: The use of hyaluronic acid as a nonsurgical treatment for various conditions within urology has been of great interest in recent literature. OBJECTIVES: In this study, we aimed to provide an updated review and analysis of the current state of hyaluronic acid use in urology, characterize its adverse effects, and briefly discuss future directions of research for hyaluronic acid in urology. METHODS: PubMed searches were run utilizing multiple terms, including "hyaluronic acid," "penile," "augmentation," "Peyronie disease," "premature ejaculation," and "cosmetic urology," among other related iterations. Relevant data extracted included International Index of Erectile Function score, intravaginal ejaculatory latency, glans circumference, penile girth, and plaque size. We also included studies which reported on complications of hyaluronic acid injections. Aggregated analysis was performed on studies with complete pre and post injection data at time closest to 6 months postinjection. RESULTS: A total of 33 studies met our inclusion criteria. Studies had marked heterogeneity in design, but most reported positive results. A total of 16 studies were included in our analysis. Intravaginal ejaculatory latency, penile girth, glans circumference, and International Index of Erectile Function were all increased on a fixed-effects model. Reduction in plaque size was not significant (P = .069). Complications were rare. CONCLUSION: Literature on hyaluronic acid for urologic issues demonstrates promising results; however, the quality of studies was variable. Our analysis of these studies largely corroborates these findings; however, the results are limited by the data available. Hyaluronic acid may be promising, but we highly implore standardization of study regimens in randomized controlled trials.

A Multicentre Prospective Cohort Study to Identify High-Risk Transient Ischemic Attack/Minor Stroke Patients Benefiting from Echocardiography.

BACKGROUND: We aimed to derive a clinical decision rule to identify transient ischemic attack (TIA)/minor stroke patients most likely to benefit from echocardiography. METHODS: This multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent a echocardiogram within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings. RESULTS: In 7,149 eligible patients, a clinically significant finding was found in 556 (7.8%). There were a further 2,421 (33.9%) with a potentially significant finding. History of heart failure (adjusted odds ratio [OR] 3.9) or coronary artery disease (OR 2.7) were the factors most strongly associated with clinically significant echocardiogram findings, while young age, male sex, valvular heart disease and infarct (any age) on neuroimaging were modestly associated (OR between 1.3 and 1.9). The model combining these predictors into a score (range 0 to 15), had a C-statistic of 0.67 (95%CI 0.65-0.70). A cut point of 6 points or more classified 6.6% of cases as high likelihood, defined as >15% for clinically significant echocardiogram findings. CONCLUSION: Echocardiography is a very useful test in the investigations of TIA/minor stroke patients. We identified high risk clinical features, combined to create a clinical decision rule, to identify which TIA/minor stroke patients are likely to have clinically significant echocardiogram findings requiring an immediate change in management. These patients should have echocardiography prioritized while others may continue to have echocardiography conducted in a less urgent fashion.

Varicose Veins as Model for Apportionment among Risk Factors for Compensation Purposes.

OBJECTIVE.­: To demonstrate a method which is being used to apportion between risk factors for occupationally related disease and compensate individuals with multiple risk factors. The application to individuals will be demonstrated for varicose veins. BACKGROUND.­: The National Insurance Institute (NII) is tasked with compensating work related injuries and illness in Israel. Population attributable fraction (PAF) has been utilized in order to estimate the amount of disease that can potentially be eliminated in a population through the elimination of individual risk factors. PAF is based on relative risks and the prevalence of these risks. METHODS.­: A review of the medical literature consisting of epidemiological studies of varicose veins and its multiple risk factors was conducted, with special attention to prolonged occupational standing. Summary, weighted, relative risks were calculated for eight different risk factors. The proposed formula then allowed for apportioning among those risk factors in the individual. RESULTS.­: The findings of the current study indicate that prolonged standing may be associated with the presence of varicose veins, however in light of the multiple other risk factors associated, its overall contribution is generally minor. CONCLUSION.­: Apportionment among multiple risk factors for varicose veins can be accomplished mathematically in individuals. This application is being applied successfully for other diseases as well.

Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.

Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score.

pQEB1: a hospital outbreak plasmid lineage carrying bla KPC-2.

