Nutritional Assessment in Inpatients With Cirrhosis Can Be Improved After Training and Is Associated With Lower Readmissions.

Malnutrition is widely prevalent in cirrhosis patients, which can worsen sarcopenia, hepatic encephalopathy (HE), and overall prognosis. We aimed to define the frequency of nutritional assessments of patients with cirrhosis in retrospective and prospective (after educational training) cohorts and to evaluate prospective changes along with their effects on 90-day readmissions. This study was conducted in 2 phases. Retrospectively, records of hospitalized patients with cirrhosis from the university and Veterans Affairs Medical Center (VAMC) settings were reviewed to assess nutritional status, if a nutrition consultation occurred, the number of days patients were nil per os (npo) and received inadequate nutrition, and if nutritional management was guideline directed. In the prospective phase, after dedicated educational efforts directed at the stakeholders regarding nutritional guidelines for patients with cirrhosis, subsequently hospitalized cirrhosis patients had nutritional and 90-day readmission data collected for comparison between groups. In total, 279 patients were included in the retrospective phase (150 university/129 VAMC), and 102 VAMC patients were in the prospective phase. Cirrhosis severity, reason for admission, and hospital course were similar between groups regardless of cohort, ie, prospective versus retrospective or VAMC versus university. The prospective group had significantly more nutritional consultations and assessments (74.5% versus 40.1%; P < 0.001) compared with the retrospective group regardless of comparisons between the VAMC and university cohorts. Both groups had a similar number of days npo, but the prospective group had fewer days of inadequate nutrition. The 90-day readmission rate was significantly lower in the prospective group versus the retrospective group (39.4% versus 28.4%; P = 0.04), which was associated with greater nutrition outpatient follow-up. In conclusion, nutritional consultation rates in inpatients with cirrhosis can be significantly improved after educational intervention and is associated with lower 90-day readmission rates.

Disproportionate Participation of Males and Females in Academic Pediatric Orthopaedics: An Analysis of Abstract Authorship at POSNA 2009-2013.

BACKGROUND: Despite increasing numbers of female orthopaedic surgeons, we hypothesized that women were not actively participating at national and international meetings in numbers proportional to their membership. METHODS: A retrospective review of the 2009-2013 POSNA Annual Meeting Final Programs was performed. The following information was recorded for all members: name, sex, membership level, years of membership, and if the individual was an author on at least 1 abstract. To compare proportion of abstract authorship between sexes across years, while controlling for years of membership, general estimating equations with a binomial model and logit link were used. The study population was limited to candidate and active POSNA members only, as this group represents the most active practicing pediatric orthopaedic surgeons. RESULTS: Over the 5-year period studied, females comprised 16.6% (204/1227) of the total POSNA membership and 20.9% (184/880) of members at candidate and active status. The percentage of females with candidate or active member status in POSNA who had at least 1 abstract presentation during the 5 years was 37% and this was significantly lower (P=0.003) than the percentage of men (49%) who presented at least 1 abstract. Analysis across the 5 years showed a consistent difference between the sexes with no trend of convergence in abstract rates (P=0.65). Controlling for years membership, female members still presented abstracts at lower rates than their male colleagues (P=0.002). CONCLUSIONS: Female members of POSNA, in the most active part of their careers, participated at significantly lower rates than their male peers as accepted abstract authors for the 2009-2013 POSNA meetings than would be expected for their proportional size of total membership.

Substitution of One Meat-Based Meal With Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet. METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups. RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups. DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.

Using a new analytic approach for genotyping and phenotyping chromosome 9p deletion syndrome.

