Abstract Background Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. Objectives This study ...performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. Methods We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. Conclusions Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.
To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of ...nasopharyngeal carcinoma (NPC).
Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
Abstract Background This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat ...peritoneal carcinomatosis (PC) from gastric cancer (GC). Methods A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m2 and docetaxel 60 mg/m2 in 6,000 mL of normal saline at (43±0.5) °C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles. Results At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC)0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy ≥6 cycles, and peritoneal cancer index ≤20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy ≥6 cycles as the independent predictor for better survival. Conclusions CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety.
To prospectively evaluate safety and efficacy of biliary stent placement with iodine-125 (
I) seeds in patients with malignant obstructive jaundice (MOJ).
From July 2011 to June 2014, 55 patients ...were enrolled (group A, 11 men and 17 women, mean age 70.93 y ± 8.58; group B, 14 men and 13 women, mean age 70.26 y ± 9.71). All patients were randomly assigned to placement of a biliary stent with
I seeds (group A) or biliary stent only (group B). After stent placement, outcomes were measured regarding relief of MOJ. Clinical success rate, survival time, and safety were recorded. P < .05 was considered to indicate significant difference.
Stents were successfully placed in all 55 patients. MOJ was relieved in all patients, and there were no significant differences in complications related to stent insertion between the 2 groups. Mean and median stent patency were 191 days ± 19.8 (95% confidence interval CI, 152-230 d) and 179 days ± 191.4 (95% CI, 87-267 d) in group A and 88.3 days ± 16.3 (95% CI, 61-114 d) and 77 days ± 88.2 (95% CI, 65-86 d) in group B (P < .001, log-rank test). Mean and median survival time were 222.6 days ± 21.0 (95% CI, 181-263 d) and 241 days ± 18.2 (95% CI, 179-270 d) in group A and 139.1 days ± 14.5 (95% CI, 110-167 d) and 142 days ± 16.3 (95% CI, 83-177 d) in group B (P < .001, log-rank test).
I seeds combined with biliary stent placement could significantly improve stent patency. The procedure seems to be safe and to extend survival compared with self-expandable biliary stent placement.
It is not clear whether low-blood pressure criterion could be removed from CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure and age ≥65 years) score to orchestrate an ...improvement in identifying patients with community-acquired pneumonia (CAP) in low-mortality rate settings.
A retrospective cohort study of 1,230 CAP patients was performed to simplify the CURB-65 scoring system by excluding low-blood pressure variable. The simplification was validated in a prospective 2-center cohort of 1,409 adults with CAP.
The hospital mortalities were 1.3% and 3.8% in the retrospective and prospective cohorts, respectively. The mortality rates in the 2 cohorts increased directly with the increasing scores, showing significant increased odds ratios for mortality. The pattern of sensitivity, specificity, positive predictive value and Youden's index of a CUR-65 (Confusion, Urea >7 mmol/L, Respiratory rate ≥30/min and age ≥65 years) score of ≥2 for prediction of mortality was better than that of a CURB-65 score of ≥3 in the retrospective cohort. Higher values of corresponding indices were confirmed in the validation cohort. The higher accuracy of CUR-65 score for predicting mortality was illustrated by the area under the receiver operating characteristic curve of 0.937, compared with 0.915 for CURB-65 score in the retrospective cohort (P = 0.0073). The validation cohort confirmed a similar paradigm (0.953 versus 0.907, P = 0.0002).
CURB-65 score could be simplified by removing low blood pressure to orchestrate an improvement in predicting mortality in CAP patients who have a low risk of death. A CUR-65 score of ≥2 might be a more valuable cutoff value for severe CAP.
Abstract Background In the first posttransplant month, the most frequent complications are due to technical problems related to complex vascular and bile duct reconstructions during the operation. ...Moreover, despite great improvements in suturing technique and materials, severe organ ischemia-reperfusion caused by time-consuming hand suturing is still an important factor in graft survival. During the operation, severe hypotension, hypoxic acidosis, hyperkalemia, and renal dysfunction may occur during the anhepatic phase due to the prolonged venous clamping time required for hand suturing. Therefore, hand suturing is a handicap in the development of further advancements in liver transplantation. In this study, we aimed to test a new “mechanical installation method” for rapid vascular reconstruction. Methods The magnetic pinning-ring device was developed consisting of paired magnetic rings coated with titanium oxide and embedded in a polypropylene shell. The rings were equipped with alternately spaced holes and titanium pins. Forty adult mongrel dogs were randomly divided into groups: A ( n = 16), all vascular and bile duct reconstruction by magnetic ring without venous bypass; B ( n = 16), all vascular and bile duct reconstruction by hand suturing with venous bypass; C ( n = 8), sham transplantation group, transection of all vessels and common bile duct followed by anastomosis with the magnetic rings without liver transplantation. From groups A and B, dogs were randomly selected as donors ( n = 8) or recipients ( n = 8) of liver transplantations. We recorded operation time, vascular and bile duct anastomosis time, anhepatic time, administration of supplemental fluids during operation, and survival; blood samples were collected for the