The dinoflagellate Noctiluca scintillans in China: A review of its distribution and role in harmful algal blooms.

The dinoflagellate Noctiluca scintillans is often reported as a worldwide HAB species and caused severe financial losses to local aquaculture. In this review, we summarized the temporal and geographical distribution of its HABs in China, as well as its position in the plankton structure. Increasing N. scintillans HABs, both frequency and coverage, have broken out in almost all Chinese coastal regions mainly from April to June, with short-term and small coverage blooms as the primary type. The HAB period seems to shift with age and latitude. Recently, increasing abundance and dominance of N. scintillans were also reported in plankton communities in Chinese coastal waters, with multiple environmental factors related. In particular, trophic relationships may play an important role in its dominance and outbreaks of HABs. However, how N. scintillans became a dominant species in China and the mechanisms responsible for its HABs require further study.

Long-term neutralizing antibody dynamics against SARS-CoV-2 in symptomatic and asymptomatic infections: a systematic review and meta-analysis

BackgroundThe kinetics of the neutralizing antibody response against SARS-CoV-2 is crucial for responding to the pandemic as well as developing vaccination strategies. We aimed to fit the antibody curves in symptomatic and asymptomatic individuals. MethodsWe systematically searched PubMed, Embase, Web of Science, and Europe PMC for articles published in English between Jan 1, 2020, and Oct 2, 2022. Studies evaluating neutralizing antibody from people who had a natural SARS-CoV-2 infection history were included. Study quality was assessed using a modified standardized scoring system. We fitted dynamic patterns of neutralizing antibody using a generalized additive model and a generalized additive mixed model. We also used linear regression model to conduct both univariate and multivariable analyses to explore the potential affecting factors on antibody levels. This study is registered with PROSPERO, CRD42022348636. Results7,343 studies were identified in the initial search, 50 were assessed for eligibility after removal of duplicates as well as inappropriate titles, abstracts and full-text review, and 48 studies (2,726 individuals, 5,670 samples) were included in the meta-analysis after quality assessment. The neutralization titer of people who infected with SARS-CoV-2 prototype strain peaked around 27 days (217.4, 95%CI: 187.0-252.9) but remained below the Omicron BA.5 protection threshold all the time after illness onset or confirmation. Furthermore, neither symptomatic infections nor asymptomatic infections could provide over 50% protection against Omicron BA.5 sub-lineage. It also showed that the clinical severity and the type of laboratory assays may significantly correlated with the level of neutralizing antibody. ConclusionsThis study provides a comprehensive mapping of the dynamic of neutralizing antibody against SARS-CoV-2 prototype strain induced by natural infection and compared the dynamic patterns between prototype and variant strains. It suggests that the protection probability provided by natural infection is limited. Therefore, timely vaccination is necessary for both previously infected symptomatic and asymptomatic individuals.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022

BackgroundAn outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February to June 2022. The government organized multiple rounds of molecular test screenings for the entire population, providing a unique opportunity to capture the majority of subclinical infections and better characterize disease burden and the full spectrum of Omicron BA.2 clinical severity. MethodsUsing daily reports from the websites of the Shanghai Municipal Health Commission, we estimated the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and Reverse Transcription-Polymerase Chain Reaction (RT{square}PCR) sensitivity, we provide estimates of clinical severity, including the infection fatality risk, symptomatic case fatality risk, and risk of developing severe/critical disease upon infection. FindingsFrom February 26 to June 30, 2022, the overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age with the highest rates of 125.29 (95% CI: 117.05-133.44) per 100,000 and 57.17 (95% CI: 51.63-62.71) per 100,000 individuals, respectively, noted in individuals aged 80 years or older. The overall fatality risk and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.08-0.10%) and 0.23% (95% CI: 0.20-0.25%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. InterpretationUnder the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Europe PMC for manuscripts published or posted on preprint servers after January 1, 2022 using the following query: ("SARS-CoV-2 Omicron") AND ("burden" OR "severity"). No studies that characterized the whole profile of disease burden and clinical severity during the Shanghai Omicron outbreak were found. One study estimated confirmed case fatality risk between different COVID-19 waves in Hong Kong; other outcomes, such as fatality risk and risk of developing severe/critical illness upon infection, were not estimated. One study based on 21 hospitals across the United States focused on Omicron-specific in-hospital mortality based on a limited sample of inpatients (565). In southern California, United States, a study recruited more than 200 thousand Omicron-infected individuals and estimated the 30-day risk of hospital admission, intensive care unit admission, mechanical ventilation, and death. None of these studies estimated infection and mortality rates or other indictors associated with disease burden. Overall, the disease burden and clinical severity of the Omicron BA.2 variant have not been fully characterized, especially in populations predominantly immunized with inactivated vaccines. Added value of this studyThe large-scale and multiround molecular test screenings conducted on the entire population during the Omicron BA.2 outbreak in Shanghai, leading to a high infection ascertainment ratio, provide a unique opportunity to capture the majority of subclinical infections. As such, our study provides a comprehensive assessment of both the disease burden and clinical severity of the SARS-CoV-2 Omicron BA.2 sublineage, which are especially lacking for populations predominantly immunized with inactivated vaccines. Implications of all the available evidenceWe estimated the disease burden and clinical severity of the Omicron BA.2 outbreak in Shanghai in February-June 2022. These estimates are key to properly interpreting field evidence and assessing the actual spread of Omicron in other settings. Our results also provide support for the importance of strategies to prevent overwhelming the health care system and increasing vaccine coverage to reduce mortality.

