Bias in the prenatal lung measurements in fetal congenital diaphragmatic hernia with intrauterine growth restriction.

OBJECTIVES: The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH). METHODS: A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week. RESULTS: Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60-1.08 and p=0.175, OR 2.40 95 % CI 0.66-1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005). CONCLUSIONS: This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation.

Electrodiagnostic Predictors of Outcomes After In Situ Decompression of the Ulnar Nerve.

PURPOSE: Patients with severe ulnar neuropathy at the elbow frequently experience suboptimal surgical outcomes. Clinical symptoms alone may not accurately represent the severity of underlying nerve injury, calling for objective assessment tools, such as electrodiagnostic studies. The goal of our study was to determine whether specific electrodiagnostic parameters can be used to predict the outcomes after in situ decompression of the ulnar nerve. METHODS: This prospective study enrolled consecutive patients aged ≥18 years diagnosed with ulnar neuropathy at the elbow. Patients completed a baseline battery of motor, sensory, functional, and electrodiagnostic tests before undergoing in situ decompression of the ulnar nerve. They were reassessed at 6 weeks, 3 months, 6 months, and 12 months after surgery. Forty-two patients completed at least 2 follow-up assessments and were included in the study. RESULTS: When controlling for other electrodiagnostic measurements and demographic factors, none of the electrodiagnostic parameters were predictive of outcomes at 12 months after surgery. Patients with decreased compound muscle action potential amplitudes demonstrated slower trends of recovery in grip strength, pinch strength, and overall scores on the Michigan Hand Outcomes Questionnaire as well as its function, work, and activities of daily living subscales, Disabilities of the Arm, Shoulder, and Hand questionnaire, and the Carpal Tunnel Questionnaire. Decreased motor nerve conduction velocity was predictive of slower recovery of 2-point discrimination and pinch strength. CONCLUSIONS: Compound muscle action potential amplitude, but not other conventional electrodiagnostic parameters, was predictive of functional outcomes after in situ decompression of the ulnar nerve. This parameter should play a role in determining the timing and prognosis of treatment for ulnar neuropathy at the elbow. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Influence of commercial starter culture on fermentation dynamics and quality characteristics of yogurts obtained with different formulations.

BACKGROUND: Four commercial starter cultures containing Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (S1, S2, S3 and S4; S3 also contained Limosilactobacillus fermentum) were compared for fermentation, volatile flavor compounds, physicochemical parameters and microbiology, in yogurt prepared from three milk base formulations with increased protein (B1, B2 and B3). RESULTS: The fermentation patterns differed among starters, with Yoflex Mild 1.0 (S4) and SLB95 (S2) showing the longest fermentation time, depending on the formulation. At 21 days, S. thermophilus counts were similar among starters and higher than 8.52 log CFU mL-1 , for all yogurts. The highest counts (6.86 log CFU mL-1 ) for L. delbrueckii subsp. bulgaricus was found for S2 yogurts made from whey protein hydrolysate (B3). Minor water-holding capacity was detected for YF-L811 (S1) yogurts. Yoflex Harmony 1.0 (S3) starter containing Lim. fermentum produced a distinctive volatile profile characterized by aldehydes with respect to yogurts prepared with S1, S2 and S4, which were characterized by ketones. CONCLUSION: Results indicate the usefulness of carrying out studies similar to the present one to select the most appropriate process conditions depending on the desired product. © 2022 Society of Chemical Industry.

A tele-health intervention to increase physical fitness in people with spinal cord injury and cardiometabolic disease or risk factors: a pilot randomized controlled trial.

