Cost-effectiveness analysis of different anesthesia strategies for transperineal MRI/US fusion prostate biopsy.

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.

Efficacy and safety analysis of a HER2-targeting antibody-drug conjugate combined with immune checkpoint inhibitors in solid tumors: a real-world study.

BACKGROUND: Disitamab Vedotin is a novel antibody-drug conjugate (ADC) drug targeting HER2, which has shown a potential synergistic effect between Disitamab Vedotin and immune checkpoint inhibitors (ICIs). Therefore, we plan to conduct a retrospective real-world study to evaluate the efficacy and safety of Disitamab Vedotin monotherapy or combined with ICIs in the treatment of advanced or metastatic solid tumors. METHODS: This retrospective study involved patients with locally advanced or metastatic solid tumors who were treated with Disitamab Vedotin monotherapy or combined with ICIs at West China Hospital of Sichuan University from July 2019 to June 2023. The observation items included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: This study included 49 patients, out of which 34 patients were treated with Disitamab Vedotin plus ICIs and 15 patients received Disitamab Vedotin alone. In all patients, the median PFS was 10 months. The 6-month and 1-year OS rates were 91.1% and 82.3%, respectively. Eighteen (36.7%) patients achieved a partial response, and sixteen (32.7%) patients had stable disease. The combination therapy of Disitamab Vedotin plus ICIs showed a higher ORR (44.1% vs. 20.0%) and a longer median PFS (14 vs. 8 months) compared to Disitamab Vedotin alone. The median PFS for patients expressed with HER2 2+/3+ was 10 months and was not reached for patients expressed with HER2 0/1+. Grade 3-4 TRAEs occurred in 14.7% of patients who received the combination treatment and in 26.7% of patients who received Disitamab Vedotin alone. CONCLUSIONS: Our study showed that Disitamab-Vedotin-based treatment, alone or in combination with ICIs, exerted considerable prognosis and good tolerance in patients with locally advanced or metastatic solid tumors, regardless of the HER2 expression levels. Whether combination therapy with ICIs provides greater therapeutic benefits compared to monotherapy needs to be further explored through randomized controlled trials.

Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Comparison of trimodality therapy and neoadjuvant chemotherapy combined with radical cystectomy for the survival of muscle-invasive bladder cancer: a population-based analysis.

BACKGROUND: Trimodality therapy (TMT) is a mature alternative to radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC) who seek to preserve their primary bladder or are inoperable due to comorbidities. To date, there has been increasing evidence of the effectiveness of TMT as an alternative to RC. In contrast, no literature has stated the effectiveness of neoadjuvant chemotherapy combined with RC (NAC + RC) compared with TMT. OBJECTIVE: We aimed to compare the prognosis between patients receiving TMT and NAC + RC. METHODS: The clinicopathological characteristics of patients with T2-4aN0M0 MIBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models and Kaplan‒Meier survival curves were used for the survival analysis. Propensity-score matching (PSM) was applied to determine the differences between the two groups. The primary outcome was cancer-specific survival (CSS), and the secondary outcome was overall survival (OS). RESULTS: In total, 1,175 patients with MIBC who underwent TMT (n = 822) or NAC + RC (n = 353) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. After 1:1 PSM, the final patient sample included 303 pairs. The prognosis of patients receiving NAC + RC was significantly better than that of patients receiving TMT in both unmatched and matched cohorts (5-year CSS: before PSM, 75.4% vs. 50.6%, P < 0.0001; after PSM, 76.3% vs. 49.5%, P < 0.0001; 5-year OS: before PSM, 71.7% vs. 37.4%, P < 0.0001; after PSM, 71.7% vs. 31.4%, P < 0.0001). The survival advantages of NAC + RC remained remarkable in the stratified analysis of most factors after PSM. Multivariate Cox regression analysis showed that being older than 68 years old, unmarried, grade III/IV, T3-4a stage, and undergoing TMT independently correlated with poor OS. CONCLUSION: Thus, in this study, patients with MIBC receiving NAC + RC presented with a better prognosis than those receiving TMT.

