Association between nurses' personal, professional and work characteristics, and engagement in hospital-based clinical research.

PURPOSE: The purpose of this study was to assess the associations between demographic, professional and other personal nurse characteristics, social support factors and comfort in conducting research with nurses' level of active participation in clinical research. DESIGN: A prospective, cross-sectional, correlational design was used. METHODS: Clinical nurses working in a multihospital healthcare system were recruited by email to complete an anonymous survey that used multiple valid and reliable scales to assess demographic and professional work characteristics, curiosity, grit, locus of control, perceived social support (for research activities), comfort in conducting research, and level of being research-active. Univariate and multivariable analyses were completed. RESULTS: Of 310 participants, 274 (88.4%) were female and mean (SD) age was 42.9 (13.1) years. After condensing 11 levels of research activity to four categories, 179 (57.7%) were not research-active, and 91 (29.4%), 26 (8.3%) and 14 (4.5%) were engaged at low, moderate, and high levels, respectively. Of 78 factors, 69 (88.5%) were associated with being research-active in univariate analyses. In multivariable analysis that adjusted for age, personal experience as a patient, years as a nurse and hours in direct patient care, professionalism characteristics, higher curiosity, internal locus of control, grit perseverance, support of a nurse scientist and nurse friends, and comfort in conducting research remained associated with higher levels of being research-active (all p < 0.01). CONCLUSION: Research-active nurses were more likely to be engaged professionally in hospital-based activities beyond their work roles and displayed higher levels of positive psychological characteristics and mentorship that supported research capacity. CLINICAL RELEVANCE: Research-active nurses were more likely to have internal factors and external resources that promoted higher levels of being research-active. A strong professional governance model may enhance clinical nurses research activities.

Changes in Emergency Department Utilization in Vulnerable Populations After COVID-19 Shelter-in-Place Orders.

OBJECTIVES: This study aims to compare emergency department (ED) utilization and admission rates for patients with a history of mental health (MH) disorders, substance use disorders (SUDs), and social determinants of health (SDOH) before and after implementing COVID-19 shelter-in-place (SIP) orders. METHODS: This was a retrospective, multicenter study leveraging electronic medical record (EMR) data from 20 EDs across a large Midwest integrated healthcare system from 5/2/2019 to 12/31/2019 (pre-SIP) and from 5/2/2020 to 12/31/2020 (post-SIP). Diagnoses were documented in the patient's medical records. Poisson and logistic regression models were used to evaluate ED utilization and admission rate changes. RESULTS: A total of 871,020 ED encounters from 487,028 unique patients were captured. Overall, 2,572 (0.53%) patients had a documented Z code for SDOH. Patients with previously diagnosed MH disorders or SUDs were more likely to seek ED care after the SIP orders were implemented (risk ratio (RR): 1.20, 95% confidence interval (CI): 1.18-1.22, p<0.001), as were patients with SDOH (RR: 2.37, 95% CI: 2.19-2.55, p<0.001). Patients with both previously diagnosed MH disorders or SUDs and a documented SDOH had even higher ED utilization (RR: 3.31, 95% CI: 2.83-3.88, p<0.001) than those with either condition alone. Patients with MH disorders and SUDs (OR: 0.89, 95% CI: 0.86-0.92, p<0.001) or SDOH (OR: 0.67, 95% CI: 0.54-0.83, p<0.001) were less likely to be admitted post-SIP orders, while patients with a history of diseases of physiologic systems were more likely to be admitted. CONCLUSION: Vulnerable populations with a history of MH disorders, SUDs, and SDOH experienced increased ED utilization but a lower rate of hospital admissions after the implementation of SIP orders. The findings highlight the importance of addressing these needs to mitigate the impact of public health crises on these populations.

Adverse Cardiovascular Outcomes in Patients With Obstructive Sleep Apnea and Obesity: Metabolic Surgery vs Usual Care.

