Hard Clinical Outcomes Research Articles

Efficacy of Hydroxychloroquine and Tocilizumab in Patients With COVID-19: Single-Center Retrospective Chart Review.

BackgroundDuring the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial.ObjectiveThe purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis.MethodsA retrospective cohort study was performed to determine the impact of HCQ and TCZ use on hard clinical outcomes during hospitalization. A total of 176 hospitalized patients with a confirmed COVID-19 diagnosis was included. Patients were divided into two comparison groups: (1) HCQ (n=144) vs no-HCQ (n=32) and (2) TCZ (n=32) vs no-TCZ (n=144). The mean age, baseline comorbidities, and other medications used during hospitalization were uniformly distributed among all the groups. Independent t tests and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios with 95% CIs, respectively.ResultsThe unadjusted odds ratio for patients upgraded to a higher level of care (ie, intensive care unit) (OR 2.6, 95% CI 1.19-5.69; P=.003) and reductions in C-reactive protein (CRP) level on day 7 of hospitalization (21% vs 56%, OR 0.21, 95% CI 0.08-0.55; P=.002) were significantly higher in the TCZ group compared to the control group. There was no significant difference in the odds of in-hospital mortality, upgrade to intensive medical care, need for invasive mechanical ventilation, acute kidney failure necessitating dialysis, or discharge from the hospital after recovery in both the HCQ and TCZ groups compared to their respective control groups. Adjusted odds ratios controlled for baseline comorbidities and medications closely followed the unadjusted estimates.ConclusionsIn this cohort of patients with COVID-19, neither HCQ nor TCZ offered a significant reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. These results are similar to the recently published preliminary results of the HCQ arm of the Recovery trial, which showed no clinical benefit from the use of HCQ in hospitalized patients with COVID-19 (the TCZ arm is ongoing). Double-blinded randomized controlled trials are needed to further evaluate the impact of these drugs in larger patient samples so that data-driven guidelines can be deduced to combat this global pandemic.

Wearables for arrhythmia care: Challenges and future prospects

Wearables for arrhythmia care: Challenges and future prospects

Torque teno viral load reflects immunosuppression in paediatric kidney-transplanted patients\u2014a pilot study

BackgroundChronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation.MethodsTTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally.ResultsTTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor–based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found.ConclusionsTTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections—common consequences of insufficient or too intense IS.

Complete Revascularization by Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: An Updated Meta-Analysis of Randomized Trials.

BackgroundFor patients with ST‐segment–elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non‐infarct‐related artery has been controversial. This up‐to‐date meta‐analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease.Methods and ResultsWe systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit‐only revascularization for multivessel disease in STEMI and performed a random‐effects meta‐analysis. The primary efficacy end point was cardiovascular death analyzed on an intention‐to‐treat basis. Secondary end points included all‐cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit‐only revascularization. Across all patients, complete revascularization was superior to culprit‐only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47–0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54–0.79; P<0.0001; I2=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28–0.51; P<0.0001; I2=64.7%). The difference in all‐cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69–1.04; P=0.108; I2=0.0%).ConclusionsFor patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI.

Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction

Recently, the Complete vs Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI (percutaneous coronary intervention) for STEMI (ST-segment elevation myocardial infarction [MI]) (COMPLETE) trial showed that angiography-guided PCI of the nonculprit lesion with the goal of complete revascularization reduced cardiovascular (CV) death or new MI compared with PCI of the culprit lesion only in STEMI. Whether complete revascularization also reduces CV mortality is uncertain. Moreover, whether the association of complete revascularization with hard clinical outcomes is consistent when fractional flow reserve (FFR)- and angiography-guided strategies are used is unknown. To determine through a systematic review and meta-analysis (1) whether complete revascularization is associated with decreased CV mortality and (2) whether heterogeneity in the association occurs when FFR- and angiography-guided PCI strategies for nonculprit lesions are performed. A systematic search of MEDLINE, Embase, ISI Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to September 30, 2019, was performed. Conference proceedings were also reviewed from January 1, 2002, to September 30, 2019. English-language randomized clinical trials comparing complete revascularization vs culprit-lesion-only PCI in patients with STEMI and multivessel disease were included. The combined odds ratio (OR) was calculated with the random-effects model using the Mantel-Haenszel method (sensitivity with fixed-effects model). Heterogeneity was measured using the I2 statistic. Publication bias was evaluated using the inverted funnel plot approach. Data were analyzed from October 2019 to January 2020. Cardiovascular death and the composite of CV death or new MI. Ten randomized clinical trials involving 7030 unique patients were included. The weighted mean follow-up time was 29.5 months. Complete revascularization was associated with reduced CV death compared with culprit-lesion-only PCI (80 of 3191 [2.5%] vs 106 of 3406 [3.1%]; OR, 0.69 [95% CI, 0.48-0.99]; P = .05; fixed-effects model OR, 0.74 [95% CI, 0.55-0.99]; P = .04). All-cause mortality occurred in 153 of 3426 patients (4.5%) in the complete revascularization group vs 177 of 3604 (4.9%) in the culprit-lesion-only group (OR, 0.84 [95% CI, 0.67-1.05]; P = .13; I2 = 0%). Complete revascularization was associated with a reduced composite of CV death or new MI (192 of 2616 [7.3%] vs 266 of 2586 [10.3%]; OR, 0.69 [95% CI, 0.55-0.87]; P = .001; fixed-effects model OR, 0.69 [95% CI, 0.57-0.84]; P < .001), with no heterogeneity in this outcome when complete revascularization was performed using an FFR-guided strategy (OR, 0.78 [95% CI, 0.43-1.44]) or an angiography-guided strategy (OR, 0.61 [95% CI, 0.38-0.97]; P = .52 for interaction). In patients with STEMI and multivessel disease, complete revascularization was associated with a reduction in CV mortality compared with culprit-lesion-only PCI. There was no differential association with treatment between FFR- and angiography-guided strategies on major CV outcomes.

AWAKEN-Ing a New Frontier in Neonatal Nephrology

In 2013, literature about the epidemiology of neonatal acute kidney injury (AKI) was limited to primarily retrospective, single center studies that suggested that AKI was common and that those with AKI had higher rates of mortality. We developed a 24-center retrospective cohort of neonates admitted to the NICU between January 1 and March 31, 2014. Analysis of the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) cohort, has allowed us to describe the prevalence, risk factors and impact of neonatal AKI for different gestational age cohorts. The ample sample size allows us to provide convincing data to show that those with AKI have an increase independent higher odds of death and prolonged hospitalization time (1). This data mirrors similar studies in pediatric (2) and adult (3) critically ill populations which collectively suggest that patients do not just die with AKI, but instead, AKI is directly linked to hard clinical outcomes. This study has allowed us to answer multiple other questions in the field which has expanded our understanding of the risk factors, complications, impact of fluid overload, the definition of neonatal AKI and suggests interventions for improving outcomes. Furthermore, this project brought together neonatologist and nephrologist within and across centers. Finally, the AWAKEN project has enabled us to build relationships and infrastructure that has launched the Neonatal Kidney Collaborative http://babykidney.org/ on its way to accomplish its stated mission to improve the health of newborns with or at risk for kidney disease through multidisciplinary collaborative research, advocacy, and education.

Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction: COMPLETE Trial

BackgroundThe COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). ObjectivesThe purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. MethodsFollowing culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. ResultsFor nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. ConclusionsAmong STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term.

Review article: impact of exercise on physical frailty in patients with chronic liver disease.

Physical frailty is common in chronic liver disease and the setting of liver transplantation. It is associated with poor quality of life, increased hospitalisation and mortality. Despite this, the impact of exercise in these patients remains poorly understood. To summarise the impact of physical exercise on physical frailty in patients with chronic liver disease until after liver transplantation. A MEDLINE and PubMed search was undertaken using the terms; "physical activity", "functional capacity", "exercise", "prehabilitation", "frailty", "liver cirrhosis", "liver failure", "liver transplantation" "chronic liver disease" and "end-stage liver disease" from January 1990 to June 2019. Eleven studies (five randomised controlled, five observational, one case study) demonstrated that exercise improves VO2 peak, anaerobic threshold, 6-minute walk distance, muscle mass/function and quality of life in patients with compensated and decompensated cirrhosis. Improvements were most significant with a combination of aerobic and resistance exercises at moderate-high intensity. The studies were small (n=1-50) and mainly focused on supervised, hospital-based exercises, excluding patients with significant liver failure (MELD>12). Seven studies (four randomised controlled and three observational) demonstrated that predominantly supervised (only one home-based) aerobic exercise after liver transplantation improves aerobic capacity, muscle mass/strength and quality of life. There was marked heterogeneity in timing, intensity and type of exercises. Exercise improves key components of physical frailty (functional/aerobic capacity, sarcopenia) and quality of life in chronic liver disease and after liver transplantation. Understanding the type, compliance, intensity and duration of exercise and its impact on hard clinical outcomes should be the focus of future large controlled clinical trials.

