Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

Relationship Between the Clinical Learning Environment and Caring Behaviors Among Baccalaureate Nursing Students During the COVID-19 Pandemic.

ABSTRACT: Caring is a fundamental professional nursing value. This study examined the effect of the clinical learning environment (CLE) on nursing students' caring behaviors during the COVID-19 pandemic. Valuing nursing work in the CLE increased the knowledge and skills aspect of caring behavior. Higher CLE scores in affordances and engagement and student centeredness increased the respectful deference of others and positive connectedness aspects of caring behaviors. These results may inform efforts to promote aspects of nursing students' caring behaviors during global health emergencies by enhancing the value of nursing work, engagement, and student-focused qualities of the CLE.

Recontact: a survey of current practices and BRCA1/2 testing in Japan.

Genetic testing advances have enabled the provision of previously unavailable information on the pathogenicity of genetic variants, frequently necessitating the recontact of former patients by clinicians. In Japan, national health insurance coverage was extended to BRCA1/2 testing for the diagnosis of hereditary breast and ovarian cancer for patients who meet certain criteria in 2020, and conditions necessitating recontact were expected to increase. Studies and discussions regarding recontact have been conducted in the U.S. and Europe; however, in Japan, the national discussion around recontact remains undeveloped. We conducted a cross-sectional study by interviewing 73 facilities accredited by the Japanese Organization of Hereditary Breast and Ovarian Cancer regarding the practice of recontacting patients at these facilities. Sixty-six facilities responded that they recontact patients, but only 17 facilities had a protocol for this. The most common reason for recontact was that it could benefit the patient. Facilities that did not recontact stated that they lacked the necessary personnel or services. Most facilities indicated that a recontact system should be implemented in their practice. The increased burden on too few medical personnel, unestablished systems, patient confusion, and the right not to know were cited as barriers to implementing recontact. Although developing recommendations on recontact would be useful for providing equitable healthcare in Japan, there is an urgent need to deepen the discussion on recontacting, as negative opinions about recontacting patients were observed.

Applying an Age-specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure.

OBJECTIVE: Neonatal acute liver failure (ALF) is a rare disease with high mortality for which no standard age-specific definition exists. To advance the understanding of neonatal ALF, we characterize the etiology, presenting features, treatment, and outcomes in infants within 1 month of life. METHODS: We performed a single-center 11-year retrospective chart review of neonates ≤30 days of life with ALF as defined by an INR of ≥2.0. Comparisons were made by etiology and survival with native liver (SNL). Estimated survival was performed using the Kaplan-Meier method. RESULTS: Forty-three patients met inclusion criteria for neonatal ALF. Etiologies included viral infection (23%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (21%), cardiac-associated ischemia (16%), other ischemia (14%), genetic etiologies (9%), Trisomy 21-associated myelodysplasia (TAM) (7%), hemophagocytic lymphohistiocytosis (HLH) (2%), and not identified (7%). Infants with viral etiologies had the highest alanine aminotransferase (ALT) at presentation (1179 IU/L, interquartile range [IQR] 683-1585 IU/L) in contrast to low levels in GALD-NH (23 IU/L, IQR 18-64 IU/L). Across all etiologies, only 33% were alive at 1 year. Overall median survival was 74 days; 17 days for viral infection and 74 days for GALD-NH. Among laboratory values at presentation, alpha-fetoprotein (AFP) was significantly higher in patients that survived with their native liver (P = 0.04). CONCLUSIONS: Overall, outcome for neonatal ALF is poor. Although initial laboratory values can differentiate viral infection or GALD-NH, further studies are needed to identify laboratory parameters that predict SNL by etiology to ultimately improve patient outcomes.

The hidden curriculum: Undergraduate nursing students' perspectives of socialization and professionalism.

BACKGROUND AND AIM: Nursing students form a professional identity from their core values, role models, and past experiences, and these factors contribute to the development of their professional identity. The hidden curriculum, a set of ethics and values learned within a clinical setting, may be part of developing a professional identity. Nursing students will develop a professional identity throughout school; however, their identity might be challenged as they attempt to balance their core values with behaviors learned through the hidden curriculum. The purpose of this project was to educate students on the hidden curriculum in the development of their professional identity. MATERIALS AND METHODS: A sample of 112 senior nursing students was recruited from a northeastern university in the United States for this study. Pre-post survey design was used, and an educational session was administered prior to the post-survey. Descriptive statistics and a valid percentage were used to describe the data within the surveys. ETHICAL CONSIDERATION: Study was approved by the author's University Institutional Review Board. FINDINGS: A significant finding was for advocacy as students would speak up if witnessing inappropriate behavior toward patients or families with a mean score increase from 2.50 (pre-survey) to 1.45 (post-survey). Also, over 95% (n = 106) found the educational session beneficial as they learned they had the ability to advocate and speak up for their patients. CONCLUSION: Students were able to use their core values and advocate for their patients and families which allows for safer patient care.

