Multicenter Study Research Articles

Bidirectional associations among gallstone disease, non-alcoholic fatty liver disease, kidney stone disease

BACKGROUND A body of evidence has suggested bidirectional relationships among gallstone disease (GSD), non-alcoholic fatty liver disease (NAFLD), and kidney stone disease (KSD). However, the results are inconsistent, and studies on this topic in China are relatively few. Our goal is to explore the bidirectional associations among these three diseases through a multicenter study, systematic review, and meta-analysis. AIM To explore the bidirectional associations among these three diseases through a multicenter study, systematic review, and meta-analysis. The results may help to investigate the etiology of these diseases and shed light on the individualized prevention of these three diseases. METHODS Subjects who participated in physical examinations in Beijing, Tianjin, Chongqing in China were recruited. Multivariable logistic regression was employed to explore the bidirectional relationships among GSD, KSD, and NAFLD. Systematic review and meta-analysis were initiated to confirm the epidemiologic evidence from previous observational studies. Furthermore, trial sequential analysis (TSA) was conducted to evaluate whether the evidence was sufficient and conclusive. RESULTS Significant bidirectional associations were detected among the three diseases, independent of potential confounding factors. The pooled results of the systematic review and meta-analysis also corroborated the aforementioned results. The combined evidence from the multicenter study and meta-analysis was significant [pooled odds ratio (OR) = 1.42, 95%CI: 1.16-1.75, KSD → GSD; pooled OR = 1.48, 95%CI: 1.31-1.67, GSD → KSD; pooled OR = 1.31, 95%CI: 1.17-1.47, GSD → NAFLD; pooled OR = 1.37, 95%CI: 1.26-1.50, NAFLD → GSD; pooled OR = 1.28, 95%CI: 1.08-1.51, NAFLD → KSD; pooled OR = 1.21, 95%CI: 1.16-1.25, KSD → NAFLD]. TSA indicated that the evidence was sufficient and conclusive. CONCLUSION The present study presents relatively sufficient evidence for the positive bidirectional associations among GSD, KSD, and NAFLD. The results may provide clues for investigating the etiology of these three diseases and offer a guideline for identifying high-risk patients.

Insights from exploring the interrelated dynamics of gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease

This article delved into the comprehensive study by Jiang et al , which meticulously examined the bidirectional relationships among gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease through a multicenter study, systematic review, and meta-analysis. The study provides significant evidence supporting these associations, offering valuable insights into the etiology and potential prevention strategies for these interconnected conditions. The clinical significance of these bidirectional relationships is profound, as they underscore the importance of recognizing these conditions not only as isolated diseases but as part of a complex network that can influence each other. These results highlight the critical need for thorough screening and personalized prevention strategies for individuals with these interconnected conditions. Explicit implications for prevention strategies and early screening practices are crucial, as they can lead to early detection and intervention, significantly altering disease progression and outcomes. Furthermore, identifying potential therapeutic targets within these shared pathways may enhance treatment efficacy and patient outcomes, making this research highly relevant to clinical practice. By comprehending the common pathophysiological mechanisms and applying specific interventions, healthcare professionals can greatly enhance patient care and lessen the impact of these widespread diseases on global health.

ResNet-Vision Transformer based MRI-endoscopy fusion model for predicting treatment response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A multicenter study.

Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.

Epidemiology and Impact of Social Hardships in Children With Multiple Sclerosis in the United States.