Controversies in the Management of Secondary Hyperparathyroidism in Chronic Kidney Disease.

Secondary hyperparathyroidism is a frequent complication of chronic kidney disease that begins early in the course of renal insufficiency as an adaptive response to maintain mineral homeostasis. This complex disorder affects the bone, leading to an increase in fracture risk and is associated with increased risks of vascular calcification and mortality. PURPOSE OF REVIEW: In this review, we examine the different strategies available to manage secondary hyperparathyroidism. Particularly, we focus on the adequate control of serum phosphorus by restricting intake and the use of phosphate binders, correction of hypocalcemia while minimizing calcium burden, and reduction in PTH levels through the use of vitamin D sterols and calcimimetics. RECENT FINDINGS: It was observed that although numerous agents directed at the correction of these abnormalities have demonstrated effectiveness on biochemical markers, there is still a relative scarcity of studies demonstrating treatment effectiveness as measured by hard clinical outcomes. In addition, most agents have side effects that may limit their use, even in patients in which the treatment has demonstrated efficacy in controlling these parameters. There is still controversy as to what therapeutic regimens to choose for a particular patient and what parameter should be used to follow their effects, including outcomes, side effects, pill burden, and costs, among others. In the present article, we analyze controversial aspects of the different therapeutic agents available. Although many tools and regimens are available, no one by itself is enough for an adequate management of the patient. But rather, combined therapy and individualization of approaches are recommended for better results. We suggest that new studies analyzing the effectiveness of therapeutic approaches to the management of secondary hyperparathyroidism should be directed not only to controlling parathyroid hormone levels but also to the evaluation of long-term outcomes, based on modification of morbidity, mortality, and end organ impact, while reducing side effects and controlling costs, among others.

New treatments/targets for primary biliary cholangitis.

SummaryPrimary biliary cholangitis (PBC) is an autoimmune, cholestatic, chronic liver disease that ultimately progresses towards cirrhosis and liver failure if untreated. While ursodeoxycholic acid has been established as standard of care for PBC in the last few decades, significant advances in second-line treatment options have recently been made and new therapeutic developments are currently under evaluation. The purpose of this article is to provide the clinician with an overview of the current treatment options and future opportunities for patients with PBC.

Early experiences with cardiology electronic consults: A systematic review

To systematically review the current literature related to electronic consultation in cardiology. Following the PRISMA guidelines, we conducted a systematic review in August 2018 of English literature. We searched PubMed, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for studies related to electronic consultation in cardiology. A total of 21 studies were included. Two of the studies were randomized controlled trials, 16 were quantitative studies with defined endpoints, and 3 were qualitative descriptions. Most studies were conducted in the United States and Canada. The available literature suggests cardiology e-consult programs can be implemented in different practice settings, have good patient and provider satisfaction, deliver greater and timelier access to outpatient cardiac care, and do so in a cost saving fashion. While studies suggest cardiology e-consultation is safe, there are no studies evaluating hard clinical outcomes. Cardiology e-consults appear to be a promising tool for increasing access to outpatient cardiac care. Further investigation is required to evaluate the effects of cardiology electronic consultation on the quality of care. Here we present the first systematic review of electronic consultation in cardiology. The available literature suggests cardiology e-consult programs can be implemented in different practice settings, have good patient and provider satisfaction, deliver greater and timelier access to outpatient cardiac care, and do so in a cost saving fashion. While studies suggest cardiology e-consultation is safe, there are no studies evaluating hard clinical outcomes. Overall, cardiology e-consults appear to be a promising tool for increasing access to outpatient cardiac care. Further investigation is required to evaluate the effects of cardiology electronic consultation on the quality of care.