Predictive value of intravascular ultrasound for the function of intermediate coronary lesions.

BACKGROUND: Intravascular ultrasound (IVUS) can provide detailed coronary anatomic parameters. The purpose of our study was to evaluate the parameters measured by IVUS for the prediction of intermediate coronary lesions function by referencing quantitative fraction ratio (QFR) ≤ 0.80 (vs. > 0.80). METHODS: Eighty four cases with 92 intermediate coronary lesions in vessels with a diameter ≥ 2.50 mm were enrolled. Paired assessment of IVUS and cQFR was available, and vessels with cQFR ≤ 0.8 were considered the positive reference standard. Logistic regression was used to select model variables by a maximum partial likelihood estimation test and receiver operating characteristic curve (ROC) analysis to evaluate the diagnostic value of different indices. RESULTS: Plaque burden (PB) and lesion length (LL) of IVUS were independent risk factors for the function of coronary lesions. The predictive probability P was derived from the combined PB and LL model. The area under the curve (AUC) of PB, (minimum lumen area) MLA, and LL and the predicted probability P are 0.789,0.732,0731, and 0.863, respectively (P < 0.01). The AUC of the predicted probability P was the biggest among them; the prediction accuracy of cQFR ≤ 0.8 was 84.8%, and the sensitivity of the diagnostic model was 0.826, specificity was 0. 725, and P < 0.01. CONCLUSION: PB and LL of IVUS were independent risk factors influencing the function of intermediate coronary lesions. The model combining the PB and LL may predict coronary artery function better than any other single parameter.

Effect of rScO2-Guided Blood Pressure Management on Postoperative Complications in Elderly Patients After Major Noncardiac Surgery: Protocol for a Randomized Controlled Trial.

Background: Postoperative complications are common after major surgical procedures, leading to increased morbidity and mortality. Regional cerebral oxygen saturation (rScO2) reflects cerebral and global perfusion, and thus it can be used to guide hemodynamic management. We aim to explore the effect of rScO2-guided blood pressure management strategy on postoperative major complications in older adults who undergo major noncardiac surgery. Methods: This randomized controlled clinical trial includes a total of 400 elderly patients receiving major noncardiac surgery and general anesthesia. Patients will be randomized (1:1) to one of two blood pressure management groups: a standard care group (targeting mean arterial pressure >65 mmHg or within 20% of baseline value), and a rScO2-guided group (absolute value of rScO2 >60% or decrease in rScO2 <10% of baseline). The primary outcome is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. Secondary outcomes include the individual components of the primary outcome by day 7 after surgery and 30-day mortality. Data will be analyzed in the modified intention-to-treat population. Discussion: This study will provide evidence for improving postoperative outcomes using the rScO2-guided blood pressure management among older adults who undergo major noncardiac surgery. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2200060816).

This is a protocol for a prospective, randomized, controlled clinical trial to evaluate the use of intraoperative individualized regional cerebral oxygen saturation (rScO₂) optimization for blood pressure management in older adults undergoing major noncardiac surgery. The primary focus of this trial is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. The secondary outcomes are the individual components of the primary outcome by day 7 after surgery and 30-day mortality. The findings of this trial will provide clinical evidence for the rScO₂-guided blood pressure management to improve postoperative outcomes in older patients who are scheduled for major noncardiac surgery.