Social determinants of health (SDOH) affect patient health outcomes, but the impact on patients with pediatric-onset multiple sclerosis (POMS) has not been well studied. Study objectives were to (1) describe the frequency of adverse SDOH, (2) evaluate social hardships as a potential barrier to the initiation of disease-modifying therapy (DMT), and (3) explore the association between adverse SDOH and disease outcomes in POMS, as well as study attrition. This was a retrospective multicenter observational study conducted through the United States Network of Pediatric MS Centers database. Participants were patients diagnosed with POMS (excluding primary progressive MS). The primary outcome was time to initiation of DMT. Secondary outcomes included most recent Expanded Disability Status Scale (EDSS) score, steroid treatment for the first event, time to second event, and study attrition. Demographic variables and clinical outcomes were compared between patients with and without hardships (maternal education of high school or less, public insurance/no insurance, or single/no-income household). Multivariable regression models were used to assess the impact of social hardship on study outcomes. There were 996 total participants (69% female, mean age at symptom onset and EDSS score [±SD] were 14.2 ± 3 and 1.2 ± 1.1, respectively). Of 768 patients with complete demographic information, 66% reported a hardship. Hardship was associated with younger age at symptom onset and diagnosis. While there was no difference in time to DMT initiation, patients with hardship were more likely to receive steroids for the first event (odds ratio [OR] 1.66, 95% CI 1.21-2.26, p = 0.002). Lack of private insurance was associated with increased risk of study attrition (OR 1.85, 95% CI 1.14-3.00, p = 0.012) and higher EDSS score (β = 0.15, 95% CI 0.01, 0.28). Living in a no-income household (vs dual-income) was associated with a shorter time to second event (hazard ratio 1.33, 95% CI 1.02-1.74, p = 0.034). The experience of hardships is common and associated with younger age at symptom onset and diagnosis, as well as shorter time to second event. Lack of private insurance is associated with study attrition and a higher EDSS score despite no difference in time to initiating DMT. There may be differences in early disease pathophysiology related to social hardship, and future studies are needed to better understand this complex relationship.

Transseptal Sheath Perfused with High Concentration Heparinized Saline for Reducing Sheath-associated Thrombus.

Transseptal catheterization is critical for atrial fibrillation (AF) ablation but risks thromboembolism. Transseptal sheaths (TSS) were suggested for continuous heparinized saline solution flush. The safety and effectiveness of a simple TSS management to reduce sheath-associated thrombus development risk was investigated. AF patients who underwent radiofrequency ablation with the simple TSS management were studied under a retrospective multi-center observation study and a prospective single-center observation study. TSS and dilators were washed and perfused with high concentration heparinized saline (20u/mL). Immediately after two successful transseptal punctures, activated clotting time ≥300s was maintained by heparin infusion. TSS aspiration with negative suction and re-perfusion with high concentration heparinized saline (20u/mL) was performed for the remaining procedure before and after catheter withdrawal. A total of 4765 AF patients underwent 5367 ablation procedures were enrolled in the retrospective study, involving 156 (2.9% per procedure) complications. No acute stroke occurred during all the procedures. Perioperative thromboembolic complications occurred in 10 (0.21%) patients and in 10 (0.19%) procedures. Thromboembolic complications occurred within 24 h, between 24-48 h, and after 48 h post-procedure in six, two, and two patients, respectively. In the prospective observation study, neither sheath- nor catheter-associated thrombus were detected by the intracardiac echocardiography during all 127 procedures, without any perioperative thromboembolic complications. No hemorrhagic cerebrovascular complication was encountered in both observational studies. For AF radiofrequency ablation, it was safe and effective for TSS high concentration heparinized saline infusion only. This approach could avoid sheath-associated thrombus for interventional procedures.

Factors Associated With Early Computed Tomography Imaging in Children Hospitalized With Severe Orbital Infections.

We identified factors associated with computed tomographic (CT) imaging within 24 hours of emergency department (ED) presentation in hospitalized children with severe orbital infections. A multicenter retrospective cohort study was conducted that included children aged 2 months to 18years between 2009 and 2018 who were admitted to the hospital with severe orbital infections, including periorbital and orbital cellulitis. Multivariable modified Poisson regression was used to identify possible factors associated with receiving a CT scan within 24 hours of ED presentation. Of 1144 children, 494 (43.2%) received a CT scan within 24 hours of ED presentation. Factors associated with receiving a CT scan within 24 hours included sex (male; adjusted relative risk [aRR], 1.18; 95% CI, 1.04-1.33), hospitalized at a children's hospital (aRR, 1.80; 95% CI, 1.32-2.45), consulted by both ophthalmology and otolaryngology (aRR, 3.12; 95% CI, 2.35-4.13) or either ophthalmology (aRR, 2.19; 95% CI, 1.66-2.90) or otolaryngology (aRR, 2.66; 95% CI, 1.84-3.86), and had proptosis (aRR, 1.39; 95% CI, 1.24-1.57) or eye swollen shut (aRR, 1.27; 95% CI, 1.13-1.43) as clinical signs upon ED presentation. Children aged younger than 5years were less likely to receive early CT imaging (aRR, 0.63; 95% CI, 0.53-0.74). There were no associations between time of ED triage, temperature greater than 38 °C, or inflammatory markers with early CT imaging. Although several patient and hospital factors associated with early CT imaging decisions in children with severe orbital infections are associated with more severe infections, newly identified risk factors, such as inflammatory markers, were not. These findings will help better the understanding of clinical management and indications for CT imaging.