STUDY DESIGN: Clinical trial. OBJECTIVES: We used a single-blind parallel-group design to test the feasibility and preliminary efficacy of a telehealth-based physical activity counseling intervention to increase physical fitness in people with SCI. SETTING: Seattle, Washington, United States. METHODS: We recruited under-active, manual wheelchair-using adults at least 1-year post-SCI who had at least two cardiometabolic risk factors/diseases. Participants underwent baseline tests of peak cardiorespiratory fitness; lipids, glucose and insulin; muscle and fat mass; self-reported physical activity, depression, pain and other factors. Participants were assigned 1:1 to treatment vs. usual care (UC) control conditions via concealed computerized randomization. Treatment was delivered via telephone and adapted from the 16-session Diabetes Prevention Program. All baseline tests were repeated at 6 months. Prespecified feasibility goals were to recruit at least nine participants/quarter and retain 85% with complete fitness testing at 6 months. Prespecified efficacy goals were to demonstrate at least a medium treatment effect size (0.50) on fitness, self-reported physical activity, and other outcomes. RESULTS: Seven participants were randomized to treatment, 8 to UC over 15 months. Maximum recruitment was only 5.4 participants/quarter. Thirteen (87%) of participants were retained. The effects of treatment on fitness and most cardiometabolic risk factors did not meet expectations, whereas the effects on self-reported physical activity, depression, and pain did meet expectations. CONCLUSIONS: The study did not meet key efficacy and feasibility objectives, yet there were some promising effects on self-report measures and lessons to be learned for designing future trials.

When primary repair is not enough: a comparison of synthetic patch and muscle flap closure in congenital diaphragmatic hernia?

PURPOSE: Primary closure is often inadequate for large congenital diaphragmatic hernia (CDH) and necessitates repair by prosthetic patch or autologous muscle flap. Our aim was to evaluate outcomes of open patch versus flap repair, specifically diaphragmatic reherniation. METHODS: A retrospective review (IRB #2017-6361) was performed on all CDH patients repaired from 2005 to 2016 at a single academic children's hospital. Patients were excluded from final analysis if they had primary or minimally invasive repair, expired, or were lost to follow-up. RESULTS: Of 171 patients, 151 (88.3%) survived to discharge, 9 expired after discharge and 11 were lost to follow up, leaving 131 (86.8%) long-term survivors. Median follow-up was 5 years. Open repair was performed in 119 (90.8%) of which 28 (23.5%) underwent primary repair, 34 (28.6%) patch repair, and 57 (47.9%) flap repair. Overall, 6/119 (5%) patients reherniated, 1/28 (3.6%) in the primary group, 3/34 (8.8%) in the patch group, and 2/57 (3.5%) in the flap group. Comparing prosthetic patch to muscle flap repair, there was no significant difference in the number of patients who recurred nor time to reherniation (3 vs. 2, p = 0.295; 5.5 ± 0.00 months vs. 53.75 ± 71.06 months, p = 0.288). One patient in the patch group recurred twice. CONCLUSIONS: Both muscle flap and patch repair of large CDH are feasible and durable with a relatively low risk of recurrence.

Fetal brain morphometry on prenatal magnetic resonance imaging in congenital diaphragmatic hernia.

BACKGROUND: Many infants with congenital diaphragmatic hernia (CDH) show brain abnormality on postnatal brain MRI related to severity of CDH, degree of lung hypoplasia, intrathoracic liver, right diaphragmatic hernia and large diaphragmatic defect. It is not known whether these factors affect brain growth in utero in CDH. OBJECTIVE: To assess prenatal brain morphometry and abnormalities on fetal MR in congenital diaphragmatic hernia. MATERIALS AND METHODS: We retrospectively reviewed 109 fetal MRIs in 63 fetuses with CDH from 2009 to 2014 (27 died before discharge, 36 survived to discharge). We compared brain injury and gestational-age-corrected z-scores of brain measurements between survivors and non-survivors. We assessed correlations between brain abnormalities and CDH severity. RESULTS: Enlarged extraaxial space was the most common abnormality, frequently seen on fetal MRI at >28 weeks of gestation, similar in survivors versus non-survivors. Anteroposterior cerebellar vermis dimension at >28 weeks of gestation was smaller in non-survivors compared to survivors (P=.02) and positively correlated with observed/expected total fetal lung volume (P=.01). Transverse cerebellar diameter at >28 weeks of gestation was also positively correlated with observed/expected total fetal lung volume (P=.04). We did not identify maturational delay, abnormal parenchymal signal or intracranial hemorrhage on fetal MRI. CONCLUSION: Enlarged extraaxial spaces in the third trimester was the most common abnormality on fetal MRI in congenital diaphragmatic hernia. Cerebellar dimensions on fetal MRI are associated with CDH severity. There was no major brain parenchymal injury on fetal MRI, even in the third trimester, in CDH survivors and non-survivors.

