A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

OBJECTIVE: The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. METHODS: This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. RESULTS: This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). CONCLUSIONS: In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Trimethylamine from Subtropical Forests Rival Total Farmland Emissions in China.

Many types of living plants release gaseous trimethylamine (TMA), making it a potentially important contributor to new particle formation (NPF) in remote areas. However, a panoramic view of the importance of forest biogenic TMA at the regional scale is lacking. Here, we pioneered nationwide mobile measurements of TMA across a transect of contiguous farmland in eastern China and a transect of subtropical forests in southern China. In contrast to the farmland route, TMA concentrations measured during the subtropical forest route correlated significantly with isoprene, suggesting potential TMA emissions from leaves. Our high time-resolved concentrations obtained from a weak photo-oxidizing atmosphere reflected freshly emitted TMA, indicating the highest emission intensity from irrigated dryland (set as the baseline of 10), followed by paddy field (7.1), subtropical evergreen forests (5.9), and subtropical broadleaf and mixed forests (4.3). Extrapolating their proportions roughly to China, subtropical forests alone, which constitute half of the total forest area, account for nearly 70% of the TMA emissions from the nation's total farmland. Our estimates, despite the uncertainties, take the first step toward large-scale assessment of forest biogenic amines, highlighting the need for observational and modeling studies to consider this hitherto overlooked source of TMA.

Efficacy and Safety of Once-Weekly Insulin Regimes on Glycemic Control for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

BACKGROUND: Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes. METHODS: We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, 2023, with no language limitations. Our aim was to conduct a systematic review of randomized controlled trials that investigated the effectiveness and safety of once-weekly insulin in individuals with type 2 diabetes. Our primary outcome was to evaluate excellent glycemic control, defined as patients achieving glycated hemoglobin levels below 7%. RESULTS: We identified a total of 7 trials involving 2829 patients. The results showed that once-weekly insulin icodec is more effective than once-weekly insulin Fc (RR 1.59 [95% CI 1.08-2.38]), once-daily degludec (RR 1.43 [95% CI 1.14-1.83]), and once-daily glargine (RR 1.15 [95% CI 1.00-1.41]). Moreover, the incidence of severe hypoglycemia was lower with once-weekly insulin icodec compared to once-daily degludec (RR 0.00016 [95% CI 0 to 0.41]). However, no significant difference in the incidence of severe hypoglycemia was observed between once-weekly insulin icodec and once-daily glargine (RR 0.39 [95% CI 0.03 to 4.83]). CONCLUSIONS: In patients with type 2 diabetes, once-weekly insulin icodec achieved superior glycemic control compared to once-weekly insulin Fc, with no significant difference in the occurrence of hypoglycemia. The ranking probability results have shown that one weekly icodec seems to be the preferred option in patients with type 2 diabetes. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023470894.

Retracted: Brain Susceptibility Weighted Imaging Signal Changes in Acute Hemorrhagic Anemia: An Experimental Study Using a Rabbit Model.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Jun Xia, Ni Xie, Yuning Feng, Anyu Yin, Pinni Liu, Ruming Zhou, Fan Lin, Guozhao Teng, Yi Lei. Brain Susceptibility Weighted Imaging Signal Changes in Acute Hemorrhagic Anemia: An Experimental Study Using a Rabbit Model. Med Sci Monit, 2014; 20: 1291-1297. DOI: 10.12659/MSM.890641.

Association of anemia with mortality in young adult patients with intracerebral hemorrhage.