While conducting genomic surveillance of carbapenemase-producing Enterobacteriaceae (CPE) from patient colonisation and clinical infections at Birmingham's Queen Elizabeth Hospital (QE), we identified an N-type plasmid lineage, pQEB1, carrying several antibiotic resistance genes, including the carbapenemase gene bla KPC-2. The pQEB1 lineage is concerning due to its conferral of multidrug resistance, its host range and apparent transmissibility, and its potential for acquiring further resistance genes. Representatives of pQEB1 were found in three sequence types (STs) of Citrobacter freundii, two STs of Enterobacter cloacae, and three species of Klebsiella. Hosts of pQEB1 were isolated from 11 different patients who stayed in various wards throughout the hospital complex over a 13 month period from January 2023 to February 2024. At present, the only representatives of the pQEB1 lineage in GenBank were carried by an Enterobacter hormaechei isolated from a blood sample at the QE in 2016 and a Klebsiella pneumoniae isolated from a urine sample at University Hospitals Coventry and Warwickshire (UHCW) in May 2023. The UHCW patient had been treated at the QE. Long-read whole-genome sequencing was performed on Oxford Nanopore R10.4.1 flow cells, facilitating comparison of complete plasmid sequences. We identified structural variants of pQEB1 and defined the molecular events responsible for them. These have included IS26-mediated inversions and acquisitions of multiple insertion sequences and transposons, including carriers of mercury or arsenic resistance genes. We found that a particular inversion variant of pQEB1 was strongly associated with the QE Liver speciality after appearing in November 2023, but was found in different specialities and wards in January/February 2024. That variant has so far been seen in five different bacterial hosts from six patients, consistent with recent and ongoing inter-host and inter-patient transmission of pQEB1 in this hospital setting.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation.

BACKGROUND: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. METHODS: Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122-125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. RESULTS: Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration ("Prion Disease", "Alzheimer's Disease", "Arachidonic Acid metabolism"). Adverse changes were independent of respiratory function during ventilation. CONCLUSIONS: Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk.

Physiological variability in pancreatic cell type gene regulation and the impact on diabetes risk is poorly understood. In this study we mapped gene regulation in pancreatic cell types using single cell multiomic (joint RNA-seq and ATAC-seq) profiling in 28 non-diabetic donors in combination with single cell data from 35 non-diabetic donors in the Human Pancreas Analysis Program. We identified widespread associations with age, sex, BMI, and HbA1c, where gene regulatory responses were highly cell type- and phenotype-specific. In beta cells, donor age associated with hypoxia, apoptosis, unfolded protein response, and external signal-dependent transcriptional regulators, while HbA1c associated with inflammatory responses and gender with chromatin organization. We identified 10.8K loci where genetic variants were QTLs for cis regulatory element (cRE) accessibility, including 20% with lineage- or cell type-specific effects which disrupted distinct transcription factor motifs. Type 2 diabetes and glycemic trait associated variants were enriched in both phenotype- and QTL-associated beta cell cREs, whereas type 1 diabetes showed limited enrichment. Variants at 226 diabetes and glycemic trait loci were QTLs in beta and other cell types, including 40 that were statistically colocalized, and annotating target genes of colocalized QTLs revealed genes with putatively novel roles in disease. Our findings reveal diverse responses of pancreatic cell types to phenotype and genotype in physiology, and identify pathways, networks, and genes through which physiology impacts diabetes risk.

Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction: A Multinational, High-volume Center Retrospective Cohort Analysis.

OBJECTIVE: A multi-national high-volume center study was undertaken to evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ). BACKGROUND: Optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. METHODS: Retrospective analysis of prospectively maintained databases from ten centers was performed. Between 01/2012-08/2023 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. Primary endpoint was overall survival (OS). RESULTS: In the cT2cNany cohort 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n=333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P<0.001) and had a higher ASA classification (P<0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P>0.4).Median OS was 51.0 months in the PS group (95% CI 31.6-70.4) versus 114.0 months (95% CI 53.9-174.1) in the NAT/S group (P=0.003) of cT2cNany patients. For cT2cN0 patients NAT/S was associated with longer OS (P=0.002) and disease-free survival (DFS) (P=0.001). After propensity score matching of cT2N0 patients, survival benefit for NAT/S remained (P=0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. CONCLUSIONS: Due to unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.

Radiomics in Oesogastric Cancer: Staging and Prediction of Preoperative Treatment Response: A Narrative Review and the Results of Personal Experience.

