Antoni Jurasz University Hospital

Importance: Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials. Objective: To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions. Data Sourcesand Study Selection: Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies. Data Extraction and Synthesis: Two investigators abstracted data and appraised risks of bias. Intervention groups were categorized as "more intensive" (more potent pharmacologic intervention) or "less intensive" (less potent, placebo, or control group). Main Outcomes and Measures: The coprimary end points were total mortality and cardiovascular mortality. Random-effects meta-regression and meta-analyses evaluated associations between baseline LDL-C level and reductions in mortality end points and secondary end points including major adverse cardiac events (MACE). Results: In 34 trials, 136 299 patients received more intensive and 133 989 received less intensive LDL-C lowering. All-cause mortality was lower for more vs less intensive therapy (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]), but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with greater reductions in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96]; P = .001; absolute risk difference [ARD], -1.05 incident cases per 1000 person-years [95% CI, -1.59 to -0.51]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Cardiovascular mortality was lower for more vs less intensive therapy (3.48% vs 4.07%; RR, 0.84 [95% CI, 0.79 to 0.89]) but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with a greater reduction in cardiovascular mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.86 [95% CI, 0.80 to 0.94]; P < .001; ARD, -1.0 incident cases per 1000 person-years [95% CI, -1.51 to -0.45]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Trials with baseline LDL-C levels of 160 mg/dL or greater had the greatest reduction in all-cause mortality (RR, 0.72 [95% CI, 0.62 to 0.84]; P < .001; 4.3 fewer deaths per 1000 person-years) in a meta-analysis. More intensive LDL-C lowering was also associated with progressively greater risk reductions with higher baseline LDL-C level for myocardial infarction, revascularization, and MACE. Conclusions and Relevance: In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels. This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C-lowering therapy may occur for patients with higher baseline LDL-C levels.

Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

BACKGROUND: inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. METHODS: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. RESULTS: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. CONCLUSIONS: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.

The objective of this report was to directly compare, by means of a systematic review and meta-analysis, redo surgical aortic valve replacement (re-sAVR) with valve-in-valve transcatheter aortic valve implantation (ViV TAVI) for patients with failed degenerated aortic bioprostheses. Multiple databases were screened for all available reports comparing ViV TAVI with re-sAVR in patients with failing degenerated aortic bioprostheses. The primary outcome was all-cause mortality determined from the longest available survival data. Five observational studies (n = 342) were included in the meta-analysis; patients in the ViV TAVI group were older and had a higher baseline risk compared to those in the re-sAVR group. Although there was no statistical difference in procedural mortality [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.18-2.97; P = 0.67], 30-day mortality (RR 1.29, 95% CI 0.44-3.78; P = 0.64) and cardiovascular mortality (RR 0.91, 95% CI 0.30-2.70; P = 0.86) at a mean follow-up period of 18 months, cumulative survival analysis favoured surgery with borderline statistical significance (ViV TAVI versus re-sAVR: hazard ratio 1.91, 95% CI 1.03-3.57; P = 0.039). ViV TAVI was associated with a significantly lower rate of permanent pacemaker implantations (RR 0.37, 95% CI 0.20-0.68; P = 0.002) and shorter intensive care unit (P < 0.001) and hospital stays (P = 0.020). In contrast, re-sAVR offered superior echocardiographic outcomes: lower incidence of patient-prosthesis mismatch (P = 0.008), fewer paravalvular leaks (P = 0.023) and lower mean postoperative aortic valve gradients in the prespecified analysis (P = 0.017). The ViV TAVI approach is a safe and feasible alternative to re-sAVR that may offer an effective, less invasive treatment for patients with failed surgical aortic valve bioprostheses who are inoperable or at high risk. Re-sAVR should remain the standard of care, particularly in the low-risk population, because it offers superior haemodynamic outcomes with low mortality rates.

