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.

Accessory cardiac bronchus with associated lung parenchyma: rare congenital tracheobronchial anomaly.

Accessory cardiac bronchus (ACB) has been described mainly as case reports finding (frequency 0.08%-0.39%). Even though 50% of all ACBs have a blind extremity, imaging studies have demonstrated that some develop into a series of bronchioles with cystic degeneration or a ventilated lobule demarcated by an anomalous fissure and extremely rare with an abnormal pulmonary artery. In this case, ACB was demonstrated on several imaging methods arising from the intermediate bronchus's medial wall with correspondent blood vessels and fissure. Although an ACB is not a pathological entity and most patients with ACB are asymptomatic, it can become symptomatic due to recurrent infection, empyema, hemoptysis, and malignant transformation.  In conclusion, both pulmonologists and radiologists should recognize normal bronchial anatomy and developmental bronchial anomalies, as these may be important to establish a correct diagnosis.

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.

Influence of deep-freezing and MGG staining on DNA and RNA quality in different types of lung adenocarcinoma cytological smears.

BACKGROUND: Preserving the optimal quality of DNA and RNA is mandatory for molecular testing in lung adenocarcinoma cytological smears (LACSs). METHODS: DNA and RNA were isolated from 90 frozen unstained and 46 May Grünwald Giemsa (MGG) stained LACSs prepared from bronchial washing (BW), bronchial brushing (BB), and pleural effusion (PE) samples during 3 years. Concentrations of nucleic acids in all LACSs were assessed by spectrophotometric analysis. Fragmentation of DNA and RNA was determined by PCR amplification of selected genes. Amplicons of 100, 200, 300, 400, and 600 bp were used for DNA and 108 bp-long HPRT1 transcript fragment for RNA fragmentation analysis. RESULTS: Among 90 frozen LACSs, significantly lower DNA concentrations of BB and RNA concentrations of BW samples frozen for 6-10 months were observed in comparison with samples frozen for longer periods (p < .05). Among 46 paired LACSs, 44 (95.7%) frozen and 15 (32.6%) MGG-stained samples showed 600 bp-long DNA amplicons. Statistically significant difference (p < .05) in the fragmentation of DNA between frozen and MGG-stained LACSs was observed (p < .05), with DNA being less fragmented in frozen LACSs. In addition, 33 (71.7%) frozen and 36 (78.2%) MGG-stained LASCs showed HPRT1 gene amplicon of 108 bp. RNA was less fragmented in 3-year old MGG-stained samples than in LACSs frozen for 3 years. CONCLUSION: DNA and RNA extracted from frozen and MGG-stained LACSs showed different results depending on the time of storage and/or type of samples, but in general all samples had adequate quantity and quality for downstream molecular testing.

The Power of Transformation and the Leadership Supporting It - Including Mental Health Perspective.

World in which we live in, has been changing so unpredictably in the recent years that has become more than ever volatile, uncertain, complex and ambiguous (VUCA) world. Especially in this post Covid-19 era in which extreme change has becomes our constant, economies around the world are suffering and today's organizations and institutions are broken. We can agree that our current approach is not working. Leadership in general and leaders of global mental health institutions in particular are failing on their goals and we have desperate need for better leaders and leadership strategies in the future. In this article, authors are going to take a dive on the leadership perspective, transformation of organizations and institutions and try to narrow the gap and support leaders to become the best version of themselves. We are going to present our perspective on what is the future bringing us in terms of leadership and leaders, as well as what would be the desired team dynamic within organizations or institutions.

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%).

Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations.

BACKGROUND: Carbohydrate sulfotransferases (CHST) were shown to be involved in carcinogenesis. The aim of the study was to assess the diagnostic value of serum CHST7 concentration in differentiation between lung cancer and non-malignant pulmonary inflammations. METHODS: Clinical case-control study involving 125 participants was conducted: the control group containing cases of pneumonia and chronic obstructive pulmonary disease was compared to the lung cancer group composed of primary and metastatic cancers. Serum concentrations of CHST7 and routinely used markers including carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for each participant using immunochemical methods. Statistical association, receiver operating characteristic (ROC) analysis and cross-validation were used for the evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker panel. RESULTS: In comparison to the control group, serum CHST7 was elevated in lung cancer (p<0.001), but no differences between the overall stages of primary cancers were detected (p=0.828). The differentiation performance in terms of ROC area under curve (AUC) was 0.848 making CHST7 superior biomarker to the NSE (p=0.031). In comparison to CEA and CYFRA 21-1, the performance differences were not detected. CHST7 was not correlated to other biomarkers, and its addition to the routine biomarker panel significantly improved the cross-validated accuracy (85.6% vs. 75.2%) and ROC AUC (p=0.004) of the differentiation using a machine learning approach. CONCLUSIONS: Serum CHST7 is a promising biomarker for the differentiation between lung cancer and non-malignant pulmonary inflammations.

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.