Background Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties. Objective To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no ...coronary heart disease. Methods A total of 116 adults with baseline non−high-density lipoprotein cholesterol (non−HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks. Results A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant ( P < .001) and clinically meaningful decreases in non−HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), triglycerides, HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase. Conclusion Xuezhikang significantly reduced non−HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.
Summary Background Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal ...metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. Methods 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1–2 study. Patients received a total dose of 27–30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov , number NCT00508443. Findings Median follow-up was 15·9 months (IQR 9·5–30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 SD 2·9 on the BPI pain-at-its-worst item at baseline, 2·1 2·4 at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 28·9% of 149 patients with strong opioid use at baseline vs 20 20·0% of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9–86·1) at 1 year and 72·4% (63·1–79·7) at 2 years. Interpretation SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. Funding National Cancer Institute of the US National Institutes of Health.
Despite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that ...represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation.
We performed a retrospective cohort study of transplant-eligible patients with end-stage liver disease using the HealthCore Integrated Research Database (2006-2014; n = 16,824) and Medicaid data from 5 states (2002-2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision-based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database.
In an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2-year wait list (95% confidence interval CI, 25.4%-33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%-12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4%-15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20-2.49). Local organ supply and wait list level demand were not associated with placement on the wait list.
In an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference.
To compare hypertension remission and relapse after bariatric surgery compared with usual care.
The effect of Roux-en-Y gastric bypass and sleeve gastrectomy on hypertension remission and relapse has ...not been studied in large, multicenter studies over long periods and using clinical blood pressure (BP) measurements.
This retrospective cohort study was set in Kaiser Permanente Washington, Northern California, and Southern California. Participants included 9432 patients with hypertension 21-65 years old who underwent bariatric surgery during 2005-2015 and 66,651 nonsurgical controls matched on an index date on study site, age, sex, race/ethnicity, body mass index, comorbidity burden, diabetes status, diastolic and systolic BP, and number of antihypertensive medications.
At 5 years, the unadjusted cumulative incidence of hypertension remission was 60% (95% confidence interval CI, 58-61%) among surgery patients and 14% (95% CI, 13-14%) among controls. At 1 year, the adjusted hazard ratio for the association of bariatric surgery with hypertension remission was 10.24 (95% CI, 9.61-10.90). At 5 years, the adjusted hazard ratio was 2.10 (95% CI, 1.57-2.80). Among those who remitted, the unadjusted cumulative incidence of relapse at 5 years after remission was 54% (95% CI, 51-56%) among surgery patients and 78% (95% CI 76-79%) among controls, although the adjusted hazard ratio was not significant (hazard ratio, 0.71; 95% CI, 0.46-1.08).
Bariatric surgery was associated with greater hypertension remission than usual care suggesting that bariatric surgery should be discussed with patients with severe obesity and hypertension. Surgical patients who experience remission should be monitored carefully for hypertension relapse.
Background Glycemic exposure activates 12-lipoxygenase (12LO) expression and formation of arachidonic acid–derived products. These products can induce cell hypertrophy, cell proliferation, and ...extracellular matrix deposition, potentially leading to diabetic nephropathy. Study Design Cross-sectional study. Settings & Participants 955 European-American siblings from 369 Diabetes Heart Study families. Participants were categorized as nondiabetic, diabetic with hemoglobin A1c level less than 6.5%, and diabetic with hemoglobin A1c level greater than 6.5% (uncontrolled type 2 diabetes mellitus). Predictor Four haplotype-tagging variants in the arachidonate 12LO gene ( ALOX12 ), glycemic control, and other covariates. Outcomes & Measurements Albuminuria measured by means of urinary albumin-creatinine ratio (ACR). Results Median ACR was 11.9 mg/g (interquartile range, 5.6 to 39.1). The overall test of the Arg261Gln genotypic association with ACR was significant ( P = 0.009). Compared with 261Arg allele carriers, adjusted mean ACR was 42% greater in the 189 carriers of two 261Gln alleles (95% confidence interval, 10 to 83; P = 0.007). This association was confined to the group with uncontrolled type 2 diabetes mellitus (N = 623) with the greatest ACRs ( P < 0.001). Adjustments for additional determinants of ACR yielded similar results. Limitations Urine ACR was measured in duplicate on only a single occasion. This study was limited to European Americans. Conclusions Consistent with animal and cellular studies, these results provide additional evidence of the importance of the 12LO pathway in the pathogenesis of human diabetic nephropathy.
Objectives This study sought to identify the origin within the pulmonary vein (PV) of reproducible atrial fibrillation (AF) triggers. Background Triggers for AF frequently originate from PVs. ...However, a systematic evaluation of the location of origin within the PV orifice and associated techniques for eliciting triggers has not been performed. Methods Spontaneous triggers and those provoked with isoproterenol (up to 20 μg/min) and/or cardioversion in 45 patients with AF were identified using multipolar catheter recordings. In identifying origin, PVs were divided into 17 equal segments from ipsilateral PVs with “carina zone” (CZ) (7 segments between the PVs) and 10 “noncarina zone” (NCZ) segments. Results Sixty-three reproducible triggers were noted in 37 of the 45 (82%) patients with 57 from PV and 6 (10%) from non-PV sites. Although triggers were identified from 26 of 34 distinct PV segments, most PV triggers (36, 63%) originated from CZ segments (p < 0.05) from both right (17 triggers) and left (19 triggers) PVs. The CZ triggers were more often spontaneous (11 of 36 in CZ vs. 2 of 21 in NCZ; p < 0.05) or elicited with CV (17 of 36 in CZ vs. 6 of 21 in NCZ; p < 0.05). In contrast, NCZ triggers were more likely to require isoproterenol to be provoked (13 of 21 62% vs. 8 of 36 22%, p < 0.05). Conclusions Reproducible spontaneous and provoked PV triggers initiating AF can be observed in most patients undergoing AF ablation. These triggers most commonly originate from the carina region of both right and left PVs. Noncarina PV triggers more commonly require provocation with isoproterenol infusion.