Left congenital diaphragmatic hernia-associated musculoskeletal deformities.

AIM: With the advancement in the treatment strategies of congenital diaphragmatic hernia (CDH), there is an increase in the survival rates. This fact leads to an increase in the morbidity and extrapulmonary complications in the long term such as failure to thrive, hernia recurrence, neurodevelopmental delay, gastrointestinal problems, and musculoskeletal anomalies. Herein, we aim to investigate the association between the long-term musculoskeletal complications in CDH patients regarding the defect size, repair type, and perinatal parameters. METHODS: After Institutional Review Board approval was obtained (2017-6361), a retrospective chart review was performed on CDH patients from 2003 to 2016. Patients who were operated due to left-sided isolated congenital diaphragmatic hernia and survived to date were included in the study. Data were collected on demographics, preoperative characteristics, operative interventions, and postoperative outcomes. Statistical analysis was performed with IBM SPSS Statistics 20.0.0 (Chicago, IL). RESULTS: There were 98 patients with left CDH of whom 33 (33.7%) had primary repair, 25 (25.5%) had patch repair, and 40 (40.8%) had muscle flap repair. The median age of the patients was 6.00 ± 3.83 years. 45 patients (45.9%) had large diaphragmatic defects, 28 patients (28.6%) had at least one type of musculoskeletal deformities, 2 of which were pectus carinatum, 16 were pectus excavatum, and 18 were scoliosis. CDH patients who had small diaphragmatic defects and repaired with a patch were less likely develop musculoskeletal deformities while who had primary abdominal closure after ventral hernia significantly have more pectus excavatum. CONCLUSION: Although there was a trend towards an increased risk of the pectus deformity and scoliosis in patients repaired with muscle flap, it did not reach statistical significance. There is a correlation between musculoskeletal deformities and the severity of the CDH.

Congenital diaphragmatic hernia: the good, the bad, and the tough.

OBJECTIVES: We aim to determine factors that are associated with better outcomes of CDH patients. METHODS: A retrospective review was performed on all CDH patients admitted to our institution between 2003 and 2016. This study was performed at a single institution which has a fetal care center. Patients admitted with CDH with at least 1-year follow-up during the analysis were included in the study. RESULTS: Twenty-six (13.8%) patients had a hernia sac, 124 (59%) patients had liver herniation, and 56 (25.1%) patients had an accompanying syndrome. Overall survival to discharge was 73.1% while overall survival to date was 69.5%. The presence of a hernia sac, liver herniation, and accompanying syndromes showed as independent predictors influencing the survival, B 1.968, p = 0.04, OR 7.158, 95% CI 0.907-56.485, B - 1.178, p = 0.01, OR 3.932, 95% CI 1.798-8.602 and B - 1.032, p = 0.05, OR 2.795, 95% CI 0.976-7.764, respectively. CONCLUSION: In our CDH cohort, the presence of a hernia sac was proven to be associated with better outcomes, while thoracic herniation of the liver was associated with worse outcomes. The accompanying syndromes although being more difficult to manage had a little effect on the outcome of the disease itself.

Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma.

BACKGROUND: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers. OBJECTIVE: We sought to determine whether γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma. METHODS: Participants with mild asthma were enrolled in a double-blinded, placebo-controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins, and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins, and cytokines. Mucociliary clearance was measured using gamma scintigraphy. RESULTS: Fifteen subjects with mild asthma completed both arms of the study. Compared with placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including mucin 5AC and reduced LPS-induced airway neutrophil recruitment 6 and 24 hours after challenge. Mucociliary clearance was slowed 4 hours postchallenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not mucin 5AC) were reduced at 24 hours postchallenge during γT treatment compared with placebo. CONCLUSIONS: When compared with placebo, γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.

Sonographic markers associated with adverse neonatal outcomes among fetuses with gastroschisis: an 11-year, single-center review.

