Conference proceedings: Inaugural meeting of the consortium for autism, genetic neurodevelopmental disorders, and digestive diseases.

OBJECTIVES: Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), often experience a higher prevalence of gastrointestinal (GI) symptoms but have complex medical and behavioral comorbidities that make diagnosis and treatment difficult. A multi-stakeholder conference was convened to (a) determine patient and family experiences related to GI symptoms in NDDs, (b) review the clinicians' and researchers' perspectives, and (c) determine actionable steps for future research. METHODS: The Consortium for Autism, Neurodevelopmental Disorders and Digestive Diseases (CANDID; www.candidgi.com) virtually over 2 days in 2022 and consisted of four key activities: (1) an electronic family survey to assess underlying NDDs and GI symptoms, (2) a session focused on family perspectives, (3) review current clinical care and research, and (4) discussion to identify key next steps. Survey results were obtained electronically via the REDCap platform, and descriptive statistics were generated. The sessions were recorded, and themes were identified. RESULTS: The pre-conference survey ran for ~2 months and 739 families provided responses, with 634 completing all items. 83% had a child with an NDD under age 18, and most patients were White (85%) and non-Hispanic (87%). Constipation (80%), gastrointestinal reflux disease (51%), and bloating (49%) were the most frequently reported symptoms. Families gave unstructured feedback that the measures used in the surveys were often difficult to answer for patients with NDDs or who were nonspeaking. Family and clinical/scientific sessions identified several common themes, including (1) the need for less invasive diagnostic modalities, (2) the need to validate or adapt existing diagnostic measures (e.g., the Rome IV criteria) and outcome assessments, and (3) the need for enhanced attention to parent and caregiver input in treatment plans. CONCLUSIONS: Those providing care to children with NDDs, especially those with communication and cognitive challenges, should be aware of the differing needs in this community and consider family perspectives in managing, treating, and measuring GI issues. Future research should focus on adapting or creating diagnostic and research measures for those with NDDs, developing new diagnostic methods to account for diversity in neurodevelopment and communication, and improving methods for family and caregiver engagement in the care of GI disorders.

Utility of new image-derived biomarkers for autosomal dominant polycystic kidney disease prognosis using automated instance cyst segmentation.

New image-derived biomarkers for patients affected by autosomal dominant polycystic kidney disease are needed to improve current clinical management. The measurement of total kidney volume (TKV) provides critical information for clinicians to drive care decisions. However, patients with similar TKV may present with very different phenotypes, often requiring subjective decisions based on other factors (e.g., appearance of healthy kidney parenchyma, a few cysts contributing significantly to overall TKV, etc.). In this study, we describe a new technique to individually segment cysts and quantify biometric parameters including cyst volume, cyst number, parenchyma volume, and cyst parenchyma surface area. Using data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study the utility of these new parameters was explored, both quantitatively as well as visually. Total cyst number and cyst parenchyma surface area showed superior prediction of the slope of estimated glomerular filtration rate decline, kidney failure and chronic kidney disease stages 3A, 3B, and 4, compared to TKV. In addition, presentations such as a few large cysts contributing significantly to overall kidney volume were shown to be much better stratified in terms of outcome predictions. Thus, these new image biomarkers, which can be obtained automatically, will have great utility in future studies and clinical care for patients affected by autosomal dominant polycystic kidney disease.

Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Comparison of early post-operative complications in primary and revisional laparoscopic sleeve gastrectomy, gastric bypass, and duodenal switch MBSAQIP-reported cases from 2015 to 2019.

