Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.
Bariatric Surgery ; Body Composition ; Body Weight ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Muscle, Skeletal ; Population Characteristics ; Weight Loss

Purpose: Preoperative identification of the intraosseous posterior superior alveolar artery (PSAA) is critical when planning sinus surgery. This study was conducted to determine the distance between the cementoenamel junction and the PSAA, as well as to identify factors influencing the detection of the PSAA on cone-beam computed tomography (CBCT). Materials and Methods: In total, 254 CBCT scans of maxillary sinuses, acquired with 2 different scanners, were examined to identify the PSAA. The distance from the cementoenamel junction (CEJ) to the PSAA was recorded at each maxillary posterior tooth position. Binomial logistic regression and multiple linear regression were employed to evaluate the effects of scanner type, CBCT parameters, sex, and age on PSAA detection and CEJ-PSAA distance, respectively. P-values less than 0.05 were considered to indicate statistical significance. Results: The mean CEJ-PSAA distances at the second molar, first molar, second premolar, and first premolar positions were 17.0±4.0 mm, 21.8±4.1 mm, 19.5±4.7 mm, and 19.9±4.9 mm for scanner 1, respectively, and 17.3±3.5 mm, 16.9±4.3 mm, 18.5±4.1 mm, and 18.4±4.3 mm for scanner 2. No independent variable significantly influenced PSAA detection. However, tooth position (b = - 0.67, P<0.05) and scanner type (b = - 1.3, P<0.05) were significant predictors of CEJ-PSAA distance. Conclusion CBCT-based estimates of CEJ-PSAA distance were comparable to those obtained in previous studies involving cadavers, CT, and CBCT. The type of CBCT scanner may slightly influence this measurement. No independent variable significantly impacted PSAA detection.

PURPOSE: There is a need to broaden protective coverage of M protein–based vaccines against group A streptococci (GAS) because coverage of the current 30-valent M protein vaccine does not extend to all emm types. An additional GAS antigen and virulence factor that could potentially extend vaccine coverage is M-related protein (Mrp). Previous work indicated that there are three structurally related families of Mrp (MrpI, MrpII, and MrpIII) and peptides of all three elicited bactericidal antibodies against multiple emm types. The purpose of this study was to determine if a recombinant form containing Mrp from the three families would evoke bactericidal antiserum and to determine if this antiserum could enhance the effectiveness of antisera to the 30-valent M protein vaccine. MATERIALS AND METHODS: A trivalent recombinant Mrp (trMrp) protein containing N-terminal fragments from the three families (trMrp) was constructed, purified and used to immunize rabbits. Anti-trMrp sera contained high titers of antibodies against the trMrp immunogen and recombinant forms representing MrpI, MrpII, and MrpIII. RESULTS: The antisera opsonized emm types of GAS representing each Mrp family and also opsonized emm types not covered by the 30-valent M protein–based vaccine. Importantly, a combination of trMrp and 30-valent M protein antiserum resulted in higher levels of opsonization of GAS than either antiserum alone. CONCLUSION: These findings suggest that trMrp may be an effective addition to future constructs of GAS vaccines.
Antibodies ; Humans ; Immune Sera ; Peptides ; Rabbits ; Staphylococcal Protein A* ; Streptococcal Vaccines* ; Streptococcus pyogenes ; Vaccines ; Virulence ; Virulence Factors

Purpose: Malignant large bowel obstruction is a surgical emergency that requires urgent decompression. Stents are increasingly being used, though reported outcomes are variable. We describe our multidisciplinary experience in using stents to manage malignant large bowel obstruction. Methods: All patients undergoing colorectal stent insertion for acute large bowel obstruction in a teaching hospital were included. Outcomes, complications, and length of stay (LOS) were recorded. Results: Over a 7-year period, 73 procedures were performed on 67 patients (37 male, mean age of 76 years). Interventional radiology was involved in all cases. Endoscopic guidance was required in 24 cases (32.9%). In 18 patients (26.9%), treatment intent was to bridge to elective surgery; 16 had successful stent placement; all had subsequent curative resection (laparoscopic resection, 8 of 18; primary anastomosis, 14 of 18). Overall LOS, including both index admission and elective admission, was 16.4 days. Treatment intent was palliative in 49 patients (73.1%). In this group, stents were successfully placed in 41 of 49 (83.7%). Complication rate within 30 days was 20%, including perforation (2 patients), per rectal bleeding (2), stent migration (1), and stent passage (5). Nineteen patients (38.8%) required subsequent stoma formation (6, during same admission; 13, during subsequent admission). Overall LOS was 16.9 days. Conclusion In our experience colorectal stents can be used effectively to manage malignant large bowel obstruction, with only selective endoscopic input. As a bridge to surgery, most patients can avoid emergency surgery and have a primary anastomosis. In the palliative setting, the complication rate is acceptable and two-thirds avoid a permanent stoma.

Background: and Purpose High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. Methods: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. Results: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). Conclusions Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.