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Cíl: Cílem práce je analýza výsledků karotického stentování u našeho souboru pacientů rutinně testovaných na účinnost protidestičkové terapie. Srovnáváme výsledky s daty z rando-mizovaných kontrolovaných studií. Metodika: Retrospektivní analýza výsledku elektivního stentování karotické tepny na Radiologické klinice Masarykovy nemocnice v Ústí nad Labem v letech 2014-2022. Stentování karotické tepny podstoupilo 241 pacientů, kteří nebyli vhodní pro chirurgické ošetření. Soubor konsekutivních pacientů je specifický nastavením účinné protidestičkové léčby před výkonem. Sledované obdobíje do 30 dnů od výkonu. Výsledky: Bylo ošetřeno 179 mužů (74,2 %) a 62 žen (25,8 %). Pět pacientů (2,0 %) ve sledovaném období utrpělo cévní mozkovou příhodu (CMP) v souvislosti s výkonem, dva (0,8 %) zemřeli na komplikaci přímo spojenou s výkonem. Tři pacienti zemřeli na příčinu nesouvisející s intervencí (1,2 %). Nesetkali jsme se s infarktem myokardu. V celém souboru bylo riziko smrti nebo vzniku cévní mozkové příhody související s výkonem statisticky významně nižší ve srovnání s výsledky studie CREST (2,0 % vs. 4,8 %, p = 0,0243). V souboru sym-ptomatických pacientů bylo riziko smrti nebo cévní mozkové příhody související s výkonem významně nižší ve srovnání se studií ICSS (2,9 % vs. 7,4 %, p = 0,0243). Závěr: V našem souboru pacientů nevhodných k chirurgickému ošetření karotické stenózy jsme hodnotili vliv účinné protidestičkové terapie na výsledek léčby karotickým stentem. Riziko periprocedurální smrti či CMP bylo statisticky signifikantně nižší než ve studiích CREST a ICSS. Výsledky prokazují, že rutinní testování protidestičkové léčby je bezpečné a může snižovat riziko vzniku CMP a periprocedurální smrti. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a case report of a boy with an acute disseminated encephalomyelitis following an infection induced by Mycoplasma pneumoniae. It is a demyelinating inflammatory disease of the central nervous system caused by the malfunction of the regulation of the immunity reaction of an organism to an infection or a vaccination. The occurrence of the disease is very rare and the diagnosis is determined by exclusion based on anamnesis data, clinical picture and examination finding of the nervous system by magnetic resonance. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Postoperative delirium (POD) is the most common complication following surgery in elderly patients. During pharmacist-led medication reconciliation (PhMR), a predictive risk score considering delirium risk-increasing drugs and other available risk factors could help to identify risk patients., Methods: Orthopaedic and trauma surgery patients aged ≥ 18 years with PhMR were included in a retrospective observational single-centre study 03/2022-10/2022. The study cohort was randomly split into a development and a validation cohort (6:4 ratio). POD was assessed through the 4 A's test (4AT), delirium diagnosis, and chart review. Potential risk factors available at PhMR were tested via univariable analysis. Significant variables were added to a multivariable logistic regression model. Based on the regression coefficients, a risk score for POD including delirium risk-increasing drugs (DRD score) was established., Results: POD occurred in 42/328 (12.8%) and 30/218 (13.8%) patients in the development and validation cohorts, respectively. Of the seven evaluated risk factors, four were ultimately tested in a multivariable logistic regression model. The final DRD score included age (66-75 years, 2 points; > 75 years, 3 points), renal impairment (eGFR < 60 ml/min/1.73m 2 , 1 point), anticholinergic burden (ACB-score ≥ 3, 1 point), and delirium risk-increasing drugs (n ≥ 2; 2 points). Patients with ≥ 4 points were classified as having a high risk for POD. The areas under the receiver operating characteristic curve of the risk score model were 0.89 and 0.81 for the development and the validation cohorts, respectively., Conclusion: The DRD score is a predictive risk score assessable during PhMR and can identify patients at risk for POD. Specific preventive measures concerning drug therapy safety and non-pharmacological actions should be implemented for identified risk patients., (© 2024. The Author(s).)

