AIM To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease. METHODS Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort – Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb. RESULTS In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57). CONCLUSIONS The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Effective postoperative pain management plays a key role in enhancing recovery of patients after surgery. Bupivacaine hydrochloride is one of the most commonly local anesthetics used for the postoperative pain control. However, the relatively short anesthesia duration of bupivacaine preparations limited their clinical application. METHODS Both guinea pig pin-prick study and rat tail-flick test were performed to evaluate the local anesthesia efficacy of HYR-PB21-LA, a new microparticle suspension injection of bupivacaine pamoate. RESULTS In the pin-prick test, the complete cutaneous trunci muscle reflex inhibitions were observed at 30 min in all treatment groups containing bupivacaine. selleck inhibitor In comparison with 6.7 mg/mL HYR-PB21-LA, both 10 and 20 mg/mL HYR-PB21-LA groups had significantly higher area under effect time curve (AUEC) values (p less then 0.001 and p less then 0.0001) and slower offset time (p less then 0.0001). Significantly higher AUEC (p less then 0.0001) and slower offset time (p less then 0.0001) were also found in 10 mg/mL HYR-PB21-LA treatment group compared with bupivacaine liposome injectable suspension (liposomal bupivacaine). In the rat tail-flick test, significantly increased local anesthesia effect was lasted for 5 hours after 2.5 mg/mL HYR-PB21-LA administration, which was fivefold longer than bupivacaine hydrochloride. The longer lasted efficacy of significantly increased local anesthesia was also observed in 5 mg/mLHYR-PB21-LA than those in liposomal bupivacaine (8 hour vs 1 hour). CONCLUSIONS The results demonstrated that the HYR-PB21-LA produced longer local anesthesia effect than current clinical preparations of bupivacaine in two animal models. These findings raise the potential clinical value of HYR-PB21-LA as a long-lasting local anesthesia for controlling postsurgical pain in humans. © American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR). RESULTS A total of 136 patients were included 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA. CONCLUSIONS The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status. CLASSIFICATION OF EVIDENCE That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse. © 2020 American Academy of Neurology.OBJECTIVE To evaluate clinical and demographic factors of patients with neurologic disorders to determine which patient characteristics are significant for predicting 30-day hospital readmissions to develop a readmission risk predictor specific to patients with neurologic disorders. METHODS We performed a retrospective single-center chart review for all patients admitted to the Department of Neurology or neurologic intensive care unit from January 1, 2013, to December 31, 2017. Clinical and demographic factors were analyzed to determine the association with readmission. Multivariable logistic regression analysis was performed and validated to develop a simple tool (Neuro R2 score) for predicting patients with neurologic disorders at high risk for hospital readmission. RESULTS After removal of planned readmissions and patients who died in the hospital, the records of 4,876 patients with 314 (6.4%) readmission events were analyzed. The strongest predictors for readmission were Charlson disease count (odds ratio [OR] 1.