Differences in performance analysis between won and lost teams in the top handball matches in the seasons before, during, and after the COVID-19 pandemic.

BACKGROUND: The study aimed to try to determine whether there are differences in performance analysis in handball matches won and lost, in Pre-COVID-19, COVID-19, and Post-COVID-19 seasons, taking into account the venue of the match. METHODS: The material was the official statistics of 493 men's handball matches of PGNiG Superliga Ltd. For comparisons between independent variables, the Mann-Whitney U Test and the Kruskal-Wallis Test were used. A Chi-square Test was used to determine the distribution of the number of games won and lost. RESULTS: The analyses conducted indicate higher values in matches won than in matches lost (P=0.00) for the variables: numbers of goals scored, accurate throws, 6 meters goals, fast breaks, fast break goals, and throwing efficiency: all throws, 9 meters, 6 meters, and goalkeeper efficiency. In losing matches teams lost have a higher number of goals defeated (P=0.00) and executed a higher number of missed throws (P=0.00) than in winning matches Effect size of the differences is large. The results show a higher number of matches won in home matches than away in the Pre-COVID-19 season (P=0.0001). CONCLUSIONS: During the three seasons, the number of throws and goals from 9 meters decreases, while the number of goals from 6 meters increases. In sports training, measures should be taken to improve and increase the effectiveness of actions that affect winning the match. The results indicate the need to shape defensive actions that prevent goals from being scored in situations that differentiate the match's outcome.

The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients.

INTRODUCTION: Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. MATERIALS AND METHODS: In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR. RESULTS: Leptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8-16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001-0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243-1.0715, p = 0.0953). CONCLUSION: Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.

Induction of seizures and initiation of epileptogenesis by pilocarpine in zebrafish larvae.

Objective: Preclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish. Methods: Local field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin (H&E) staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis. Results: Acute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains. Significance: Here, we comprehensively investigated a new model of PILO-induced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes.

Gut resistome of NSCLC patients treated with immunotherapy.

Background: The newest method of treatment for patients with NSCLC (non-small cell lung cancer) is immunotherapy directed at the immune checkpoints PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1). PD-L1 is the only validated predictor factor for immunotherapy efficacy, but it is imperfect. Some patients do not benefit from immunotherapy and may develop primary or secondary resistance. This study aimed to assess the intestinal resistome composition of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors in the context of clinical features and potentially new prediction factors for assessing immunotherapy efficacy. Methods: The study included 30 advanced NSCLC patients, 19 (57%) men and 11 (33%) women treated with first- or second-line immunotherapy (nivolumab, pembrolizumab or atezolizumab). We evaluated the patient's gut resistome composition using the high sensitivity of targeted metagenomics. Results: Studies have shown that resistome richness is associated with clinical and demographic factors of NSCLC patients treated with immunotherapy. Smoking seems to be associated with an increased abundance of macrolides, lincosamides, streptogramins and vancomycin core resistome. The resistome of patients with progression disease appears to be more abundant and diverse, with significantly higher levels of genomic markers of resistance to lincosamides (lnuC). The resistance genes lnuC, msrD, ermG, aph(6), fosA were correlated with progression-free survival or/and overall survival, thus may be considered as factors potentially impacting the disease. Conclusion: The results indicate that the intestinal resistome of NSCLC patients with immune checkpoint inhibitors treatment differs depending on the response to immunotherapy, with several distinguished markers. Since it might impact treatment efficacy, it must be examined more deeply.

Immunological insights: assessing immune parameters in medical professionals exposed to SARS-CoV-2.

BACKGROUND: The immunological background responsible for the severe course of COVID-19 and the immune factors that protect against SARS-CoV-2 infection are still unclear. The aim of this study was to investigate immune system status in persons with high exposure to SARS-CoV-2 infection. METHODS: Seventy-one persons employed in the observation and infectious diseases unit were qualified for the study between November 2020 and October 2021. Symptomatic COVID-19 was diagnosed in 35 persons. Anti-SARS-CoV-2 antibodies were also found in 8 persons. Peripheral blood mononuclear cells subpopulations were analyzed by flow cytometry, and the concentrations of cytokines and anti-SARS-CoV-2 antibodies were determined by ELISA. RESULTS: The percentages of cytotoxic T lymphocytes (CTLs), CD28+ and T helper (Th) cells with invariant T-cell receptors were significantly higher in persons with symptomatic COVID-19 than in those who did not develop COVID-19' symptoms. Conversely, symptomatic COVID-19 persons had significantly lower percentages of: a) CTLs in the late stage of activation (CD8+/CD95+), b) NK cells, c) regulatory-like Th cells (CD4+/CTLA-4+), and d) Th17-like cells (CD4+/CD161+) compared to asymptomatic COVID-19' persons. Additionally, persons with anti-SARS-CoV-2 antibodies had a significantly higher lymphocyte count and IL-6 concentration than persons without these antibodies. CONCLUSION: Numerous lymphocyte populations are permanently altered by SARS-CoV-2 infection. High percentages of both populations: NK cells-as a part of the non-specific response, and T helper cells' as those regulating the immune response, could protect against the acute COVID-19 symptoms development. Understanding the immune background of COVID-19 may improve the prevention of this disease by identifying people at risk of a severe course of infection. TRIAL REGISTRATION: This is a retrospective observational study without a trial registration number.

TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice.

Cytoplasmic polyadenylation plays a vital role in gametogenesis; however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of four TENT5 poly(A) polymerases in mouse fertility and gametogenesis. TENT5B and TENT5C play crucial yet redundant roles in oogenesis, with the double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display a gain-of-function infertility effect, with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, as shown by the sterility in males following the knockout of either gene. Finally, Tent5a knockout substantially lowers fertility, although the underlying mechanism is not directly related to gametogenesis. Through direct RNA sequencing, we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motif analysis and reporter mRNA assays reveal that the presence of an endoplasmic reticulum-leader sequence represents the primary determinant of TENT5-mediated regulation.

Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection.

Endometrial cancer (EC) accounts for 90% of uterine cancer cases. It is considered not only one of the most common gynecological malignancies but also one of the most frequent cancers among women overall. Nowadays, the differentiation of EC subtypes is based on immunohistochemistry and molecular techniques. It is considered that patients' prognosis and the implementation of the appropriate treatment depend on the cancer subtype. Patients with pathogenic variants in POLE have the most favorable outcome, while those with abnormal p53 protein have the poorest. Therefore, in patients with POLE mutation, the de-escalation of postoperative treatment may be considered, and patients with abnormal p53 protein should be subjected to intensive adjuvant therapy. Patients with a DNA mismatch repair (dMMR) deficiency are classified in the intermediate prognosis group as EC patients without a specific molecular profile. Immunotherapy has been recognized as an effective treatment method in patients with advanced or recurrent EC with a mismatch deficiency. Thus, different adjuvant therapy approaches, including targeted therapy and immunotherapy, are being proposed depending on the EC subtype, and international guidelines, such as those published by ESMO and ESGO/ESTRO/ESP, include recommendations for performing the molecular classification of all EC cases. The decision about adjuvant therapy selection has to be based not only on clinical data and histological type and stage of cancer, but, following international recommendations, has to include EC molecular subtyping. This review describes how molecular classification could support more optimal therapeutic management in endometrial cancer patients.

Predictors of outcomes of patients ≥ 80 years old admitted to intensive care units in Poland - a post-hoc analysis of the VIP2 prospective observational study.

INTRODUCTION: Elderly patients pose a significant challenge to intensive care unit (ICU) clinicians. In this study we attempted to characterise the population of patients over 80 years old admitted to ICUs in Poland and identify associations between clinical features and short-term outcomes. MATERIAL AND METHODS: The study is a post-hoc analysis of the Polish cohort of the VIP2 European prospective observational study enrolling patients > 80 years old admitted to ICUs over a 6-month period. Data including clinical features, clinical frailty scale (CFS), geriatric scales, interventions within the ICU, and outcomes (30-day and ICU mortality and length of stay) were gathered. Univariate analyses comparing frail (CFS > 4) to non-frail patients and survivors to non-survivors were performed. Multivariable models with CFS, activities of daily living score (ADL), and the cognitive decline questionnaire IQCODE as predictors and ICU or 30-day mortality as outcomes were formed. RESULTS: A total of 371 patients from 27 ICUs were enrolled. Frail patients had significantly higher ICU (58% vs. 44.45%, P = 0.03) and 30-day (65.61% vs. 54.14%, P = 0.01) mortality compared to non-frail counterparts. The survivors had significantly lower SOFA score, CFS, ADL, and IQCODE than non-survivors. In multivariable analysis CFS (OR 1.15, 95% CI: 1.00-1.34) and SOFA score (OR 1.29, 95% CI: 1.19-1.41) were identified as significant predictors for ICU mortality; however, CFS was not a predictor for 30-day mortality ( P = 0.07). No statistical significance was found for ADL, IQCODE, polypharmacy, or comorbidities. CONCLUSIONS: We found a positive correlation between CFS and ICU mortality, which might point to the value of assessing the score for every patient admitted to the ICU. The older Polish ICU patients were characterised by higher mortality compared to the other European countries.