Effects of opioid-free total intravenous anesthesia on postoperative nausea and vomiting after treatments of lower extremity wounds: protocol for a randomized double-blind crossover trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common after general anesthesia and surgery. This study aims to compare the effects of total intravenous opioid-free anesthesia (OFA) with conventional opioid-based anesthesia (OBA) on PONV in patients following treatments for wounds of lower extremities. METHODS: This randomized, double-blind, crossover trial will include a total of 72 adult patients scheduled for at least two separate surgical treatments of lower extremity wounds under general anesthesia. Patients will be randomized to 1 of 2 anesthesia sequences of OFA and OBA. Patients in sequence 1 will receive OFA in the first treatment procedure and OBA in the second procedure, while patients in sequence 2 will receive the two anesthesia regimens in the reverse order. The washout period is at least 5 days. OFA will be delivered with intravenous esketamine, lidocaine, dexmedetomidine, and propofol. OBA will be delivered with intravenous sufentanil and propofol. The primary endpoint is the incidence of PONV within the first 48 h postoperatively. The secondary endpoints are the severity of PONV, antiemetic rescue therapy, postoperative pain scores, the worst pain, need for rescue analgesia, postoperative sedation, hypotension, bradycardia, hypertension, tachycardia, hypoxemia, psychotomimetic or dissociative effects, time to extubation, and length of postanesthesia care unit stay. Patients who complete two surgical procedures with designated anesthesia regimens will be included in the final analyses. DISCUSSION: This crossover trial will determine whether total intravenous OFA reduces PONV in patients following treatments for lower extremity wounds. The results of this trial will also represent an important step to understand the benefits and possible risks of OFA in surgical patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061511).

Combining MOE Bioinformatics Analysis and In Vitro Pseudovirus Neutralization Assays to Predict the Neutralizing Ability of CV30 Monoclonal Antibody on SARS-CoV-2 Variants.

Combining bioinformatics and in vitro cytology assays, a predictive method was established to quickly evaluate the protective effect of immunity acquired through SARS-CoV-2 infection against variants. Bioinformatics software was first used to predict the changes in the affinity of variant antigens to the CV30 monoclonal antibody by integrating bioinformatics and cytology assays. Then, the ability of the antibody to neutralize the variant antigen was further verified, and the ability of the CV30 to neutralize the new variant strain was predicted through pseudovirus neutralization experiments. The current study has demonstrated that when the Molecular Operating Environment (MOE) predicts |ΔBFE| ≤ 3.0003, it suggests that the CV30 monoclonal antibody exhibits some affinity toward the variant strain and can potentially neutralize it. However, if |ΔBFE| ≥ 4.1539, the CV30 monoclonal antibody does not display any affinity for the variant strain and cannot neutralize it. In contrast, if 3.0003 < |ΔBFE| < 4.1539, it is necessary to conduct a series of neutralization tests promptly with the CV30 monoclonal antibody and the variant pseudovirus to obtain results and supplement the existing method, which is faster than the typical procedures. This approach allows for a rapid assessment of the protective efficacy of natural immunity gained through SARS-CoV-2 infection against variants.

Lung Large Cell Neuroendocrine Carcinoma: A Population-Based Retrospective Cohort Study.

BACKGROUNDS: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. In this study, we aim to construct a prognostic nomogram that integrates the clinical features and treatment options to predict disease-specific survival (DSS). METHODS: A total of 713 patients diagnosed with LCNEC were from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010-2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010-2018. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Additionally, we conducted a subgroup analysis of data available in the external cohort that may impact prognosis but was not recorded in the SEER database. RESULTS: Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group, respectively. Moreover, the calibration curves for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all Area Under Curve (AUC) > 0.8). DCA exhibited the favorable clinical applicability of the nomogram in the prediction of LCNEC survival. A risk classification system was built which could perfectly classify LCNEC patients into high-, medium- and low-risk groups (p < 0.001). The survival analysis conducted on the West China Hospital cohort indicated that whole brain radiation therapy (WBRT), prophylactic cranial irradiation (PCI), surgical procedures, tumor grade, Ki-67, and PD-L1 expression were not significantly associated with DSS. CONCLUSION: This study has effectively developed a prognostic nomogram and a corresponding risk stratification system, which demonstrate promising potential for predicting the DSS of patients with LCNEC.

Impact of the COVID-19 pandemic on cancer healthcare utilization in southwestern China on March 2021.