BACKGROUND: No therapy has been shown to reduce the risk of major adverse cardiovascular events (MACE) and death in patients with obstructive sleep apnea (OSA). OBJECTIVES: The authors sought to investigate the long-term relationship between metabolic surgery and incident MACE in patients with OSA and obesity. METHODS: Adult patients with a body mass index 35 to 70 kg/m2 and moderate-to-severe OSA at a U.S. health system (2004-2018) were identified. Baseline characteristics of patients who underwent metabolic surgery were balanced with a nonsurgical control group using overlap-weighting methods. Multivariable Cox regression analysis estimated time-to-incident MACE. Follow-up ended in September 2022. RESULTS: A total of 13,657 patients (7,496 [54.9%] men; mean age 52.0 ± 12.4 years; median body mass index 41.0 kg/m2 [Q1-Q3: 37.6-46.2 kg/m2]), including 970 patients in the metabolic surgery group and 12,687 patients in the nonsurgical group, with a median follow-up of 5.3 years (Q1-Q3: 3.1-8.4 years) were analyzed. The mean between-group difference in body weight at 10 years was 26.6 kg (95% CI: 25.6-27.6 kg) or 19.3% (95% CI: 18.6%-19.9%). The 10-year cumulative incidence of MACE was 27.0% (95% CI: 21.6%-32.0%) in the metabolic surgery group and 35.6% (95% CI: 33.8%-37.4%) in the nonsurgical group (adjusted HR: 0.58 [95% CI: 0.48-0.71]; P < 0.001). The 10-year cumulative incidence of all-cause mortality was 9.1% (95% CI: 5.7%-12.4%) in the metabolic surgery group and 12.5% (95% CI: 11.2%-13.8%) in the nonsurgical group (adjusted HR: 0.63 [95% CI: 0.45-0.89]; P = 0.009). CONCLUSIONS: Among patients with moderate-to-severe OSA and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE and death.

The Long-Term Effect of Weight Loss on the Prevention of Progression to Cirrhosis among Patients with Obesity and MASH-Related F3 Liver Fibrosis.

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08-0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21-8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01-1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.

Differential impact of sex on regulation of skeletal muscle mitochondrial function and protein homeostasis by hypoxia-inducible factor-1α in normoxia.

Hypoxia-inducible factor (HIF)-1α is continuously synthesized and degraded in normoxia. During hypoxia, HIF1α stabilization restricts cellular/mitochondrial oxygen utilization. Cellular stressors can stabilize HIF1α even during normoxia. However, less is known about HIF1α function(s) and sex-specific effects during normoxia in the basal state. Since skeletal muscle is the largest protein store in mammals and protein homeostasis has high energy demands, we determined HIF1α function at baseline during normoxia in skeletal muscle. Untargeted multiomics data analyses were followed by experimental validation in differentiated murine myotubes with loss/gain of function and skeletal muscle from mice without/with post-natal muscle-specific Hif1a deletion (Hif1amsd). Mitochondrial oxygen consumption studies using substrate, uncoupler, inhibitor, titration protocols; targeted metabolite quantification by gas chromatography-mass spectrometry; and post-mitotic senescence markers using biochemical assays were performed. Multiomics analyses showed enrichment in mitochondrial and cell cycle regulatory pathways in Hif1a deleted cells/tissue. Experimentally, mitochondrial oxidative functions and ATP content were higher with less mitochondrial free radical generation with Hif1a deletion. Deletion of Hif1a also resulted in higher concentrations of TCA cycle intermediates and HIF2α proteins in myotubes. Overall responses to Hif1amsd were similar in male and female mice, but changes in complex II function, maximum respiration, Sirt3 and HIF1ß protein expression and muscle fibre diameter were sex-dependent. Adaptive responses to hypoxia are mediated by stabilization of constantly synthesized HIF1α. Despite rapid degradation, the presence of HIF1α during normoxia contributes to lower mitochondrial oxidative efficiency and greater post-mitotic senescence in skeletal muscle. In vivo responses to HIF1α in skeletal muscle were differentially impacted by sex. KEY POINTS: Hypoxia-inducible factor -1α (HIF1α), a critical transcription factor, undergoes continuous synthesis and proteolysis, enabling rapid adaptive responses to hypoxia by reducing mitochondrial oxygen consumption. In mammals, skeletal muscle is the largest protein store which is determined by a balance between protein synthesis and breakdown and is sensitive to mitochondrial oxidative function. To investigate the functional consequences of transient HIF1α expression during normoxia in the basal state, myotubes and skeletal muscle from male and female mice with HIF1α knockout were studied using complementary multiomics, biochemical and metabolite assays. HIF1α knockout altered the electron transport chain, mitochondrial oxidative function, signalling molecules for protein homeostasis, and post-mitotic senescence markers, some of which were differentially impacted by sex. The cost of rapid adaptive responses mediated by HIF1α is lower mitochondrial oxidative efficiency and post-mitotic senescence during normoxia.

