First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension

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Presence of tumour capsule on contrast-enhanced CT is associated with improved outcomes of stereotactic body radiation therapy in hepatocellular carcinoma patients

Purpose Stereotactic body radiation therapy (SBRT) is a novel local therapy for the treatment of hepatocellular carcinoma (HCC). While effective, there is currently noreliable radiological marker to guide patient selection. In this study, we investigated the prognostic value of capsule appearanceon contrast-enhanced computed tomography (CT) for patients undergoing SBRT. Materials and Methods Between 2006 and 2017, 156 consecutive patients with Child-Pugh score class A/B and HCC ≥5cm that underwent SBRT were retrospectively analysed. Baseline triple-phase CTs of the abdomen were reviewed for the presence of capsule appearances and correlated with objective response rate (ORR), overall survival (OS), and pattern of treatment failure. Results Capsule appearance on CT was present in 83 (53.2%) patients.It was associated with improved ORR by Response Evaluation Criteria in Solid Tumours (RECIST) (60.2% vs 24.7%; p<0.001) andModified Response Evaluation Criteria in Solid Tumours(mRECIST) (ORR 78.3% vs 34.2%; p<0.001). The presence of a capsule was also associated with superior 2-year local control (89.1% vs. 51.4%; p<0.001) and 2-year OS (34.1% vs. 14.8%, p<0.01). Hepatic out-field failure was the dominant mode of progression, which was less common in patients with intact capsule (54.2% vs. 60.3%, p=0.01). Conclusion Capsule appearance on CT could potentially be a non-invasive prognostic marker for selecting HCC patients undergoing SBRT. Larger cohort is warranted to validate our findings

The effects of a mindfulness-based family psychoeducation intervention for the caregivers of young adults with first-episode psychosis: A randomized controlled trial

Objective: In this study, we investigated the effects of a mindfulness-based family psychoeducation (MBFPE) program on the mental-health outcomes of both caregivers and young adults with first-episode psychosis with an onset in the past three years through a multi-site randomized controlled trial. We also studied the outcomes of three potential mediating effects of interpersonal mindfulness, expressed emotions, and non-attachment on the program. Method: We randomly assigned 65 caregivers of young adults with psychosis to MBFPE (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32); among them, 18 young adults in recovery also participated in the evaluation of outcomes. Results: Intent-to-treat analyses were conducted. No significant time × group interaction effects of MBFPE and FPE programs were found in any of the caregivers’ outcomes. However, the young adults with psychosis reported higher levels of recovery after the MBFPE program than after the ordinary FPE program (F = 8.268, p = 0.012, d = 1.484). They also reported a larger reduction in over-involvement of their caregivers (F = 4.846, p = 0.044, d = 1.136), showing that MBFPE had a superior effect to FPE in promoting recovery and reducing over-involvement. Conclusions: A brief psychoeducation program may not reduce the burden on or improve the mental-health outcome of caregivers of individuals with recent-onset psychosis. However, integrating mindfulness into a conventional family psychoeducation program may reduce the expressed emotions of caregivers, especially over-involvement. Further studies should explore how psychoeducation programs can reduce the impact of psychosis on family through sustainable effects in terms of reducing their burden and expressed emotions, using a rigorous study and adequate sample size

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The Vascular-Renal Connection in Patients Hospitalized With Hypertensive Crisis: A Population-Based Study

Objective: To determine the risks of acute kidney injury development and long-term clinical outcomes of patients with hypertensive crisis. Patients and Methods: This was a population study of Olmsted County residents with hypertensive crisis between January 1, 2000, and December 31, 2008, with follow-up until June 30, 2016. Results: The results demonstrated that those with underlying chronic kidney disease upon admission for hypertensive crisis, defined as a systolic blood pressure above 180 mm Hg or diastolic blood pressure above 120 mm Hg, were more likely to develop acute kidney injury during hospitalization (odds ratio, 6.04; 95% CI, 1-26; P=.02). Hospitalization length of stay was increased when patients developed acute kidney injury during hypertensive crisis hospitalization (7.6±9 vs 3.4±4 days; P=.04). Furthermore, those who developed acute kidney injury had increased cardiac rehospitalization frequency over 10 years (87% vs 46%; P=.009). These results suggest that those with poor renal reserve are more likely to have further acute kidney damage in the setting of hypertensive crisis, likely due to decreased renal perfusion and neurohormonal dysregulation. Conclusion: In patients hospitalized for hypertensive crisis, chronic renal insufficiency was a risk factor associated with acute kidney injury development during hospitalization. Those who developed acute kidney injury had longer hospitalizations with increased rehospitalization frequency. Future studies are warranted to further investigate whether the preservation of renal function will improve clinical outcomes in hospitalized patients with hypertensive crisis