Increased Grades of Rectal Intussusception: Role of Decline in Pelvic Floor Integrity and Association With Dyssynergic Defecation.

INTRODUCTION: The natural history of rectal intussusception (RI) is poorly understood. We hypothesized that decline in pelvic floor integrity and function leads to increasing RI grades. METHODS: Retrospective analysis of a registry of patients with defecatory disorders with high-resolution anorectal manometry and magnetic resonance defecography was performed. Association of risk factors on increasing RI grades was assessed using logistic regression. RESULTS: Analysis included a total of 238 women: 90 had no RI, 43 Oxford 1-2, 49 Oxford 3, and 56 Oxford 4-5. Age ( P = 0.017), vaginal delivery ( P = 0.008), and prior pelvic surgery ( P = 0.032) were associated with increased Oxford grades. Obstructive defecation symptoms and dyssynergic defecation were observed at relatively high rates across groups. Increased RI grades were associated with less anal relaxation at simulated defecation yet, higher rates of normal balloon expulsion ( P < 0.05), linked to diminished anal sphincter. Indeed, increased RI grades were associated with worsening fecal incontinence severity, attributed to higher rates of anal hypotension. Levator ani laxity, defined by increased levator hiatus length and its excessive descent at straining, was associated with increasing RI grades, independent of age, history of vaginal delivery, and pelvic surgeries and could independently predict increased RI grades. Concurrent anterior and posterior compartments, and visceral prolapse were associated with higher Oxford grades. DISCUSSION: Our data suggest that decline in pelvic floor integrity with abnormal levator ani laxity is associated with increased RI grades, a process that is independent of age, history of vaginal deliveries, and/or pelvic surgeries, and perhaps related to dyssynergic defecation.

Linear hair growth rates in preschool children.

BACKGROUND: Human scalp hair is a validated bio-substrate for monitoring various exposures in childhood including contextual stressors, environmental toxins, prescription or non-prescription drugs. Linear hair growth rates (HGR) are required to accurately interpret hair biomarker concentrations. METHODS: We measured HGR in a prospective cohort of preschool children (N = 266) aged 9-72 months and assessed demographic factors, anthropometrics, and hair protein content (HPC). We examined HGR differences by age, sex, race, height, hair pigment, and season, and used univariable and multivariable linear regression models to identify HGR-related factors. RESULTS: Infants below 1 year (288 ± 61 µm/day) had slower HGR than children aged 2-5 years (p = 0.0073). Dark-haired children (352 ± 52 µm/day) had higher HGR than light-haired children (325 ± 50 µm/day; p = 0.0019). Asian subjects had the highest HGR overall (p = 0.016). Younger children had higher HPC (p = 0.0014) and their HPC-adjusted HGRs were slower than older children (p = 0.0073). Age, height, hair pigmentation, and HPC were related to HGR in multivariable regression models. CONCLUSIONS: We identified age, height, hair pigment, and hair protein concentration as significant determinants of linear HGRs. These findings help explain the known hair biomarker differences between children and adults and aid accurate interpretation of hair biomarker results in preschool children. IMPACT: Discovery of hair biomarkers in the past few decades has transformed scientific disciplines like toxicology, pharmacology, epidemiology, forensics, healthcare, and developmental psychology. Identifying determinants of hair growth in children is essential for accurate interpretation of hair biomarker results in pediatric clinical studies. Childhood hair growth rates define the time-periods of biomarker incorporation into growing hair, essential for interpreting the biomarkers associated with environmental exposures and the mind-brain-body connectome. Our study describes age-, sex-, and height-based distributions of linear hair growth rates and provides determinants of linear hair growth rates in a large population of children. Age, height, hair pigmentation, and hair protein content are determinants of hair growth rates and should be accounted for in child hair biomarkers studies. Our findings on hair protein content and linear hair growth rates may provide physiological explanations for differences in hair growth rates and biomarkers in preschool children as compared to adults.

Understanding Wheelchair Use in Older Adults From the National Health and Aging Trends Study.

