Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes

Background: Congenital dilatation of the bile-duct (CDD) is a rare, mostly sporadic, disorder that results in bile retention with severe associated complications. CDD affects mainly Asians. To our knowledge, no genetic study has ever been conducted. Methods: We aim to identify genetic risk factors by a “trio-based” exome-sequencing approach, whereby 31 CDD probands and their unaffected parents were exome-sequenced. Seven-hundred controls from the local population were used to detect gene-sets significantly enriched with rare variants in CDD patients. Results: Twenty-one predicted damaging de novo variants (DNVs; 4 protein truncating and 17 missense) were identified in several evolutionarily constrained genes (p < 0.01). Six genes carrying DNVs were associated with human developmental disorders involving epithelial, connective or bone morphologies (PXDN, RTEL1, ANKRD11, MAP2K1, CYLD, ACAN) and four linked with cholangio- and hepatocellular carcinomas (PIK3CA, TLN1 CYLD, MAP2K1). Importantly, CDD patients have an excess of DNVs in cancer-related genes (p < 0.025). Thirteen genes were recurrently mutated at different sites, forming compound heterozygotes or functionally related complexes within patients. Conclusions: Our data supports a strong genetic basis for CDD and show that CDD is not only genetically heterogeneous but also non-monogenic, requiring mutations in more than one genes for the disease to develop. The data is consistent with the rarity and sporadic presentation of CDD

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Ethical Decision-Making in College: Choosing Between Right, Wrong, and the Space in Between

It is important to understand how students’ changing belief structures influence their values and behaviors, including their ethical beliefs and decision-making patterns. As such, this study will address the following research questions: 1) what are students’ ethical beliefs and their perceptions of students’ ethical behaviors; and 2) how do students’ personal values and perceptions of behaviors differ? Using data from the 2006 University of California Undergraduate Experience Survey, survey items about ethical decisions are grouped according to their association with the following themes: academic integrity and honesty, social activities, and behaviors influenced by perceptions of convenience. When analyzing student responses to the UCLA wildcard module within UCUES with these thematic constructs, it is possible to identify patterns of personal ethical belief, perceptions of ethics among peers, and differences between these two classes of variables. Our research indicates that students’ perceptions of their peers’ beliefs and behaviors are the best predictors of the respondents’ own ethical behavior. Within academia, particularly in subject areas that engender greater competition such as science and engineering, it is important that institutions promote an explicit code of conduct. If students are taking cues from their peers as to the what beliefs and behaviors are appropriate, a strong message from the institution, the faculty, and staff can intervene in this process in order to promote ethical decision making skills and practices

Ethical Decision-Making in College: Choosing Between Right, Wrong, and the Space in Between

It is important to understand how students’ changing belief structures influence their values and behaviors, including their ethical beliefs and decision-making patterns. As such, this study will address the following research questions: 1) what are students’ ethical beliefs and their perceptions of students’ ethical behaviors; and 2) how do students’ personal values and perceptions of behaviors differ? Using data from the 2006 University of California Undergraduate Experience Survey, survey items about ethical decisions are grouped according to their association with the following themes: academic integrity and honesty, social activities, and behaviors influenced by perceptions of convenience. When analyzing student responses to the UCLA wildcard module within UCUES with these thematic constructs, it is possible to identify patterns of personal ethical belief, perceptions of ethics among peers, and differences between these two classes of variables. Our research indicates that students’ perceptions of their peers’ beliefs and behaviors are the best predictors of the respondents’ own ethical behavior. Within academia, particularly in subject areas that engender greater competition such as science and engineering, it is important that institutions promote an explicit code of conduct. If students are taking cues from their peers as to the what beliefs and behaviors are appropriate, a strong message from the institution, the faculty, and staff can intervene in this process in order to promote ethical decision making skills and practices

Ethical Decision-Making in College: Choosing Between Right, Wrong, and the Space in Between

It is important to understand how students’ changing belief structures influence their values and behaviors, including their ethical beliefs and decision-making patterns. As such, this study will address the following research questions: 1) what are students’ ethical beliefs and their perceptions of students’ ethical behaviors; and 2) how do students’ personal values and perceptions of behaviors differ? Using data from the 2006 University of California Undergraduate Experience Survey, survey items about ethical decisions are grouped according to their association with the following themes: academic integrity and honesty, social activities, and behaviors influenced by perceptions of convenience. When analyzing student responses to the UCLA wildcard module within UCUES with these thematic constructs, it is possible to identify patterns of personal ethical belief, perceptions of ethics among peers, and differences between these two classes of variables. Our research indicates that students’ perceptions of their peers’ beliefs and behaviors are the best predictors of the respondents’ own ethical behavior. Within academia, particularly in subject areas that engender greater competition such as science and engineering, it is important that institutions promote an explicit code of conduct. If students are taking cues from their peers as to the what beliefs and behaviors are appropriate, a strong message from the institution, the faculty, and staff can intervene in this process in order to promote ethical decision making skills and practices.Curriculum and Instruction