BACKGROUND: Sleeve gastrectomy (SG) is now the most performed bariatric surgery, though gastric bypass (GB) and duodenal switch (DS) remain common, especially as conversion/revision (C/R) procedures. This analysis compared early postoperative outcomes of primary and C/R laparoscopic SG to DS and GB; and primary procedures of each vs C/R counterparts. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) dataset was queried for SG, GB, and DS cases from 2015 to 2019. Multivariable logistic regression calculated crude and adjusted odds ratios for surgical site infection (SSI), reoperation, and readmission at 30 days in two initial comparisons: (1) primary SG vs DS or GB and (2) C/R SG vs DS or GB. A secondary analysis compared primary GS, GB, or DS with C/R counterparts. Models were adjusted for confounding demographics and comorbidities. RESULTS: Of 755,968 primary cases, most were SG (72.8%), followed by GB (26.3%), then DS (0.9%). Compared to SG, GB and DS demonstrated higher odds of SSI (aOR 3.02 [2.84, 3.2]), readmission (aOR 1.97 [1.92, 2.03]), and reoperation (aOR 2.74 [2.62, 2.86]), respectively. Of 68,716 C/R cases, SG was most common (43.2%), followed by GB (37.5%), then DS (19.2%). C/R GB and DS demonstrated greater risk of SSI (aOR 2.28 [1.98, 2.62]), readmission (aOR 2.10 [1.94, 2.27]), and reoperation (aOR 2.3 [2.04, 2.59]) vs SG, respectively. C/R SG and DS demonstrated greater risk of SSI (OR 2.09 [1.66, 2.63]; 1.63 [1.24, 2.14), readmission (OR 1.13 [1.02, 1.26]), and reoperation (OR 1.27 [1.06, 1.52]; 1.58 [1.24, 2.0]), vs primary procedures. C/R DS demonstrated greater risk of SSI (OR 1.23 [1.66, 2.63]). CONCLUSIONS: Early complications are comparable between GB and DS, and greater than SG. In C/R procedures, GB and DS demonstrate greater risk than SG. Overall, C/R procedures demonstrate greater risk of most, but not all, early postoperative complications.

Comparison of robot-assisted sleeve gastrectomy outcomes in multiple staple line treatment modalities from 2015 to 2019: a 5-year propensity score-adjusted MBSAQIP® analysis.

BACKGROUND: Robot-assisted sleeve gastrectomy (RSG) is an increasingly common approach to sleeve gastrectomy (SG). Staple line reinforcement (SLR) is well-discussed in laparoscopic SG literature, but not RSG- likely due to the absence of dedicated robotic SLR devices. However, most RSG cases report SLR. This retrospective analysis compares outcomes in RSG cases reporting (1) any staple line treatment (SLT) vs none and (2) SLR vs oversewing. METHODS: MBSAQIP was queried for adults who underwent RSG from 2015 to 2019. Open procedures, Natural Orifice Transluminal Endoscopic Surgery, hand-assisted, single-incision, concurrent procedures, and illogical BMIs were excluded (n = 3444). Final sample included 52,354 patients. Two comparisons were made: SLT (n = 34,886) vs none (n = 17,468) and SLR (n = 22,217) vs oversew (n = 5620). We fitted multivariable regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) and performed propensity score analysis with inverse probability of treatment weight based on patient factors. RESULTS: Most RSG cases utilized SLT (66.6%). Cases with SLT had a reduced risk of organ space SSI (RR 0.68 [0.49, 0.94]), 30-day reoperation (RR 0.77 [0.64, 0.93]), 30-day re-intervention (RR 0.80 [0.67, 0.96]), sepsis (RR 0.58 [0.35, 0.96]), unplanned intubation (RR 0.59 [0.37, 0.93]), extended ventilator use (RR 0.46 [0.23, 0.91]), and renal failure (RR 0.40 [0.19, 0.82]) compared to no-treatment cases. In single-treatment cases (n = 27,837), most utilized SLR (79.8%). Cases with oversew had a higher risk of any SSI (RR 1.70 [1.19, 2.42]), superficial incisional SSI (RR 1.71 [1.06, 2.76]), septic shock (RR 6.47 [2.11, 19.87]), unplanned intubation (RR 2.18 [1.06, 4.47]), and extended ventilator use (> 48 h) (RR 4.55 [1.63, 12.71]) than SLR. CONCLUSIONS: Our data suggest SLT in RSG is associated with reduced risk of some adverse outcomes vs no-treatment. Among SLT, SLR demonstrated lower risk than oversewing. However, risk of all-cause mortality, cardiac arrest, and unplanned ICU admission were not significant.

Cheilectomy Alone in Patients With Elevatus Yields Poor 5-Year Survival Rate.