Application value of overlap guiding tube (OGT) in assisting overlap esophagojejunostomy during laparoscopic total gastrectomy for gastric/gastroesophageal junction (G/GEJ) tumors.

BACKGROUND: The overlap guiding tube (OGT) method, which was designed by our team to assist in overlap esophagojejunostomy, could potentially provide new perspectives for esophagojejunostomy. The application of the OGT-assisted method was first explored by our team and has not yet been reported. METHODS: This cohort study analyzed the 3 month outcomes of 38 gastric/gastroesophageal junction (G/GEJ) tumor patients who underwent OGT-assisted overlap esophagojejunostomy. RESULTS: There were 27 males and 11 females, aged 40-82 years. All patients underwent surgery successfully. The success rate of inserting anvil fork into esophageal lumen at first attempt was 97.4%. The total operation time, esophagojejunostomy time, volume of intraoperative blood loss, and length of surgical incision were 317.6 ± 51.5 min, 20.8 ± 3.8 min, 50.0 (range 15.0-200.0) ml, and 5.0 (range 4.0-8.0) cm, respectively. No procedures were converted to other laparoscopic anastomosis techniques or open approaches. The time to postoperative initial flatus, liquid diet intake, soft diet intake, and length of postoperative hospital stay were 3.0 (range 1.0-6.0) days, 4.0 (range 2.0-9.0)days, 6.0 (range 3.0-11.0) days, and 8.5 (range 6.0-16.0) days, respectively. Overall, postoperative complications were observed in 8 (21.1%) patients. Among them, one patients developed esophagojejunal anastomotic leakage. After 3 months of follow-up, none of the patients developed anastomotic stenosis or experienced unplanned secondary surgery or perioperative death. CONCLUSIONS: OGT-assisted overlap esophagojejunostomy for patients with G/GEJ tumors is safe and feasible, with good short-term effects. OGT method has a satisfactory success rate of inserting anvil fork into esophageal lumen at first attempt and could prevent from developing esophageal submucosa pseudocanals.

Application value of Overlap guiding tube in Overlap esophagojejunostomy of laparoscopic total gastrectomy / 中华消化外科杂志

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint

Evidence on vaccine-specific protection over time and boosting impact against the Delta variant across different clinical endpoints and age groups is urgently needed. To address this, we used a previously published model, combined with neutralization data for four vaccines - mRNA-1273, BNT162b2, NVX-CoV2373, and CoronaVac - to evaluate long-term dynamics of neutralizing antibody and to predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. We found that booster vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacies of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95%CI: 51.4-67.3%) and 78.4% (95%CI: 72.2-83.5%), respectively, 14-30 days after the second dose, and that efficacies decreased to 36.0% (95%CI: 24.1-58.0%) and 38.5% (95%CI: 28.7-49.1%) 6-8 months later. After administration of booster doses, efficacies against the Delta variant would be 97.0% (95%CI: 96.4-98.5%) and 97.2% (95.7-98.1%). All four vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and booster vaccination. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants are needed to inform COVID-19 pandemic preparedness.

