Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous‐flow left ventricular assist devices

Continuous‐flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24‐h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow‐up did not differ between groups and patients with major bleeding were not more likely to have a supra‐therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.     

Clinical features of patients undergoing hemodialysis with COVID‐19

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID‐19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality‐related risk factors for those who undergoing hemodialysis with COVID‐19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID‐19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36‐89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty‐eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground‐glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID‐19, and similar manifestations could be found in patients without SARS‐CoV‐2 infection. In conclusion, for hemodialysis patients with COVID‐19, lymphocytopenia and ground‐glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS‐CoV‐2 infection.     

Low molecular weight heparin versus unfractioned heparin for anticoagulation during perioperative extracorporeal membrane oxygenation: A single center experience in 102 lung transplant patients

Extracorporeal membrane oxygenation (ECMO) is gaining importance in the perioperative management of lung transplant patients. To date, the ideal substance for anticoagulation of ECMO patients is still a matter of debate. In this study, we describe our experience with the use of low molecular weight heparin (LMWH) in comparison with unfractioned heparin (UFH) in lung transplant patients undergoing perioperative ECMO support. We retrospectively analyzed data from all lung transplant patients who underwent perioperative ECMO support at our institution between 2013 and 2017. Bleeding events served as primary outcome parameter. Secondary outcome parameters consisted of thromboembolic events. 102 patients were included in this study, of which 22 (21.6%) received UFH for anticoagulation, and 80 (78.4%) received LMWH. There was no difference between the two groups in regard to serious bleeding events (22.7% in the UFH group vs 12.5% in the LMWH group, P = .31). However, the proportion of patients experiencing thromboembolic events was significantly higher in the UFH group than in the LMWH group (50% vs 20%, P = .01). After adjusting for baseline differences between the two groups, we still observed a difference with respect to thromboembolic events. These data remain to be validated in future prospective, randomized trials.     

Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat‐related post‐traumatic stress disorder: a double‐blind,randomized and placebo‐controlled study

OBJECTIVE

To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat‐related post‐traumatic stress disorder (PTSD).

PATIENTS AND METHODS

In all, 266 combat‐exposed war veterans with ED (aged 37–59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician‐Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. Patients with comorbid conditions (diabetes mellitus, hypercholesterolaemia, hypertension, Peyronie’s disease) and smokers of more than five cigarettes daily were excluded. The patients were randomly divided into a group of 133 who received 100 mg of on‐demand sildenafil 0.75–2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use ≥16 doses or attempts at home. The efficacy of the treatments was assessed every four attempts during treatment, and at the end of the study, using responses to the 15‐question International Index of Erectile Function (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, patients’ event logs of sexual activity, and a Global Assessment Question about erections.

RESULTS

Sildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures (P = 0.08). A normal EF domain score (≥26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively (P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo (P = 0.08). The incidences of treatment‐emergent adverse events were significantly greater in the sildenafil arm than in the placebo group (P = 0.01).

CONCLUSIONS

Sildenafil is no better than placebo in treating PTSD‐emergent ED. Further randomized clinical trials are warranted in combat veterans and other populations with PTSD to better elucidate the role of phosphodiesterase type 5 inhibitors in treating PTSD‐emergent ED.     

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial

BackgroundLong-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations.MethodsThis was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models.ResultsThirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2–0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, −0.11 to −0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4–9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0–8.0, p = .001). Dietary phosphorus intake was not related to cFGF23.ConclusionsIncreased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.     

External and internal bone micro‐architecture in normal and Kienböck's lunates: A whole‐bone micro‐computed tomography study

Kienböck's disease is idiopathic osteonecrosis of the lunate, leading to its fracture and collapse. This study compares internal and external bone micro‐architecture of normal and fractured lunates (Kienböck's), by using high‐resolution three‐dimensional (3D) micro‐computed tomography (micro‐CT) on the whole bone of the two lunate types, and histology. Fractured Kienböck‐diseased lunates were obtained from patients undergoing proximal‐row‐carpectomy, while normal cadaveric lunates served as controls. 3D‐micro‐CT‐imaging of control lunates revealed an encircling cortex surrounding trabecular bone. Trabeculae were arranged in a radial pattern, spanning from the distal to the proximal subchondral plate. Kienböck's lunates exhibited clear fracture lines, with fragmented bone, both proximally and distally, in areas the radially‐patterned trabeculae and enveloping cortex were absent, producing height loss. In trabecular bone, Kienböck's lunates revealed increased bone volume fraction, trabecular thickness and number, and decreased trabecular separation and structure model index. Histologically, Kienböck's lunates revealed osteonecrosis, as well as remodeling fronts with osteoblasts and osteoid surrounding bone marrow. Whole‐bone high‐resolution 3D examination of normal and Kienböck's diseased lunates contributes to a better understanding of micro‐architectural changes occurring in the pathology. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:826–833, 2014.     

Construct damage and loosening around glenoid implants: A longitudinal micro‐CT study of five cadaver specimens

The evolution of failure of bone and cement leading to loosening of glenoid components following shoulder arthroplasty is not well understood. The purpose of this study was to identify and visualize potential mechanisms of mechanical failure within cadavers, cemented with two types of components, and subject to cyclic loading. Five glenoid cadaver bones were implanted with either a three‐pegged polyethylene component, or prototype posteriorly augmented component which addresses posterior bone loss. Specimens were loaded by constant glenohumeral compression combined with cyclic anterior–posterior displacement of the humeral head relative to the glenoid. At six time points across 100,000 cycles, implant loosening micromotions were optically measured, and specimens were imaged by micro‐computed tomography. Scans were 3D registered and inspected for crack initiation and progression, and micro‐CT based time‐lapse movies were created. Cement cracking initiated at stress concentrations and progressed with additional cyclic loading. Failure planes within trabecular bone and the bone–cement interface were identified in four of the five specimens. Implant subsidence increased to greater than 1.0 mm in two specimens. Cemented glenoid structural failure can occur within the cement, along planes of trabecular bone, or at the bone cement interface. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1053–1060, 2016.     

Bleeding risk in breast cancer patients during concomitant administration of warfarin and tamoxifen: A population‐based nested case‐control study

We aimed to investigate whether the concomitant use of tamoxifen with warfarin is associated with higher risk for bleeding among patients with early estrogen‐receptor (ER)‐positive breast in a population‐based nested case‐control study. We identified 1787 patients taking warfarin and 92 cases hospitalized for bleeding and found an adjusted odds ratio (OR) of 1.42 (95% confidence interval (CI): 0.84‐2.40) for the risk of bleeding in patients treated with warfarin that initiated tamoxifen within the previous 30 days. As a result, we could not definitively rule out a potential association between tamoxifen use during warfarin and bleeding risk in patients with breast cancer.     

Association of mineral content outside of bone with coronary artery calcium and 1‐year cardiovascular prognosis in maintenance hemodialysis patients

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease‐mineral and bone disorder (CKD‐MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35‐63) years old were enrolled and followed up to 12 (11‐12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD‐MBD and 1‐year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue.     

EOS789, a broad-spectrum inhibitor of phosphate transport,is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients

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