Continuous Glucose Monitoring Using the Dexcom G6 in Cardiac Surgery During the Postoperative Period.

OBJECTIVE: Cardiac surgery is associated with hyperglycemia, which in turn is associated with adverse postsurgical outcomes such as wound infections, acute renal failure, and mortality. This pilot study seeks to determine if Dexcom G6Pro continuous glucose monitor (Dexcom G6Pro CGM) is accurate during the postoperative cardiac surgery period when fluid shifts, systemic inflammatory response syndrome, and vasoactive medications are frequently encountered, compared to standard glucose monitoring techniques. METHODS: This study received institutional review board approval. In this prospective study, correlation between clinical and Dexcom glucose readings was evaluated. Clinical glucose (blood gas, metabolic panel, and point of care) data set included 1428 readings from 29 patients, while the Dexcom G6Pro CGM data included 45 645 data points following placement to upper arm. Additionally, average clinical measurements of day and overnight temperatures and hemodynamics were evaluated. Clinical and Dexcom data were restricted to being at least 1 hour after prior clinical reading Matching Dexcom G6Pro CGM data were required within 5 minutes of clinical measure. Data included only if taken at least 2 hours after Dexcom G6Pro CGM insertion (warm-up time) and analyzed only following intensive care unit (ICU) admission. Finally, a data set excluding the first 24 hours after ICU admission was created to explore stability of the device. Patients remained on Dexcom G6Pro CGM until discharge or 10 days postoperatively. RESULTS: The population was 71% male, 14% with known diabetes; 66% required intravenous insulin infusion. The Clarke error grid plot of all measures post-ICU admission showed 53.5% in zone A, 45.9% in zone B, and 0.6% (n = 5) in zones D or E. The restricted dataset that excluded the first 24 hours post-ICU admission showed 55.9% in zone A, 43.9% in zone B, and 0.2% in zone D. Mean absolute relative difference between clinical and Dexcom G6Pro CGM measures was 20.6% and 21.6% in the entire post-ICU admission data set, and the data set excluding the first 24 hours after ICU admission, respectively. In the subanalysis of the 12 patients who did not have more than a 5-minute tap in the operating room, a consensus error grid, demonstrated that after ICU admission, percentage in zone A was 53.9%, zone B 45.4%, and zone C 0.7%. Similar percentages were obtained removing the first 24 hours post-ICU admission. These numbers are very similar to the entire cohort. A consensus error grid created post-ICU admission demonstrated: (zone A) 54%, (zone B) 45%, (zone C) 0.9%, and the following for the dataset created excluding the first 24 hours: (zone A) 56%, (zone B) 44%, (zone C) 0.4%, which demonstrated very close agreement with the original Clarke error grid. No adverse events were reported. CONCLUSIONS: Almost 100% of Dexcom G6Pro CGM and clinical data matching points fell within areas considered as giving clinically correct decisions (zone A) and clinically uncritical decisions (zone B). However, the relatively high mean absolute relative difference precludes its use for both monitoring and treatment in the clinical context. As technology evolves, interstitial glucose monitoring may become an important tool to limit iatrogenic anemia and mitigate glycemic fluctuations.

Association Between Disease-Modifying Therapy and Information Processing Speed in Multiple Sclerosis.

BACKGROUND: Cognitive impairment (CI) is common in multiple sclerosis (MS). Processing speed (PS) is often affected, making it an ideal target for monitoring CI. This study aims to evaluate the association between disease-modifying therapy (DMT) use and intensity and longitudinal changes in Processing Speed Test (PST) scores for individuals with MS. METHODS: A retrospective analysis of individual PST scores at a single MS center was conducted. Individuals with 2 or more PST assessments were included. Scores on the PST were compared longitudinally between those who had been on a DMT for 2 or more years and those who had been off a DMT for 2 or more years and between those on high-efficacy DMTs and those on low-/moderate-efficacy DMTs. A linear regression model was approximated to evaluate the rate of cognitive change over time. A propensity score adjustment was conducted using a multivariable logistic regression. RESULTS: The cohort was 642 individuals, 539 on DMT and 103 off DMT. Median age and disease duration was 49.7 (IQR 42.4-57.9) and 16.6 years (IQR 9.3-23.0) in the DMT group, and 58.9 (IQR 52.2-65.3) and 20.0 years (IQR 14.1-31.4) in the non-DMT group. Both cohorts were predominantly female (75% DMT, 79.6% non-DMT), with a mean of 4 assessments (IQR 3-5), and an average monitoring duration of 1.9 years (1.2-2.4) in the DMT group, and 1.8 years (1.4-2.4) in the non-DMT group. After adjusting for multiple factors, DMT status and intensity were not found to be significant predictors of longitudinal PST change. CONCLUSIONS: Neither DMT status nor intensity was a significant predictor of cognitive processing speed over a period of approximately 2 years. Future prospective studies are needed to further support these findings.

