ESPGHAN recommendations on treatment of chronic hepatitis C virus infection in adolescents and children including those living in resource-limited settings.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV-related liver disease has advanced considerably thanks to development and improvements in therapy. Direct-acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype-specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age-specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource-limited settings.

The Overlooked Microbiome-Considering Archaea and Eukaryotes Using Multiplex Nanopore-16S-/18S-rDNA-Sequencing: A Technical Report Focusing on Nasopharyngeal Microbiomes.

In contrast to bacteria, microbiome analyses often neglect archaea, but also eukaryotes. This is partly because they are difficult to culture due to their demanding growth requirements, or some even have to be classified as uncultured microorganisms. Consequently, little is known about the relevance of archaea in human health and diseases. Contemporary broad availability and spread of next generation sequencing techniques now enable a stronger focus on such microorganisms, whose cultivation is difficult. However, due to the enormous evolutionary distances between bacteria, archaea and eukaryotes, the implementation of sequencing strategies for smaller laboratory scales needs to be refined to achieve as a holistic view on the microbiome as possible. Here, we present a technical approach that enables simultaneous analyses of archaeal, bacterial and eukaryotic microbial communities to study their roles in development and courses of respiratory disorders. We thus applied combinatorial 16S-/18S-rDNA sequencing strategies for sequencing-library preparation. Considering the lower total microbiota density of airway surfaces, when compared with gut microbiota, we optimized the DNA purification workflow from nasopharyngeal swab specimens. As a result, we provide a protocol that allows the efficient combination of bacterial, archaeal, and eukaryotic libraries for nanopore-sequencing using Oxford Nanopore Technologies MinION devices and subsequent phylogenetic analyses. In a pilot study, this workflow allowed the identification of some environmental archaea, which were not correlated with airway microbial communities before. Moreover, we assessed the protocol's broader applicability using a set of human stool samples. We conclude that the proposed protocol provides a versatile and adaptable tool for combinatorial studies on bacterial, archaeal, and eukaryotic microbiomes on a small laboratory scale.

Affect dynamics and well-being: explanatory power of the model of intraindividual variability in affect (MIVA).

Affective experience is inherently dynamic and short-term changes in affect are supposed to offer important insights into well-being. Past years have shown a tremendous rise in investigations into the relation between affect dynamics and well-being. The indicators that have been introduced to capture unique dynamical aspects of affect, however, have been criticised for being purely statistical measures without theoretical foundation and were shown to have little added value for explaining well-being over and above mean levels of affect. To address these concerns, we applied our newly developed theory-based MIVA model to data on daily affective experience. The MIVA model allows estimating parameters for anchoring, reactivity, and regulation based on affective states in combination with daily events. Everyday affective experience was measured with a high temporal resolution, multiple indicators of well-being (e.g. life satisfaction, depression) were assessed, and the incremental value of the MIVA model parameters in predicting well-being was determined. The MIVA model parameters reflect essential processes that accounted for observed fluctuations in affective experience. Incremental validity for predicting well-being over and above mean levels of affect, however, was low. Together, our results suggest that research on affect dynamics needs to identify how affect dynamics can be assessed more validly.

Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection.

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty-four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%-100%). The patient who did not achieve SVR12 was a 4-year-old who discontinued treatment after 3 days because of "abnormal drug taste." The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3-year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.

The practice of emergency radiology throughout Europe: a survey from the European Society of Emergency Radiology on volume, staffing, equipment, and scheduling.