Obstetric units' preparedness to manage critically ill women. The second report from the MaCriCare study.

PURPOSE: We aimed to describe the availability of 31 distinct services and facilities to diagnose, resuscitate, and treat critically unwell obstetric patients. METHODS: Using a network of anesthesiologists, intensive care clinicians, obstetricians, critical care nurses, and midwives (MaCriCare) from September 2021 to January 2022, we conducted a descriptive international multicenter cross-sectional survey in centers with obstetric units (OUs) in the WHO Europe Region. RESULTS: The MaCriCare network covers 26 countries and received 1133 responses, corresponding to 2.5 million annual deliveries. The survey identified significant disparities in the availability of the measured 31 services among the OUs, with some services not immediately available and some not available at all. Point-of-care hemoglobin measurements were lacking in 13.8% of OUs. 15.2% of OUs lacked pointof-care lactate measurement, and 11% lacked transfusion services. 23.8% of OUs lacked the ability to administer hypotensive agent infusions in the labor ward. Samebuilding access to cell saver and thromboelastometry was unavailable to 45.5% and 64.4% of OUs, respectively. Access to invasive ventilation was unavailable to 3.4% of OUs, 11.7% were unable to offer same-building access to non-invasive ventilation, and extracorporeal membranous oxygenation was unavailable to 38.3% of the OUs. CONCLUSION: Critically ill obstetric patients have access to markedly different resources in the WHO Europe Region depending on the OU where they are managed. Consensus on which facilities and services should be universally available is urgently needed.

Synthesis and Catalytic Performance of High-Entropy Rare-Earth Perovskite Nanofibers: (Y0.2La0.2Nd0.2Gd0.2Sm0.2)CoO3 in Low-Temperature Carbon Monoxide Oxidation.

This study investigated the catalytic properties of low-temperature oxidation of carbon monoxide, focusing on (Y0.2La0.2Nd0.2Gd0.2Sm0.2)CoO3 synthesized via a glycothermal method using 1,4-butanediol and diethylene glycol at 250 °C. This synthesis route bypasses the energy-intensive sintering process at 1200 °C while maintaining a high-entropy single-phase structure. The synthesized material was characterized structurally and chemically by X-ray diffraction and SEM/EDX analyses. The material was shown to form nanofibers of (Y0.2La0.2Nd0.2Gd0.2Sm0.2)CoO3, thereby increasing the active surface area for catalytic reactions, and crystallize in the model Pbnm space group of distorted perovskite cell. Using a custom setup to investigate catalytic properties of (Y0.2La0.2Nd0.2Gd0.2Sm0.2)CoO3, the CO oxidation behavior of those high-entropy perovskite oxide was investigated, showing an overall conversion of 78% at 50 °C and 97% at 100 °C. These findings highlight the effective catalytic activity of nanofibers of (Y0.2La0.2Nd0.2Gd0.2Sm0.2)CoO3 under mild conditions and their versatility in various catalytic processes of robust CO neutralization. The incorporation of rare-earth elements into a high-entropy structure could impart unique catalytic properties, promoting a synergistic effect that enhances performance.

Transitioning to a Personalized Approach in Molecularly Subtyped Small-Cell Lung Cancer (SCLC).

Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung cancer (SCLC) is characterized by aggressive and rapid growth, poor differentiation, and neuroendocrine features. Typically, SCLC is diagnosed at an advanced stage (extensive disease, ED-SCLC), with distant metastases, and is strongly associated with tobacco smoking and has a poor prognosis. Recent clinical trials, such as CASPIAN and IMpower133, have demonstrated promising outcomes with the incorporation of immune checkpoint inhibitors in first-line chemotherapy, leading to prolonged progression-free survival and overall survival in patients with ED-SCLC compared to standard chemotherapy. Other studies have emphasized the potential for future development of molecularly targeted therapies in SCLC patients, including inhibitors of IGF-1R, DLL3, BCL-2, MYC, or PARP. The molecular subdivision of SCLC based on transcriptomic and immunohistochemical analyses represents a significant advancement in both diagnostic and clinical approaches in SCLC patients. Specific molecular pathways are activated within distinct transcriptome subtypes of SCLC, offering the potential for personalized treatment strategies, such as targeted therapies and immunotherapies. Such tailored approaches hold promise for significantly improving outcomes in SCLC patients.