OBJECTIVE: To identify the trends of wheelchair use and physical characteristics among older people who used wheelchairs relative to those who did not. DESIGN: Cohort and survey. SETTING: General community. PARTICIPANTS: 7026 participants (N=7026) were selected from the 2011 cohort of the National Health and Aging Trends Study (NHATS), which is made up of Medicare beneficiaries over the age of 65. Repeated observations among participants in the 2011 cohort were analyzed in the 4 following rounds: 2013 (N=4454), 2015 (N=3327), 2017 (N=2623), and 2019 (N=2091). Participants were divided into 2 groups: those who used and did not use wheelchairs. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Physical characteristics, including pain, strength limitation, balance problems, mobility disability, as well as the frequency of going outside. RESULTS: The number of older adults who use wheelchairs had increased significantly from 4.7 per 100 people in 2011 to 7.1 in 2019 (P<.001). The logistic regression analysis indicated that participants who reported less frequently going out were at least 4.27 times more likely to be wheelchair users than non-wheelchair users (P<.01). Participants who reported health and physical problems were at least 2.48 times more likely to be wheelchair users than non-wheelchair users from 2011 to 2017 (P<.0001). Balance or coordination problems increased (24%-38%) significantly among non-wheelchair users from 2011 to 2019 (all P<.05). CONCLUSIONS: Current wheelchair users reported more physical difficulties and were much less likely to go outside. This lower outdoor mobility could be due to physical difficulties or potential barriers in physical and socio-cultural environments. In addition, older adults who do not use wheelchairs showed increasing physical problems over time (including balance or coordination problems). Clinicians should consider older wheelchair users' health and physical limitations when prescribing wheelchairs.

Adherence to Screen Time and Physical Activity Guidelines is Associated with Executive Function in US Toddlers Participating in the STRONG Kids 2 Birth Cohort Study.

OBJECTIVE: To test the hypothesis that healthy weight status and adherence to American Academy of Pediatrics (AAP) guidelines for diet and physical activity would extend to greater executive function (EF) at age 24 months. STUDY DESIGN: Parents of 24-month-old children from the STRONG Kids 2 cohort study (n = 352) completed the Behavioral Rating Inventory of Executive Function for Preschoolers (BRIEF-P) and reported physical activities, diet, and screen time. Toddlers met AAP guidelines if they consumed at least 5 servings of fruits and vegetables, were physically active, refrained from sugar-sweetened beverages, and limited daily screen time to <60 minutes. Relationships between EF, 24-month weight status, and meeting AAP guidelines were tested independent of child sex, ethnicity, socioeconomic status, weight status at birth, and maternal pregnancy weight status. RESULTS: Weight-for-length z-score had no effect on EF. Toddlers meeting the screen time guideline had greater EF (ß, -0.125; 95% CI, 0.234 to -0.008), inhibitory self-control (ß, -0.142; 95% CI, -0.248 to -0.029), and emergent metacognition (ß, -0.111; 95% CI, -0.221 to 0.002), indicated by lower BRIEF-P scores. Those with more minutes of screen time had poorer overall EF (ß, 0.257; 95% CI, 0.118-0.384), inhibitory self-control (ß, 0.231; 95% CI, 0.099-0.354), cognitive flexibility (ß, 0.217; 95% CI, 0.082-0.342), and emergent metacognition (ß, 0.257; 95% CI, 0.120-0.381). Daily physical activity was associated with greater emergent metacognition (ß, -0.116; 95% CI, -0.225 to -0.005). CONCLUSIONS: Meeting AAP guidelines for physical activity and screen time was related to greater EF in a demographically homogenous sample of toddlers. Future randomized control trials and more diverse samples are needed to confirm the directionality of this relationship. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03341858.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Racial disparities in opioid administration and prescribing in the emergency department for pain.