This study aimed to examine the association of hemoglobin concentration with a 90-day mortality of young adult patients with ICH in a large retrospective cohort. A retrospective observational study was conducted between December 2013 and June 2019 in two tertiary academic medical centers in China. We defined patients with hemoglobin concentration < 80 g/L as severe anemia and 80-120/130 g/L as mild to moderate anemia. We also defined patients with hemoglobin concentration > 160 g/L as high hemoglobin. Associations of hemoglobin and outcomes were evaluated in multivariable regression analyses. The primary outcome was mortality at 90 days. We identified 4098 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, the 90-day mortality rate was significantly higher in young patients with severe anemia (OR, 39.65; 95% CI 15.42-101.97), moderate anemia (OR, 2.49; 95% CI 1.24-5.00), mild anemia (OR, 1.89; 95% CI 1.20-2.98), and high hemoglobin (OR, 2.03; 95% CI 1.26-3.26) group than in young patients of the normal group. The younger age was associated with a higher risk of death from anemia in patients with ICH (P for interaction = 0.01). In young adult patients with ICH, hemoglobin concentration was associated with 90-day mortality, and even mild to moderate anemia correlated with higher mortality. We also found that in ICH patients with anemia, younger age was associated with higher risk.

Association Between Red Blood Cell Distribution width and Long-Term Mortality in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between the red cell distribution width (RDW) and long-term mortality in patients with intracerebral hemorrhage (ICH) has not been clearly established. METHODS: We conducted a retrospective cohort study of patients with ICH admitted to two tertiary hospitals. The primary outcome was long-term mortality, and the effect of elevated RDW (RDW coefficient of variation [RDW-CV]; RDW standard deviation [RDW-SD]) on outcomes was assessed by using logistic regression analysis. Serum RDW levels was divided into four levels by quartiles (the lowest quartile [Q1]; the highest quartile [Q4]). RESULTS: This study included 4223 patients with ICH. After adjustment for potential confounders, admission RDW-CV (Quartile 4 [Q4] vs. Quartile 1 [Q1], adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.34-1.92) and median RDW-CV within the first month after admission (Q4 vs. Q1, adjusted HR 1.69, 95% CI 1.40-2.04) were both associated with 1-year mortality following ICH. Parallel results were found for RDW-SD. In the receiver operating characteristic analyses, both RDW-CV and RDW-SD outperformed some inflammatory biomarkers, such as albumin, hemoglobin, total cholesterol, platelet count, lymphocyte, and fibrinogen, in predicting long-term mortality following ICH. Additionally, compared with admission RDW, median RDW-CV and RDW-SD (areas under the curve [AUC] 0.668 and 0.652, respectively) was superior to predict long-term mortality, (P < 0.001). Furthermore, median RDW-CV level was a better predictor than RDW-SD (P = 0.03). CONCLUSIONS: In patients with ICH, RDW independently predicted long-term mortality. Median RDW levels within the first month after admission were better predictors of long-term mortality compared with RDW levels on admission. Additionally, median RDW-CV showed superior predictive capacity than median RDW-SD for long-term mortality following ICH.

Lower versus higher oxygen targets for out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is commonly administered to patients after out-of-hospital cardiac arrest. However, the findings from studies on oxygen targeting for out-of-hospital cardiac arrest are inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of lower oxygen target compared with higher oxygen target on patients after out-of-hospital cardiac arrest. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, from inception to February 6, 2023, for randomized controlled trials comparing lower and higher oxygen target in adults (aged ≥ 18 years) after out-of-hospital cardiac arrest. We screened studies and extracted data independently. The primary outcome was mortality at 90 days after cardiac arrest. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study was registered with PROSPERO, number CRD42023409368. RESULTS: The analysis included 7 randomized controlled trials with a total of 1451 participants. Compared with lower oxygen target, the use of a higher oxygen target was not associated with a higher mortality rate (relative risk 0.97, 95% confidence intervals 0.82 to 1.14; I2 = 25%). Findings were robust to trial sequential, subgroup, and sensitivity analysis. CONCLUSION: Lower oxygen target did not reduce the mortality compared with higher oxygen target in patients after out-of-hospital cardiac arrest.

Obesity Paradox for Postoperative Mortality in Young Chinese Patients Undergoing Craniotomy for Brain Tumor Resection.