Hierarchically Positioning Laparoscopic Microwave Ablation in the Therapeutic Span of Early Hepatocellular Carcinoma: A Real-Life Comparative Analysis.

Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment. A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population. Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups (p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) (p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death (p = 0.004) than the TACE-treated patients (p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths. The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

Role of Minimally Invasive Reoperation for Postoperatively Diagnosed T2 Gallbladder Cancer: Multicenter Retrospective Cohort Study.

Although T2 gallbladder cancer (GBC) incidentally diagnosed after cholecystectomy requires additional resection, the surgical approaches are technically difficult due to inflammatory adhesion or fibrosis around the hepatoduodenal ligament and gallbladder bed. In this study, we sought to compare the surgical and oncologic outcomes of open and minimally invasive reoperation for postoperatively diagnosed T2 GBC. Patients who underwent open (n = 110) and laparoscopic (n = 38) reoperation for T2 GBC between November 2004 and October 2022 at five tertiary referral centers were included in this multicenter retrospective cohort study. The short- and long-term outcomes were compared between the two groups. There were no differences in clinicopathological characteristics between the open and laparoscopic groups. Liver resection was more frequent in the open group (101 [91.8%] vs. 21 [55.3%], P < 0.001). Compared with open surgery, laparoscopic reoperation was associated with shorter postoperative hospital stay (9.0 [8.0-10.0] vs. 6.0 [3.8-8.3] days, P < 0.001) and a lower postoperative complication rate (24 [21.8%] vs. 1 [2.6%], P = 0.013). Among patients who underwent liver resection, the postoperative hospital stay was shorter in the laparoscopic group (9.0 [8.0-10.0] vs. 6.0 [4.0-9.0] days, P = 0.004). The 5-year disease-free survival (66.7% vs. 76.1%, P = 0.749) and overall survival (75.2% vs. 73.7%, P = 0.789) rates were not significantly different between the two groups. The results indicate that laparoscopic reoperation for postoperatively diagnosed T2 GBC has favorable postoperative outcomes and similar oncologic safety compared with open surgery.

Comparison of rigid and elastic registration methods in software-based targeted prostate biopsy: a multi-center cohort study

Comparison of rigid and elastic registration methods in software-based targeted prostate biopsy: a multi-center cohort study

Effectiveness and Safety Profile of Urethral Bulking with Bulkamid® for Stress Urinary Incontinence: A French Multi-Center Cohort Study.

Various treatment options are currently available for the management of stress urinary incontinence (SUI). This study was aimed at determining the effectiveness and safety profile of Bulkamid®, and identify predictive factors of clinical success. This retrospective study conducted in two French urogynecology university centers between September 2019 and December 2023 included all patients with urinary incontinence who received Bulkamid®. Among the 320 patients included (median age 58.2years), the median follow-up was 24 months. Urethral hypermobility was found in 93.4% of patients (n = 282) and 92% (n = 275) had a positive cough test. At 1 month, 68.7% of patients (n = 220) achieved clinical success, 25.6% (n = 82) improved, and 5.6% (n = 18) reported failure. At last follow-up, 63.7% of patients (n = 204) were still cured, 21.9% (n = 70) had improved, and 14.4% (n = 46) reported failure. Among the 16 patients with overactive bladder (OAB) 43.7% had a Patient Global Improvement (PGI) score of 1-2 at 1month and 50.0% at last follow-up, with significant difference compared with patients without OAB, 81.0% had a PGI score of 1-2 at 1month and 74.8% at last follow-up (p = 0.0006 and p = 0.04 respectively). Regarding complications, acute urinary retention occurred in 3.1% of patients (n = 10), urinary infections in 2.2% (n = 7), and transient hematuria in 7.2% (n = 23). In multivariate analysis, follow-up time was significantly associated with failure compared with improvement/cure (OR = 1.05, 95%CI 1.02-1.08, p = 0.0002). The present large series of patients reported the effectiveness of Bulkamid® injection, a minimally invasive procedure providing good clinical outcomes at 2years' follow-up.

Sex-Specific Obesity Paradox in Critically Ill Patients With Severe Acute Kidney Injury: A Retrospective Analysis.

