Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID‐19) complications and deaths. We aimed ...to describe cases of SARS‐CoV‐2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID‐19 vaccine dose. The SECURE‐Liver and COVID‐Hep international reporting registries were used to identify laboratory‐confirmed COVID‐19 in CLD and LT patients who received a COVID‐19 vaccination. Of the 342 cases of lab‐confirmed SARS‐CoV‐2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID‐19 vaccination, including 12 who were fully vaccinated (≥2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID‐19 occurred in patients who had a single vaccine dose within the last 1‐2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID‐19 infections among patients with CLD and LT recipients who had received the COVID‐19 vaccination. Vaccination against SARS‐CoV‐2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients.
Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that ...early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis.
We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment.
We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m
, p < 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p < 0.001), mid-circumferential strain (- 20.8 ± 4.9 to - 19.1 ± 3.7, p = 0.02), apical circumferential strain (- 26.0 ± 5.3 to - 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003).
LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes.
ISRCTN registry number: 57475376 (assigned 25/06/2015).
Objective To investigate the degree to which ionising radiation confers risk of mortality from heart disease and stroke.Design Prospective cohort study with more than 50 years of follow-up.Setting ...Atomic bomb survivors in Hiroshima and Nagasaki, Japan.Participants 86 611 Life Span Study cohort members with individually estimated radiation doses from 0 to >3 Gy (86% received <0.2 Gy).Main outcome measures Mortality from stroke or heart disease as the underlying cause of death and dose-response relations with atomic bomb radiation.Results About 9600 participants died of stroke and 8400 died of heart disease between 1950 and 2003. For stroke, the estimated excess relative risk per gray was 9% (95% confidence interval 1% to 17%, P=0.02) on the basis of a linear dose-response model, but an indication of possible upward curvature suggested relatively little risk at low doses. For heart disease, the estimated excess relative risk per gray was 14% (6% to 23%, P<0.001); a linear model provided the best fit, suggesting excess risk even at lower doses. However, the dose-response effect over the restricted dose range of 0 to 0.5 Gy was not significant. Prospective data on smoking, alcohol intake, education, occupation, obesity, and diabetes had almost no impact on the radiation risk estimates for either stroke or heart disease, and misdiagnosis of cancers as circulatory diseases could not account for the associations seen.Conclusion Doses above 0.5 Gy are associated with an elevated risk of both stroke and heart disease, but the degree of risk at lower doses is unclear. Stroke and heart disease together account for about one third as many radiation associated excess deaths as do cancers among atomic bomb survivors.
Purpose We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for ...lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. Results Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. Conclusions Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.
Abstract
Background
Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn’s-like disease of the pouch. Antibiotics alter the gut ...microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn’s-like disease of the pouch.
Methods
We conducted a retrospective cohort study of patients with CADP or Crohn’s-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes.
Results
Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 67% vs 11 of 180 6%; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%).
Conclusion
Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA.
Summary Background Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic ...castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial. Methods Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form BPI-SF questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses. This study is registered with ClinicalTrials.gov , number NCT00887198. Findings 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2–24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months 95% CI 19·3–not estimable) than in those assigned to placebo plus prednisone (18·4 months 14·9–not estimable; hazard ratio HR 0·82, 95% CI 0·67–1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months 95% CI 9·3–13·0 vs 7·4 months 6·4–8·6; HR 0·79, 95% CI 0·67–0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months 95% CI 19·4–not estimable) than with placebo plus prednisone (19·4 months 16·6–not estimable), but the difference was not significant (HR 0·85, 95% CI 0·69–1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months 95% CI 11·1–14·0 vs 8·3 months 7·4–10·6; HR 0·78, 95% CI 0·66–0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months 8·6–13·8 vs 5·8 months 5·5–8·3; HR 0·70, 95% CI 0·60–0·83; p<0·0001). Interpretation Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population. Funding Janssen Research & Development.
Background
Human rhinoviruses (HRVs) are a common cause of upper respiratory infection (URI) in hematopoietic stem cell transplant (HSCT) recipients; yet, their role in lower respiratory illness is ...not well understood.
Methods
We performed a retrospective chart review of HSCT recipients with HRV infection from the time molecular detection methods were implemented at our institution in 2008. Factors associated with proven or possible HRV pneumonia at the first HRV detection were evaluated by univariate and multivariate analysis. We then characterized all episodes of proven and possible HRV pneumonia from the initial HRV infection through a 1‐year follow‐up period.