detection of liver damage (alanine aminotransferase ALT and aspartate aminotransferase AST) and tumor necrosis factor α level. Patency was confirmed using ultrasound scans at various time points as late as 24 wk after surgery. Angiography was used to evaluate the anastomoses formed with magnetic rings. In group C, gross observation, histologic staining, and scanning electron microscopy were used to evaluate the vessels and bile ducts 12 wk postoperatively. Results In group A, the total operation time, inferior vena cava, and portal vein anastomosis times were significantly shortened, and the anhepatic phase was reduced to about one-fifth that of group B, which was a significant difference between the two groups ( P < 0.01). The mean total operative time was 2.54 ± 0.45 h. In order to maintain adequate blood pressure, the mean fluid volume infused was 800.56 ± 60.56 mL in the recipients of group A, which was lower than that in group B (2241.67 ± 390.78 mL, P < 0.01). Use of a pressor agent in group A was unnecessary. After operation, five of eight animals in group A survived more than 7 d after operation. The main cause of death was acute rejection. Only three of eight animals in group B survived more than 1 wk after operation due to chronic anastomotic bleeding, kidney failure, heart failure, and gastrointestinal bleeding. There was a statistically significant difference ( P < 0.01) between the short-term survival rate in the two groups (75.0% versus 37.5%). The ALT (1544.46 ± 286.27) U/L and AST (1710.74 ± 252.27) U/L levels after operation in the animals with hand suturing were significantly higher than those in the sutureless group (ALT = 1116.41 ± 210.55 U/L; AST = 1176.95 ± 248.25) U/L after reperfusion ( P < 0.01). The serum tumor necrosis factor α levels (45.56 ± 10.78) ng/L in group B were significantly higher than those of group A (26.64 ± 10.84) ng/L after reperfusion ( P < 0.01). Re-endothelialization was confirmed in all vessels in group C, with neither formation of aneurysms nor thickening of the vascular wall noted after 12 wk. The bile duct anastomoses also healed well. Conclusions The magnetic pinning-ring device offers a simple, fast, reliable, and efficacious technique for nonsuturing vascular and bile duct anastomoses. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of tissue. Application of the magnetic ring anastomosis technique can effectively reduce the complications caused by hand suturing, and can reduce the extent of ischemia-reperfusion injury, leading to smoother operations and improved prognosis.
Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA ...vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD).
This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212).
Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one 5% of 20 in the 5 μg group, 13 65% of 20 in the 10 μg group, 17 85% of 20 in the 15 μg group, 19 95% of 20 in the 20 μg group, 16 100% of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.
ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale.
National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.
Background:
Traditional laparoscopic No.12a lymph node dissection in radical gastrectomy for gastric cancer may damage the peripheral blood vessels, and is not conducive to the full exposure of the ...portal vein and the root ligation of the left gastric vein. We recommend a new surgical procedure, the portal vein approach, to avoid these problems.
Methods:
25 patients with advanced gastric cancer underwent radical laparoscopic gastrectomy and No.12a lymph node were dissected by portal vein approach, including 7 cases with total gastrectomy, 18 cases with distal gastric resection, 14 males and 11 females. Operative time, intraoperative blood loss, time to first flatus, postoperative hospital stay, number of total lymph node dissection and No.12a lymph node dissection, No.12a lymph node metastasis rate and postoperative complications were statistically observed.
Results:
All the patients were operated successfully and No.12a lymph node were cleaned by portal vein approach. A total of 683 lymph nodes were dissected, with the average number of lymph nodes dissection and positive lymph nodes were (27.3 ± 12.7) and (3.8 ± 5.6) respectively. The average number of No.12a lymph node dissection was (2.4 ± 1.95) and the metastasis rate of No.12a lymph node was 16% (4/25). The average operation time of radical laparoscopic distal and total gastrectomy were (239.2 ± 51.4) min and (295.1 ± 27.7) min respectively. The mean intraoperative blood loss was (134.0 ± 65.7) ml, and postoperative first anal exhaust time was (2.24 ± 0.86) d. The mean time to fluid intake was (4.2 ± 1.7) d, and postoperative hospitalization time was (9.6 ± 5.0) d. Without portal vein injure, anastomotic leakage, gastrointestinal bleeding, intestinal obstruction and other complications were observed in all patient.
Conclusion:
Our results show that the laparoscopic No.12a lymph node dissection by portal vein approach for gastric cancer is safe, feasible and has certain clinical application value.
Objective Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, yet effective therapeutic approaches are lacking. This study aimed to determine the effects of application of berberine ...gelatin in the treatment of minor RAS (MiRAS). Methods A randomized, double-blind, placebo-controlled, clinical trial was performed. The gelatin containing berberine (5 mg/g) or vehicle only was applied 4 times per day for 5 days. Clinical evaluation included pain level, size, erythema, and exudation of certain ulcers on days 1, 2, 4, and 6. Results A total of 84 subjects fulfilled the study without obvious side effects. Berberine gelatin treatment reduced the ulcer pain score compared with placebo gelatin ( P < 0.05). Ulcer size was significantly reduced ( P < 0.05) and lower erythema ( P < 0.05) and exudation ( P < 0.05) levels were associated with berberine treatment. Conclusions Berberine gelatin may be a safe and effective treatment for MiRAS.
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