The Current Status of Ultrasound Education in United States Medical Schools.

OBJECTIVES: Ultrasound is used by nearly every medical specialty. Medical schools are integrating ultrasound education into their curriculum but studies show this to be inconsistent. The purpose of this study was to provide an updated description of ultrasound in the curricula of United States Accredited Medical Schools (USAMS). METHODS: In 2019, USAMS curricular offices were contacted. Institutions were asked about the presence of ultrasound curriculum and for contact information for faculty involved with education. Schools reporting ultrasound curriculum were surveyed regarding details of their curriculum. RESULTS: Two hundred USAMS were contacted with a response rate of 84%. Of 168 schools, 72.6% indicated they have an ultrasound curriculum. For schools with a curriculum, 79 (64.8%) completed our survey. The majority of survey respondents, 66 (83.5%), indicated having mandatory ultrasound. Ultrasound is primarily integrated into courses (73.8% in basic science courses, 66.2% in clinical skills courses, and 35.4% in clinical rotations). Emergency medicine physicians accounted for 54.7% of course directors. Ten or fewer faculty participate in education in 68.4% of schools and mostly as volunteers. Dedicated machines for education were reported by 78.5% of schools. CONCLUSIONS: Compared to prior studies, this study had a higher response rate at 84%, and more schools reported ultrasound in their curricula. Emergency medicine represents the majority of leadership in ultrasound education. Despite increased integration of ultrasound into American medical school curricula, its instruction is still inconsistent.

Occurrence, outcomes and predictors of portal hypertension in cystic fibrosis: A longitudinal prospective birth cohort study.

BACKGROUND: The reported prevalence of portal hypertension (PH) in Cystic Fibrosis is variable, incidence rates rarely provided and the utility of liver function tests (LFT's) early in life to predict PH is questionable. The aims were to (1) determine PH prevalence (P) and incidence rate (IR) and combined mortality transplant (MTX) data in PH vs non-PH patients and (2) to assess association of LFTs in early life with liver disease and PH. METHOD: (1) A double centre longitudinal cohort study of 577 CF patients diagnosed by newborn screening (NBS) with annual examinations for PH up to 18.5 years of age (max) was performed over 28 years for P, IR, and MTX data; (2) Cox proportional hazard models were used to assess the association of elevated LFTs on 2 or more occasions over 0-6.5 years and PH. RESULTS: 51/577(8.8%) developed PH with an average IR of near 3/1000 patient years per 5 year interval representing young, mid and late childhood respectively in patients 3-18 years of age. Combined mortality/liver transplant occurred in 12/51 (23.5%) PH and 25/526 (4.8%) non-PH (p < 0.001). Elevated enzymes particularly GGT (HR:5.71, 95% CI 3.11-10.47); ALT/GGT (HR: 5.56, 95% CI 2.82-10.98); and ALP/GGT (HR: 5.74, 95% CI 2.78-11.86) were associated with the onset of PH. CONCLUSION: This birth cohort with annual examination for PH provides an accurate assessment of the prevalence, and IR of PH and MTX of PH vs non-PH. Early elevated LFTs are associated with onset of MBC/PH.

Sonographic Detection of Cutaneous Myiasis.

Cutaneous maggots are occasionally encountered in the emergency department. We present a case in which maggots were visually identified and ultrasound was used to detect additional maggots below the skin crevices in a patient with elephantiasis nostras verrucosa.

Echogenicity and ultrasound visibility of peripheral nerves of the upper extremity.

