Tricuspid Regurgitation and Kidney Transplant Recipient Outcomes.

Rationale & Objective: Kidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain. Study Design: Retrospective observational cohort. Setting & Participants: Kidney transplant recipients from a single center between 2016 and 2019. Exposure: Significant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation. Outcomes: Primary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease. Analytical Approach: Propensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point. Results: Among 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P < 0.01), 50.0 mL/min/1.73 m2 versus 60.3 mL/min/1.73 m2 at 3 months (P < 0.01), and 49.4 mL/min/1.73 m2 versus 61.2 mL/min/1.73 m2 at 1 year (P < 0.01). Delayed graft function was observed in 41.7% of the patients with significant TR compared to 12.5% of those without significant TR (P < 0.01). No patients with significant TR required dialysis after 1 year. 1-year major adverse cardiac events were nonsignificantly higher among patients with significant TR (20.8% vs 8.1%; P = 0.16). Limitations: Retrospective design and relatively small TR population. Conclusions: The presence of significant TR among kidney transplant recipients was associated with a lower eGFR at 2 weeks, 3 months, and 1 year following transplant, although all remained dialysis independent at 1 year.

Significant tricuspid regurgitation (TR) is associated with increased mortality rates and kidney failure, but its impact on kidney transplant recipients is poorly investigated. We examined how significant TR diagnosed pretransplantation affects kidney function within the first posttransplant year in a retrospective cohort study. Among 24 patients with significant TR, there was a consistent pattern of lower kidney function at 2 weeks, 3 months, and 1 year following transplantation, compared to 72 matched controls based on a propensity score. Results were statistically significant at all time points within the first year after transplant. These findings suggest that selected individuals with significant TR are able to undergo successful kidney transplantation, although with worse kidney function following transplantation.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post Kidney Transplantation - a retrospective analysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered as contraindication for kidney transplant although some patients demonstrate myocardial recovery post-transplant. We aim to identify and characterize the phenomenon of reverse myocardial remodelling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplant between 2016-2019 (n=604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. RESULTS: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal or above 5%, whereas 36 (12%) patients had a LVEF improvement 10% or more post transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5% and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion Renal transplantation might lead to improved LV systolic function in some patients.

Interaction between anemia and renal dysfunction in relation to long-term survival following acute myocardial infarction.

BACKGROUND: Anemia and chronic kidney disease (CKD) adversely affect prognosis following acute myocardial infarction (AMI). We aimed to assess their interaction regarding long-term survival post-AMI. METHODS: This is a single-center, retrospective analysis of consecutive AMI survivors. Stratified by admission-time anemia status and CKD grade, as determined by hemoglobin and creatinine levels, the cohort was evaluated for all-cause mortality at 10 years after hospital discharge. RESULTS: A total of 11,395 patients (69.1% males, mean age 65.8 ± 13.9 years, 49.6% with ST elevation MI) were included, of whom 29.9% had anemia and 15.9% - grade 3b or higher CKD. CKD was more advanced among anemic patients and the prevalence of anemia rose as CKD grade increased (p for trend < 0.001). At 10 years, 47.8% of patients died. Notwithstanding differences in baseline characteristics, presentation, and treatment between those with various anemia status and CKD grades, anemia presence (HR 1.40, 95% CI 1.32-1.49, p < 0.001) and increasing CKD grade (HR 1.10, 95% CI 1.02-1.20, p for trend < 0.001) were independently associated with a higher mortality risk. The incremental hazard imposed by either anemia or more advanced CKD was limited to patients with normal renal function and up to grade 3a (in the total cohort and the conservative treatment subgroup) or 4 (in the invasive revascularization subgroup) CKD. The added risk associated with increasing CKD grade also affected non-anemic individuals irrespective of the specific CKD grade. CONCLUSION: Anemia and more advanced CKD are associated with reduced long-term survival post-AMI, inflicting higher risk when conjoined in lower-grade CKD.

Progression of Non-Significant Mitral and Tricuspid Regurgitation after Surgical Aortic Valve Replacement for Aortic Regurgitation.

Little is known about the natural history of non-significant mitral and tricuspid regurgitation (MR and TR) following surgical aortic valve replacement (SAVR) for aortic regurgitation (AR). We retrospectively analyzed 184 patients (median age 64 (IQR, 55-74) years, 76.6% males) who underwent SAVR for AR. Subjects with significant non-aortic valvulopathies, prior/concomitant valvular interventions, or congenital heart disease were excluded. The cohort was evaluated for MR/TR progression and, based on the latter's occurrence, for echocardiographic and clinical indices of heart failure and mortality. By 5.8 (IQR, 2.8-11.0) years post-intervention, moderate or severe MR occurred in 20 (10.9%) patients, moderate or severe TR in 25 (13.5%), and either of the two in 36 (19.6%). Patients who developed moderate or severe MR/TR displayed greater biventricular disfunction and functional limitation and were less likely to be alive at 7.0 (IQR, 3.4-12.1) years compared to those who did not (47.2 vs. 79.7%, p < 0.001). The emergence of significant MR/TR was associated with preoperative atrial fibrillation/flutter, symptomatic heart failure, and above-mild MR/TR as well as concomitant composite graft use, but not with baseline echocardiographic measures of biventricular function and dimensions, aortic valve morphology, or procedural aspects. In conclusion, among patients undergoing SAVR for AR, significant MR/TR developed in one fifth by six years, correlated with more adverse course, and was anticipated by baseline clinical and echocardiographic variables.

