TMEM244 Is a Long Non-Coding RNA Necessary for CTCL Cell Growth.

Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular processes. To date, the expression of the TMEM244 protein has not been experimentally confirmed, and its function has not been clarified. Recently, the expression of the TMEM244 gene was acknowledged to be a diagnostic marker for Sézary syndrome, a rare cutaneous T-cell lymphoma (CTCL). In this study, we aimed to determine the role of the TMEM244 gene in CTCL cells. Two CTCL cell lines were transfected with shRNAs targeting the TMEM244 transcript. The phenotypic effect of TMEM244 knockdown was validated using green fluorescent protein (GFP) growth competition assays and AnnexinV/7AAD staining. Western blot analysis was performed to identify the TMEM244 protein. Our results indicate that TMEM244 is not a protein-coding gene but a long non-coding RNA (lncRNA) that is necessary for the growth of CTCL cells.

Time-Resolved Fluorescence Spectroscopy of Blood, Plasma and Albumin as a Potential Diagnostic Tool for Acute Inflammation in COVID-19 Pneumonia Patients.

Fluorescence lifetime measurements of blood or plasma offer valuable insights into the microenvironment and molecular interactions of fluorophores, particularly concerning albumin. Neutrophil- and hypoxia-induced oxidative stress in COVID-19 pneumonia patients leads to hyperinflammation, various oxidative modifications of blood proteins, and potential alterations in the fluorescence lifetime of tryptophan-containing proteins, especially albumin. The objective of this study was to investigate the efficacy of time-resolved fluorescence spectroscopy of blood and plasma as a prompt diagnostic tool for the early diagnosis and severity assessment of COVID-19-associated pneumonia. This study examined a cohort of sixty COVID-19 patients with respiratory symptoms. To investigate whether oxidative stress is the underlying cause of the change in fluorescence lifetime, human serum albumin was treated with chloramine T. The time-resolved spectrometer Life Spec II (Edinburgh Instruments Ltd., Livingston, UK), equipped with a sub-nanosecond pulsed 280 nm diode, was used to measure the fluorescence lifetime of blood and plasma. The findings revealed a significant reduction in the fluorescence lifetime of blood (diluted 200 times) and plasma (diluted 20 times) at 360 nm in COVID-19 pneumonia patients compared with their respective values recorded six months post-infection and those of healthy individuals. Significant negative correlations were observed between the mean fluorescence lifetime of blood and plasma at 360 nm and several severity biomarkers and advanced oxidation protein products, while a positive correlation was found with albumin and the albumin-globulin ratio. The time-resolved fluorescence spectroscopy method demonstrates the potential to be used as a preliminary screening technique for identifying patients who are at risk of developing severe complications. Furthermore, the small amount of blood required for the measurements has the potential to enable a rapid fingerstick blood test.

The Impact of COVID-19 on Cellular Factors Influencing Red Blood Cell Aggregation Examined in Dextran: Possible Causes and Consequences.

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.

Aptamers-Diagnostic and Therapeutic Solution in SARS-CoV-2.

The SARS-CoV-2 virus is currently the most serious challenge to global public health. Its emergence has severely disrupted the functioning of health services and the economic and social situation worldwide. Therefore, new diagnostic and therapeutic tools are urgently needed to allow for the early detection of the SARS-CoV-2 virus and appropriate treatment, which is crucial for the effective control of the COVID-19 disease. The ideal solution seems to be the use of aptamers-short fragments of nucleic acids, DNA or RNA-that can bind selected proteins with high specificity and affinity. They can be used in methods that base the reading of the test result on fluorescence phenomena, chemiluminescence, and electrochemical changes. Exploiting the properties of aptamers will enable the introduction of rapid, sensitive, specific, and low-cost tests for the routine diagnosis of SARS-CoV-2. Aptamers are excellent candidates for the development of point-of-care diagnostic devices and are potential therapeutic tools for the treatment of COVID-19. They can effectively block coronavirus activity in multiple fields by binding viral proteins and acting as carriers of therapeutic substances. In this review, we present recent developments in the design of various types of aptasensors to detect and treat the SARS-CoV-2 infection.

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences.

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.

Generation of Inducible BCL11B Knockout in TAL1/LMO1 Transgenic Mouse T Cell Leukemia/Lymphoma Model.

The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.