AIM: Regional anesthesia with ultrasound-guidance is an excellent option for pain control if nerves are adequately visualized. Gender, body mass index (BMI), history of diabetes, neck and forearm circumference may affect echotexture and visualization. This study evaluates patient characteristics for their ability to predict the echogenicity or visibility of upper extremity peripheral nerves. MATERIAL AND METHODS: This is a prospective observational study. A convenience sample of adult emergency department patients were enrolled. Gender, BMI, history of diabetes, neck circumference and arm circumference were recorded. Sonographic images of the brachial plexus at interscalene and supraclavicular levels, the median, the radial and ulnar nerves were recorded. Three reviewers independently graded the echogenicity and visibility using subjective scales. RESULTS: 395 peripheral nerves were included. Nerves of the forearm (median, ulnar, radial nerves) were found to be more echogenic (OR=9.3; 95% CI: 5.7, 15.3) and visible (OR=10.0; 6.3, 16.0) than more proximal nerves (brachial plexus at interscalene and supraclavicular levels). Gender, BMI, and history of diabetes mellitus were not significantly related to nerve visibility (p=0.9, 0.2, 0.2, respectively) or echogenicity (p=0.3, 0.8, 0.3). Neck circumference was not related to visibility or echogenicity of proximal nerves. Increased forearm circumference improved echogenicity (OR=1.25; 1.09, 1.43) but not visibility of forearm nerves. CONCLUSIONS: Gender, BMI and presence of diabetes were not related to echogenicity or visibility of upper extremity nerves. Increasing forearm circumference was associated with increased echogenicity of the adjacent nerves, but not visibility. Neck circumference was not associated with either nerve visibility or echogenicity of brachial plexus nerve bundles.

Incomplete total body protein recovery in adolescent patients with anorexia nervosa.

Background: Bone health and growth during adolescence require adequate total body protein (TBPr). Renutrition for patients with anorexia nervosa (AN) should aim to normalize body composition and to recover both fat mass and TBPr. Objective: We intended to analyze predictors of protein status, including exercise status, in adolescents with AN and to investigate whether weight gain would replenish body protein deficits. Methods: We assessed TBPr in a longitudinal, observational study as height-adjusted nitrogen index (NI) using in vivo neutron activation analysis in 103 adolescents with AN [mean ± SD age, 15.6 ± 1.4 y; body mass index (BMI, in kg/m2), 16.5 ± 1.6] at the commencement of inpatient refeeding (T0), in 56 of these patients 7 mo thereafter as outpatients (T1), and in age-matched controls (C; n = 51, 15.5 ± 2.1 y, BMI 20.7 ± 1.9). Lean tissue and fat mass were assessed by dual-energy X-ray absorptiometry. BMI, BMI standard deviation score, and lean tissue mass were tested as predictors of protein status using receiver operating characteristic analysis. Results: At T0, NI was decreased in AN (AN, 0.88 ± 0.10 compared with C, 1.00 ± 0.08, P < 0.001). In 34%, the patients showed protein depletion. Patients classified as ``exercisers'' had a higher NI than did ``nonexercisers'' (0.89 ± 0.11 compared with 0.85 ± 0.08, P = 0.045). BMI, BMI standard deviation score, and lean tissue mass did not show potential as predictors of protein status. Despite increases in weight (+6.9 ± 4.5 kg), and BMI (+2.5 ± 1.7), protein status did not improve (TBPr T0, 8.0 ± 1.1 kg; T1, 8.1 ± 1.0 kg, P = 0.495). In an AN subgroup at 7 mo matched with controls in age (AN, 16.5 ± 1.1 y; C, 16.2 ± 1.8 y) and BMI (AN, 20.5 ± 1.4; C, 20.7 ± 1.3), protein status was still not normalized in AN (NI: AN, 0.89 ± 0.09 compared with C, 1.00 ± 0.07, P < 0.001). Conclusions: Adolescents recovering from AN remained protein depleted at 7 mo after baseline assessment, even though they were weight restored.

13C-Mixed Triglyceride Breath Test and Fecal Elastase as an Indirect Pancreatic Function Test in Cystic Fibrosis Infants.

BACKGROUND: The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. OBJECTIVE: Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. METHODS: C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. RESULTS: Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. CONCLUSIONS: The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.

Bile salt stimulated lipase: Inhibition by phospholipids and relief by phospholipase A2.

