Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

The efficacy and safety of stereotactic body radiotherapy combined with systematic therapy for metastatic renal cell carcinoma: a systematic review and meta-analysis.

There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1-year local control rate (1-yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%-95%, I 2 = 67%) and 52% (95% CI: 37%-67%, I 2 = 90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1-yr LCR (p < 0.01) and ORR (p = 0.02). Regarding survival benefits, the pooled 1-year progression-free survival (1-yr PFS) and 1-year overall survival (1-yr OS) rates were 45% (95% CI: 29%-62%, I 2 = 91%) and 85% (95% CI: 76%-91%, I 2 = 66%), respectively. 1-yr PFS and 1-yr OS in different disease settings demonstrated significant difference (p < 0.01). As for toxicity, the pooled incidence of grade 3-4 adverse events was 14% (95% CI: 5%-26%, I 2 = 90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.

Engineering Nano-Sized Silicon Anodes with Conductive Networks toward a High Average Coulombic Efficiency of 90.2% via Plasma-Assisted Milling.

Si-based anode is considered one of the ideal anodes for high energy density lithium-ion batteries due to its high theoretical capacity of 4200 mAh g-1. To accelerate the commercial progress of Si material, the multi-issue of extreme volume expansion and low intrinsic electronic conductivity needs to be settled. Herein, a series of nano-sized Si particles with conductive networks are synthesized via the dielectric barrier discharge plasma (DBDP) assisted milling. The p-milling method can effectively refine the particle sizes of pristine Si without destroying its crystal structure, resulting in large Brunauer-Emmett-Teller (BET) values with more active sites for Li+ ions. Due to their unique structure and flexibility, CNTs can be uniformly distributed among the Si particles and the prepared Si electrodes exhibit better structural stability during the continuous lithiation/de-lithiation process. Moreover, the CNT network accelerates the transport of ions and electrons in the Si particles. As a result, the nano-sized Si anodes with CNTs conductive network can deliver an extremely high average initial Coulombic efficiency (ICE) reach of 90.2% with enhanced cyclic property and rate capability. The C-PMSi-50:1 anode presents 615 mAh g-1 after 100 cycles and 979 mAh g-1 under the current density of 5 A g-1. Moreover, the manufactured Si||LiNi0.8Co0.1Mn0.1O2 pouch cell maintains a high ICE of >85%. This work may supply a new insight for designing the nano-sized Si and further promoting its commercial applications.

Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial.

Background: Postoperative sleep disturbance (PSD) is a common and serious postoperative complication and is associated with poor postoperative outcomes. Aims: This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on PSD in older patients undergoing lower limb major arthroplasty. Methods: In this prospective, double-blind, pilot, randomised, sham-controlled trial, patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS (a-tDCS) or sham tDCS (s-tDCS). The primary outcomes were the objective sleep measures on postoperative nights (N) 1 and N2. Results: 116 inpatients were assessed for eligibility, and a total of 92 patients were enrolled; 47 received a-tDCS and 45 received s-tDCS. tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups; the respective comparisons were as follows: the promotion of rapid eye movement (REM) sleep time on N1 (64.5 (33.5-105.5) vs 19.0 (0.0, 45.0) min, F=20.10, p<0.001) and N2 (75.0 (36.0-120.8) vs 30.0 (1.3-59.3) min, F=12.55, p<0.001); the total sleep time on N1 (506.0 (408.0-561.0) vs 392.0 (243.0-483.5) min, F=14.13, p<0.001) and N2 (488.5 (455.5-548.5) vs 346.0 (286.5-517.5) min, F=7.36, p=0.007); the deep sleep time on N1 (130.0 (103.3-177.0) vs 42.5 (9.8-100.8) min, F=24.4, p<0.001) and N2 (103.5 (46.0-154.8) vs 57.5 (23.3-106.5) min, F=8.4, p=0.004); and the percentages of light sleep and REM sleep on N1 and N2 (p<0.05 for each). The postoperative depression and anxiety scores did not differ significantly between the two groups. No significant adverse events were reported. Conclusion: In older patients undergoing lower limb major arthroplasty, a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures. However, this benefit was temporary and was not maintained over time.