STUDY OBJECTIVE: To investigate the holistic characteristics of patients administered or prescribed opioids to treat pain in the emergency department (ED). METHODS: We used National Hospital Ambulatory Medical Care Survey (NHAMCS) data for 2018 to examine the administration and prescribing of opioids for pain-related ED visits. Weighted logistic regression models were developed to evaluate the association between opioid administration and prescribing (OAP) in the ED and patients' pain/severity of conditions, demographic/socioeconomic factors, behavioral factors, contextual factors, and organizational factors. Then, subgroup analyses were conducted by type of pain. RESULTS: Nearly 55% of the ED visits in 2018 involved pain as a main reason for visiting the ED. The odds of receiving opioids were 45% less in black patients than in white patients when other covariates were adjusted (OR: 0.55; CI: 0.430-0.703). Compared to patients with private insurance, Medicaid beneficiaries and uninsured/self-pay patients had a 45% (OR: 0.55; CI: 0.423-0.706) and 44% (OR: 0.56; CI: 0.386-0.813) lower chance of receiving or being prescribed opioids for a pain-related ED visit when all covariates were adjusted. Other significant predictors of OAP for pain in EDs included older age, higher pain level, ED arrival by ambulance, admission to hospital, ED arrival during a night shift, geographic region of the ED. Behavioral factors, such as ED return within 72 h and whether a patient has substance/alcohol abuse or dependence, were not significantly associated with OAP. The subgroup analysis indicated that black patients had lower odds of OAP than their white counterparts only for certain pain categories. CONCLUSION: Despite increasing awareness of potential implicit bias in managing pain in the ED, racial disparities in OAP still existed. More education and training on implicit bias would help with reduce the disparities. Also, our study result indicated that non-clinical factors may play a role in emergency physicians' decision making in OAP. Increased recognition of the variation and systemic efforts to address factors affecting the variability are needed.

Fear of Falling, Community Participation, and Quality of Life Among Community-Dwelling People Who Use Wheelchairs Full Time.

OBJECTIVES: To examine the differences in community participation and quality of life (QOL) among individuals who use wheelchairs full time with and without fear of falling (FOF). DESIGN: Cross-sectional study design. SETTING: University research laboratory. PARTICIPANTS: Individuals (N=85) who use a manual or power wheelchair full time who are living with various health conditions and have a history of at least 1 fall in the past 12 months (age, 45.4±15.8y; disability duration, 21.5±13.6y) were included. Forty-six (54%) were manual wheelchair users. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: To quantify FOF, participants responded (yes/no) to the question: "Are you worried or concerned that you might fall?" Community participation and QOL were indexed by the Community Participation Indicator (CPI) and the World Health Organization Quality of Life-Brief version (WHOQOL-BREF), respectively. A multivariate analysis of variance (MANOVA) was performed to examine the differences in CPI and WHOQOL-BREF scores among wheelchair users who reported FOF and no FOF. RESULTS: A total of 54 participants (63.5%) reported that they were worried or concerned about falling. The MANOVA revealed significant differences in overall CPI (F2,82=4.714; P=.012; Wilks' λ=0.897) and WHOQOL-BREF (F4,63=3.32; P=.016; Wilks' λ=.826) scores. Participants who reported FOF demonstrated significantly lower CPI and WHOQOL-BREF scores compared with those who did not report FOF. CONCLUSIONS: FOF and associated activity curtailment are prevalent and may be a factor influencing full time wheelchair users' community participation and QOL. Prospective research is needed to better understand how FOF influences community participation and QOL among individuals who use wheelchairs full time. Findings would support the development of interventions, specifically for individuals who use wheelchairs full time, to reduce FOF and improve community participation and QOL.

The Emerging Adult Reasons for Substance Use (EARS): Preliminary Support for Multidimensionality, Validity and Reliability.

Introduction: Substance use peaks during the transition to adulthood, beckoning additional research on its developmental influences. This article reports initial findings on the validity and reliability of the Emerging Adult Reasons for Substance use (EARS), a new measure of substance use motives based on Arnett's (2000) proposed emerging adult dimensions. Method: Content experts in emerging adulthood theory generated EARS items and collected data from a large online sample. We completed exploratory (EFA) and confirmatory factor analyses (CFA) on split halves of the total sample (n = 750). Then, we tested for invariance across genders and age cohorts, as well as examined cross-correlations with the Inventory of Dimensions of Emerging Adulthood (IDEA), Drinking Motives Questionnaire (DMQ-Revised), and measures of substance use. Results: The EFA identified three internally consistent factors: Normative Expectancy, Developmental Strain, and Subjective Invulnerability. Confirmatory factor analyses supported the three factor model, but fit indices were slightly below published standards (RSMEA = .82, CFI = .85, TLI = .83, SRMR = .07). For Normative Expectancy and Developmental Strain, intercepts varied across age cohorts, with higher intercepts for emerging relative to older adults. The patterns of correlations generally supported the construct validity of the EARS subscales. Conclusion: The EARS is reliable and valid, and appears to measure developmentally specific motives for substance use. Additional studies may further validate this promising instrument.

