Aytekin Idikut

Introduction: CFTR modulators have transformed Cystic Fibrosis (CF) care. However, their influence on CF-related diabetes (CFRD) and liver disease (CFLD) requires detailed evaluation. Methods: Among a cohort of 249 CF patients, 103 patients receiving modulator therapy were analyzed. Clinical data from the pre-treatment period and after at least 90 days of therapy were compared. Patients with CFRD (n=48) were evaluated for glycemic response. Hepatobiliary assessment included all patients on medication, with a specific focus on those exhibiting baseline ultrasonographic (US) findings such as hepatomegaly or splenomegaly. Liver fibrosis was monitored via non-invasive FIB-4 and APRI scores. Results: Modulator therapy significantly increased BMI [20.5 vs 22.1 kg/m², p<0.001] and FEV1% [64% vs 75%, p=0.005]. In the CFRD group, HbA1c showed a numerical decrease [6.7% vs 6.5%], with a significant reduction specifically in non-homozygous F508del patients (p=0.028). Regarding hepatobiliary status, significant increases were found in ALT [20 vs 26 U/L, p=0.028] and direct bilirubin [0.13 vs 0.20 mg/dL, p=0.005]. Platelet counts significantly decreased [244.5 vs 199.0 x10³/µL, p<0.001]. Consequently, both FIB-4 [0.51 vs 0.62, p=0.009] and APRI [0.25 vs 0.26, p=0.006] scores increased post-treatment. Interestingly, patients without baseline US findings exhibited a more significant increase in fibrosis markers (p=0.031) than those with preexisting involvement. Conclusion: CFTR modulators markedly improve nutritional outcomes but are associated with significant elevations in liver enzymes and non-invasive fibrosis markers. These results highlight the need for rigorous hepatobiliary monitoring, regardless of baseline US findings.

Frailty Enhances Prognostic Accuracy Compared to CURB-65 in Community-Acquired Pneumonia - European Journal of Geriatrics and Gerontology

Background and Objectives: Nutritional impairment and systemic inflammation contribute to disease progression and poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). The geriatric-nutritional-risk-index (GNRI) and prognostic-nutritional-index (PNI) are practical markers reflecting both nutritional and immune status. In elderly COPD patients, malnutrition-related exacerbations often worsen quality of life and increase hospitalization. Identifying reliable predictors of exacerbation risk is therefore important for improving disease management. This study evaluated the association between GNRI, PNI and exacerbation frequency across different age groups in COPD. Materials and Methods: This multicenter retrospective study included 302 patients with COPD from 10 medical centers. All patients were classified as GOLD Group-E according to exacerbation history. Demographic characteristics, pulmonary function tests, Charlson-Comorbidity-Index (CCI), pharmacological treatments, dyspnea scores, and annual exacerbation frequency were obtained from hospital databases. Laboratory parameters including complete blood count, C-reactive protein, albumin, and total protein were recorded. GNRI, PNI, and neutrophil-to-lymphocyte ratio (NLR) were calculated to evaluate nutritional and inflammatory status. Results: The mean age of participants was 67.9 ± 9.6 years and 26.5% were female. Elderly patients had significantly higher CCI scores, longer disease duration, greater cumulative smoking exposure, and more frequent exacerbations than younger patients (p < 0.001). Pulmonary function parameters were significantly lower in the elderly group, while long-term oxygen therapy and nebulizer use were more common (p < 0.001). Baseline and exacerbation NLR levels were higher in elderly patients, whereas GNRI and PNI values were lower during both stable disease and exacerbation periods. Patients with more than four exacerbations per year had significantly higher NLR and lower GNRI values. Conclusions: Elderly COPD patients in GOLD Group-E demonstrate marked inflammatory and nutritional burden. Lower PNI values were independently associated with increased annual exacerbation frequency, while lower GNRI values were observed in patients with greater inflammatory and nutritional burden. Routine immune-nutritional assessment may improve risk stratification and help identify patients who could benefit from early multidisciplinary management.

Background/Objectives: To elucidate the factors that contribute to individual variability in the progression of COVID-19, experiments on endothelial nitric oxide synthase polymorphisms have been reported. Nitric oxide synthase (NOS3) is located in the endothelium and is involved in the regulation of inflammation and vascular homeostasis. In this study, we investigated the association between COVID-19 severity and NOS3 G894T and NOS3 27-bp VNTR 4b/a genetic polymorphisms. Methods: Patients with COVID-19 (n = 178) were divided into Group 1 (mild disease) and Group 2 (severe disease) based on oxygen saturation levels in room air (Group 1, SpO₂ ≥ 93%, n = 107; and Group 2, SpO₂ < 93%, n = 73) and hospitalization requirements. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: Overall, genotype and allele frequencies of the NOS3 genetic polymorphisms were similar across the two study groups (p > 0.05). However, the subgroup analysis showed a notable trend for the 4b/4a allele distribution between Groups 1 and 2. In the younger subgroup of patients (≤50 years old) without chronic obstructive pulmonary disease, Group 2 tended to have a higher frequency of the 4b allele than Group 1 (97.4% vs. 85.4% p = 0.06) and a higher occurrence of 4b/4b genotype (94.7% vs. 74.0%, p = 0.05). Additionally, a rarely observed 4c allele was detected only in two subjects within Group 2 but not in Group 1. Conclusions: These findings suggest a trend of association between COVID-19 severity and NOS3 27-bp VNTR 4b/a genetic polymorphism. Genetic analysis may reveal patient susceptibility to disease, prognosis risk factors, and drug responsiveness.

