Background and purpose
Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke.
Methods
Between January 2009 and December ...2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr), these patients were divided into dehydrated (BUN/Cr ≥ 15) and non‐dehydrated (BUN/Cr < 15) groups. Demographics, admission costs and discharge outcomes including modified Rankin scale (mRS) and Barthel index (BI) were examined. Data were analyzed using multivariate analysis of two‐stage least squares including logistic and linear regression.
Results
Acute ischaemic stroke with admission dehydration had higher infection rates (P = 0.006), worse discharge BI (62.8 ± 37.4 vs. 73.4 ± 32.4, P < 0.001, adjusted P < 0.001), worse mRS (2.7 ± 1.6 vs. 2.3 ± 1.5, P < 0.001, adjusted P = 0.009) and higher admission costs (2470.8 ± 3160.8 vs. 1901.2 ± 2046.8 US dollars, P < 0.001, adjusted P = 0.013) than those without dehydration. However, acute hemorrhagic stroke with or without admission dehydration showd no difference in admission costs (P = 0.618) and discharge outcomes (BI, P = 0.058; mRS, P = 0.058).
Conclusion
Admission dehydration is associated with worse discharge outcomes and higher admission costs in acute ischaemic stroke but not in hemorrhagic stroke.
Microsatellite-stable metastatic colorectal cancer is typically unresponsive to immunotherapy. This phase 3 study was designed to assess atezolizumab plus cobimetinib in metastatic colorectal cancer. ...Here, we report the comparison of atezolizumab plus cobimetinib or atezolizumab monotherapy versus regorafenib in the third-line setting.
IMblaze 370 is a multicentre, open-label, phase 3, randomised, controlled trial, done at 73 academic medical centres and community oncology practices in 11 countries. Patients aged at least 18 years with unresectable locally advanced or metastatic colorectal cancer, baseline Eastern Cooperative Oncology Group performance status of 0–1, and disease progression on or intolerance to at least two previous systemic chemotherapy regimens were enrolled. We used permuted-block randomisation (block size four) to assign patients (2:1:1) via an interactive voice and web response system to atezolizumab (840 mg intravenously every 2 weeks) plus cobimetinib (60 mg orally once daily for days 1–21 of a 28-day cycle), atezolizumab monotherapy (1200 mg intravenously every 3 weeks), or regorafenib (160 mg orally once daily for days 1–21 of a 28-day cycle). Stratification factors were extended RAS status (wild-type vs mutant) and time since diagnosis of first metastasis (<18 months vs ≥18 months). Recruitment of patients with high microsatellite instability was capped at 5%. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. IMblaze370 is ongoing and is registered with ClinicalTrials.gov, number NCT02788279.
Between July 27, 2016, and Jan 19, 2017, 363 patients were enrolled (183 patients in the atezolizumab plus cobimetinib group, 90 in the atezolizumab group, and 90 in the regorafenib group). At data cutoff (March 9, 2018), median follow-up was 7·3 months (IQR 3·7–13·6). Median overall survival was 8·87 months (95% CI 7·00–10·61) with atezolizumab plus cobimetinib, 7·10 months (6·05–10·05) with atezolizumab, and 8·51 months (6·41–10·71) with regorafenib; the hazard ratio was 1·00 (95% CI 0·73–1·38; p=0·99) for the combination versus regorafenib and 1·19 (0·83–1·71; p=0·34) for atezolizumab versus regorafenib. Grade 3–4 adverse events were reported in 109 (61%) of 179 patients in the atezolizumab plus cobimetinib group, 28 (31%) of 90 in the atezolizumab group, and 46 (58%) of 80 in the regorafenib group. The most common all-cause grade 3–4 adverse events in the combination group were diarrhoea (20 11% of 179), anaemia (ten 6%), increased blood creatine phosphokinase (12 7%), and fatigue (eight 4%). Serious adverse events were reported in 71 (40%) of 179 patients in the combination group, 15 (17%) of 90 in the atezolizumab group, and 18 (23%) of 80 in the regorafenib group. Two treatment-related deaths occurred in the combination group (sepsis) and one in the regorafenib group (intestinal perforation).
