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Background Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. Methods This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. Results A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. Conclusions In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia–analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. Methods Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural–general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. Results Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural–general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural–general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural–general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). Conclusions Epidural anesthesia–analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Experimental and observational research suggests that combined epidural–general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural–general anesthesia improves long-term survival in elderly patients. Methods This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. Results Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural–general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural–general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural–general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural–general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. Conclusions In elderly patients having major thoracic and abdominal surgery, combined epidural–general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The association between cerebral desaturation and postoperative delirium in thoracotomy with one-lung ventilation (OLV) has not been specifically studied.A prospective observational study performed in thoracic surgical patients. Cerebral tissue oxygen saturation (Scto2) was monitored on the left and right foreheads using a near-infrared spectroscopy oximeter. Baseline Scto2 was measured with patients awake and breathing room air. The minimum Scto2 was the lowest measurement at any time during surgery. Cerebral desaturation and hypersaturation were an episode of Scto2 below and above a given threshold for ≥15 seconds during surgery, respectively. The thresholds based on relative changes by referring to the baseline measurement were80%,85%,90%,95%, and100% baseline for desaturation and105%,110%,115%, and120% baseline for hypersaturation. The thresholds based on absolute values were50%,55%,60%,65%, and70% for desaturation and75%,80%,85%, and90% for hypersaturation. The given area under the threshold (AUT)/area above the threshold (AAT) was analyzed. Delirium was assessed until postoperative day 5. The primary analysis was the association between the minimum Scto2 and delirium using multivariable logistic regression controlled for confounders (age, OLV time, use of midazolam, occurrence of hypotension, and severity of pain). The secondary analysis was the association between cerebral desaturation/hypersaturation and delirium, and between the AUT/AAT and delirium using multivariable logistic regression controlled for the same confounders. Multiple testing was corrected using the Holm-Bonferroni method. We additionally monitored somatic tissue oxygen saturation on the forearm and upper thigh.Delirium occurred in 35 (20%) of 175 patients (65 ± 6 years old). The minimum left or right Scto2 was not associated with delirium. Cerebral desaturation defined by90% baseline for left Scto2 (odds ratio [OR], 5.82; 95% confidence interval [CI], 2.12-19.2; corrected P =.008) and85% baseline for right Scto2 (OR, 4.27; 95% CI, 1.77-11.0; corrected P =.01) was associated with an increased risk of delirium. Cerebral desaturation defined by other thresholds, cerebral hypersaturation, the AUT/AAT, and somatic desaturation and hypersaturation were all not associated with delirium.Cerebral desaturation defined by90% baseline for left Scto2 and85% baseline for right Scto2, but not the minimum Scto2, may be associated with an increased risk of postthoracotomy delirium. The validity of these thresholds needs to be tested by randomized controlled trials.

BACKGROUND Moderate-to-severe pain exists in the early postoperative period after laparoscopic renal surgery. OBJECTIVE We investigated the analgesic effect of quadratus lumborum block (QLB) via two approaches in patients undergoing laparoscopic renal nephrectomy. DESIGN A randomised controlled trial. SETTING An academic tertiary care hospital in Beijing, China. PARTICIPANTS Ninety-six patients aged 18 to 70 years who were scheduled for elective laparoscopic radical or partial nephrectomy. INTERVENTIONS Eligible patients were allocated randomly to a control group (no block), lateral QLB group or posterior QLB group. Ultrasound-guided QLB was performed via either the lateral or posterior approach with 30 ml of 0.4% ropivacaine before surgery. MAIN OUTCOME MEASURES The primary outcome was sufentanil equivalent consumption within 24 h. Among secondary outcomes, somatic and visceral pain intensity at rest and on coughing were assessed with a numerical rating scale (where 0 = no pain and 10 = the worst pain) until 24 h postoperatively. RESULTS Sufentanil equivalent consumption did not differ among the three groups (118 ± 36 μg in the control group, 115 ± 47 μg in the lateral QLB group and 119 ± 40 μg in the posterior QLB group; P = 0.955). However, both somatic (lateral QLB vs. control, median difference -1, P

Background Both selective and nonselective α-blockade are used for preoperative preparation in patients with pheochromocytomas and paragangliomas (PPGLs). However, the effects of different types of α-blockade on perioperative outcomes remain inconclusive. This study was designed to assess the association between the choice of α-blockade and the amount of intraoperative hypertension in patients undergoing surgery for PPGLs. Methods In this propensity-matched retrospective cohort study, data of patients who received either selective or nonselective α-blockade preoperatively and underwent surgery for PPGLs were collected. The primary end point was the time-weighted average above the systolic blood pressure (SBP) of 160 mm Hg (TWA-SBP >160 mm Hg), which was calculated as the total area of the SBP-time curve above the SBP of 160 mm Hg and divided by anesthesia duration. Results A total of 286 patients were included in analysis; of them, 156 received selective α-blockade and 130 nonselective α-blockade. After propensity score matching, 89 patients remained in each group. Patients who received nonselective α-blockade had a lower TWASBP >160 (median 0.472 mm Hg, interquartile range [IQR], 0.081-1.300) versus those who received selective α-blockade (median 1.114 mm Hg, IQR, 0.162-2.853; median difference -0.391, 95% confidence interval [CI], -0.828 to -0.032; P = .016); they also had a lower highest SBP during surgery (193 ± 24 mm Hg versus 205 ± 34 mm Hg; mean difference -12, 95% CI, -20 to -3; P = .008). Postoperative outcomes did not differ significantly between the 2 groups. Conclusions For patients undergoing surgery for PPGLs, preoperative nonselective α-blockade was associated with less intraoperative hypertension when compared with selective α-blockade.

Background Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation–guided intraoperative care reduces postoperative nausea and vomiting. Methods This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation–guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality. Results Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation–guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation–guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study. Conclusions In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation–guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

No significant progress has been made in the study of orthopedic surgical site infection (SSI) after different orthopedic surgery, and the analysis and prevention of risk factors for orthopedic SSI urgently need to be solved. A total of 154 patients underwent orthopedic surgery from April 2018 to December 2020. General information such as gender, age, marriage, diagnosis, surgical site, and anesthesia method was recorded. Statistical methods included Pearson chi-square test, univariate and multivariate logistic regression analyses, and receiver operating characteristic (ROC) curves. Based on Pearson's chi-square test, sex (P = .005), age (P = .027), marriage (P = .000), diagnosis (P = .034), and surgical site (P = .000) were significantly associated with SSI after orthopedic surgery. However, in the multiple linear regression analysis, only the surgical site (P = .035) was significantly associated with SSI after orthopedic surgery. In terms of multivariate logistic regression level, surgical site (odds ratio [OR] = 1.568, P = .039) was significantly associated with SSI. ROC curves were constructed to determine the effect of the surgical site on SSI after different orthopedic surgery (area under the curve [AUC] = 0.577, 95% CI = 0.487-0.0.666). In summary, the surgical site is an independent risk factor for SSI after orthopedic surgery, and "trauma" is more likely to develop SSI than spine, arthrosis, and others.

