Motilitätsstörungen des Ösophagus

Zusammenfassung: Motilitätsstörungen des Ösophagus umfassen ein heterogenes Spektrum von Erkrankungen. Primäre Fehlbildungen des Ösophagus sind heute zwar einer verbesserten chirurgischen und gastroenterologischen Therapie zugänglich, führen jedoch zu langfristig persistierender ösophagealer Dysmotilität. Die Achalasie resultiert aus einer gestörten Relaxation des gastroösophagealen Sphinkters. Systemische Erkrankungen können mit einer sekundären ösophagealen Motilitätsstörung einhergehen. Zahlreiche neuromuskuläre Erkrankungen mit viszeraler Manifestation zeigen eine ösophageale Beteiligung. Selten kann eine Aganglionose bis in den Ösophagus reichen. Die wachsende Gruppe der Myopathien schließt metabolische und mitochondriale Störungen ein, deren zunehmende Charakterisierung genetischer Defekte vereinzelt bereits therapeutische Ansätze eröffnet. Infektbedingte Ösophagitiden zeigen besonders bei immunkompromittierten Patienten eine schwere Störung der Motilität. Immunologisch vermittelte Entzündungsprozesse im und um den Ösophagus werden allmählich besser verstanden. Schließlich können seltene Tumoren und tumorartige Läsionen eine Dysmotilität des Ösophagus verursache

Pediatric Gastrointestinal Endoscopy: European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and European Society of Gastrointestinal Endoscopy (ESGE) Guidelines

ABSTRACT: This Guideline refers to infants, children and adolescents aged 0–18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileo-colonoscopy; endoscopy for foreign body ingestion; corrosive ingestion and stricture/stenosis endoscopic management; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangio-pancreatography and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) has been dealt with in other Guidelines [1–3] and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance are to be dealt with in an imminent sister publication to this

Evolution of International Pediatric Endoscopic Practice Changes During the Coronavirus Disease 2019 Pandemic

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered endoscopic practices. We initially reported the international impact of COVID-19 on pediatric endoscopic practice. This follow-up study aimed to assess changes 7 months following the initial survey to delineate practice change patterns as the pandemic evolved. METHODS: Pediatric gastroenterologists who responded to the initial survey were re-surveyed seven months later using Research Electronic Data Capture (REDCap). The survey recorded information on changes in pediatric endoscopic practice patterns, including COVID-19 screening and testing processes and personal protective equipment (PPE) utilization. Additionally, endoscopists\u27 risk tolerance of COVID-19 transmission was evaluated. RESULTS: Seventy-five unique institutions from 21 countries completed surveys from the 145 initial responses (51.7% response rate). Procedural volumes increased at most institutions (70.7%) and most were performing previously postponed cases (90.7%). Ninety-seven percent of institutions were performing pre-endoscopy screening with 78.7% testing all patients. Many institutions (34.7%) have performed procedures on COVID-19 positive patients. There was significantly less PPE reuse (P  \u3c 0.05) and fewer institutions recommending full PPE for all endoscopies (43.2% vs 59.2%, P = 0.013). Overall, pediatric endoscopists\u27 risk tolerance of COVID-19 transmission is low. CONCLUSIONS: This is the first survey to highlight the evolution of pediatric endoscopic practices related to the COVID-19 pandemic, underscoring the need for ongoing pandemic-related guidance for pediatric endoscopic practice

Inhibitory NKG2A⁺ and absent activating NKG2C⁺ NK cell responses are associated with the development of EBV⁺ lymphomas

