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IntroductionGranulomatosis with polyangiitis (GPA) is a small vessel vasculitis with a complex pathomechanism. Organ damage in GPA is also mediated by extracellular trap formation (NETosis). We analyzed the functional status of phosphoproteins modulating NETosis in neutrophils by the mammalian target of rapamycin (mTOR) pathway in GPA along with NETosis biomarkers.MethodsPhosphoproteins levels measured in isolated neutrophils from 42 patients with GPA (exacerbation n=21; remission n=21) and 21 healthy controls were compared to serum biomarkers of the disease.ResultsNeutrophils in active disease manifested lowered levels of phosphorylated mTOR(Ser2448), PTEN(Ser380) and ULK1(Ser555), whereas phosphorylated GSK-3α/β(Ser21/Ser9) was elevated. Exacerbation of GPA was characterized by elevated neutrophil dsDNA in serum, circulating mitochondrial DNA, and DNA-MPO complexes. A significant negative correlation between mTOR or PTEN phosphoproteins and biomarkers of GPA activity was also present, reflecting the clinical activity score of GPA. Positive correlations between phosphorylated GSK-3 α/β and circulating mtDNA, DNA-MPO complexes, neutrophil-released dsDNA, or circulating proteins were also significant. Increased serum levels of IGFBP-2, TFF-3, CD147, and CHI3L1 accompanied GPA exacerbation, whereas DPP-IV levels were the lowest in active GPA. Using a principal component analysis basigin, PTEN and mTOR had the highest loadings on the discrimination function, allowing classification between active, remission, and control subjects with 98% performance.ConclusionsWe present evidence that inhibited mTOR signaling accompanies NETosis in patients with GPA. The functional status of phosphoproteins suggests simultaneous activation of NETosis and autophagy. These results give rise to the study of autophagy as a mechanism underlying granuloma formation in GPA.

Ultrasonic haptic technology is one of the more interesting novel technologies being intensively developed in recent years. Such technology has a number of undoubted advantages and potential applications, but it can also be a source of ultrasonic noise. Pursuant to the provisions of the labor law, ultrasonic noise at a high sound pressure level can be a harmful factor for human health. The article presents the results of the assessment of ultrasonic noise emitted by an ultrasonic haptic device and the assessment of exposure to noise of a person using the device. The tests were carried out using one of the haptic devices readily available on the market. Ultrasonic noise emission tests were carried out around the device, at selected points placed on the surface of a hemisphere of a radius of 0.5 m, for various haptic objects. The analyzed parameter was the equivalent sound pressure level in the 1~3 octave band with a center frequency of 40 kHz. Variable sound pressure levels ranged from 96 dB to 137 dB. Noise exposure tests were carried out both using the KEMAR measurement dummy and with test participants of different heights. In most cases, the sound pressure level exceeded 110 dB, and in the worst case it exceeded 131 dB. Comparison of the results of ultrasonic noise assessments with the permissible values of this noise in the working environment shows that in the case of prolonged or improper use of the device, the permissible values may be exceeded.

In this article, the authors present the geometry and measurements of the properties of an acoustic metamaterial with a structure composed of multiple concentric rings. CAD models of the structure were developed and subsequently used in numerical studies, which included the study of resonant frequencies using the Lanczos method and an analysis of sound pressure level distribution under plane wave excitation using the finite element method. Subsequently, experimental tests were carried out on models with the same geometry produced with three different materials (PLA, PET-G, and FLEX) using a fused deposition modeling 3D printing technique. These tests included: determining insertion loss for a single model based on tests using the measurement window of a reverberation chamber and determining transmission loss through tests in a semi-anechoic chamber. Sound wave resonance was obtained for frequencies ranging from 1700 to 6000 Hz. Notably, the experimental studies were carried out for the same structure for which numerical tests were conducted. The physical models of a metamaterial were manufactured using three different readily available 3D printing materials. The results of laboratory tests confirm that the created acoustic metamaterial consisting of multi-ring structures reduces noise in medium and high frequencies.