Coronary Computed Tomography Angiography and Abdominal Aortic Calcification Screening among High-Risk Living Kidney Donors.

BACKGROUND: A unique scanning protocol combining coronary computed tomography angiography (CTA) with routine abdominal CTA is being used at the Rabin Medical Center as a method of screening high-risk candidates for living kidney donation. We aim to evaluate the potential impact of coronary CTA on the decision regarding eligibility for kidney donation and its correlation with abdominal aortic calcification (AAC). METHODS: CCTA and abdominal CTA results of potential living kidney donors evaluated for donation between September 2020 and November 2021 were retrieved. A retrospective analysis of the abdominal CTA was used to calculate the AAC. Patients' demographic, clinical, and imaging data were collected from the electronic files, as well as the final decision regarding eligibility for donation. RESULTS: A total of 62 potential kidney donors were evaluated for donation using the combined scan. The mean age was 53.8 years, with male predominance (59.7%). Significant coronary artery stenosis (≥70% luminal stenosis) was present in two patients (3.2%), whereas five patients (8%) had moderate stenosis (50-69%). Thirteen patients (21%) were disqualified from donation due to moderate-to-significant coronary artery disease or abdominal atherosclerosis. The correlation between the coronary artery calcium score and the AAC was found to be positive, with a Pearson correlation coefficient of 0.88 (p < 0.001). CONCLUSIONS: The use of coronary CTA in the evaluation of potential kidney donors may has a potential impact on the decision regarding eligibility for donation. A high correlation between the coronary artery calcium score and the AAC was found.

The prognostic value of pre-operative coronary evaluation in kidney transplanted patients.

Aims: Non-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients. Methods and results: We retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization. Conclusion: Pre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

Chronic Renal Failure and Cardiovascular Disease: A Comprehensive Appraisal.

Coronary artery disease is highly prevalent in patients with chronic kidney disease. The concomitant renal disease often poses a major challenge in decision making as symptoms, cardiac biomarkers and noninvasive studies for evaluation of myocardial ischemia have different sensitivity and specificity thresholds in this specific population. Moreover, the effectiveness and safety of intervention and medical treatment in those patients is of great doubt as most clinical studies exclude patients with advance CKD. In the present paper, we discuss and review the literature in the diagnosis, treatment and prevention of CAD in the acute and chronic setting, in patients with CKD.

Preoperative evaluation of pulmonary hypertension in lung transplant candidates: echocardiography versus right heart catheterization.

BACKGROUND: Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the performance of echocardiographic PASP as an indicator of pulmonary hypertension in LT candidates, in order to assess the necessity of RHC. METHODS: From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015-2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods-echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. RESULTS: The mean value of PASP estimated by echocardiography was 49.5 ± 20.0 mmHg, compared to 42.5 ± 18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson's correlation: r = 0.609, p < 0.01). Echocardiography PASP measurements were moderately discriminative to diagnose PH, with an area under the curve (AUC) of 0.72 (95% CI 0.66-0.77). Echocardiographic overestimation of PASP of more than 10 mmHg was found in 35.0% of the patients, and underestimation was found in 11.6% of the patients. CONCLUSION: In the pre-surgical evaluation of LT candidates, echocardiographic estimation of PASP had moderate correlation and limited accuracy compared to the PASP measured by RHC. We thus recommend performing routine RHC to all LT candidates, regardless of the echocardiographic estimation of PASP.

Worse outcomes of ACS patients without versus with traditional cardiovascular risk factors.

