Summary Background High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood ...pressure variability in participants of INTERACT2, an open-label randomised controlled trial ( ClinicalTrials.gov number NCT00716079 ). Methods INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150–220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2–7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. Findings We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05–1·90; ptrend =0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14–2·17; ptrend =0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14–1·80; ptrend =0·0014; for the acute phase OR 1·46, 95% CI 1·13–1·88; ptrend =0·0044). Interpretation Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. Funding National Health and Medical Research Council of Australia.
We describe observed properties of the Type Iax class of supernovae (SNe Iax), consisting of SNe observationally similar to its prototypical member, SN 2002cx. The class currently has 25 members, and ...we present optical photometry and/or optical spectroscopy for most of them. SNe Iax are spectroscopically similar to SNe Ia, but have lower maximum-light velocities, typically lower peak magnitudes, and most have hot photo-spheres. There is a correlation between luminosity and light-curve shape, similar to that of SNe Ia, but offset from that of SNe Ia and with larger scatter. Being the largest class of peculiar SNe, thousands of SNe Iax will be discovered by LSST. Future detailed observations of SNe Iax should further our understanding of both their progenitor systems and explosions as well as those of SNe Ia.
We report the discovery of WASP-4b, a large transiting gas-giant planet with an orbital period of 1.34 days. This is the first planet to be discovered by the SuperWASP-South observatory and CORALIE ...collaboration and the first planet orbiting a star brighter than 16th magnitude to be discovered in the southern hemisphere. A simultaneous fit to high-quality light curves and precision radial velocity measurements leads to a planetary mass of 1.22 super(+) sub(-) super(0) sub(0) super(.) sub(.) super(0) sub(0) super(9) sub(8) M sub(Jup) and a planetary radius of 1.42 super(+) sub(-) super(0) sub(0) super(.) sub(.) super(0) sub(0) super(7) sub(1) R sub(Jup). The host star is USNO-B1.0 0479-0948995, a G7 V star of visual magnitude 12.5. As a result of the short orbital period, the predicted surface temperature of the planet is 1761 K, making it an ideal candidate for detections of the secondary eclipse at infrared wavelengths.
The morphology of ventricular septal defects (VSDs) that are doubly committed and juxtaarterial places the patient at risk for aortic valvar prolapse and aortic valvar insufficiency (AI). Surgical ...repair of this type of defect often involves placing sutures through the base of one or more of the leaflets of the pulmonary valve, raising concern for late pulmonary valvar insufficiency (PI). The purpose of this review was to analyze the postoperative follow-up relating to potential late complications with the aortic and pulmonary valves.
Between 1980 and 2012, 106 patients with doubly committed juxtaarterial VSD underwent intracardiac repair. Median age at repair was 1.1 years. Preoperative evaluation showed 69 patients (65%) had aortic valvar prolapse and 51 (48%) had AI. Operative approach was through the pulmonary trunk in 88 (83%) of the patients. In 81 patients (76%), sutures securing the VSD patch had been placed through the base of the pulmonary valvar leaflets.
Operative survival was 100%. Follow-up ranges from 6 months to 17 years, with a mean of 4.9 years. No patient had heart block or residual shunting. Of the 70 patients with long-term contemporary echocardiographic follow-up, 66 (94%) had trivial or no AI and 4 (6%) had mild AI. Of these patients, 49 (70%) had trivial or no PI, and 21 (30%) had mild PI. In 1 patient having aortic valvoplasty at the time of VSD closure, the aortic valve was replaced 7 months later. No other patient had worrisome progression of their AI or PI.
The incidence of aortic valvar prolapse and AI in the setting of doubly committed juxtaarterial VSD is quite high. The optimal surgical approach is through the pulmonary trunk. Sutures placed through the base of the pulmonary valvar leaflets do not predispose to clinically significant late pulmonary valvar insufficiency. Timely surgical closure of this type of defect prevents progression of AI.
We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) ...treated with or without neoadjuvant chemotherapy.
Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed.
The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ⩽10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001).
The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies.
Total shoulder arthroplasty (TSA) is an increasingly common procedure. This study looked at trends in TSA using a nationwide registry, with a focus on patient demographics, comorbidities, and ...complications.
The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent TSA from 2005 to 2018. Cohorts were created based on year of surgery: 2005-2010 (N = 1116), 2011-2014 (N = 5920), and 2015-2018 (N = 16,717). Patient demographics, comorbidities, operative time, hospital length of stay, discharge location, and complications within 30 days of surgery were compared between cohorts using bivariate and multivariate analysis.
Bivariate analysis revealed significantly more comorbidities among patients in the 2015-2018 cohort compared with the 2005-2010 cohort, specifically American Society of Anesthesiologist class III or IV (57.0% vs. 44.3%, P < .001), morbid obesity (10.8% vs. 7.8%, P < .001), diabetes (17.8% vs. 12.1%, P < .001), and chronic obstructive pulmonary disease (6.7% vs. 4.1%, P = .003). The use of regional anesthesia has decreased (5.6% in 2005-2010 vs. 2.8% in 2015-2018, P < .001), as has operative time (▵: −16 minutes, P < .001) and length of stay (▵: −0.6 days, P < .001). There were also significant decreased rates of perioperative blood transfusion (OR odds ratio, 0.46), non-home discharge (OR, 0.79), urinary tract infection (OR, 0.47), and sepsis (OR, 0.17), (P < .001 for all comparisons) between the 2005-2010 and 2015-2018 cohorts.