Structure-functional characterization of Lactococcus AbiA phage defense system.

Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK and Abi-P2 are abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi RTs apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in a template- and primer-independent manner. Structures of AbiK and Abi-P2 representatives have recently been determined, but there are no structural data available for AbiA. Here, we report the crystal structure of Lactococcus AbiA polymerase in complex with a single-stranded polymerization product. AbiA comprises three domains: an RT-like domain, a helical domain that is typical for Abi polymerases, and a higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain that is common for many antiviral proteins. AbiA forms a dimer that distinguishes it from AbiK and Abi-P2, which form trimers/hexamers. We show the DNA polymerase activity of AbiA in an in vitro assay and demonstrate that it requires the presence of the HEPN domain which is enzymatically inactive. We validate our biochemical and structural results in vivo through bacteriophage infection assays. Finally, our in vivo results suggest that AbiA-mediated phage defense may not rely on AbiA-mediated cell death.

MicroRNA-126 selected with broad-spectrum analysis of microRNAs - a new predictive factor for the effectiveness of immunotherapy or chemoimmunotherapy in advanced NSCLC patients?

Introduction: Expression of PD-L1 on cancer cells is the only validated predictive factor for immunotherapy in NSCLC (Non-Small Cell Lung Cancer) patients. However, on this basis, it is difficult to predict the occurrence of resistance to immune checkpoint inhibitors (ICIs). MicroRNAs are widely studied as biomarkers of cancers. Our study was designed to determine whether microRNAs can be sensitive predictive factors in the qualification of NSCLC patients to first-line immunotherapy or chemoimmunotherapy. Material and methods: The two-stage research on validation group (n=20) and study group (n=35) of patients with advanced NSCLC was conducted. Analysis of microRNAs expression by qPCR in plasma collected prior to the start of immunotherapy (pembrolizumab) or chemoimmunotherapy (combination of pembrolizumab with chemotherapy) was made. Broad-spectrum analysis of microRNAs expression was used in the studied group. Three microRNAs selected in that group as important for the effectiveness of ICIs were then examined in the validation group. Results: In the studied group, significantly higher expression of miRNA-126-3p, miR-144-3p and miR-146-5p was observed in patients with long PFS compared to those with short PFS. In the validation group, low miRNA-126 expression indicated lower median progression-free survival and overall survival (2.3 vs. 5.0 months and 5.2 vs 11.2, respectively). These patients had a significantly higher risk of progression (HR= 2.92, 95% CI: 1.01 to 8.40, p=0.04) and death (HR=3.64, 95% CI: 1.22 to 10.84, p=0.02). Conclusion: Our study showed that the expression of miR-126 in blood plasma may be a predictive factor for the effectiveness of first-line immunotherapy or chemoimmunotherapy in advanced NSCLC patients.

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice.

Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

Abnormalities in the KRAS Gene and Treatment Options for NSCLC Patients with the G12C Mutation in This Gene-A Literature Review and Single-Center Experience.

Mutations in the KRAS gene are among the most common mutations observed in cancer cells, but they have only recently become an achievable goal for targeted therapies. Two KRAS inhibitors, sotorasib and adagrasib, have recently been approved for the treatment of patients with advanced non-small cell lung cancer with the KRAS G12C mutation, while studies on their efficacy are still ongoing. In this work, we comprehensively analyzed RAS gene mutations' molecular background, mutation testing, KRAS inhibitors' effectiveness with an emphasis on non-small cell lung cancer, the impact of KRAS mutations on immunotherapy outcomes, and drug resistance problems. We also summarized ongoing trials and analyzed emerging perspectives on targeting KRAS in cancer patients.

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients.

Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC.

Preparedness for severe maternal morbidity in European hospitals: The MaCriCare study.