BACKGROUND: Oesophageal, gastroesophageal, and gastric malignancies are often diagnosed at locally advanced stage and multimodal therapy is recommended to increase the chances of survival. However, given the significant variation in treatment response, there is a clear imperative to refine patient stratification. The aim of this narrative review was to explore the existing evidence and the potential of radiomics to improve staging and prediction of treatment response of oesogastric cancers. METHODS: The references for this review article were identified via MEDLINE (PubMed) and Scopus searches with the terms "radiomics", "texture analysis", "oesophageal cancer", "gastroesophageal junction cancer", "oesophagogastric junction cancer", "gastric cancer", "stomach cancer", "staging", and "treatment response" until May 2024. RESULTS: Radiomics proved to be effective in improving disease staging and prediction of treatment response for both oesophageal and gastric cancer with all imaging modalities (TC, MRI, and 18F-FDG PET/CT). The literature data on the application of radiomics to gastroesophageal junction cancer are very scarce. Radiomics models perform better when integrating different imaging modalities compared to a single radiology method and when combining clinical to radiomics features compared to only a radiomics signature. CONCLUSIONS: Radiomics shows potential in noninvasive staging and predicting response to preoperative therapy among patients with locally advanced oesogastric cancer. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic features may even increase the effectiveness of these predictive and prognostic models.

Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations.

Rationale: Hyper IgE syndrome (STAT3-HIES), also known as Job's syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense. Objectives: To identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection. Methods: STAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1ß) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed. Measurements and Main Results: Mucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1ß expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1ß exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a γ-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells. Conclusions: STAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.

Reconstruction Techniques and Associated Morbidity in Minimally Invasive Gastrectomy for Cancer - Insights from the GastroBenchmark and GASTRODATA databases.

OBJECTIVE/BACKGROUND: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. METHODS: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed 2017-2021 in 44 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. RESULTS: Three major anastomotic techniques (circular stapled (CS); linear stapled (LS); hand sewn (HS)), and three major bowel reconstruction types (Roux (RX); Billroth I (BI); Billroth II (BII)) were identified in miTG (n=878) and miDG (n=3334). Postoperative complications including AL (5.2% vs. 1.1%), overall (28.7% vs. 16.3%) and major morbidity (15.7% vs. 8.2%), as well as 90-day mortality (1.6% vs. 0.5%) were higher after miTG compared with miDG. After miTG, AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as predictive factor for AL, overall and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, RX 1.2%), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%,) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, RY: 1.1%%) were not affected by bowel reconstruction. CONCLUSION: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to surgeon's preference.

On the pathogenesis of obesity: causal models and missing pieces of the puzzle.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

Prevalence and predictors of radiographic pneumonia in children with wheeze: A systematic review and meta-analysis.

BACKGROUND: Diagnostic uncertainty exists surrounding the identification of radiographic pneumonia in children with wheeze. It is important to determine the prevalence and clinical predictors of pneumonia in this population to limit chest radiography (CXR) and promote judicious antibiotic use. OBJECTIVES: The objectives were to (1) estimate the prevalence of radiographic pneumonia in children with wheeze and (2) systematically review the diagnostic accuracy of clinical findings for the identification of radiographic pneumonia. METHODS: Data sources were MEDLINE, PubMed Central, Cochrane Library, CINAHL, and Web of Science (January 1995 to September 2023). For study selection, two reviewers identified high-quality studies reporting on clinical characteristics associated with radiographic pneumonia in wheezing children (age 0-21 years). Using Covidence software, data regarding study characteristics, methodologic quality, and results were extracted. Data were pooled using random-effects meta-analysis. RESULTS: A total of 8333 unique titles and abstracts were reviewed. Twelve studies, representing 7398 patients, were included. Fifteen percent of children with wheeze undergoing CXR had pneumonia. Findings associated with radiographic pneumonia included temperature ≥ 38.4°C (positive likelihood ratio [LR+] 2.1, 95% CI 1.2-3.6, specificity 85%), oxygen saturation < 92% (LR+ 3.6, 95% CI 1.4-8.9, specificity 89%), and grunting (LR+ 2.7, 95% CI 1.6-4.4, pooled specificity 91%). Factors associated with the absence of radiographic pneumonia included lack of fever (negative likelihood ratio [LR-] 0.67, 95% CI 0.52-0.85) and oxygen saturation ≥ 95% (LR- 0.64, 95% CI 0.42-0.98). Tachypnea and auscultatory findings were not associated with radiographic pneumonia. DISCUSSION: Heterogeneity across studies limits generalizability. Additionally, all included studies overestimate the rate of radiographic pneumonia given the fact that all subjects had a CXR performed due to clinical suspicion of pneumonia. CONCLUSIONS: Radiographic pneumonia occurs in 15% of wheezing children undergoing CXR for pneumonia. Auscultatory findings and tachypnea do not differentiate children with and without pneumonia, and the rate of radiographic pneumonia is very low in the absence of fever and hypoxemia.

Derivation of a clinical prediction score for the diagnosis of clinically significant symptomatic carotid artery disease.