Due to the demographic change and the rising mobility of older adults in comparison with former generations, the number of old persons involved in road traffic has been continuously growing. The safety of all participating parties in road traffic necessitates a successful interaction of each individual's visual, motor and cognitive functions. These might be negatively affected by age-related physiological changes with a large individual variation. In addition, old age is affected to varying degrees by multimorbidity and the resulting medication can further influence the ability to drive. There are, however, several options to compensate for potential functional losses in road traffic. Maintaining the mobility of old people for as long as possible and at the same time maintaining traffic safety for all participants represents a challenge for society and medicine when dealing with older adults. This article discusses the old person in road traffic from a geriatrics point of view., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Pediatric acute pancreatitis (AP) is rare but increasing. Severe AP is associated with higher morbidity and mortality. However, there are no universally accepted prognostic criteria for AP., Methods: This retrospective study included children with AP admitted to an intensive care unit (ICU) of our tertiary pediatric center between January 2009 and December 2018. The severity of organ dysfunction in AP was assessed according to the modified Atlanta criteria using the Pediatric Sequential Organ Failure Assessment (pSOFA) and Computed Tomography Severity Index (CTSI)., Results: Seventy acute episodes of AP were evaluated in 55 children with primary pancreatitis. In addition, secondary AP was diagnosed in 15 patients originally admitted to ICU for different indications. Mild AP [no organ dysfunction, normal computed tomography (CT) finding] was the most prevalent (64/85 episodes in 49 children), followed by moderate AP (15 children; pSOFA 2-9 points, CTSI 3-4 points on admission). Severe AP (pSOFA 4-17 points, CTSI 6-10 points) was diagnosed in 6 children with traumatic or secondary AP. The most frequent etiologies of primary AP episodes were idiopathic (39%) and biliary (31%). Children with idiopathic AP had frequent relapses and comorbidities. Hereditary AP was typically mild, but presented with high pancreatic enzyme levels and recurrence rates. Admission at ICU and an interval without enteral nutrition (EN) were relatively short in drug-induced AP and relatively long in secondary and traumatic AP. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 13 patients with biliary AP and in 4 patients with traumatic AP. No AP-related death was observed., Conclusion: pSOFA score accurately reflects the severity and prognosis of AP in children., (Copyright © 2022. Published by Elsevier B.V.)

In the treatment of proximal humeral fractures (PHF), patients are often recommended to wear a sling or orthosis and to perform physiotherapy. However, some patients, especially elderly ones, struggle to comply with these rehabilitation regimens. Therefore, the aim of the study was to evaluate whether these incompliant patients have a worse functional outcome than those who adhere to the rehabilitation protocol. After receiving a diagnosis of a PHF, patients were divided into four groups according to fracture morphology: conservative with sling, operative with sling, conservative with abduction orthosis, and operative with abduction orthosis. At the 6-week follow-up, compliance regarding brace use and physiotherapy performance were assessed, as well as the constant score (CS) and complications or revision surgeries. The CS as well as the complications and revision surgeries were also surveyed after one year. In 149 participants, with a mean age of 73.9 ± 7.2 years, only 37% terminated orthosis and only 49% underwent physiotherapy as recommended. The statistical analysis showed no significant difference in the CS, complications, and revision surgeries between the groups.

