Conjugated hyperbilirubinemia is associated with increased morbidity and mortality after neonatal heart surgery.

BACKGROUND: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality. METHODS: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020. Patient- and surgery-specific data were abstracted from local registry data and review of the medical record. Conjugated hyperbilirubinemia was defined as perioperative maximum conjugated bilirubin level > 1 mg/dL. The primary outcome was in-hospital mortality. Survival analysis was conducted using the Kaplan-Meier survival function. RESULTS: Conjugated hyperbilirubinemia occurred in 8.5% of patients during the study period. Neonates with conjugated hyperbilirubinemia were more likely to be of younger gestational age, lower birth weight, and non-Caucasian race (all p < 0.001). Patients with conjugated hyperbilirubinemia were more likely to have chromosomal and non-cardiac anomalies and require ECMO pre-operatively. In-hospital mortality among patients with conjugated hyperbilirubinemia was increased compared to those without (odds ratio 5.4). Post-operative complications including mechanical circulatory support, reoperation, prolonged ventilator dependence, and multi-system organ failure were more common with conjugated hyperbilirubinemia (all p < 0.04). Patients with higher levels of conjugated bilirubin had worst intermediate-term survival, with patients in the highest conjugated bilirubin group (>10 mg/dL) having a 1-year survival of only 6%. CONCLUSIONS: Conjugated hyperbilirubinemia is associated with post-operative complications and worse survival following neonatal heart surgery. Cholestasis is more common in patients with chromosomal abnormalities and non-cardiac anomalies, but the underlying mechanisms have not been delineated.

Evaluation of the Use of Naltrexone for Cholestatic Pruritus.

OBJECTIVE: Pruritus is a common symptom of liver disease, managed with various medications including opioid antagonists like naltrexone. Current literature surrounding the safety and efficacy of naltrexone for cholestatic pruritus is limited. Our objective was to describe naltrexone prescribing practices for cholestatic pruritus. METHODS: We conducted a single-center, retrospective review of inpatients who received naltrexone for cholestatic pruritus. We gathered information on naltrexone dosing, frequency, dose adjustments, duration, elevations in liver function tests (LFTs), and use of additional antipruritic agents. RESULTS: Thirty-nine patients and 122 dosing regimens were included for analysis. Most patients were male (56.4%) with a median age of 6.32 years (range, 0.63-18.89). The median weight-based doses of naltrexone were 1.45 mg/kg/dose (IQR, 0.84-2.81) and 1.86 mg/kg/day (IQR, 0.97-3.37). The median flat doses were 25 mg/dose (IQR, 12.25-50) and 50 mg/day (IQR, 25-50). The median number of additional antipruritic agents used before and after naltrexone initiation was 3 (IQR, 2-4) and 4 (IQR, 3-5), respectively (p < 0.001). The most common elevated LFTs were total bilirubin and alanine aminotransferase (ALT), occurring in 15% of patients. CONCLUSIONS: Naltrexone dosing ranged between 1 and 2 mg/kg/dose once or twice daily, with larger weight-based doses prescribed in younger and lower-weight patients. Naltrexone was commonly added as a fourth-line agent and did not lead to discontinuation of other antipruritic therapies. Larger, prospective, controlled studies are needed to assess the safety and efficacy of naltrexone for cholestatic pruritus.

Monitoring Practices After Pediatric Liver Transplantation.

OBJECTIVES: This study sought to understand the current monitoring practices after pediatric liver transplantation (LT), specifically regarding follow-up clinic visits, outpatient laboratory testing, protocol biopsies, and diagnostic imaging, and to identify potential center and provider characteristics associated with such practices. METHODS: A cross-sectional survey of pediatric LT providers at centers participating in the Society of Pediatric Liver Transplantation (SPLIT) registry was conducted from February 2020 to April 2021. RESULTS: The overall response rate was 79% (38/48 SPLIT centers), with the majority representing large volume centers (>10 LTs per year). Frequency of clinic visits and laboratory monitoring varied by center, but all centers decreased frequency after the first post-transplant year. The most common practice included an annual clinic visit and laboratory sampling every 2-3 months. Surveillance liver biopsy is seldom done during the first post-transplant year, while being routinely performed by 50% of centers after this time period. Centers forgoing surveillance biopsies assert that the results would likely not change management. Only 39% of centers have a hepatologist perform the liver biopsy while the remaining centers consult interventional radiology. Most diagnostic imaging is obtained only as needed. Routine abdominal ultrasounds were obtained by only 50% of responding centers after the first year post-transplant. CONCLUSIONS: SPLIT centers vary widely in the routine management of LTs after the first year post-transplant. While common themes emerge, future studies will be needed to connect protocols to outcomes to determine best practice.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Overview of autoimmune liver disease: Prevalence, risk factors, and role of autoantibodies.

