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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 .

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. 

Plasmapheresis is one of the methods of extracorporeal blood purification involving the removal of inflammatory mediators and antibodies. The procedure is used in a variety of conditions, including autoimmune diseases. The aim of the present study was to analyse the incidence of plasmapheresis-related complications in patients treated in the intensive care unit (ICU). The analysis involved 370 plasmapheresis procedures in 54 patients. The data were collected from patients' medical records, including procedure protocols. The most common diseases treated with plasmapheresis included: myasthenia gravis (33.3%), Guillain-Barre syndrome (14%), Lyell's syndrome (9.3%), systemic lupus erythematosus (7.4%), and thrombotic thromcytopenic purpura (7.4%). The adverse side effects observed most frequently during plasma filtration were: fall in arterial blood pressure (8.4% of all procedures), arrhythmias (3.5%), sensations of cold with temporarily elevated temperature and paresthesias (1.1%, each). In most cases the symptoms were mild and transient. Severe and life-threatening episodes, i.e. shock, fall in arterial blood pressure requiring pressor amines, persistent arrhythmias and haemolysis, developed in 2.16% of procedures. Plasmapheresis can be considered a relatively safe method of treatment of ICU patients. Continuous observation and proper monitoring of patients provided by highly trained medical personnel are essential for its safety.

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.

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.

ANCA-associated vasculitides (AAV) is a group of rare disorders where inflammation and damage of the small blood vessels lead to dysfunction of the supplied organs. In severe flares of the disease patients may require intensive care unit (ICU) admission and treatment. The study aims to characterize Polish patients with AAV who were admitted to the ICU and compare them to the others. An observational, retrospective study based on the POLVAS - registry of Polish adult patients with AAV was carried out. Patients admitted to the ICU (ICU group) were identified and compared with the patients who did not require ICU admission (non-ICU group). Characteristics and comparison between groups were made using standard statistic descriptive methods. 30 patients admitted to the ICU were identified among 573 cases included in the registry. All patients in the ICU group with available data were ANCA positive. The clinical manifestations related to the ICU admission were respiratory, renal and central nervous system involvement. The treatment regimen for remission induction was similar in both groups. Almost half of the patients in the ICU-group (48.3%) required dialysis, whereas in the non-ICU group it was 21.8% (P = 0.01). Infections were also more frequent in the ICU group (72.4% vs. 36.9% P < 0.001). The mortality rate among patients who needed ICU treatment was significantly higher when compared to the rest of the patients (53.6% vs. 7.8%; P < 0.001). In the Polish AAV cohort one in twenty patients required ICU admission. This group was characterized by multiple organ involvement and high mortality.

Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p<0·0001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0·91 (95% CI 0·72 to 1·14) and absolute risk reduction (ARR) of 1% (−1 to 3; p=0·40). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0·97 (0·83 to 1·13) and an ARR of 1% (−2 to 4; p=0·71). Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Canadian Institutes of Health Research.