Congenital portosystemic shunt: characterization of a multisystem disease

OBJECTIVES Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. METHODS We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. RESULTS We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. CONCLUSIONS In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Trastornos de autoagresión hacia las uñas. Autoagressive nail disoreders

Background and objective: Autoaggressive nail disorders span a wide range of clinical changes, but they often remain undiagnosed. This article is intended to help the practitioner to make the correct diagnosis and institute an accepted treatment. Material and method: The patient charts of 1800 patients seen by the author between the years 2000-2011 in 6 different European countries were evaluated using photographs of finger and toenails. Results: The most common condition is onycholysis induced by overzealous manicure. The habit tic of maniacally pushing back the proximal nail fold of one or both thumb nails is frequent and often misdiagnosed. Heller’s median canaliform dystrophy is probably also due to a similar injury mechanism. Onychophagia is relatively com- mon and seen both in children and adults. Onychotillomania is less frequent and almost exclusively seen in adults. Onychotemnomania is even less frequent. Onychoteiromania is sowhere between the latter two habits. Onychodaknomania is exceptional and usually a sign of an underlying psychiatric disorder. There was no substantial difference in the prevalence of these conditions among the different countries visited. Conclusions: Auto aggressive nail injury is common, but often difficult to diagnose. Patient care requires not only an in-depth knowledge of virtually all nail diseases, but also a cautious and empathic patient examination and treatment

Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers.

CONTEXT Dementia care giving can lead to increased stress, physical and psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer's Disease (AD). OBJECTIVES This pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD. It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice. METHODS The charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and participants whose spouse had died were identified. Of these, those who received hospice care (n=10) were compared to those who did not (n=22) for various physiological and psychological measures of stress, both before and after the death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath scores as the dependent variable and pre-death scores as covariates, was used for all variables. RESULTS Significant group differences were found in postdeath depressive symptoms (HAM-D; F(1,29)=6.10, p<0.05) and anxiety symptoms (HAM-A; F(1,29)=5.71, p<0.05). Most psychological outcome variables demonstrated moderate effect sizes with a Cohen's d of>0.5 between groups. CONCLUSIONS These data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on these pilot data, further prospective investigation is warranted.

The Swiss Neonatal Quality Cycle, a monitor for clinical performance and tool for quality improvement

BACKGROUND We describe the setup of a neonatal quality improvement tool and list which peer-reviewed requirements it fulfils and which it does not. We report on the so-far observed effects, how the units can identify quality improvement potential, and how they can measure the effect of changes made to improve quality. METHODS Application of a prospective longitudinal national cohort data collection that uses algorithms to ensure high data quality (i.e. checks for completeness, plausibility and reliability), and to perform data imaging (Plsek's p-charts and standardized mortality or morbidity ratio SMR charts). The collected data allows monitoring a study collective of very low birth-weight infants born from 2009 to 2011 by applying a quality cycle following the steps 'guideline - perform - falsify - reform'. RESULTS 2025 VLBW live-births from 2009 to 2011 representing 96.1% of all VLBW live-births in Switzerland display a similar mortality rate but better morbidity rates when compared to other networks. Data quality in general is high but subject to improvement in some units. Seven measurements display quality improvement potential in individual units. The methods used fulfil several international recommendations. CONCLUSIONS The Quality Cycle of the Swiss Neonatal Network is a helpful instrument to monitor and gradually help improve the quality of care in a region with high quality standards and low statistical discrimination capacity.

Intellectual Property and Traditional Cultural Expressions in a Digital Environment. Preface

In the face of increasing globalisation, there is a pressing need for innovative trans-disciplinary analyses of the value of traditional cultural expressions (TCE) that also suggest appropriate protection mechanisms for them. The book to which this preface belongs combines approaches from history, philosophy, anthropology, sociology and law, and charts previously untravelled paths for developing new policy tools and legal designs that go beyond conventional copyright models. It reflects also upon the specific features of the digital environment, which, despite enhancing the risks of misappropriation of traditional knowledge and creativity, may equally offer some opportunities for revitalising indigenous peoples' values and provide for the sustainability of TCE.

Functional and anatomical outcome of eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab following an exit strategy regimen.

AIMS To assess the functional and morphological outcome of eyes with neovascular AMD treated with intravitreal ranbizumab following an exit strategy treatment regime. METHODS The Bern treatment regime for neovascular AMD has a fixed injection schedule, even in the non-active stage of the disease. The regimen has been adapted from the PIER study treatment protocol. Eyes with non-active AMD will receive 4 injections in the first year, and 2 injections in the second year of follow-up before treatment stops. Patients that received ranibizumab for treatment and reached the exit criteria were identified, and charts were reviewed to assess functional and morphological outcome. RESULTS Only 2.6% of all patients (15 out of 575 patients) reached the exit criteria. Mean change in best corrected ETDRS visual acuity (VA) was 4.5±16.9 letters when comparing baseline VA to 4 weeks after the last injection (p=0.32). OCT mean foveal thickness was significantly thinner after last treatment (247.9±43.0 µm) compared to baseline (332.5±83.1 µm, p=0.002). The mean total number of ranibizumab injections was 15.6±8.0, and the mean total treatment period was 40.9±18.3 months. Twenty percent of eyes had geographic atrophy present at baseline versus 46.6% at the end of treatment. CONCLUSIONS Even with a fixed treatment regime and a defined treatment exit strategy, only a small percentage of patients reach exit criteria. Retinal thickness has been significantly reduced by repeated intravitreal ranibizumab injections, and geographic atrophy became more frequent.