Cambio en la enolasa neuroespecífica de los supervivientes de parada cardiorrespiratoria extrahospitalaria: herramienta útil para predecir el pronóstico neurológico

Introduction and objectivesNeuron-specific enolase (NSE) is a prognostic marker in out-of-hospital cardiopulmonary arrest (OHCA) survivors treated with mild therapeutic hypothermia (MTH). The objectives were to analyze the correlation between dynamic changes in NSE and outcomes and to determine the measurement timing that best predicts neurological status. MethodsMulticenter cohort study including patients admitted after shockable rhythm OHCA and treated with MTH. Serum NSE was sampled at 2 different times and Δ-NSE (%) was calculated as 100 x (NSE2-NSE1)/NSE1. In-hospital mortality and neurological outcome, as assessed by the Cerebral Performance Category (CPC) scale, were evaluated during admission and after a 6-month follow-up. ResultsWe included 166 patients admitted to 4 hospitals. In-hospital mortality was 31.9%. Almost 60% of patients had a good neurological recovery (CPC 1-2). On univariate and multivariate logistic regression analyses, an increase in NSE levels was associated with higher in-hospital mortality and worse CPC on discharge and after 6-months (P<.001). Positive Δ-NSE showed an OR=9.28 (95% CI 4.40-19.57) for mortality, OR=11.23 (95% CI 5.24-24.11) for CPC 3-5 at discharge and OR=11.14 (95% CI 5.05-24.55) for CPC 3-5 after 6-months’ follow-up (P<.001). The first NSE measurement, conducted at 18 to 24hours, and the second measurement at 69 to 77hours after OHCA showed a high area under the curve in predicting CPC at discharge (0.9389 and 0.9909, respectively; 0.8096 for the whole cohort). ConclusionsDynamic changes in NSE serum levels are good markers of hard clinical outcomes after an OHCA due to shockable rhythm in an MTH-treated cohort. NSE measurements at specific intervals after OHCA may predict events even more precisely.

Health-related quality of life as predictor of mortality in end-stage renal disease patients: an observational study

BackgroundHealth-related quality of life (HRQoL) is an important component of patient-centered outcomes and a useful parameter for monitoring quality of care. We assessed HRQoL, its determinants, and associations with mortality in patients with end-stage renal disease (ESRD).MethodsShort Form-36 was used to assess HRQoL, its domain components, and physical (PCS) and mental (MCS) composite summary scores in altogether 400 (338 incident and 62 prevalent) dialysis patients with median age 64 years, 37% women, 24% diabetes mellitus (DM), 49% cardiovascular disease (CVD), and median estimated glomerular filtration rate (eGFR) of 5.3 (3.0–9.4) ml/min/1.732. Results were analyzed separately for 338 incident patients starting on hemodialysis (HD; 68%) or peritoneal dialysis (PD; 32%), and 62 prevalent PD patients. Mortality risk was analyzed during up to 60 months (median 28 months).ResultsLinear multivariate regression analysis showed that in incident dialysis patients, 1-SD higher PCS associated negatively with 1-SD higher age, DM and CVD, and positively with 1-SD higher hemoglobin and sodium (adjusted r2 = 0.17). In 62 prevalent PD patients, 1-SD higher PCS was negatively associated with 1-SD higher age. MCS was not associated to any of the investigated factors. Multivariate Cox regression analysis showed that in incident dialysis patients, 1-SD increase of PCS associated with lower all-cause mortality, hazard ratio 0.65 (95% confidence interval 0.52–0.81), after adjustments for age, sex, DM, CVD, plasma albumin, C-reactive protein and eGFR whereas 1-SD lower MCS did not associate with mortality. In PD patients, neither PCS nor MCS associated with mortality.ConclusionsMCS did not associate with any of the investigated clinical factors, whereas lower PCS associated with higher age, CVD, DM, and lower hemoglobin and sodium levels. MCS was not associated with mortality, whereas lower PCS associated with increased mortality risk. These results suggest that HRQoL - in addition to its role as patient-centered outcome - matters also for hard clinical outcomes in ESRD patients. Our knowledge about factors influencing MCS in ESRD patients is limited and should motivate further studies.