BACKGROUND: Gastroschisis complicates 1 in 2000 births and is readily identifiable during prenatal ultrasound scans. Outcomes in fetuses that are affected by gastroschisis vary widely from stillbirth or neonatal death to uncomplicated surgical correction, which makes prenatal counseling challenging. OBJECTIVE: The goal of our study was to identify sonographic markers that are associated with perinatal death and morbidity that include significant bowel injury, necrotizing enterocolitis, and the need for bowel resection in fetuses with gastroschisis. STUDY DESIGN: We identified a cohort of fetuses that were diagnosed with gastroschisis from 2003-2014. Sonographic markers that were reviewed included growth restriction, abdominal circumference, oligohydramnios, bowel dilation, and gastric bubble characteristics. We evaluated these markers both at diagnosis and near delivery. Four adverse perinatal outcomes were assessed: perinatal death, necrotizing enterocolitis, need for bowel resection, and a composite of significant bowel injury, which included a diagnosis of bowel atresia or necrosis at the time of surgical exploration. Logistic regression was performed to calculate odds ratios and 95% confidence intervals for each marker and outcome. RESULTS: One hundred seventy-seven patients were identified, and 154 of these patients met inclusion criteria after exclusions for delivery <24 weeks gestation, other associated anomalies, lethal karyotype, or lost to follow-up evaluation. Markers at the time of diagnosis (median gestational age, 21 weeks [25th,75th interquartile range, 19, 24 weeks]) that were associated with perinatal death were abdominal circumference <5th percentile (odds ratio, 5.56; 95% confidence interval, 1.25-24.76), abnormal gastric bubble (odds ratio, 11.20; 95% confidence interval, 2.15-58.33), and abnormal stomach location (odds ratio, 17.1; 95% confidence interval, 2.99-97.85). An abnormal stomach location (odds ratio, 5.53; 95% confidence interval, 1.03-29.72) before delivery was associated with perinatal death. Gastric dilation before delivery (odds ratio, 4.36; 95% confidence interval, 1.10-17.34)] was associated with the need for bowel resection. CONCLUSION: Early sonographic markers of increased perinatal mortality rates include abdominal circumference <5th percentile and an abnormal gastric bubble.

Exopolysaccharide from Lactobacillus fermentum Lf2 and its functional characterization as a yogurt additive.

Lactobacillus fermentum Lf2 is a strain which is able to produce high levels (approximately 1 g/l) of crude exopolysaccharide (EPS) when it is grown in optimised conditions. The aim of this work was to characterize the functional aspects of this EPS extract, focusing on its application as a dairy food additive. Our findings are consistent with an EPS extract that acts as moderate immunomodulator, modifying s-IgA and IL-6 levels in the small intestine when added to yogurt and milk, respectively. Furthermore, this EPS extract, in a dose feasible to use as a food additive, provides protection against Salmonella infection in a murine model, thus representing a mode of action to elicit positive health benefits. Besides, it contributes to the rheological characteristics of yogurt, and could function as a food additive with both technological and functional roles, making possible the production of a new functional yogurt with improved texture.

Effects of prandial challenge on triglyceridemia, glycemia, and pro-inflammatory activity in persons with chronic paraplegia.

CONTEXT/OBJECTIVE: Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. DESIGN: Descriptive trial. METHODS: Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points -30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. RESULTS: Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. CONCLUSIONS: Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard.

Predictors of functional outcomes after simple decompression for ulnar neuropathy at the elbow: a multicenter study by the SUN study group.