BACKGROUND: Oncological care has been disrupted worldwide during the COVID-19 pandemic. We aimed to quantify the long-term impact of the pandemic on cancer care utilization and to examine how this impact varied by sociodemographic and clinical factors in southwestern China, where the Dynamic Zero-COVID Strategy was implemented. This strategy mainly included lockdowns, stringent testing, and travel restrictions to prevent the spread of COVID-19. METHOD: We identified 859,497 episodes of the utilization of cancer care from electronic medical records between January 1, 2019, and March 31, 2021, from the cancer center of a tertiary hospital serving an estimated population of 8.4 million in southwestern China. Changes in weekly utilization were evaluated via segmented Poisson regression across service categories, stratified by cancer type and sociodemographic factors. RESULTS: A sharp reduction in utilization of in-person cancer services occurred during the first week of the pandemic outbreak in January 2020, followed by a quick rebound in February 2020. Although there were few COVID-19 cases from March 2020 until this analysis, the recovery of most in-person services was slow and remained incomplete as of March 31, 2021. The exceptions were outpatient radiation and surgery, which increased and exceeded pre-pandemic levels, particularly among lung cancer patients; meanwhile, telemedicine utilization increased substantially after the onset of the pandemic. Care disruptions were most prominent for women, rural residents, uninsured, and breast cancer patients. CONCLUSIONS: As of March 2021, despite few COVID-19 cases, the COVID-19 pandemic has had a strong and continuing impact on in-person oncology care utilization in southwestern China under the Dynamic Zero-COVID Strategy. Equitable and timely access to cancer care requires adjustment in strict policies for COVID-19 prevention and control, as well as targeted remedies for the most vulnerable populations during and beyond the pandemic. Future studies should monitor the long-term effects of the COVID-19 pandemic and response strategies on cancer care and outcomes.

Response of seed germination and seedling emergence of Haloxylon ammodendron to rain frequency and temperature change from four desert ecosystems, Northwest China.

Climate change will result in variation of rain frequency and amount and warming in arid zones, which is expected to affect seed germination and seedling emergence in desert ecosystems. However, the effects of unpredictable rainfall and increasing temperature on seed germination and seedling emergence of dominant desert plants remain unclear across different deserts, which are important for population regeneration and community succession in desert ecosystems. Seed germination and seedling emergence of Haloxylon ammodendron across four deserts in Northwest China were examined at different rain frequencies with same total amount, and constant and alternating temperatures, to investigate their response to climate change. Rain frequency determined seed germination and seedling emergence of H. ammodendron in the Tengger Desert, Badain Jaran Desert, Gurbantonggut Desert and Mutthar Desert, which was maximal at rain frequency of 10 times per month and decreased with a decrease of rain frequency. Temperature was not a restricting factor for seed germination of H. ammodendron in the Tengger Desert, Badain Jaran Desert and Gurbantonggut Desert, varying from 10 °C to 25 °C and from 20/10 °C to 30/15 °C, respectively. However, the highest temperature of 25 °C and 30/15 °C inhibited seed germination of H. ammodendron in the Mutthar Desert. Thus, H. ammodendron has an opportunistic germination strategy. Under climate change in the future, seed germination and seedling emergence of H. ammodendron would be restricted by the combination of less frequent rainfall and increased temperature in desert ecosystems. The regeneration of the H. ammodendron community should be promoted by irrigation and seedling transplant.

Neutralization Effect of Sera against Delta and Omicron in Patients Recovering from COVID-19 and Inactivated Vaccine Recipients.