Decisional regret and impacts on quality of life following genitourinary reconstruction for neurogenic bladder: A comparison between acquired and congenital spinal cord injury.

INTRODUCTION: Patient expectations and baseline health are important drivers of outcomes following major genitourinary reconstructive surgery for neurogenic bladder (NGB). Differences in expectations and quality of life (QoL) improvements among different populations with NGB remain insufficiently explored in the literature. OBJECTIVE: To compare decisional regret (DR) and urinary-related QoL (UrQoL) in patients undergoing urinary diversion for NGB arising from spinal cord injury of acquired (A-SCI) and congenital (C-SCI) etiologies. We hypothesize that patients with A-SCI have higher expectations of improvement in QoL following surgery when compared with C-SCI, which may lead to higher DR and decreased UrQoL, postoperatively. DESIGN: In this cross-sectional survey study, we compared A-SCI to C-SCI in terms of DR, UrQoL, and postoperative changes in self-reported physical health, mental health, and pain using validated patient-reported outcome measures. SETTING: Participants were enrolled from a quaternary care institution via mail and MyChart. PARTICIPANTS: The A-SCI group consistied of 17 patients with traumatic spinal cord injury the C-SCI group was composed of 20 patients with spina bifida. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Decisional Regret Scale, Short form- Qualiveen (SF-Qualiveen), and Patient-reported outcomes measurement Information system-10 (PROMIS-10) Global Health surveys. RESULTS: The A-SCI group displayed poorer preoperative physical health than the C-SCI cohort, but absolute postoperative changes in this score, along with mental health score and pain level, were not significant after adjusting for baseline scores and follow-up time. SF-Qualiveen scores revealed significantly worse impact of NGB in UrQoL for A-SCI than for C-SCI when adjusted for other factors. No differences in DR were seen between the groups. CONCLUSIONS: Patients with A-SCI demonstrate lower self-reported baseline physical health compared with patients with C-SCI, which may have implications in setting patient expectations when undergoing urinary diversion. In this small cohort, we found a milder self-reported postoperative impact of NGB in UrQoL in patients with C-SCI.

An Obesity-Centric Approach with and Without Anti-Obesity Medications Compared to the Usual-Care Approach to Management of Patients with Obesity and Type 2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial (EMPOWER-T2D).

INTRODUCTION: This study aimed to compare weight loss and glycated hemoglobin (HbA1c)-reduction effects of two obesity-centric, weight-loss management approaches (with or without anti-obesity medication) versus usual glucose-centric care in patients with obesity and type 2 diabetes. METHODS: Single-center, randomized, open-label, 3-armed, parallel-group, pragmatic, noninferiority trial, July 2020 to August 2022. Adults enrolled in the Cleveland Clinic Employee Health Plan (body mass index [BMI] ≥ 30 kg/m2, type 2 diabetes diagnosis, HbA1c > 7.5%) were randomized to usual glucose-centric management ("Usual-Care" group) or one of two obesity-centric management strategies: participation in a weight management program plus anti-obesity medication ("WMP + AOM" group), or WMP participation without anti-obesity medication ("WMP-Only" group). Primary endpoints were changes in weight and HbA1c, baseline to month 12. RESULTS: Due to enrollment and retention challenges, largely related to COVID-19, only 74/300 planned participants were randomized and the study was terminated early. Participants were predominantly female (59%), median (interquartile range [IQR]) age 53.5 (47, 60) years, 68% white, with baseline median (IQR) BMI and HbA1c of 37.4 (34.2, 42.7) kg/m2 and 8.8% (7.9%, 10.4%), respectively. At month 12, mean (90% confidence interval [CI]) percentage weight change in the Usual-Care, WMP-Only, and WMP + AOM groups was - 4.5% (- 6.5%, - 2.5%), - 6.7% (- 8.7%, - 4.7%), and - 8.7% (- 10.7%, - 6.8%), respectively; mean (90% CI) HbA1c change was - 1.7% (- 2.1%, - 1.2%), - 2.2% (- 2.7%, - 1.8%), and - 2.2% (- 2.6%, - 1.7%), respectively. WMP + AOM was superior to Usual-Care for weight change (P = 0.02); both WMP + AOM and WMP-Only were noninferior (P ≤ 0.01) to Usual-Care for change in HbA1c. CONCLUSIONS: Including anti-obesity medication was associated with superior weight loss with noninferior HbA1c reductions, warranting further evaluation in larger study populations of obesity-focused approaches to type 2 diabetes management. Graphical abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov NCT03799198.

