Risk factors and severity of functional impairment in long COVID: a single-center experience in Croatia.

AIM: To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID. METHODS: The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS). RESULTS: The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID. CONCLUSION: Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.

Ruxolitinib as monotherapy in a patient with anaplastic lymphoma kinase positive lung adenocarcinoma.

We present unusual treatment outcome in a 59-year-old male diagnosed with metastatic lung adenocarcinoma with a very good response to ruxolitinib as monotherapy. In June 2017, this patient was diagnosed with myeloproliferative neoplasm - Janus-associated kinases 2 positive - and in December 2017 ruxolitinib therapy was started. At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis. Because of partial regression of tumor size noted on the computed tomography (CT) scans during tumor investigation, we did not apply any therapy for lung adenocarcinoma. A follow-up CT scan done in March 2018 showed further size reduction of tumor lesion in lower left lobe (91%), while follow-up CT scan done in June 2018 showed further size reduction of tumor lesion in lower right lobe (82%).

Tracheal complications of mechanical ventilation for COVID-19: a plot twist for survivors.

Tracheal complications should be suspected in mechanically ventilated COVID-19 survivors with respiratory symptoms. Treatment requires a multimodal approach of interventional bronchoscopy and surgery with tight follow-up due to a high rate of restenosis. https://bit.ly/3iw05xQ.

Tranexamic Acid vs Adrenaline for Controlling Iatrogenic Bleeding During Flexible Bronchoscopy: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are limited. RESEARCH QUESTION: Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline? STUDY DESIGN AND METHODS: We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 ° C, 5 mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe). RESULTS: A total of 2,033 FBs were performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline arm and 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 ± 1.3 [n = 1.8 ± 0.8]; TXA: mean VAS score, 5.3 ± 1.4 [n = 1.8 ± 0.8]). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P = .008 and P = .012, respectively) and required more applications for severe bleeding (3.0 ± 0 and 2.4 ± 0.5, respectively) than moderate bleeding (1.7 ± 0.8 and 1.7 ± 0.8, respectively) control (P = .006 and P = .002, respectively). We observed no drug-related adverse events in either group. INTERPRETATION: We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04771923; URL: www. CLINICALTRIALS: gov.

Efficacy and safety of nintedanib and docetaxel in patients with previously treated lung non-squamous non-small cell lung cancer: a multicenter retrospective real-world analysis.

BACKGROUND: The standard first-line systemic treatment for patients with non-oncogene addicted advanced nonsquamous non-small cell lung cancer (NSCLC) is immunotherapy with immune checkpoint inhibitors (ICI) and/or chemotherapy (ChT). Therapy after failing ICI +/- ChT remains an open question, and docetaxel plus nintedanib represent a valid second line option. PATIENTS AND METHODS: A multicenter retrospective trial of real-life treatment patterns and outcomes of patients with advanced lung adenocarcinoma treated with docetaxel plus nintedanib after the failure of ICI and/or ChT was performed. Patients from 2 Slovenian and 1 Croatian oncological center treated between June 2014 and August 2022 were enrolled. We assessed objective response (ORR), disease control rate (DCR), median progression free survival (PFS), median overall survival (OS), and safety profile of treatment. RESULTS: There were 96 patients included in the analysis, with ORR of 18.8%, DCR of 57.3%, median PFS of 3.0 months (95% CI: 3.0-5.0 months), and a median OS of 8.0 months (95% CI: 7.0-10.0 months). The majority of patients (n = 47,49%) received docetaxel plus nintedanib as third-line therapy. The ORR for this subset of patients was 19.1%, with a DCR of 57.4%. The highest response rate was observed in patients who received second-line docetaxel plus nintedanib after first-line combination of ChT-ICI therapy (n = 24), with an ORR of 29.2% and DCR of 66.7% and median PFS of 4.0 months (95% CI: 3.0-8.0 months). Fifty-three patients (55.2%) experienced adverse events (AEs), most frequently gastrointestinal; diarrhea (n = 29, 30.2%), and increased liver enzyme levels (n = 17, 17.7%). CONCLUSIONS: The combination of docetaxel and nintedanib can be considered an effective therapy option with an acceptable toxicity profile for patients with advanced NSCLC after the failure of ICI +/- ChT.

Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

AIM: Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities. CASE PRESENTATION: During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism. CONCLUSION: Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

Cancer-related inflammation as predicting tool for treatment outcome in locally advanced and metastatic non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer deaths and the non-small cell lung cancer (NSCLC) represents 80% of all cases. In most cases when diagnosed, it is in locally advanced or metastatic stage, when platinum based doublet chemotherapy is the established therapeutic option for majority of the patients. Predictive factors to filter the patients who will benefit the most from the chemotherapy are not clearly defined. Objective of this study was to explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen and their interaction, for the response to the frontline chemotherapy. METHODS: In this retrospective cohort study 170 patients with locally advanced and metastatic NSCLC were included. Relationship between baseline level of CRP and fibrinogen and response to the frontline chemotherapy was assessed. RESULTS: We found that pre-treatment CRP and fibrinogen values were statistically significantly correlated. Chemotherapy and CRP, fibrinogen, and their interaction were independently significantly associated with disease control rate at re-evaluation. There was statistically significant difference in median pre-treatment CRP level between the patients with disease control or progression at re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman technique we found that in patients with initial fibrinogen value below 3.5 g/L, CRP level was significantly associated with disease control or progression of the disease. Above this fibrinogen value the association of CRP and disease control was lost. CONCLUSIONS: The findings from this study support the growing evidence of inflammation and cancer relationship, where elevated pre-treatment level of CRP has negative predictive significance on the NSCLC frontline chemotherapy response.