Comparing efficacies of different exercises on androgen deprivation therapy adverse effects in prostate cancer patients: a network meta-analysis.

INTRODUCTION: Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS: Literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL). 19 studies (1184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS: NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI [0.38; 11.46]) and resistance exercise (RE) (MD = 5.62, 95% CI [2.70; 8.55]) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI [-17.67; -4.11]) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI [78.75; 157.25]) and chest strength (MD = 13.30 [4.07; 22.53]). RE ranked first for strength improvements of leg and chest. CONCLUSION: ART showed better efficacy for the QoL, and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.

Second-line treatment options in metastatic castration-resistant prostate cancer after progression on first-line androgen-receptor targeting therapies: A systematic review and Bayesian network analysis.

OBJECTIVE: To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs) for biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: Studies published in English up to May 2023 were identified in PubMed, Web of Science and ASCO-GU 2023. Studies accessing the efficacy and safety of second-line systematic therapies after first-line ARTs for biomarker-unselected mCRPC patients were eligible for current systematic review and network meta-analysis (NMA). RESULTS: Thirty-two studies with 5388 patients and 10 unique treatment modalities met our inclusion criteria. Current evidence suggested that docetaxel (DOC) combined with the same ART as first-line (ART1) (ART1 + DOC) were associated with significantly improved PSA response, PSA progression-free survival (PFS) and clinical or radiographic PFS (rPFS) compared with other reported second-line systematic therapies, including DOC. An increase in toxicity was observed with ART1 + DOC. Our NMA indicated that DOC monotherapy was only inferior to ART1 + DOC in improvement disease outcomes. The incidence of toxicity between patients received second-line DOC and an alternative ART (ART2) was similar. CONCLUSION: The available evidence reviewed in our work suggested a clinical benefit of DOC nomotherapy and DOC plus ART1 as the second-line systematic therapy for biomarker-unselected mCRPC patients progressed on a first-line ART. More studies and RCTs are needed to evaluate the optimal second-line treatments for mCRPC patients with one prior first-line ART.

High-intensity interval training versus moderate-intensity continuous training for localized prostate cancer under active surveillance: a systematic review and network meta-analysis.

BACKGROUND: High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been increasingly adopted for localized prostate cancer (PCa) under active surveillance (AS). However, it is unclear which training modality is the most favorable in terms of cardiorespiratory fitness and biochemical progression. METHODS: We searched PubMed, Cochrane and Embase for relevant RCTs. PRISMA guideline was adopted to ensure optimal conduct of this study. Serum prostate specific antigen (PSA) and peak VO2 were selected as primary outcomes and PSA doubling time (PSADT) and testosterone were selected as secondary outcomes. Only articles written in English were included. Cochrane risk-of-bias tool was used for risk of bias evaluation. RESULTS: A total of 501 studies were selected. Six RCTs with 222 patients were included for data extraction and analysis. High-intensity interval training (HIIT) group demonstrated significantly lower PSA compared with usual care (UC) (MD = -1.4; 95%CI = -2.77 to -0.03) and moderate-intensity continuous training (MICT) group (MD = -1.67; 95%CI = -3.30 to -0.05). Both HIIT and MICT showed significantly improved peak VO2 compared with UC. No significant difference was observed in PSADT and testosterone among different training modalities and UC. Regarding peak VO2, MICT had the highest surface under cumulative ranking curve (SUCRA) scores (98.1%). For serum PSA, HIIT had the highest probability (97.8%) to be the training with the highest efficacy. The potential source of bias mainly came from poorly performed allocation concealment and blinding strategies. CONCLUSIONS: The present study indicated that HIIT and MICT showed considerable cardiorespiratory benefits for localized PCa. HIIT was preferred over MICT in biochemical progression control in terms of decreasing serum PSA levels. However, MICT was favored over HIIT regarding cardiorespiratory benefits. The findings of this study may facilitate future lifestyle intervention, particularly in the form of physical training, for individuals diagnosed with localized PCa under AS.