BACKGROUND: There is little evidence regarding the association of body mass index (BMI) with postoperative mortality after craniotomy, especially in the Asian population. Our study aimed to explore the association between BMI and postoperative 30-day mortality in Chinese patients undergoing craniotomy for brain tumor resection. METHODS: This large retrospective cohort study, Supplemental Digital Content 9, http://links.lww.com/JNA/A634 collected data from 7519 patients who underwent craniotomy for brain tumor resection. On the basis of the World Health Organization obesity criteria for Asians, included patients were categorized as underweight (<18.5 kg/m2), normal weight (18.5 to 22.9 kg/m2), overweight (23to 24.9 kg/m2), obese I (25 to 29.9 kg/m2), and obese II (≥30 kg/m2). We used a multivariable logistic regression model to explore the association between different BMI categories and 30-day postoperative mortality. In addition, we also conducted stratified analyses based on age and sex. RESULTS: Overweight (adjusted odds ratio 0.63, 95% CI 0.40-0.99) and obese I (adjusted odds ratio 0.44, 95% CI 0.28-0.72) were associated with decreased 30-day postoperative mortality compared with normal-weight counterparts. Such associations were prominent among younger (age younger than 65 y) patients but not older patients, and there was an interaction between age and overweight versus normal weight on mortality (P for interaction=0.04). CONCLUSIONS: We found that among Chinese patients undergoing craniotomy for brain tumors, there was a J-shaped association between BMI and postoperative 30-day mortality, with lowest mortality at 27 kg/m². Moreover, in young patients, overweight and obese I were both associated with decreased risk of 30-day mortality.

Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Implantable cardiac monitors (ICM) can facilitate the detection of asymptomatic atrial fibrillation episodes. We performed a systematic review and meta-analysis to investigate whether ICM can prevent stroke in patients with prior stroke and risk factors for stroke. METHODS: This study included randomized controlled trials comparing ICM with conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. We searched Medline, Embase, and CENTRAL from inception until January 5, 2022, without language restriction. Quantitative pooling of the data was undertaken using a random-effects model. The primary outcome was ischemic stroke at the longest follow-up. RESULTS: Four trials comprising 7237 patients were included. ICM was significantly associated with decreased risk of ischemic stroke (RR 0.76; 95% CI, 0.59-0.97; moderate-quality evidence) in patients with prior stroke and risk factors for stroke. ICM was associated with higher detection of atrial fibrillation (RR 4.21, 95% CI 2.26-7.85) and use of oral anticoagulants (RR 2.29, 95% CI 2.07-2.55). CONCLUSIONS: ICM results in a significantly lower risk of ischemic stroke than conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. Due to the clinical heterogeneity of study population and limited related studies, more trials were needed to furtherly explore the topic in patients with prior stroke or high risk of stroke.

Association between intraoperative steroid and postoperative mortality in patients undergoing craniotomy for brain tumor.

Background: Despite the widespread use of intraoperative steroids in various neurological surgeries to reduce cerebral edema and other adverse symptoms, there is sparse evidence in the literature for the optimal and safe usage of intraoperative steroid administration in patients undergoing craniotomy for brain tumors. We aimed to investigate the effects of intraoperative steroid administration on postoperative 30-day mortality in patients undergoing craniotomy for brain tumors. Methods: Adult patients who underwent craniotomy for brain tumors between January 2011 to January 2020 were included at West China Hospital, Sichuan University in this retrospective cohort study. Stratified analysis based on the type of brain tumor was conducted to explore the potential interaction. Results: This study included 8,663 patients undergoing craniotomy for brain tumors. In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality (adjusted OR 1.98, 95% CI 1.09-3.57). However, in patients with malignant brain tumors, no significant association was found between intraoperative steroid administration and postoperative 30-day mortality (adjusted OR 0.86, 95% CI 0.55-1.35). Additionally, administration of intraoperative steroids was not associated with acute kidney injury (adjusted OR 1.11, 95% CI 0.71-1.73), pneumonia (adjusted OR 0.89, 95% CI 0.74-1.07), surgical site infection (adjusted OR 0.78, 95% CI 0.50-1.22) within 30 days, and stress hyperglycemia (adjusted OR 1.05, 95% CI 0.81-1.38) within 24 h after craniotomy for brain tumor. Conclusion: In patients undergoing craniotomy for benign brain tumors, intraoperative steroids were associated with 30-day mortality, but this association was not significant in patients with malignant brain tumors.