Content available: Author Interview and Audio Recording.

Severe Hepatitis in Pediatric Coronavirus Disease 2019.

ABSTRACT: Hepatic involvement in coronavirus disease 2019 (COVID-19) is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of four previously healthy children who presented with significant hepatitis as the primary manifestation of COVID-19 infection. Two of these patients met criteria for acute liver failure. None of the patients had respiratory symptoms. One patient was found to have complement dysfunction resulting in microangiopathic features and was treated successfully with eculizumab. This case is in line with adult post-mortem data showing that more severe cases of hepatic dysfunction secondary to COVID-19 infection may be associated with complement activation and microangiopathic features. Liver function should be evaluated in cases of severe COVID-19, and severe acute respiratory syndrome coronavirus 2 infection should be considered as a cause of acute severe hepatitis even in patients without significant respiratory or other systemic symptoms.

A Comparison of Perceived Lifetime Breast Cancer Risk to Calculated Lifetime Risk Using the Gail Risk Assessment Tool.

Background: Understanding the accuracy of a woman's perceived breast cancer risk can enhance shared decision-making about breast cancer screening through provider and patient discussion. We aim to report and compare women's perceived lifetime breast cancer risk to calculated lifetime breast cancer risk. Methods: Women presenting to Mayo Clinic in Arizona and Minnesota in July 2016 completed a survey assessing their perceived breast cancer risk. Lifetime Gail risk scores were calculated from questions pertaining to health history and were then compared with perceived breast cancer risk. Results: A total of 550 predominantly white, married, and well-educated (≥college) women completed surveys. Using lifetime Gail risk scores, 5.6% were classified as high risk (>20% lifetime risk), 7.7% were classified as intermediate risk (15%-20%), and 86.6% were classified as average risk (<15%). Of the 27 women who were classified as high risk, 18 (66.7%) underestimated their risk and of the 37 women who were intermediate risk, 12 (32.4%) underestimated risk. Women more likely to underestimate their risk had a reported history of an abnormal mammogram and at least one or more relative with a history of breast cancer. Surveyed women tended to overestimate risk 4.3 (130/30) times as often as they underestimated risk. Conclusion: In a group of predominantly white, educated, and married cohort of women, there was a large portion of women in the elevated risk groups who underestimated risk. Specific aspects of medical history were associated with underestimation including a history of abnormal mammogram and family history of breast cancer. Overall, in our sample, more women overestimated than underestimated risk.

A Quality Improvement Initiative to Improve Patient Safety Event Reporting by Residents.

INTRODUCTION: Residents play a key role in patient care at academic medical centers and have unique insights into safety improvement opportunities. At our institution, <1% of safety events were reported by resident trainees. The primary objective of this quality improvement (QI) initiative was to increase the monthly incidence of event reporting by pediatric residents by 20% from baseline within 12 months. METHODS: A QI team used the model for improvement to identify barriers to submitting safety event reports. The team used multiple intervention cycles to increase knowledge and promote engagement in event reporting. Interventions included educational tip sheets, a hospital-wide Morbidity and Mortality (M&M) conference, peer recognition and acknowledgment by senior leadership for report submission, and an interactive reporting activity. The outcome measure was monthly number of reports filed by residents. The process measure was the number of unique residents submitting a report each month. Time to complete a report was a balancing measure. RESULTS: The number of reports placed by residents increased significantly, with a centerline shift from 15 to 29 reports per month (statistical process control chart-Fig. 3). The number of unique residents submitting reports increased from 10 to 22 per month. The time to complete a report was unchanged. CONCLUSIONS: Engaging residents in patient safety initiatives through education, experiential learning, and recognition can increase safety event reporting by residents. Future planned interventions include enhancing safety event reporting technology, developing patient safety faculty and resident champions, and increasing transparency regarding outcomes of safety event reports.

Compensatory and Lifestyle-Based Brain Health Program for Subjective Cognitive Decline: Self-Implementation versus Coaching.

Although recent studies have explored the potential of multidomain brain health programs, there is a dearth of literature on operationalizing this research to create a clinical treatment program specifically for subjective cognitive decline (SCD). Patients seen by geriatricians in primary care and by behavioral neurology services at our institution presenting with SCD were recruited via a patient-appropriate flyer. After all participants had a 1-h brain health consultation with a neuropsychologist and were provided with program materials, they were randomized to attend a 10-week intervention designed to support program implementation (N = 10) or the control group of implementing the program on their own (N = 11). The program included (1) a calendar-based executive and memory support system for compensatory training and (2) training in healthy lifestyle. There were no significant differences between groups for any outcomes. Participants across both groups showed significant improvements with moderate effect sizes in compensatory strategy use, anxiety symptoms, and daily functioning, which were sustained through 6-month follow-up. They also increased physical activity by the end of the intervention period but did not sustain this through 6-month follow-up. Our pilot study demonstrates preliminary feasibility of a cognitive compensatory and lifestyle-based brain health program. Additional research is recommended to further develop two potentially scalable implementation strategies-coaching and self-implementation after brief consultation.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Screening Women for Anal Cancers: Guidance for Health Care Professionals.