Patients with autoimmune diseases constitute a relatively low percentage of the intensive care unit (ICU) population but their prognosis is particularly poor, partially due to involvement of multiple organs as well as complications related to immunosuppressive treatment. Diffuse alveolar haemorrhage (DAH) is one of the most life-threatening presentations of autoimmune diseases, associated with worse outcomes. The aim of this study is to report about clinical factors associated with DAH in the ICU setting and to assess the survival in 5-year follow-up. This is an observational, retrospective, cohort study performed in the ICU of the University Hospital in Krakow, Poland. We enrolled 21 patients treated for the first time in the ICU due to autoimmune diseases, who developed DAH. Severity of patients' clinical condition was assessed on the first day using APACHE II, APACHE III, SAPS II and SOFA scores. Mortality was assessed during the ICU stay and in 5-year follow-up. The median age of the study population was 53 (18-78) years and 13 (61.9%) of patients were females. The most common diagnoses were granulomatosis with polyangiitis (38.1%), systemic lupus erythematosus (23.8%) and microscopic polyangiitis (14.3%). Most of the patients required mechanical ventilation (85.7%), renal replacement therapy (57.1%) and blood product transfusions (71.4%). Mortality in the ICU was 52.4%, while in both 1-year and 5-year follow-up it was 76.2%. Patients who develop DAH in the course of autoimmune diseases and are treated in the ICU have a poor prognosis and often require advanced therapeutic measures.

COVID-19 has disturbed the functioning of Polish healthcare for the past two years. Due to the high proportion of patients requiring admission to the intensive care unit (ICU), these wards are particularly overwhelmed and are considered the bottleneck of the healthcare system. The aim of this study was to describe clinical outcomes of critically ill patients treated in a single tertiary ICU in Poland, assess factors associated with mortality and compare outcomes of patients treated during the 2nd and 3rd waves of the pandemic. This is a retrospective single-centre study including patients admitted to the ICU between October 2020 and May 2021 (the 3rd wave) with confirmed SARS-CoV-2 infection. Patients were followed up until death or 90 days after ICU admission. The co-primary endpoints of this study included ICU, 30-day and 90-day mortality. We enrolled 108 patients at a mean age of 64.3 (SD = 12) years, the majority of whom were male (63.9%). Mortality in the ICU, after 30 days and 90 days was 44.4% (48/108), 50.0% (54/108), and 57.9% (62/108), respectively. Mortality at 90 days was associated with increasing age (OR = 3.97, 95% CI: 1.87-8.41) and was significantly higher during the 2nd wave (65.6 vs. 46.5%, log-rank P = 0.043) compared to the 3rd wave of the pandemic. This retrospective single-centre study confirms the high mortality rate among critically ill patients with COVID-19. Moreover, it suggests a significant association between 90-day mortality and increasing age as well as differences in mortality between the 2nd and 3rd waves of the pandemic in Poland.

Systemic autoimmune diseases are a heterogeneous group of disorders associated with dysfunction of multiple organs and unpredictable course. Complicated management and treatment become even more challenging when patients require critical care. This study aims to compare outcomes of small-vessel vasculitides (SVV) and other systemic autoimmune diseases (SAD) patients admitted to the intensive care unit (ICU). Retrospective, observational study conducted in the ICU of Allergy and Immunology Department at the University Hospital in Krakow, Poland, between years 2001–2014, with 5-years follow-up and no lost to follow-up patients. 74 patients with autoimmune diseases were enrolled in the study - 23 with SVV and 51 with SAD. Patients in the SVV group achieved higher scores in APACHE II and III SAPS II and SOFA at ICU admission. The SVV patients required renal replacement techniques, blood products transfusion and immunosuppressive treatment more often. SVV patients had higher ICU mortality (60.9% vs. 35.3%, p = .04), however after discharge from ICU, in long term follow-up (1 year and 5 years) mortality was similar in both studied groups. Among systemic autoimmune diseases small vessel vasculitides appear to be associated with the highest ICU mortality, higher requirement for advanced procedures and aggressive immunosuppressive therapy. •Autoimmune diseases are associated with high ICU mortality•Small vessel vasculitides patients have worst prognosis during ICU stay•Small vessel vasculitides patients require advanced ICU procedures more often•Differences among mortality rate disappear after ICU discharge