Background Severe labour pain is an important risk factor of postpartum depression, and early depression is associated with an increased risk of long-term depression; whereas the use of epidural analgesia during labour decreases the risk of postpartum depression. Objective To investigate whether neuraxial labour analgesia was associated with a decreased risk of 2-year depression. Design This was a multicentre, prospective, longitudinal study. Setting The study was performed in Peking University First Hospital, Beijing Obstetrics and Gynecology Hospital and Haidian Maternal and Child Health Hospital in Beijing, China, between 1 August 2014 and 25 April 2017. Patients Five hundred ninety-nine nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery were enrolled. Main outcome measure Depressive symptoms were screened with the Edinburgh Postnatal Depression Scale at delivery-room admission, 6-week postpartum and 2 years after childbirth. A score of 10 or higher was used as the threshold of depression. The primary endpoint was the presence of depression at 2 years after childbirth. The association between the use of neuraxial labour analgesia and the development of 2-year depression was analysed with a multivariable logistic regression model. Results Five hundred and eight parturients completed 2-year follow-up. Of these, 368 (72.4%) received neuraxial analgesia during labour and 140 (27.6%) did not. The percentage with 2-year depression was lower in those with neuraxial labour analgesia than in those without (7.3 [27/368] vs. 13.6% [19/140]; P = 0.029). After correction for confounding factors, the use of neuraxial analgesia during labour was associated with a significantly decreased risk of 2-year depression (odds ratio 0.455, 95% confidence interval 0.230 to 0.898; P = 0.023). Conclusion For nulliparous women with single-term cephalic pregnancy planning for vaginal delivery, the use of neuraxial analgesia during labour was associated with a reduced risk of maternal depression at 2 years after childbirth. Trial registration www.chictr.org.cn: ChiCTR-OCH-14004888 and ClinicalTrials.gov: NCT02823418.

BACKGROUND: Diastolic dysfunction is common and may increase the risk of cardiovascular complications. This study investigated the hypothesis that, in patients with isolated left ventricular diastolic dysfunction, higher grade diastolic dysfunction was associated with greater risk of major adverse cardiovascular events (MACEs) after surgery. METHODS: This was a retrospective cohort study. Data of adult patients with isolated echocardiographic diastolic dysfunction (ejection fraction, ≥50%) who underwent noncardiac surgery from January 1, 2015 to December 31, 2015 were collected. The primary end point was the occurrence of postoperative MACEs during hospital stay, which included acute myocardial infarction, congestive heart failure, stroke, nonfatal cardiac arrest, and cardiac death. The association between the grade of diastolic dysfunction and the occurrence of MACEs was assessed with a multivariable logistic model. RESULTS: A total of 2976 patients were included in the final analysis. Of these, 297 (10.0%) developed MACEs after surgery. After correction for confounding factors, grade 3 diastolic dysfunction was associated with higher risk of postoperative MACEs (odds ratio, 1.71; 95% confidence interval, 1.28–2.27; P < .001) when compared with grades 1 and 2. Patients with grade 3 diastolic dysfunction developed more non-MACE complications when compared with grades 1 and 2 (uncorrected odds ratio, 1.44; 95% confidence interval, 1.07–1.95; P = .017). CONCLUSIONS: In patients with isolated diastolic dysfunction undergoing noncardiac surgery, 10.0% develop MACEs during hospital stay after surgery; grade 3 diastolic dysfunction is associated with greater risk of MACEs.

Introduction: Puerto Rican (PR) adults living on the US mainland are at high risk for developing type 2 diabetes (T2D), and dietary factors may contribute to this increased risk. Network analysis is a data-reduction tool that can identify correlated clusters of co-regulated metabolites that reflect mechanisms underlying diet-T2D associations. Hypothesis: Diet quality will associate with T2D-associated metabolite clusters among PR adults. Methods: We used LC/MS to measure fasting plasma metabolites (>700) among Boston PR Health Study participants, aged 45-75 years, with (n=258) and without (n=421) T2D. We applied an unsupervised correlation network-based method to identify metabolite clusters within a global metabolite network and calculated a score for each cluster using a weighted sum of metabolite concentrations. To estimate diet quality, we calculated a modified version of a previously validated American Heart Association diet score (AHA-DS). Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D, and linear regression was used to assess associations between the continuous AHA-DS and T2D-associated metabolite clusters among controls, adjusting for potential confounders and correcting for multiple testing. Results: We identified 7 metabolite clusters that were associated with prevalent T2D ( p Conclusions: In individuals of PR descent, we identified a cluster of acylcholine metabolites where concentrations are higher among those with better diet quality and lower among those with prevalent T2D.

Purpose of review There is increasing interest in the use of noncerebral somatic tissue oxygen saturation (SstO2) monitoring on the basis of near-infrared spectroscopy in patients undergoing surgery or residing in intensive care unit. The relevant question is whether SstO2 monitoring can improve the quality of care. In this article, we reviewed the clinical application of SstO2 monitoring in acute care, focusing on its use in patients undergoing surgery. Recent findings Multiple small cohort studies conducted on pediatric patients reported close associations of SstO2 measurements over different regions such as the splanchnic and renal tissue beds with systemic oxygenation, transfusion, hemodynamic indices, morbidity, and mortality. Conversely, there is paucity of literature on SstO2 monitoring in adult patients. The limited number of reports suggests that SstO2 levels over bulk muscles such as the thenar eminence, forearm, and lower leg during surgery are correlated with postoperative outcomes including postoperative nausea and vomiting and the length of hospital stay in adult patients undergoing surgery. The only pilot, randomized interventional study based on 50 patients undergoing surgery did not find a difference in outcomes on the basis of the use of SstO2 monitoring. Summary Somatic tissue oxygenation may represent an essential aspect of human physiology in acute care, and it is likely outcome-relevant based on observational cohort studies. Future research should examine whether SstO2-guided care can further improve patient outcomes using randomized controlled trials.

Background: The relation of red meat to risk of coronary heart disease (CHD) is of great interest, but this is likely to depend on the foods to which red meat is compared. Objective: We investigated the associations between total, processed and unprocessed red meat consumption and CHD risk and also estimated the effects of substituting other protein sources for red meat. Methods: We prospectively followed 43,259 men in the Health Professionals Follow up Study (1986-2012) who had no known history of cancer or cardiovascular disease. Diet was assessed by a standardized and validated food frequency questionnaire that was updated every 4 years. Multivariate Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of CHD risk across categories of red meat consumption. Substitution analyses were done by comparing coefficients in models including alternative foods as continuous variables. Results: During 932,968 person-years of follow-up, we documented 4,148 incident CHD cases of which 1,680 were fatal CHD cases. After multivariate adjustment for dietary and nondietary risk factors, both total and processed red meat intake were associated with a modestly higher risk of CHD (HR for a one serving/day increment: 1.08; 95% CI, 1.01-1.14 for total and HR=1.13; 95% CI, 1.03-1.22 for processed red meat). Substitutions of 1-serving per day of other foods (including nuts, legumes, soy, whole grains, low- and high-fat dairy) for 1-serving per day of total red meat were associated with a 10%-47% lower CHD risk. Stronger inverse associations were observed between some of these substitutions for red meat and risk of fatal CHD [substituting nuts (-17%, -27% to -6%) or whole grains (-48%, -60% to -32%), and were more pronounced when replacing processed red meat. Conclusions: Our results suggest that red meat consumption, particularly processed red meat, is associated with higher risk of CHD. Substituting high-quality plant foods such as legumes, nuts, soy, and whole grains for red meat may substantially lower CHD risk.