Nonsurgical salvage options for locally recurrent prostate cancer after primary definitive radiotherapy: a systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis to provide the latest evidence of nonsurgical local salvage options in the first-line radiotherapy (RT) failure setting for localized prostate cancer patients. BACKGROUND: Recurrence of localized prostate cancer after primary RT remains a clinical challenge. There is no consensus on optimal nonsurgical local salvage therapies, which mainly consist of cryotherapy (CRYO), high-intensity focused ultrasound (HIFU), high/low-dose-rate brachytherapy (HDR/LDR), and stereotactic body radiotherapy (SBRT). METHODS: Our study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The authors systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov up to September 2023 to identify potentially relevant studies. The risk of bias was assessed using the European Association of Urology (EAU) items. Biochemical recurrence-free survival (bRFS) and genitourinary/gastrointestinal toxicities were the outcomes of interest. Pooled rates with 95% CIs were evaluated. RESULTS: A total of 99 studies comprising 8440 patients were included. The pooled rate of 1-year biochemical control (BC) was highest for LDR (0.88, 95% CI: 0.72-0.95) and lowest for SBRT (0.68, 95% CI: 0.49-0.83). The pooled rate of 5-year BC was highest for CRYO (0.52, 95% CI: 0.33-0.69) and lowest for HDR (0.23, 95% CI: 0.08-0.51). HIFU presented the worst outcome of grade ≥3 genitourinary toxicities (GU3), with a rate of 0.22 (95% CI: 0.12-0.3). Conversely, CRYO (0.09, 95% CI: 0.04-0.14), HDR (0.05, 95% CI: 0.02-0.07), LDR (0.10, 95% CI: 0.06-0.14), and SBRT (0.06, 95% CI: 0.03-0.09) presented low rates of GU3. All subgroups induced a quite low incidence of grade ≥3 gastrointestinal toxicities (GI3). CONCLUSIONS: Nonsurgical salvage therapies are promising modalities for prostate cancer in the local radiorecurrence setting. Based on the preliminary evidence from this study, CRYO and SBRT might present a relatively steady efficacy of BC with acceptable treatment-related toxicities.

Evaluation of Survival Outcomes Among Black and White Patients with Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Meta-analysis.

Context: Data on racial disparities among patients with metastatic castration-resistant prostate cancer (mCRPC) are limited and there is no uniform conclusion on differences by race in this setting. Objective: To provide the latest evidence on racial disparities in survival outcomes between Black and White patients receiving systemic therapies for mCRPC. Evidence acquisition: Our study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We systematically searched the PubMed, Web of Science, and Cochrane Library databases up to September 2023 to identify potentially relevant studies. Overall survival (OS) and progression-free survival (PFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were evaluated. Evidence synthesis: Nine studies involving 9462 patients with mCRPC (2058 Black and 7404 White men) met the eligibility criteria and were included. Pooled estimates demonstrated significantly better OS for Black than for White men (HR 0.75, 95% CI 0.70-0.80; p < 0.0001). The results were similar in a subgroup of men receiving androgen receptor-targeted therapies (HR 0.72, 95% CI 0.66-0.78; p < 0.0001) and a subgroup of men receiving other treatments (HR 0.79, 95% CI 0.71-0.88; p < 0.0001). Likewise, significantly favorable PFS was observed for Black men receiving ARTs in comparison to their White counterparts (HR 0.84, 95% CI 0.71-0.99; p = 0.0373). Conclusions: Overall, our meta-analysis of survival outcomes for men with mCRPC stratified by race revealed a significant survival benefit for Black men in comparison to their White counterparts, regardless of systemic therapeutic agent. Patient summary: Both biological and nonbiological factors could account for racial differences in the efficacy of systemic treatments for metastatic prostate cancer that is resistant to hormone therapy. Our review provides the latest reliable evidence showing better survival outcomes for Black than for White men. The results will be helpful in further understanding the molecular mechanisms that might explain racial differences in this disease stage and in planning treatment.

An umbrella review of the evidence associating occupational carcinogens and cancer risk at 19 anatomical sites.