Objective. To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/μl) (GPA HE) to develop a differentiating strategy. Methods. A retrospective analysis of the POLVAS registry. Results. The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p <0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/μl, p <0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion. Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Background Myocardial injury is a major cause of death after noncardiac surgery and is associated with long-term cardiovascular outcomes. Perioperative tachycardia increases this risk. Although perioperative beta blockers prevent myocardial injury, they increase the risk of death and stroke, which analyses suggest is due to a significant increase in hypotension. Ivabradine, a selective heart rate-lowering drug, may offer a safer alternative. The primary objective of the PREVENT-MINS trial is to determine whether perioperative administration of ivabradine is superior to placebo for the prevention of myocardial injury after noncardiac surgery (MINS) in patients with or at risk of atherosclerotic disease having noncardiac surgery.  Methods The PREVENT-MINS trial is a multicentre, parallel-group, blinded, placebo-controlled trial conducted in 26 hospitals in Poland. It will enroll 2500 patients aged ≥ 45 years undergoing noncardiac surgery with at least one risk factor for myocardial injury. Participants will be randomized in a 1:1 ratio to receive ivabradine 5 mg orally twice daily for 7 days starting 1 h before surgery or placebo. The primary outcome is MINS within 30 days after randomization; independent experts will adjudicate this outcome. Secondary outcomes include vascular complications, mortality, haemodynamics, and quality of life at 30 days. Additional tertiary and 1-year outcomes will assess long-term cardiovascular and surgical complications. Analyses will follow an intention-to-treat approach. For the primary outcome, a chi-squared test will be conducted, with results presented as unadjusted relative risk (RR) accompanied by 95% confidence intervals (CIs) and p -values.  Discussion This trial will generate high-quality, generalizable data due to its large population and rigorous design, including blinding. Moreover, it will be one of the first large-scale trials specifically focused on preventing MINS. Trial registration ClinicalTrials.gov NCT05279651. Registered on 4 March 2022. 

Background ICU patients are particularly susceptible to vitamin D3 deficiencies. This can be due to the severity of their underlying disease, the type of treatment they are on, and malnutrition before and inadequate nutrition during the hospitalization preceding ICU admission as well as advanced age. Literature provides no guidance on how to supplement vitamin D3 in severely deficient patients who are undergoing continuous renal replacement therapy (CRRT). Most serum 25(OH)D3 is bound with vitamin D binding protein in a complex whose molecular weight is 10 kDa. This means it can be removed during CRRT via convection mechanism. Critically ill patients undergoing CRRT can therefore be particularly prone to develop severe vitamin D3 deficiency. Methods As the trial design, a randomized controlled, single blinded, multicenter, parallel group approach was chosen to compare a single administration of 750,000 IU of vitamin D3 via the enteral or oral route in ICU patients with severe vitamin D3 deficiency (measured serum 25(OH)D3 levels ≤ 12.5 ng/ml) undergoing CRRT with a single administration of 500,000 IU of vitamin D3. The trial will be performed in up to five university hospitals in Poland. The primary outcome is the percentage of patients that achieved serum 25(OH)D3 levels ≥ 30 ng/ml on days 3 and 7 following vitamin D3 administration. Assuming a drop-out rate of approximately 10%, the number of recruited patients should be 138. Discussion Considering the potential pathophysiological mechanisms underlying hypovitaminosis D in critically ill patients under CRRT, it seems conceivable that these patients will require greater supplementation doses to correct severe deficiency. The study is meant to help answer the question whether increasing the supplementation dose by 50% will ensure a more effective replenishment of vitamin D3 in critically ill patients undergoing CRRT. Trial registration ClinicalTrials.gov Identifier: NCT05657678, registered: December 12 2022, https://clinicaltrials.gov/study/NCT05657678?cond=NCT05657678&rank=1 .

The relevant assets of the NEWS include the possibility to carry out standardised assessment of the patient’s condition, early identification of sudden health deterioration, observation of its time-related changeability and adjustment of the intensity of interventions to the obtained outcome. [...]the above scale necessitates the regularity of measurements and provides nurses with the objective basis for informing the physician that some intervention is required, which may help to overcome possible communication barriers. Every fifth request for help was made directly by nurses; in some hospitals, the percentage of calls made by nurses significantly exceeded 50%. [...]in some hospitals the number of calls caused by difficulties in care of particularly demanding patients decreased after suitable trainings of the ward staff provided by the RRT regarding care of the central line or tracheostomy insertion sites. According to the expectations based on the experience of other countries, mutual education of the personnel of various wards is a significant added value of the introduction of the system to Polish hospitals [4]. In every fifth hospital, the nursing staff is supported by paramedics normally working in hospital emergency departments.