Rerupture outcome of conservative versus open repair versus minimally invasive repair of acute Achilles tendon ruptures: A systematic review and meta-analysis.

OBJECTIVE: To compare the rerupture rate after conservative treatment, open repair, and minimally invasive surgery management of acute Achilles tendon ruptures. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 2022. METHODS: Randomised controlled trials involving different treatments for Achilles tendon rupture were included. The primary outcome was rerupture. Bayesian network meta-analysis with random effects was used to assess pooled relative risks (RRs) and 95% confidence intervals. We evaluated the heterogeneity and publication bias. RESULTS: Thirteen trials with 1465 patients were included. In direct comparison, there was no difference between open repair and minimally invasive surgery for rerupture rate (RR, 0.72, 95% CI 0.10-4.4; I2 = 0%; Table 2). Compared to the conservative treatment, the RR was 0.27 (95% CI 0.10-0.62, I2 = 0%) for open repair and 0.14 (95% CI 0.01-0.88, I2 = 0%) for minimally invasive surgery. The network meta-analysis had obtained the similar results as the direct comparison. CONCLUSION: Both open repair and minimally invasive surgery were associated with a significant reduction in rerupture rate compared with conservative management, but no difference in rerupture rate was found comparing open repair and minimally invasive surgery.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90 days. METHODS: A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. RESULTS: We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, including neutrophil (AUC = 0.64) , lymphocyte (AUC = 0.57), albumin (AUC = 0.57), and platelet count (AUC = 0.53), p < 0.001 for WBC vs. neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). CONCLUSIONS: In patients with ICH, WBC count on admission was associated with all-cause mortality at 90 days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

Association of preoperative glucose concentration with mortality in patients undergoing craniotomy for brain tumor.

OBJECTIVE: Hyperglycemia is associated with worse outcomes in ambulatory settings and specialized hospital settings, but there are sparse data on the importance of preoperative blood glucose measurement before brain tumor craniotomy. The authors sought to investigate the association between preoperative glucose level and 30-day mortality rate in patients undergoing brain tumor resection. METHODS: This retrospective cohort study included patients undergoing craniotomy for brain tumors at West China Hospital, Sichuan University, from January 2011 to March 2021. Surgical mortality rates were evaluated in patients who had normal glycemia (< 5.6 mmol/L) as well as mild (5.6-6.9 mmol/L), moderate (7.0-11.0 mmol/L), and severe hyperglycemia (> 11.0 mmol/L). RESULTS: The study included 12,281 patients who underwent tumor resection via craniotomy. The overall 30-day mortality rate was 2.0% (242/12,281), whereas the rates for normal glycemia and mild, moderate, and severe hyperglycemia were 1.5%, 2.5%, 3.8%, and 6.5%, respectively. Compared with normal glycemia, the odds of mortality at 30 days were higher in patients with mild hyperglycemia (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.05-2.00), moderate hyperglycemia (OR 2.04, 95% CI 1.41-2.96), and severe hyperglycemia (OR 3.76, 95% CI 1.96-7.20; p < 0.001 for trend). When blood glucose was analyzed as a continuous variable, for each 1 mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.13 (95% CI 1.08-1.19). The addition of a preoperative glucose level significantly improved the area under the curve and categorical net reclassification index for prediction of mortality. CONCLUSIONS: In patients undergoing craniotomy for brain tumors, even mild hyperglycemia was associated with an increased mortality rate, at a glucose level that was much lower than the commonly applied level.