IMblaze370 did not meet its primary endpoint of improved overall survival with atezolizumab plus cobimetinib or atezolizumab versus regorafenib. The safety of atezolizumab plus cobimetinib was consistent with those of the individual drugs. These results underscore the challenge of expanding the benefit of immunotherapy to patients whose tumours have lower baseline levels of immune inflammation, such as those with microsatellite-stable metastatic colorectal cancer.
F Hoffmann-La Roche Ltd/Genentech Inc.
Highlights • Detection of irisin immunoreactivity in skeletal muscle and cardiomyocyte. • Presence of irisin immunoreactivity in the Purkinje cells of the cerebellum. • Co-expression of irisin ...immunoreactivity and glutamate decarboxylase (GAD) immunoreactivity in the Purkinje cells of the cerebellum. • Hypothetical neurocircuitry connecting the cerebellum to the fat tissue that may regulate adipocyte metabolism.
Background
This is the fourth updated Enhanced Recovery After Surgery (ERAS
®
) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded ...recommendations for each ERAS item within the ERAS
®
protocol.
Methods
A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
Results
All recommendations on ERAS
®
protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly.
Conclusions
The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS
®
Society in this comprehensive consensus review.
Direct solar-powered production of value-added chemicals from CO2 and H2O, a process that mimics natural photosynthesis, is of fundamental and practical interest. In natural photosynthesis, CO2 is ...first reduced to common biochemical building blocks using solar energy, which are subsequently used for the synthesis of the complex mixture of molecular products that form biomass. Here we report an artificial photosynthetic scheme that functions via a similar two-step process by developing a biocompatible light-capturing nanowire array that enables a direct interface with microbial systems. As a proof of principle, we demonstrate that a hybrid semiconductor nanowire–bacteria system can reduce CO2 at neutral pH to a wide array of chemical targets, such as fuels, polymers, and complex pharmaceutical precursors, using only solar energy input. The high-surface-area silicon nanowire array harvests light energy to provide reducing equivalents to the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production of acetic acid under aerobic conditions (21% O2) with low overpotential (η < 200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200 h). The resulting acetate (∼6 g/L) can be activated to acetyl coenzyme A (acetyl-CoA) by genetically engineered Escherichia coli and used as a building block for a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB) polymer, and three different isoprenoid natural products. As such, interfacing biocompatible solid-state nanodevices with living systems provides a starting point for developing a programmable system of chemical synthesis entirely powered by sunlight.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.
We examined the number of tropical cyclones and cyclone days as well as tropical cyclone intensity over the past 35 years, in an environment of increasing sea surface temperature. A large increase ...was seen in the number and proportion of hurricanes reaching categories 4 and 5. The largest increase occurred in the North Pacific, Indian, and Southwest Pacific Oceans, and the smallest percentage increase occurred in the North Atlantic Ocean. These increases have taken place while the number of cyclones and cyclone days has decreased in all basins except the North Atlantic during the past decade.
Summary
Background
Rifaximin might decrease the risk of portal hypertension‐related complications by controlling small intestinal bacterial overgrowth.
Aim
To evaluate whether rifaximin was ...associated with the risk of death and cirrhotic complications.
Methods
We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non‐HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding.
Results
In the non‐HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio aHR, 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile‐associated diarrhoea was not different between the groups (aHR, 0.028; P = .338).
Conclusions
In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
Linked Content
This article is linked to Juang, Kang et al, Wang et al, and Borentain et al papers. To view these papers visit https://doi.org/10.1111/apt.14325, https://doi.org/10.1111/apt.14343, https://doi.org/10.1111/apt.14353 and https://doi.org/10.1111/apt.14516.
Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or ...nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.
Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative ...outcomes among patients with aortic stenosis who are at intermediate surgical risk.
We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement.
A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval Bayesian analysis for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group.
TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).
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