OBJECTIVE: To identify predictors of surgical outcome for ulnar neuropathy at the elbow (UNE). DESIGN: Prospective cohort followed for 1 year. SETTING: Clinics. PARTICIPANTS: Patients diagnosed with UNE (N=55). INTERVENTION: All subjects had simple decompression surgery. MAIN OUTCOME MEASURES: The primary outcome measure was patient-reported outcomes, such as overall hand function through the Michigan Hand Outcomes Questionnaire (MHQ). Predictors included age, duration of symptoms, disease severity, and motor conduction velocity across the elbow. RESULTS: Multiple regression models with change in the overall MHQ score as the dependent variable showed that at 3 months postoperative time, patients with <3 months duration of symptoms showed 12 points (95% confidence interval [CI], 0.9-23.5) greater improvement in MHQ scores than those with ≥3 months symptom duration. Less than 3 months of symptoms was again associated with 13 points (95% CI, 2.9-24) greater improvement in MHQ scores at 6 months postoperative, but it was no longer associated with better outcomes at 12 months. A worse baseline MHQ score was associated with significant improvement in MHQ scores at 3 months (coefficient, -0.38; 95% CI, -.67 to -.09), and baseline MHQ score was the only significant predictor of 12 month MHQ scores (coefficient, -.40; 95% CI, -.79 to -.01). CONCLUSIONS: Subjects with <3 months of symptoms and worse baseline MHQ scores showed significantly greater improvement in functional outcomes as reported by the MHQ. However, duration of symptoms was only predictive at 3 or 6 months because most patients recovered within 3 to 6 months after surgery.

Metabolic responses to 4 different body weight-supported locomotor training approaches in persons with incomplete spinal cord injury.

OBJECTIVE: To describe metabolic responses accompanying 4 different locomotor training (LT) approaches. DESIGN: Single-blind, randomized controlled trial. SETTING: Rehabilitation research laboratory, academic medical center. PARTICIPANTS: Individuals (N=62) with minimal walking function due to chronic motor-incomplete spinal cord injury. INTERVENTION: Participants trained 5 days/week for 12 weeks. Groups were treadmill-based LT with manual assistance (TM), transcutaneous electrical stimulation (TS), and a driven gait orthosis (DGO) and overground (OG) LT with electrical stimulation. MAIN OUTCOME MEASURES: Oxygen uptake (V˙o2), walking velocity and economy, and substrate utilization during subject-selected "slow," "moderate," and "maximal" walking speeds. RESULTS: V˙o2 did not increase from pretraining to posttraining for DGO (.00 ± .18L/min, P=.923). Increases in the other groups depended on walking speed, ranging from .01 ± .18 m/s (P=.860) for TM (slow speed) to .20 ± .29 m/s (P=.017) for TS (maximal speed). All groups increased velocity but to varying degrees (DGO, .01 ± .18 Ln[m/s], P=.829; TM, .07 ± .29 Ln[m/s], P=.371; TS, .33 ± .45 Ln[m/s], P=.013; OG, .52 ±.61 Ln[m/s], P=.007). Changes in walking economy were marginal for DGO and TM (.01 ± .20 Ln[L/m], P=.926, and .00 ± .42 Ln[L/m], P=.981) but significant for TS and OG (.26 ± .33 Ln[L/m], P=.014, and .44 ± .62 Ln[L/m], P=.025). Many participants reached respiratory exchange ratios ≥ 1 at any speed, rendering it impossible to statistically discern differences in substrate utilization. However, after training, fewer participants reached this ceiling for each speed (slow: 9 vs 6, n=32; moderate: 12 vs 8, n=29; and maximal 15 vs 13, n=28). CONCLUSIONS: DGO and TM walking training was less effective in increasing V˙o2 and velocity across participant-selected walking speeds, while TS and OG training was more effective in improving these parameters and also walking economy. Therefore, the latter 2 approaches hold greater promise for improving clinically relevant outcomes such as enhanced endurance, functionality, or in-home/community ambulation.

Heavy reliance on carbohydrate across a wide range of exercise intensities during voluntary arm ergometry in persons with paraplegia.