Background and Study Purpose: The conversion of plant lignans to enterolignans for absorption is mediated through the gut microbiota. We explored the interconnections between the intake of dietary lignans, circulating concentrations of plasma enterolignans, the gut microbiome, and cardio-metabolic risk factors (LDL-cholesterol, HDL-cholesterol, & triglycerides). Design and method: The study was a repeated cross-sectional survey of up to 4 stool samples. Dietary lignan intake was assessed by two 7 day weighed records administered to coincide with fecal sample collection. DNA was extracted from 916 samples provided by 301 participants, and RNA was extracted from 369 samples from a subgroup of 96 participants. P Results: A high ratio of plasma enterolactone to dietary lignan was significantly associated with the relative abundance of 35 species (24 enriched and 11 depleted species), including 8 Bacteroidetes and 13 Firmicutes species. Greater dietary lignan was only significantly associated with a lower plasma ratio of triglyceride to HDL when plasma enterolactone was high. The association between dietary lignans and ratio of TG to HDL was mainly mediated by plasma enterolactone level (mediation effect: 74.3%, P=0.002), which was partially captured by the weighted species score (mediation effect: 28.6%, P=0.02). We observed several significant interactions between dietary lignans and presence of species on ratio of TG to HDL, suggesting that the protective effect of dietary lignans on CVD risk factor depends on the presence/abundance of certain microbiota. The relative abundance of microbial pathways involved in I-isoleucine biosynthesis and glutaryl-coa degradation pathways were significantly greater in in participants with a higher level of plasma enterolactone. Conclusion: The health benefits of dietary lignans on lipid levels may be modified by the greater enrichment of biologically relevant microbiota species. FIGURE

Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat intake and poor cardiovascular health. The relationship between diet, microbial metabolism, circulating TMAO levels, and cardiometabolic health in free-living individuals, is yet to be elucidated. Hypothesis: Specific microbial taxa may modulate associations of choline/L-carnitine and red meat intake with plasma TMAO levels and cardiometabolic traits. Method: We collected 2 pairs of fecal samples (n=925) and, simultaneously, 2 blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study in 2012. We performed Shotgun metagenomic sequencing using fecal samples and identified microbial taxonomic features using MetaPhlAn2. We measured hemoglobin A1c (HBA1c), and plasma levels of TMAO, lipids, and other cardiometabolic risk markers. Diet was assessed repeatedly using validated food-frequency questionnaires and dietary records. Results: Multivariable random-effect linear regressions identified 10 bacterial species that were significantly associated with TMAO levels ( FDR Figure A ), and these species significantly modified the associations of dietary choline/L-carnitine and/or red meat intake with TMAO levels ( P interaction Alistipes s hahii and Clostridium c itroniae significantly strengthened the association between red meat intake and TMAO levels, whereas Eubacterium b iforme attenuated this association ( P interaction A. s hahii and C. c itroniae or in the absence of E. b ifome ( Figure B ). Conclusions: We identified microbial taxa that modify the associations of red meat intake with circulating TMAO levels and cardiometabolic traits, in free-living men, suggesting an interplay between diet and microbial metabolism in producing TMAO and affecting cardiometabolic health.

Introduction: The 2015-2020 Dietary Guidelines for Americans (DGAs) recommend three major healthy dietary patterns: the Healthy US-Style Eating Pattern, the Healthy Mediterranean-Style Eating Pattern, and the Healthy Vegetarian Eating Pattern, for all Americans with diverse cultural and personal food traditions. However, few studies have systematically examined the potential differences in associations of adherence to these recommended dietary patterns with long-term risk of cardiovascular disease (CVD). Hypothesis: We hypothesized that all three DGA-recommended dietary patterns were associated with lower risk of CVD, coronary heart disease (CHD), and stroke. Method: We evaluated data on 74 661 women in the Nurses’ Health Study (NHS), 90 864 women in NHS II, and 41 837 men in the Health Professionals Follow-Up Study (HPFS), who had repeated dietary data and had no history of type 2 diabetes, CVD, or cancer at baseline. Using the food and nutrient components, we calculated the Healthy Eating Index (HEI)-2015, Alternate Mediterranean Diet score (AMED), Healthful Plant-based Diet Index (HPDI), to measure adherence to the Healthy US-Style Eating Pattern, Healthy Mediterranean-Style Eating Pattern, and Healthy Vegetarian Eating Pattern, respectively. Multivariable Cox proportional-hazards regression was used to assess the associations of healthy eating index with CVD risk. Results: We documented 9 262 incident CVD cases (6 628 CHD and 2 701 stroke) during 1 976 026 person years of follow-up in the NHS, 1 916 CVD cases (1 267 CHD and 660 stroke) during 2 173 162 person years of follow-up in NHS II, and 10 203 CVD cases (8 750 CHD and 1 775 stroke) during 873 053 person years of follow-up in HPFS. When comparing the highest to the lowest quintiles, the pooled HRs (95% CIs) of CVD were 0.80 (0.77 to 0.84) for HEI-2015, 0.83 (0.79 to 0.87) for AMED, and 0.85 (0.81 to 0.89) for HPDI (all P for trend Conclusions: In three large prospective cohorts with up to 32 years of follow-up, higher adherence to various healthy eating patterns was associated with lower risk of CVD, CHD, and stroke. Our findings support the DGA recommendations for multiple healthy eating patterns.

Introduction: Little is known about whether the effect of a healthy diet on diabetes mellitus (DM) is modified by the gut microbiome in human. Hypothesis: We hypothesize that the gut microbiome modifies the inverse association between the Mediterranean diet (MedDiet) and risk of DM. Methods: This study included 543 DM cases, 805 with impaired glucose tolerance (IGT) and 394 with normal glucose regulation (NGR) in adults 23-83yrs old from the HCHS/SOL. Fecal samples were profiled using 16s rRNA gene sequencing. We applied QIIME 2 to cluster sequences into OTUs and assign taxonomies, and PICRUSt to predict metagenomic gene functions. Adherence to the MedDiet was evaluated by a MedDiet index using the average of two 24-hr dietary recalls. We applied MaAsLin2 to quantify associations between the MedDiet index and microbial features with adjustment for confounding factors listed in the caption of Fig. 1. Results: MedDiet was associated with phylogenetically diverse, rare, and abundant gut microbes (Fig. 1a). For example, a higher MedDiet index was associated with a higher relative abundance of Faecalibacterium Prausnitzii [FDR-adjusted p (q) =0.002], but a lower relative abundance of Collinsella aerofaciens ( q =0.009). We found that several microbial functions related to plant-derived polysaccharide degradation such as fructuronate reductase ( q =0.02), and short-chain fatty acid fermentation such as butyryl-CoA dehydrogenase ( q =0.002) were enriched in participants with higher MedDiet index. We found that the inverse association between MedDiet and risk of DM was more pronounced in participants with greater abundance of Prevotella copri , but weaker in participants whose gut microbial communities were dominated by Bacteroides ( P interaction =0.02 for IGT/DM vs NGR, Fig. 1b). Conclusions: Adherence to the MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between MedDiet and risk of DM might be modified by gut microbiome composition. 1