Practice Trends among US Gastroenterologists following the 2020 American Gastroenterological Association Guidelines on Gastric Intestinal Metaplasia: Data from a Tertiary Care Center.

BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.

Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) often accompanies dementia-associated pathologies and is important in the context of anti-amyloid monoclonal therapies and risk of hemorrhage. METHODS: We conducted a retrospective neuropathology-confirmed study of 2384 participants in the National Alzheimer Coordinating Center cohort (Alzheimer's disease [AD], n = 1175; Lewy body pathology [LBP], n = 316; and mixed AD and LBP [AD-LBP], n = 893). We used logistic regression to evaluate age, sex, education, APOE ε4, neuritic plaques, and neurofibrillary tangles (NFTs) in CAA risk. RESULTS: APOE ε4 increased CAA risk in all three groups, while younger age and higher NFT stages increased risk in AD and AD-LBP. In AD-LBP, male sex and lower education were additional risk factors. The odds of APOE ε4 carrier homozygosity related to CAA was higher in LBP (25.69) and AD-LBP (9.50) than AD (3.17). DISCUSSION: AD and LBPs modify risk factors for CAA and should be considered in reviewing the risk of CAA. HIGHLIGHTS: Lewy body pathology modifies risk factors for cerebral amyloid angiopathy (CAA) when present along with Alzheimer's disease (AD) neuropathology. In the context of anti-amyloid monoclonal therapies and their associated risks for hemorrhage, the risk of underlying CAA in mixed dementia with Lewy body pathology needs to be considered.

Are there specific cytologic features that can predict BRAFV600E mutational status of papillary thyroid carcinoma in fine-needle aspiration specimens?

BACKGROUND: BRAFV600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features. METHODS: A computerized search for diagnosed PTC surgical pathology cases tested for BRAFV600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAFV600E mutational status and histologic subtypes. RESULTS: Study cohort consisted of 113 cases (74 BRAFV600E mutated, 39 BRAFV600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status. CONCLUSION: CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

Ibudilast reduces slowly enlarging lesions in progressive multiple sclerosis.

BACKGROUND: Ibudilast has shown beneficial effects on several imaging outcomes in progressive multiple sclerosis (MS). Slowly enlarging lesions are a proposed imaging biomarker of compartmentalized inflammation within chronic active lesions. OBJECTIVE: To assess the treatment effect of ibudilast on slowly enlarging lesion volumes over 96 weeks from a phase II clinical trial of ibudilast (Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]). METHODS: In total, 255 participants with progressive MS from 28 sites were randomized to oral ibudilast or placebo. Participants with at least four analyzable magnetic resonance imaging (MRI) were included. Slowly enlarging lesions were quantified using Jacobian determinant maps. A linear model was used to assess the effect of ibudilast. Magnetization transfer ratio within slowly enlarging lesions was assessed to determine the effect of ibudilast on tissue integrity. RESULTS: In total, 195 participants were included in this analysis. Ibudilast significantly decreased slowly enlarging lesion volume (23%, p = 0.003). Ibudilast also reduced magnetization transfer ratio change in slowly enlarging lesions: 0.22%/year, p = 0.04. CONCLUSION: Ibudilast showed a significant effect on baseline volume of lesions that were slowly enlarging and magnetization transfer ratio in slowly enlarging lesions. The results support the use of slowly enlarging lesions for assessment of compartmentalized inflammation represented by chronic active lesions and provide further support for the neuroprotective effects of ibudilast in progressive MS.