Hypomethylation of the promoter region drives ectopic expression of TMEM244 in Sézary cells.

Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) characterized by the presence of circulating malignant CD4+ T cells (Sézary cells) with many complex changes in the genome, transcriptome and epigenome. Epigenetic dysregulation seems to have an important role in the development and progression of SS as it was shown that SS cells are characterized by widespread changes in DNA methylation. In this study, we show that the transmembrane protein coding gene TMEM244 is ectopically expressed in all SS patients and SS-derived cell lines and, to a lower extent, in mycosis fungoides and in a fraction of T-cell lymphomas, but not in B-cell malignancies and mononuclear cells of healthy individuals. We show that in patient samples and in the T-cell lines TMEM244 expression is negatively correlated with the methylation level of its promoter. Furthermore, we demonstrate that TMEM244 expression can be activated in vitro by the CRISPR-dCas9-induced specific demethylation of TMEM244 promoter region. Since both, TMEM244 expression and its promoter demethylation, are not detected in normal lymphoid cells, they can be potentially used as markers in Sézary syndrome and some other T-cell lymphomas.

Analysis of the level of selected parameters of inflammation, circulating immune complexes, and related indicators (neutrophil/lymphocyte, platelet/lymphocyte, CRP/CIC) in patients with obstructive diseases.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder of the airways. An important element of COPD assessment is the evaluation of immune mechanisms involved in non-specific and specific response to ongoing inflammation. AIM OF THE STUDY: To evaluate the level of selected inflammatory and immunological parameters in patients with COPD, including C-reactive protein (CRP) and circulating immune complexes (CIC), as well as CRP/CIC index. MATERIAL AND METHODS: The study group consisted of 49 patients with obstructive pulmonary diseases (COPD, asthma, and asthma-COPD overlap syndrome) hospitalised in the Department of Pulmonary Diseases, Kuyavian-Pomeranian Pulmonology Centre in Bydgoszcz. Patients with COPD were divided into two subgroups, taking into account the severity of the disease according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; stages B and D). The control group consisted of 30 healthy persons. Levels of CIC were determined by the method of Hasková, and the concentration of CRP in serum by the standard immunoturbidimetric method. RESULTS: The median values of examined parameters (neutrophils, lymphocytes, platelets, neutrophil/lymphocyte ratio - NLR, platelet/lymphocyte ratio - PLR, CRP, CIC, and CRP/CIC index) were significantly higher among patients with obstructive diseases than in the control group. A tendency towards higher lymphocyte count, CRP, and CRP/CIC index in COPD stage D, compared to stage B, was observed. CONCLUSIONS: Based on our results, we suggest that the role of non-specific inflammatory mechanisms may increase in more advanced COPD stages (D), compared to less advanced stages (B).

[Smoking habit among parents of kids with respiratory system allergies during 10 years observation].

Allergies of the respiratory system are very often at children and are a global problem and still increasing. Passive smoking may predispose to allergies. Assuming that anti-smoking education conducted among of the children's parents during each control visit to the Allergy Clinic affects the behavior of the parents, we decided to analyze its effectiveness. Materials and Methods: The study comprised parents of 946 children at the Allergy Clinic, who were diagnosed and treated in years 2005-2014. The anti-nicotine education was applied by whole period of observation during routine medical visits. The outcome of an anti-smoking education achieved nearly 70 % efficiency. Results: Anti-nicotine education of the children's parents diseased on chronic allergic diseases of respiratory system is very good restrictive agent their exposition on smoking the tobacco. Contemporaneously in eftective way influences on decisions of adults about cessation smoking and the healthy style ot life promotes.

Submicroscopic genomic rearrangements change gene expression in T-cell large granular lymphocyte leukemia.