Gone, But Not Forgotten? Survey of Resident Attitudes Toward a Cultural Standardized Patient Examination for a General Surgery Residency Program

Purpose: Various tools have been utilized for cultural competency training in residency programs, including cultural standardized patient examinations. However, it is unknown whether residents feel the training they received has a long-term impact on how they care for patients. The purpose of this study was to assess whether surgical residents who participated in a cultural standardized patient examination view the experience as beneficial. Methods: Surgical residents who completed a standardized patient examination from Fall 2009 to Spring 2015 were asked to complete a 13-question survey assessing the following: (1) did participants feel prepared when dealing with patients from different cultural backgrounds, (2) did they feel the standardized patient experience was beneficial or improved their ability to care for patients, and (3) did they perceive that cultural competence was important when dealing with patients. Results: Sixty current/former residents were asked to participate and 24 (40%) completed the survey. All agreed cross-cultural skills were important and almost all reported daily interaction with patients from different cultural backgrounds. Sixteen participants (67%) reported the cultural standardized patient examination aided their ability to care for culturally dissimilar patients, and 13 (54%) said the training helped improve their communication skills with patients. Thirteen (54%) reported they would participate in another cultural standardized patient examination. Conclusion: Development of effective cultural competency training remains challenging. This study provides some preliminary results that demonstrate the potential lasting impact of cultural competency training. Participants found the skills gained from cultural standardized patient examinations helpful

Biliary-enteric reconstruction with hepaticoduodenostomy following laparoscopic excision of choledochal cyst is associated with better postoperative outcomes: a single-centre experience

© 2014, Springer-Verlag Berlin Heidelberg. Background: With the advent of laparoscopic surgery, more choledochal cysts are excised laparoscopically. In this study, we compared the outcomes from laparoscopic hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD) for biliary-enteric reconstruction. Methods: A retrospective analysis of patients who had undergone laparoscopic choledochal cyst excision between February 2005 and January 2014 in a tertiary referral centre was performed. Demographics data, operative techniques and surgical outcomes were analysed according to the way of biliary-enteric reconstruction. Results: A total of 31 patients were identified, 20 of whom underwent HJ and 11 underwent HD. There were no significant differences in terms of demographics. Median operative time was significantly shorter in HD group (211.0 ± 96.4 vs. 386.0 ± 90.4 min, p = 0.001). Although postoperative enteral feeding was initiated later in HD group (5.0 ± 0.8 vs. 4.0 ± 3.6 days, p = 0.036), postoperative stay in intensive care unit (ICU) (0.7 ± 1.0 vs. 2.4 ± 1.7 days, p = 0.007) and overall hospital stay (9.1 ± 1.0 vs. 14.4 ± 12.2 days, p = 0.157) favoured HD group. There was no perioperative mortality. Median follow-up duration was 24.0 (±11.0) months in HD group and 67.5 (±23.7) months in HJ group. One patient in HJ group had postoperative cholangitis related to anastomotic stricture whereas no cholangitis noted in HD group. In total, five patients in HJ group required second operation for complications and residual diseases whereas none in HD group required reoperation. Conclusions: Laparoscopic excision of choledochal cyst with hepaticoduodenostomy reconstruction is safe and feasible with shorter operative time, ICU stay and overall hospital stay. It is not inferior to HJ in terms of short-term postoperative outcomes.Link_to_subscribed_fulltex

Iatrogenic diaphragmatic hernia in paediatric patients

© 2015, Springer-Verlag Berlin Heidelberg. Background and methods: Iatrogenic diaphragmatic hernia in childhood is rare, with only scanty case reports available in the literature. It is a potentially life-threatening condition resulting in intestinal obstruction and bowel strangulation. In this study, we retrospectively reviewed four patients with iatrogenic diaphragmatic hernia following right hepatic trisectionectomy with caudate lobectomy and liver transplantation in a tertiary referral centre. The patient characteristics, clinical presentation and risk factors were assessed. Conclusions: Iatrogenic diaphragmatic hernia should be considered in differential diagnosis in paediatric patients presenting with intestinal obstruction or respiratory distress after hepatic resection or liver transplantation for early diagnosis and management.Link_to_subscribed_fulltex

Cytomegalovirus-associated colitis mimicking necrotizing enterocolitis – A near miss diagnosis of neonatal colonic stricture

Although cytomegalovirus (CMV) is a common congenital infection in neonates, most patients are asymptomatic. Gastrointestinal manifestation is unusual. In this report, we described a newborn with perinatal CMV infection presented with symptoms mimicking necrotizing enterocolitis. We hope to alert clinicians about this possible diagnosis when managing newborn gastrointestinal diseases