Work Personality, Core Self-evaluation and Perceived Career Barriers in Young Adult Central Nervous System Cancer Survivors.

PURPOSE: The purpose of this study is to examine the relationship between work personality, core self-evaluation (CSE), and perceived internal and external barriers to employment in a group of young adult CNS survivors. METHODS: The participants consisted of 110 young adult survivors of pediatric central nervous system (CNS) tumors aged between 18 and 30 years old (M = 23.05, SD = 3.36). Mediation analysis with structural equational modeling (SEM) technique was used to correlate a number of different measures (Work Personality [WP], Perceived Employment Barriers [PEB], and Core-Self Evaluation [CSE]). RESULTS: Results revealed an exceptionally well-fitting model to our data with work personality predicting CSE positively: ß = 0.34, SE = 0.07, 95% CI (0.18, 0.47) while CSE inversely predicts Perceived Barriers to Employment, ß = - 0.60, SE = 0.06, 95% CI (- 0.70, - 0.49). There is a direct pathway from WP to PEB once CSE was accounted for ß = - 0.20, SE = 0.07, 95% CI (- 0.33, - 0.06). The presence of both significant direct and indirect effects of WP on PEB implied that there was a partial mediating effect of CSE on the association between WP and PEB. CONCLUSIONS: Work personality is a robust construct that can be applied to young adult CNS survivors in effort to gain more insight into the personality and psychological factors that impact career development and employment in this group. The major finding of this study was that work personality and CSE had a significant direct effect on perceived career barriers and that there was a significant indirect effect with CSE acting as a mediator between developmental work personality and perceived career barriers.

Fresh- and lean-pork intake in relation to functional limitations among US older adults, 2005-2016.

BACKGROUND: Pork consumption, in particular fresh/lean-pork consumption, provides protein and other essential micronutrients that older adults need daily and may hold the potential to prevent functional limitations resulting from sub-optimal nutrition. AIM: Assess fresh/lean-pork intake in relation to functional limitations among older adults in the USA. METHODS: Individual-level data came from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 waves. Nineteen validated questions assessed five functional limitation domains: activities of daily living (ADLs); instrumental activities of daily living (IADLs); leisure and social activities (LSAs); lower extremity mobility (LEM); and general physical activities (GPAs). Logistic regressions were performed to examine pork, fresh-pork and fresh lean-pork intake in relation to functional limitations among NHANES older adults (n = 6135). RESULTS: Approximately 21, 18 and 16% of older adults consumed pork, fresh pork and fresh lean pork, respectively. An increase in pork consumption by 1 oz-equivalent/day was associated with a reduced odds of ADLs by 12%, IADLs by 10% and any functional limitation by 7%. An increase in fresh-pork consumption by 1 oz-equivalent/day was associated with a reduced odds of ADLs by 13%, IADLs by 10%, GPAs by 8%, and any functional limitation by 8%. Similar effects were found for fresh lean-pork consumption on ADLs, IADLs, GPAs and any functional limitation. CONCLUSION: This study found some preliminary evidence linking fresh/lean-pork consumption to a reduced risk of functional limitations. Future studies with longitudinal/experimental designs are warranted to examine the influence of fresh/lean-pork consumption on functional limitations.

Cumulative exposure to work-related traumatic events and current post-traumatic stress disorder in New York City's first responders.

BACKGROUND AND OBJECTIVES: Cumulative exposure to work-related traumatic events (CE) is a foreseeable risk for psychiatric disorders in first responders (FRs). Our objective was to examine the impact of work-related CE that could serve as predictor of posttraumatic stress disorder (PTSD) and/or depression in FRs. DESIGN: Cross-sectional examination of previous CE and past-month PTSD outcomes and depression in 209 FRs. METHODS: Logistic (probable PTSD; probable depression) and Poisson regressions (PTSD score) of the outcomes on work-related CE indexes, adjusting for demographic variables. Differences across occupational groups were also examined. Receiver operating characteristic analysis determined the sensitivity and specificity of CE indexes. RESULTS: All indexes were significantly and differently associated with PTSD; associations with depression were non-significant. The index capturing the sheer number of different incidents experienced regardless of frequency ('Variety') showed conceptual, practical and statistical advantages compared to other indexes. In general, the indexes showed poor to fair discrimination accuracy. CONCLUSIONS: Work-related CE is specifically associated with PTSD. Focusing on the variety of exposures may be a simple and effective strategy to predict PTSD in FRs. Further research on sensitivity and specificity of exposure indexes, preferably examined prospectively, is needed and could lead to early identification of individuals at risk.