INTRODUCTION: The risk of professional burnout is constituted by job-related as well as individual factors. The latter involve affective temperament, which influences the perception of job-related stress. The aim of the present study was to assess the affective temperament, the level of job stress and professional burnout, as well as the relationships between these variables, in public servants and nurses. MATERIAL AND METHODS: 100 civil servants and 100 nurses were enrolled in the study. Affective temperament and burnout were assessed by means of TEMPS-A and MBI questionnaires, respectively. To measure the level of job-related stress, we have designed a 6-item self-reported questionnaire, which considered stressors common for both professions. RESULTS: Compared to the civil servants, nurses showed higher rate of anxious temperament and experienced greater intensity of job-related stress. The groups did not differ in the intensity of burnout symptoms. The rates of cyclothymic and anxious temperaments correlated with the intensity of stress, and burnout symptoms in the group of nurses. Within the civil servants group, the level of stress correlated with intensity of burnout, however no correlations with affective temperament were observed. The regression analysis performed in both groups revealed the significant effect of stress and cyclothymic temperament on burnout, while the effect of anxious temperament was not significant. CONCLUSIONS: Cyclothymic and anxious temperaments are related to the level of experienced job stress and the risk of burnout. In professions like nursing, where employees show elevated rates of these temperaments, burnout prevention and stress management education is of particular importance.

Berberine is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and hypolipidemic activities. The research proves that it also strongly impacts carbohydrate metabolism. The compound also protects pancreatic β-cells and increases sensitivity to insulin in peripheral tissues via the induction of GLUT-1, GLUT-4 and insulin type 1 (Ins-1) receptors activity. It also stimulates glycolysis and leads to a decrease in insulin resistance by macrophages polarization, lipolytic processes induction and energy expenditure enhancement (by reducing body mass and limiting insulin resistance caused by obesity). In liver berberine inhibits FOX01, SREBP1 and ChREBP pathways, and HNF-4α (hepatocyte nuclear factor 4 alpha) mRNA that hinder gluconeogenesis processes. In the intestines it blocks α-glucosidase contributing to glucose absorption decrease. Its interference in intestinal flora reduces levels of monosaccharides and suppresses diabetes mellitus complications development.

Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world's population. According to current knowledge, psoriasis is a complex disease that involves various genes and environmental factors, such as stress, injuries, infections and certain medications. The chronic inflammation of psoriasis lesions develops upon epidermal infiltration, activation, and expansion of type 1 and type 17 Th cells. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the target cells and antigens that drive pathogenic T cell responses in psoriatic lesions are still unproven and the autoimmune basis of psoriasis still remains hypothetical. However, since the identification of the Th17 cell subset, the IL-23/Th17 immune axis has been considered a key driver of psoriatic inflammation, which has led to the development of biologic agents that target crucial elements of this pathway. Here we present the current understanding of various aspects in psoriasis pathogenesis.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) has been shown to reduce the risk of neurologic complications as compared to coronary artery bypass grafting performed with cardiopulmonary bypass. Side-clamping of the aorta while constructing proximal anastomoses, however, still carries substantial risk of cerebral embolization. We aimed to perform a comprehensive meta-analysis of studies assessing 2 clampless techniques: aortic "no-touch" and proximal anastomosis devices (PAD) for OPCAB. METHODS AND RESULTS: PubMed, CINAHL, CENTRAL, and Google Scholar databases were screened for randomized controlled trials and observational studies comparing "no-touch" and/or PAD with side-clamp OPCAB and reporting short-term (≤30 days) outcomes: cerebrovascular accident and all-cause mortality. A total of 18 studies (3 randomized controlled trials) enrolling 25 163 patients were included. Aortic "no-touch" was associated with statistically lower risk of cerebrovascular accident as compared to side-clamp OPCAB: risk ratio 95% CI: 0.41 (0.27-0.61); P<0.01; I(2)=0%. Event rates were 0.36% and 1.28% for "no-touch" and side-clamp OPCAB, respectively. No difference was seen between PAD and side-clamp OPCAB: 0.71 (0.33-1.55); P=0.39; I(2)=39%. A trend towards increased 30-day all-cause mortality with PAD and no difference with "no-touch" were observed when compared to side-clamp OPCAB. In a subset analysis, "no-touch" consistently reduced the risk of cerebrovascular accident regardless of patients' baseline risk characteristics. A benefit with PAD was observed in low-risk patients. CONCLUSIONS: Aortic "no-touch" technique was associated with nearly 60% lower risk of postoperative cerebrovascular events as compared to conventional side-clamp OPCAB with effect consistent across patients at different risk.