Objectives: To investigate the association between a plant-based diet index and microbial composition and functionality, as well as the inter-relationships between plant-based diets, gut microbiome, and cardiometabolic risk markers. Design and method: Metagenomic profiling was performed on 916 fecal samples collected among 301 men who participated in the Men’s Lifestyle Validation Study. Using data from a food frequency questionnaire, a Plant-based Diet Index (PDI) was derived to assess the adherence to a plant-based diets. The associations between PDI adherence and the relative abundance of microbial species and pathways were evaluated using Multivariate Association with Linear Models (MaAsLin2). P values below 0.25 after false discovery rate correction following the Benjamini-Hochberg method were considered statistically significant. Results: After multivariate adjustment, the value of the PDI score was significantly and positively associated with the ratio of Firmicutes to Bacteroidetes (Spearman r=0.10, P=0.005). Specifically, the PDI was significantly associated with the relative abundance of 77 taxa (including 39 species) out of 506 filtered taxa and 15 pathways (out of 80 filtered features). In particular, a higher adherence to the PDI was significantly, positively, associated with of the relative abundance of Firmicutes and of pathways involving degradation of complex plant carbohydrates. It was also inversely associated with the relative abundance of Bacteroidetes and Proteobacteria, as well as pathways involved in the urea cycle and amino acid biosynthesis. We also found that 14 species significantly interacted with PDI in modulating plasma ratio of TG to HDL-C. The association of PDI with lower TG to HDL ratio was significantly strengthened in the presence of the species positively correlated with the PDI score, such as Ruminococcus lactaris , Haemophilus parainfluenzae, and Methanobrevibacter smithii or in the absence of the species inversely correlated with the PDI score, such as Paraprevotella spp. Conclusions: A greater adherence to a plant-based diet was associated with a microbial profile featured by higher abundance of species in Firmicutes and depletion of species in Bacteroidetes and Proteobacteria, and such a profile may further strengthen the favorable associations between plant-based diets and human cardiometabolic risk.

Purpose of review We reviewed evidences regarding occurrence, risk factors, harmful effects, prevention, and management of sleep disturbances in patients after surgery. Recent findings Normal sleep is important to maintain physical and mental health. Sleep disturbances frequently occur in patients after surgery. Factors associated with the development of postoperative sleep disturbances include old age, preoperative comorbidity, type of anesthesia, severity of surgical trauma, postoperative pain, environment stress, as well as other factors leading to discomfort of patients. Development of sleep disturbances produces harmful effects on postoperative patients, that is, leading to higher risk of delirium, increased sensitivity to pain, more cardiovascular events, and poorer recovery. Both nonpharmacological and pharmacological measures (such as zolpidem, melatonin, and dexmedetomidine) can be used to improve postoperative sleep. Recent evidences show that sleep promotion may improve patients’ outcome, but requires further evidences. Summary Sleep disturbances are common in patients after surgery and produce harmful effects on postoperative recovery. Sleep-promotion therapy may be helpful to improve postoperative recovery, but long-term effects deserve further study.

Rhinophyma, the final stage of acne rosacea, severely influences the patient's appearance and can only be treated by surgical methods. This case reports a simple, safe, effective, and economical surgical method-five-blade scratcher. After the surgical treatment, the overall nasal contour of the patient, a male with severe rosacea, was restored without scar formation. Thus, this surgical method reported in this case is feasible and easy to operate, and worthy of clinical promotion.

Background Patients admitted to the intensive care unit (ICU) after surgery often develop sleep disturbances. The authors tested the hypothesis that low-dose dexmedetomidine infusion could improve sleep architecture in nonmechanically ventilated elderly patients in the ICU after surgery. Methods This was a pilot, randomized controlled trial. Seventy-six patients age 65 yr or older who were admitted to the ICU after noncardiac surgery and did not require mechanical ventilation were randomized to receive dexmedetomidine (continuous infusion at a rate of 0.1 μg kg−1 h−1; n = 38) or placebo (n = 38) for 15 h, i.e., from 5:00 pm on the day of surgery until 8:00 am on the first day after surgery. Polysomnogram was monitored during the period of study-drug infusion. The primary endpoint was the percentage of stage 2 non–rapid eye movement (stage N2) sleep. Results Complete polysomnogram recordings were obtained in 61 patients (30 in the placebo group and 31 in the dexmedetomidine group). Dexmedetomidine infusion increased the percentage of stage N2 sleep from median 15.8% (interquartile range, 1.3 to 62.8) with placebo to 43.5% (16.6 to 80.2) with dexmedetomidine (difference, 14.7%; 95% CI, 0.0 to 31.9; P = 0.048); it also prolonged the total sleep time, decreased the percentage of stage N1 sleep, increased the sleep efficiency, and improved the subjective sleep quality. Dexmedetomidine increased the incidence of hypotension without significant intervention. Conclusions In nonmechanically ventilated elderly patients who were admitted to the ICU after noncardiac surgery, the prophylactic low-dose dexmedetomidine infusion may improve overall sleep quality.

Few studies have investigated the use of dexmedetomidine in patients with a high risk of postoperative nausea and vomiting (PONV) following gynaecological laparoscopic surgery.To investigate if the intra-operative use of dexmedetomidine could reduce the incidence of PONV in this patient population.A randomised, double-blind, placebo-controlled trial.A tertiary hospital in Beijing, China.130 adult patients scheduled for gynaecological laparoscopic surgery.Patients in the dexmedetomidine group (Dex group, n = 65) received a loading dose of dexmedetomidine (0.5 μg kg over 10 min) before induction of anaesthesia, followed by a continuous infusion (0.1 μg kg h) until the end of surgery. Patients in the control group (Ctrl group, n = 65) received volume-matched normal saline. Propofol and remifentanil were used for induction and maintenance of anaesthesia. Intravenous patient-controlled analgesia with morphine was provided after surgery.The incidence of 24-h PONV.The incidence of nausea within the first 2 postoperative hours was lower in the Dex group than in the Ctrl group [0% (0/65) vs. 9% (6/65), P = 0.037]. The overall incidence of PONV within the first 2 postoperative hours was slightly lower in the Dex group than in the Ctrl group, but the difference was not statistically significant [5% (3/65) vs. 14% (9/65), P = 0.069]. There was no significant difference between the two groups regarding the incidence of 24-h PONV.For adult patients undergoing gynaecological laparoscopic surgery, supplemental use of dexmedetomidine during general anaesthesia reduced the incidence of early postoperative nausea but not vomiting within the 24 h after surgery.Chinese Clinical Trial Registry ChiCTR-IPR-15006914.