This study was performed to evaluate the efficacy of the cheilectomy procedure for different degrees of elevatus. The study was Institutional Review Board approved and patients were evaluated retrospectively at Ascension St. John Hospital, St. John Surgery Center and St. John Macomb Township Surgery Center between 9/8/2012 and 1/8/2016. These were all performed by the same surgeon. The pre- and postoperative radiographs were analyzed and Seiberg's index was calculated. Charts were also reviewed, and demographic information was obtained. A telephone survey was performed, and Visual Analog Pain score and Foot and Ankle Ability Measure was obtained. Body mass index, age, calcaneal inclination angle, Seiberg's index, Foot and Ankle Ability Measure, and visual analog score were analyzed using chi-square test, bivariate regression analysis and independent t test. Seiberg's index had a statistically significant influence on 5-year survival rate for the cheilectomy procedure (p ≤ .05). For patients with Seiberg's index less than 0.20 cm demonstrated FAAM, and VAS p values .18 and .37 with 87.0% 5-year survival. Seiberg's index between 0.20 and 0.40 cm had FAAM and VAS scores with p values <.01 and .02 with 62.0% 5-year survival. Seiberg's index ≤0.40 cm p values <.01 and .55 with 5-year survival rate of 0.0%. Therefore, if Seiberg's index is greater than 0.20 cm based on this research a cheilectomy alone as a sole treatment is at greater risk of failure.

Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate. METHODS: We included consecutive HCC patients transplanted 2000-2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses. RESULTS: The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23-4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34-10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis. CONCLUSIONS: Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

Association Between Continuous Kidney Replacement Therapy Clearance and Outcome in Pediatric Patients With Hyperammonemia Not Due to Inborn Error of Metabolism.

OBJECTIVES: To describe a single-center experience of pediatric patients with hyperammonemia not due to inborn errors of metabolism and determine the association between use of continuous kidney replacement therapy (CKRT) treatment and outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary-care children's hospital. PATIENTS: All children less than 21 years old admitted to the hospital with hyperammonemia defined as an elevated ammonia levels (>100 µmol/L) not due to inborn error of metabolism. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Of 135 children with hyperammonemia, the most common reason for admission was infection in 57 of 135 (42%), congenital heart disease in 20 of 135 (14%), and bone marrow transplantation in 10 of 135 (7%). The overall mortality was 61% (82 of 135), which increased with degree of hyperammonemia (17 of 23 [74%] in those with ammonia >250 µmol/L). After multivariable regression, hyperammonemia severity was not associated with mortality (aOR, 1.4; 95% CI, 0.92-2.1; p = 0.11). Of the 43 patients (32%) receiving CKRT, 21 were prescribed standard clearance and 22 high clearance. The most common indications for CKRT were fluid overload in 17 of 43 (42%) and acute kidney injury or uremia in 16 of 43 (37%). Mean CKRT duration was 13 days. There was no difference between standard and high clearance groups in risk of death (76% vs 86%; p = 0.39), cerebral edema on CT scan (19% vs 27%; p = 0.52), nor decrease in ammonia levels after 24 or 48 hours of CKRT ( p = 0.20, p = 0.94). Among those receiving CKRT, we failed to find an association between high clearance and decreased risk of death in multivariable analysis (aOR, 1.2; 95% CI, 0.64-2.3; p = 0.55). CONCLUSIONS: In our single-center retrospective study, we failed to find an association between clearance on CKRT and improved survival nor decreased cerebral edema on head imaging. In fact, we failed to find an association between ammonia level and mortality, after controlling for illness severity.

Mortality, Risk Factors and Disparities Associated with Esophageal Variceal Bleeding in Children's Hospitals in the US.

OBJECTIVES: To use a large administrative database to determine the mortality, risk factors, and comorbidities of esophageal variceal bleeding in children. STUDY DESIGN: Retrospective cohort study using Pediatric Health Information System data from 50 tertiary children's hospitals in the US. International Classification of Diseases (ICD) codes (FY 2020 ICD-10 update and revision 10 of ICD-9) from 2004 through 2019 identified children 18 years and younger with variceal bleeding and complications. Univariate analyses used the Student t -test for continuous variables (age) and the χ2 test for categorical variables (all others). A mixed-effects linear regression was performed for multiple variables. RESULTS: There were 1902 patients who had 3399 encounters for esophageal variceal bleeding. The mortality rate for variceal bleeding was 7.3%, increasing to 8.8% by 6 weeks; any mortality during the study was 20.1%. Transfusion was required in 54.7% of encounters, and 42.6% were admitted to the intensive care unit. Variceal bleeding encounters were complicated by peptic ulcer disease (6.9%), bacteremia (11.4%), acute renal failure (5.1%), mechanical ventilation (18%), ascites (21.3%), and peritonitis (3.3%). Multivariable mixed-effects logistic regression showed that Black race (OR, 2.59; P < .001) or Hispanic ethnicity (OR, 2.31; P = .001), but not sex, household income, or insurance type, were associated with increased mortality. Bacteremia, peritonitis, mechanical ventilation, acute renal failure, and transfusion were associated with higher mortality (ORs of 2.29, 2.18, 1.93, 6.33, and 1.81, respectively; P < .001, .005, .011, <.001, and .005, respectively). CONCLUSIONS: The 6-week mortality rate for variceal bleeding in children is 8.8%. Black or Hispanic children are at higher risk of dying. Serious morbidities associated with variceal hemorrhage impact mortality. These data can inform consideration of prophylactic or therapeutic interventions for children at risk.