Objective Postoperative atrial fibrillation complicating general thoracic surgery increases morbidity and stroke risk. We aimed to determine whether preoperative atrial dysfunction or other ...echocardiographic markers are associated with postoperative atrial fibrillation. Methods In 191 patients who had undergone anatomic lung or esophageal resection, preoperative clinical and echocardiographic data were compared between patients with and without postoperative atrial fibrillation. Presence of postoperative atrial fibrillation lasting more than 5 minutes during hospitalization was detected using continuous telemetry or 12-lead electrocardiography. Maximal left atrial volume and indices of left atrial function were assessed. Results Patients with postoperative atrial fibrillation (33/191, 17%) were older (71 ± 5 years vs 64 ± 12 years, P < .0001), were taking β-blockers more often, had greater left atrial volume, had decreased left atrial emptying fraction, and had lower E′ and A′ septal velocities compared with patients without postoperative atrial fibrillation. The incidence of postoperative atrial fibrillation in patients with left atrial volume 32 mL/m2 or greater was 37% (11/30) and greater than in those with left atrial volume less than 32 mL/m2 (14%, 22/160, P = .002). Length of hospital stay was significantly increased in patients with postoperative atrial fibrillation compared with patients without ( P = .04). Older age was significantly associated with greater β-blocker use and left atrial volume and lower left atrial emptying fraction. On multivariate analysis, lower left atrial emptying fraction (odds ratio, 1.03 per unit decrement; 95% confidence interval, 1.002–1.065; P = .04) and preoperative use of β-blockers (odds ratio, 2.82; 95% confidence interval, 1.18–6.77; P = .02) were the only independent risk factors associated with postoperative atrial fibrillation. Conclusions These data show that an echocardiogram before major thoracic surgery, increased use of preoperative β-blockers, and decreased left atrial emptying fraction were associated with postoperative atrial fibrillation. Echocardiographic predictors of left atrial mechanical dysfunction may prove clinically useful in risk stratifying patients in whom postoperative atrial fibrillation is more likely to develop and to benefit from prevention strategies aimed at mitigating atrial function before surgery.
Background With the recent rise in the number of Tommy John surgeries, a proportionate rise in revisions is expected. However, much is unknown regarding the current revision rate of Tommy John ...surgery, return to play, and change in performance in Major League Baseball (MLB) pitchers. Methods Publicly available databases were used to obtain a list of all MLB pitchers who underwent primary and revision Tommy John surgery. Pitching performance preoperatively and postoperatively for pitchers who returned to 1 or more MLB games after revision surgery was compared with controls matched for age and position. Results Since 1999, 235 MLB pitchers have undergone Tommy John surgeries; 31 pitchers (13.2%) underwent revision surgery, and 37% underwent revision within 3 years of the index procedure. Twenty-six revisions had more than 2 years of follow-up; 17 pitchers (65.4%) returned to pitch at least 1 major league game, whereas only 11 (42.3%) returned to pitch 10 or more games. Of those who returned to MLB competition, the average length of recovery was 20.76 months. Compared with controls matched for age and position, MLB pitchers undergoing revision surgery had a statistically shorter career after revision surgery (4.9 vs 2.6 seasons, P = .002), pitched fewer innings, and had fewer total pitches per season. Conclusions The rate of revision Tommy John surgery is substantially higher than previously reported. For MLB pitchers, return to play after revision surgery is much lower than after primary reconstruction. The overall durability of MLB pitchers after revision ulnar collateral ligament reconstruction decreases significantly compared with controls matched for age and matched controls.
Background Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. ...Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance. Objectives We sought to investigate the expression of pendrin and the mucus-related protein Muc5AC in sinonasal tissues of control subjects and patients with CRS and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro. Methods The expression and distribution of pendrin in sinonasal tissues was analyzed by using real-time PCR, immunoblot analysis, and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression. Results Increased pendrin expression was observed in nasal polyp (NP) tissue of patients with CRS. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells might induce pendrin expression. Furthermore, both pendrin and periostin levels (a biomarker in asthma) correlated with IL-13 levels, suggesting that pendrin can be induced by this cytokine in sinonasal tissues. Expression of the mucus component protein Muc5AC correlated weakly with pendrin expression, indicating that pendrin might modulate mucus production in NPs. In cultured NECs pendrin expression was induced by TH 2 cytokines and induced synergistically when TH 2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13–induced pendrin expression. Dexamethasone suppressed pendrin expression, suggesting that the therapeutic benefit of dexamethasone in asthmatic patients and those with CRS might involve regulation of pendrin expression. Conclusions TH 2-mediated pendrin expression is increased in NPs of patients with CRS and might lead to increased inflammation, mucus production, and decreased mucociliary clearance.
Abstract Background Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid ...arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD). Methods Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months. Results We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval CI, 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075). Conclusion Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.
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