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Background Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia. Methods A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. Results In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, − 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2 = 101–200. Conclusions Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration ClinicalTrials.gov, NCT04345614. Submitted on 7 April 2020. Graphical abstract

Background. End-stage renal disease (ESRD) patients are prescribed numerous medications. The United States Renal Data System (USRDS) reported on medication prescribing patterns in 1998. Since then, several new medications, treatment guidelines and recommendations have been introduced. The objective was to analyse and compare haemodialysis (HD) patient medication prescribing patterns between the Dialysis Clinic, Inc. (DCI) database and the USRDS report. Methods. Point-prevalent (01/01/03) medication use data from the DCI national database was obtained. Data collected included patient demographics, reason for and duration of ESRD, and medication listed on profile. All medications were classified similar to the USRDS and by where taken (clinic vs home). Medication prescribing patterns were compared between DCI and USRDS databases. Comparisons between age groups (

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

article i nfo Objective. The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malig- nant pelvis masses in Asian women. Methods. This was a prospective, multicenter (n=6) study with patients from six Asian countries. Pa- tients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, posi- tive predictive value (PPV) and negative predictive value (NPV). Results. A total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensi- tivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk. Conclusion. ROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.

Enteric-coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side-effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side-effect profile of MPS remain. Therefore, the purpose of this study is to review a single-center's experience with mycophenolate mofetil (MMF) and MPS.This retrospective, sequential cohort analysis of de novo renal and pancreas transplants (n = 198) compared MMF 500 mg b.i.d. to MPS 360 mg b.i.d. in conjunction with antibody induction, tacrolimus, and steroids.There were fewer adverse event driven drug manipulations in the MPS group at 90 d (4% MPS vs. 17% MMF) and 180 d (10% MPS vs. 24% MMF, p = 0.006, log-rank) after transplantation. There was a trend toward fewer GI-related hospital admissions in the MPS arm (7% MPS vs. 13% MMF, p = 0.18). Allograft outcomes including patient survival, graft survival, acute rejection, serum creatinine, and infection were similar.This single-center, sequential cohort study demonstrates that MPS is associated with fewer adverse event driven drug manipulations while maintaining similar safety and allograft outcomes.

Objective The purpose of this study was to develop a risk prediction score for distinguishing benign ovarian mass from malignant tumors using CA-125, human epididymis protein 4 (HE4), ultrasound findings, and menopausal status. The risk prediction score was compared to the risk of malignancy index and risk of ovarian malignancy algorithm (ROMA). Methods This was a prospective, multicenter (n=6) study with patients from six Asian countries. Patients had a pelvic mass upon imaging and were scheduled to undergo surgery. Serum CA-125 and HE4 were measured on preoperative samples, and ultrasound findings were recorded. Regression analysis was performed and a risk prediction model was developed based on the significant factors. A bootstrap technique was applied to assess the validity of the HE4 model. Results A total of 414 women with a pelvic mass were enrolled in the study, of which 328 had documented ultrasound findings. The risk prediction model that contained HE4, menopausal status, and ultrasound findings exhibited the best performance compared to models with CA-125 alone, or a combination of CA-125 and HE4. This model classified 77.2% of women with ovarian cancer as medium or high risk, and 86% of women with benign disease as very-low, low, or medium-low risk. This model exhibited better sensitivity than ROMA, but ROMA exhibited better specificity. Both models performed better than CA-125 alone. Conclusion Combining ultrasound with HE4 can improve the sensitivity for detecting ovarian cancer compared to other algorithms.

Hemodialysis (HD) patients are at risk for medication-related problems. Patient characteristics associated with the number of medication-related problems in HD patients have not been investigated.Patient records were reviewed to identify medical problems, prescribed medications, medication indication(s), and medication-related problems. Medication classes and medication-related problems were compared between patients with and without diabetes mellitus (DM). Correlations were performed to determine whether associations exist between medication-related problems, number of medications, number of medication doses per day, number of comorbid conditions, patient age, and duration of end-stage renal disease while controlling for DM status.Medical records of 133 patients were evaluated. Patients were 60.5 +/- 15.2 years old, prescribed 11.0 +/- 4.2 medications, and had 6.0 +/- 2.3 comorbidities. Medication-related problems were identified in 97.7% of patients. Four hundred seventy-five medication-related problems were identified, averaging 3.6 +/- 1.8 medication-related problems per patient. Patients with DM had more medication-related problems identified than those without DM (303 versus 172 medication-related problems, respectively; P0.05). Medication-related problems correlated positively with number of patient comorbidities (P0.001).Medication-related problems are prevalent in virtually all HD patients. The number of medication-related problems in an individual patient increases as the number of comorbid conditions increases. The most frequent medication-related problems were drug without indication (30.9%), laboratory (27.6%), indication without drug use (17.5%), and dosing errors (15.4%). Patients with DM are at increased risk for medication-related problems. Health care providers taking care of HD patients should be aware of this problem, and efforts to avoid or resolve medication-related problems should be undertaken at all HD clinics.