Presentation and treatment of biliary atresia

Biliary atresia (BA) is a rare disease of infancy in which obliteration of the biliary tract results in cholestasis and if left untreated in progressive liver failure and death at very young age. Kasai surgery is the only treatment that can postpone or prevent liver failure. Timely surgical correction is an important prognostic factor. However, two-thirds of patients still need a liver transplantation at child age. The aim of this thesis was to identify targets for improvement in diagnosis and treatment of BA. Therefore, we used our nationwide registry with patient data of all BA patients since 1987. Insufficient recognition of early symptoms of BA, such as acholic stools, might be an important underlying contributor to the delay in diagnosis and therefore to late surgery. Implementation of the Infant Stool Colour Card might lead to earlier diagnosis and treatment of BA, and thereby to significantly improved outcome. Our data show that the Dutch regimen of vitamin K prophylaxis in form of oral vitamin K drops fails to prevent Vitamin K Deficiency Bleeding in breastfed infants with BA. Based on our results, in 2017 the Health Council of the Netherlands recommended adaption of the Dutch guideline towards a regimen of a single injection of vitamin K at birth. Until now, the minister has not yet implemented this advice. Reaching native liver survival at the age of 2 years is an important prognostic milestone for BA patients. Almost 90% of these patients reach adulthood, and the majority even without liver transplantation

High sensitivity (1)H-NMR spectroscopy of homeopathic remedies made in water

BACKGROUND: The efficacy of homeopathy is controversial. Homeopathic remedies are made via iterated shaking and dilution, in ethanol or in water, from a starting substance. Remedies of potency 12 C or higher are ultra-dilute (UD), i.e. contain zero molecules of the starting material. Various hypotheses have been advanced to explain how a UD remedy might be different from unprepared solvent. One such hypothesis posits that a remedy contains stable clusters, i.e. localized regions where one or more hydrogen bonds remain fixed on a long time scale. High sensitivity proton nuclear magnetic resonance spectroscopy has not previously been used to look for evidence of differences between UD remedies and controls. METHODS: Homeopathic remedies made in water were studied via high sensitivity proton nuclear magnetic resonance spectroscopy. A total of 57 remedy samples representing six starting materials and spanning a variety of potencies from 6 C to 10 M were tested along with 46 controls. RESULTS: By presaturating on the water peak, signals could be reliably detected that represented H-containing species at concentrations as low as 5 μM. There were 35 positions where a discrete signal was seen in one or more of the 103 spectra, which should theoretically have been absent from the spectrum of pure water. Of these 35, fifteen were identified as machine-generated artifacts, eight were identified as trace levels of organic contaminants, and twelve were unexplained. Of the unexplained signals, six were seen in just one spectrum each. None of the artifacts or unexplained signals occurred more frequently in remedies than in controls, using a p < .05 cutoff. Some commercially prepared samples were found to contain traces of one or more of these small organic molecules: ethanol, acetate, formate, methanol, and acetone. CONCLUSION: No discrete signals suggesting a difference between remedies and controls were seen, via high sensitivity (1)H-NMR spectroscopy. The results failed to support a hypothesis that remedies made in water contain long-lived non-dynamic alterations of the H-bonding pattern of the solvent

Clinical Effects of Hypertension on the Mortality of Patients with Acute Myocardial Infarction

The incidence of ischemic heart disease has been increased rapidly in Korea. However, the clinical effects of antecedent hypertension on acute myocardial infarction have not been identified. We assessed the relationship between antecedent hypertension and clinical outcomes in 7,784 patients with acute myocardial infarction in the Korea Acute Myocardial Infarction Registry during one-year follow-up. Diabetes mellitus, hyperlipidemia, cerebrovascular disease, heart failure, and peripheral artery disease were more prevalent in hypertensives (n=3,775) than nonhypertensives (n=4,009). During hospitalization, hypertensive patients suffered from acute renal failure, shock, and cerebrovascular event more frequently than in nonhypertensives. During follow-up of one-year, the incidence of major adverse cardiac events was higher in hypertensives. In multi-variate adjustment, old age, Killip class ≥III, left ventricular ejection fraction <45%, systolic blood pressure <90 mmHg on admission, post procedural TIMI flow grade ≤2, female sex, and history of hypertension were independent predictors for in-hospital mortality. However antecedent hypertension was not significantly associated with one-year mortality. Hypertension at the time of acute myocardial infarction is associated with an increased rate of in-hospital mortality