Landscape of SARS-CoV-2 genomic surveillance, public availability extent of genomic data, and epidemic shaped by variants: a global descriptive study

BackgroundGenomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021. Characterizing global genomic surveillance, sequencing coverage, the extent of publicly available genomic data coupled with traditional epidemiologic data can provide evidence to inform SARS-CoV-2 surveillance and control strategies. MethodsWe collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data. We divided countries into three levels of genomic surveillance and sequencing availability based on predefined criteria. We downloaded the merged and deduplicated SARS-CoV-2 sequences from multiple public repositories, and used different proxies to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. FindingsSince the start of 2021, the COVID-19 global epidemic clearly featured increasing circulation of Alpha, which was rapidly replaced by the Delta variant starting around May 2021 and reaching a global prevalence of 96.6% at the end of July 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020, with the lowest sequencing coverage in the WHO regions of Eastern Mediterranean, South East Asia, and Africa. Across different variants, 28-52% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. More than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. InterpretationOur findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability. Research in context Evidence before this studyOn September 3, 2021, we searched PubMed for articles in any language published after January 1, 2020, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("Global" OR "Region") AND ("genomic surveillance" OR "sequencing" OR "spread"). Among 43 papers identified, few papers discussed the global diversity in genomic surveillance, sequencing, public availability of genomic data, as well as the global spread of SARS-CoV-2 variants. A paper from Furuse employed the publicly GISAID data to evaluate the SARS-CoV-2 sequencing effort by country from the perspectives of "fraction", "timeliness", and "openness". Another viewpoint paper by Case Western Reserve Universitys team discussed the impediments of genomic surveillance in several countries during the COVID-19 pandemic. The paper as reported by Campbell and colleagues used the GISAID data to present the global spread and estimated transmissibility of recently emerged SARS-CoV-2 variants. We also found several studies that reported the country-level genomic surveillance and spread of variants. To our knowledge, no research has quantitatively depicted the global SARS-CoV-2 genomic surveillance, sequencing ability, and public availability extent of genomic data. Added value of this studyThis study collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data as of 20 August 2021. We found that genomic surveillance strategies and sequencing availability is globally diverse. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020. Our analysis of publicly deposited SARS-CoV-2 sequences and officially reported number of variants implied that the public availability extent of genomic data is low in some countries, and more than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. We also described the pandemic dynamics shaped by VOCs. Implications of all the available evidenceOur study provides a landscape for global sequencing coverage and public availability extent of sequences, as well as the evidence for rapid spread of SRAS-CoV-2 variants. The pervasive spread of Alpha and Delta variants further highlights the threat of SARS-CoV-2 mutations despite the availability of vaccines in many countries. It raised an urgent need to do more work on defining the ideal sampling schemes for different purposes (e.g., identifying new variants) with an additional call to share these data in public repositories to allow for further rapid scientific discovery.

Prediction of vaccine efficacy of the Delta variant

The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.

Comprehensive mapping of neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination

BackgroundImmunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. MethodsWe systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. FindingsWe identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). InterpretationOur findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. FundingChinese National Science Fund for Distinguished Young Scholars Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. Added value of this studyIn this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Implications of all the available evidenceOur findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.

Clinical efficacy of laparoscopic and open distal gastrectomy for gastric cancer in elderly patients: an interim analysis of prospective study / 中华消化外科杂志