OBJECTIVES: To obtain information from radiology departments throughout Europe regarding the practice of emergency radiology METHODS: A survey which comprised of 24 questions was developed and made available online. The questionnaire was sent to 1097 chairs of radiology departments throughout Europe using the ESR database. All data were collected and analyzed using IBM SPSS Statistics software, version 20 (IBM). RESULTS: A total of 1097 radiologists were asked to participate, 109 responded to our survey. The response rate was 10%. From our survey, 71.6% of the hospitals had more than 500 beds. Ninety-eight percent of hospitals have an active teaching affiliation. In large trauma centers, emergency radiology was considered a dedicated section. Fifty-three percent of institutions have dedicated emergency radiology sections. Less than 30% had all imaging modalities available. Seventy-nine percent of institutions have 24/7 coverage by staff radiologists. Emergency radiologists interpret cross-sectional body imaging, US scans, and basic CT/MRI neuroimaging in more than 50% of responding institutions. Cardiac imaging examinations/procedures are usually performed by cardiologist in 53% of institutions, while non-cardiac vascular procedures are largely performed and interpreted by interventional radiologists. Most people consider the European Diploma in Emergency Radiology an essential tool to advance the education and the dissemination of information within the specialty of emergency radiology. CONCLUSION: Emergency radiologists have an active role in the emergency medical team. Indeed, based upon our survey, they have to interact with emergency physicians and surgeons in the management of critically ill patients. A broad skillset from ultrasonography and basic neuroimaging is required. KEY POINTS: • At most major trauma centers in Europe, emergency imaging is currently performed by all radiologists in specific units who are designated in the emergency department. • Radiologists in the emergency section at present have a broad skillset, which includes cross-sectional body imaging, ultrasonography, and basic neuroimaging of the brain and spine. • A dedicated curriculum that certifies a subspecialty in emergency radiology with a diploma offered by the European Society of Emergency Radiology demonstrates a great interest by the vast majority of the respondents.

Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B.

OBJECTIVE: Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. METHODS: Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. RESULTS: Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. CONCLUSIONS: The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE-an avoidable health risk: the SAFE randomised trial.

BACKGROUND: Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement. METHODS: In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order. RESULTS: 39-53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation. CONCLUSIONS: Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard. Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS-German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018-Retrospectively registered). Trial protocol can be accessed online.

Emergency radiology training in Germany: current status and future directions.

BACKGROUND: Emergency radiology (ER) is an important part of radiology. But what exactly is ER? How can the required competencies be acquired in a good and feasible way? Who should be in charge of this? OBJECTIVES: Discussion of ER contents and suggestions for the improvement of the acquisition of respective competencies during radiology training. MATERIALS AND METHODS: General literature review, in particular the current German blueprint for medical specialist training regulations (Weiterbildungsordnung, WBO 2020), publications by the German Radiological Society (DRG), the European Society of Radiology (ESR), the European Society of Emergency Radiology (ESER) and the American Society of Emergency Radiology (ASER). RESULTS AND CONCLUSIONS: As proof of competence in ER in Germany, confirmation from the authorised residency training supervisor as to whether there is 'competence to act' either 'independently' or 'under supervision' in the case of 'radiology in an emergency situation …, e.g. in the case of polytrauma, stroke, intensive care patients' is sufficient. The ESER refers to all acute emergencies with clinical constellations requiring an immediate diagnosis 24/7 and, if necessary, acute therapy. The ESER and ASER offer, among other things, practical fellowships in specialised institutions, while the ESER complements this with a European Diploma in Emergency Radiology (EDER). On a national level, it would be advisable to use existing definitions, offers and concepts, from the ESR, ESER and ASER. Specialised institutions could support the acquisition of ER competencies with fellowships. For Germany, it seems sensible to set up a separate working group (Arbeitsgemeinschaft, AG) on ER within the DRG in order to drive the corresponding further ER development.

The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review.

There is a lack of knowledge regarding the connection between the ocular and nasal epithelia. This narrative review focuses on conjunctival, corneal, ultrastructural corneal stroma, and nasal epithelia as well as an introduction into their interconnections. We describe in detail the morphology and physiology of the ocular surface, the nasolacrimal ducts, and the nasal cavity. This knowledge provides a basis for functional studies and the development of relevant cell culture models that can be used to investigate the pathogenesis of diseases related to these complex structures. Moreover, we also provide a state-of-the-art overview regarding the development of 3D culture models, which allow for addressing research questions in models resembling the in vivo situation. In particular, we give an overview of the current developments of corneal 3D and organoid models, as well as 3D cell culture models of epithelia with goblet cells (conjunctiva and nasal cavity). The benefits and shortcomings of these cell culture models are discussed. As examples for pathogens related to ocular and nasal epithelia, we discuss infections caused by adenovirus and measles virus. In addition to pathogens, also external triggers such as allergens can cause rhinoconjunctivitis. These diseases exemplify the interconnections between the ocular surface and nasal epithelia in a molecular and clinical context. With a final translational section on optical coherence tomography (OCT), we provide an overview about the applicability of this technique in basic research and clinical ophthalmology. The techniques presented herein will be instrumental in further elucidating the functional interrelations and crosstalk between ocular and nasal epithelia.