Using a new analytic method ("unique non-overlapping region" (UNOR) analysis), we characterized the genotypes and phenotypes of a large cohort of individuals diagnosed with chromosome 9p deletion syndrome (9PMS) and defined critical genomic regions. We extracted phenotypic information from 48 individuals with 9PMS from medical records and used a guided interview with caregivers to clarify ambiguities. Using high-resolution whole-genome sequencing for breakpoint definition, we aligned deletions and drew virtual breakpoints to obtain UNORs associated with phenotypic characteristics. We next extracted genotype and phenotype data for 57 individuals identified from a systematic review of the 9PMS literature and analyzed these as above. Common phenotypic features included developmental delay/intellectual disability, dysmorphic features, hypotonia, genital defects in XY individuals, psychiatric diagnoses, chronic constipation, atopic disease, vision problems, autism spectrum disorder, gastroesophageal reflux disease, trigonocephaly, congenital heart disease, and neonatal hypoglycemia. Our approach confirmed previous literature reports of an association of FREM1 with trigonocephaly and suggested a possible modifier element for this phenotype. In conclusion, the UNOR approach delineated phenotypic characteristics for 9PMS and confirmed the critical role of FREM1 and a possible long-distance regulatory element in pathogenesis of trigonocephaly that will need to be replicated in future studies.

Evaluating Antibiotic Use in a Veterans Affairs Skilled Nursing Facility.

Objective To examine antibiotic use in long-term care residents at a VA skilled nursing facility. Design Quality improvement project. Setting Long-term care residents admitted to the Community Living Center of a Midwestern VA medical center. Patients Inclusion criteria were long-term care residents admitted to the VA skilled nursing facility who were prescribed an oral (including via percutaneous endoscopic gastrostomy tube) antibiotic from January 1, 2018, to December 31, 2018. Residents were excluded if they were admitted for hospice care, rehabilitation, or short-term skilled nursing. Residents were also excluded if they were on intravenous or topical antibiotics. Results Fifty-six unique antibiotic courses consisting of 13 different antibiotics were evaluated. Median days of therapy per 1,000 resident days was 39.7 overall, for quarter 1 was 51, quarter 2 was 42, quarter 3 was 49.3, and quarter 4 was 17.5. Average antibiotic days of therapy was 7.6 days. Fluoroquinolones comprised 26.8% of the courses, followed by beta-lactamase inhibitors at 25%. Of the 56 courses, 85.7% were found to have appropriate dose/frequency, while 73.2% had appropriate duration. No reports of Clostridioides difficile infection were noted. Thirty-one antibiotic courses had cultures obtained, of which 29 did not deescalate therapy. Of these, 5 (17.2%) were indicated for de-escalation. Conclusion Antibiotic use in this skilled nursing facility have opportunities for intervention, including reducing fluoroquinolone use, optimizing de-escalation, and shortening days of therapy. The implementation of an antimicrobial stewardship monitoring program within the long-term care setting could assist in maximizing therapy while reducing antibiotic exposure.

From karyotypes to precision genomics in 9p deletion and duplication syndromes.

While 9p deletion and duplication syndromes have been studied for several years, small sample sizes and minimal high-resolution data have limited a comprehensive delineation of genotypic and phenotypic characteristics. In this study, we examined genetic data from 719 individuals in the worldwide 9p Network Cohort: a cohort seven to nine times larger than any previous study of 9p. Most breakpoints occur in bands 9p22 and 9p24, accounting for 35% and 38% of all breakpoints, respectively. Bands 9p11 and 9p12 have the fewest breakpoints, with each accounting for 0.6% of all breakpoints. The most common phenotype in 9p deletion and duplication syndromes is developmental delay, and we identified eight known neurodevelopmental disorder genes in 9p22 and 9p24. Since it has been previously reported that some individuals have a secondary structural variant related to the 9p variant, we examined our cohort for these variants and found 97 events. The top secondary variant involved 9q in 14 individuals (1.9%), including ring chromosomes and inversions. We identified a gender bias with significant enrichment for females (p = 0.0006) that may arise from a sex reversal in some individuals with 9p deletions. Genes on 9p were characterized regarding function, constraint metrics, and protein-protein interactions, resulting in a prioritized set of genes for further study. Finally, we achieved precision genomics in one child with a complex 9p structural variation using modern genomic technologies, demonstrating that long-read sequencing will be integral for some cases. Our study is the largest ever on 9p-related syndromes and provides key insights into genetic factors involved in these syndromes.

What diet should I recommend my patient with Hepatic Encephalopathy?