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60 th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH 2 O (IQR, 5–6 cmH 2 O). No PEEP values were higher than 10 cmH 2 O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073 .

Background This study aims to assess the efficacy of transconjunctival approach (TCA) for the treatment of orbital fractures (OF) comprehensively and systematically. Methods In this study, we plan to search electronic databases of Cochrane Library, MEDLINE, EMBASE, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and for relevant randomized controlled trials. All these databases will be searched from inception to the March 1, 2020 without limitations of language and publication status. Two independent authors will carry out study selection, data collection, and study quality assessment. Any disagreements will be resolved by discussion with another author if necessary. The study quality will be assessed using Cochrane risk of bias tool. Statistical analysis will be conducted using RevMan 5.3 software. Results This study will be the first 1 to exert direct evidence to evaluate the efficacy of TCA for the treatment of OF. Conclusions The findings of this study will provide an exhaustive view of TCA for the treatment of OF. Study registration number INPLASY202040154.

Background Although several previous studies have reported the efficacy of remifentanil in cesarean section (CS) under general anesthesia, no study has specifically addressed its neonatal effect (NE) in CS under general anesthesia systematically. Thus, this study will systematically investigate the NE of remifentanil in CS under general anesthesia. Methods Electronic databases including MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be systematically retrieved with the assistance of a specialist librarian to check randomized controlled trials reporting NE in CS under general anesthesia. We will retrieve all electronic databases from their initial time to March 20, 2020 without restrictions of language. All process of study selection, data extraction, and risk of bias evaluation will be carried out by 2 independent authors. We will invite another senior expert to solve the problems that arise between 2 authors. Data will be pooled and analyzed using RevMan V.5.3 software. Results Outcomes consist of assessment of neonatal adaptation, requirements for postoperative respiratory support of neonates, systolic and diastolic noninvasive blood pressure, mean blood pressure, heart rate, electrocardiography, umbilical cord blood gas analysis, and adverse events. Conclusion This study will present evidence of the NE of remifentanil in CS under general anesthesia. This information may inform benefits of intervention to guide the usage of remifentanil in CS under general anesthesia. Study registration INPLASY202040028.

Background: Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population. Methods: Using data from the Nurses’ Health Study (1980–2014; n=78 865) and the Health Professionals Follow-up Study (1986–2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m 2 , ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0–5 scale) with mortality. We used data from the NHANES (National Health and Nutrition Examination Surveys; 2013–2014) to estimate the distribution of the lifestyle score and the US Centers for Disease Control and Prevention WONDER database to derive the age-specific death rates of Americans. We applied the life table method to estimate life expectancy by levels of the lifestyle score. Results: During up to 34 years of follow-up, we documented 42 167 deaths. The multivariable-adjusted hazard ratios for mortality in adults with 5 compared with zero low-risk factors were 0.26 (95% confidence interval [CI], 0.22–0.31) for all-cause mortality, 0.35 (95% CI, 0.27–0.45) for cancer mortality, and 0.18 (95% CI, 0.12–0.26) for cardiovascular disease mortality. The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6–66.7) for all-cause mortality, 51.7% (95% CI, 37.1–62.9) for cancer mortality, and 71.7% (95% CI, 58.1–81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3–29.8) for women and 25.5 years (95% CI, 24.7–26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3–44.9) for women and 37.6 years (95% CI, 35.8–39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8–16.2) longer among female Americans with 5 low-risk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1–14.2). Conclusions: Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults.

Introduction: The strength and dose-response relationship between fruit and vegetable intake and mortality are still subjects of debate. Hypothesis: We hypothesized that higher fruit and vegetable intake was associated with lower total and cause-specific mortality in a nonlinear dose-response manner. Methods: We followed 66,719 women from the Nurses’ Health Study (1984-2012) and 42,016 men from the Health Professionals Follow-up Study (1986-2012) who were free from cardiovascular disease (CVD), cancer and diabetes at baseline. Diet was assessed using food frequency questionnaires at baseline and updated every 2 to 4 years. Results: Our study documented 28,333 deaths during follow-up. The 3rd quintile of fruit and vegetable intake was associated with the lowest hazard ratio (HR) of total mortality (HR, 0.87, 95% CI, 0.83-0.90, P nonlinear Conclusions: Higher fruit and vegetable intake was associated with lower mortality; the lowest mortality was observed among those who consumed 5 servings of fruit and vegetables per day (2 servings of fruit and 3 servings of vegetables daily). Our findings also suggest the presence of heterogeneity in the health benefits of individual fruits and vegetables.

PURPOSE Previous strabismus appearance studies using images from real face photographs could not preclude the effect of other facial landmarks, such as position and contour of brow, nose, and facial outline, from pure effect of ocular deviation itself. With conceptualized drawings of eyes, we simulated strabismus deviation and collected the responses of observers. METHODS The experiments consisted of three sessions: (1) one-eye, (2) two-eye cornea, and (3) two-eyelid deviation simulations. On a monitor, eight different ocular deviations in increments of 6 prism diopters of horizontal or vertical deviations were simulated. Nine ophthalmology residents were asked to choose between esotropia and exotropia for horizontal simulations and hypotropia or hypertropia for vertical simulations. Psychometric function fitting was performed. Detection sensitivity, point of subjective equality, and 95% thresholds were calculated. RESULTS Between cornea and lid deviation simulations, there was no difference in 95% thresholds, points of subjective equality, and sensitivity (all p values > 0.10), reflecting that the relative location of cornea and lid was the determinant factor in recognizing ocular deviation. The sensitivities of vertical deviation simulations were higher than that of horizontal in two-eye cornea and lid comparisons (p values < 0.04) but not in one-eye (p value = 0.37). CONCLUSIONS Our results suggest that the appearance of strabismus depends not on the absolute ocular alignment but rather on the reciprocal relationship of cornea and lid margin. Vertical misalignment was more apparent than horizontal misalignment.

Background: Metabolites associated with betaine and choline metabolism and the gut-microbiota-dependent metabolite trimethylamine N-oxide (TMAO) have been linked to the risk of cardiovascular disease (CVD). However, the relationship between plasma concentrations of other gut microbiota-related metabolites and major CVD endpoints remains unclear. Objectives: To evaluate the association between gut microbiota-related metabolites and risk of incident CVD and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods: We designed a case-cohort study nested within the PREDIMED trial. We used liquid chromatography–tandem mass spectrometry to measure plasma gut microbiota-related metabolites. A score including the sum of quartile values of 8 metabolites was constructed (TMAO, betaine, choline, phosphocholine, alphaglycerophosphocholine, proline, hydroxyproline, allantoin). The primary outcome was a composite of myocardial infarction, stroke, and cardiovascular death. Blood samples from a randomly selected PREDIMED sub-cohort (n=751) and all available incident CVD cases (n=229) after 4.8-y of follow-up were included in the analysis. We used weighted Cox regression models to estimate multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals (CI). Models were adjusted for age, sex, BMI, family history of premature heart disease, and smoking, physical activity (metabolic equivalent tasks in min/d), hypertension, dyslipidemia, diabetes and was stratified by intervention group. Results: Baseline plasma concentrations of choline and hydroxyproline were associated with higher CVD risk independent of traditional risk factors, while no significant association between plasma concentrations of TMAO and CVD was found. The HRs comparing extreme quartiles (lowest quartile as the reference) were 1.72 (95% CI: 1.05, 2.81; P for trend=0.01) and 1.65 (95% CI: 1.03, 2.65; P for trend =0.04), respectively. The microbiota metabolite score was associated with a 2.13-fold higher risk of CVD across extreme quartiles (95% CI: 1.32, 3.43; P for trend Conclusions: Plasma gut microbiota-related metabolites were associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk, independent of traditional CVD risk factors.