OBJECTIVES: To better understand the molecular pathogenesis of T-cell large granular lymphocyte leukemia (T-LGL), we decided to search for those genetic alterations in T-LGL patients and MOTN-1 cell line (established from T-LGL patient) that have an impact on gene expression and as a result can influence cell biology. METHODS: Multicolor fluorescence in situ hybridization (mFISH) analysis of the MOTN-1 cell line was performed as well as paired-end next-generation sequencing (NGS; Illumina HiSeq2000) of this cell line and one T-LGL patient. In addition, chosen 6q region was characterized in three T-LGL patients using high-resolution comparative genomic hybridization (FT-CGH) and LM-PCR. Gene expression was studied by RNA sequencing (RNAseq; SOLID5500). RESULTS: Rearrangements were detected within 1p and 2q in MOTN-1 affecting expression of FGR, ZEB2, and CASP8, and within 6q in MOTN-1 and one T-LGL patient affecting MAP3K5 and IFNGR1. Nineteen genes, among them FOXN3, RIN3, AKT1, PPP2R5C, were overexpressed as a result of an amplification in 14q in one T-LGL patient. Two novel fusion transcripts were identified: CASP8-ERBB4 in MOTN-1 and SBF1-PKHD1L1 in T-LGL patient. CONCLUSIONS: This study showed that submicroscopic genomic rearrangements change gene expression in T-LGL. Several genes involved in rearrangements were previously linked to cancer and survival pattern that characterizes T-LGL cells.

Research on the occurrence of Mycobacterium tuberculosis antigens in the circulating immune complexes, isolated from serum of patients with tuberculosis.

BACKGROUND: Tuberculosis is one of the most dangerous infectious diseases and has among the highest mortality rates of all infectious diseases. There are 9 million cases of active tuberculosis reported annually; however, an estimated one-third of the world's population is infected with Mycobacterium tuberculosis and remains asymptomatic. Despite the great progress in its diagnosis and treatment, tuberculosis is still a serious health and social problem. The contact between the immune system and Mycobacterium tuberculosis initiates cell-specific (Th1) and humoral-specific (Th2) responses. Many studies about the presence of antituberculotic antibodies in the serum have produced inconsistent results because of a high proportion of false-positive or false-negative results. The purpose of this study was to confirm whether circulating immune complexes (CIC) isolated from the serum of patients with tuberculosis are accompanied by antigenic proteins typical of Mycobacterium tuberculosis. MATERIAL AND METHODS: We assayed serum samples from 42 patients with tuberculosis. The control group consisted of the sera samples taken from 45 healthy subjects. The immunochemical analysis of dissociated immune complexes using the dot blot method demonstrated positive reaction on the presence of Mycobacterium tuberculosis antigens in all patients with tuberculosis. RESULTS: All patients with tuberculosis demonstrated a high serum concentration of CIC protein. The mean serum concentration of CIC protein was significantly higher in patients than in controls: 0.081 g/l in the control group and 0.211 g/l in the tuberculosis patients. CONCLUSIONS: The analysis of CIC suggests that it may be a helpful test for patients with tuberculosis because of its quickness, simplicity of the idea, and limited invasiveness.

Alcoholism and other socio-demographic risk factors for adverse TB-drug reactions and unsuccessful tuberculosis treatment - data from ten years' observation at the Regional Centre of Pulmonology, Bydgoszcz, Poland.

BACKGROUND: Tuberculosis (TB) is one of the most dangerous infectious diseases and has one of the highest mortality rates. For decades a strong association has been evident between certain socio-economic factors and TB adverse events and failure of treatment, yet there is a limited quantity of literature available on this subject, especially in the Polish literature. MATERIAL AND METHODS: We examined epidemiological data from 2025 TB patients treated at the Regional Centre of Pulmonology in Bydgoszcz, Poland between 2001 and 2010. This article focuses on the association between all forms of unsuccessful TB treatment outcomes or adverse drug reaction (ADR) and socio-demographic characteristics, condition on admission, and other biological, clinical, social, and healthcare access factors. RESULTS: The rate of TB-ADR during hospitalization was 38.9%. Multivariate logistic regression analysis showed that age (P<0.001) and alcohol abuse (P=0.007) were independently associated with the occurrence of TB-ADR. The rate of unsuccessful TB treatment was 10.5%. After adjusting for confounding variables, age (P<0.001), alcohol abuse (P=0.002), and education (P=0.01) were significantly associated with unsuccessful treatment. Smoking did not have any significant influence on occurrence of either TB-ADR during hospitalization or unsuccessful treatment. CONCLUSIONS: Among our TB patients treated between 2001 and 2010, alcohol abuse significantly worsened the treatment outcome. This information will be crucial in developing strategies targeted at this demographic group.

Unemployment in TB patients - ten-year observation at regional center of pulmonology in Bydgoszcz, Poland.