PURPOSE OF REVIEW: The burden of malnutrition is high in patients with cirrhosis, especially in those with hepatic encephalopathy (HE). This has a bearing on increased morbidity and mortality. Heightened attention needs to be paid to screen the patients at high nutritional risk both in the outpatient and hospitalized settings. This review summarizes the current evidence for nutritional support in HE patients and compares the recommendations about nutritional requirement as laid out by various organizations. RECENT FINDINGS: On survey of the literature, there is a consensus on avoiding protein restriction of the diets in HE patients along with uniform recommendations on caloric requirements. An exciting field of manipulating the gut microbiome in nutritional sciences may hold promise as well as there may be a future role for branched chain amino acids in nutritional management of HE patients. SUMMARY: Even though the data suggest that nutritional improvement lead to better outcomes including lower readmission rates in cirrhosis, operationalizing these into practice remains a challenge. To achieve this, a multi-disciplinary approach with nutritional education of the frontline care providers, earlier nutritional risk screening of patients, involvement of the nutrition professionals as part of the team and repeated dietary counseling for the patient and caregiver/s is required. Ultimately, this may need more focus, resource allocation and uniform guidelines across all countries to make this a success.

Abusive fracture incidence over three decades at a level 1 pediatric trauma center.

Few studies have examined the incidence of abusive fractures in children. Only one study to date, from a single pediatric trauma center,has reported on the incidence of abusive fractures over time. That study showed a decrease in abusive fractures over a 24-year period. Our objective for this current study was to compare these published data with recent data from this same trauma center, allowing for a detailed comparison of the incidence of abusive fractures over a 30-year period. We included children <36months of age who presented to the emergency department of a level 1 pediatric trauma center (2007-2010) with≥1 fracture. Six experts from 3 different fields rated each case on the likelihood the fracture(s) was caused by abuse using an established 7- point scale, and a consensus rating was agreed upon for each case. The incidence of abusive fractures was calculated per 10,000 children <36months of age living in the geographic region and per 10,000 ED visits and was compared to previously published data for three prior time periods (1979-1983, 1991-1994, and 1999-2002) at the same pediatric trauma center. From 2007-2010, 551 children were identified, including 31 children who were rated as abused. The incidence of a child presenting with an abusive fracture in the county per year was 2.7/10,000 children <36months of age. The previous three time periods showed a countywide incidence of 3.2/10,000 (1979-1983), 1.7/10,000 (1991-1994), and 2.0/10,000 (1999-2002) (p for trend 0.34). The incidence per ED visit was 2.5/10,000 in the recent time period compared to 6.0/10,000 (1979-1983), 3.4/10,000 (1991-1994), and 2.5/10,000 (1999-2002) (p for trend <0.001). In this single institution review of fractures in children <36months of age, the incidence of abusive fractures has remained relatively constant over a 30-year period.

Inter-rater reliability of physical abuse determinations in young children with fractures.

As there is no "gold standard" in determining whether a fracture is caused by accident or abuse, agreement among medical providers is paramount. Using abstracted medical record data from 551 children <36months of age presenting to a pediatric emergency department, we examined the extent of agreement between specialists who evaluate children with fractures for suspected abuse. To simulate clinical scenarios, two pediatric orthopaedists and two child abuse pediatricians (CAPs) reviewed the full abstraction and imaging, whereas the two pediatric radiologists reviewed a brief history and imaging. Each physician independently rated each case using a 7-point ordinal scale designed to distinguish accidental from abusive injuries. For any discrepancy in independent ratings, the two specialists discussed the case and came to a joint rating. We analyzed 3 types of agreement: (1) within specialties using independent ratings, (2) between specialties using joint ratings, and (3) between clinicians (orthopaedists and CAPs) with more versus less experience. Agreement between pairs of raters was assessed using Cohen's weighted kappa. Orthopaedists (κ=0.78) and CAPs (κ=0.67) had substantial within-specialty agreement, while radiologists (κ=0.53) had moderate agreement. Orthopaedists and CAPs had almost perfect between-specialty agreement (κ=0.81), while agreement was much lower for orthopaedists and radiologists (κ=0.37) and CAPs and radiologists (κ=0.42). More-experienced clinicians had substantial between-specialty agreement (κ=0.80) versus less-experienced clinicians who had moderate agreement (κ=0.60). These findings suggest the level of clinical detail a physician receives and his/her experience in the field has an impact on the level of agreement when evaluating fractures in young children.

