Improved nutritional outcomes and gastrointestinal symptoms in adult cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor.

INTRODUCTION: CFTR modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with CF on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only one patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 µg/g to 442.1 µg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). CONCLUSION: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

Next-generation sequencing in children with epilepsy: The importance of precise genotype-phenotype correlation.

AIM: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. METHODS: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed. RESULTS: Out of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype-phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype-phenotype correlation. INTERPRETATION: We emphasize a complex genotype-phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.

Impulsivity in patients with borderline personality disorder: a comprehensive profile compared with healthy people and patients with ADHD.

BACKGROUND: Impulsivity is a core symptom of borderline personality disorder (BPD). Impulsivity is a heterogeneous concept, and a comprehensive evaluation of impulsivity dimensions is lacking in the literature. Moreover, it is unclear whether BPD patients manifest impaired cognitive functioning that might be associated with impulsivity in another patient group, such as ADHD, a frequent comorbidity of BPD. METHODS: We tested 39 patients with BPD without major psychiatric comorbidities and ADHD, 25 patients with ADHD, and 55 healthy controls (HC) using a test battery consisting of a self-report measure of impulsivity (UPPS-P questionnaire), behavioral measures of impulsivity - impulsive action (Go/NoGo task, stop signal task) and impulsive choice (delay discounting task, Iowa gambling task), and standardized measures of attention (d2 test), working memory (digit span), and executive functioning (Tower of London). RESULTS: Patients with BPD and ADHD, as compared with HC, manifested increased self-reported impulsivity except sensation seeking and increased impulsive choice; patients with ADHD but not BPD showed increased impulsive action and deficits in cognitive functioning. Negative urgency was increased in BPD as compared to both HC and ADHD groups and correlated with BPD severity. CONCLUSIONS: Patients with BPD without ADHD comorbidity had increased self-reported impulsivity and impulsive choice, but intact impulsive action and cognitive functioning. Controlling for ADHD comorbidity in BPD samples is necessary. Negative urgency is the most diagnostically specific impulsivity dimension in BPD.

Causes of Intensive Care Unit Admissions in Children with SARS-CoV-2: A Single-Centre Observational Study.

Background: The proportion of intensive care unit (ICU) admissions in children that have and have not been directly caused by SARS-CoV-2 remains unclear. The aim of the study is to analyse a cohort of children admitted to the ICU with SARS-CoV-2 and determine whether the infection was the primary cause of their hospitalisation, a significant contributor, a suspected accomplice, or an incidental finding. Methods: This was a retrospective observational study of all the children admitted to the ICU with SARS-CoV-2 from March 2020 to February 2022 from the South Moravia region. The aim of the study was to assess whether the hospitalisation was likely to be directly caused by the virus (i.e., patients with acute COVID-19; the COVID group), whether the virus was a significant contributor to the hospitalisation (i.e., patients with multisystem inflammatory syndrome in children due to COVID-19; the MIS-C group), whether it may have contributed to the worsening of their underlying disease (the WORSENING group), or whether it was an incidental finding very likely unrelated to hospitalisation where SARS-CoV-2 positivity merely placed patients in the COVID-19 unit (the ISOLATION group). The groups were compared using a series of secondary outcomes. Results: The study population represented 150 paediatric ICU cases (age 8.6; IQR 3.5−13.3 years), with 66.7% being male. The COVID group represented 32.7% of cases (49/150); MIS-C, 30% (45/150); WORSENING, 14.7% (22/150); and ISOLATION, 22.7% (34/150). The median length of hospitalisation was found for the MIS-C group (11 days; 9 days in the ICU), the COVID group (6 days; five days in the ICU), WORSENING group (4.5 days; 4.5 days in the ICU) and the ISOLATION group (5.5 days; 3.5 days in the ICU), where the difference was significant (p < 0.001). Asymptomatic and mild cases were most common in the WORSENING (36.4% and 63.6%) and ISOLATION (52.9% and 44.1%) groups. Severe and critical cases were only present in the COVID (6.1% and 12.2%) and MIS-C (4.4% and 11.1%) groups; the severity difference was significant (p < 0.001). The groups did not differ significantly in the proportion of complete recovery and short- and long-term sequelae (p = 0.09). Conclusions: Patients with acute COVID-19 accounted for one-third of all ICU admissions, patients with MIS-C accounted for approximately another third, patients with worsening underlying disease accounted for 15%, and patients with incidental findings of SARS-CoV-2 positivity accounted for one-fifth of ICU admissions. A more significant disease was seen with acute COVID-19 and MIS-C.