Effects of mycophenolic acid on highly sensitized patients awaiting kidney transplant

Background10–30% of dialysis population awaiting renal transplantation is sensitized. Mycophenolic acid (MPA) has been shown to reduce panel reactive antibody (PRA) formation in kidney transplant recipients. Our aim was to investigate whether MPA could effectively reduce anti-HLA antibody levels and allow successful transplantation.MethodsA total of 40 highly sensitized patients were treated orally with MPA. All patients had T-cell PRA values greater than 30% (73% of patients were ≥ 75%). The PRAs, T-cell/B-cell flow cytometry crossmatch (FCXM) mean channel shift (MCS), patient/graft survival, acute rejection, and serum creatinine (SCr) were recorded.ResultsAll 40 patients showed a decrease in PRA levels. Eighteen of the 40 patients (40%) received a transplant. All four living donor recipients converted to a negative crossmatch. There was a significant decrease in FCXM MCS in all 18 transplanted patients. The mean SCr at 24 months was 1.00 ± 0.25 mg/dL. Five patients (28%) experienced acute rejection. The overall one year actuarial patient and graft survival were 94% and 88%, respectively.ConclusionsThese findings suggest that MPA therapy is effective in reducing PRAs and increases the likelihood of successful transplantation in sensitized recipients in a potentially simpler and more cost effective manner than the current regimens employed.     

Multimodality imaging of fat-containing adrenal metastasis from hepatocellular carcinoma

A biopsy-proven fat-containing metastasis to the adrenal gland in a patient with hepatocellular carcinoma demonstrated low density on nonenhanced CT, heterogeneity on contrast-enhanced CT, and marked signal loss on opposed-phase gradient-echo MRI, mimicking an adrenal adenoma. However, the mass was not present on older studies and showed increased FDG uptake on PET. The possibility of a fat-containing metastasis should be considered for an apparent adrenal adenoma in a patient with a primary hepatocellular carcinoma.     

Zinc in Ruminants: Metabolism and Homeostasis

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Zinc is one of the most studied minerals of the twenty-first century as it is practically involved in every...     

Predialysis Systolic BP Variability and Outcomes in Hemodialysis Patients

BP variability (BPV) is an important predictor of outcomes in the general population, but its association with clinical outcomes in hemodialysis patients is not clear. We identified 11,291 patients starting dialysis in 2003–2008 and followed them through December 31, 2008 (median=22 months). Predialysis systolic BPV was assessed over monthly intervals. Outcomes included factors associated with BPV, mortality (all-cause and cardiovascular), and first cardiovascular event (cardiovascular death or hospitalization). Patients'' mean age was 62 years, 55% of patients were men, and 58% of patients were white. Modifiable factors associated with higher BPV included obesity, higher calcium–phosphate product levels, and lower hemoglobin concentration; factors associated with lower BPV included greater fluid removal, achievement of prescribed dry weight during dialysis, higher hemoglobin concentration, and antihypertensive regimens without β-blockers or renin-angiotensin system blocking agents. In total, 3200 deaths occurred, including 1592 cardiovascular deaths. After adjustment for demographics, comorbidities, and clinical factors, higher predialysis BPV was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.18; 95% confidence interval [95% CI] per 1 SD increase in BPV, 1.13 to 1.22), cardiovascular mortality (HR, 1.18; 95% CI, 1.12 to 1.24), and first cardiovascular event (HR, 1.11; 95% CI, 1.07 to 1.15). Results were similar when BPV was categorized in tertiles and patients were stratified by baseline systolic BP. In summary, predialysis systolic BPV is an important, potentially modifiable risk factor for death and cardiovascular outcomes in incident hemodialysis patients. Studies of BP management in dialysis patients should focus on both absolute BP and BPV.Hypertension is highly prevalent in hemodialysis patients, occurring in over 90% of patients, but optimal strategies for management of hypertension in these patients remain unclear.^1–4 A great majority of prior studies have focused on the association between patients’ mean predialysis BP levels and outcomes^5–9; however, nearly all patients receiving dialysis also experience fluctuations in their BP (referred to here as BP variability [BPV]). BPV can be seen with different BP components, including systolic BP, diastolic BP, and pulse pressure, as well as predialysis, intradialytic, and postdialysis BPs. The factors associated with intradialytic BPV have recently been described,¹⁰ but the factors associated with predialysis BPV and its association with clinical outcomes are not well understood.BPV reflects the disruption of BP homeostasis. It can result from both micro- and macrovascular disease, resulting in greater susceptibility to BP fluctuations in response to environmental stimuli.^11,12 In hypertensive patients not on dialysis, CKD is associated with higher BPV, and BPV has been associated with higher risk of vascular events, such as stroke and myocardial infarction.¹³ Patients on hemodialysis are particularly prone to increased BPV because of a high prevalence of vascular disease combined with unique dialysis-related factors, such as stress, volume shifts, unusual antihypertensive medication schedules, and dialyzability of antihypertensive medications.^2,10Although recent studies have begun to show an association between BPV and mortality in patients on hemodialysis, many studies have not accounted for factors that can influence BPV, such as patients’ dialysis volume management or BP medication regimens.¹⁴ Thus, they have had limited ability to make causal links between BPV and patient outcomes. If BPV is indeed associated with greater mortality among hemodialysis patients (who already have extremely poor survival rates),¹⁵ studies better elucidating factors that decrease BPV could aid efforts to reduce excess mortality.Predialysis systolic BP is generally used to make clinical decisions regarding management of hypertension in hemodialysis patients. Systolic BP is also the major contributor to pulse pressure. We therefore decided to assess the factors associated with predialysis systolic BPV and quantified the association of BPV with morbidity and mortality in a cohort of 11,291 incident hemodialysis patients.     