Patient factors associated with treatment time for stroke before and after the onset of COVID-19.

OBJECTIVES: Prior to our study, little was known about factors related to time-to-treatment for stroke pre- and post-COVID-19. DESIGN: This was a retrospective cohort study to evaluate factors associated with delayed door-to-needle time among patients with acute ischemic stroke over two time-periods. RESULTS: Final sample consisted of 932 charts with mean age of 68.1(±15.6). Significant factors associated with shorter door-to-needle time included ≤ four hours since symptom onset and stroke occurring during post-Covid-19 time-period. Those on anti-coagulants had 72 % higher odds of longer door-to-needle time. As patients got older and stroke symptoms were more severe, less time was spent in door-to-imaging. CONCLUSION: Results highlight the importance of early recognition of stroke symptoms and rapid transport to the hospital. Faster response times in post-Covid-19 time-period may be attributable to systematic processes put in place to address pandemic-related challenges. Outcomes may depend on research to identify gaps in stroke treatment.

Can Nonalcoholic Steatohepatitis Be Surgically Cured?: Liver Histologic Comparison After Metabolic Surgery Versus Usual Care.

OBJECTIVE: To compare histologic outcomes in patients with fibrotic nonalcoholic steatohepatitis (NASH) and obesity after metabolic surgery versus nonsurgical care. BACKGROUND: There are no published data comparing the effects of metabolic surgery versus nonsurgical care on histologic progression of NASH. METHODS: Repeat liver biopsies were performed in patients with body mass index >30 kg/m 2 at a US health system whose baseline liver biopsy between 2004 and 2016 confirmed a histologic diagnosis of NASH including the presence of liver fibrosis, but without cirrhosis. Baseline characteristics of liver histology for patients who underwent simultaneous liver biopsy at the time of metabolic surgery were balanced with a nonsurgical control group using overlap weighting methods. The primary composite endpoint required both resolution of NASH and improvement of at least 1 fibrosis stage in the repeat liver biopsy. RESULTS: A total of 133 patients (42 metabolic surgery and 91 nonsurgical controls) had a repeat liver biopsy with a median interval of 2 years. Overlap weighting provided balance for baseline histologic disease activity, fibrosis stage, and time interval between liver biopsies. In overlap-weighted patients, 50.1% in the surgical and 12.1% in the nonsurgical group met the primary endpoint (odds ratio=7.3; 95% CI, 2.8-19.2, P <0.001). NASH resolution and fibrosis improvement occurred in 68.5% and 64.1% of surgical patients, respectively. Surgical and nonsurgical patients who met the primary endpoint lost more weight than their counterparts who did not meet the primary endpoint [mean weight loss difference in the surgical group: 12.2% (95% CI, 7.3%-17.2%) and in the nonsurgical group: 11.6% (95% CI, 6.2%-16.9%)]. CONCLUSIONS: Among patients with fibrotic noncirrhotic NASH, metabolic surgery resulted in simultaneous NASH resolution and fibrosis improvement in half of patients.

Are 99mTC-Sestamibi Single Photon Emission Computed Tomography Scan Results Associated to the Parathyroid Cell Type in Primary Hyperparathyroidism?

INTRODUCTION: 99mTC-sestamibi scintigraphy (SPECT-CT) is a common imaging modality for parathyroid localization in primary hyperparathyroidism (PHPT). Prior studies have suggested that the cellular composition of parathyroid adenomas influences SPECT-CT imaging results. Other biochemical and anatomical factors may also play a role in false negative results. Therefore, after controlling for confounding variables, we sought to determine whether the histologic composition of parathyroid adenomas is associated to SPECT-CT results in patients with single gland disease causing PHPT. METHODS: A retrospective review of patients with PHPT due to confirmed single gland disease was performed over a 2-y period. A 1:1 propensity score matching was done between patients with positive and negative SPECT-CT results with regard to demographical, biochemical, and anatomical characteristics followed by blinded pathologic examination of cell composition in the matched pairs. RESULTS: Five hundred forty two patients underwent routine four gland exploration and 287 (53%) patients were found to have a single adenoma. Of those, 26% had a negative SPECT-CT result. There were significant differences between groups with regards to biochemical profile, gland location, and gland size. All of which became nonsignificant after propensity score matching. Adenomas were primarily composed of chief cells, with no difference between groups (95% versus 97%, P = 0.30). In the positive SPECT-CT group, chief cells were the dominant cell type in 68% of the cases, followed by mixed type (13%), oxyphil cells (12%), and clear cells (7%). This was similar to the negative SPECT-CT group (P = 0.22). CONCLUSIONS: While certain patient's clinical characteristics are associated with SPECT-CT imaging results, histologic cell type is not significantly associated.