INTRODUCTION: Bile salt stimulated lipase (BSSL; Enzyme Commission (EC) number 3.1.1.13) has been a candidate triglyceridase for improving enzyme therapy for pancreatic insufficiency; however, its efficacy is near absent. We hypothesise that similarly to pancreatic lipase, BSSL is inhibited by phospholipids and this inhibition is relieved by Phospholipase A2 (PLA2; EC 3.1.1.4), and the present study was undertaken to explore this possibility. MATERIALS AND METHODS: Synthetic emulsions of triglyceride and phosphatidylcholine (PC) or lysophosphatidylcholine (LPC)/bile salt mixed micelles were used as a model of intestinal digestion-media. The effect of PLA2 treatment of systems containing PC on BSSL activity was also explored. Automatic titration at constant pH (pH-stat) and nuclear magnetic resonance (NMR) spectroscopy were used to measure the rate and identify products of lipolysis. RESULTS: PC was inhibitory to BSSL activity, while LPC became inhibitory only above an LPC/bile salt concentration ratio of 0.3. PLA2 treatment relieved the inhibition only below this ratio, despite its complete phospholipid-hydrolysing action. Thus, LPC had an inhibitory effect at higher concentrations. CONCLUSIONS: These results may implicate a change in the design of enzyme therapy in patients with pancreatic exocrine insufficiency. Supplementation of BSSL with PLA2 could improve patient health with adequate manipulation of phospholipid and lysophospholipid concentrations in the intestinal fluid.

Pediatric-to-adult Transition and Medication Adherence in Patients with Inflammatory Bowel Disease.

BACKGROUND: Medication nonadherence is common in inflammatory bowel disease and is associated with poor outcomes. There has been no study on pediatric-to-adult transition as a risk factor for nonadherence in inflammatory bowel disease, which has been demonstrated in other diseases. We aimed to assess whether transitioned (TR) patients have higher nonadherence rates than young adults (YAs) diagnosed in adulthood. METHODS: Consecutive ambulatory subjects were prospectively recruited and completed the validated Medication Adherence Reporting Scale (MARS), with the primary outcome being adherence differences between group age-matched TR and YA groups. Pediatric subjects were taken as the control group. Perceptions of medication-related necessity and concerns were assessed with the Beliefs about Medicines Questionnaire (BMQ). Nonadherers (defined as MARS ≤16) received the Inflammatory Bowel Diseases Pharmacist Adherence Counselling (IPAC) intervention and adherence change was reassessed after 6 months as a secondary outcome. RESULTS: Adherence in TR patients (n = 38, mean age 20.4, 13.2% nonadherent) was noninferior to and numerically better than YAs diagnosed in adulthood (n = 41, mean age 21.2, 24.4%). Nonadherence in the pediatric control group (n = 50, mean age 14.7) was 8.0%. YAs had significantly higher medication-related concerns (14.6 versus 11.9, P = 0.02) than the pediatric group. The IPAC intervention reduced nonadherence rates by 60% (P = 0.004). CONCLUSIONS: TR patients did not have worse adherence than YAs diagnosed in adulthood. Protective factors may include previous treatment in pediatric centers and the salient symptomatology of inflammatory bowel disease, whereas increasing concerns over medications contribute to nonadherence in YAs. Pharmacist-led counselling improves adherence in these patients.

Are We Overdoing Pediatric Lower Gastrointestinal Endoscopy?

INTRODUCTION: Lower gastrointestinal endoscopy (LGIE)/colonoscopy is frequently performed for rectal bleeding, recurrent abdominal pain, and the diagnosis of inflammatory bowel disease (IBD). Although these are common indications, the causes of isolated rectal bleeding and recurrent abdominal pain in the otherwise well child have not been described. METHODS: A retrospective analysis of patients who had had an LGIE/colonoscopy from January 2001 to December 2010 was performed. The following data were collected: demographic data, indication, distance reached, macroscopic findings, microscopic findings, diagnosis, additional procedures, and complications. RESULTS: There were a total of 999 colonoscopies. The colonoscopy was normal in 390 of 999 (39%). The commonest indication for colonoscopy was a diagnosis of suspected IBD, 449 of 999 (45%). IBD was confirmed in 282 of 449 (63%), but colonoscopy was normal in 143 of 449 (32%) of suspected IBD. Colonoscopy was performed for rectal bleeding in 197 of 999 (20%) of whom 141 of 197 (72%) were normal. There were 46 (5%) colonoscopies performed for recurrent abdominal pain, which were all normal. Our completion rate to the cecum and beyond was 521 of 999 (52%). Our perforation rate during the 10 years was 0.2%. CONCLUSIONS: Colonoscopy is a safe procedure in pediatrics; however, 39% of colonoscopies in this series were normal. Many of these could have been avoided by eliminating colonoscopy in patients with recurrent abdominal pain in the absence of other clinical features, conservative management with laxatives for those with fresh blood per rectum typical of anal fissures, and fecal calprotectin screening before endoscopy in patients with suspected IBD.

Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era.

OBJECTIVES: To evaluate children with cystic fibrosis (CF) who had a late diagnosis of CF (LD-CF) despite newborn screening (NBS) and compare their clinical outcomes with children diagnosed after a positive NBS (NBS-CF). STUDY DESIGN: A retrospective review of patients with LD-CF in New South Wales, Australia, from 1988 to 2010 was performed. LD-CF was defined as NBS-negative (negative immunoreactive trypsinogen or no F508del) or NBS-positive but discharged following sweat chloride < 60 mmol/L. Cases of LD-CF were each matched 1:2 with patients with NBS-CF for age, sex, hospital, and exocrine pancreatic status. RESULTS: A total of 45 LD-CF cases were identified (39 NBS-negative and 6 NBS-positive) with 90 NBS-CF matched controls. Median age (IQR) of diagnosis for LD-CF and NBS-CF was 1.35 (0.4-2.8) and 0.12 (0.03-0.2) years, respectively (P <.0001). Estimated incidence of LD-CF was 1 in 45 000 live births. Compared with NBS-CF, LD-CF had more respiratory manifestations at time of diagnosis (66% vs 4%; P <.0001), a higher rate of hospital admission per year for respiratory illness (0.49 vs 0.2; P = .0004), worse lung function (forced expiratory volume in 1 second percentage of predicted, 0.88 vs 0.97; P = .007), and higher rates of chronic colonization with Pseudomonas aeruginosa (47% vs 24%; P = .01). The LD-CF cohort also appeared to be shorter than NBS-CF controls (mean height z-score -0.65 vs -0.03; P = .02). CONCLUSIONS: LD-CF, despite NBS, seems to be associated with worse health before diagnosis and worse later growth and respiratory outcomes, thus providing further support for NBS programs for CF.

Inspissated bile syndrome; Safe and effective minimally invasive treatment with percutaneous cholecystostomy in neonates and infants.

PURPOSE: Inspissated bile syndrome (IBS) is a rare cause of obstructive jaundice in neonates and infants with several treatment options reported. We present our experience with the use of minimally invasive ultrasound-guided percutaneous cholecystostomy drain catheter placement with ongoing saline lavage in neonates and infants. METHODS: Retrospective chart review of patients treated with percutaneous cholecystostomy, from February 2010 till June 2015. We reviewed the technical and clinical success along with complications of the procedure. RESULTS: There were 6 patients, mean age 17weeks (range 4-40). Most had significant risk factors for IBS presenting with biliary obstruction. A total of 7 procedures performed on the 6 patients, with a technical success rate of 6/7. One patient required cannulation of the intrahepatic biliary system. Drains were flushed for a median of 26days (10-70). Clinical success was achieved in all patients. 3 had displacement of the drain, one of which required re-insertion. Another developed a small sub-hepatic collection post procedure with pyrexia. On long term follow up one was found to have a forme fruste choledochal cyst. CONCLUSION: Centers with suitable interventional radiology services ultrasound-guided percutaneous cholecystostomy drain catheter placement with ongoing saline lavage is a safe and effective minimally invasive treatment for IBS in neonates and infants.

Point-of-care echocardiography in simulation-based education and assessment.