Occupational exposure to carcinogens of increasing cancer risk have been extensively suggested. A robust assessment of these evidence is needed to guide public policy and health care. We aimed to classify the strength of evidence for associations of 13 occupational carcinogens (OCs) and risk of cancers. We searched PubMed and Web of Science up to November 2022 to identify potentially relevant studies. We graded the evidence into convincing, highly suggestive, suggestive, weak, or not significant according to a standardized classification based on: random-effects p value, number of cancer cases, 95% confidence interval of largest study, heterogeneity between studies, 95% prediction interval, small study effect, excess significance bias and sensitivity analyses with credibility ceilings. The quality of meta-analysis was evaluated by AMSTAR 2. Forty-eight articles yielded 79 meta-analyses were included in current umbrella review. Evidence of associations were convincing (class I) or highly suggeastive (class II) for asbestos exposure and increasing risk of lung cancer among smokers (RR = 8.79, 95%CI: 5.81-13.25 for cohort studies and OR = 8.68, 95%CI: 5.68-13.24 for case-control studies), asbestos exposure and increasing risk of mesothelioma (RR = 4.61, 95%CI: 2.57-8.26), and formaldehyde exposure and increasing risk of sinonasal cancer (RR = 1.68, 95%CI: 1.38-2.05). Fifteen associations were supported by suggestive evidence (class III). In summary, the current umbrella review found strong associations between: asbestos exposure and increasing risk of lung cancer among smokers; asbestos exposure and increasing risk of mesothelioma; and formaldehyde exposure and higher risk of sinonasal cancer. Other associations might be genuine, but substantial uncertainty remains.

Targeting histone modifiers in bladder cancer therapy - preclinical and clinical evidence.

Bladder cancer in the most advanced, muscle-invasive stage is lethal, and very limited therapeutic advances have been reported for decades. To date, cisplatin-based chemotherapy remains the first-line therapy for advanced bladder cancer. Late-line options have historically been limited. In the past few years, next-generation sequencing technology has enabled chromatin remodelling gene mutations to be characterized, showing that these alterations are more frequent in urothelial bladder carcinoma than in other cancer types. Histone modifiers have functional roles in tumour progression by modulating the expression of tumour suppressors and oncogenes and, therefore, have been considered as novel drug targets for cancer therapy. The roles of epigenetic reprogramming through histone modifications have been increasingly studied in bladder cancer, and the therapeutic efficacy of targeting those histone modifiers genetically or chemically is being assessed in preclinical studies. Results from preclinical studies in bladder cancer encouraged the investigation of some of these drugs in clinical trials, which yield mixed results. Further understanding of how alterations of histone modification mechanistically contribute to bladder cancer progression, drug resistance and tumour microenvironment remodelling will be required to facilitate clinical application of epigenetic drugs in bladder cancer.

Revealing the Subzero-Temperature Electrochemical Kinetics Behaviors in Ni-Rich Cathode.

The sluggish kinetics in Ni-rich cathodes at subzero temperatures causes decreased specific capacity and poor rate capability, resulting in slow and unstable charge storage. So far, the driving force of this phenomenon remains a mystery. Herein, with the help of in-situ X-ray diffraction and time of flight secondary ion mass spectrometry techniques, the continuous accumulation of both the cathode electrolyte interphase (CEI) film formation and the incomplete structure evolution during cycling under subzero temperature are proposed. It is presented that excessively uniform and thick CEI film generated at subzero temperatures would block the diffusion of Li+ -ions, resulting in incomplete phase evolution and clear charge potential delay. The incomplete phase evolution throughout the Li+ -ion intercalation/de-intercalation processes would further cause low depth of discharge and poor electrochemical reversibility with low initial Coulombic efficiency, as well. In addition, the formation of the thick and uniform CEI film would also consume Li+ -ions during the charging process. This discovery highlights the effects of the CEI film formation behavior and incomplete phase evolution in restricting electrochemical kinetics under subzero temperatures, which the authors believe would promote the further application of the Ni-rich cathodes.

ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression.

BACKGROUND: Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. METHODS: The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. RESULTS: ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. CONCLUSIONS: In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

Combining Novel Hormonal Therapies with a Poly (ADP-Ribose) Polymerase Inhibitor for Metastatic Castration-Resistant Prostate Cancer: Emerging Evidence.