Change in neuron specific enolase levels in out-of-hospital cardiopulmonary arrest survivors as a simple and useful tool to predict neurological prognosis.

Neuron-specific enolase (NSE) is a prognostic marker in out-of-hospital cardiopulmonary arrest (OHCA) survivors treated with mild therapeutic hypothermia (MTH). The objectives were to analyze the correlation between dynamic changes in NSE and outcomes and to determine the measurement timing that best predicts neurological status. Multicenter cohort study including patients admitted after shockable rhythm OHCA and treated with MTH. Serum NSE was sampled at 2 different times and Δ-NSE (%) was calculated as 100 x (NSE2-NSE1)/NSE1. In-hospital mortality and neurological outcome, as assessed by the Cerebral Performance Category (CPC) scale, were evaluated during admission and after a 6-month follow-up. We included 166 patients admitted to 4 hospitals. In-hospital mortality was 31.9%. Almost 60% of patients had a good neurological recovery (CPC 1-2). On univariate and multivariate logistic regression analyses, an increase in NSE levels was associated with higher in-hospital mortality and worse CPC on discharge and after 6-months (P<.001). Positive Δ-NSE showed an OR=9.28 (95% CI 4.40-19.57) for mortality, OR=11.23 (95% CI 5.24-24.11) for CPC 3-5 at discharge and OR=11.14 (95% CI 5.05-24.55) for CPC 3-5 after 6-months' follow-up (P<.001). The first NSE measurement, conducted at 18 to 24hours, and the second measurement at 69 to 77hours after OHCA showed a high area under the curve in predicting CPC at discharge (0.9389 and 0.9909, respectively; 0.8096 for the whole cohort). Dynamic changes in NSE serum levels are good markers of hard clinical outcomes after an OHCA due to shockable rhythm in an MTH-treated cohort. NSE measurements at specific intervals after OHCA may predict events even more precisely.

Achievement of renal anemia KDIGO targets by two different clinical strategies \u2013 a European hemodialysis multicenter analysis

BackgroundThe optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse.MethodsA total of 1247 maintenance HD patients from 12 dialysis centers in Portugal (n = 730) and Poland (n = 517) were considered. We assessed achievement of KDIGO renal anemia targets with focus on treatment strategies, which typically differ between countries. In Poland the use and dose of IV iron was 35–72% higher than that in Portugal (p < 0.001) during three consecutive months; use and dose of ESA was 61% higher in Portugal (5034 vs 3133 IU (adjusted)/week, p < 0.001).ResultsMean Hb concentration was similar (11.0 vs 11.0 g/dL) in patients treated in both countries and the proportion of patients within KDIGO anemia target was 69.5% in Poland vs 65.8% in Portugal (NS). Ferritin and TSAT levels and the proportion of patients with TSAT > 20 and > 50% were both significantly higher in patients in Poland (88.8 and 14.6%) than in Portugal (76.3 and 5.7% respectively, p < 0.001). Significantly more patients in Poland had a ferritin concentration > 800 μg/L (35.6%) compared to Portugal (15.8%, p < 0.001). The ESA resistance index (ERI) was significantly higher in patients treated in Portugal (p < 0.001). Correlation analyses showed confounding by treatment indication in unadjusted models. Multiple and logistic regression analyses showed that with ferritin within KDIGO recommended range of 200–800 μg/L the odds for Hb within guidelines increased significantly. Annual gross mortality was 16% in Poland and 13% in Portugal (NS); there were no differences in cause-specific mortality.ConclusionsAdministration of high doses of IV iron in routine clinical HD practice may not be associated with considerable harm. However, large randomized controlled trials are needed to provide absolute evidence of iron safety.

Current approach to the diagnosis of atherosclerotic coronary artery disease: more questions than answers.

Despite its commonality in routine clinical practice, the approach to a diagnosis of atherosclerotic coronary artery disease remains complex and, in part, contentious. The traditional dogma linking ischaemia to hard clinical outcomes has been questioned and reframed over the years; rather than being a predictor of hard clinical outcomes, the degree of ischaemia may simply be a marker of atherosclerotic disease burden. A renewed interest in the imaging of plaque burden has spawned the contemporary role of CT imaging for not only diagnosis and prognosis, but also for dictating downstream management. As the technology develops and evidence expands, decisions on investigative modalities remain centred around patient factors, local availability, test performance and cost. This review summarizes the available methods for diagnosis in the symptomatic patient and provides an overview of the current evidence behind functional and anatomical approaches.