A new method to facilitate valid and consistent grading cardiac events in childhood cancer survivors using medical records

BACKGROUND Cardiac events (CEs) are among the most serious late effects following childhood cancer treatment. To establish accurate risk estimates for the occurrence of CEs it is essential that they are graded in a valid and consistent manner, especially for international studies. We therefore developed a data-extraction form and a set of flowcharts to grade CEs and tested the validity and consistency of this approach in a series of patients. METHODS The Common Terminology Criteria for Adverse Events version 3.0 and 4.0 were used to define the CEs. Forty patients were randomly selected from a cohort of 72 subjects with known CEs that had been graded by a physician for an earlier study. To establish whether the new method was valid for appropriate grading, a non-physician graded the CEs by using the new method. To evaluate consistency of the grading, the same charts were graded again by two other non-physicians, one with receiving brief introduction and one with receiving extensive training on the new method. We calculated weighted Kappa statistics to quantify inter-observer agreement. RESULTS The inter-observer agreement was 0.92 (95% CI 0.80-1.00) for validity, and 0.88 (0.79-0.98) and 0.99 (0.96-1.00) for consistency with the outcome assessors who had the brief introduction and the extensive training, respectively. CONCLUSIONS The newly developed standardized method to grade CEs using data from medical records has shown excellent validity and consistency. The study showed that the method can be correctly applied by researchers without a medical background, provided that they receive adequate training.

Sammlung Ryhiner. Karten, Pläne und Ansichten aus dem 16. bis 19. Jahrhundert

Vierbändiger, gedruckter Katalog zur Kartensammlung Ryhiner. Die Kartensammlung Ryhiner zählt zu den wertvollsten und bedeutendstenden der Welt. Sie umfasst ca. 16'000 Landkarten, Pläne und Ansichten aus dem 16. bis frühen 19. Jahrhundert, wobei die Bestände den ganzen Erdball abdecken. Zusammen mit den 20'000 Manuskriptkarten des Staatsarchivs verfügt Bern damit über ein weltweites geographisches Gedächtnis. Karto-bibliographischer Katalog der Sammlung Ryhiner in vier Bänden mit 1786 Seiten und 16258 Katalognummern (ohne Illustrationen).

Recent developments and open questions in the field of semantic roles

This introductory chapter briefly introduces a few milestones in the voluminous previous literature on semantic roles, and charts the territory in which the papers of this volume aim to make a contribution. This territory is characterized by fairly disparate conceptualizations of semantic roles and their status in theories of grammar and the lexicon, as well as by diverse and probably complementary ways of deriving or identifying them based on linguistic data. Particular attention is given to the question of how selected roles appear to relate to each other, and we preliminarily address the issue of how roles, subroles, and role complexes are best thought of in general.

Age, trauma and the critical shoulder angle accurately predict supraspinatus tendon tears.

BACKGROUND The pathogenesis of full-thickness tears of the rotator cuff remains unclear. Apart from age and trauma, distinct scapular morphologies have been found to be associated with rotator cuff disease. The purpose of the present study was to evaluate whether a score formed using these established risk factors was able to predict the presence of a rotator cuff tear reliably. METHODS We retrospectively assessed a consecutive series of patients with a minimal age of 40 years old, who had true antero-posterior (AP) radiographs of their shoulders, as well as a magnetic resonance (MR) gadolinium-arthrography, between January and December 2011. In all of these patients, the critical shoulder angle (CSA) was determined, and MR images were assessed for the presence of rotator cuff tears. Additionally, the patients' charts were reviewed to obtain details of symptom onset. Based on these factors, the so-called rotator cuff tear (RCT) score was calculated. RESULTS Patients with full-thickness RCTs were significantly older and had significantly larger CSAs than patients with intact rotator cuffs. Multiple logistic regression, using trauma, age and CSA as independent variables, revealed areas under the curve (AUCs) for trauma of 0.55, for age of 0.65 and for CSA of 0.86. The combination of all three factors was the most powerful predictor, with an AUC of 0.92. CONCLUSION Age, trauma and the CSA can accurately predict the presence of a posterosuperior RCT. LEVEL OF EVIDENCE Level IV. Case series with no comparison groups.

Apoptotic enteropathy caused by antimetabolites and TNF-α antagonists.