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, which infects over 90% of the adult human population worldwide. After primary infections, EBV is recurrently reactivating in most adult individuals. It is, however, unclear, why these EBV reactivations progress to EBV+ Hodgkin (EBV+HL) or non-Hodgkin lymphomas (EBV+nHL) only in a minority of EBV-infected individuals. The EBV LMP-1 protein encodes for a highly polymorphic peptide, which upregulates the immunomodulatory HLA-E in EBV-infected cells, thereby stimulating the inhibitory NKG2A-, but also the activating NKG2C-receptor on natural killer (NK) cells. Using a genetic-association approach and functional NK cell analyses, we now investigated, whether these HLA-E-restricted immune responses impact the development of EBV+HL and EBV+nHL. Therefore, we recruited a study cohort of 63 EBV+HL and EBV+nHL patients and 192 controls with confirmed EBV reactivations, but without lymphomas. Here, we demonstrate that in EBV+ lymphoma patients exclusively the high-affine LMP-1 GGDPHLPTL peptide variant-encoding EBV-strains reactivate. In EBV+HL and EBV+nHL patients, the high-expressing HLA-E*0103/0103 genetic variant was significantly overrepresented. Combined, the LMP-1 GGDPHLPTL and HLA-E*0103/0103 variants efficiently inhibited NKG2A+ NK cells, thereby facilitating the in vitro spread of EBV-infected tumor cells. In addition, EBV+HL and EBV+nHL patients, showed impaired pro-inflammatory NKG2C+ NK cell responses, which accelerated the in vitro EBV-infected tumor cells spread. In contrast, the blocking of NKG2A by monoclonal antibodies (Monalizumab) resulted in efficient control of EBV-infected tumor cell growth, especially by NKG2A+NKG2C+ NK cells. Thus, the HLA-E/LMP-1/NKG2A pathway and individual NKG2C+ NK cell responses are associated with the progression toward EBV+ lymphomas.</p

Torque teno viruses exhaust and imprint the human immune system via the HLA-E/NKG2A axis

The ubiquitous Torque teno virus (TTV) establishes a chronically persistent infection in the human host. TTV has not been associated with any apparent disease, but, as part of the human virome, it may confer a regulatory imprint on the human immune system with as yet unclear consequences. However, so far, only few studies have characterized the TTV-specific immune responses or the overall immunological imprints by TTV. Here, we reveal that TTV infection leads to a highly exhausted TTV-specific CD8+ T-cell response, hallmarked by decreased IFN-γ production and the expression of the inhibitory NKG2A-receptor. On a functional level, we identified a panel of highly polymorphic TTV-encoded peptides that lead to an expansion of regulatory NKG2A+ natural killer, NKG2A+CD4+, and NKG2A+CD8+ T cells via the stabilization of the non-classical HLA-E molecule. Our results thus demonstrate that TTV leads to a distinct imprint on the human immune system that may further regulate overall human immune responses in infectious, autoimmune, and malignant diseases

Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa

El complejo esclerosis tuberosa (CET) es una enfermedad rara, hereditaria, multisistémica y con un amplio espectro fenotípico. Su manejo requiere de la colaboración de múltiples especialistas. Así como en la edad pediátrica cobra un especial relieve el neurólogo pediatra, en la edad adulta la afectación renal es la causante de la mayor morbimortalidad. Existen diversas recomendaciones sobre el manejo general del paciente con CET, pero ninguna que se centre en la afectación renal. Las presentes recomendaciones responden a la necesidad de proporcionar pautas para facilitar un mejor conocimiento y manejo diagnóstico-terapéutico de la afectación renal del CET mediante un uso racional de las pruebas complementarias y el empleo correcto de los tratamientos disponibles. Su elaboración se ha basado en el consenso dentro del grupo de trabajo de enfermedades renales hereditarias de la SEN/REDINREN. Ha contado con la participación de especialistas en CET no nefrólogos también con el fin de ampliar la visión de la enfermedad

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

Drugs in focus: Botulinum toxin in the therapy of gastrointestinal disorders in children

What is Known Botulinum toxin (BoNT) causes muscle relaxation by inhibiting acetylcholine release from presynaptic motor neurons at the neuromuscular junction. What is New In children with achalasia, BoNT can be considered only in patients in whom rapid weight gain is important to improve surgical outcomes. BoNT has been suggested for treating cricopharyngeal achalasia and delayed gastric emptying. Anal achalasia and constipation after Hirschsprung disease corrective surgery are very promising indications for BoNT use. In selected children with resistant type of functional constipation and chronic anal fissure, BoNT is a viable option for treating

Treatment and long-term outcome in primary nephrogenic diabetes insipidus

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0–60) years and at last follow-up 14.0 (0.1–70) years. In adults, height was normal with a mean (standard deviation) score of −0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems

Nephrectomy in autosomal dominant polycystic kidney disease: A consensus statement of the ERA Genes &amp; Kidney Working Group

\ua9 2025 The Author(s). A substantial number of patients with autosomal dominant polycystic kidney disease (ADPKD) undergo a nephrectomy, especially in workup for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians about which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant surgeons. These sources were used to develop practice points about indications, complications, mortality, and timing and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy were explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes &amp; Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the workup for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision-making, preferably after multidisciplinary consultation