High-density lipoprotein in uremic patients: metabolism,impairment, and therapy

Several studies have shown that HDL has altered antioxidant and anti-inflammatory effects in chronic uremia, either by the reduction in its antioxidant enzymes or by the impairment of their activity. Systemic oxidative stress, which is highly prevalent in chronic kidney disease (CKD) patients, has been shown to decrease antioxidant and anti-inflammatory effects of HDL and even transform it into a pro-oxidant and pro-inflammatory agent. For this reason, we believe that the propensity for accelerated cardiovascular disease in CKD is facilitated by a few key features of this disease, namely, oxidative stress, inflammation, hypertension, and disorders of lipid metabolism. In a nutshell, oxidative stress and inflammation enhance atherosclerosis leading to increased cardiovascular mortality and morbidity in this population. In this detailed review, we highlight the current knowledge on HDL dysfunction and impairment in chronic kidney disease as well as the available therapy.     

Association of blood group with COVID-19 disease susceptibility and severity in Saudi Arabia

Background

Novel SARS-CoV-2 (COVID-19) virus has rapidly spread worldwide and was declared a pandemic, making identifying and prioritizing individuals most at risk a critical challenge. The literature describes an association between blood groups and the susceptibility to various viral infections and their severity. Knowing if a specific blood group has more susceptibility to COVID-19 may help improve understanding the pathogenesis and severity of the disease. We aimed to assess the association between ABO/RhD and COVID-19 susceptibility and severity, and to compare results with similar studies in Saudi Arabia.

Study Design and Methods

This study was conducted between March and October 2021 on 600 patients confirmed positive for COVID-19 infection. Patients' data were collected and analyzed. As a control, 8423 healthy blood donors were enrolled as a sample representative of the population for blood group distribution.

Results

More individuals had blood group B in the COVID-19 group in comparison with the control group (24.2% vs. 18%), The opposite was observed among individuals of group O (39.5% vs. 47.3%). The B blood group was predictive of higher risk of mortality. No significant difference in the distribution of RhD was observed between the COVID-19 and the control groups. Neither ABO nor RhD was significantly associated with the severity of COVID-19.

Discussion

Although there was no significant association with the disease severity, the B blood group may be associated with a higher risk for COVID-19 infection. Further studies with a larger sample size are necessary to evaluate this correlation.     

Unmet Needs for Transdermal Patch Management in Electronic Medication Administration Records: An Analysis of Data from 66 Aged Care Facilities

Background  Transdermal medication patches have caused serious adverse events in residential aged care facilities (RACFs). Preliminary research suggests that facilities are using a workaround consisting of manually entered reminders in their electronic medication administration records (eMARs) to prompt staff to check and remove patches, because the eMAR does not support these tasks. However, the prevalence and factors associated with use of this workaround among facilities is unknown. Objectives  The objectives of this study were to (1) examine the frequency and consistency with which manual reminders to check and remove transdermal patches were used in facility eMARs, and (2) identify resident and facility factors associated with reminder use, to inform eMAR redesign. Methods  This was a retrospective cross-sectional analysis of eMAR data from 66 Australian RACFs including 4,787 permanent residents, aged ≥65 years in January 2017. Prevalence of the use of reminders to check and remove patches, and consistency in their application within facilities were examined. Generalized estimating equations were used to determine factors associated with use of manual reminders. Results  One in five ( n  = 937) residents used a patch, and 83.6% of patches contained opioids, a high-risk medicine. 56.9% of facilities implemented manually entered check patch reminders in the eMAR, and 72.3% implemented remove reminders. The reminders were applied inconsistently, with only half of these facilities having reminders for all residents with patches. Residents in facilities in regional areas were more likely to have a check reminder compared with those in major cities (adjusted odds ratio = 4.72 [95% confidence interval: 1.69–13.20]). Conclusion  Transdermal patches containing high-risk medicines are frequently used in RACFs, but their safe administration is not supported by a widely implemented eMAR. The frequent, but inconsistent use of a workaround to manually enter reminders indicates an unmet need for new eMAR functionality to improve safety.