Although obesity is typically correlated with adverse outcomes in various diseases, certain acute critical illnesses exhibit a phenomenon known as the obesity paradox. This study evaluated sex-specific differences in the prognostic implications of the body mass index (BMI) of patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). A multicenter retrospective cohort study. Data from eight tertiary hospitals in Korea. A total of 3805 critically ill patients receiving CRRT. Patients were categorized into four BMI groups: underweight, normal weight, overweight, and obese. None. There were 2308 male and 1497 female patients. The 90-day mortality risk significantly differed among BMI groups in the overall patient population and the male subpopulation but not the female subpopulation. Following adjustment for confounding variables, the 90-day mortality risk was higher in the underweight group than in the obese group (hazard ratio [HR], 1.20; 95% CI, 1.05-1.36; p = 0.006). Among male patients, the 90-day mortality risk was higher in both the underweight and normal weight groups than in the obese group (underweight: HR, 1.30; 95% CI, 1.10-1.53; p = 0.002 and normal weight: HR, 1.18; 95% CI, 1.04-1.35; p = 0.010); however, no such association was observed among female patients. Subgroup analysis demonstrated the obesity paradox in male patients of old age, with septic AKI, or with low albumin levels. There were sex differences in the association between BMI and mortality in critically ill patients with severe AKI. Although the precise distribution of fat mass and muscle mass was not identified, obese male patients had a more favorable prognosis, which was not evident among female patients. These findings highlight the importance of considering sex-specific factors in understanding the complex relationship between obesity and mortality in critically ill patients with AKI.

Intravenous thrombolysis in young adults with ischemic stroke: A cohort study from the international TRISP collaboration.

Previous observational data indicate that young adults treated with intravenous thrombolysis (IVT) for acute ischemic stroke have more favorable outcomes and less complications when compared to older adults. Given the limited data on this topic, we aimed to provide more evidence on clinical outcomes and safety in such patients, using a large international thrombolysis registry. In this prospective multicenter study, we used data from the Thrombolysis in Ischemic Stroke Patients (TRISP) registry from 1998 to 2020. Patients who received endovascular treatment (EVT), as only treatment or in addition to IVT, were not included in this cohort. Using multivariable regression models, we compared thrombolysed young patients aged 18-49 years with those aged ⩾50 years with regards to the following outcomes: favorable outcome in stroke survivors (modified Rankin Scale ⩽2), symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II (ECASS II) criteria, and three-months all-cause death. Of the 16,651 IVT treated patients, 1346 (8.1%) were 18-49 years. Young adults in TRISP were more often male (59.6% vs 54.0%), had a lower median NIHSS score on admission, 7 (4-13) versus 8 (5-15), and had less cardiovascular risk factors except for smoking (42.0% vs 19.0%) when compared to older patients. When compared to thrombolysed patients aged ⩾50 years, a favorable functional outcome was more likely in young adults: 81.9% versus 56.4%, aOR 2.30 (1.80-2.95), whilst sICH 1.6% versus 4.6%, aOR 0.45 (0.23-0.90) and death 2.3% versus 14.2%, aOR 0.21 (0.11-0.39) were less likely. Intravenous thrombolysis in young adults is independently associated with higher rates of favorable outcomes and lower rates of complications.

End-to-end deep learning patient level classification of affected territory of ischemic stroke patients in DW-MRI.

To develop an end-to-end DL model for automated classification of affected territory in DWI of stroke patients. In this retrospective multicenter study, brain DWI studies from January 2017 to April 2020 from Center 1, from June 2020 to December 2020 from Center 2, and from November 2019 to April 2020 from Center 3 were included. Four radiologists labeled images into five classes: anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior circulation (PC), and watershed (WS) regions, as well as normal images. Additionally, for Center 1, clinical information was encoded as a domain knowledge vector to incorporate into image embeddings. 3D convolutional neural network (CNN) and attention gate integrated versions for direct 3D encoding, long short-term memory (LSTM-CNN), and time-distributed layer for slice-based encoding were employed. Balanced classification accuracy, macro averaged f1 score, AUC, and interrater Cohen's kappa were calculated. Overall, 624 DWI MRIs from 3 centers were utilized (mean age, interval: 66.89 years, 29-95 years; 345 male) with 439 patients in the training, 103 in the validation, and 82 in the test sets. The best model was a slice-based parallel encoding model with 0.88 balanced accuracy, 0.80 macro-f1 score, and an AUC of 0.98. Clinical domain knowledge integration improved the performance with 0.93 best overall accuracy with parallel stream model embeddings and support vector machine classifiers. The mean kappa value for interrater agreement was 0.87. Developed end-to-end deep learning models performed well in classifying affected regions from stroke in DWI. The end-to-end deep learning model with a parallel stream encoding strategy for classifying stroke regions in DWI has performed comparably with radiologists.