Anal cancer is rare in the general population but is steadily increasing in incidence over the past decade especially in women. Identification and screening of women with high risk facilitates detection of anal precancer and early-stage cancer, improves survival, and potentially uses less invasive therapies compared with the conventional chemoradiation treatments used for advanced cancers. No recently published guidelines currently describe details about screening women for anal squamous cell cancer (ASCC). The available evidence supports the existence of groups of women with higher prevalence of ASCC (e.g., women with human immunodeficiency virus, immune suppression, or previous lower-genital high-grade lesion or cancer) who would likely benefit from screening with some combination of anal cytology and human papillomavirus testing. Additional research is needed to establish the cost-effectiveness and the influence of screening on ASCC mortality rates.

TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.

TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrome, myopathy, and cardiomyopathy have been reported. Recent studies suggested that provision of exogenous L-cysteine or N-acetylcysteine may ameliorate the effects of disease-causing variants and improve the natural history of the disease. Here, we report six infants with biallelic TRMU variants, including four previously unpublished patients, all treated with exogenous cysteine. We highlight the first report of an affected patient undergoing orthotopic liver transplantation, the long-term effects of cysteine supplementation, and the ability of the initial presentation to mimic multiple inborn errors of metabolism. We propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia, and that combined N-acetylcysteine and L-cysteine supplementation should be considered prior to molecular diagnosis, as this is a low-risk approach that may increase survival and mitigate the severity of the disease course.

Reframing aging in dermatology: The role of the dermatologist in healthy aging.

Dermatology is often tasked with balancing the clinical appearance of aging skin with the reality of what healthy aging means. In this article, we review some of the core principles of healthy aging and explore common misconceptions, both from patients and physicians, regarding aging. Recognition of the basics of healthy aging and awareness of these aging myths can empower providers to advise patients accurately and productively regarding their aging goals.

Acute liver dysfunction with delayed peak of serum aminotransferase levels as a presentation of ornithine transcarbamylase deficiency in females.

We describe 10 females with ornithine transcarbamylase (OTC) deficiency and liver dysfunction, revealing a unique pattern of hepatocyte injury in which initial hyperammonemia and coagulopathy is followed by a delayed peak in aminotransferase levels. None of the patients required urgent liver transplantation, though five eventually underwent transplant for recurrent metabolic crises. We intend that this novel observation will initiate further investigations into the pathophysiology of liver dysfunction in OTC-deficient patients, and ultimately lead to the development of therapies and prevent the need for liver transplant.

Breast Cancer Screening: Women's Attitudes and Beliefs in Light of Updated United States Preventive Services Task Force and American Cancer Society Guidelines.

BACKGROUND: In recently updated breast cancer screening guidelines, the American Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF) recommended increasing mammography screening intervals for various age groups. In addition, ACS does not recommend clinical breast examination (CBE) for routine screening among average-risk women. Our study explores women's attitudes regarding screening mammography and CBE and evaluates the impact of the updated USPSTF and ACS guidelines on these attitudes. MATERIALS AND METHODS: Six hundred fourteen patients presenting to Mayo Clinic, Arizona and Minnesota, in July 2016 completed a self-administered survey, which included a summary of the updated guidelines. RESULTS: A majority of the 555 women who fit the inclusion criteria reported that CBE and mammogram are useful in detecting breast cancer and should be performed annually, and 51% of participants were unaware of the updated guidelines. Before reviewing the guidelines, 77% believed yearly CBE and 76% believed yearly mammogram was needed for routine screening. After reviewing the guidelines, the percentage of women who planned to continue with yearly CBE and mammogram decreased significantly to 61% and 64%, respectively (p < 0.001 and p < 0.001). Nearly half the participants (48%) believed the most influential reason for the guideline change was to decrease healthcare spending. CONCLUSION: Breast cancer screening is well received among patients, and a majority of surveyed women were unaware of recent guideline changes. After reviewing the guidelines, there was a significant downward shift in intended screening frequency, although the majority still planned to undergo annual screening. Informing women about updated evidence-based guidelines may influence their knowledge, preferences, and opinions.