OBJECTIVES: Coronary artery bypass grafting (CABG) remains the standard of care in patients with extensive coronary artery disease. Yet the use of cardiopulmonary bypass (CPB) is believed to be a major determinant of perioperative morbidity. Novel techniques are sought to tackle the shortcomings of CPB, among them off-pump coronary artery bypass (OPCAB) and miniaturized extracorporeal circulation (MECC) systems have been extensively tested in randomized controlled trials (RCTs). To assess perioperative safety and efficacy of MECC and OPCAB when compared with conventional extracorporeal circulation (CECC). METHODS: Published literature and major congress proceedings were screened for RCTs evaluating the safety and efficacy of MECC, OPCAB and CECC. Selected end-points such as 30-day all-cause mortality, myocardial infarction (MI), cerebral stroke, postoperative atrial fibrillation (POAF) and renal dysfunction were assessed in a Bayesian-framework network meta-analysis. RESULTS: A total of 134 studies with 22 778 patients were included. When compared with CECC, both OPCAB and MECC significantly reduced 30-day all-cause mortality [odds ratios (95% credible intervals): 0.75 (0.51-0.99) and 0.46 (0.22-0.91)], respectively. No differences in respect to MI were demonstrated with either strategy. OPCAB, when compared with CECC, reduced the odds of cerebral stroke [0.57 (0.34-0.80)]; 60% reduction was observed with MECC when compared with CECC [0.40 (0.19-0.78)]. Both OPCAB and MECC reduced the odds of POAF [0.66 (0.48-0.90) and 0.62 (0.35-0.98), respectively] when compared with CECC. OPCAB conferred over 30% reduction of renal dysfunction when compared with CECC [0.69 (0.46-0.92)]. MECC reduced these odds by more than 50% [0.47 (0.24-0.89)]. Ranking of treatments emerging from the probability analysis (highest to lowest SUCRA values) was MECC followed by OPCAB and CECC. CONCLUSIONS: MECC and OPCAB both improve perioperative outcomes following coronary bypass surgery when compared with conventional CABG performed with extracorporeal circulation. MECC may represent an attractive compromise between OPCAB and CECC.

AIMS: The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. METHODS AND RESULTS: From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020. CONCLUSIONS: Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19.

BACKGROUND: Studies have repeatedly highlighted the need for homogenisation of training content and opportunities in infection prevention and control (IPC) across European countries. OBJECTIVES: To map current training opportunities for IPC professionals, define local needs and highlight differences, across 11 European countries (Cyprus, France, England, Germany, Greece, Italy, Netherlands, Poland, Romania, Spain, Switzerland). SOURCES: From July 2018 to February 2019, IPC experts directly involved in IPC training and education in their countries and/or internationally were invited to complete a prespecified set of questions in order to provide a detailed description of IPC training opportunities and needs in their country. CONCLUSIONS: IPC training among nurses and doctors varies greatly across countries, with differences in content and type of training (e.g., standardised curriculum, educational programme, clinical experience) duration, as well as in assessment and recognition/accreditation. The observed heterogeneity in IPC training between European countries can be eliminated through establishment of interdisciplinary region-wide training programmes, with common learning objectives, shared know-how and supported by national and international professional bodies.