Prevalence of SARS-COV-2 infection and outcomes in Greek sarcoidosis patients.

There is limited data on the prevalence of SARS-COV-2 in sarcoidosis patients and the underlying parameters linked to severity. We aimed to conduct a national multicenter study to explore the prevalence of SARS-COV-2 in sarcoidosis patients and investigate its impact on hospitalization and infection rates, describe the characteristics of the infected population and assess the role of these characteristics in determining the likelihood of infection or hospitalization. We recruited all the adult sarcoidosis patients with who were examined across eight Greek Health Interstitial Lung Disease Referral Centers from the beginning of the pandemic until August 1, 2022. All the data was collected using structured questionnaires. 530 sarcoidosis patients with a mean age of 54±12 years, 60% of whom were females, were recruited. 43% of them were under corticosteroid treatment, and 39% were under additional immunosuppression. 18% of Greek sarcoidosis patients were infected by the virus, which is a lower rate than the general population. The infection was mainly mild. Only one-fifth of the infected sarcoidosis patients required hospitalization, and no deaths or ICU admissions were recorded. Vaccination was found to be associated with a reduced likelihood of infection. Younger age, a longer period since diagnosis, abnormal PET-CT findings, and immunosuppression were associated with an increased probability of infection. The COVID-19 infection rate among Greek sarcoidosis patients was lower than the general population. Fewer than 20% needed hospitalization. There were no deaths or ICU admissions. Vaccination reduces the likelihood of infection. Younger age, longer diagnosis, abnormal PET-CT findings, and immunosuppression increased the chance of infection.

COmplexity of CARE and Discharge barriers: the 'modern internal medicine patient'. Results from the CO-CARED Study.

The ongoing demographic, epidemiological and social changes are dramatically raising the clinical and care complexity of patients admitted to internal medicine (IM) departments. Collecting evidence for a better characterization of patients is crucial to tailor future interventions based on patient's real needs. The aim of this prospective multicenter study was to describe the complexity of care of patients hospitalized in IM by calculating the complexity of care (ICC) score, through the combination of clinical instability (NEWS score) and care dependency scales (mICD). Furthermore, social frailty was assessed according to potential difficulty in discharge planning. 3912 patients were enrolled (median age 78years); 71% had a Charlson Comorbidity Index ≥ 5. The ICC score was high in 14.7% of patients, while 15% exhibited a NEWS score at least moderate. One in four patients presented moderate to critical social frailty. The length of stay was correlated with social frailty, mICD and ICC scores, but not with NEWS. In-hospital mortality was correlated with the severity of all the considered scores. A relevant proportion of IM patients exhibited a high complexity of care. Our data support a model in which approximately 15% of IM beds are designated for clinically unstable patients managed in intermediate care sub-units. The substantial burden of social frailty highlights the urgency of national plans allowing at the same time to cover the needs of not self-sufficient and socially disadvantaged patients, and to efficiently address the issue of emergency department boarding.

Surgical Timing for Patients with Thyroid Eye Disease Treated with Teprotumumab: A Collaborative Multicenter Study.

To compare regression rates, characteristics, and surgical outcomes of thyroid eye disease patients who underwent orbit, strabismus, or eyelid surgery at various times during or after teprotumumab treatment. Multicenter, retrospective, observational cohort study. Adult patients (age >18) with a minimum of 4 infusions of teprotumumab treatment for thyroid eye disease who had had eye surgery during or after treatment. Two groups were formed based on surgery timing: group 1 (G1) (<180 days since last infusion) and group 2 (G2) (≥180 days since last infusion). The primary outcome was postoperative regression rates. Secondary outcomes were postoperative regression characteristics, regression treatment, and orbital decompression proptosis reduction. This study evaluated 53 patients (81% female) who underwent 78 surgeries. G1 comprised 24 individuals with 34 surgeries, while G2 comprised 29 patients with 44 surgeries. Regression rates did not significantly differ between G1 and G2 (20.8% vs. 14.7%, p = 0.611). Compared with G1 patients, patients in G2 who regressed showed a significant mean increase in Clinical Activity Score (4.2 vs. 6.1, p = 0.027) and a nonsignificant yet measured increase in proptosis when compared with those in G1 (2.9 vs. 4.25, p = 0.298) at the time of regression. Compared with G1 patients, G2 patients who regressed were equally likely to undergo a repeat course of teprotumumab as group 1 (p = 0.14) but underwent a higher number of additional surgical procedures (p = 0.057). Thyroid stimulating immunoglobin levels uptrended more often in patients who regressed. Our study suggests that while the rate of regression may not differ significantly, the severity, clinical impact, and need for additional surgery might be more pronounced for patients who have surgery more than 6 months after their last teprotumumab dose.