Circulating trace elements for the prediction of preeclampsia and small for gestational age babies.

INTRODUCTION: Poor gestational outcomes due to placental insufficiency can have lifelong consequences for mother and child. OBJECTIVE: There is a need for better methods of diagnosis, and elemental metabolomics may provide a means to determine the risk of gestational disorders. METHODS: This study used blood plasma samples collected at 36 weeks' gestation from women who later developed preeclampsia (n = 38), or small-for-gestational age babies (n = 91), along with matched controls (n = 193). Multi-element analysis was conducted by inductively coupled plasma mass spectrometer (ICP-MS), allowing simultaneous measurement of 28 elements. RESULTS: Women who later developed PE, exhibited significantly increased concentrations of K, Rb and Ba. For SGA pregnancies, there was a significant increase in Cu and a decrease in As concentrations. Despite significant differences in single elements, the elemental profile of groups indicated no clustering of control, PE, or SGA samples. Positive predicative values correctly identified approximately 60% of SGA and 70% of PE samples. CONCLUSION: This is the first-time elemental metabolomics has been used to predict SGA and PE at 36 weeks. Though significant changes were identified, routine clinical use may be limited but may contribute to a multi marker test. Future analysis should include other biomarkers, metabolic data or clinical measurements made throughout gestation.

Factors Affecting Higher Readmission Rates and Costs in Pediatric Patients With Hirschsprung Disease.

BACKGROUND: Hirschsprung disease is a relatively uncommon disorder of the developing gastrointestinal tract that requires surgical intervention to restore long-term function. While readmission for Hirschsprung-related complications is a known concern in these patients, we sought to identify patient-level factors associated with a prolonged hospital stay, increased costs at the time of a pull-through operation, as well as the risk for all-cause inpatient readmission after surgery. We hypothesized that higher level of care requirement during the operative stay, age at operation, and length of stay (LOS) would portend increased readmissions and disease-related complications such as Hirschsprung-associated enterocolitis. METHODS: Data was obtained from the Pediatric Health Information System database on all Hirschprung patients who underwent a pull-through operation between 2004 and 2019. Regression analyses were performed on this cohort of 3345 patients. Multivariable regression models were utilized to analyze the key outcome variables of postoperative LOS and adjusted charges. RESULTS: Post-operative LOS was significantly increased by the presence of a surgical complication, congenital/genetic defect, or neurologic/neuromuscular defect. Increased LOS was also seen in Black patients. The cost of pull-through operations was significantly higher in patients admitted to the NICU and ICU during index hospitalization, with a cost increase of approximately $75,000 and $57,000 respectively. Presence of a surgical complication, comorbid congenital/genetic defect, and need for mechanical ventilation were associated with higher odds of inpatient readmission. CONCLUSION: The management of patients with Hirschsprung disease is longitudinal and complex. Identification of key patient metrics can aid clinicians in developing targeted care and education strategies to minimize readmission and excessive hospital charges.

Synchrotron-Based Imaging Reveals the Fate of Selenium in Striped Marsh Frog Tadpoles.

Synchrotron-based X-ray fluorescence microscopy (XFM) coupled with X-ray absorption near-edge structure (XANES) imaging was used to study selenium (Se) biodistribution and speciation in Limnodynastes peronii tadpoles. Tadpoles were exposed to dissolved Se (30 µg/L) as selenite (SeIV) or selenate (SeVI) for 7 days followed by 3 days of depuration. High-resolution elemental maps revealed that Se partitioned primarily in the eyes (specifically the eye lens, iris, and retinal pigmented epithelium), digestive and excretory organs of SeIV-exposed tadpoles. Speciation analysis confirmed that the majority of accumulated Se was converted to organo-Se. Multielement analyses provided new information on Se colocalization and its impact on trace element homeostasis. New insights into the fate of Se on a whole organism scale contribute to our understanding of the mechanisms and risks associated with Se pollution.