BACKGROUND: Current guidelines recommend culprit-only revascularisation (COR) in haemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel (MV) disease. Contrarily, growing body of evidence available from recent randomised controlled trials (RCTs) demonstrates improved outcomes with complete MV-percutaneous coronary intervention (PCI). METHODS AND RESULTS: We performed a meta-analysis of RCTs comparing complete MV-PCI with non-complete MV-PCI in STEMI and MV disease. Complete MV-PCI was defined as revascularisation to non-infarct-related artery lesions during index procedure, non-complete MV-PCI-encompassed COR and staged approaches. Multiple databases and congress proceedings from major cardiovascular societies' meetings were screened for relevant studies. Primary endpoint was the composite of major adverse cardiac events (MACE) typically defined as death, recurrent myocardial infarction (MI) and repeat revascularisation. Secondary endpoints were cardiovascular mortality, recurrent MI and repeat revascularisation. Outcomes were analysed at longest available follow-up with differences accounted for with adjusted models by person-years. Seven RCTs (N=1303) were included. The median follow-up was 12 months. Complete MV-PCI reduced the odds of MACE compared with non-complete MV-PCI (OR (95% CIs) 0.59 (0.36 to 0.97), p=0.04) driven by reduction in recurrent MI (0.48 (0.27 to 0.85), p=0.01) and repeat revascularisation (0.51 (0.31 to 0.84), p=0.008). Complete MV-PCI was associated with a non-significant trend towards reduced cardiovascular mortality (0.54 (0.26 to 1.10), p=0.09) as well. In a sensitivity analysis, none of the baseline clinical variables significantly influenced overall estimates. CONCLUSIONS: In STEMI and MV disease, complete MV-PCI as compared with non-complete strategy reduces MACE by 41%, driven by a 52% reduction in recurrent MI and 49% reduction in repeat revascularisation.

This study compared wound healing efficacy of two silver dressings, AQUACEL(®) Ag and Urgotul(®) Silver, against venous ulcers at risk of infection, over 8 weeks of treatment. The primary objective was to show non inferiority of AQUACEL(®) Ag to Urgotul(®) Silver. Patients (281) were randomised into two groups. The AQUACEL(®) Ag group had 145 patients treated with AQUACEL(®) Ag for 4 weeks followed by AQUACEL for another 4 weeks. TheUrgotul(®) Silver group had 136 patients treated with Urgotul(®) Silver for 4 weeks followed by Urgotul(®) for another 4 weeks. In both groups, ulcer size and depth, safety events and ulcer healing were compared. After 8 weeks of treatment, the AQUACEL(®) Ag group had a relative wound size reduction (49·65% ± 52·53%) compared with the Urgotul(®) Silver group (42·81% ± 60·0%). The non inferiority of the AQUACEL(®) Ag group to the Urgotul(®) Silver group was established based on the difference between them (6·84% ± 56·3%, 95% confidence interval -6·56 to 20·2) and the pre-defined non inferiority margin (-15%). Composite wound healing analysis showed that the AQUACEL(®) Ag group had statistically higher percentage of subjects with better wound progression (66·9% versus 51·9%, P = 0·0108). In general, both dressings were effective at promoting healing of venous ulcers.