OBJECTIVES: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus). However, most TIA patients do not have these findings, so it is inefficient to image all TIA patients in crowded emergency departments (ED). Our objectives were to derive and internally validate a clinical prediction score for clinically significant carotid artery disease in TIA patients. METHODS: This was a planned secondary analysis of a prospective cohort study from 14 Canadian EDs. Among 11555 consecutive adult ED patients with TIA/minor stroke symptoms over 12 years, 9882 had vascular imaging and were included in the analysis. Our main outcome was clinically significant carotid artery disease, defined as extracranial internal carotid stenosis ≥ 50%, dissection, or thrombus in the internal carotid artery, with contralateral symptoms. RESULTS: Of 9882 patients, 888 (9.0%) had clinically significant carotid artery disease. Logistic regression was used to derive a 13-variable reduced model. We simplified the model into a score (Symcard [Symptomatic carotid artery disease] Score), with suggested cut-points for high, medium, and low-risk stratification. A substantial portion (38%) of patients were classified as low-risk, 33.8% as medium risk, and 28.2% as high risk. At the low-risk cut-point, sensitivity was 92.9%, specificity 41.1%, and diagnostic yield 1.7%. CONCLUSIONS: This simple score can predict carotid artery disease in TIA patients using readily available information. It identifies low-risk patients who can defer vascular imaging to an outpatient or specialty clinic setting. Medium-risk patients may undergo imaging immediately or with slight delay, depending on local resources. High-risk patients should undergo urgent vascular imaging.

RéSUMé: OBJECTIFS: L'imagerie vasculaire émergente permet d'identifier un sous-ensemble de patients nécessitant des soins spécialisés immédiats (c.-à-d. sténose carotidienne >50 %, dissection ou thrombus flottant). Cependant, la plupart des patients atteints de RTI ne présentent pas ces résultats, il est donc inefficace d'effectuer une imagerie de tous les patients atteints de RTI dans les services d'urgence (ER) surpeuplés. Nos objectifs étaient de calculer et de valider en interne un score de prédiction clinique pour la maladie carotide cliniquement significative chez les patients atteints d'une AIT MéTHODES: Il s'agissait d'une analyse secondaire planifiée d'une étude de cohorte prospective menée auprès de 14 DE canadiens. Parmi les 11555 patients adultes consécutifs atteints d'un EI présentant des symptômes d'AIT/AVC mineur au cours des 12 dernières années, 9882 ont reçu une imagerie vasculaire et ont été inclus dans l'analyse. Notre principal critère de jugement était la maladie carotide cliniquement significative, définie comme une sténose extracrânienne de la carotide interne à 50 %, une dissection ou un thrombus dans l'artère carotide interne, avec des symptômes contralatéraux. RéSULTATS: Sur 9882 patients, 888 (9,0 %) présentaient une maladie de l'artère carotide cliniquement significative. La régression logistique a été utilisée pour obtenir un modèle réduit à 13 variables. Nous avons simplifié le modèle en un score (Symcard [Symptomatic carotid artery disease] Score), avec des points de coupure suggérés pour la stratification à risque élevé, moyen et faible. Une proportion importante (38,0 %) des patients ont été classés à faible risque, 33,8 % à risque moyen et 28,2 % à risque élevé. Au seuil de faible risque, la sensibilité était de 92,9 %, la spécificité de 41,1 % et le rendement diagnostique de 1,7 %. CONCLUSIONS: Ce score simple permet de prédire la maladie de l'artère carotide chez les patients atteints d'AIT en utilisant des informations facilement disponibles. Il identifie les patients à faible risque qui peuvent reporter l'imagerie vasculaire à un établissement de consultation externe ou de spécialité. Les patients à risque moyen peuvent subir une imagerie immédiatement ou avec un léger délai, selon les ressources locales. Les patients à haut risque doivent subir une imagerie vasculaire urgente.

A translational model of chronic diabetic nephropathy in the Nile grass rat.