The Effects of Patient Demographics on Outpatient Endoscopy Utilization in Children With Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that requires esophagogastroduodenoscopy (EGD) for diagnosis and treatment monitoring. We aimed to identify the frequency of endoscopic monitoring in children with EoE and observe the effect of age, race, socioeconomic factors, and atopy on the rate of endoscopy. METHODS: We queried the Pediatric Health Information System over a 15-year period for ambulatory EGDs in children with EoE. Subjects with at least 1 year of data were included. Age, sex, ethnicity, race, insurance type, median household income, and atopy were collected for each subject. RESULTS: 16,517 subjects were included (mean age 8.5 years). 3211 (19%) of subjects had ≥1 EGD per subject year (EGD/SY). Subjects >13 years old were more likely to have ≥1 EGD/SY compared to children 6-12 years (odds ratio [OR] 2.29, P < 0.001, 95% confidence interval [CI] = 2.06-2.54). Males were more likely to have ≥1 EGD/SY compared to females (OR 1.19, P < 0.001, 95% CI = 1.08-1.31). African-American subjects were 16% less likely than Caucasian subjects to have ≥1 EGD/SY (OR 0.84, P = 0.05, 95% CI = 0.71-1.00). Subjects with allergic rhinitis or anaphylaxis, food allergy, and/or oral allergy syndrome were more likely to have ≥1 EGD/SY (OR 1.67, P < 0.001, 95% CI = 1.47-1.90 and OR 3.65, P < 0.001, 95% CI = 3.25-4.11, respectively). CONCLUSIONS: Nineteen percent of subjects had ≥1 EGD/SY. Older age, male sex, allergic rhinitis, and food allergies were associated with more frequent endoscopic monitoring in children with EoE. Caucasian subjects had more frequent endoscopy than African-American subjects. This study raises awareness about underrecognized variation in the care of children with EoE.

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

OBJECTIVES: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children. METHODS: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models. RESULTS: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy. CONCLUSION: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).

COVID-19 in a Mississippi Community Hospital.

OBJECTIVES: Mississippi recorded the first case of coronavirus disease 2019 (COVID-19) on March 11, 2020. This report describes the initial COVID-19 experience of the single healthcare system serving Jackson County, Mississippi. The intent of this retrospective review of COVID-19 hospitalized patients was to identify any characteristics or interventions amenable to improving care management and clinical outcomes for patients within our community hospital. METHODS: All hospitalized patients 18 years of age and older in our health system with positive tests for COVID-19 (severe acute respiratory syndrome-coronavirus-2 [SARS CoV-2]) by reverse transcriptase-polymerase chain reaction between March 15 and April 10, 2020 are included in this retrospective observational report. RESULTS: During the study period, 158 patients of the 1384 tested (11.4%) were positive for COVID-19 infection. Of the 158 patients, 41 (26%) were hospitalized, with 17 (41%) admitted to the intensive care unit (ICU). The remaining 24 patients did not require ICU admission. The mean age of the 158 COVID-19-positive patients was 55 years (range 2-103). Obesity was noted in 68% of the hospitalized patients, including 13 (54%) of the non-ICU patients and 15 (88%) of the ICU patients. All 9 deceased patients were obese. Twelve of 17 patients received invasive mechanical ventilation (IMV) and 3 patients received only high-flow nasal cannula oxygen. Only 25% (3 of 12) of the IMV patients were successfully extubated during the study period. The median duration on IMV was 17 days (range 4-35). The mortality in the 158 COVID-19-positive patients was 5.7% (9 of 158). None of the 24 non-ICU patients died. The ICU mortality rate was 53% (9 of 17). CONCLUSIONS: This report describes a community hospital experience with COVID-19. Patient outcome was comparable to that reported at larger centers. Obesity was a major comorbidity and correlated with adverse outcomes. Amidst the initial wave of COVID-19 with high demand for inpatient treatment, it is reassuring that appropriate care can be provided in a community health system.

Cardiopulmonary Exercise Testing in the Coronavirus Disease - 2019 Era: Safety and Protocol Considerations.

ABSTRACT: Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.