BACKGROUND: Emergency medicine milestones released by the Accreditation Council for Graduate Medical Education require residents to demonstrate competency in bedside ultrasound (US). The acquisition of these skills necessitates a combination of exposure to clinical pathology, hands-on US training, and feedback. OBJECTIVES: We describe a novel simulation-based educational and assessment tool designed to evaluate emergency medicine residents' competency in point-of-care echocardiography for evaluation of a hypotensive patient with chest pain using bedside US. METHODS: This was a cross-sectional study conducted at an academic medical center. A simulation-based module was developed to teach and assess the use of point-of-care echocardiography in the evaluation of the hypotensive patient. The focus of this module was sonographic imaging of cardiac pathology, and this focus was incorporated in all components of the session: asynchronous learning, didactic lecture, case-based learning, and hands-on stations. RESULTS: A total of 52 residents with varying US experience participated in this study. Questions focused on knowledge assessment demonstrated improvement across the postgraduate year (PGY) of training. Objective standardized clinical examination evaluation demonstrated improvement between PGY I and PGY III; however, it was noted that there was a small dip in hands-on scanning skills during the PGY II. Clinical diagnosis and management skills also demonstrated incremental improvement across the PGY of training. CONCLUSION: The 1-day, simulation-based US workshop was an effective educational and assessment tool at our institution.

Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease.

BACKGROUND & AIMS: Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents. METHODS: We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture. RESULTS: We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-κB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores. CONCLUSIONS: In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

Sonography and hypotension: a change to critical problem solving in undergraduate medical education.

STUDY OBJECTIVES: Multiple curricula have been designed to teach medical students the basics of ultrasound; however, few focus on critical problem-solving. The objective of this study is to determine whether a theme-based ultrasound teaching session, dedicated to the use of ultrasound in the management of the hypotensive patient, can impact medical students' ultrasound education and provide critical problem-solving exercises. METHODS: This was a cross-sectional study using an innovative approach to train 3rd year medical students during a 1-day ultrasound training session. The students received a 1-hour didactic session on basic ultrasound physics and knobology and were also provided with YouTube hyperlinks, and links to smart phone educational applications, which demonstrated a variety of bedside ultrasound techniques. In small group sessions, students learned how to evaluate patients for pathology associated with hypotension. A knowledge assessment questionnaire was administered at the end of the session and again 3 months later. Student knowledge was also assessed using different clinical scenarios with multiple-choice questions. RESULTS: One hundred and three 3rd year medical students participated in this study. Appropriate type of ultrasound was selected and accurate diagnosis was made in different hypotension clinical scenarios: pulmonary embolism, 81% (95% CI, 73%-89%); abdominal aortic aneurysm, 100%; and pneumothorax, 89% (95% CI, 82%-95%). The average confidence level in performing ultrasound-guided central line placement was 7/10, focused assessment with sonography for trauma was 8/10, inferior vena cava assessment was 8/10, evaluation for abdominal aortic aneurysm was 8/10, assessment for deep vein thrombus was 8/10, and cardiac ultrasound for contractility and overall function was 7/10. Student performance in the knowledge assessment portion of the questionnaire was an average of 74% (SD =11%) at the end of workshop and 74% (SD =12%) 3 months later (P=0.00). CONCLUSION: At our institution, we successfully integrated ultrasound and critical problem-solving instruction, as part of a 1-day workshop for undergraduate medical education.

Novel de novo mutations of the interleukin-10 receptor gene lead to infantile onset inflammatory bowel disease.

BACKGROUND AND AIMS: Defects in the interleukin 10 (IL-10) signalling pathway have been shown to cause very early onset inflammatory bowel disease (IBD). We report a patient with severe infantile-onset IBD with a compound heterozygous IL-10 receptor alpha subunit (IL-10RA) mutation, one of which was paternally-inherited and the other occurring de novo. METHODS: Deep sequencing of IL-10, IL-10RA and IL-10 receptor beta subunit (IL-10RB) were performed. Peripheral blood mononuclear cell (PBMC) surface expression of IL-10RA was analysed by flow cytometry. IL-10 signalling pathway was examined by measuring phosphorylated STAT3 in PBMC cultured in the presence of IL-6 or IL-10. RESULT: We identified a missense mutation in exon 4 of IL-10RA (c.583T>C) in one allele and a nonsense mutation in exon 7 of IL-10RA (c.1368G>T) in the other allele. Neither mutation has been reported previously. The patient has functional IL-10RA deficiency despite normal IL-10RA expression. CONCLUSION: This represents the first case report of a de novo mutation of IL-10RA that is associated with very early onset severe IBD. Therefore, IL-10 pathway defect should be considered in patients with infantile-onset IBD even if the parents are non-consanguineous.