BACKGROUND: Interventional diagnostic and therapeutic procedures requiring intravascular iodinated contrast steadily increase patient exposure to the risks of contrast-induced acute kidney injury (CIAKI), which is associated with death, nonfatal cardiovascular events, and prolonged hospitalization. The aim of this study was to investigate the efficacy of pharmacological and non-pharmacological treatments for CIAKI prevention in patients undergoing cardiovascular invasive procedures with iodinated contrast. METHODS AND FINDINGS: MEDLINE, Google Scholar, EMBASE and Cochrane databases as well as abstracts and presentations from major cardiovascular and nephrology meetings were searched, up to 22 April 2016. Eligible studies were randomized trials comparing strategies to prevent CIAKI (alone or in combination) when added to saline versus each other, saline, placebo, or no treatment in patients undergoing cardiovascular invasive procedures with administration of iodinated contrast. Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. Eighteen strategies aimed at CIAKI prevention were identified. The primary outcome was the occurrence of CIAKI. Secondary outcomes were mortality, myocardial infarction, dialysis and heart failure. The data were pooled using network meta-analysis. Treatment estimates were calculated as odds ratios (ORs) with 95% credible intervals (CrI). 147 RCTs involving 33,463 patients were eligible. Saline plus N-acetylcysteine (OR 0.72, 95%CrI 0.57-0.88), ascorbic acid (0.59, 0.34-0.95), sodium bicarbonate plus N-acetylcysteine (0.59, 0.36-0.89), probucol (0.42, 0.15-0.91), methylxanthines (0.39, 0.20-0.66), statin (0.36, 0.21-0.59), device-guided matched hydration (0.35, 0.12-0.79), prostaglandins (0.26, 0.08-0.62) and trimetazidine (0.26, 0.09-0.59) were associated with lower odds of CIAKI compared to saline. Methylxanthines (0.12, 0.01-0.94) or left ventricular end-diastolic pressure-guided hydration (0.09, 0.01-0.59) were associated with lower mortality compared to saline. CONCLUSIONS: Currently recommended treatment with saline as the only measure to prevent CIAKI during cardiovascular procedures may not represent the optimal strategy. Vasodilators, when added to saline, may significantly reduce the odds of CIAKI following cardiovascular procedures.

BACKGROUND/AIM: Cytomegalovirus (CMV) infection is one of the major causes of morbidity following hematopoietic cell transplantation (HCT). Allogeneic HCT (allo-HCT) recipients are at the highest risk of clinically significant CMV reactivation. While letermovir has been approved for prophylactic use in CMV seropositive adults, reports on pediatric data are very limited. The objective of the study was to examine the use of letermovir for prophylaxis from CMV infection in children undergoing allo-HCT in a single center. PATIENTS AND METHODS: This retrospective matched-pair analysis study included 39 CMV-seropositive pediatric patients undergoing allo-HCT receiving letermovir as a primary prophylaxis for CMV infection on a compassionate-use basis (LMV group, n=13) or not (control group, n=26). There were no differences in basic characteristics between the analyzed groups. Among patients of the study group, 12 received primary prophylaxis with letermovir from day +1 after HCT. One patient, previously treated with ganciclovir received secondary prophylaxis from day +18. RESULTS: Prophylactic dose of letermovir was adjusted to cyclosporine co-administration, varied in between 120-480 mg, and given orally, once daily. No CMV reactivation was observed during administration of letermovir. Cumulative incidence of CMV reactivation was significantly higher for the control group not receiving prophylaxis. Of the 13 patients of the study group, three died; however, deaths were not attributable to CMV infection. We did not observe any toxicities related to letermovir. CONCLUSION: Our data support letermovir prophylaxis efficacy and safety in pediatric patients after allo-HCT. Compared with the historical group, prophylactic use of letermovir decreased the number of CMV reactivations in children.

BACKGROUND: The increasing population of very old intensive care patients (VIPs) is a major challenge currently faced by clinicians and policymakers. Reliable indicators of VIPs' prognosis and purposefulness of their admission to the intensive care unit (ICU) are urgently needed. METHODS: This is a report from the Polish sample of the VIP1 multicentre cohort study (NCT03134807). Patients ≥ 80 years of age admitted to the ICU were included in the study. Information on the type and reason for admission, demographics, utilisation of ICU procedures, ICU length of stay, organ dysfunction and the decision to apply end-of-life care was collected. The primary objective was to investigate the impact of frailty syndrome on ICU and 30-day survival of VIPs. Frailty was assessed with the Clinical Frailty Scale (≥ 5 points on a scale of 1-9). RESULTS: We enrolled 272 participants with a median age of 84 (81-87) years. Frailty was diagnosed in 170 (62.5%) patients. The ICU and 30-day survival rates were equal to 54.6% and 47.3% respectively. Three variables were found to significantly increase the odds of death in the ICU in a multiple logistic regression model: SOFA score (OR = 1.16; 95%CI 1.16-1.24), acute mode of admission (OR = 5.1; 95%CI 1.67-15.57) and frailty (OR = 2.25; 95%CI 1.26-4.01). CONCLUSION: Measuring frailty in critically ill older adults can facilitate making more informed clinical decisions and help avoid futile interventions.