CONTEXT/OBJECTIVE: To describe and compare substrate oxidation and partitioning during voluntary arm ergometry in individuals with paraplegia and non-disabled individuals over a wide range of exercise intensities. DESIGN: Cross-sectional study. SETTING: Clinical research facility. PARTICIPANTS: Ten apparently healthy, sedentary men with paraplegia and seven healthy, non-disabled subjects. INTERVENTIONS: Rest and continuous progressive voluntary arm ergometry between 30 and 80% of peak aerobic capacity (VO2peak). OUTCOME MEASURES: Total energy expenditure and whole body rates of fat and carbohydrate oxidation. RESULTS: A maximal whole body fat oxidation (WBFO) rate of 0.13 ± 0.07 g/minute was reached at 41 ± 9% VO2peak for subjects with paraplegia, although carbohydrate became the predominant fuel source during exercise exceeding an intensity of 30-40% VO2peak. Both the maximal WBFO rate (0.06 ± 0.04 g/minute) and the intensity at which it occurred (13 ± 3% VO2peak) were significantly lower for the non-disabled subjects than those with paraplegia. CONCLUSION: Sedentary individuals with paraplegia are more capable of oxidizing fat during voluntary arm ergometry than non-disabled individuals perhaps due to local adaptations of upper body skeletal muscle used for daily locomotion. However, carbohydrate is the predominant fuel source oxidized across a wide range of intensities during voluntary arm ergometry in those with paraplegia, while WBFO is limited and maximally achieved at low exercise intensities compared to that achieved by able-bodied individuals during leg ergometry. These findings may partially explain the diminished rates of fat loss imposed by acute bouts of physical activity in those with paraplegia.

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

IMPORTANCE: Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE: To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/µL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS: Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES: Reaching a CD4 cell count less than 200/µL until May 2008; after this date, reaching a CD4 cell count of 250/µL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS: There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/µL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/µL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. CONCLUSIONS AND RELEVANCE: In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

Cardiometabolic risk clustering in spinal cord injury: results of exploratory factor analysis.

BACKGROUND: Evidence suggests an elevated prevalence of cardiometabolic risks among persons with spinal cord injury (SCI); however, the unique clustering of risk factors in this population has not been fully explored. OBJECTIVE: The purpose of this study was to describe unique clustering of cardiometabolic risk factors differentiated by level of injury. METHODS: One hundred twenty-one subjects (mean 37 ± 12 years; range, 18-73) with chronic C5 to T12 motor complete SCI were studied. Assessments included medical histories, anthropometrics and blood pressure, and fasting serum lipids, glucose, insulin, and hemoglobin A1c (HbA1c). RESULTS: The most common cardiometabolic risk factors were overweight/obesity, high levels of low-density lipoprotein (LDL-C), and low levels of high-density lipoprotein (HDL-C). Risk clustering was found in 76.9% of the population. Exploratory principal component factor analysis using varimax rotation revealed a 3-factor model in persons with paraplegia (65.4% variance) and a 4-factor solution in persons with tetraplegia (73.3% variance). The differences between groups were emphasized by the varied composition of the extracted factors: Lipid Profile A (total cholesterol [TC] and LDL-C), Body Mass-Hypertension Profile (body mass index [BMI], systolic blood pressure [SBP], and fasting insulin [FI]); Glycemic Profile (fasting glucose and HbA1c), and Lipid Profile B (TG and HDL-C). BMI and SBP formed a separate factor only in persons with tetraplegia. CONCLUSIONS: Although the majority of the population with SCI has risk clustering, the composition of the risk clusters may be dependent on level of injury, based on a factor analysis group comparison. This is clinically plausible and relevant as tetraplegics tend to be hypo- to normotensive and more sedentary, resulting in lower HDL-C and a greater propensity toward impaired carbohydrate metabolism.

Compound Muscle Action Potential Amplitude as a Predictor of Functional and Patient-Reported Outcomes in Ulnar Neuropathy at the Elbow.