Expanding the clinical spectrum of dermal hyperneury: report of nine new cases and a review of the literature.

AIMS: Dermal hyperneury is defined as the hypertrophy of small nerves in the dermis. It has been described in a variety of settings. We present a series of nine new cases with a distinctive clinical presentation and review the existing literature. The aim of the study was to summarise the clinical, histopathological and immunohistochemical findings in a case series of dermal hyperneury with unique clinical presentation. METHODS AND RESULTS: Nine cases were identified from the referral practice of one of the authors. Clinical characteristics, including demographic details, were collated. The histopathological features and novel immunohistochemical findings were analysed. Four cases presented with multiple skin lesions. Clinical evaluation revealed no associated syndromic stigmata. The histology in all cases was that of dermal hyperneury. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and RET was supportive of the lack of syndromic association. CONCLUSION: The presentation of dermal hyperneury with multiple cutaneous lesions and no syndromic associations is distinctive, and no study with PTEN and RET immunohistochemistry has previously been reported. Comparisons with recent reports of multiple non-syndromic mucocutaneous neuromas are discussed.

Norovirus strain types found within the second infectious intestinal diseases (IID2) study an analysis of norovirus circulating in the community.

BACKGROUND: Norovirus is the commonest cause of infectious intestinal disease (IID) worldwide. In the UK community incidence of norovirus has been estimated at 59/1000 population, equating to four million cases a year. Whilst norovirus infects people of all ages, a substantial burden occurs in infants and young children. The population of viruses found in sporadic cases among infants has been observed to be more diverse than that associated with outbreaks. In this study, we analysed norovirus-positive specimens collected during the second study of infectious intestinal diseases (IID2 Study) a national community cohort study conducted between April 2008 and August 2009 We examined the data for differences in circulating norovirus strains between two arms of a community cohort, and differences between genotypes and disease outcomes such as illness duration and symptom profiles. METHODS: Analysis was conducted to assess genetic diversity of noroviruses in the community. We also assessed differences in the cycle threshold (Ct) value, as a proxy for viral load, between norovirus genogroups and genotypes, and differences in reported symptoms or length of illness in relation to genogroup and genotype. RESULTS: There were 477 samples where norovirus was detected. Whilst 85% of people recovered within two days for vomiting; diarrhoea symptoms were reported to day 4 for 83% of the cases, and 10% of people reported symptoms of diarrhoea lasting between five and six days. Both diarrhoea and vomiting symptoms lasted longer in children aged < 5 years compared to adults. There was a significantly higher proportion of GII.4 in samples obtained from the GP arm of the study (chi-square = 17.8, p < 0.001) compared to samples received via post in the self-reporting arm. In the latter group, the prevalence of GII.6 was significantly higher (chi-square = 7.5, p < 0.001). CONCLUSIONS: We found that there is a difference in disease severity by age group. Children aged < 5 years had longer duration of illness, with 10% still having diarrhoea at seven days, and vomiting of between four and five days. The duration of illness reported is higher overall than one might expect for cases in the community in otherwise healthy individuals which has implications for infection control. No differences were observed in relation to duration of vomiting and or diarrhoea by genotype.

How to conduct good quality research on violence against children with disabilities: key ethical, measurement, and research principles.