BACKGROUND: Ticagrelor is an oral platelet P2Y12 receptor antagonist which is recommended for patients suffering from myocardial infarction, both with and without persistent ST segment elevation. Morphine is the first choice drug in pain alleviation in the same clinical subset. Recently a possible negative influence of morphine on the pharmacokinetics and antiplatelet effects of P2Y12 receptor blockers has been postulated. METHODS/DESIGN: The IMPRESSION study is a phase IV, single center, randomized, double-blind, placebo-controlled clinical trial that is designed to assess the influence of morphine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with myocardial infarction. The study is planned to include up to 100 patients with myocardial infarction who will be randomized into one of two arms in a 1:1 ratio. Subjects in the intervention arm prior to the loading dose of ticagrelor (180 mg) will receive morphine (5 mg) intravenously, whereas patients in the control arm will receive a placebo prior to the loading dose of ticagrelor (180 mg). The pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry. Platelet function testing in each patient will be performed using up to four different methods (platelet vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry, VerifyNow, and light transmission aggregometry). DISCUSSION: This study is expected to provide essential evidence-based data on the impact of morphine on the absorption of ticagrelor in patients with myocardial infarction as well as to shed some light on the suspected connection between morphine use and antiplatelet activity of ticagrelor in the same group of patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).

BACKGROUND: Historically, impaired glucose metabolism has been associated with early and late complicated clinical outcomes after cardiac surgery; however, such a condition is not specific to subjects with diabetes mellitus and involves a larger patient population. METHODS: Databases were screened (January 2000 to December 2020) to identify eligible articles; studies that evaluated the association between preoperative metabolic status, as assessed by glycosylated hemoglobin levels and clinical outcomes, were considered. The studies were stratified in thresholds by baseline glycosylated hemoglobin level (lower vs higher). RESULTS: Thirty studies, involving 34,650 patients, were included in the review. In a meta-analysis stratified by glycosylated hemoglobin levels, early mortality was numerically reduced in each threshold comparison and yielded the highest reductions when less than 5.5% versus greater than 5.5% glycosylated hemoglobin levels were compared (risk ratio, 0.39; 95% confidence interval, 0.18-0.84; P = .02). Comparing higher glycosylated hemoglobin threshold values yielded comparable results. Late mortality was reduced with lower levels of glycosylated hemoglobin. Low preoperative glycosylated hemoglobin was associated with the lowest risk of sternal wound infections (risk ratio, 0.50; 95% confidence interval, 0.32-0.80; P = .003 and risk ratio, 0.53; 95% confidence interval, 0.39-0.70; P &lt; .0001) for comparisons of less than 7.5% versus greater than 7.5% and less than 7.0% versus greater than 7.0% glycosylated hemoglobin thresholds, respectively. Additionally, levels of glycosylated hemoglobin lower than 7% were associated with reduced hospital stay, lower risk of stroke/transient ischemic attack (risk ratio 0.53; 95% confidence interval, 0.39-0.70; P &lt; .0001), and acute kidney injury (risk ratio, 0.65; 95% confidence interval, 0.54-0.79; P &lt; .0001). CONCLUSIONS: Lower levels of glycosylated hemoglobin in patients undergoing cardiac surgery are associated with a lower risk of early and late mortality, as well as in the incidence of postoperative acute kidney injury, neurologic complications, and wound infection, compared with higher levels.