From Perviousness to Plaque Imaging in Acute Basilar Occlusions: The Impact of Underlying Stenosis and How to Detect It.

Background and Purpose- Recent studies show that mechanical thrombectomy of acute basilar artery occlusions (BAO) results in high rates of successful recanalization and good outcomes, but predictors are not completely established yet. Varying occlusion types may benefit differently, and especially, an underlying basilar stenosis (BS) seems to have an impact. Aim of this study was to investigate angiographic and clinical differences in BAO subtypes and to test the potential of perviousness measures for a preinterventional identification of clinically relevant different occlusion types. Methods- All consecutive patients with acute BAO, endovascular treated at a single comprehensive stroke center, were included. Different occlusion patterns, especially underlying BS, were identified and analyzed in respect of angiographic and clinical (National Institutes of Health Stroke Scale/modified Rankin Scale) outcome parameters (N=115). Thrombus perviousness measures (change in thrombus attenuation Δt and corrected void fraction ε) were assessed in admission computed tomography imaging and correlated to different etiological subgroups. Results- Despite comparable rates of successful recanalization (87% for BAO with BS versus 95% without BS), the BS group showed worse clinical outcome with higher National Institutes of Health Stroke Scale/modified Rankin Scale values (P=0.002/0.003). The group of BS turned out to have lower thrombus density values in unenhanced scans (mean, 42.0 Hounsfield units) and higher perviousness measures Δt (mean, 34.6 Hounsfield units) and ε (mean, 0.23) than thrombi without an underlying BS (mean, 53.6 Hounsfield units/13.1 Hounsfield units/0.08, P=0.01/ 0.004/ 0.001). Conclusions- In agreement with previous studies, outcome of mechanical thrombectomy of BAO seems to depend on pathogenesis with less clinical benefit for underlying BS, raising the question of early identification of this subgroup. Perviousness showed a high potential to differentiate acute BAO with and without BS, possibly usable as an admission imaging marker for BS.

Multicenter Analysis of Acquired Undescended Testis and Its Impact on the Timing of Orchidopexy.

OBJECTIVE: To assess whether late orchidopexy for undescended testis represents delayed treatment of primary undescended testis or later-occurring acquired undescended testis. STUDY DESIGN: We examined boys undergoing orchidopexy for cryptorchidism regarding age at surgery and entity of undescended testis. We characterized differences between primary undescended testis and acquired undescended testis and evaluated the knowledge regarding the diagnosis and management of acquired undescended testis among practicing physicians. We conducted an observational study using a mixed-method multicenter cross-sectional design. A total of 310 consecutive boys undergoing orchidopexy for undescended testis at 6 pediatric medical centers in Germany between April 2016 and June 2018 were investigated regarding testicular position at birth and age at surgery. In addition, a survey on acquired undescended testis management was carried out in 1017 multidisciplinary physicians and final-year medical students. RESULTS: Only 13% of all patients were operated on in their first year of life. Among patients with known previous testicular position (67%), primary undescended testis (n = 103) and acquired undescended testis (n = 104) were equally frequent. More than one-half (56%) of orchidopexies performed after the first year of life were due to acquired undescended testis. Remarkably, only 15% of physicians considered acquired undescended testis as an indication for late surgery. CONCLUSIONS: Acquired undescended testis is more common than previously perceived and accounts for a significant proportion of "late" orchidopexies in patients with undescended testis. Acquired undescended testis needs to be better recognized in clinical practice and screening should continue in older children with previously descended testes. TRIAL REGISTRATION: German Clinical Trials Registry: DRKS00015903.

[Interventional radiology as emergency therapy]. / Interventionelle Radiologie als Notfalltherapie.