BACKGROUND: Tuberculosis (TB) affects the poorest of the poor and is an example of a disease that can contribute to the "disease-poverty trap". The variable epidemiological situation is associated with social risk factors, such as unemployment, which may favor the occurrence of this disease. The aim of this study was to analyze unemployment as a factor that can influence the incidence and course of the disease. MATERIAL AND METHODS: We analyzed TB patients with confirmed status of employment or unemployment admitted to the Regional Center of Pulmonology in Bydgoszcz in during the years 2001 to 2010. Out of 1130 patients, 604 were unemployed and the other confirmed their employment. RESULTS: The unemployed patients were mostly single men over age 40, with a low level of education, and living in a city. We observed that the proportions of smokers and alcohol abusers were significantly higher among the unemployed patients. The advanced radiological lesions, smear-positive pulmonary TB, and extra-pulmonary sites were diagnosed significantly more often in this group. The rate of death in the course of hospitalization was significantly higher in the group of unemployed patients. CONCLUSIONS: Unemployment among TB patients is a serious problem. We found that more advanced radiological lesions were associated with more frequent treatment interruptions and a higher rate of death in the course of hospitalization. Increased efforts are needed to reduce and eliminate the problem of unemployment among patients with TB. This may, indirectly, contribute to a decrease in notifications of TB cases and improve treatment outcomes.

[10 years comparative clinico-epidemiological analysis of smoking and alcohol consumption in TB patients (Myc. Tuberculosis) and with mycobacteriosis (Myc. Kansas]. / 10 letnia porównawcza analiza kliniczno-epidemiologiczna palenia i spoycia alkoholu u chorych na grulice (Myc. Tuberculosis) i mykobakterioe (Myc. Kansasi).

INTRODUCTION: Smoking and alcohol consumption are a major public health problem. More and more are mentioned, also, these two drugs, tobacco and alcohol as risk factors for tuberculosis and mycobacteriosis. AIM OF STUDY: Comparative analysis of epidemiological and clinical patients with tuberculosis and mycobacteriosis M.kansasii smoking cigarettes and abuse alcohol. MATERIAL AND METHOD: The study included 2025 patients with tuberculosis and 140 patients with diagnosed lung mycobacteriosis hospitalized in Kuyavian-Pomeranian Center of Pulmonology in the years 2003-2013. Data were obtained from the central database of the hospital on admission to the hospital. RESULTS: There were 1403 smokers (69.3%) of tuberculosis patients and 79 (56.4%) with mycobacteriosis, and alcohol dependence were 534 (26.4%) and 16 (11.4%) respectively. Both of smokers and drinkers, men prevailed. Smokers who have developed tuberculosis were significantly younger than patients with mycobacteriosis, often touched their homelessness and unemployment, and often lived in rural areas. Conversely, smokers with mycobacteriosis are people often married, professionally active. In the group of abusers, patients with tuberculosis were younger, living in the country. side, often unemployed, homeless and single compared to patients with my. cobacteriosis. The clinical picture of patients with tuberculosis and mycobacteriosis did not differ significantly between the groups. CONCLUSIONS: A retrospective study of patients with tuberculosis and my. cobacteriosis showed significantly more use of tobacco and alcohol abuse than in the general Polish population. It should be noted that cigarette smoking and alcohol abuse are major risk and mycobacteriosis. Therefore, it is important to conduct anti-tobacco education and prevention of alcohol abuse.

T-cell lymphoma patient harboring BCL11B mutations had favorable overall survival.

BACKGROUND: Molecular genetics serve a critical role in constructing risk stratification for hematological malignancies, but T-cell lymphoma (TCL) still lacks molecular genetic information for supplement risk stratification in predicting the prognosis of TCL patients. In the present study, we characterized the mutation patterns of B-cell leukemia/lymphoma 11B gene (BCL11B) and its prognostic importance in TCL patients. METHODS: BCL11B mutations were characterized based on the data from two datasets, one is from our clinical center (GDPH dataset, n = 79) and the other is from COSMIC dataset (n = 154). RESULTS: The overall mutation rate of BCL11B was 6.4% (15/233) in TCL, and there were no hotspot mutation sites in TCL. Among these mutations, the missense and splice site mutation were significantly prominent. Moreover, TCL patients harboring BCL11B mutations had a favorable overall survival (OS) in our center (GDPH dataset) (adjusted hazard ratio [HR] = .001, p = 0.109), although there were not yet significantly statistical at this point. In addition, TCL patients harboring BCL11B mutation had a longer 5-year restricted mean survival time (RMST) than those without a BCL11B mutation (60 vs. 32 months). Notably, BCL11B mutations were not associated with TCL entities having better prognosis. CONCLUSIONS: BCL11B mutations were associated with favorable clinical outcome for TCL patients; it might be considered as a novel biomarker for TCL prognostic stratification.