BACKGROUND: Approximately one billion children experience violence every year. Violence against children is an urgent global public health concern and violation of children's rights. It is also a risk factor for serious negative health and social outcomes and is therefore addressed within the Sustainable Development Goals (SDGs). Children with disabilities, who make up one in 20 children worldwide, are particularly vulnerable to violence although good quality data are lacking on causes and means of prevention of violence against children with disabilities. Key challenges exist in the measurement of disability and violence, which in part explains the dearth in evidence. IMPROVING RESEARCH ON VIOLENCE AGAINST CHILDREN WITH DISABILITIES: This paper provides guidance on how to conduct good quality, ethical, and inclusive research on violence against children with disabilities, particularly in low-income settings. The lack of an international agreed 'gold standard' frustrates efforts to measure violence across settings and time. Careful consideration must be given to the design of survey tools. Qualitative and participatory research methods also offer important opportunities to explore children's subjective understanding and experiences of violence. Challenges also exist around the measurement of disability. Disability may be measured by asking directly about disability, through self-reported functioning, or through the presence of impairments or health conditions. These approaches have strengths and limitations and should build on what children are able to do and include appropriate adaptations for specific impairments where necessary. Ethical research also requires adherence to ethical guidelines and approvals, obtaining informed consent, appropriate child protection responses, and careful consideration of interviewer-related issues including their selection, training, and welfare. Key methodological gaps remain - how to include children with severe communication challenges in research; how to respond in instances of weak child protection systems; designing sampling procedures that adequately represent children with disabilities in large-scale violence surveys; and determining how best to ask about violence safely in large-scale surveys and monitoring data. This paper further advocates for the dissemination of research results in inclusive and accessible formats. CONCLUSION: With careful planning, challenges in collecting data on disability and violence can be overcome to generate evidence in this neglected area.

The Effects of Gestational Alloimmune Liver Disease on Fetal and Infant Morbidity and Mortality.

OBJECTIVES: To evaluate pregnancy outcomes in pedigrees of neonatal hemochromatosis to determine the spectrum of gestational alloimmune liver disease (GALD) in a large cohort. STUDY DESIGN: We prospectively collected data from women with a prior offspring with proven neonatal hemochromatosis between 1997 and 2015 and analyzed pregnancy outcomes. RESULTS: The pedigrees from 150 women included 350 gestations with outcomes potentially related to GALD. There were 105 live-born infants without liver disease, 157 live-born infants with liver failure, and 88 fetal losses. Fetal loss occurred in 25% of total gestations. Ninety-seven pedigrees contained a single affected offspring, whereas 53 contained multiple affected offspring. Analysis of these 53 pedigrees yielded a per-pregnancy repeat occurrence rate of 95%. Notably, the first poor outcome occurred in the first pregnancy in 60% of pedigrees. Outcomes of the 157 live-born infants with liver failure were poor: 18% survived, 82% died. Of the 134 live-born infants with treatment data, 20 received intravenous immunoglobulin with or without double-volume exchange transfusion of which 9 (45%) survived; 14 infants (10%) received a liver transplant of which 6 (43%) survived. CONCLUSIONS: GALD is a significant cause of both fetal loss and neonatal mortality with a high rate of disease recurrence in untreated pregnancies at risk. Poor outcomes related to GALD commonly occur in the first gestation, necessitating a high index of suspicion to diagnose this disorder at first presentation.

Liver Biopsy Can Be Safely Performed in Pediatric Acute Liver Failure to Aid in Diagnosis and Management.

OBJECTIVES: Liver biopsy can be a valuable tool to help determine the etiology of pediatric acute liver failure (PALF), but is often not performed due to safety concerns. The primary aim was to describe the incidence of major complications after liver biopsy performed in the setting of PALF. METHODS: Medical records from 2006 to 2016 were reviewed. Patients age 0 to 17 years, who met criteria for PALF, and had a liver biopsy performed while their international normalized ratio (INR) was ≥1.5 were included. RESULTS: A total of 26 cases of liver biopsy in the setting of PALF were identified. The majority (n = 22, 85%) of patients had primary liver disease. Most biopsies (n = 17, 65%) were performed by the transjugular route, with 5 (19%) performed percutaneously under ultrasound guidance and 4 (15%) during a surgical procedure. Median INR before biopsy was 2.1 (IQR = 1.73-2.9). Blood products were given before or during the procedure in 23 (88%) cases. One patient (3.8%) had a major complication of biopsy-associated bleeding requiring a blood transfusion. An additional 3 patients had a hemoglobin decrease of 2.1 to 2.9 g/dL post-biopsy that was attributed to the procedure but no interventions were necessary. Biopsy results contributed to establishing a diagnosis in 62% (n = 16) of cases, and influenced treatment decisions in 9 of those cases. CONCLUSIONS: Liver biopsy is safe in the majority of patients with PALF and associated with infrequent major complications. Clinicians should consider performing liver biopsy in this setting, especially when the transjugular approach is feasible, since findings may guide diagnosis and therapy.