INTRODUCTION: Up to 20% of patients presenting with acute coronary syndrome (ACS) have no traditional cardiovascular risk-factors (RFs). Data regarding the determinants, management, and outcomes of these patients are scarce. OBJECTIVES: To evaluate the management, outcomes, and time-dependent changes of ACS patients without RFs. METHODS: Evaluation of clinical characteristics, management strategies, and outcomes as well as time-dependent changes [by 3 time periods: early (2000-2006), mid (2008-2013), and late (2016-2018)] of ACS patients without RFs (diabetes mellitus, hypertension, dyslipidemia, family history of ischemic heart disease, and smoking) or known coronary artery disease, enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. We compared ACS patients without RFs (no-RF group) to those with ≥1 RFs (RF group). RESULTS: Overall, 554/9,683 (5.7%) eligible ACS patients did not have any RFs [median age 63 (IQR 52-76) years, 25% females]. The no-RF group were older, with lower body mass index and prevalence of other cardiovascular comorbidity and chronic kidney disease compared with the RF group. The in-hospital percutaneous coronary intervention rates were lower among the no-RF vs. the RF group (55% vs. 66%, respectively p<0.001). Furthermore, lower rate of guideline-recommended medical therapy upon discharge was prescribed in the no-RF group. The rate of in-hospital complications was greater in the no-RF vs. RF group (31.6% vs. 26.1%, respectively p=0.005). The rates of 30-day major adverse cardiovascular events (MACE; 17.6% vs.12.8%, respectively, p=0.002) and of 30-day and 1-year all-cause mortality (8.4% vs. 4.2%, p<0.001 and 11.4% vs. 7.7%, p=0.003 respectively) were higher among patients with no-RF vs. RF. Following propensity score matching 30-day MACE, 30-day and 1-year mortality risk remained higher in the no-RF group. The rate of 30-day MACE decreased between the early and the late study period in the no-RF group (21.5% vs. 10.5%, p=0.003, respectively). CONCLUSIONS: ACS patients without traditional cardiovascular risk-factors comprise a unique group with reduced prevalence of comorbidities yet significantly worse outcomes. Additional research to identify unique risk-factors and targets for interventions to improve outcomes of this group of patients is warranted.

Albumin as a Prognostic Marker for Atrial Fibrillation Recurrence following Cryoballoon Ablation of Pulmonary Venous.

Introduction: Atrial fibrillation (AF) recurrence following pulmonary vein isolation (PVI) ablation has clinical significance. Identifying risk factors for AF recurrence is important. We investigated serum albumin (SA) levels (g/dL) as a prognostic factor for the recurrence of AF following cryoballoon PVI ablation. Methods: We included patients who underwent cryoballoon PVI ablation at our institution between the years 2013 and 2018. The primary outcome was recurrence of AF during follow up. Results: Our cohort consisted of 126 patients (67% males, mean age 61.8 ± 10.0 years). The pattern of AF amongst the cohort was paroxysmal in 62.5%, persistent in 25.4%, and longstanding persistent in 6.3%. Those with lower SA levels had a mean AF duration significantly less than those with higher SA levels (2.81 years, 7.34 years, and 6.37 years for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p = 0.003). Patients with lower SA levels were significantly more likely to have had more previous cardioversions and a larger left atrial area and volume. The mean follow-up was 380 days, in which the AF recurrence rate was 20.6%. Patients with lower SA level had significantly more AF recurrences (47.4%, 16.7%, and 2.2% for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p < 0.001). Upon multivariate analysis, an SA level < 3.8 was associated with a higher risk of AF recurrence (OR = 5.422 95% CI 1.134; 25.910; p < 0.001). Conclusion: SA levels were found to be a strong independent marker for AF recurrence following PVI ablation.

Acute Kidney Injury Following Admission with Acute Coronary Syndrome: The Role of Diabetes Mellitus.

PURPOSE: To evaluate the role of diabetes mellitus in the incidence, risk factors, and outcomes of AKI (acute kidney injury) in patients admitted with ACS (acute coronary syndrome). METHODS: We performed a comparative evaluation of ACS patients with vs. without DM who developed AKI enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. AKI was defined as an absolute increase in serum creatinine (≥0.5 mg/dL) or above 1.5 mg/dL or new renal replacement therapy upon admission with ACS. Outcomes included 30-day major adverse cardiovascular events (MACE) and 1-year all-cause mortality. RESULTS: The current study included a total of 16,879 patients, median age 64 (IQR 54-74), 77% males, 36% with DM. The incidence of AKI was significantly higher among patients with vs. without DM (8.4% vs. 4.7%, p < 0.001). The rates of 30-day MACE (40.8% vs. 13.4%, p < 0.001) and 1-year mortality (43.7% vs. 10%, p < 0.001) were significantly greater among diabetic patients who developed vs. those who did not develop AKI respectively, yet very similar among patients that developed AKI with vs. without DM (30-day MACE 40.8% vs. 40.3%, p = 0.9 1-year mortality 43.7 vs. 44.8%, p = 0.8, respectively). Multivariate analyses adjusted to potential confounders, showed similar independent predictors of AKI among patients with and without DM, comprising; older age, chronic kidney disease, congestive heart failure, and peripheral arterial disease. CONCLUSIONS: Although patients with DM are at much greater risk for AKI when admitted with ACS, the independent predictors of AKI and the worse patient outcomes when AKI occurs, are similar irrespective to DM status.