Prophylactic Dosing of Vitamin K to Prevent Bleeding

BACKGROUND AND OBJECTIVES: Based on a high incidence of Vitamin K deficiency bleeding (VKDB) in breastfed infants with thus far unrecognized cholestasis, such as biliary atresia (BA), the Dutch regimen to prevent VKDB in breastfed infants was changed from a daily oral dosage of 25 mu g to 150 mu g vitamin K. Infants continued to receive 1 mg of vitamin K orally at birth. We compared the efficacy of the 150-mu g regimen with the 25-mu g regimen and with the Danish regimen of a single intramuscular (IM) dose of 2 mg vitamin K at birth. METHODS: Data were retrieved from the national BA registries: 25 mu g group (Netherlands, January 1991 to February 2011); 150 mu g group (Netherlands, March 2011 to January 2015); and IM 2 mg group (Denmark, July 2000 to November 2014). We compared the incidence of VKDB in the groups. RESULTS: VKDB occurred in 45 of 55 (82%) infants of the 25 mu g group, in 9 of 11 (82%) of the 150 mu g group, but in only 1 of 25 (4%) of the IM 2 mg group (P CONCLUSIONS: A vitamin K prophylactic regimen of 1 mg of vitamin K orally at birth followed by a daily oral dosage of either 25 or 150 mu g fails to prevent VKDB in breastfed infants with still unrecognized BA. The data support 2 mg vitamin K IM at birth as prophylaxis against VKDB

Early Detection of Neonatal Cholestasis: Inadequate Assessment of Stool Color by Parents and Primary Healthcare Doctors

IntroductionEarly diagnosis and surgery (<60 days of age) improve outcomes in children with biliary atresia. Only 56% of patients undergo timely surgery in the Netherlands. Lack of acquaintance with symptoms such as discolored stools might underlie this delay. We analyzed whether Dutch parents, youth healthcare doctors, or general practitioners recognized discolored stools and evaluated the effect of the Infant Stool Color Card (ISCC) on recognizing discolored stools. Material and MethodsWe asked 100 parents, 33 youth healthcare doctors, and 50 general practitioners to classify photographs of stools as normal or abnormal. Subsequently, we asked whether parents would seek medical help and doctors would refer the patient for medical investigation. Finally, parents scored stools using the ISCC. ResultsTwo-third of both parents and youth healthcare doctors recognized all discolored stools. Only half of them would seek medical help for all discolored stools resp. refer patient for medical investigation. Only one-third of the general practitioners recognized all discolored stools and would refer for medical investigation for all discolored stools. Using the ISCC, the percentage of parents recognizing all discolored stool increased from 66 to 87% (p ConclusionNeither parents nor youth healthcare doctors nor general practitioners reliably recognize discolored stool. The ISCC is an effective screening method for discolored stool. Our data indicate that the ISCC should be accompanied by unequivocal advices regarding referral for medical investigation upon detection of discolored stools

Variceal Bleeds in Patients with Biliary Atresia

Introduction Portal hypertension often occurs in biliary atresia (BA). The subsequent development of esophageal varices and bleeding from these varices are a well-known complication. We aim to describe the incidence and severity of variceal bleeding in patients with BA. In addition, we describe the characteristics of patients who experienced variceal bleeds. Materials and Methods We included all infants treated for BA at our center between March 1987 and August 2015. Variceal bleeding was defined as hematemesis and/or melena with presence of varices at endoscopy. Findings at endoscopy and ultrasound, laboratory tests, clearance of jaundice, fibrosis-grade at Kasai portoenterostomy, and several varices prediction scores were documented. Routine endoscopies were not performed. Results In this study, 74 patients were included. During follow-up, 18 out of 74 patients (24%) developed variceal bleeding at an age of 9 months (range, 4-111). Twelve patients were listed for liver transplantation at the time of bleeding. Patients who did not clear their jaundice developed variceal bleeds more often and earlier in life. Bleeds were treated with sclerotherapy, banding, or octreotide. Four patients did not receive treatment. No bleeding-related mortality occurred. Conclusion One-fourth of the children diagnosed with BA experience variceal bleeds during follow-up. Most of these children are younger than 1 year and often already listed for transplantation. Major complications did not occur after variceal bleeding

Prognosis of Biliary Atresia After 2-year Survival With Native Liver: A Nationwide Cohort Analysis

OBJECTIVES: To determine the prognosis of patients with biliary atresia (BA) after two years of native liver survival (NLS) and to identify prognostic factors for continued NLS after two years of age. METHODS: We retrospectively analyzed perioperative, laboratory and outcome parameters of all BA patients in The Netherlands between January 1987-June 2015 with NLS of at least two years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS-). RESULTS: We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89, 72, 60, 54%, respectively. Corresponding overall survival rates were 98, 90, 87, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS- patients (each P < .05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of two were irreversible jaundice and portal hypertension. CONCLUSIONS: Eighty-seven percent of patients with two-year NLS reach adult age, and more than 50% with their native liver. However, a pre-transplant mortality of 6% exists among patients who reach the age of two years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after two years of age