Objective:To analyze the interim clinical efficacy of laparoscopic and open distal gastrectomy for gastric cancer in elderly patients.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 102 patients aged ≥65 years who underwent distal gastrectomy for gastric cancer in the Nanfang Hospital of Southern Medical University from September 2014 to May 2018 were collected. After excluding 6 patients, 96 patients were finally included. Based on random number table, patients were allocated into two groups. Patients undergoing laparoscopic distal gastrectomy were allocated into laparoscopic group, and patients undergoing open distal gastrectomy were allocated into open group, respectively. Obser-vation indicators: (1) grouping situations of the enrolled patients; (2) intraoperative situations; (3) postoperative situations; (4) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect complications in the postoperative 30 days up to July 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter Mann-Whitney U test. Results:(1) Grouping situations of the enrolled patients: a total of 96 patients were selected for eligibility. There were 66 males and 30 females, aged from 65 to 85 years, with a median age of 69 years. There were 49 of 96 patients in the laparoscopic group and 47 patients in the open group. (2) Intraoperative situations: patients in the two groups underwent distal gastrectomy successfully with D 2 lymphadenectomy, without intra-operative conversion to laparotomy. The volume of intraoperative blood loss and surgical incision length were 50 mL(50 mL,100 mL) and (7.1±1.7)cm for the laparoscopic group, respectively, versus 100 mL(100 mL,200 mL) and (19.1±1.7)cm for the open group, showing significant differences between the two groups ( Z=?3.779, t=?34.880, P<0.05) . (3) Postoperative situations: the number of lymph node dissected, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative first semi-liquid food intake, time to drainage tube removal, duration of postoperative hospital stay were 49(35,62), 1.9 days(1.3 days,2.9 days), 2.6 days(2.2 days,2.9 days), 3.4 days(2.7days,4.0 days), 5.9 days(4.7 days,7.7 days), 4.9 days(3.5 days,6.8 days), 7.7 days(6.7 days,8.9 days) for the laparoscopic group, respectively, versus 40(27,51), 2.5 days (1.8 days,3.3 days), 2.6 days(2.2 days,2.9 days), 3.9 days(2.9 days,5.7 days), 4.9 days(3.9 days, 5.9 days), 6.3 days(4.7 days,8.9 days), 8.7 days(6.9 days,11.7 days), showing significant differences between the two groups ( Z=?2.354, ?2.210, ?2.743, ?2.474, ?2.906, ?2.503, ?2.359, P<0.05). (4) Follow-up: patients in the two groups received 30 days of follow-up. During the follow-up, 8 patients in the laparoscopic group had postoperative complications, including 1 case with Clavien-Dindo grade Ⅰ complications, 7 cases with Clavien-Dindo grade Ⅱ complications, and no patient with Clavien-Dindo grade Ⅲ complications. Thirteen patients in the open group had postoperative complications, including 2 cases with Clavien-Dindo grade Ⅰ complications, 10 cases with Clavien-Dindo grade Ⅱ complications, and 1 case with Clavien-Dindo grade Ⅲ complications. There was no significant difference in the above indicators between the two groups ( χ2=1.135, 1.973, 1.054, P>0.05). The overall complication rate was 16.3%(8/49) and 27.7%(13/47) for the laparoscopic group and open group, respectively, showing no significant difference between the two groups ( χ2=1.803, 99.7% confidence interval as ?∞ to 2.4%, P>0.05). The upper limit of 99.7% confidence interval was less than non-inferiority level of 15%, interim analysis of which showed that the complication rate of the laparoscopic group was non-inferior to the open group. Conclusion:For elderly patients undergoing laparoscopic or open distal gastrectomy for gastric cancer, laparoscopic surgery does not increase intraoperative or postoperative complications, and has advantages of minimally invasiveness, fine operation, quicker recovery, and shorter hospital stay. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT02246153.

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field / 医学前沿

Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host's immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

Progress in the Treatment of Tachyarrhythmia by Pulsed Electric Field Ablation Catheter Ablation / 中国医疗器械杂志

Pulsed electric field(PEF) provides high-energy instantaneous pulse and release energy to myocardial cell membrane, resulting in irreversible electroporation and causes myocardial cell contents leakage, destruction of intracellular homeostasis, cell death, and slight inflammatory response. PEF as non-thermal energy promotes the design and application of arrhythmia ablation catheter to enter a new stage. There are currently limited clinical studies that have proved the safety and effectieness of Farawave PEF catheter, PVAC GOLD PEF catheter, Lattice-tip Sphere-9 PEF and radiofrequency (RF) catheter used for atrial fibrillation ablation, but still need further discussion. The research of atrial fibrillation ablation with PEF is under study in China. In this paper, the design and application of PEF ablation for tachyarrhythmia are reviewed.

Global, regional, and national estimates of target population sizes for COVID-19 vaccination

BackgroundCOVID-19 vaccine prioritization and allocation strategies that maximize health benefit through efficient use of limited resources are urgently needed. We aimed to provide global, regional, and national estimates of target population sizes for COVID-19 vaccination to inform country-specific immunization strategies on a global scale. MethodsBased on a previous study of international allocation for pandemic COVID-19 vaccines, we classified the entire world population into eleven priority groups. Information on priority groups was derived from a multi-pronged search of official websites, media sources and academic journal articles. The sizes of different priority groups were projected for 194 countries globally. ResultsOverall, the size of COVID-19 vaccine recipient population varied markedly by goals of the vaccination program and geography. The general population aged <60 years without any underlying condition accounts for the majority of the total population (5.2 billion people, 68%), followed by 2.3 billion individuals at risk of severe disease, and 246.9 million essential workers which are critical to maintaining a functional society. Differences in the demographic structure, presence of underlying conditions, and number of essential workers led to highly variable estimates of target populations both at the WHO region and country level. In particular, Europe has the highest share of essential workers (6.8%) and the highest share of individuals with underlying conditions (37.8%), two priority categories to maintain societal functions and reduce severe burden. In contrast, Africa has the highest share of healthy adults, school-age individuals, and infants (77.6%), which are the key groups to target to reduce community transmission. InterpretationThe sizeable distribution of target groups on a country and regional bases underlines the importance of equitable and efficient vaccine prioritization and allocation globally. The direct and indirect benefits of COVID-19 vaccination should be balanced by considering local differences in demography and health.

Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis

BackgroundA rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. PurposeTo evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sourcesWe searched PubMed, Embase, Web of Science, and 4 pre-print servers for English-language papers published from December 1, 2019 to September 25, 2020. Study selectionSerological studies evaluating SARS-CoV-2 seroprevalence in humans. Data extractionTwo investigators independently extracted data from studies. Data SynthesisMost of 230 serological studies, representing tests in >1,400,000 individuals, identified were of low quality based on a standardized study quality scale. In the 51 studies of higher quality, high-risk healthcare workers had higher seroprevalence of 17.1% (95% CI: 9.9-24.4%), compared to low-risk healthcare workers and general population of 5.4% (0.7-10.1%) and 5.3% (4.2-6.4%). Seroprevalence varied hugely across WHO regions, with lowest seroprevalence of general population in Western Pacific region (1.7%, 0.0-5.0%). Generally, the young (<20 years) and the old ([≥]65 years) were less likely to be seropositive compared to middle-aged (20-64 years) populations. Seroprevalence correlated with clinical COVID-19 reports, with pooled average of 7.7 (range: 2.0 to 23.1) serologically-detected-infections per confirmed COVID-19 case. LimitationsSome heterogeneity cannot be well explained quantitatively. ConclusionsThe overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given the relatively narrow range of estimates of the ratio of serologically-detected infections to confirmed cases across different locales, reported case counts may help provide insights into the true proportion of the population infected. Primary Funding sourceNational Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).

Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China

The pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95%CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had higher burden than the 2009 influenza pandemic or seasonal influenza, and that clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China

BackgroundSeveral parameters driving the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear, including age-specific differences in infectivity and susceptibility, and the contribution of inapparent infections to transmission. Robust estimates of key time-to-event distributions remain scarce as well. MethodsWe collected individual records for 1,178 SARS-CoV-2 infected individuals and their 15,648 contacts identified by contact tracing and monitoring over the period from January 13 to April 02, 2020 in Hunan Province, China. We provide descriptive statistics of the characteristics of cases and their close contacts; we fitted distributions to time-to-key-events distributions and infectiousness profile over time; and we used generalized linear mixed model to estimate risk factors for susceptibility and transmissibility of SARS-CoV-2. ResultsWe estimated the mean serial interval at 5.5 days (95%CI -5.0, 19.9) and the mean generation time at 5.5 days (95%CI 1.7, 11.6). The infectiousness was estimated to peak 1.8 days before symptom onset, with 95% of transmission events occurring between 7.6 days before and 7.3 days after the date of symptom onset. The proportion of pre-symptomatic transmission was estimated to be 62.5%. We estimated that at least 3.5% of cases were generated asymptomatic individuals. SARS-CoV-2 transmissibility was not significantly different between working-age adults (15-59 years old) and other age groups (0-14 years old: p-value=0.16; 60 years and over: p-value=0.33), whilst susceptibility to SARS-CoV-2 infection was estimated to increase with age (p-value=0.03). In addition, transmission risk was higher for household contacts (p-value<0.001), decreased for higher generations within a cluster (second generation: odds ratio=0.13, p-value<0.001; generations 3-4: odds ratio=0.05, p-value<0.001, relative to generation 1), and decreased for infectors with a larger number of contacts (p-value=0.04). InterpretationOur findings warn of the possible relevant contribution of children to SARS-CoV-2 transmission. When lockdown interventions are in place, we found that odds of transmission are highest in the household setting but, with the relaxation of interventions, other settings (including schools) could bear a higher risk of transmission. Moreover, the estimated relevant fraction of pre-symptomatic and asymptomatic transmission highlight the importance of large-scale testing, contact tracing activities, and the use of personnel protective equipment during the COVID-19 pandemic.

Health seeking behaviors of patients with acute respiratory infections during the outbreak of novel coronavirus disease 2019 in Wuhan, China

We conducted two surveys to evaluate the health-seeking behaviors of individuals with acute respiratory infections (ARI) during the COVID-19 outbreak in Wuhan, China. Among 351 participants reporting ARI (10.3%, 351/3,411), 36.5% sought medical assistance. Children were more likely to seek medical assistance than other age groups (66.1% vs. 28.0%-35.1%).

Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study

BackgroundThe COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. MethodsWe collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. ResultsThe median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. ConclusionOur findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.