Between 2005 and 2018, patients undergoing TSA had increasingly more comorbidities but experienced lower rates of short-term complications, in the context of shorter hospitalizations and more frequent discharge to home.
This phase II trial examined the addition of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, to mFOLFOX6 as front-line therapy for patients with advanced gastric/GEJ ...or esophageal adenocarcinoma. A survival benefit was not observed in the ITT population, but an exploratory analysis suggested a potential benefit for ramucirumab in the gastric/GEJ cancer subgroup.
We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ).
Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure–response analysis was undertaken.
Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS 6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69–1.37) or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure–response analysis indicated that patients with higher ramucirumab exposure had longer OS.
The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population.
NCT01246960.
Bisphosphonates comprise the most common treatment for patients with osteoporosis and fracture risk. Large randomized trials have shown that these therapies may increase the risk of atrial ...fibrillation (AF). Controversy over the arrhythmia risk prompted the Federal Drug Administration to recently pursue an ongoing safety review to determine the cardiac risk across the entire drug class. Study patients came from 2 large prospective databases (ongoing registry of consecutive patients who underwent coronary angiography and the Intermountain Healthcare health plans database). Medical details regarding bisphosphonate use and cardiovascular risk factors were abstracted from the records. End points included AF, myocardial infarction, and death. In the angiographic database (n = 9,623), patients treated with bisphosphonates were older and more likely to have hypertension, a previous myocardial infarction, heart failure, and osteoporosis. Over 1,481 ± 1,024 days we found no increased risk of AF in the drug-treated group (hazard ratio 0.90, 95% confidence interval 0.48 to 1.68, p = 0.74). In the Intermountain Healthcare health plans database (n = 37,485), patients treated with bisphosphonates were older and were more likely to have hyperlipidemia and osteoporosis. Over 1,667.5 ± 557.0 days, there was no increased risk of AF (hazard ratio 0.82, 95% confidence interval 0.66 to 1.01, p = 0.63). In the 2 databases there was no statistical difference in long-term rates of myocardial infarction or mortality. In conclusion, in a long-term study of >47,000 patients, we were unable to find an association between bisphosphonate therapy and AF. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials.
To investigate the longitudinal performance of a surgically implanted neuroprosthesis for lower-extremity exercise, standing, and transfers after spinal cord injury.
Case series.
Research or ...outpatient physical therapy departments of 4 academic hospitals.
Subjects (N=15) with thoracic or low cervical level spinal cord injuries who had received the 8-channel neuroprosthesis for exercise and standing.
After completing rehabilitation with the device, the subjects were discharged to unrestricted home use of the system. A series of assessments were performed before discharge and at a follow-up appointment approximately 1 year later.
Neuroprosthesis usage, maximum standing time, body weight support, knee strength, knee fatigue index, electrode stability, and component survivability.
Levels of maximum standing time, body weight support, knee strength, and knee fatigue index were not statistically different from discharge to follow-up (P>.05). Additionally, neuroprosthesis usage was consistent with subjects choosing to use the system on approximately half of the days during each monitoring period. Although the number of hours using the neuroprosthesis remained constant, subjects shifted their usage to more functional standing versus more maintenance exercise, suggesting that the subjects incorporated the neuroprosthesis into their lives. Safety and reliability of the system were demonstrated by electrode stability and a high component survivability rate (>90%).
This group of 15 subjects is the largest cohort of implanted lower-extremity neuroprosthetic exercise and standing system users. The safety and efficiency data from this group, and acceptance of the neuroprosthesis as demonstrated by continued usage, indicate that future efforts toward commercialization of a similar device may be warranted.
Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as ...assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus. Type-VI lesions were associated with older age (odds ratio OR = 2.6 per 5 years increase, p <0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR = 4.1, p = 0.01), higher levels of lipoprotein(a) (OR = 2.0 per 1 SD increase, p = 0.02), and larger percent wall volume (PWV OR = 4.6 per 1 SD increase, p <0.001) but, were negatively associated with metabolic syndrome (OR = 0.2, p = 0.02). Presence of LRNC was associated with the male gender (OR = 3.2, p = 0.02) and PWV (OR = 3.8 per 1 SD, p <0.001); however, it was negatively associated with diabetes (OR = 0.4, p = 0.02) and high-density lipoprotein cholesterol levels (OR = 0.7 per 1 SD, p = 0.02). Increased percent LRNC was associated with PWV (regression coefficient = 0.36, p <0.001) and negatively associated with ApoA1 levels (regression coefficient = −0.20, p = 0.03). In conclusion, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher lipoprotein(a), and lower high-density lipoprotein cholesterol or ApoA1 level have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population.
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