This study aims to analyze the serum neutralization capacity against Delta and Omicron variants in three clusters of individuals, including those who had recovered from COVID-19 and those who had received two and three doses of inactivated vaccine. Pseudovirus neutralization tests were performed on serum samples. The neutralizing titers between different groups were compared using the Wilcoxon's signed-rank test. Among the two-dose vaccinees, the neutralization titers of the Omicron variant were reduced by approximately 3.1-fold compared to the wild-type virus (p < 0.05). Meanwhile, among the three-dose vaccinees, the neutralization titers for Delta and Omicron variants were 3.5-fold (p < 0.05) and 5.0-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. In addition, among the recovering patients, the neutralization titers for Delta and Omicron variants were 3.9-fold (p < 0.05) and 29.1-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. Overall, only 12.0% (11/92) of participants showed neutralizing titers against Omicron above the detection limit. The ability to neutralize wild-type pseudovirus was significantly boosted in three-dose vaccinees as compared to two-dose vaccinees. Sera from recovered patients showed greater neutralizing titers for the wild-type and Delta pseudoviruses than the two- and three-dose inactivated vaccine groups. The present study revealed a loss of neutralizing activity against the Omicron variant in almost all samples. Moreover, the immunization effect obtained through natural infection is more robust than that from the active immunization method of vaccination.

Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study.

Metformin, a biguanide drug, is the most commonly used first-line medication for type 2 diabetes mellites due to its outstanding glucose-lowering ability. After oral administration of 1 g, metformin peaked plasma concentration of approximately 20-30 µM in 3 h, and then it mainly accumulated in the gastrointestinal tract, liver and kidney. Substantial studies have indicated that metformin exerts its beneficial or deleterious effect by multiple mechanisms, apart from AMPK-dependent mechanism, also including several AMPK-independent mechanisms, such as restoring of redox balance, affecting mitochondrial function, modulating gut microbiome and regulating several other signals, such as FBP1, PP2A, FGF21, SIRT1 and mTOR. On the basis of these multiple mechanisms, researchers tried to repurpose this old drug and further explored the possible indications and adverse effects of metformin. Through investigating with clinical studies, researchers concluded that in addition to decreasing cardiovascular events and anti-obesity, metformin is also beneficial for neurodegenerative disease, polycystic ovary syndrome, aging, cancer and COVID-19, however, it also induces some adverse effects, such as gastrointestinal complaints, lactic acidosis, vitamin B12 deficiency, neurodegenerative disease and offspring impairment. Of note, the dose of metformin used in most studies is much higher than its clinically relevant dose, which may cast doubt on the actual effects of metformin on these disease in the clinic. This review summarizes these research developments on the mechanism of action and clinical evidence of metformin and discusses its therapeutic potential and clinical safety.

A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis.

Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or malignant ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract and ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities. However, malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction. Here, we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA, which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment. Interestingly, we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells. Based on this feature, a novel PD-L1-targeting chimeric switch receptor (PD-L1.BB CSR) was designed, which can bind to PD-L1, switching the inhibitory signal into an additional 4-1BB signal. When co-expressed with a 2nd-generation CAR, PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment, causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models. Further investigations revealed elevated expressions of T-cell activation, proliferation, and cytotoxicity-related genes, and we confirmed that PD-L1 scFv and 4-1BB intracellular domain, the two important components of PD-L1.BB CSR, were both necessary for the functional improvements of CAR-T cells. Overall, our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells. Based on this study, a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis (NCT04684459).

Effect of Vaccination Time Intervals on SARS-COV-2 Omicron Variant Strain Infection in Guangzhou: A Real-World Matched Case-Control Study.

In April 2022, a COVID-19 outbreak caused by the Omicron variant emerged in Guangzhou. A case-control study was conducted to explore the relationship between vaccination intervals and SARS-CoV-2 infection in the real world. According to the vaccination dose and age information of the cases, a 1:4 matched case-control sample was established, finally including n = 242 for the case group and n = 968 for the control group. The results indicated that among the participants who received three vaccine doses, those with an interval of more than 300 days between the receipt of the first vaccine dose and infection (or the first contact with a confirmed case) were less likely to be infected with SARS-CoV-2 than those with an interval of less than 300 days (OR = 0.67, 95% CI = 0.46-0.99). After age-stratified analysis, among participants aged 18-40 years who received two doses of vaccine, those who received the second dose more than 30 days after the first dose were less likely to be infected with SARS-CoV-2 (OR = 0.53, 95% CI = 0.30-0.96). Our findings suggest that we need to extend the interval between the first dose and the second dose and further explore the optimal interval between the first and second and between the second and third doses in order to improve vaccine efficacy.