Effects of hydrolyzed polymaleic anhydride addition combined with vermicomposting on maturity and bacterial diversity in the final vermicompost from the biochemical residue of kitchen waste.

A large amount of kitchen waste is produced all over the world. Biochemical disposal is an effective method for the reduction and safe utilization of kitchen waste. However, high salinity, low maturity and poor biocompatibility were encountered when utilizing the biochemical residue of kitchen waste (BRKW) as a kind of soil amendment. To reduce the high salinity, accelerate the maturity and improve the biocompatibility in the BRKW, this study used the BRKW as the main feedstock for earthworms after hydrolyzed polymaleic anhydride (HPMA) was added and focused on revealing the effect of HPMA addition combined with the vermicomposting process on the growth of earthworms and on the basic physicochemical properties and the microbial diversity of the derived vermicompost. The results showed that HPMA addition can promote earthworm growth and reproduction. The pH, electric conductivity, organic matter content, C/N and NH4+-N/NO3--N were decreased in the final vermicompost, while total nitrogen, total phosphorus and total potassium contents, and the seed germination index were increased. Scanning electron microscopy analysis showed that there was more disintegration in the final vermicompost. Meanwhile, adding the HPMA also helped to decrease the total number of fungi while increasing the populations of nitrogen-fixing bacteria, phosphorus-solubilizing bacteria and potassium-solubilizing bacteria as well as amount of total bacteria and actinomycetes. The vermicomposting process increased the bacterial phyla that promote the degradation of OM, such as Actinobacteria, Firmicutes and Acidobacteria, decreased the pathogenic Enterobacter and increased the bacterial genera that promote the maturity and quality, such as Cellvibrio and Pseudomonas. Thus, HPMA addition combined with vermicomposting can promote the growth of beneficial bacteria that promote the degradation of lignocelluloses and accelerate maturity while inhibiting some potential bacterial pathogens, which helps guarantee the safety of vermicomposting products from BRKW. Hence, employing HPMA to promote BRKW vermicomposting can possibly reduce salt content and improve the maturity and biocompatibility of the final vermicompost. This approach may help realize the safe utilization of BRKW and further promote the biochemical disposal of kitchen waste.

Preimplantation Genetic Testing for Aneuploidy With Comprehensive Chromosome Screening in Patients Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the effect of comprehensive chromosome screening-based preimplantation genetic testing for aneuploidy (PGT-A) in women undergoing in vitro fertilization (IVF) treatment, we conducted this meta-analysis to compare pregnancy outcomes of women who did and did not undergo such testing. DATA SOURCES: We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception until February 28, 2022, for randomized controlled trials focusing on PGT-A treatment without any language restrictions. METHODS OF STUDY SELECTION: Randomized controlled trials involving women undergoing IVF with or without PGT-A and comprehensive chromosome testing. Pooled relative risks (RRs) with 95% CIs were calculated for the primary outcome using a random-effects model with the Mantel-Haenszel method. RESULTS: A total of nine trials with 3,334 participants were included. Overall, PGT-A was not associated with an increased live-birth rate (RR 1.13, 95% CI 0.96-1.34, I 2 =79%). However, PGT-A raised the live-birth rate in women of advanced maternal age (RR 1.34, 95% CI 1.02-1.77, I 2 =50%) but not in women of nonadvanced age (RR 0.94, 95% CI 0.89-0.99, I 2 =0%). CONCLUSION: Preimplantation genetic testing for aneuploidy increases the live-birth rate in women of advanced maternal age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022311540.

Differentiation of Meningiomas and Gliomas by Amide Proton Transfer Imaging: A Preliminary Study of Brain Tumour Infiltration.