Fat-soluble vitamin deficiency in children and adolescents with cystic fibrosis.

AIMS: Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010. METHODS: A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed. RESULTS: Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%-35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient. CONCLUSIONS: This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.

Cholestasis and meconium ileus in infants with cystic fibrosis and their clinical outcomes.

OBJECTIVE: To identify the incidence and outcomes of cholestasis and meconium ileus (MI) in infants with cystic fibrosis (CF). DESIGN: Retrospective cohort study. SETTING: Single-centre study. PATIENTS: From January 1986 to December 2011, 401 infants with CF (69 with MI) presented to our centre. MAIN OUTCOME MEASUREMENTS: (1) incidence of cholestasis, (2) identification of risk factors for cholestasis, (3) association between the presence of cholestasis and MI and the development of clinically significant CF-associated liver disease (CFLD) defined as multilobular cirrhosis with portal hypertension. RESULTS: Cholestasis occurred in 23 of 401 infants (5.7%). There was a significantly higher incidence of cholestasis in infants with MI (27.1%) compared to those without MI (1.2%) (p<0.001). Infants with MI had a 30.36-fold increased risk of developing cholestasis compared to those without MI (p<0.001). Cholestasis resolved in all children, at a median (range) age of 9.2 (0.8-53.2) months in the MI group and 10.2 (2.0-19.4) months in the non-MI group. The majority of cholestatic infants (87.0%) and infants with MI (92.8%) did not develop clinically significant CFLD, not significantly different than either the 93.9% of non-cholestatic infants nor the 93.7% infants without MI. CONCLUSIONS: Cholestasis is an uncommon condition in CF affecting only 5.7% of the screened newborn CF population. The greatest risk factor for developing cholestasis is the presence of MI. However, the presence of MI appears not to be associated with the development of CFLD. An effect of neonatal cholestasis on the development of CFLD cannot be excluded by this study.

Prophylactic gastrectomy in a 16-year-old.

We performed a total gastrectomy in a 16-year-old asymptomatic CDH1 gene mutation carrier in whom two prior gastroscopies with biopsies were normal. The patient's mother died aged 39 years and her aunt died aged 21 years of gastric cancer. A germline CDH1 mutation (associated with hereditary diffuse gastric cancer) was initially identified in her mother at diagnosis and was later identified by predictive testing in this patient. Our patient is the youngest CDH1 carrier to date to have a prophylactic gastrectomy, and is several years below the age at which existing guidelines recommend consideration of gastrectomy. Multiple foci of early-stage carcinoma were found in her gastrectomy specimen. Given the family history of advanced gastric cancer in the late second decade, the unpredictable time course to development of advanced gastric cancer, and the futility of gastroscopic surveillance, we recommend consideration of prophylactic gastrectomy in adolescent asymptomatic CDH1 mutation carriers on an individual basis.

Liver disease in cystic fibrosis.

The survival of patients with cystic fibrosis (CF) has progressively increased over recent decades, largely attributable to early diagnosis through newborn screening and advances in nutritional and respiratory care. As the life expectancy of patients with CF has improved, non-respiratory complications such as liver disease have become increasingly recognized. Biochemical derangements of liver enzymes in CF are common and may be attributed to a number of specific hepatobiliary abnormalities. Among them, Cystic Fibrosis-associated Liver Disease (CFLD) is clinically the most significant hepatic complication and is believed to have a significant impact on morbidity and mortality. However, there remains much conjecture about the extent of the adverse prognostic implications that a diagnosis of CFLD has on clinical outcomes. The purpose of this review is to give an overview of the current knowledge regarding liver disease in children with CF.