Coagulase-negative staphylococci (CoNS) are the most frequently isolated bacteria from the blood and the predominant cause of nosocomial infections. Macrolides, lincosamides and streptogramin B (MLSB) antibiotics, especially erythromycin and clindamycin, are important therapeutic agents in the treatment of methicillin-resistant staphylococci infections. Among CoNS, Staphylococcus hominis represents the third most common organism. In spite of its clinical significance, very little is known about its mechanisms of resistance to antibiotics, especially MLSB. Fifty-five S. hominis isolates from the blood and the surgical wounds of hospitalized patients were studied. The erm(C) gene was predominant in erythromycin-resistant S. hominis isolates. The methylase genes, erm(A) and erm(B), were present in 15 and 25% of clinical isolates, respectively. A combination of various erythromycin resistance methylase (erm) genes was detected in 15% S. hominis isolates. The efflux gene msr(A) was detected in 18% of isolates, alone in four isolates, and in different combinations in a further six. The lnu(A) gene, responsible for enzymatic inactivation of lincosamides was carried by 31% of the isolates. No erythromycin resistance that could not be attributed to the genes erm(A), erm(B), erm(C) and msr(A) was detected. In S. hominis, 75 and 84%, respectively, were erythromycin resistant and clindamycin susceptible. Among erythromycin-resistant S. hominis isolates, 68% of these strains showed the inducible MLSB phenotype. Four isolates harbouring the msr(A) genes alone displayed the MSB phenotype. These studies indicated that resistance to MLSB in S. hominis is mostly based on the ribosomal target modification mechanism mediated by erm genes, mainly the erm(C), and enzymatic drug inactivation mediated by lnu(A).

BACKGROUND: Chronic insulin resistance, exacerbated in the course of pregnancy, is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). We hypothesise that the degree of insulin resistance, assessed at diagnosis of GDM, is a parameter of its pathophysiologic heterogeneity and/or severity. Thus, it offers potential to open new avenues for the personalization of therapy in affected women. METHODS: 1254 Polish Caucasian women with GDM were recruited into the study. The following parameters were assessed in the course of the study: body mass index (BMI), parity, weight gain during pregnancy, glycated haemoglobin, glucose level during an oral glucose tolerance test (OGTT), insulin, insulin resistance and insulin secretion. The severity of GDM was assessed based on insulin use and daily insulin dose during gestation. In order to evaluate insulin secretion and insulin resistance the homeostatic method was used (HOMA-B and HOMA-IR, respectively). We compared all the metabolic parameters and methods of treatment of GDM in women subdivided by quartiles of insulin resistance. RESULTS: The HOMA-IR in the whole population ranged from 0.34 to 20.39. The BMI, fasting insulin, fasting glucose and insulin dose per day increased along with increasing quartiles (HOMA-IR > 1.29). We observed a decrease of HOMA-B in the third quartile (1.92-2.89) compared with the first quartile (0.34-1.29). Insulin treatment was associated with HOMA-IR (<1.29 vs. >2.89), OR: 3.37, fasting glucose (≤6.11 vs. >6.11 mmol/dl), OR: 2.61, age (≤30 vs. >30 y. o.), OR: 1.54, and BMI (<25 vs. ≥25 kg/m2), OR: 1.45. Maximum insulin dose was associated with HOMA-IR, OR: 2.00, after adjustment for family history of diabetes, and 2-h OGTT glucose. CONCLUSION: Insulin resistance assessed by the HOMA index at diagnosis is associated with the severity and pathophysiological heterogeneity of GDM. A HOMA-IR >1.29 points to the major role of insulin resistance, indicating the need for a treatment aimed at improving tissue sensitivity to insulin. A HOMA-IR 1.29-2.89 suggests reduced insulin secretion, which is an indication for the introduction of insulin therapy. A HOMA-IR >2.89 indicates insufficient compensation for insulin resistance, which suggests the need for a treatment aimed at improving susceptibility of tissues to insulin combined with insulin therapy.