Impact of Vaccination and Control Measures on the Fatality of COVID-19: An Ecological Study.

BACKGROUND: During the COVID-19 pandemic, reducing the case fatality rate (CFR) becomes an urgent goal. OBJECTIVE: This study explored the effect of vaccination and variants on COVID-19 fatality and provide a basis for the adjustment of control measures. METHODS: This study collected epidemiological information on COVID-19 from January to October 2021. By setting different lag times, we calculated the adjusted CFR. The Spearman correlation coefficient and beta regression were used to explore factors that may affect COVID-19 fatality. RESULTS: Every 1% increase in the percentage of full vaccinations may reduce the 3 weeks lagging CFR by 0.66%. Increasing the restrictions on internal movement from level 0 to 1, restrictions on international travel controls from level 2 to 3, and stay-at-home restrictions from level 0 to 2 were associated with an average reduction in 3 weeks lagging CFR of 0.20%, 0.39%, and 0.36%, respectively. Increasing strictness in canceling public events from level 0 to 1 and 2 may reduce the 3 weeks lagging CFR by 0.49% and 0.37, respectively. Increasing the severity of school and workplace closures from level 1 or level 0 to 3 may increase the 3 weeks lagging CFR of 0.39% and 0.83, respectively. Every 1-point increase in the Global Health Security (GHS) index score may increase the 3 weeks lagging CFR by 0.12%. CONCLUSION: A higher percentage of full vaccinations, higher levels of internal movement restrictions, international travel control restrictions, cancelations of public events, and stay-at-home restrictions are factors that may reduce the adjusted CFR.

Opioid-free total intravenous anesthesia for thyroid and parathyroid surgery: Protocol for a randomized, double-blind, controlled trial.

Background: Opioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery. Methods: This two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population. Discussion: We hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR2200059656.

Effectiveness of COVID-19 Vaccine Booster Shot Compared with Non-Booster: A Meta-Analysis.

The analysis of the effectiveness of booster shots compared with primary vaccination is extremely vital. This paper aimed to summarize the results of all available evidence studies on the effectiveness of booster vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Articles published up to 21 June 2022 were systematically searched through PubMed and EMBASE databases. The searched studies were independently assessed for quality using the Newcastle-Ottawa Scale. Results: Seven studies (nine datasets) met the criteria and were included in this study. The pooled results demonstrated a 71% (OR = 0.29, 95% CI = 0.17-0.48) reduction in SARS-CoV-2 infection rates among subjects who received a booster shot compared with those who did not receive a booster shot of coronavirus disease (COVID-19) vaccine. In addition, this analysis emphasized that during the period when the Delta variant was predominant, subjects who received the booster shot showed an 82% (OR = 0.18, 95% CI = 0.13-0.25) reduction in infection rates. Moreover, during the period of dominance of the Omicron variant, subjects who received the booster vaccination displayed a 47% (OR = 0.53, 95% CI = 0.35-0.81) reduction in infection rates. This finding confirmed that booster vaccination against the Omicron variant is significantly less effective than that against the Delta variant. In pandemic periods, correlations between the dominant variant and the efficacy of the COVID-19 vaccine booster should be considered when making vaccine booster plans.

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy.

Cancer is a major disease endangering human health. More and more studies have shown that microorganisms play an extremely important role in the occurrence, development and treatment of tumors. As a very promising tumor treatment strategy, immunotherapy has also been proved to have a great relationship with microorganisms. Here, the authors review the contribution of the microbiota to cancer and the research on its impact on cancer immunotherapy. We also highlight the possible mechanism of their interaction and outlined the potential application of microbiota in tumor immunotherapy.