Talc pleurodesis improves survival of patients with malignant pleural effusions: case-control study.

AIM: The aim of this study is to investigate whether there was a considerable difference in the survival of patients with malignant pleural effusion (MPE) depending on the pleural effusion treatment option. METHODS: One hundred and seven patients with proven MPE (metastatic lung and breast cancer) were included in the retrospective study. Fifty six patients were treated with talc pleurodesis and a control group of 51 patients with similar characteristics (in age, sex and disease) were treated with serial thoracentesis. The patients of both groups underwent chemotherapy and/or radiotherapy. The overall survival and the survival in subgroups of patients with different tumour types and different performance status (PS) equal 1, 2 and 3 were compared. RESULTS: The patients who underwent talc pleurodesis had a longer average survival interval (MS) than the patients without such a treatment (n = 56; MS = 21,5 and n = 51; MS = 9 weeks, respectively; p < 0.001). The best results were achieved in patients with PS 1 (n = 16; MS = 35.5 and n = 10; MS = 11 weeks in the groups with and without talc pleurodesis, respectively; p < 0,001) and PS 2 (n = 27; MS = 21 and n = 30; MS = 10 weeks in the groups with and without talc pleurodesis, respectively; p < 0.001), whereas talc pleurodesis was not effective in PS 3 patients (n = 13; MS = 10 and n = 11; MS = 7 weeks in the groups with and without talc pleurodesis, respectively; p = 0.08). Patients with the breast cancer showed a longer average survival interval after pleurodesis than those with the lung cancer (n = 12; MS = 37.5 and n = 4; MS = 20 weeks in the group with the breast cancer and with the lung cancer, respectively; p < 0.001), whereas the median survival was not significantly different between those patients without pleurodesis (n = 10; MS = 10 and n = 41; MS = 9 weeks in the group with the breast cancer and lung cancer, respectively; p = 0.11). CONCLUSION: The patients treated with talc pleurodesis had a significantly longer average survival than the patients without such a treatment, especially in the group with the breast cancer and in groups with better performance status. This may indicate that talc pleurodesis, apart from its symptomatic effect on the cessation of pleural effusion, may have a direct antitumour effect as well.

Serum leptin and skeletal differences between obese and non-obese patients with chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) affects body composition, adipokine secretion, and skeletal integrity. The aim was to determine the association between leptin, body mass (BM) and body composition parameters - fat mass (FM) and fat mass index (FMI), lean tissue mass (LTM), lean tissue mass index (LTMI) and bone mineral density (BMD) in 67 male COPD patients. METHODS: BM, body composition and biochemical indicators were measured or calculated using standard methods. Data were analyzed according to groups: non-obese (N = 48, BMI 21.0-29.9 kg/m(2)) and obese (N = 19, BMI ≥ 30.0 kg/m(2)). RESULTS: In the non-obese group statistically significant correlations were observed: negative ones of age with most BMD T scores, positive ones of BMI with all T scores, FM, FMI, LTMI and leptin, of FMI with leptin and all T scores, and of LTMI with most T scores. In the obese group also statistically significant correlations were found: positive ones of BMI with FMI, LTM, leptin and T scores (trochanter, total hip); of FMI with leptin; and of leptin with total hip T score. CONCLUSION: A positive relationship between FMI and BMD was found only in non-obese but not in obese COPD patients. Leptin concentration was associated positively with the total hip T score only in obese COPD patients, suggesting its protective role on the skeleton of obese COPD patients.

A novel AAAS gene mutation (p.R194X) in a patient with triple A syndrome.

OBJECTIVE: The clinical and molecular data of a patient with triple A syndrome are reported. PATIENT: A 21-year-old male who was diagnosed for adrenal insufficiency at the age of 2 years after a severe attack of adrenal crisis. At the age of 4 years, achalasia and alacrima were diagnosed. Puberty started at the age of 17 years. At the same time, symptoms of central, peripheral, and autonomic nervous system dysfunction were noted. Later on, at the age of 20 years, a bone age delay of 6 years and severe osteoporosis was diagnosed. RESULTS: A compound heterozygous AAAS mutation consisting of two mutations was found: a C > T transition in exon 7 resulting in a change of arginine at amino acid position 194 into a stop codon (Arg194X) at one allele, and a C > T transition in exon 12 resulting in a change of glutamine at amino acid position 387 into a stop codon (Gln387X) on the other allele. CONCLUSION: The mutation in exon 7 (p.R194X) of the AAAS gene is a novel mutation which has not been found in any other family so far, whereas the second was already found in some other families. This case adds to the clinical and molecular spectrum of triple A syndrome and may provide a new insight into the functions of AAAS gene.