CLINICAL ISSUE: Both the progress of surgical techniques and the demographic development with increasing numbers of multimorbid patients demand and also encourage radiology in the setting of trauma and acute emergencies. In addition to a fast and precise diagnostics, this also includes image-guided, minimally invasive therapy to control and treat several acute pathologies. STANDARD RADIOLOGICAL PROCEDURES: Computed tomography (CT) is not only important for the diagnosis of abscesses, active bleeding or other acute pathologies, but also allows minimally invasive therapy. While digital subtraction angiography (DSA) guides catheter-based procedures, e.g., to control bleedings or to place percutaneous transhepatic cholangiodrain (PTCD), fluoroscopy allows the 3D-visualization to drain abdominal and thoracic abscesses. METHODOLOGICAL INNOVATION AND EVALUATION: Radiology has established itself in the treatment of acute emergencies or acute complications through gentle and usually fast minimally invasive procedures. Presumably, MRI interventions will become increasingly important in the near future and, thus, complement the portfolio. PRACTICAL RECOMMENDATIONS: Every clinical radiologist who works on night shifts should be able to safely carry out some basic interventional techniques in order to stabilize the patient and at least ensure medically safe bridging to the next routine workday. Due to the diversity of materials and the rarity and difficulty of some procedures, the full portfolio requires years of expertise and will therefore remain restricted to specialized interventional radiologists.

[Sudden chest pain and lower abdominal pain : The usual suspects]. / Plötzlicher Brustschmerz und Unterleibsschmerzen : Die üblichen Verdächtigen.

CLINICAL PROBLEM: Sudden chest pain and sudden abdominal pain are among the most common reasons that lead patients to the emergency room. The heterogeneous field of possible, sometimes serious diagnoses requires a structured and rapid interdisciplinary clarification in order to be able to promptly provide patients with an adequate therapy. STANDARD RADIOLOGICAL PROCEDURES: Knowing the "usual suspects" of sudden chest and abdominal pain enables the radiologist to quickly select the appropriate imaging method that allows a diagnosis to be made without delay. In addition to pain localization and character, age, gender, any previous illnesses and laboratory results are taken into account in the differential diagnosis. METHODICAL INNOVATION AND EVALUATION: The technical state of computer tomography (CT) now ensures that most diagnoses can be clarified due to its excellent spatial and temporal resolution. In the abdomen, however, ultrasound should continue to be used at least for primary evaluation. Only if there is a further need for abdominal imaging afterwards is CT indicated for clarification. Magnetic resonance imaging is rarely used in the emergency setting of abdominal pain except to avoid radiation exposure in children or pregnant women. RECOMMENDATION FOR THE PRACTICE: Knowledge of the usual diagnoses that cause sudden chest or abdominal pain, as well as knowledge of the appropriate examination procedures and classic radiological signs are essential to avoid errors and delays in the emergency diagnosis of sudden chest and abdominal pain.

[Quality of findings, interpretation, and self-assessment of readers of chest x-rays acquired in one plane depending on the use of an anatomical viewing scheme and reader expertise]. / Qualität von Befunderstellung, Beurteilung und Selbsteinschätzung bei der Auswertung von Radiographien des Thorax in einer Ebene in Abhängigkeit von der Verwendung eines anatomischen Betrachtungsschemas und der Auswerterexpertise.

PURPOSE: To objectify effects of an anatomical viewing scheme on the respective correctness of (a) findings, (b) interpretations, and (c) self-assessments of readers in chest radiographs acquired in one plane and the assessment of other influencing factors. MATERIALS AND METHODS: In all, 20 radiologists with 3-60 months of full-time radiography experience evaluated 12 chest radiographs of varying difficulty: once with and once without using an anatomical viewing scheme with at least 1 month in between (n = 480). In consensus of 3 radiological experts (a) and (b) were determined by means of a current computed tomography. The self-assessment (c) of readers was queried. RESULTS: (a) Findings were either missed or not described in 21%. Another 20% were recognized, but incorrectly described, (b) 62% of interpretations and 31% of derived clinical consequences were wrong and (c) in 39% of items the readers overestimated themselves. Experts were faster and better than novices, but for the scheme usage no further significant differences were detected (p > 0.5, respectively). The most pronounced effect was found in comparison with the routine report produced by the joint evaluation of novices and experts being clearly superior even to the expert study results (a), (b) and (c) alone (p < 0.001, respectively). CONCLUSION: Reporting of chest X­rays acquired in one plane was often incomplete or even wrong, and the evaluators overestimated themselves, which was not influenced by the use of the anatomical viewing scheme. Since errors between the evaluators sometimes differed greatly, duplicate evaluation of the radiographs by two different radiologists, which is already the case in many training facilities, may possibly be advisable in general.