Using active methicillin-resistant Staphylococcus aureus surveillance nasal swabs to predict clinical respiratory culture results.

PURPOSE: Results of a study to determine the utility of methicillin-resistant Staphylococcus aureus (MRSA) active surveillance via nasal-swab screening in predicting the results of clinical respiratory cultures are reported. METHODS: A retrospective chart review-based descriptive analysis was conducted at a Veterans Affairs (VA) medical center. VA databases were used to identify adult patients admitted to the facility over a one-year period who underwent both respiratory culture testing and active MRSA surveillance nasal-swab screening during the hospitalization; only data on patients who had a MRSA surveillance swab within 48 hours before or after respiratory culture testing were included in the analysis. The sensitivity, specificity, and positive and negative predictive values of the MRSA screening method were calculated. RESULTS: Data on a total of 297 respiratory cultures and corresponding nasal-swab results were reviewed. The positive predictive value of the nasal-swab method of MRSA surveillance screening was calculated as 37.5% (95% confidence interval [CI], 21.1-56.3%); the negative predictive value was 99.3% (95% CI, 97.3-99.9%). MRSA screening by nasal swab had a calculated specificity of 92.9% (95% CI, 89.3-95.6%) and sensitivity of 87.5% (95% CI, 57.2-98.2%). Using Fisher's exact test, it was determined that there was a significant association between swab and culture results (p < 0.001). CONCLUSION: This analysis demonstrated a notable association between negative results of nasal-swab screening for MRSA and an absence of MRSA growth on respiratory clinical cultures at the study site, suggesting that airway swab screening can be a useful tool for streamlining antimicrobial therapy.

Microtubules that form the stationary lattice of muscle fibers are dynamic and nucleated at Golgi elements.

Skeletal muscle microtubules (MTs) form a nonclassic grid-like network, which has so far been documented in static images only. We have now observed and analyzed dynamics of GFP constructs of MT and Golgi markers in single live fibers and in the whole mouse muscle in vivo. Using confocal, intravital, and superresolution microscopy, we find that muscle MTs are dynamic, growing at the typical speed of ∼9 µm/min, and forming small bundles that build a durable network. We also show that static Golgi elements, associated with the MT-organizing center proteins γ-tubulin and pericentrin, are major sites of muscle MT nucleation, in addition to the previously identified sites (i.e., nuclear membranes). These data give us a framework for understanding how muscle MTs organize and how they contribute to the pathology of muscle diseases such as Duchenne muscular dystrophy.

Dystrophin is a microtubule-associated protein.

Cytolinkers are giant proteins that can stabilize cells by linking actin filaments, intermediate filaments, and microtubules (MTs) to transmembrane complexes. Dystrophin is functionally similar to cytolinkers, as it links the multiple components of the cellular cytoskeleton to the transmembrane dystroglycan complex. Although no direct link between dystrophin and MTs has been documented, costamere-associated MTs are disrupted when dystrophin is absent. Using tissue-based cosedimentation assays on mice expressing endogenous dystrophin or truncated transgene products, we find that constructs harboring spectrinlike repeat 24 through the first third of the WW domain cosediment with MTs. Purified Dp260, a truncated isoform of dystrophin, bound MTs with a K(d) of 0.66 microM, a stoichiometry of 1 Dp260/1.4 tubulin heterodimer at saturation, and stabilizes MTs from cold-induced depolymerization. Finally, alpha- and beta-tubulin expression is increased approximately 2.5-fold in mdx skeletal muscle without altering the tubulin-MT equilibrium. Collectively, these data suggest dystrophin directly organizes and/or stabilizes costameric MTs and classifies dystrophin as a cytolinker in skeletal muscle.