Reliability and Validity of Proposed DSM-5 ADHD Symptoms in a Clinical Sample of Adults.

The DSM-5 ADHD and Disruptive Behaviors Work Group proposed two major changes for diagnosis of attention deficit hyperactivity disorder (ADHD) in adults: (1) inclusion of four new impulsivity symptoms and (2) reduction in the number of symptoms required for assigning an ADHD diagnosis. In this case-control study, the performance of these modifications was assessed in a clinical sample of 133 adult subjects (68 ADHD cases and 65 non-ADHD control subjects). The proposed new impulsivity symptoms for adults do not improve ADHD diagnosis enough to overcome potential negative effects of changing the criteria. However, fewer symptoms than the six-of-nine threshold required by DSM-IV provided the best cutoff point for identifying adults who are impaired.

Interorganizational relationships among family support organizations and child mental health agencies.

This study examined: (1) qualitative aspects of close working relationships between family support organizations and child mental health agencies, including effective and ineffective characteristics of the relationship and aspects that they would change, and (2) the impact of the working relationship upon the family support organization. Semi-structured interviews were conducted with 40 directors of family support organizations characterized as having a close working relationship with a child mental health agency. Three main themes emerged regarding the quality of the working relationship: (a) interactional factors, including shared trust, communication, collaboration and service coordination; (b) aspects of the inner context of the family support organization, mental health agency, or both, including alignment of goals and values and perceptions of mental health services; and (c) outer contextual factors external to the organizations, such as financial and county regulations. Responses to the perceived impact of the relationship was divided into two themes: positive impacts (e.g. gained respect, influence and visibility), and negative impacts (e.g. lack of trust). This study lays the foundation for future research to better understand the mechanisms underlying interorganizational relationships in communities among different types of providers to create a more seamless continuum of services for families of children with mental health conditions.

Impact of an Interactive, Animation-Based Electroencephalography Curriculum on Learner Confidence and Knowledge.

BACKGROUND: There is a national need for innovative electroencephalography (EEG) education with efficacy evaluated by rigorous statistical analysis. We created a dynamic, online resource that includes a series of animated videos at a single academic medical center. METHODS: For the animations and interactive module, we used VideoScribe and Articulate, respectively. The module comprised three chapters: (1) Origin & Technical Aspects of EEG, (2) Normal Adult EEG in Wakefulness & Sleep, and (3) Abnormal EEG, with appendices on artifacts, variants, activation procedures, seizure/epilepsy classification, and neonatal/pediatric EEG. The curriculum and knowledge assessments were reviewed independently by two fellowship-trained physicians before distribution. Linear mixed-effects models with bootstrapping were used to compare paired pre- and post-tests as well as Likert scale questionnaires. RESULTS: Forty-nine learners participated in the pretest survey; 38 matched participants completed post-tests (78%). Learners across fields perceived benefit (100% would recommend to colleagues), indicated improved self-efficacy (P < 0.0001), and performed better on post-test knowledge assessments (54.1 vs 88.2%, P < 0.0001). In the neurology providers subgroup (n = 20), pretest scores correlated with years in training (Spearman r = 0.52, P = 0.039), neurology rotations (r = 0.70, P = 0.003), epilepsy/EEG rotations (r = 0.6, P = 0.014), and EEG teaching hours (r = 0.62, P = 0.01); content knowledge and self-efficacy improvement for neurology providers remained significant in a multivariate model adjusting for these covariates. CONCLUSIONS: This animation-based, interactive EEG module proved effective in elevating learner confidence and knowledge across several medical specialties and training levels. Further study across institutions and subspecialties is needed to substantiate broad applicability, but our data appear promising for early EEG learners.