[Update polytrauma and computed tomography in ongoing resuscitation : ABCDE and "diagnose first what kills first"]. / Update Polytrauma und Computertomographie unter Reanimationsbedingungen : ABCDE und "diagnose first what kills first".

CLINICAL ISSUE: The mean number of trauma room admissions and applied CT dose increase as the severity of injuries decreases. Therefore, appropriateness of established procedures should be re-evaluated. STANDARD RADIOLOGICAL METHODS: Considering severely injured patients with an Injury Severity Score (ISS) ≥16, whole body CT (WB-CT) compared to selective CT decreased mortality by about 25%. Thus, the ISS is a good indicator for the severity of injuries. However, since ISS can only be determined after diagnosis, it does not help with the primary assessment. METHODOLOGICAL INNOVATION AND EVALUATION: In addition to the currently used very fast WB-CT protocol with the highest diagnostic precision, a second protocol should be established applying a substantially lower dose. Under ongoing resuscitation, WB-CT often makes a substantial contribution towards targeted therapy or to justifying the discontinuation of resuscitation measures. The WB-CT findings should be performed several times and, at least in the acute emergency situation, it should follow the ABCDE scheme as close as possible. PRACTICAL RECOMMENDATIONS: In the trauma room it should be initially decided whether the classification as polytrauma is to be maintained. If yes, every institution should provide a dose-reduced WB-CT protocol in addition to the maximum variant used so far. Dose-reduced WB-CT seems to be appropriate for stable and oriented patients, who receive a CT primarily because of the trauma mechanism. Even under resuscitation conditions, WB-CT is easy to perform and medically as well as ethically of high value. The reporting and communication should be structured according to "diagnose first what kills first".

[Resuscitation room diagnostics]. / Schockraumdiagnostik.

CLINICAL PROBLEM: The indication for resuscitation room care is an acute (potentially) life-threatening patient condition. Typical causes for this are polytrauma, acute neurological symptoms, acute chest and abdominal pain or the cause remains unclear at first. The care is always provided in a suitably composed interdisciplinary team. This requires cause-specific standards tailored to the care facility and requires a mutual understanding of the partners involved with regard to specialist interests and care processes. STANDARD RADIOLOGICAL METHODS: Whole-body CT is established for polytrauma imaging and usually each institution has already defined an institutional standard. For the other causes, first imaging with CT is just as common, but the protocols and procedures to be used are often not as clear as in the case of polytrauma. METHODICAL INNOVATION AND EVALUATION: For polytrauma service, ATLS and procedures according to ABCDE already serve as a largely standardized framework in the resuscitation room. For every other group of causes, comparable concepts should be developed and institutionally strive for objectification of continuous improvement. This refers not only to the resuscitation room stay but also to the interfaces before and after resuscitation room service. PRACTICAL RECOMMENDATIONS: After the patient has arrived, it has to be determined whether the assessment of a vital risk is retained. If so, institutionally defined care standards must be followed for the various causes. This concerns the interface logistics, the definition of a team leader including associated tasks, the supply processes including the CT examination protocols as well as the close communication.

Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study.

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 µg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.

Survey of Impediments to Prevention of Mother-to-infant Transmission of Hepatitis B Virus by International Societies.

OBJECTIVE: Mother-to-infant transmission (MIT) is the leading cause of hepatitis B virus (HBV) infections globally. The aim of this international study was to assess the impediments to prevention of (MIT) of HBV. METHODS: A cross-sectional survey was developed by the Federation of the International Societies for Pediatric Gastroenterology, Hepatology and Nutrition. (FISPGHAN) The survey was sent to HBV experts of the 5-member societies of FISPGHAN, and 63 of 91 countries/regions responded. Main outcome measures include percentage of countries having vaccine programs, timing of the first dose of HBV vaccine, availability of HBV vaccine for outborn neonates, payment of HBV vaccine and hepatitis B immune globulin, screening HBV markers during pregnancy, and antivirals to highly infectious pregnant mothers. RESULTS: Among the participating countries/regions, 11% did not implement infant HBV immunization programs. The first dose of vaccine was given >24 hours in 36% of the total countries and 100% of African countries. The recommended birth dose was unavailable for outborn neonates in 45% of the total countries, including 92% of African and 50% of Latin American countries/regions. During pregnancy, 44% countries do not screen maternal viral markers, and 46% do not provide third trimester antiviral therapy for highly viremic pregnant mothers. CONCLUSIONS: Our study demonstrated multiple obstacles to achieving the goal of preventing MIT of HBV. Comprehensive public health programs to enhance vaccine coverage rate, supply HBV vaccine for out-born neonates, screening maternal HBV markers, treating highly viremic pregnant mothers are proposed to overcome these obstacles and achieve the goal of preventing MIT of HBV.