BACKGROUND: Ulnar neuropathy at the elbow (UNE) is a debilitating upper extremity condition that often leaves patients with residual symptoms even after surgical treatment. The role of electrodiagnostic studies in guiding the treatment of UNE is not well established, and conventional electrodiagnostic parameters may not reflect the severity of disease. Compound muscle action potential (CMAP) amplitude is a parameter that corresponds with axonal injury and motor symptoms and may more accurately predict the severity of neurologic injury. METHODS: This prospective multicenter study recruited 78 patients in the Surgery of the Ulnar Nerve project. Patients underwent electrodiagnostic testing and clinical assessment of motor and sensory function, and completed patient-reported outcome questionnaires, including the Michigan Hand Outcome Questionnaire; the Disabilities of the Arm, Shoulder and Hand questionnaire; and the Carpal Tunnel Questionnaire (CTQ). Correlations were measured among each of the electrodiagnostic parameters and outcomes and predictive models for each outcome were subsequently developed. RESULTS: Of all the electrodiagnostic parameters measured, only CMAP amplitude was predictive of scores on the Michigan Hand Outcome Questionnaire; Disabilities of the Arm, Shoulder and Hand questionnaire; CTQ function scale, and motor impairment in grip and pinch strength. None of the parameters were predictive of scores on the CTQ symptom scale or sensory impairments as measured with two-point discrimination or Semmes-Weinstein monofilament testing. CONCLUSIONS: CMAP amplitude, but not other conventional electrodiagnostic parameters, is predictive of functional outcomes in UNE. This electrodiagnostic measurement can alert the clinician to severe cases of UNE and inform surgical decision-making. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Prevalence of different LI-RADS v2018 categories in high-risk patients undergoing CT- or MRI-based screening for hepatocellular carcinoma.

PURPOSE: To estimate the prevalence of Liver Imaging Reporting and Data System (LI-RADS, LR) v2018 categories reported on CT or MRI performed for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS: This retrospective study included all reports for CT and MRI exams performed for HCC screening patients between 8/2018 and 4/2020. Patients with ultrasound, CT, or MRI of the abdomen within two years of the index exam were excluded. From each radiology report, we extracted number of reported liver observations, and LI-RADS v2018 category for each observation. RESULTS: There were 329 patients (170 [52%] male, mean age 59 years [SD 12]), of whom 177 (54%) had MRI with gadoxetate, 72 (22%) had MRI with extracellular contrast, 7 (2%) had MRI with unspecified contrast, and 73 (22%) had CT. Of 329 patients, 199 (60%) had no reported observations; 130 patients had 166 reported observations: 114 (68.7%) LR-1, 8 (4.8%) LR-2, 21 (12.6%) LR-3, 6 (3.6%) LR-4, 13 (7.8%) LR-5, 3 (1.8%) LR-M, and 1 (0.6%) LR-TIV. Of 114 LR-1 observations, 78 (68%) were cysts, 17 (15%) were hemangiomas, 12 (11%) were vascular shunts, 3 (3%) were focal nodular hyperplasia, 2 (2%) were siderotic nodules, 1 (1%) was a lipoma, and 1 (1%) was biliary hamartoma. There were 23 observations with probably or definitely malignant categories (LR-4, LR-5, LR-M or LR- TIV), reported in 20/329 (6%) of patients. CONCLUSION: In a cohort of at-risk patients undergoing contrast-enhanced CT/MRI for HCC screening, 60% of had no liver observations, and 6 % had probably or definitely malignant observations. IMPLICATIONS FOR PATIENT CARE: The prevalence of LI-RADS v2018 categories on CT or MR exams used for HCC screening can help develop screening criteria and assess cost-effectiveness of surveillance strategies with CT and MRI.

PEGylation of Chrysin Improves Its Water Solubility while Preserving the In Vitro Biological Activity.

Chrysin is a natural flavonoid that despite having numerous biological properties, its therapeutic value is limited due to its very low solubility in aqueous media. In this work, chrysin was conjugated with methoxypolyethylene glycols (mPEGs) of different molecular weights (350, 500, 750, and 2000 g/mol), affording PEGylated chrysins with high yields and excellent purities. In all cases, an increase in the water solubility of the conjugates was observed, which was highest when 500 g/mol of mPEG was used in the PEGylation reaction. Furthermore, in aqueous solution, PEGylated chrysins formed aggregates of ellipsoid shape. Electrochemical studies showed that the redox properties were conserved after PEGylation. While in vitro antibacterial and antifungal studies probed that the intrinsic activity was conserved, in vitro antitumor activities against HepG2 (liver carcinoma cells) and PC3 (prostate cancer cell) showed that PEGylated chrysins retained the cytotoxic activity and the ability of induction of apoptosis for the evaluated human cancer cells.