Introduction: Cystic fibrosis transmembrane conductance regulator modulator therapies (CFTR‐MT) have altered management, reducing exacerbations and slowing pulmonary function decline. Nevertheless, it is still uncertain if the benefits of CFTR‐MTs last when they are stopped. This study aimed to assess pulmonary function changes, and exacerbation rates during and after CFTR‐MT use in adult cystic fibrosis patients. Methods: Between 2018 and 2022, we conducted a study involving adult CF patients who initially used CFTR‐MTs but later discontinued them due to reimbursement issues. The study was divided into three phases: predrug (T1), in‐drug (T2), and postdrug (T3). We recorded pulmonary function tests, laboratory and culture results, and the number of exacerbations. Results: The study involved 33 patients, with 28 (84.8%) receiving Elexacaftor/Tezacaftor/Ivacaftor and 5 (15.2%) receiving Ivacaftor. The median treatment and interruption durations were 3.1 (IQR = 2.9–5.7), and 2.5 (IQR = 1.5–4.0) months, respectively. The mean FEV1% was 54.3% (± 26.6), 70.4% (± 27.4), and 60.2% (± 26.5) during T1, T2, and T3, respectively ( p < 0.001). The mean FVC% was 65.5% (± 23.9) in T1, increased to 81.5% (± 24.5) in T2, and decreased to 71.6% (± 25.9) in T3 ( p < 0.001). The number of Psedomonas aeruginosa , and Aspergillus positive sputum cultures decreased significantly with drug use (T1: 72.7%, 39.4%; T2: 48.5%, 9.1%; T3: 45.5%, 18.2%; p = 0.014, p = 0.004, respectively). The median number of hospitalizations was 1.0 (0–5.0) in T1, 0 (0–0) in T2, and 0 (0–1.0) in T3. Conclusion: This study revealed that CFTR‐MTs are effective even in the short term for adult CF patients, but their beneficial effects quickly diminish after discontinuation. Real‐life data obtained as a result of discontinuation of drugs due to reimbursement problems has highlighted the significance of regular and uninterrupted use of modulators.

Introduction: Fibrothorax, characterized by the widespread thickening of the pleura, can develop as a result of several disorders and can be seen as a consequence of empyema. After a very long latent period, reactivation or infection may occur. Hemothorax, empyema, asbestos exposure, and tuberculosis are frequent etiologies. This can occur frequently with bronchopleural fistula or pleurocutaneous fistula. In our article, we will present a case with a stable lesion containing fluid between calcified pleural sheets for many years, but a fistula has not yet developed, and recurrent hospital admissions with vague clinical findings. Case presentation: A 96-year-old man patient was admitted due to experiencing difficulty in breathing. He has been diagnosed with hypertension and heart failure and does not have a history of regular drug usage. According to his medical records, he had pulmonary tuberculosis around 65 years ago. He has been experiencing a chronic cough, expectoration of mucus, and dyspnea for approximately two decades. He received oral antibiotic treatments, but as his symptoms began to improve, he did not attend follow-up appointments. Upon reviewing the patient’s past examinations, it was observed that thoracic CT scans conducted in 2010, 2022, and 2024 revealed the presence of pleural thickening, areas with fluid density, and calcifications in the right hemithorax. Additionally, areas with fluid density were consistently observed within the stable calcific mass lesion throughout this period. A close clinical monitoring protocol was instituted due to the patient’s refusal to undergo thoracentesis, stable lung imaging for 14, and normal acute phase reactants and sputum cultures. Conclusion: In chronic calcified pleurisy, which is evaluated in favor of sequelae in patients with appropriate history and clinical findings, the etiology should be clarified by informing the patients, and treatment options should be evaluated without further degrading the patient’s clinical.

Aim: The place of death is one of the indicators of the quality of end-of-life care, which has become an essential public health issue with the aging of the population and the increase in life expectancy. There is a lack of data regarding the location of deaths caused by chronic obstructive pulmonary disease (COPD), the third-leading cause of mortality worldwide. This retrospective, cross-sectional study aimed to investigate the places of death of patients with COPD in Turkey and their trends over the years.Methods: The study included patients who had a COPD International Classification of Diseases code in the hospital information system and were provided a medication report for this disease in a university hospital's chest diseases outpatient clinic between January 1, 2014, and December 31, 2021. The place and date of death were obtained from the death notification system and recorded as an in-hospital or out-of-hospital death.Results: A total of 1402 (77.3%) patients died in the hospital and 412 (22.7%) died outside the hospital, and when comparing the pandemic period and before, no significant difference was observed between the places of death. Sixty-three (49.6%) of 127 patients over the age of 90 years died outside the hospital, and a significant relationship was observed between advanced age and out-of-hospital mortality (P < 0.005).Conclusion: According to our findings, a substantial number of patients with COPD in Turkey die in hospitals. The insufficiency of nursing homes and lack of hospice care cause more hospital deaths. Our data are expected to guide the development of end-of-life care policies for patients with COPD in our country. Geriatr Gerontol Int 2023; center dot center dot: center dot center dot-center dot center dot.