Common Indications and The Diagnostic Yield of Esophagogastroduodenoscopy in Children with Gastrointestinal Distress.

BACKGROUND: The number of inconspicuous results of esophagogastroduodenoscopies (EGDs) in childhood appears to be disturbingly high. The aim of this study was to analyze the diagnostic yield of EGD and to determine its relevance of specific clinical indications. METHODS: We performed a retrospective analysis of 380 consecutive pediatric patients who underwent diagnostic EGD in two German level I pediatric gastroenterology departments in 2015 and 2016. RESULTS: 44% of the 380 patients were male and 17% were younger than 5 years old. 55% of all EGDs (n=210) did not yield a pathological result. 27% (n=104) of all EGDs were performed due to nonspecific symptoms (epigastralgia, nausea). Strikingly, in this group, 88% (n=91) showed normal results and in only 12% a diagnosis was made: reflux esophagitis (n=5), Helicobacter pylori (HP) gastritis (n=6) or hemorrhagic gastritis (n=1). Fewer inconspicuous EGDs were performed in patients with dysphagia (68%) or heartburn and reflux (61%). 59 patients were examined due to serologically elevated celiac antibodies. Here, the diagnosis could be confirmed histopathologically in 78% (n=46). Of the 37 patients with abdominal pain and a previously positive non-invasive HP test, EGD served to establish the diagnosis of HP gastritis in 84%. CONCLUSIONS: The diagnostic yield for EGDs is increased in patients with more specific symptoms (i. e. dysphagia, heartburn, HP, celiac disease). Consequently, as an invasive procedure, EGD warrants a strict indication.

Sofosbuvir and ribavirin in adolescents 12-17 years old with hepatitis C virus genotype 2 or 3 infection.

Children with chronic hepatitis C virus infection have limited treatment options. We evaluated the all-oral combination of sofosbuvir and ribavirin in adolescents aged 12-17 with hepatitis C virus genotype 2 or 3 (ClinicalTrials.gov NCT02175758). Fifty-two patients received sofosbuvir 400 mg once daily and weight-based ribavirin twice daily for 12 (genotype 2) or 24 (genotype 3) weeks. The pharmacokinetics of sofosbuvir and its metabolite GS-331007 were evaluated by intensive plasma sampling at day 7 in the first 10 patients enrolled and by sparse sampling in all patients throughout treatment. The primary efficacy endpoint was the percentage of patients with a sustained virologic response 12 weeks after treatment (SVR12). The median age of patients was 15 years, and 75% had genotype 3. Eighty-three percent of patients were treatment-naive, and 73% were infected by vertical transmission. Forty percent were assessed as not having cirrhosis; the remainder did not have a cirrhosis determination. Overall, SVR12 was achieved by 98% of patients (51/52; 95% confidence interval, 90%-100%). SVR12 rates were 100% (13/13) for patients with genotype 2 and 97% (38/39) for those with genotype 3. The single patient who did not achieve SVR12 was lost to follow-up after achieving SVR4. The most commonly reported adverse events were nausea (27%) and headache (23%). When compared with the exposure in adults treated in phase 2 and 3 sofosbuvir studies, the area under the curve and maximum concentration for sofosbuvir and GS-331007 in adolescents were within predefined pharmacokinetic equivalence boundaries of 50%-200%. CONCLUSION: Sofosbuvir and ribavirin was safe and highly effective in adolescents with chronic hepatitis C virus genotype 2 or 3 infection. (Hepatology 2017;66:1102-1110).