Characterization of Shigella flexneri serotype 6 strains from geographically diverse low- and middle-income countries.

Shigella flexneri serotype 6 (Sf6) is one of the most common serotypes recovered from surveillance studies of moderate to severe diarrhea. Despite the clinical significance of Sf6, this serotype is understudied. In this work, we have performed both serotype-specific genomic and phenotypic comparisons of Sf6 isolates to one another and non-S. flexneri serotypes. Comparative genomic analyses identified significant nucleotide homology between Sf6 strains (n = 325), despite a broad range of collection timeframes and geographic locations. We identified Sf6 specific factors, including a potential novel Shigella virulence factor (type II secretion system). Additionally, we identified established Shigella virulence genes (ospG) and metabolic genes (rutABCDEFGR) that were absent in Sf6 strains while present in the majority of 728 non-Sf6 strains. Complete sequencing of 11 clinical Sf6 strains, demonstrated that the Sf6 virulence plasmid (pINV) is ~38 kb smaller than the average non-Sf6 pINV (~228 kb). Comparisons of S. flexneri species level antibiotic susceptibility highlighted that clinical Sf6 isolates from Africa in the Global Enteric Multicenter Study (GEMS) and Vaccine Impact on Diarrhea in Africa (VIDA) study demonstrated geographic, serotype-specific susceptibility pattern. Phenotypic analyses of Sf6 identified reduced intracellular invasion and cytokine induction from HT-29 cells, as well as reduced Ipa protein effector secretion, compared with S. flexneri serotype 2a strain 2457T. Together these data highlight conserved and unique serotype-specific genotypic and phenotypic features for Sf6. This level of conservation has not been noted for other S. flexneri serotypes and is promising for vaccine and diagnostic assays to provide global Sf6-specific coverage.IMPORTANCEShigellosis is an ongoing global public health crisis with >270 million annual episodes among all age groups; however, the greatest disease burden is among children in low- and middle-income countries (LMIC). The lack of a licensed Shigella vaccine and the observed rise in antimicrobial-resistant Shigella spp. highlights the urgency for effective preventative and interventional strategies. The inclusion of S. flexneri serotype 6 (Sf6) is a necessary component of a multivalent vaccine strategies based on its clinical and epidemiological importance. Given the genomic diversity of Sf6 compared with other S. flexneri serotypes and Sf6 unique O-antigen core structure, serotype-specific characterization of Sf6 is a critical step to inform Shigella-directed vaccine and alternative therapeutic designs. Herein, we identified conserved genomic content among a large collection of temporally and geographically diverse Sf6 clinical isolates and characterized genotypic and phenotypic properties that separate Sf6 from non-Sf6 S. flexneri serotypes.

Comparison between in situ fixation and fixation after closed reduction in valgus impacted femoral neck fractures: A Multicenter Study.