Background: Metabolomics technologies can efficiently profile a large number of structurally diverse lipids, e.g., glycerophospholipids, sphingolipids, and glycerolipids, that may play differential roles in pathogenesis of cardiovascular disease (CVD). However, existing studies were focused more on discovering individual lipid metabolites for CVD risk prediction than inferring perturbed pathways responsible for the pathological processes. Hypothesis: We hypothesized that different lipid metabolic pathways, captured by network analysis, were divergently associated with CVD risk; the associations could be modified by the Mediterranean diet (MedDiet) intervention. Methods: We conducted this study in the PREDIMED trial with participants randomized to three intervention diets: MedDiet with extra-virgin olive oil, MedDiet with nuts, or a low-fat control diet. This study comprises a subcohort of 788 participants randomly selected from the PREDIMED cohort and 230 cases. The outcome was a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke and cardiovascular death. We performed network analysis using Gaussian graphic model among 200 targeted lipid metabolites and subsequent dimensionality reduction using Greedy Modularity Optimization to detect subnetworks. We calculated the subnetwork scores by summing up the products of the topological connectivity weight (representing network structure) and metabolite level and included the scores into Cox proportional hazards model with simultaneous adjustment for other subnetwork scores and covariates. The Benjamini-Hochberg procedure was applied to detect smaller subnetworks of specific interest for further investigation. Results: We detected 4 major subnetworks of lipid metabolic pathway. Most lipid metabolites with larger numbers of carbon atom and double bond clustered within a same subnetwork (subnetwork 2), while those with smaller numbers of carbon atom and double bond clustered within other 3 subnetworks (subnetworks 1, 3 and 4). The hazard ratio (HR) of CVD across quartiles of the subnetwork score 2 was 0.56 (95% CI, 0.35, 0.91, P trend =0.008) after multivariable adjustment. The HRs of CVD comparing extreme quartiles of subnetwork scores 3 and 4 were 1.85 (95% CI, 1.15, 2.97, P trend =0.02) and 1.93 (95% CI, 1.19, 3.14, P trend =0.01), respectively. The MedDiet appeared to enhance the inverse association between subnetwork score 2 and CVD ( P interaction =0.03). We detected several smaller subnetworks with functional interpretation related to CVD pathogenesis such as the ceramide pathway and the pathway including phospholipids with high unsaturation. Conclusions: Based on topological structure of lipid metabolic pathways, we detected biologically meaningful pathways. We found divergent associations between subnetworks and CVD and smaller subnetworks with functional interpretation.

Introduction: The role of dietary fat intake in body weight regulation remains controversial and few studies have examined long-term changes in types of dietary fat and weight change in longitudinal studies. Methods: We examined the association between changes in energy from dietary fat and weight change in three large, prospective cohorts including 102, 123 U.S. women and men who were free of diabetes, cardiovascular disease and cancer at baseline. Linear mixed model was used to assess the association between changes in energy from specific dietary fat and weight changes at 4-year intervals with multivariable adjustment for age, baseline body-mass index at each period, and simultaneous changes in dietary factors (total energy, energy from protein, cereal fiber) and lifestyle factors (smoking, physical activity, television watching, sleep duration). Results: Increased intake of polyunsaturated fatty acid (PUFA) was inversely associated with weight gain. A 5% increment in energy from total PUFA was associated with less weight gain (-1.8 lb, 95% CI: -1.95 to -1.65, ptrans -fat was associated with 1.97 lb (95% CI: 1.86 to 2.08) greater weight gain within each 4-year period. Conclusion: Different types of dietary fats have divergent associations with long-term weight change: higher intakes of PUFA (both n-6 and n-3 PUFA) and plant-based MUFA were associated with less weight gain, whereas increasing saturated and trans -fat intakes were associated with greater weight gain. Our results support the current dietary guidelines that recommend unsaturated fats as replacements for saturated and trans -fats.

Rationale: Rhizobium radiobacter is a Gram-negative pathogen present in soil and plants. Cases of R radiobacter infection in immunocompromised hosts have been sporadically reported. However, septic shock caused by R radiobacter is rarely seen. Patient concerns: Here, we describe an elderly patient with a rapid progression of watery diarrhea, anorexia, fever, weakness, oliguria, and shock. Blood results showed increased total white blood cell count and C-reactive protein. Arterial blood gas results showed hypoxia and elevated lactate level. The Sequential Organ Failure Assessment score was 11. Blood culture at admission showed Gram-negative bacteria, which were later confirmed as R radiobacter. Diagnosis: Septic shock caused by R Radiobacter. Interventions: The patient was treated with intravenous cefoperazone/sulbactam and sequential oral levofloxacin. Outcomes: The patient recovered completely. Conclusion: R radiobacter may be considered as a potential opportunistic pathogen that may cause severe sepsis in elderly patients, especially those with multiple underlying diseases.

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after

Introduction: Previous studies have shown distinct associations between specific types of dietary fat and cardiovascular disease. However, studies of specific types of fat in relation to total and cause-specific mortality remain limited and inconsistent. Hypothesis: We hypothesized that specific types of dietary fat were differentially associated with total and cause-specific mortality. Methods: We investigated 83,349 women from the Nurses’ Health Study (1980-2012) and 42,884 men from the Health Professionals Follow-up Study (1986-2012) who were free from cardiovascular disease, cancer and diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Results: We documented 33,304 deaths during 3,439,954 person-years of follow-up. After adjustment for known and suspected risk factors, the hazard ratios (HRs) of total mortality comparing extreme quintiles of intake was 1.08, (95% confidence interval (CI), 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fat, 0.89 (95% CI, 0.84-0.94) for monounsaturated fat and 1.13 (95% CI, 1.07-1.18) for trans fat (P for trend Conclusions: Higher saturated fat intake was associated with higher mortality, whereas dietary polyunsaturated fat and monounsaturated fat intakes were inversely associated with mortality. These findings support current dietary recommendations to replace saturated fat with unsaturated fats.

