Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still ...diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.
Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research ...aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (
= 23) and healthy tissues (
= 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (
= 225) and GTEx healthy donors' cohorts (
= 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (
< 0.001), LLGL1 (
= 0.0015), and SLC4A3 (
= 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (
= 0.0029) and LILRA5 (
= 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.
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.
Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline?
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).
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.
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.
ClinicalTrials.gov; No.: NCT04771923; URL: www.clinicaltrials.gov
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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.
Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline?
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).
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.
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.
ClinicalTrials.gov; No.: NCT04771923; URL: www.
gov.
A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, ...preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6 months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6 months after the change of therapy (visit 2). Following 6 months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (
p
< 0.001). Values in subjects enrolled into the patient assistance programme did not differ significantly from the values in subjects that were not (
p
= 0.399) except for the domain convenience (
p
= 0.026). This study demonstrates significantly higher satisfaction in patients who switched from the weekly bisphosphonate therapy regimen to monthly ibandronate in all observed aspects of treatment. Patients expressed preference for monthly bisphosphonate (ibandronate) in comparison with weekly bisphosphonates and found it to be a more convenient method of treatment. At the time of study, however, it was not known that the anti-fracture effect of ibandronate was smaller for hip fractures than with other bisphosphonates.
Maligni pleuralni mezoteliom rijetka je i agresivna primarna novotvorina mezotelnih stanica pleure. Glavni rizični čimbenik je izloženost azbestu, najčešće uz latenciju od 30–50 godina. Unatoč ...terapiji medijan preživljenja je od 4 do 18 mjeseci, ovisno o izvoru. Cilj istraživanja bio je odrediti karakteristike bolesnika oboljelih od malignoga pleuralnog mezotelioma te ishode njihova liječenja na KBC Zagreb u razdoblju od 1999. do 2012. godine. Ispitane su karakteristike 101 bolesnika dijagnosticiranog i liječenog na KBC Zagreb u razdoblju od rujna 1999. do rujna 2012. Analizirali smo ukupno preživljenje (OS), preživljenje bez progresije bolesti (PFS) te preživljenje ovisno o histološkom podtipu tumora, dobi, kliničkom stadiju, pleurodezi talkom i modalitetu liječenja. Koristili smo Kaplan-Meierovu metodu za izradu krivulje preživljenja. 89 bolesnika bilo je muškog, 12 ženskog spola, a medijan dobi 62 godine. Prema TNM klasifikaciji stadij IV je utvrđen kod 69,3%, stadij III kod 26,73%, te stadij II kod samo 3,96% bolesnika. 73,26% bolesnika imalo je epiteloidni, 4,95% sarkomatoidni, 1% mješoviti te 20,79% NOS (nespecifirani) histološki podtip bolesti. Kirurški je liječeno 14,85% bolesnika, kemoterapijom 55,44%, dok je radioterapija primijenjena kod 9,9% bolesnika. Medijan OS iznosi 11 mjeseci, dok je PFS 10 mjeseci. Prema histološkom podtipu medijan OS iznosio je 11 mjeseci za epiteloidni, 12,5 za NOS te 5,5 za sarkomatoidni, a prema kliničkom stadiju 7 mjeseci za stadij II, 17,5 mjeseci za stadij III te 11 mjeseci za stadij IV. Medijan OS bio je dulji u skupini bolesnika mlađoj od 65 godina (12 naspram 8,5 mjeseci, p=0.28), skupini sa učinjenom pleurodezom (13 naspram 7,5 mjeseci, p=0.06) te u skupini liječenoj kemoterapijom (12,5 naspram 7,5 mjeseci, p=0.10). Očekivano preživljenje bolesnika oboljelih od malignoga pleuralnog mezotelioma u Republici Hrvatskoj u skladu je s podatcima iz literature. Ispitane metode liječenja relativno skromno utječu na preživljenje bolesnika.
The interplay between purinergic receptors as well as pattern recognition receptors like Toll-like receptors (TLRs) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) might have a role in ...the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine and compare the concentrations of the damage-associated molecular patterns (DAMPs) heat shock protein 70 (Hsp70) and adenosine triphosphate (ATP), and gene expression of their respective receptors as well as NLRP3 inflammasome-related molecules in the peripheral blood of patients with end-stage COPD before and 1 year after lung transplantation (LT). Lung function was assessed by spirometry and diffusion capacity for carbon monoxide (DLCO). Quantitative polymerase chain reaction (qPCR) was applied for detection of TLR2, TLR4, P2X7R, P2Y2R, IL1B, CASP1, and NLRP3 expression. High-sensitivity ELISA kits were used for extracellular (e) Hsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in the plasma of end-stage COPD patients and significantly decreased after LT. In addition, TLR4, P2Y2R, IL1B, CASP1, and NLRP3 expression was up-regulated in COPD patients before LT, while it was significantly suppressed after LT. In conclusion, it could be assumed that NLRP3 inflammasome is activated in the peripheral blood of end-stage COPD patients and that eHsp70 and eATP could be responsible for its activation through triggering their receptors. On the other hand, previously enhanced pro-inflammatory reactions seem to be suppressed to the healthy population levels in lung recipients without allograft rejection.
Summary
Background
The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors ...for developing NTM pulmonary disease (NTM-PD) in this setting.
Methods
We conducted a retrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records.
Results
Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (
n
= 137) or no disease (
n
= 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was a significant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23
p
= 0.003).
Conclusion
The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.
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