Background: Gliomas are more malignant and invasive than meningiomas. Objective: To distinguish meningiomas from low-grade/high-grade gliomas (LGGs/HGGs) using amide proton transfer imaging (APT) combined with conventional magnetic resonance imaging (MRI) and to explore the application of APT in evaluating brain tumour invasiveness. Materials and Methods: The imaging data of 50 brain tumors confirmed by pathology in patients who underwent APT scanning in our centre were retrospectively analysed. Of these tumors, 25 were meningiomas, 10 were LGGs, and 15 were HGGs. The extent of the tumour-induced range was measured on APT images, T2-weighted imaging (T2WI), and MRI enhancement; additionally, and the degree of enhancement was graded. Ratios (RAPT/T2 and RAPT/E) were obtained by dividing the range of changes observed by APT by the range of changes observed via T2WI and MR enhancement, respectively, and APTmean values were measured. The Mann-Whitney U test was used to compare the above measured values with the pathological results obtained for gliomas and meningiomas, the Kruskal-Wallis test was used to compare LGGs, HGGs and meningiomas, and Dunn's test was used for pairwise comparisons. In addition, receiver operating characteristic (ROC) curves were drawn. Results: The Mann-Whitney U test showed that APTmean (p=0.005), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) values were statistically significant in the identification of meningioma and glioma. The Kruskal-Wallis test showed that the parameters APTmean, RAPT/T2, RAPT/E and the degree of enhancement are statistically significant. Dunn's test revealed that RAPT/T2 (p=0.004) and RAPT/E (p=0.008) could be used for the identification of LGGs and meningiomas. APTmean (p<0.001), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) could be used for the identification of HGGs and meningiomas. APTmean (p<0.001) was statistically significant in the comparison of LGGs and HGGs. ROC curves showed that RAPT/T2 (area under the curve (AUC)=0.947) and RAPT/E (AUC=0.919) could be used to distinguish gliomas from meningiomas. Conclusion: APT can be used for the differential diagnosis of meningioma and glioma, but APTmean values can only be used for the differential diagnosis of HGGs and meningiomas or HGGs and LGGs. Gliomas exhibit more obvious changes than meningiomas in APT images of brain tissue; this outcome may be caused by brain infiltration.

A phase 1b study of atezolizumab in combination with guadecitabine for the treatment of acute myeloid leukemia.

This phase 1 b study evaluated the safety, efficacy, and pharmacokinetics of atezolizumab in combination with guadecitabine in patients with relapsed/refractory (R/R) or first-line acute myeloid leukemia (AML). Patients received atezolizumab 840 mg (days [D] 8 and 22) and guadecitabine 60 mg/m2 (D1 and D5) over 28-day cycles. Sixteen patients (median age 73.0 years) enrolled (R/R cohort, n = 11; first-line cohort, n = 5). All patients reported at least 1 AE; 15 patients (93.8%) reported grade ≥ 3 AEs, and 15 patients (93.8%) reported SAEs. Fourteen of the 16 patients (87.5%) died during the trial period due to disease progression (8/14) or AEs (6/14), hence the study was terminated early. One patient (from the R/R AML cohort) achieved a response (CR with incomplete platelet recovery) with a DOR of 27.8 months at study termination. Atezolizumab plus guadecitabine had limited clinical activity in AML and an overall unfavorable benefit-risk profile at the investigated dose levels.

Rosette-forming glioneuronal tumours: two case reports and a review of the literature.

Rosette-forming glioneuronal tumour (RGNT) is a rare central nervous system (CNS) neoplasm that typically arises in the fourth ventricle. It is even more uncommon to arise outside the midline. In this paper, we report two cases of RGNT: one located in the fourth ventricle (a typical site), and the other in the right cerebellar hemisphere (a rare site). Both cases were misdiagnosed on imaging, and the results were inconsistent with the pathological diagnosis. The aim of the article is to deepen medical practitioners' understanding of RGNT by learning from these two cases, summarising cases located in the cerebellar hemispheres and systematically reviewing RGNT.

Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial.

BACKGROUND: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. METHODS: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. RESULTS: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. CONCLUSIONS: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. CLINICAL TRIALS REGISTRATION: NCT04363736.