The Definition of "Acute Kidney Injury" Following Percutaneous Coronary Intervention and Cardiovascular Outcomes.

Acute kidney injury (AKI) is a complication of percutaneous coronary intervention (PCI), known to increase rates of adverse medical events. We aimed to identify the optimal definition of AKI in predicting adverse cardiovascular outcomes and mortality post PCI. From a large registry of patients undergoing PCI between 2006-2018 (n = 25,690) at our medical center, consecutive patients were assessed for the presence of AKI according to four different definitions: a relative elevation of ≥25% or ≥50%; or an absolute elevation of ≥0.3 mg/dL or ≥0.5 mg/dL in serum creatinine at 48 hours post PCI. We assessed the calculated rates of AKI according to the different definitions. The discriminant capacity for 30-day and 1-year mortality and MACE (MACE: all-cause death, myocardial infarction, target-vessel revascularization and coronary artery bypass graft surgery) of each definition was calculated using ROC curves and AUCs. Data of 15,153 patients was available for the final analysis. Rates of AKI were 12.1%, 3.2%, 8.1% and 3.9% according to the four definitions, respectively. The discriminant capacity of adverse outcomes was highest among those defined as AKI according to the third definition - an absolute elevation of ≥0.3 mg/dL in serum creatinine with an AUC of 0.82 (95% CI 0.80-0.84) for 30-day mortality (P value = 0.036) and an AUC of 0.78 (CI 0.76-0.79) for 30-day MACE. In conclusion, an absolute elevation of ≥ 0.3 mg/dL in serum creatinine 48 hours post PCI predicts overall mortality and MACE most accurately.

Temporal trends of acute kidney injury in patients undergoing percutaneous coronary intervention over a span of 12 years.

BACKGROUND: AKI is a known complication of PCI and is associated with higher rates of adverse events. We assessed temporal trends in rates of AKI, factors associated with risk of AKI and prognosis. METHODS: From a prospective registry of patients undergoing PCI at two hospitals of the Rabin Medical Center, 15,153 consecutive patients were assessed at two time periods: 2006-2012 and 2012-2018. AKI was defined as either a relative elevation of ≥25% in serum creatinine or an absolute elevation of ≥0.5 mg/dl in serum creatinine at 48 h post PCI. RESULTS: Data for 7913 patients from 2006 to 2012 and 7240 during 2012-2018 was available for analysis. Mean age was 65.0 ± 11.9y and 66.0 ± 12.3y (p < 0.001) and baseline creatinine was 1.08 ± 0.87 mg/dl and 1.15 ± 0.97 mg/dl, respectively (p < 0.001). Rates of AKI were 11.1% in the early and 7.3% in the late period (p < 0.001). Following adjustment, risk of AKI was lower in the late period (OR- 0.72; 95% CI 0.61-0.85, p < 0.001). AKI was associated with increased MACE (HR 1.62; 95% CI 1.44-1.82, p < 0.001 for the early period and HR 2.11; 95% CI 1.80-2.46, P < 0.001 for the late period) and death (HR 1.86; 95% CI 1.64-2.11, p < 0.001; HR 2.4; 95% CI 2.02-2.86; p < 0.001) in both time periods. CONCLUSIONS: Over time, there was an improvement in the rates of post-PCI AKI. Increased adverse outcomes were evident at both periods. Further research is warranted, to further reduce peri-procedural AKI which is associated with impaired prognosis.

Corticosteroids for pneumonia.

BACKGROUND: Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011. OBJECTIVES: To assess the efficacy and safety of corticosteroids in the treatment of pneumonia. SEARCH METHODS: We searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible. MAIN RESULTS: We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93). AUTHORS' CONCLUSIONS: Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.

Antiviral prophylaxis in haematological patients: systematic review and meta-analysis.

PURPOSE: Antiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios. METHODS: Randomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported. RESULTS: HSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2-2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65-0.95), NNT 12 (7-50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53-0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14-0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2-4, CER 37.4%) and infection rates, with no effect on mortality. CONCLUSIONS: Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced.

Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To determine and quantify differences in efficacy between treatment regimens for brucellosis. DESIGN: Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis. DATA SOURCES: PubMed, CENTRAL, Lilacs, conference proceedings, and bibliographies with no restrictions on language, study year, or publication status. Review methods Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality independently performed in duplicate. Primary outcomes were relapse and overall failure resulting from primary failure or relapse. Relative risks with 95% confidence intervals were calculated and pooled with a fixed effect model. RESULTS: 30 trials and 77 treatment arms were included. Overall failure was significantly higher with doxycycline-rifampicin compared to doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk 2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity). Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45, 0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were significantly less effective than doxycycline combined with rifampicin or streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations. CONCLUSIONS: There are significant differences in effectiveness between currently recommended treatment regimens for brucellosis. The preferred treatment should be with dual or triple regimens including an aminoglycoside.