What Is Known and Objective: A 'renal pharmacist consultant service' (RPCS) reviewing patients' charts with renal impairment (RI) for drug-related problems (DRP) can foster patient safety. However, the benefit of this service in the new setting of a computerized physician order entry (CPOE)-system with a clinical decision support (CDS)-system is unknown. The aim of our study was to evaluate the general need for an RPCS on wards with a CPOE-CDS-system already in use and its effectiveness on prescription changes to ensure in-hospital patient safety., Methods: Over a period of 3 months (02-04/2021), elective orthopaedic and trauma patients with eGFR absolute /CrCl <60 ml/min at a German University Hospital received a medication review by a renal pharmacist for all medication entered into the CPOE-system (Meona®) by the treating physicians. Written consultations explaining identified DRP and recommending interventions to solve them, for example, dose or drug adaptation, were shared with the physicians directly in the drug chart tab of Meona®. In complex cases, DRP were additionally discussed via phone. The prescription changes were evaluated retrospectively., Results and Discussion: During 53 working days, 712 (30.5%) of 2331 screened patients were included with an eGFR non-indexed /CrCl <60 ml/min and a pharmacist-led medication review was performed for all medication presented in the CPOE-system (Meona®). In 79 of 712 (11.1%) patients, one or more DRP were detected (median 1 DRP (1-3) per patient) and written recommendations concerning 106 of 1090 (9.7%) drugs were shared via Meona®. In total, 104 DRP were identified, mostly caused by 'dosage too high' (n = 55, 52.9%), 'dosage regime wrong' (n = 13, 12.5%), and 'contraindication' (n = 9, 8.7%). Acceptance rate of recommendations was 74.0% (n = 77/104). In nine cases (8.7%), despite of specific recommendations, no adjustment of drugs was made because of lack of alternatives. In 11 (10.6%) cases, prescription remained unchanged for unknown reasons and in seven (6.7%) cases, the result was unknown due to discharge., What Is New and Conclusion: In the setting of prescribing in a CPOE-CDS-system, that provides physicians with advice for drug or dose adaption, the pharmacist-led medication reviews still identified DRP in orthopaedic and trauma patients with RI. A RPCS forwarding recommendations to solve DRP via the electronic medical record increased appropriate prescribing by physicians and, thus, may further improve patient safety., (© 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children., Approach and Results: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05)., Conclusions: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population., (© 2021 by the American Association for the Study of Liver Diseases.)

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS ( p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.

Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC., Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well., Conclusions: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials., (© 2020 by the American Association for the Study of Liver Diseases.)

M systems are mathematical models of morphogenesis developed to gain insights into its relations to phenomena such as self-assembly, self-controlled growth, homeostasis, self-healing and self-reproduction, in both natural and artificial systems. M systems rely on basic principles of membrane computing and self-assembly, as well as explicit emphasis on geometrical structures (location and shape) in 2D, 3D or higher dimensional Euclidean spaces. They can be used for principled studies of these phenomena, both theoretically and experimentally, at a computational level abstracted from their detailed implementation. In particular, they afford 2D and 3D models to explore biological morphogenetic processes. Theoretical studies have shown that M systems are powerful tools (e.g., computational universal, i.e. can become as complex as any computer program) and their parallelism allows for trading space for time in solving efficiently problems considered infeasible on conventional computers (NP-hard problems). In addition, they can also exhibit properties such as robustness to injuries and degrees of self-healing. This paper focuses on the experimental side of M systems. To this end, we have developed a high-level morphogenetic simulator, Cytos, to implement and visualize M systems in silico in order to verify theoretical results and facilitate research in M systems. We summarize the software package and make a brief comparison with some other simulators of membrane systems. The core of the article is a description of a range of experiments inspired by aspects of morphogenesis in both prokaryotic and eukaryotic cells. The experiments explore the regulatory role of the septum and of the cytoskeleton in cell fission, the robustness of cell models against injuries, and, finally, the impact of changing nutrient concentration on population growth., (Copyright © 2020. Published by Elsevier B.V.)

Background: Autoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF)., Methods: Forty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH)., Results: Acute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient., Conclusion: Rapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH., (Copyright © 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC., Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic., Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy., Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