To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery.Prospective, randomized, double-blind, and placebo-controlled trial in two centers.Intensive care units of two large tertiary teaching hospitals.Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery.Haloperidol (0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs; n = 229) or placebo (n = 228) was randomly administered from intensive care unit admission.The primary end point was the incidence of delirium within the first 7 days after surgery. Secondary end points included time to onset of delirium, number of delirium-free days, length of intensive care unit stay, all-cause 28-day mortality, and adverse events. Delirium was assessed using the confusion assessment method for the intensive care unit.The incidence of delirium during the first 7 days after surgery was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = .031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% confidence interval 5.9-6.4] vs. 5.7 days [95% confidence interval 5.4-6.0]; p = .021; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days; p = .027, respectively), whereas the median length of intensive care unit stay was significantly shorter (21.3 hrs [95% confidence interval 20.3-22.2] vs. 23.0 hrs [95% confidence interval 20.9-25.1]; p = .024) in the haloperidol group than in the control group. There was no significant difference with regard to all-cause 28-day mortality between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = .175). No drug-related side effects were documented.For elderly patients admitted to intensive care unit after noncardiac surgery, short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium. The therapy was well-tolerated.

Rationale: The purpose of this study was to estimate the efficacy and safety of percutaneous periacetabular screw (PPS) insertion assisted by screw view model of navigation (SVMN) to treat fracture of acetabulum. Patient concerns: A 61-year-old male patient was injured in a motorcycle accident, which caused pain, swelling, deformity and limited mobility on his right hip. Diagnoses: He was diagnosed with fracture of acetabulum. Interventions: We used PPS insertion assisted by SVMN to treat fracture of acetabulum in this patient. Outcomes: The follow up lasted 24 months. Totally 2 screws were inserted into anterior and posterior column of acetabulum respectively and both of them displayed grade 0. Compared with the preoperative gap and step of fracture displacement, the postoperative ones were significantly reduced. It took 11.7 minutes for designing the screws, 6.7 minutes for implanting the guide wire, and 45.5 minutes for placing the screws. Intraoperative blood loss was 29 mL and total fluoroscopic time was 4.1 minutes. No clinical complications such as nerve vascular injury, infection and screw loosening were found after the operation. Lessons: The study indicated that SVMN is favorable to the PPS insertion for acetabular fracture. Our lesson is that the relative position between the acetabular and the patient tracker must be static to ensure the accuracy of the entire system throughout the operation.

Postoperative cognitive dysfunction (POCD) can be a debilitating complication after coronary artery bypass graft (CABG) surgery. Cerebral microemboli during cardiopulmonary bypass (CPB) are believed to be an important etiologic factor of POCD. In this study, we examined whether avoidance of CPB with "off-pump" surgery reduces the number of cerebral microemboli and the incidence of POCD after CABG surgery in Chinese population.Two hundred twenty-seven patients were enrolled in this prospective cohort study. Fifty-nine patients underwent CABG surgery with CPB and 168 underwent off-pump surgery. Cerebral microemboli were measured continuously with bilateral transcranial Doppler ultrasonography of the middle cerebral arteries. A neuropsychological test battery that included seven tests with nine subscales was administered at baseline, as well as at 1 wk and 3 mo after surgery. POCD was defined using the international study of POCD1 definition.The median total number of cerebral microemboli for the case was 430 (range: 155-2088) in patients undergoing surgery with CPB and 2 (0-66) in the off-pump patients (P0.001). There were no differences in the incidence of POCD between the patients having surgery with or without CPB either at 1 wk (55.2% or 32 of 58 patients [95% confidence interval: 41.5%-68.3%] vs 47.0% or 78 of 166 patients [39.2%-54.9%], P = 0.283) or 3 mo (6.4% or 3 of 47 patients [1.3%-17.5%] vs 13.1% or 16 of 122 of patients [7.7%-20.4%], P = 0.214) after surgery. Increasing age and shorter duration of postoperative hospital stay were independently associated with cognitive dysfunction at 1 wk after surgery. Increasing age and a history of diabetes mellitus were independently associated with cognitive dysfunction 3 mo after surgery. CPB or cerebral microemboli were not significantly related to the occurrence of POCD.In Chinese population, avoidance of CPB during CABG surgery significantly decreased the number of cerebral microemboli, but it did not decrease the incidence of POCD at either 1 wk or 3 mo after CABG. Neither CPB nor cerebral microemboli was independently associated with the risk of POCD.

Background Failure of balloon catheter passing through the occluded segment accounts for 10% - 15% of all procedures during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). We sought to investigate an original technique for facilitating balloon catheter passing by multi-wire plaque crushing. Methods Between July 2000 and October 2007, 152 patients with 164 CTO lesions who had failed balloon passing were treated by multi-wire plaque crushing technique. The main process of this technique was to insert 1 or 2 wires along with the original wire located in the true lumen of CTO lesions after balloon failure for plaque crushing and then to withdraw the crushing wires to get an enlarged lumen inside of the occlusion segment, thus facilitating the balloon passing. Results Both overall lesion and technique success rates were 91.5% (150/164). A total of 211 crushing wires were used during PCI, including 1 crushing wire for 117 (71.3%) lesions and 2 crushing wires for 47 (28.7%) lesions. Approximately 57.3% (121/211) of all crushing wires were those already used in the same procedure. Technique failure occurred in 14 lesions (8.5%). Technique failure was due to crushing wires entering false lumen (92.9%, 13/14) and coronary perforation (7.1%, 1/14). Major procedural complications included coronary perforation (1 case) and severe coronary dissection (2 cases), all of which were successfully treated. Conclusions Multi-wire plaque crushing technique is effective in facilitating balloon catheter passing during CTO PCI. It is feasible, economical and relatively safe with a low rate of procedural complications.

Objectives: To determine the occurrence rate, outcomes, and the characteristics of severe sepsis in surgical intensive care units in multiple medical centers within China and to assess the cost and resource use of severe sepsis in China. Design and Setting: Prospective, observational study of surgical intensive care unit patients at ten university hospitals in six provinces in China. Patients: All adult admissions in studied intensive care units from December 1, 2004, to November 30, 2005. Interventions: None. Measurements and Main Results: The criteria of severe sepsis were based on the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definition. Analysis of data from 3,665 intensive care unit admissions identified 318 (8.68%) cases of severe sepsis, 64.8% of which were men. The median age (interquartile range) of patients with severe sepsis was 64 (47‐74) yrs. Microbes had been isolated from 228 (71.7%) patients, including 171 (53.8%) with Gram-negative bacteria and 146 (45.9%) with Gram-positive bacteria. A total of 90 (22.0%) patients had invasive fungal infection, 20 (6.3%) of which had fungemia. The abdomen was the most common site of infections (72.3%), followed by lung (52.8%). The overall hospital mortality of severe sepsis was 48.7%. Risk factors for hospital mortality included age, chronic comorbidity of malignant neoplasm, Gram-positive bacterial infection, invasive fungal infection, admission Acute Physiology Score, and admission Sequential Organ Failure Assessment score of respiratory dysfunction and cardiovascular dysfunction. The median Therapeutic Intervention Scoring System-28 score was 43 (38‐49). The mean hospital cost was $11,390 per patient and $502 per patient per day. Conclusions: Severe sepsis is a common, expensive, and frequently fatal syndrome in critically ill surgical patients in China. Other than the microbiological patterns, the incidence, mortality, and major characteristics of severe sepsis in Chinese surgical intensive care units are close to those documented in developed countries. (Crit Care Med 2007; 35:2538‐2546)

Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. Methods Between February 1990 to August 2004, 206 patients (138 men and 68 women, mean aged (59 +/- 11) years) who were initially diagnosed as multiple myeloma in Changzheng Hospital (Shanghai, China) and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. Results The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum beta(2) microglobulin and high C-reactive protein. Among these, only C-reactive protein, beta(2) microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. Conclusions High beta(2) microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.

Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces p53-independent apoptosis in cancer cells, but not in normal human cells. This study presents an approach for inhibiting p53-deficient tumor cell growth by using protein-based E4orf4 that had been genetically fused to epidermal growth factor (EGF) to ensure selective targeting of EGF receptor-overexpressing tumor cells. EGF-E4orf4 enables binding onto the cell surface and is then internalized into Saos-2 cells. The success of the process had been demonstrated by immunofluorescence assay and confocal laser microscopy. After prolonged exposure, E4orf4 remained mostly in the nuclei. EGF-E4orf4 treatment of Saos-2 cells showed dose-dependent cytotoxicity. Nearly 50% of the Saos-2 cells were killed at a concentration of 250 nmol/l. In contrast, EGF-E4orf4 showed no significant inhibitory effect iresn primary cells of human umbilical vein endothelial cells. To confirm the ability of EGF-E4orf4 to induce apoptosis, DNA fragmentation was detected using BrdUTP end-labeling. Flow cytometric analysis revealed a significant increase of apoptotic cells in Saos-2 cells treated with EGF-E4orf4, but not in the case of cells cultured in plain medium (t=0.028, P

BACKGROUND Angioplasty in the unprotected left main coronary artery (LMCA) has been controversial. This study aims to evaluate the safety and clinical effectiveness of stenting, including bare metal stent and drug eluting stent (DES), for treatment of unprotected LMCA disease. METHODS Between September 1997 and December 2005, a total of 297 consecutive patients underwent percutanous coronary intervention (PCI) on LMCA lesions in our hospital. Their in-hospital data and clinical follow-up outcomes were analyzed and those in pre-DES "era" (group I, from September 1997 to December 2002) were compared with those in DES "era" (group II, from January 2003 to December 2004. Patients in 2005 for the time of follow-up less than one year were not included in this group). RESULTS Altogether 368 coronary stents were successfully deployed in 295 patients. Stents failed to be implanted after balloon predilation in two patients, who received coronary artery bypass graft (CABG) successfully. Bifurcation techniques for distal LMCA executed in 206 patients (69.4%, 206/297), included crossover stenting in 156 (75.7%), T stenting in 4 (1.9%), provisional T stenting in 28 (13.6%), kissing stenting in 5 (2.4%) and stent crushing in 13 (6.3%) patients. During their hospital stay, 5 (1.7%) patients died after PCI procedure, of which 4 died from cardiac origin and one of renal failure. The total in-hospital major adverse cardiac events (MACE) were 2.0% (6/297). In the follow-up period, 19 patients (6.5%) died [15 (5.1%) of cardiac death and 4 of non-fatal myocardial infarction (MI)]. Besides, 2 (0.7%) developed subacute thrombosis (SAT) and 16 (5.4%) performed target lesion revascularization (TLR). The total follow-up MACE was 14.5% (43/297). Further analysis also showed that, compared with patients in group I, those in group II apparently had more multi-vessel involvement (14.7% vs 81.9%, P < 0.001), and more bifurcation lesions (32.4% vs 72.2%, P < 0.001). After PCI, in-hospital MACE of group II was significantly lower than that in group I (1.1% vs 9.4%, P < 0.05). And the incidences of MACE, TLR and angiographic restenosis in group II were all significantly lower than those in group I (all P < 0.05) after one year follow-up. CONCLUSIONS As new PCI strategies and intervention devices such as DES are developed, coronary stenting, which might have brought better in-hospital and long-term outcomes than CABG, are proved to be technically successful and can be safely applied for the treatment of LMCA lesions in the experienced center for coronary intervention.

We investigated the effect of lidocaine on the incidence of cognitive dysfunction in the early postoperative period after cardiac surgery. One-hundred-eighteen patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB) were randomized to receive either lidocaine (1.5 mg/kg bolus followed by a 4 mg/min infusion during operation and 4 mg/kg in the priming solution of CPB) or placebo. A battery of nine neuropsychological tests was administered before and 9 days after surgery. A postoperative deficit in any test was defined as a decline by more than or equal to the preoperative sd of that test in all patients. Any patient showing a deficit in two or more tests was defined as having postoperative cognitive dysfunction. Eighty-eight patients completed pre- and postoperative neuropsychological tests. Plasma lidocaine concentrations (g/mL) were 4.78 0.52 (mean sd), 5.38 0.95, 4.52 0.39, 5.82 0.76, and 7.10 1.09 at 10 min before CPB; 10, 30, and 60 min of CPB; and at the end of operation, respectively. The proportion of patients showing postoperative cognitive dysfunction was significantly reduced in the lidocaine group compared with that in the placebo group (18.6% versus 40.0%; P 0.028). We conclude that intraoperative administration of lidocaine decreased the occurrence of cognitive dysfunction in the early postoperative period.

BACKGROUND We have previously reported that activated CD8+TCRalphabeta+ cells that express high levels of the beta7 integrin CD103 (formerly alphaE, MLA) are present at the graft site during clinical renal allograft rejection. This observation potentially provides new insight into the mechanisms underlying renal allograft destruction because the ligand of CD103 is the epithelial cell-specific molecule E-cadherin, which is known to be expressed by critical graft functional elements such as the renal tubular epithelium. We herein used combined fluorescence-activated cell sorter (FACS) and immunohistochemical (IHC) analyses of transplant nephrectomy (TN) specimens to demonstrate that CD103+ cytolytic T lymphocytes (CTLs) specifically home to the graft epithelium during rejection episodes. METHODS Serial sections of TN specimens undergoing histologically confirmed cellular rejection (n=7) were stained with anti-CD8 or anti-CD103 and were scored for the presence of positively stained cells within the tubular basement membrane. Freshly isolated graft-infiltrating lymphocytes were subjected to three-color FACS analyses to define the extended phenotypic characteristics of CD103+ cells detected by IHC. RESULTS CD103+ cells in all specimens were biased towards an intratubular localization. On average, the percentage of CD103+ cells with an intraepithelial localization was 52.2+/-13.1 compared to 12.0+/-3.5 for pan CD8+ cells (mean+/-SE, n=5). FACS analyses confirmed that CD103+ cells detected by IHC exhibited the salient characteristics of CD8+ CTLs (large CD8+TCRalphabeta+CD62L-CD11a(hi)perforin+). The CD103- subset of graft-infiltrating CD8 cells also exhibited a CTL phenotype, but these were predominantly restricted to the graft interstitium. CONCLUSIONS These data implicate CD103 as a homing receptor that targets graft-infiltrating CD8+ CTLs to the graft epithelium. Given the strong association of tubulitis with clinical rejection, these data are consistent with a role for the CD103+ CTL subset as an effector mechanism in renal allograft destruction.