This study showed that Peristeen TAI resulted in a significant time reduction in colonic cleansing, increased independence from the carer and improved QoL in paediatric patients with ARMs and SCLs.

We observed a sustained improvement in bowel management and quality of life in SB and ARM children during the study, more significant in the short term than in mid-long term. To maintain success rates in the mid-long term and to reduce the dropout rate, we propose patient training and careful follow-ups.

Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

Based on the scoring system outcome colovaginoplasty seems to be an excellent choice to manage vaginal agenesis and ensure good quality of general and sexual life.

p.(Arg320His) mutation in the KCNC1 gene in human 11p15.1 has recently been identified in patients with progressive myoclonus epilepsies, a group of rare inherited disorders manifesting with action myoclonus, myoclonic epilepsy, and ataxia. This KCNC1 variant causes a dominant-negative effect. Here we describe three patients from the same family with intellectual disability and dysmorphic features. The three affected individuals carry a c.1015C>T (p.(Arg339*)) nonsense variant in KCNC1 gene. As previously observed in the mutant mouse carrying a disrupted KCNC1 gene, these findings reveal that individuals with a KCNC1 loss-of-function variant can present intellectual disability without seizure and epilepsy.

X-linked alpha thalassemia mental retardation (ATR-X) syndrome is associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Patients with ATR-X syndrome frequently present with gastrointestinal problems, in particular feeding difficulties, regurgitation and vomiting, abdominal pain, distension, and chronic constipation. Parental reports of prolonged food refusal and distress in these children are common and although these episodes are suspected to be gastro-intestinal in origin they are rarely investigated. Death in early childhood from aspiration of vomitus or from pneumonia presumed to be secondary to aspiration has been recorded in a number of ATR-X cases. In this report we review the gastrointestinal phenotype of ATR-X syndrome in 128 cases. We also demonstrate that in two siblings, regurgitation was secondary to gastric pseudo-volvulus, a condition in which the stomach does not have a normal system of peritoneal ligaments and changes position with possible torsion around itself. Furthermore, ultra-short Hirschsprung disease with colonic hypoganglionosis was shown and this may contribute to the severe constipation affecting these children.

No abstract

Venetoclax (VEN) belongs the BH3-mimetic class that selectively targets BCL-2, activating apoptosis. The combination of VEN and azacitidine (AZA) has changed the paradigm of treatment of newly diagnosed (ND) acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. There is scarce evidence for the use of VEN–AZA for relapsed or refractory (R/R) AML. We compared the outcome of 39 R/R AML and 38 ND AML patients treated between 01/20 and 12/21. The median age was 69 (22–86) and 73 (61–81) in the R/R and ND groups, respectively. Adverse cytogenetics were found in 36% of patients in the R/R group and 59% of patients in the ND group. Overall response rate was 37% in R/R AML, including 13% CR, 8% CRi, 3% PR and 13% MLFS, and 58% in the ND AML, including 32% CR, 13% CRi and 13% MLFS. Adverse cytogenetics was associated with treatment failure in the R/R group (Relative Risk = 0.13, p = 0.005). Median overall survival (OS) was 5.9 months in the R/R group and 9.4 months in the ND group. Median OS was 2.2 months in the adverse cytogenetics group versus 8.7 months in the intermediate cytogenetics group in the R/R group (p = 0.02). Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months), indicating that VEN–AZA can be an efficient salvage treatment for selected R/R AML patients. In conclusion, VEN–AZA is a promising treatment for ND AML and for selected R/R AML patients.