Preclinical and clinical studies have suggested potential synergies of combining poly (ADP-ribose) polymerase (PARP) inhibitors and novel hormonal therapies (NHT) for patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, ClinicalTrials.gov and ASCO-GU annual meeting abstracts up to March 2023 to identify potential phase III trials reporting the use of combining PARP inhibitors with NHT in the first-line setting for mCRPC. A total of four phase III trials met the criteria for subsequent review. Emerging data suggested that the radiographic progression-free survival (rPFS) was significantly longer in the PARP inhibitor combined with NHT group versus the placebo plus NHT group for the first-line setting of biomarker-unselected mCRPC patients, especially for patients with homologous recombination repair (HRR) mutation (HRR m), and with the greatest benefit for BRCA1/2 mutation (BRCA1/2 m) populations. Final overall survival (OS) data of the PROpel trial indicated a significant improvement in median OS for mCRPC patients with HRR m and BRCA1/2 m receiving olaparib + abiraterone. Prior taxane-based chemotherapy might not influence the efficacy of the combination. Compared with the current standard-of-care therapies, combining NHT with PARP inhibitors could achieve a significant survival benefit in the first-line setting for mCRPC patients with HRR and BRCA1/2 mutations.

A machine learning diagnostic model for Pneumocystis jirovecii pneumonia in patients with severe pneumonia.

BACKGROUND: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse prognosis. This study aimed to develop a rapid, easily available, noninvasive machine learning diagnostic model for PCP among patients with severe pneumonia. METHODS: A retrospective study was performed in West China Hospital among consecutive patients with severe pneumonia who had undergone bronchoalveolar lavage for etiological evaluation between October 2010 and April 2021. Factors associated with PCP were identified and four diagnostic models were established using machine learning algorithms including Logistic Regression, eXtreme Gradient Boosting, Random Forest (RF) and LightGBM. The performance of these models were evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: Ultimately, 704 patients were enrolled and randomly divided into a training set (n = 564) and a testing set (n = 140). Four factors were ultimately selected to establish the model including neutrophil, globulin, ß-D-glucan and ground glass opacity. The RF model exhibited the greatest diagnostic performance with an AUC of 0.907. The calibration curve and decision curve analysis also demonstrated its accuracy and applicability. CONCLUSIONS: We constructed a PCP diagnostic model in patients with severe pneumonia using four easily available and noninvasive clinical indicators. With satisfying diagnostic performance and good clinical practicability, this model may help clinicians to make early diagnosis of PCP, reduce the delays of treatment and improve the prognosis among these patients.

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta-analysis.

Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1-year/2-year progression-free survival [PFS], and overall survival [OS]) and safety (vaccine-related grade 3-5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non-small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6-17.0%) and 34.6% (95%CI, 24.1-45.9%). The estimates for 1-year and 2-year PFS were 38.4% (95%CI, 24.8-53.0%) and 20.0% (95%CI, 10.4-31.7%), respectively. The estimates for 1-year and 2-year OS were 75.3% (95%CI, 62.4-86.3%) and 45.5% (95%CI, 34.0-57.2%), respectively. The estimate for vaccine-related grade 3-5 AEs was 1.0% (95%CI, 0.2-2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3-5 AEs.

Association between dietary inflammatory index and urinary flow rate: a nationwide study, NHANES 2009-2016.

Some evidence have suggested that various nutrients and inflammatory factors might influence the lower urinary tract function. However, the correlation between diet and urinary flow rate (UFR) is not clear. Our study aimed to evaluate the association between the dietary inflammatory index (DII) and UFR. We performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) database from 2009-2016. The dependent and independent variables were UFR and DII score, respectively. Dietary information was collected by 24-hour dietary recall interviews method, and DII scores were computed based on it. Tertiles group was divided according to DII scores. The study included 17,114 participants for whom data on DII and UFR were available, with a mean age of 35.68 ± 20.96 years. Participants with higher DII score presented lower UFR levels (ß= -0.05; 95% CI: [-0.06-0.04]). In addition, the risk of UFR decline elevated significantly gradual across DII score tertiles (p for trend <0.001). Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with decreased UFR. These results might be useful for the public health system to provide primary prevention recommendations for lower urinary tract voiding problem, but further high-quality prospective research is needed.