Telehealth is effective for pelvic health physical therapy.

BACKGROUND: Telehealth utilization, largely spurred by the COVID-19 pandemic, has become popular due to convenience and access. We assessed the effectiveness of telehealth for delivering pelvic health physical therapy (PHPT) in patients with pelvic floor disorders (PFD). METHODS: In this IRB approved, cross-sectional study, 812 patients who underwent PHPT treatment by telehealth or in combination with in-person visits were surveyed. Post intervention effectiveness was analyzed using Patient Global Impression of Change (PGIC) and short form Pelvic Floor Impact Questionnaire (PFIQ-7). RESULTS: One hundred and forty-one patients, 80% female, mean (SD) age of 52 (17) completed the study. The mean number of encounters was 4.55 (4.25) with 2.81 (2.08) telehealth visits. A total of 42 (30%) patients reported no change/worse, 27 (19%) minimal, and 72 (51%) moderate/much improvement of symptoms consistent with a lower PFIQ-7 scores. Patients who reported improvement were significantly younger (p < 0.002). Age was the only independent factor that could predict response to PHPT. Patients <50 years old reported significantly more symptom improvement (p < 0.02), symptom resolution (p < 0.002), meeting personal goals (p < 0.0001), improved muscle strength, coordination, and relaxation (p < 0.05), greater satisfaction with bowel movements, and less negative impact of bowel on quality of life (p < 0.005) than older patients. Regardless of age, 89 (64%) patients preferred hybrid telehealth visits. CONCLUSION & INFERENCES: Utilizing telehealth alone or in a hybrid format combined with in-person visits for PHPT appears to be preferred by patients and associated with subjective report of improvement of symptoms. However, efficacy of telehealth interventions in older adults warrants further studies.

Chemerin Levels in Individuals with Type 2 Diabetes and a Normal Weight versus Individuals with Type 2 Diabetes and Obesity: An Observational, Cross-Sectional Study.

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity.

No differences in outcomes with stopping or continuing antibiotic suppression in periprosthetic joint infections.

The data on long-term antibiotic use following debridement, antibiotics, and implant retention (DAIR) for treatment of periprosthetic joint infections are limited. In this single-center retrospective study, we show that patients with eventual cessation of antibiotic suppression after DAIR had similar outcomes to those who remained on chronic antibiotic suppression.

Combination Antifungal Therapy for Invasive Mucormycosis in Immunocompromised Hosts: A Single-Center Experience.

Combination antifungal therapy for invasive mucormycosis remains controversial and is inconsistently defined in prior studies. In a cohort of patients with immunocompromised status and invasive mucormycosis, we found no difference in 6-week mortality with up-front or salvage combination therapy as compared with monotherapy.

Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial.

Importance: There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC). Objective: To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms. Design, Setting, and Participants: This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration. Interventions: Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days. Main Outcomes and Measures: Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline. Results: Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade. Conclusions and Relevance: The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC. Trial Registration: ClinicalTrials.gov Identifier: NCT05576662.

Skin blood flow response to locally applied mechanical and thermal stresses in the diabetic foot.

Diabetic foot ulcers are one of the most common complications in diabetics, causing significant disabilities and decreasing the quality of life. Impaired microvascular reactivity contributes to the development of diabetic foot ulcers. However, underlying physiological mechanisms responsible for the impaired microvascular reactivity in response to extrinsic causative factors of foot ulcers such as mechanical and thermal stresses have not been well investigated. A total of 26 participants were recruited into this study, including 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls. Laser Doppler flowmetry was used to measure skin blood flow at the first metatarsal head in response to a mechanical stress at 300mmHg and a fast thermal stress at 42°C. Wavelet analysis of skin blood flow oscillations was used to assess metabolic, neurogenic and myogenic controls. Our results indicated that diabetics have significantly decreased metabolic, neurogenic and myogenic responses to thermal stress, especially in the neurogenic and myogenic controls during the first vasodilatory response and in the metabolic control during the second vasodilatory response. Diabetics have a significantly decreased myogenic response to mechanical stress during reactive hyperemia. Our findings demonstrate that locally applied mechanical and thermal stresses can be used to assess microvascular reactivity and risk of diabetic foot ulcers.