The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by the degeneration of motor neurons innervating skeletal muscle. The mechanisms underlying neurodegeneration in ALS are not yet fully elucidated, and with current therapeutics only able to extend lifespan by a matter of months there is a clear need for novel therapies to increase lifespan and patient quality of life. Here, we evaluated whether moderate-intensity treadmill exercise and/or treatment with metallothionein-2 (MT2), a neuroprotective protein, could improve survival, behavioural or neuropathological outcomes in SOD1G93A familial ALS mice. Six-week-old female SOD1G93A mice were allocated to one of four treatment groups: MT2 injection, i.m.; moderate treadmill exercise; neither MT2 nor exercise; or both MT2 and exercise. MT2-treated mice survived around 3% longer than vehicle-treated mice, with this mild effect reaching statistical significance in Cox proportional hazards analysis once adjusted for potential confounders. Mixed model body weight trajectories over time indicated that MT2-treated mice, with or without exercise, reached maximum body weight at a later age, suggesting a delay in disease onset of around 4% compared to saline-treated mice. Exercise alone did not significantly increase survival or delay disease onset, and neither exercise nor MT2 substantially ameliorated gait abnormalities or muscle strength loss. We conclude that neither exercise nor MT2 treatment was detrimental in female SOD1G93A mice, and further study could determine whether the mild effect of peripheral MT2 administration on disease onset and survival could be improved via direct administration of MT2 to the central nervous system.

Cytomegalovirus serologic matching in deceased donor kidney allocation optimizes high- and low-risk (D+R- and D-R-) profiles and does not adversely affect transplant rates.

Cytomegalovirus (CMV) is a major cause of infection-related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high-risk D+R- were reduced from 18.5% to 2.9%, whereas low-risk D-R- were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R- after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high-risk CMV seroprofiles and potentially improve CMV-related outcomes in kidney transplantation.

Variation in hospital admission from the emergency department for children with cancer: A Pediatric Health Information System study.

BACKGROUND: Children with cancer experience a wide range of conditions that require urgent evaluation in the emergency department (ED), yet variation in admission rates is poorly documented. PROCEDURE: We performed a retrospective cohort study using the Pediatric Health Information System of ED encounters by children with cancer between July 2012 and June 2015. We compared demographics for admitted versus discharged using univariate statistics, and calculated admission rates by hospital, diagnosis, day of the week, and weekend versus weekday. We assessed the degree of interhospital admission rates using the index of dispersion (ID). RESULTS: Children with cancer had 60 054 ED encounters at 37 hospitals. Overall, 62.5% were admitted (range 43.2%-92.1%, ID 2.6) indicating overdispersed admission rates with high variability. Children with cancer that visited the ED for a primary diagnosis of fever experienced the largest amount of variability in admission with rates ranging from 10.4% to 74.1% (ID 8.1). Less variability existed among hospital admission rates for both neutropenia (range 60%-100%, ID 1.0) and febrile neutropenia (FN) (range 66.7%-100%, ID 0.83). Admission rates by day of the week did not demonstrate significant variability for any of the scenarios examined (overall P = 0.91). There were no differences by weekend versus weekday either (overall P = 0.52). CONCLUSION: The percentage of children with cancer admitted through the ED varies widely by institution and diagnosis. Standardization of best practices for children with cancer admitted through the ED should be an area of continued improvement.

Variation in hospital admission of sickle cell patients from the emergency department using the Pediatric Health Information System.

BACKGROUND: Universal newborn screening and improved treatment options have led to increased survival in sickle cell disease (SCD). However, patients with SCD still rely heavily on acute care services. OBJECTIVE: To determine the variation seen in hospitalizations for the top complaints for ED visits for children with SCD nationally. METHODS: We performed a retrospective review of the Pediatric Health Information Systems (PHIS) Database between October 2011 and September 2015. Emergency department (ED) encounters were selected by using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes for SCD with and without crisis, fever, and pain. Univariate analyses were performed, as well as index of dispersion (ID) to assess variation by day of the week and region. ANOVA and t-test were used to determine statistical significance. RESULTS: A total of 68 661 ED encounters at 36 hospitals met the criteria for inclusion. Of those encounters, 50.1% were admitted to the hospital. Pain and fever were the most common primary diagnoses among this population. Although variation in hospitalization was seen overall, as well as for a primary diagnosis of pain or fever, this variation was not explained by weekday/weekend designation. CONCLUSION: The results of our study confirm pain and fever as the most common primary diagnoses for children with SCD who seek acute care, as well as demonstrate that while significant variation in hospitalization exists, it is not associated with day of the week. Further studies to elucidate patient- and hospital-level factors that influence admission variation are necessary.