Diabetic nephropathy (DN) is a major healthcare challenge for individuals with diabetes and associated with increased cardiovascular morbidity and mortality. The existing rodent models do not fully represent the complex course of the human disease. Hence, developing a translational model of diabetes that reproduces both the early and the advanced characteristics of DN and faithfully recapitulates the overall human pathology is an unmet need. Here, we introduce the Nile grass rat (NGR) as a novel model of DN and characterize key pathologies underlying DN. NGRs spontaneously developed insulin resistance, reactive hyperinsulinemia, and hyperglycemia. Diabetic NGRs evolved DN and the key histopathological aspects of the human advanced DN, including glomerular hypertrophy, infiltration of mononuclear cells, tubular dilatation, and atrophy. Enlargement of the glomerular tufts and the Bowman's capsule areas accompanied the expansion of the Bowman's space. Glomerular sclerosis, renal arteriolar hyalinosis, Kimmelsteil-Wilson nodular lesions, and protein cast formations in the kidneys of diabetic NGR occurred with DN. Diabetic kidneys displayed interstitial and glomerular fibrosis, key characteristics of late human pathology as well as thickening of the glomerular basement membrane and podocyte effacement. Signs of injury included glomerular lipid accumulation, significantly more apoptotic cells, and expression of KIM-1. Diabetic NGRs became hypertensive, a known risk factor for kidney dysfunction, and showed decreased glomerular filtration rate. Diabetic NGRs recapitulate the breadth of human DN pathology and reproduce the consequences of chronic kidney disease, including injury and loss of function of the kidney. Hence, NGR represents a robust model for studying DN-related complications and provides a new foundation for more detailed mechanistic studies of the genesis of nephropathy, and the development of new therapeutic approaches.

Preferences for Management of Pediatric Pneumonia: A Clinician Survey of Artificially Generated Patient Cases.

BACKGROUND: It is unknown which factors are associated with chest radiograph (CXR) and antibiotic use for suspected community-acquired pneumonia (CAP) in children. We evaluated factors associated with CXR and antibiotic preferences among clinicians for children with suspected CAP using case scenarios generated through artificial intelligence (AI). METHODS: We performed a survey of general pediatric, pediatric emergency medicine, and emergency medicine attending physicians employed by a private physician contractor. Respondents were given 5 unique, AI-generated case scenarios. We used generalized estimating equations to identify factors associated with CXR and antibiotic use. We evaluated the cluster-weighted correlation between clinician suspicion and clinical prediction model risk estimates for CAP using 2 predictive models. RESULTS: A total of 172 respondents provided responses to 839 scenarios. Factors associated with CXR acquisition (OR, [95% CI]) included presence of crackles (4.17 [2.19, 7.95]), prior pneumonia (2.38 [1.32, 4.20]), chest pain (1.90 [1.18, 3.05]) and fever (1.82 [1.32, 2.52]). The decision to use antibiotics before knowledge of CXR results included past hospitalization for pneumonia (4.24 [1.88, 9.57]), focal decreased breath sounds (3.86 [1.98, 7.52]), and crackles (3.45 [2.15, 5.53]). After revealing CXR results to clinicians, these results were the sole predictor associated with antibiotic decision-making. Suspicion for CAP correlated with one of 2 prediction models for CAP (Spearman's rho = 0.25). Factors associated with a greater suspicion of pneumonia included prior pneumonia, duration of illness, worsening course of illness, shortness of breath, vomiting, decreased oral intake or urinary output, respiratory distress, head nodding, focal decreased breath sounds, focal rhonchi, fever, and crackles, and lower pulse oximetry. CONCLUSIONS: Ordering preferences for CXRs demonstrated similarities and differences with evidence-based risk models for CAP. Clinicians relied heavily on CXR findings to guide antibiotic ordering. These findings can be used within decision support systems to promote evidence-based management practices for pediatric CAP.

Determining barriers to submitting antimicrobial-resistant isolates among hospitals in Texas Public Health Region 8.

Background: The Antimicrobial Resistance Laboratory Network (AR Lab Network) was developed by the CDC to detect emerging antimicrobial-resistant (AR) threats and prevent outbreaks. However, low submission rates of AR isolates limit the potential of the AR Lab Network to address antimicrobial resistance (AMR). Aim: The aim of this study was to investigate barriers to submission of AR isolates in acute care hospitals (ACHs) and critical access hospitals (CAHs) within Texas Public Health Region 8 (PHR8) counties. Methods: A survey was designed and emailed to laboratory professionals to identify barriers to AR isolate submission. Responses were analyzed using 2-sided Fisher's exact tests to identify associations between responses and respondent characteristics. Results: Of the 33 hospitals within PHR8 invited to participate in the survey, responses were received from 21, a response rate of 63.6%. Lack of awareness of the AR Lab Network was the most frequently cited barrier to submission (65.4% of respondents). Other reported barriers to submission included lack of laboratory staff time (57.7%), lack of training with the submission process (34.6%), lack of personnel certified to ship infectious substances (23.1%), and lack of laboratory/shipping supplies (23.1%). Discussion: Regardless of the respondent's role, time in that role, or type of hospital in which they worked, the most common barrier to isolate submission was lack of awareness of the AR Lab Network. In the future, we will address the identified barriers by implementing educational outreach programs about AMR and the AR Lab Network for hospitals and other healthcare facilities within PHR8.