[Mechanisms of programmed cell death of effector T lymphocytes]. / Mechanizmy zaprogramowanej smierci efektorowych limfocytów T.

T cell adequate function is critical for defense against pathogens. Transient disruption of T cell homeostasis occurs when primarily naive cells undergo antigen-driven expansion and acquire effector functions. Effector T cells then either undergo programmed cell death (PCD, it occurs usually as massive apoptosis during the contraction phase of the immune response) or survive to become memory cells. Two main pathways of effector T cell PCD are discussed in the review: activation induced cell death (AICD), which is a form of extrinsic apoptosis, and neglect-induced death (NID), which is an intrinsic one. Initial studies using in vitro models supported a role of AICD, mostly initiated by TCR receptor triggering in immune contraction. However, it was not finally supported by either recent in vivo experiments or current review authors' clinical studies concerning primed T cell apoptosis in chronic inflammatory lower airway diseases. Actually, Bcl-2 family members seem to be critical for the culling of T cell responses. The antiapoptotic molecule Bcl-2 and its proapoptotic antagonist Bcl-2, both under upstream control of autocrine interleukin-2, are the most probable candidates for regulators of T cell contraction. Other possible mechanisms regulating the process of contraction such as death receptor ligation, the impact of cytokines, as well as the importance of transcription factor NF-κB, are discussed. Additionally, attention is turned to the potential role of T cell survival/apoptosis regulation in future therapies of some diseases, including tumors and lung fibrosis.

[Analysis of occurrence atypical proteins in the serum at smoking and non-smoking cigarettes patients with lung cancer]. / Analiza wystepowania atypowych bialek w surowicy u chorych na raka pluc palacych i niepalacych papierosy.

The acting correctly immunological setting responds on every signal connected with appearing in the organism of the substance having of immunogenic properties. The smoking of cigarettes is connected with the continuous stimulation of the defensive mechanisms of the system both about the cellular character as and humoral. The important group of the proteins which he appears after immunostimulation in the intercellular space are particles built from the antigens of the various origin and antibodies. The analysis of the level of circulating immunological complexes (CIC) was the aim of the work at patients with the lung cancer and study the occurrence of the HSP-70 protein in circulating immunological complexes at patients with lung cancer smoking non-smoking cigarettes. Human serum was the analysed material, received from the blood taken from the ulnar vein from 39 patients with recognized neoplastic disease in age from 42 to 83 years ,13 non-smoking and 26 smoking. The marks of the levels of immunological complexes was conducted Haskova method and reactions on the presence of HSP-70 protein was conducted Dot Blot method by use the mice's antibodies mAbHSP-70. It was confirmed: are raised level CIC in sera of patients with lung cancer; higher levels CIC in smoking patients with lung cancer in comparison with control group and not smoking patients with lung cancer group; positive reactions on the presence of the isolated from sera of patients with lung cancer; positive reactions on the presence of the HSP-70 protein in CIC isolated from sera of smoking patients with lung cancer.

[An attempt of evaluation the impact of smoking on postural stability in patients with diseases of the respiratorv system--a pilot]. / Próba oceny wplywu palenia tytoniu na stabilnosc posturalna chorych ze schorzeniami ukladu oddechowego--badania pilotazowe.

For many years, the negative effects of cigarette smoking is a major social problem. The influence of smoking on various aspects of human life is intensively investigated, but still it is difficult to find studies on postural stability of smokers and non-smokers. Therefore, this paper attempts to analyse the results of the posturographic measurements in two groups of patients with the respiratory system diseases. Pilot studies indicate that smokers obtain higher values of posturographic parameters than nonsmokers. It may indicate a worse postural stability and greater risk of uncontrolled falls in smokers group.

Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians' Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland.

BACKGROUND: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. OBJECTIVE: To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. DESIGN: Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. MATERIAL AND METHODS: The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. RESULTS: There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22-88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. CONCLUSIONS: NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).