Late Referral and Patient Transfer is Associated with Worse Outcomes for Patients Presenting with Initially Uncomplicated Type B Aortic Dissections.

BACKGROUND: Acute type B aortic dissections (TBADs) can become complicated at any time point, necessitating surgical repair. We sought to investigate the effect of interhospital transfer on the development of delayed complications in acute type B aortic dissection (dcTBAD). METHODS: All patients who presented with acute TBAD to a tertiary aortic center from 2015 to 2019 were analyzed. Patients were divided into initially complicated type B aortic dissection (icTBAD) (0-24 hours from symptom onset), dcTBAD (25 hours to 14 days), and uncomplicated type B aortic dissection (ucTBAD) groups. Criteria for complicated dissection were aortic rupture, malperfusion, or rapid aortic growth. Demographics, patient history, the timing of presentation, imaging findings, and clinical outcomes were compared between groups. RESULTS: Of 120 acute TBADs included, 27 (22%) were initially complicated (aortic rupture, n = 9; malperfusion, n = 18). Twenty-one (18%) developed delayed complications (aortic rupture, n = 3; malperfusion, n = 14; rapid growth, n = 4) at a median of 7.0 [4.0, 9.0] days from symptom onset. Seventy-two (60%) remained uncomplicated. Overall, 111 (93%) presented as transfers from outside hospitals (icTBAD, n = 25; dcTBAD, n = 21; ucTBAD, n = 65). Of those, dcTBADs were more likely to have a prolonged delay between presentation to the outside hospital and referral to the tertiary center compared to ucTBADs (median = 1.00 [0.0, 5.0] days delayed vs. 0.00 [0.0, 0.0] days delayed; P < 0.001). Initially uncomplicated patients referred for transfer ≥24 hours from presentation went on to develop dcTBAD more often than those transferred in <24 hours (73% vs 13%; P < 0.001). Of dcTBADs, 38% had no high-risk features on initial imaging. Patients with dcTBAD had significantly longer length of stay (median = 12 vs 7 days; P = 0.006). In-hospital mortality was significantly higher in dcTBADs than ucTBADs (9.5% vs 0%; P = 0.047). In-hospital mortality was not significantly different between dcTBADs and icTBADs (9.5% vs. 11%; P > 0.05). CONCLUSIONS: The incidence and consequence of dcTBADsare not insignificant. Late referral and transfer to a tertiary aortic center (≥24 hours from initial presentation) was associated with dcTBADsrequiring surgical intervention. The development of dcTBADwas associated with increased length of stay and increased in-hospital mortality.

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases.

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcoma and myxoid malignant fibrous histiocytoma arising in patients aged ≤40 years with clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34 cm (median 4.1 cm). Anatomic sites included proximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P = .025, P = .005), while tumor depth was also associated with worse EFS (P = <.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis.

Efficacy of One Dose of Laxative on Postoperative Constipation Following Total Knee Arthroplasty.

Postoperative constipation is a common problem among orthopaedic surgical patients leading to discomfort, increased length of stay, and other complications. The primary purpose of this study was to determine the effectiveness of polyethylene glycol compared with docusate sodium for the prevention of constipation, after total knee arthroplasty. The secondary purpose was to examine the effectiveness of polyethylene glycol on pain and strain with bowel movement. A two-group nonequivalent cohort design was used to evaluate the effect of one 17-g dose of polyethylene glycol by mouth on postoperative day 1 compared with usual care with docusate sodium 100 mg starting the day of surgery and continued twice daily at home. There was no significant difference in the rate of constipation between the two cohorts in the 3 days after surgery. There was no difference in reported pain and strain. Future research should focus on the use of pharmacologic and nursing interventions together for prevention of postoperative constipation in patients with arthroplasty surgery.