Objective: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis., Study Design: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year., Results: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not., Conclusions: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event-free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver-related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P = not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P = 0.002), but 5-year event-free survival was similar (74% versus 77%, P = NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5-year event-free survival was better (91% versus 67%, P < 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5-year event-free survival 88% versus 61%, P = 0.005). Conclusion: A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome., Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: Clinically symptomatic vasospasm leading to delayed ischemic neurological deficits occurs in up to 30% of patients with subarachnoid hemorrhage (SAH). Vasospasm can result in a serious decline in clinical conditions of patients with SAH, yet the algorithm for vasospasm treatment and prevention remains unclear. Intra-arterial administration of vasodilators is one of the modalities used for vasospasm therapy., Methods: Over the last 7 years, we have treated 27 female and 7 male patients with vasospasm using intra-arterial administration of either nimodipine or milrinone; all had suffered aneurysm rupture. Of these patients, 28 were treated surgically (clip), and 6 patients had their aneurysm coiled. Spasmolytics were applied from day 2 to day 18 after rupture., Results: Of the 53 procedures, angiographic improvement was documented in 92% of cases with a mean flow velocity decrease of 65 cm/s. Brain metabolism changes were monitored after the procedure. The highest level of immediate clinical improvement was observed in conscious patients with a focal neurological deficit (aphasia, hemiparesis). Overall clinical outcomes (Glasgow outcome scale, GOS) were as follows: GOS 5 (12 patients), GOS 4 (5 patients), GOS 3 (5 patients), GOS 2 (6 patients), and GOS 1 (6 patients)., Conclusions: Intra-arterial administration of spasmolytics is a safe and potent method of vasospasm treatment. It is most effective when applied to conscious patients with a focal deficit. For unconscious patients, its therapeutic benefits are inconclusive. Patients in severe clinical states would further require use of other diagnostic tools such as multimodal brain monitoring to complement vasospasm therapy.

Background and Aims: Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase., Patients and Methods: Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests - TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls - in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12., Results: The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder., Conclusion: Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder resulting from mutations in the PHOX2B gene located on chromosome 4p12.3, characterized by hypoventilation secondary to missing responses to both hypercapnia and hypoxia., Case Report: Proband. A girl, hospitalised 5 times for respiratory failure from 6 weeks old, presented at 4 years of age severe cyanosis related to pneumonia. Tracheostomy was done, and she was discharged home using a portable positive pressure ventilator during sleep. Proband's father: The father was retrospectively found out to suffer from severe headache and excessive daytime sleepiness. Molecular genetic evaluation of PHOX2B gene was performed and casual polyalanine repeat expansion mutation c.741&#95;755dup15 in exon 3 was found both in proband and her father in heterozygous form. The proband's grandmother died of respiratory failure after administration of benzodiazepine at the age of fifty years. Considering the grandmother's history, she is highly suspected of having had CCHS as well., Conclusion: Repeated respiratory failure of girl was explained by PHOX2B mutation and Ondina curse. Proband´s father has incompletely penetrated PHOX2B heterozygous mutation as well and proband´s grandmother died probably from the consequences of drug interaction with PHOX2B mutated background as well. Both daughter and father currently require overnight mechanical ventilatory support. Although most PHOX2B mutations occur de novo, our case is a rare three generation family affected by autosomal dominant inheritance with incomplete penetrance manifested as the late-form of CCHS and proven PHOX2B mutation in two generations.

A novel capillary electrophoresis-tandem mass spectrometry method for the enantioseparation and identification of 2-hydroxyglutaric acid enantiomers without derivatization for clinical purposes was described. Vancomycin chloride was used as an efficient chiral selector for the discrimination of 2-hydroxyglutaric acid enantiomers by capillary electrophoresis employed complete capillary filling method. The obtained resolution was 2.05. Hyphenation of CE with tandem mass spectrometry allows a reliable identification of separated enantiomers as well as their quantification. The method was validated and applied for the separation, identification and determination of 2-hydroxyglutaric enantiomers in urine samples obtained from healthy patients and two urine samples obtained from child patients suffering from high urine excretion of 2-hydroxyglutaric acid. Abnormal excretion of d-hydroxyglutaric acid was found in both child urine samples (104.5±2.1 and 2200.0±12.6mmol/mol of creatinine, respectively). The limits of detection for d- and l-hydroxyglutaric acid were 31 and 38nmol/L, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Sclerosing cholangitis (SC) is a chronic cholestatic hepatobiliary disease with uncertain long-term prognosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC., Methods: We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangiographic findings. Patients fulfilling diagnostic criteria for probable or definite autoimmune hepatitis at the time of diagnosis were defined as having autoimmune sclerosing cholangitis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hypertension, advanced liver disease and death associated with the primary disease., Results: Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were significantly younger at the time of diagnosis (12.3 vs 15.4 years, P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L, P=0.003). The mentioned complications occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications., Conclusion: In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.