Autologous Cell Therapy for Vascular Regeneration: The Role of Proangiogenic Cells.

Autologous cell therapy represents a novel treatment option for vascular regeneration in different disease conditions, with experimental and clinical studies indicating a therapeutic potential for proangiogenic cells (PCs), including endothelial progenitor cells, in the treatment of coronary and peripheral artery disease. To provide a summary of the therapeutic potential of PCs administration or mobilization in peripheral artery disease, ischemic heart and cerebrovascular diseases, diabetic microvascular complications and inflammatory rheumatic diseases. We undertook a search of bibliographic databases for peer-reviewed research literature on the role of PCs in vascular regeneration in preclinical and clinical models. Improvement of ischemic symptoms has been reported in different trials evaluating PCs for the treatment of critical limb ischemia. However, in this setting, contrasting results from meta-analyses question the long-term clinical efficacy of PC-based approaches. Preclinical studies and clinical trials support the safety and feasibility of PC therapy in the treatment of ischemic heart and cerebrovascular diseases, while evidence indicating a benefit on hard clinical outcomes is uncertain. Despite accumulating experimental results support a therapeutic role for PCs in diabetic retinopathy, results from randomized clinical trials are lacking. Whether PC therapy may limit premature atherosclerosis and reduce cardiovascular risk in inflammatory rheumatic diseases needs to be investigated. Although the potential clinical applications of PCs are accumulating, there is also evidence of multiple limitations for autologous PC therapy. Thus, novel strategies aimed at improving PC viability and angiogenic function are warranted in order to improve the efficacy of cell therapy applications.

Effects of Trypanocidal Treatment on Echocardiographic Parameters in Chagas Cardiomyopathy and Prognostic Value of Wall Motion Score Index: A BENEFIT Trial Echocardiographic Substudy

Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. A prospective substudy was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2years, and final follow-up (5.4years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7±12.7% to 52.1±14.6% vs 56.3±12.7% to 52.8±14.1%) and LV WMSI similarly increased (1.31±0.41 to 1.49±0.03 and 1.27±0.38 to 1.51±0.03) for the benznidazole and placebo groups, respectively (P>.05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76±0.517 vs 1.271±0.393, P<.0001). There was a significant (P<.0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1<LV WMSI<1.5 and LV WMSI>1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes.

Continuous positive airway pressure for adults with obstructive sleep apnea and cardiovascular disease: a meta-analysis of randomized trials

BackgroundIt remains uncertain whether continuous positive airway pressure (CPAP) therapy would significantly impact hard clinical outcomes in patients with obstructive sleep apnea (OSA). This meta-analysis aimed to assess the effects of CPAP in survival and secondary prevention of major cardiovascular events in patients with OSA and cardiovascular disease (CVD). MethodsPubMed, Cochrane CENTRAL, LILACS, and SciElo databases (up to January 2018) were searched for randomized trials that compared CPAP with no active treatment in adults with OSA and CVD. The primary outcomes were all-cause death, cardiovascular death, acute myocardial infarction, stroke, and any major cardiovascular event. We used risk ratios (RR) and 95% confidence interval (CI) as the effect measures for dichotomous data, and weighted mean difference (WMD) and 95% CI for continuous variables. We used the random-effects method for meta-analysis. ResultsNine trials involving 3314 patients contributed data for meta-analysis of at least one outcome. The duration (median) of CPAP treatment varied from one month to 56.9 months. The pooled RR (95% CI) was 0.86 (0.60–1.23, I2 = 0.0%) for all-cause death, 0.58 (0.19–1.74, I2 = 47%) for cardiovascular death, 1.11 (0.76–1.62, I2 = 0.0%) for myocardial infarction, 0.77 (0.46–1.28, I2 = 16%) for stroke, and 0.93 (0.70–1.24, I2 = 49%) for any major cardiovascular event. The quality of evidence for these outcomes was low. ConclusionsLow-quality evidence suggests that CPAP therapy does not significantly improve survival or prevent major cardiovascular events in adults with OSA and cardiovascular disease.

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and exvivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and exvivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased exvivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.