Beyond the 10%: Unraveling the genetic diversity in Turkish cystic fibrosis patients not eligible for CFTR modulators.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by variants of CFTR gene. Over 2000 variants have been identified, and new drugs called CFTR modulators have been developed to target specific defects in the CFTR protein. However, these drugs are only suitable for patients with certain variants of CFTR, and eligibility rates vary depending on race and geographical region. This study aimed to reveal the detailed genotype and clinical characteristics of people with CF (pwCF) at our center in Turkey, a developing country, who are not eligible for CFTR modulators. METHODS: A total of 445 pwCF followed up at Marmara University were reviewed retrospectively. Variants of the patients ineligible to CFTR modulators were classified based on American College of Medical Genetics guidelines, CFTR classification, the change in the encoded protein, and the variant type. RESULTS: The study revealed that 139 (31.2%) patients weren't eligible for CFTR modulators. There were 60 different variants in the 276 alleles, as two were missing. The majority of patients had missense or nonsense variants, and that the most common variant was c.1545_1546del, which can be said unique to this geography. CONCLUSION: The study highlights the importance of detecting the variants of ineligible patients in detail to guide future approaches for more targeted and effective interventions in CF care. Testing the effectiveness of CFTR modulators for rare or newly occurring variants is crucial to ensure equal access for pwCF to these therapies from different racial backgrounds and ethnic minorities.

Implementation of a high fidelity simulation based training program for physicians of children requiring long term invasive home ventilation: a study by ISPAT team.

Introduction: The number of children requiring long-term invasive home ventilation (LTIHV) has increased worldwide in recent decades. The training of physicians caring for these children is crucial since they are at high risk for complications and adverse events. This study aimed to assess the efficacy of a comprehensive high-fidelity simulation-based training program for physicians caring for children on LTIHV. Methods: A multimodal training program for tracheostomy and ventilator management was prepared by ISPAT (IStanbul PAediatric Tracheostomy) team. Participants were subjected to theoretical and practical pre-tests which evaluated their knowledge levels and skills for care, follow-up, and treatment of children on LTIHV. Following the theoretical education and hands-on training session with a simulation model, theoretical and practical post-tests were performed. Results: Forty-three physicians from 7 tertiary pediatric clinics in Istanbul were enrolled in the training program. Seventy percent of them had never received standardized training programs about patients on home ventilation previously. The total number of correct answers from the participants significantly improved after the theoretical training (p < 0.001). The number of participants who performed the steps correctly also significantly increased following the hands-on training session (p < 0.001). All of the 43 participants who responded rated the course overall as good or excellent. Conclusion: The knowledge and skills of clinicians caring for children on LTIHV can be enhanced through a comprehensive training program consisting of theoretical training combined with hands-on training in a simulation laboratory.

An unusual case of childhood sarcoidosis: Un caso clínico infrecuente / Sarcoidosis infantil

Sarcoidosis is a systemic granulomatous disease of unknown etiology that may affect many systems, mainly lungs. Most of the patients present at stages I and II lung involvement. Pulmonary infltrates without hilar lymphadenopathy (state III) rarely occurs. Extrapulmonary organ involvement is common in pediatric sarcoidosis. The aim of this report is to present an unusual case of childhood sarcoidosis with stage III lung involvement without any extrapulmonary organ involvement. A 7-year-old girl presented with the complaints of malaise, fatigue, weight loss and dyspnea. There was patchy, bilateral ground glass view at high resolution computer tomography. Video assisted thoracoscopic lung biopsy was performed and histopathological examination showed nonnecrotising epitheloid-cell granulomas with giant cells. She did not have any hilar or extrapulmonary organ involvement and pulmonary sarcoidosis at stage III was diagnosed. Sarcoidosis should be considered in the differential diagnosis of children with interstitial lung disease.

La sarcoidosis es una enfermedad granulomatosa sistémica de etiología desconocida que puede afectar varios órganos, principalmente el pulmón. La mayoría de los pacientes presentan estadios I y II de compromiso pulmonar. Los infltrados pulmonares, sin linfadenopatías hiliares (estadio III), son infrecuentes. El compromiso de órganos extrapulmonares es común en la sarcoidosis infantil. El objetivo es presentar un caso infrecuente de sarcoidosis infantil con compromiso pulmonar en estadio III sin afectación de los órganos extrapulmonares. Una niña de 7 años consultó por malestar general, fatiga, pérdida de peso y disnea. En la tomografía computarizada de alta resolución se observó un infltrado bilateral de tipo esmerilado. Se realizó una biopsia pulmonar por videotoracoscopia. La histopatología mostró granulomas no necrosantes de células epitelioides con células gigantes. No había compromiso hiliar ni de otros órganos, por lo que el diagnóstico fue de sarcoidosis en estadio III. La sarcoidosis debe considerarse en el diagnóstico diferencial de los niños con enfermedad intersticial pulmonar.

An unusual case of childhood sarcoidosis: an unusual clinical case / An unusual case of childhood sarcoidosis: an unusual clinical case.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that may affect many systems, mainly lungs. Most of the patients present at stages I and II lung involvement. Pulmonary infltrates without hilar lymphadenopathy (state III) rarely occurs. Extrapulmonary organ involvement is common in pediatric sarcoidosis. The aim of this report is to present an unusual case of childhood sarcoidosis with stage III lung involvement without any extrapulmonary organ involvement. A 7-year-old girl presented with the complaints of malaise, fatigue, weight loss and dyspnea. There was patchy, bilateral ground glass view at high resolution computer tomography. Video assisted thoracoscopic lung biopsy was performed and histopathological examination showed nonnecrotising epitheloid-cell granulomas with giant cells. She did not have any hilar or extrapulmonary organ involvement and pulmonary sarcoidosis at stage III was diagnosed. Sarcoidosis should be considered in the differential diagnosis of children with interstitial lung disease.