The Role of cGAS-STING in Age-Related Diseases from Mechanisms to Therapies.

With aging, the incidence of age-related diseases increases. Hence, age-related diseases are inevitable. However, the mechanisms by which aging leads to the onset and progression of age-related diseases remain unclear. It has been reported that inflammation is closely associated with age-related diseases and that the cGAS-STING signaling pathway, which can sense the aberrant presence of cytosolic DNA during aging and induce an inflammatory response, is an important mediator of inflammation in age-related diseases. With a better understanding of the structure and molecular biology of the cGAS-STING signaling axis, numerous selective inhibitors and agonists targeting the cGAS-STING pathway in human age-related diseases have been developed to modulate inflammatory responses. Here, we provide a narrative review of the activity of the cGAS-STING pathway in age-related diseases and discuss its general mechanisms in the onset and progression of age-related diseases. In addition, we outline treatments targeting the cGAS-STING pathway, which may constitute a potential therapeutic alternative for age-related diseases.

Pyroptosis in urinary malignancies: a literature review.

Urinary neoplasms refer to malignant tumours occurring in any part of the urinary system, including the kidney, renal pelvis, ureter, bladder, prostate, etc. The worldwide incidence of urinary system tumours has been increasing yearly. Available methods include surgical treatment, radiotherapy, chemotherapy, endocrine therapy, molecular targeted therapy, and immune therapy. In recent years, emerging evidence has demonstrated that cell pyroptosis plays an important role in the occurrence and progression of malignant urinary tumours. Pyroptosis is a new type of cell death that involves inflammatory processes regulated by gasdermins (GSDMs) and is characterized by membrane perforation, cell swelling and cell rupture. Recent studies have shown that pyroptosis can inhibit and promote the development of tumours. This manuscript reviews the role of pyroptosis in the development and progression of prostate cancer, kidney cancer and bladder cancer and introduces the latest research results in these fields to discuss the therapeutic potential of the pyroptosis pathway in urinary malignancies.

Different predictive values of microvessel density for biochemical recurrence among different PCa populations: A systematic review and meta-analysis.

BACKGROUND: Several studies have explored the relationship between intratumoral microvessel density (MVD) and the risk of postoperative biochemical recurrence (BCR) in prostate cancer (PCa), although the results are contradictory. Therefore, we conducted a meta-analysis to investigate the effect of MVD on BCR in PCa. METHOD: We searched PubMed, MEDLINE, Science Direct/Elsevier, the Cochrane Library, CNKI, and EMBase databases from inception through January 2022, with no year or language restrictions, and used NOS guidelines to evaluate the quality of the 19 eligible studies. The derived hazard ratio (HR) and 95% confidence interval (95%CI) were used to assess each endpoint. Data synthesis was performed with RevMan to assess the prognostic value of MVD in PCa and its heterogeneity, while the publication bias was examined using STATA 16.0. RESULTS: Our meta-analysis included 19 articles (4 for T1-2, 6 for T1-3, and 9 for T1-4) on postoperative biochemical recurrence of PCa, among which, 3933 patients were pooled. The predictive ability of intratumoral MVD for different stages of PCa on BCR was T1-2 (HR, 2.46; 95% CI, 1.08-5.58; p = 0.03; I2  = 83%), T1-3 (HR, 2.38, 95% CI, 1.41-4.01; p = 0.001; I2  = 82%), T1-4 (HR, 1.61; 95% CI, 1.19-2.19; p = 0.002; I2  = 61%).The subgroup analyses based on European and immunohistochemical antibody none-factor VII were consistent with primary one. Sensitivity analysis excluding those studies judged to be at high risk of bias in T1-2 showed a HR of 2.99[1.70,5.27] (I2  = 38%, p = 0.0001), demonstrating the robustness of risk estimates of MVD for the assessment of biochemical recurrence. CONCLUSION: Microvessel density is a predictor of BCR among patients with PCa, and earlier T stage PCa with a stronger MVD is associated with BCR. Further studies are needed to investigate neoangiogenesis in different T stages of PCa and whether MVD will be of benefit to the EAU-recommended tool for biochemical recurrence risk assessment.