Results
Between 2008 and 2011, 63 HSCT recipients had ≥1 documented HRV infections. At first HRV detection, 36 (57%) patients had HRV URI and 27 (43%) had proven or possible HRV pneumonia; in multivariate analysis, hypoalbuminemia (odds ratio OR 9.5, 95% confidence interval CI 1.3–71.7; P = 0.03) and isolation of respiratory co‐pathogen(s) (OR 24.2, 95% CI 2.0–288.4; P = 0.01) were independently associated with pneumonia. During the study period, 22 patients had 25 episodes of proven HRV pneumonia. Fever (60%), cough (92%), sputum production (61%), and dyspnea (60%) were common symptoms. Fifteen (60%) episodes demonstrated bacterial (n = 7), fungal (n = 5), or viral (n = 3) co‐infection. Among the remaining 10 (40%) cases of HRV monoinfection, patients’ oxygen saturations ranged from 80% to 97% on ambient air, and computed tomography scans showed peribronchiolar, patchy, ground glass infiltrates.
Conclusions
HRV pneumonia is relatively common after HSCT and frequently accompanied by bacterial co‐infection. As use of molecular assays for respiratory viral diagnosis becomes widespread, HRV will be increasingly recognized as a significant cause of pneumonia in immunocompromised hosts.
A distinguishing trait of the three known Galactic recurrent novae with the shortest orbital periods, T Pyx, IM Nor, and CI Aql, is that their optical decline time-scales are significantly longer ...than those of the other recurrent systems. On the other hand, some estimates of the mass of the ejecta, the velocity of the ejecta, and the duration of the soft X-rays emission of these systems are of the order of those of the other recurrent systems and the fast classical novae. We put forth a tentative explanation of this phenomenon. We propose that in these systems part of the material transferred from the companion during the first few days of the eruption remains within the Roche lobe of the white dwarf, preventing the radiation from ionizing the ejecta of the system and increasing the optical decline time-scale. We explain why this phenomenon is more likely in systems with a high mass transfer rate and a short orbital period. Finally, we present a schematic model that shows that the material transferred from the companion is sufficient to absorb the radiation from the white dwarf in these systems, ultimately supporting this scenario as quantitatively realistic.
ModraDoc006, an oral formulation of docetaxel, is co-administered with the cytochrome P450–3A4 and P-glycoprotein inhibitor, ritonavir (r): ModraDoc006/r. The preliminary efficacy and safety of oral ...ModraDoc006/r was evaluated in a global randomized phase II trial and compared to the current standard chemotherapy regimen of intravenous (i.v.) docetaxel and prednisone.
103 mCRPC patients, chemotherapy-naïve with/without abiraterone and/or enzalutamide pretreated, with adequate organ function and evaluable disease per RECIST v1.1 and PCWG3 guidelines were randomized 1:1 into two cohorts. In Cohort 1, 49 patients received docetaxel 75 mg/m2 i.v. every 3 weeks (Q3W). In Cohort 2, 52 patients received ModraDoc006/r; 21 patients with a starting dose of ModraDoc006 30 mg with ritonavir 200 mg in the morning and ModraDoc006 20 mg with ritonavir 100 mg in the evening (30–20/200–100 mg) bi-daily-once-weekly (BIDW) on Days 1, 8, and 15 of a 21-day cycle. To alleviate tolerability, the starting dose was amended to ModraDoc006/r 20–20/200–100 mg in another 31 patients. All patients received prednisone 10 mg daily. Primary endpoint was rPFS.
There was no significant difference in rPFS between the 2 arms (p = 0.1465). Median rPFS was 9.5 months and 11.1 months (95% CI) for ModraDoc006/r and i.v. docetaxel, respectively. Partial response was noted in 44.1% and 38.7% measurable disease patients, and 50% decline of PSA was seen in 23 (50%) and 26 (56.5%) evaluable cases treated with ModraDoc006/r and i.v. docetaxel, respectively. The safety profile of ModraDoc006/r 20–20/200–100 mg dose was significantly better than i.v. docetaxel, with mild (mostly Grade 1) gastrointestinal toxicities, no hematologic adverse events, and neuropathy and alopecia incidence of 11.5% and 25%, respectively.
ModraDoc006/r potentially represents a widely applicable, convenient, effective, and better tolerated oral taxane therapy option for mCRPC. Further investigation of ModraDoc006/r in a large randomized trial is warranted.
•Docetaxel chemotherapy effectively prolongs survival in metastatic prostate cancer.•ModraDoc006/r is an oral formulation of docetaxel, combined with ritonavir.•ModraDoc006/r safety was favorable, and efficacy appeared comparable to docetaxel.•It has potential to make chemotherapy convenient and widely accessible in mCRPC.
PDF