PURPOSE: To evaluate obstetric units (OUs) and intensive care units (ICUs) preparedness for severe maternal morbidity (SMM). METHODS: From September 2021 to January 2022, an international multicentre cross-sectional study surveyed OUs in 26 WHO Europe Region countries. We assessed modified early obstetric warning score usage (MEOWS), approaches to four SMM clinical scenarios, invasive monitoring availability in OUs, and access to high-dependency units (HDUs) and onsite ICUs. Within ICUs, we examined the availability of trained staff, response to obstetric emergencies, leadership, and data collection. RESULTS: 1133 responses were evaluated. MEOWS use was 34.5%. Non-obstetric early warning scores were being used. 21.4% (242) of OUs provided invasive monitoring in the OU. A quarter lacked access to onsite HDU beds. In cases of SMM, up to 13.8% of all OUs indicated the need for transfer to another hospital. The transfer rate was highest (74.0%) in small units. 81.9% of centers provided onsite ICU facilities to obstetric patients. Over 90% of the onsite ICUs provided daily specialist obstetric reviews but lacked immediate access to key resources: 3.4% - uterotonic drugs, 7.5% - neonatal resuscitation equipment, 9.2% - neonatal resuscitation team, 11.4% - perimortem cesarean section equipment. 41.2% reported obstetric data to a national database. CONCLUSION: Gaps in provision exist for obstetric patients with SMM in Europe, potentially compromising patient safety and experience. MEOWS use in OUs was low, while access to invasive monitoring and onsite HDU and ICU facilities was variable. ICUs frequently lacked resources and did not universally collect obstetric data for quality control.

Prevalence of life-sustaining treatment limitations in Polish very old intensive care patients (VIPs). A post-hoc analysis of two prospective observational studies.

PURPOSE: Several initiatives have recently focused on raising awareness about limitations of treatment in Poland. We aimed to assess if the propensity to limit LST among elderly patients in 2018-2019 increased compared to 2016-2017. METHODS: We analysed Polish cohorts from studies VIP1 (October 2016 - May 2017) and VIP2 (May 2018 - May 2019) that enrolled critical patients aged >80. We collected data on demographics, clinical features limitations of LST. Primary analysis assessed factors associated with prevalence of limitations of LST, A secondary analysis explored differences between patients with and without limitations of LST. RESULTS: 601 patients were enrolled. Prevalence of LST limitations was 16.1% in 2016-2017 and 20.5% in 2018-2019. No difference was found in univariate analysis (p = 0.22), multivariable model showed higher propensity towards limiting LST in the 2018-2019 cohort compared to 2016-2017 cohort (OR 1.07;95%CI, 1.01-1.14). There was higher mortality and a longer length of stay of patients with limitations of LST compared to the patients without limitations of LST. (11 vs. 6 days, p = 0.001). CONCLUSIONS: The clinicians in Poland have become more proactive in limiting LST in critically ill patients ≥80 years old over the studied period, however the prevalence of limitations of LST in Poland remains low.

The influence of plasma sPD-L1 concentration on the effectiveness of immunotherapy in advanced NSCLC patients.

INTRODUCTION: PD-L1 (Programmed Cell Death Ligand 1) is currently the only recognised marker of response to immunotherapy with anti-PD-1 or anti-PD-L1 antibodies in patients with advanced non-small cell lung cancer (NSCLC). However, this marker is not perfect. Soluble PD-L1 (sPD-L1) may be a novel predictor of immunotherapy efficacy in NSCLC patients. MATERIAL AND METHODS: We enrolled 120 patients (median age 68 ± 6.81 years, 70 males and 50 females) with locally advanced (stage IIIB; 10 patients) or advanced (stage IV; 110 patients) NSCLC. PD-L1 expression in tumour cells was assessed by immunohistochemistry (IHC) in 117 (97.5%) patients. The soluble PD-L1 concentration in plasma samples was measured using enzyme-linked immunosorbent assay (ELISA). The response to immunotherapy, progression-free survival (PFS), and overall survival (OS), calculated from the start of immunotherapy, were assessed in 119 patients. RESULTS: Patients with disease control had significantly lower (p = 0.0006) concentrations of sPD-L1 in blood plasma than patients with progression during the first months of immunotherapy or chemoimmunotherapy Patients with ≥ 6 month progression-free survival had a significantly higher (p = 0.013) percentage of tumor cells with PD-L1 expression than patients with shorter PFS. Patients with ≥ 6 months OS had significantly lower (p = 0.0142) plasma sPD-L1 concentrations than those with shorter overall survival. The median PFS was significantly higher in patients with low sPD-L1 concentrations than in those with high concentrations of this protein (5.8 vs. 2.5 months, HR = 0.6021, p = 0.0156). Similarly, patients with low sPD-L1 levels had a significantly higher median overall survival than those with sPD-L1 levels above the median (16.5 vs. 7 months, HR = 0.5354, p = 0.0071). There was no significant correlation between the percentage of tumour cells expressing PD-L1 and the concentration of sPD-L1 in the blood plasma. CONCLUSION: High sPD-L1 concentration is a negative predictor of immunotherapy efficacy in patients with NSCLC. It is worthwhile to determine sPD-L1 concentration to predict the risk of resistance to anti-PD-1 or anti-PD-L1 antibodies with greater certainty.