The objective of this study was to compare clinical outcomes between in situ fixation and fixation after closed reduction (CR) in patients aged 50 and above with valgus impacted femoral neck fractures using data from multiple centers. Design: Retrospective multicenter cohort study. Five tertiary-care university hospitals. Patients aged 50 and above, treated with operative fixation of valgus impacted femoral neck fractures using multiple cannulated screws from 2003 to 2019. Complications such as fixation failure, osteonecrosis of femoral head (ONFH), and reoperation were compared between the groups (in situ fixation group and fixation after CR group). Postoperative EuroQol-5 Dimension (EQ-5D), Harris Hip Score (HHS), and Koval's grade were compared. The mean age of the 206 patients (161 in situ fixation group, 45 in fixation after CR group) who met the inclusion criteria was 68.9 ± 10.9 years (range, 50 to 95 years). There were 39 men and 167 women. Fixation failure occurred in 11.2% (6.8% of in situ fixation group vs 26.7% of fixation after CR group, p = 0.002). Reoperation was required for 10.2% (7.5% of in situ fixation group vs 20% of fixation after CR group, p = 0.023). Fixation failure and reoperation rates were significantly higher in the fixation after CR group than in the in-situ fixation group (odds ratio = 4.757, p = 0.002 and odds ratio = 3.104, p = 0.023, respectively). At the two-year follow-up, ONFH occurred in 5.8% (9 out of 161, in situ fixation group vs 3 out of 45, fixation after CR group). There was no significant difference in the occurrence of ONFH between the two groups (p = 0.727). The Koval's grade at 6 and 12 months demonstrated better results in the in-situ group (p = 0.027, 0.044, respectively). Postoperative EQ-5D and HHS scores showed no statistically significant differences between the two groups. In patients aged 50 years or older with valgus impacted femoral neck fractures, when fixation was done after reduction, the reoperation rate was higher due to fixation failure compared to in-situ fixation. There was no significant difference in the incidence of ONFH in valgus impacted femoral neck fractures regardless of whether reduction was performed. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Use of the high-flow helmet CPAP non-invasive ventilation device designed in Peru in patients with severe acute respiratory syndrome (COVID-19): A prospective multicenter study

High-flow non-invasive ventilation (NIV) devices reduce the morbidity and mortality of COVID-19. The objective was to evaluate the use of the non-invasive ventilation device with high-flow helmet CPAP designed in Peru in patients with severe acute respiratory syndrome (COVID-19) hospitalized in the emergency services of five hospitals. Prospective multicenter and cross-sectional observational study from five hospitals from July to August 2020. 19 patients were recruited and divided into two groups (G-1 n = 10; G-2 n = 9) applying clinical and gasometric parameters as indicators of disease evolution upon hospital admission and within 24 hours. A progressive increase in these parameters was observed in those patients who used the NIVCPAP helmet within the first 24 hours. In G-01, improvement was evident in 90% (n = 9/10): PaO2 (range 48–137; average: 82.49 ± 8.07; p-value = 0.008), CO2 (25.2–51.0; 36.62 ± 2.62; p-value p = 0.327), and the PaO2/FiO2 coefficient (87–318; 191.5 ± 18.68). 10% of patients did not progress optimally, being subjected to endotracheal intubation and invasive mechanical ventilation. In G-02 the values ​​were %SatO2 (range 92–98; 96 ± 0.76) and the SaO2/FiO2 coefficient (214–228; 223.2 ± 1.80), indicating significant improvement within 24 hours (p &amp;lt; 0.001). It is concluded that the use of the CPAP helmet non-invasive ventilation (NIV) device contributes to improving gasometric values ​​and clinical condition. Being an alternative to recover typical cases of COVID-19 in all hospitals in Peru.

Preventing Severe COVID-19 with Tixagevimab-Cilgavimab in Hematological Patients Treated with Anti-CD20 Monoclonal Antibodies: An International Multicenter Study.

Despite the declining public health emergency status, COVID-19 still poses significant risks, especially for immunocompromised individuals. We aimed to evaluate the effectiveness of tixagevimab-cilgavimab (T-C) prophylaxis in preventing severe COVID-19 in patients with hematologic malignancies (HM) treated with anti-CD20 therapy during the early Omicron variant phase of the pandemic. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Respiratory Viruses (ESGREV) conducted a multicenter retrospective cohort study involving 15 centers from 5 countries. The study included 749 patients with HM treated with anti-CD20 between February 15 and June 30, 2022, comparing 215 who received T-C prophylaxis to 534 who did not. The study revealed a significant reduction in the risk of COVID-19 among patients who received T-C prophylaxis compared to those who did not (11.2% vs 23.4%, p < 0.001), with hazard ratio (HR) of 0.40 (95% CI 0.26-0.63), adjusted for age, sex, vaccination status, baseline HM malignancy and type of anti-CD-20. We also demonstrated a reduction for severe-critical diseases within all study populations, 1.4% vs 5.2%, p = 0.017, HR 0.26 (95% CI 0.08-0.84). T-C prophylaxis effectively prevented COVID-19 and severe-critical COVID-19 in patients with HM treated with anti-CD20 monoclonal antibodies during the early Omicron variant phase of the pandemic. Even though T-C is ineffective against current variants, these findings highlight the importance of additional protective measures and the continued development of monoclonal antibodies to protect immunocompromised individuals to mitigate the impact of COVID-19 and other respiratory viral diseases.