AIMS To investigate whether drugs others than mycophenolic acid and ipilimumab might cause graft-versus-host-like apoptotic enteropathy, the clinicopathological findings in four patients were examined who had developed watery diarrhoea and apoptotic enteropathy (three cases from colon and one case from ileal pouch) after intake of antimetabolites (methotrexate and capecitabine) and/or tumour necrosis factor-α inhibitors (etanercept and infliximab). METHODS The clinical charts, endoscopy reports and intestinal biopsies from all endoscopies were reviewed for all patients. Biopsies were evaluated semiquantitatively for apoptosis of basal crypts, dilated damaged crypts, defined as cystically dilated crypts with flattened degenerated epithelium containing apoptotic debris and few neutrophils, and mucosal architecture. Further, the presence of intraepithelial lymphocytes, chronic inflammatory cells in the lamina propria and mucosal ulcerations was recorded and immunohistochemical analysis for human cytomegalovirus and herpes simplex virus was performed. RESULTS Endoscopic examination revealed normal mucosa in two patients, whereas the other two showed focal ulcerations. Histological changes included increased apoptosis of basal crypts, the presence of dilated damaged crypts and architecture distortion. In all cases, a temporal association between drug intake and/or dose increase, and onset of diarrhoea, was observed, and no convincing evidence of other potentially underlying causes of colitis/enteritis was found, including infections. CONCLUSIONS Pathologists should be aware of the expanding spectrum of drugs that can cause apoptotic enteropathy, including antimetabolites and tumour necrosis factor-α inhibitors.

Increased ambulatory arterial stiffness index in obese children.

OBJECTIVE Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Ambulatory arterial stiffness index (AASI, defined as one minus the regression slope of diastolic on systolic blood pressure values derived from a 24 h arterial blood pressure monitoring, ABPM) is an upcoming and readily available marker of arterial stiffness. Our hypothesis was that AASI is increased in obese children compared to age- and gender matched healthy subjects. METHODS AASI was calculated from ABPM in 101 obese children (BMI ≥ 1.88 SDS according to age- and sex-specific BMI charts), 45% girls, median BMI SDS 2.8 (interquartile range (IQR) 2.5-3.4), median age 11.5 years (9.1-13.4) and compared with an age and gender matched healthy control group of 71 subjects with median BMI SDS 0.0 (-0.8-0.5). Multivariate regression analysis was applied to identify significant independent factors explaining AASI variability in this population. RESULTS AASI was significantly higher in obese children compared to controls (0.388 (0.254-0.499) versus 0.190 (0.070-0.320), p < 0.0001), but blood pressure values were similar. In a multivariate analysis including obese children only, AASI was independently predicted by 24-h systolic blood pressure SDS (p = 0.012); in a multivariate analysis including obese children and controls BMI SDS and pulse pressure independently influenced AASI (p < 0.001). CONCLUSIONS This study shows that AASI, a surrogate marker of arterial stiffness, is increased in obese children. AASI seems to be influenced by BMI and pulse pressure independently of systolic and diastolic blood pressure values, suggesting that other factors are involved in increased arterial stiffness in obese children.

Creating LaTeX documents from within Stata using texdoc

At least since Thomas Piketty's best-selling "Capital in the Twenty-First Century" (2014, Cambridge, MA: The Belknap Press), percentile shares have become a popular approach for analyzing distributional inequalities. In their work on the development of top incomes, Piketty and collaborators typically report top-percentage shares, using varying percentages as thresholds (top 10%, top 1%, top 0.1%, etc.). However, analysis of percentile shares at other positions in the distribution may also be of interest. In this paper I present a new Stata command called pshare that estimates percentile shares from individual-level data and displays the results using histograms or stacked bar charts.

Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation

BACKGROUND Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high inter-individual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. METHODS Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped and clinical data were retrieved from patient charts. RESULTS While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (P = 0.031). ERL dose requirement was 0.02 mg/kg/day higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (P = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 ml/min/1.73m(2) ) in patients with baseline kidney dysfunction. CONCLUSION ERL pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability. This article is protected by copyright. All rights reserved.

Ulnar nerve transposition at the elbow under local anesthesia: a patient satisfaction study

BACKGROUND Ulnar nerve decompression at the elbow traditionally requires regional or general anesthesia. We wished to assess the feasibility of performing ulnar nerve decompression and transposition at the elbow under local anesthesia. METHODS We examined retrospectively the charts of 50 consecutive patients having undergone ulnar nerve entrapment surgery either under general or local anesthesia. Patients were asked to estimate pain on postoperative days 1 and 7 and satisfaction was assessed at 1 year. RESULTS On day 1, pain was comparable among all groups. On day 7, pain scores were twice as high when transposition was performed under general anesthesia when compared with local anesthesia. Patient satisfaction was slightly increased in the local anesthesia group. These patients were significantly more willing to repeat the surgery. CONCLUSION Ulnar nerve decompression and transposition at the elbow can be performed under local anesthesia without added morbidity when compared with general anesthesia.