THE ASSOCIATION BETWEEN AMINOGLYCOSIDE EXPOSURE AND OTOTOXICITY IN CHILDREN WITH CYSTIC FIBROSIS.

INTRODUCTION: Pulmonary exacerbations increase the requirement of aminoglycoside (AG) antibiotics in people with cystic fibrosis (pwCF). Several studies have shown that AGs have a cumulative effect on ototoxicity. We aimed to investigate the relationship between AG exposure and ototoxicity by using three different methods in patients with CF. MATERIALS-METHODS: The multicenter study included 121 pwCF aged between 5-18 years with a history of parenteral AG exposure. Standard pure tone audiometry (sPTA), extended high frequency audiometry (EHF-PTA), and distortion-product otoacoustic emissions (DPOAE) tests were performed. Mitochondrial mutation analysis for m1555G>A was performed in 61 patients. RESULTS: Median age was 12.85 years and 52.1% (n=63) were male. 18.2% (n=22) of the patients had received parenteral AGs more than 5 courses/lifetime. Ototoxicity was detected in at least one of the tests in 56.2% (n= 68) of the patients. Only 10.7 % (n=13) of the patients had reported a symptom indicating ototoxicity. 30.3% (n=30) of the patients had ototoxicity in the low-exposure group while it was 45.5% (n=10) in the high-exposure group according to EHF-PTA (p>0.05). Median number of parenteral amikacin courses was significantly higher in the ototoxic group [2(1.25-5.75) vs 2(1-3); p=0.045]. No m1555A>G mutation was detected in 61 patients who screened for mitochondrial mutation analysis. CONCLUSION: As AG ototoxicity occurs primarily at high frequencies, EHF-PTA is important in early detecting otoxicity. EHF-PTA and DPOAE detected ototoxicity in some patients with normal PTA results. All pwCF with a history of AG exposure should be evaluated for hearing loss since symptoms may only be noticed in the late period.

Exploring Turkey's mosaic of novel variants and complex alleles in cystic fibrosis genetics.

BACKGROUNDS: Genetic variants in CF transmembrane conductance regulator (CFTR) gene causes cystic fibrosis (CF), a prevalent autosomal recessive disorder. More than 2000 variants in CFTR have been described as disease causative. This study aims to delineate the genotypic and phenotypic landscape of CF among people with CF (pwCF) followed at the largest CF center in Turkey. METHODS: We conducted a descriptive and retrospective analysis of 481 patients registered with the European CF Society Patient Registry and followed at Marmara University Selim Çöremen CF Center from 2015 onwards. Comprehensive CFTR analysis was utilized for genetic diagnosis. Besides the whole cohort, novel variants and complex alleles were also described. RESULTS: Our cohort exhibited a broad spectrum of CFTR variants, with 136 different variants detected, indicating substantial genetic diversity. The F508del variant was less prevalent in our cohort compared to US and European averages, which could reflect unique genetic and demographic characteristics of the Turkish population. Additionally, we identified nine novel variants in 12 alleles, which enhances the understanding of CF's genetic complexity in this region, and complex alleles in 32 pwCF. CONCLUSION: Our research underscores the heterogeneity of CFTR variants in Turkey and highlights the necessity for extensive genetic profiling particularly for diverse populations to provide effective personalized treatment strategies. It is crucial to understand the full spectrum of CFTR variants with the advent of CFTR modulators.

Assessment of patients' baseline cystic fibrosis knowledge levels following translation and adaptation of the CF R.I.S.E translation program into Turkish.

BACKGROUND: Cystic fibrosis (CF) patients have a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. The goal of this project was to introduce the transition program CF R.I.S.E (Responsibility. Independence. Self-care. Education.) to a CF center with limited resources at Marmara University (MU). METHODS: The program was adapted and translated into Turkish with the CF Foundation's permission. A team of experts collaborated to develop educational materials for patients and families. After translation and implementation of the CF S.O.B.E program, 11 Knowledge Assessment Questionnaire (KQA) tests were administered online to the patients aged between 16 and 25 years to assess the lack of patient knowledge. RESULTS: The CF R.I.S.E program was successfully implemented within 6 months. A pilot study showed positive feedback from randomly selected patients, indicating the program's effectiveness and understandability. The mean age of the patients was 19.4 ± 2.9 years, and 42 (52%) were female. The mean forced expiratory volume (FEV1pp) was 76.3 ± 23.2. Fourteen (17.3%) and 4 (4.9%) of the patients colonized with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. Fifteen (18.5%) were on modulator therapy. Eleven Knowledge Assessment Questionnaires (KAQ) surveys were administered to 81 patients. The percentage of correct responses to the KAQs ranged from 47.9% to 68.3%. CONCLUSION: MU CF Center in Turkey implemented the CF S.O.B.E (Responsibility, Self-care, Independence, and Education in Turkish) program. The center aims to make the program a regular practice and expand collaboration with adult clinics. Future studies will assess its long-term impact and applicability in different health settings. The final goal is to disseminate the program's resources and promote structured transition practices across the country.

Unveiling the Respiratory Muscle Strength in Duchenne Muscular Dystrophy: The Impact of Nutrition and Thoracic Deformities, Beyond Spirometry.

BACKGROUND/OBJECTIVES: Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, the predictability of upright-supine spirometry in terms of diaphragm involvement, and the impact of nutrition on muscle strength. METHODS: This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. The effects of the ambulatory status, kyphoscoliosis, chest deformity, and low BMI on respiratory parameters were investigated. RESULTS: Forty-four patients were included in the study. The mean patient age was 10.8 ± 2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and non-ambulatory patients (p < 0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with a low BMI than in those without (p < 0.05). CONCLUSIONS: To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for nutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

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.

Depression, anxiety, and sleep quality of caregivers of children with spinal muscular atrophy.

BACKGROUND: The aim of this study was to evaluate the prevalence of anxiety, depression, sleep, and associated factors in caregivers of children with spinal muscular atrophy (SMA). MATERIALS AND METHODS: Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory-State (STAI-S), the State-Trait Anxiety Inventory-Trait (STAI-T), and Pittsburgh Sleep Quality Index (PSQI) were used to assess the anxiety, depression, and sleep quality of the caregivers of children with SMA. Higher scores indicated worse outcome for all three questionnaires. RESULTS: Fifty-six caregivers of children with SMA were included in the study. Median age of children was 6 (3.2-10) years and mean age of the caregivers was 37.0 ± 6.5 years. Median scores of the BDI, STAI-S, STAI-T, and PSQI were 12 (7.2-17), 35.5 (31-44), 40.5 (35-48), and 7.0 (5.0-10.0), respectively. There was a positive correlation between BDI and PSQI scores (p < 0.05). There was a negative correlation between the age of the caregivers and PSQI, BDI, STAI-T scores (p = 0.01, r = -0.341; p = 0.006, r = -0.364; p = 0.003, r = -0.395, respectively). There was a negative correlation between the age of the patients and the PSQI scores of the caregivers (p = 0.01, r = -0.33). There was a negative correlation between BDI scores and household income (p = 0.01, r = -0.34). CONCLUSION: Caregivers of children with SMA had elevated depression and anxiety levels and they also had decreased sleep quality. Economic and social support resources are needed to help caregivers of those children.