TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer.

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

OBJECTIVE: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. METHODS: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. RESULTS: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. CONCLUSIONS: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

Racial Disparities in Low-Value Care in the Last Year of Life for Medicare Beneficiaries With Neurodegenerative Disease.

Background and Objectives: There are racial disparities in health care services received by patients with neurodegenerative diseases, but little is known about disparities in the last year of life, specifically in high-value and low-value care utilization. This study evaluated racial disparities in the utilization of high-value and low-value care in the last year of life among Medicare beneficiaries with dementia or Parkinson disease. Methods: This was a retrospective, population-based cohort analysis using data from North and South Carolina fee-for-service Medicare claims between 2013 and 2017. We created a decedent cohort of beneficiaries aged 50 years or older at diagnosis with dementia or Parkinson disease. Specific low-value utilization outcomes were selected from the Choosing Wisely initiative, including cancer screening, peripheral artery stenting, and feeding tube placement in the last year of life. Low-value outcomes included hospitalization, emergency department visits, neuroimaging services, and number of days receiving skilled nursing. High-value outcomes included receipt of occupational and physical therapy, hospice care, and medications indicated for dementia and/or Parkinson disease. Results: Among 70,650 decedents, 13,753 were Black, 55,765 were White, 93.1% had dementia, and 7.7% had Parkinson disease. Adjusting for age, sex, Medicaid dual enrollment status, rural vs urban location, state (NC and SC), and comorbidities, Black decedents were more likely to receive low-value care including colorectal cancer screening (adjusted hazard ratio [aHR] 1.46 [1.32-1.61]), peripheral artery stenting (aHR 1.72 [1.43-2.08]), and feeding tube placement (aHR 2.96 [2.70-3.24]) and less likely to receive physical therapy (aHR 0.73 [0.64-0.85)], dementia medications (aHR 0.90 [0.86-0.95]), or Parkinson disease medications (aHR 0.88 [0.75-1.02]) within the last year of life. Black decedents were more likely to be hospitalized (aHR 1.28 [1.25-1.32]), more likely to be admitted to skilled nursing (aHR 1.09 [1.05-1.13]), and less likely to be admitted to hospice (aHR 0.82 [0.79-0.85]) than White decedents. Discussion: We found racial disparities in care utilization among patients with neurodegenerative disease in the last year of life, such that Black decedents were more likely to receive specific low-value care services and less likely to receive high-value supportive care than White decedents, even after adjusting for health status and socioeconomic factors.

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications.

Liver cancer remains as the third leading cause of cancer-related death globally as of 2020. Despite the significant progress made in the field of liver cancer treatment, there is still a lack of effective therapies in patients with advanced cancer and the molecular mechanisms underlying liver cancer progression remain largely elusive. N6-methyladenosine (m6A) modification, as the most prevalent and abundant internal RNA modification in eukaryotic RNAs, plays an essential role in regulating RNA metabolism including RNA splicing, stability, translation, degradation. To date, there is mounting evidence showing that m6A dysregulation is closely associated with the onset and development of many tumors including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatoblastoma (HB). In this review, we summarize the last research progress regarding the functions of m6A-related regulators in liver cancer and its underlying mechanisms. Additionally, we also discuss the therapeutic applications of m6A-based inhibitors in liver cancer treatment.

Copper-Promoted Intramolecular Oxidative Dehydrogenation for Synthesizing Dihydroisocoumarins and Isocoumarins.

Isocoumarins and dihydroisocoumarins are important skeletons with a wide range of biological activities, such as anti-bacterial, anti-allergy, anti-fungal, anti-tumor, and anti-HIV properties. Herein, we demonstrated divergent syntheses of isocoumarins and 3,4-dihydroisocoumarins by intramolecular dehydrogenative cyclization of 2-(3-oxobutyl) benzoic acids. This transformation undergoes Csp3-H bonds and O-H bonds coupling in air using copper salt. The reactions may undergo free radical process.

Fear of disease progression among breast cancer patients in China: a meta-analysis of studies using the fear of progression questionnaire short form.

Background: Fear of disease progression (FoP) is among the most prevalent and major psychological burdens breast cancer patients encounter. Excessive FoP may result in serious adverse effects for patients. FoP in breast cancer patients has gained attention recently; however, its prevalence in China is unknown. Objectives: This meta-analysis and systematic review aimed to assess the overall FoP among Chinese breast cancer patients to make recommendations for treatment and care. Methods: Systematic search databases included PubMed, EMbase, The Cohrane Library, Web of Science, CINAHL, PsycINFO and 4 Chinese databases (Wan Fang Data, CBM, VIP and CNKI). The retrieval time ranged from the database's establishment to March 20, 2023. After two researchers independently evaluated the literature, retrieved information, and assessed the risk of bias for the included literature, Stata 15.1 software was used to conduct a meta-analysis. Results: A total of 37 moderate or high-quality studies involving 9,689 breast cancer patients were included. Meta-analysis showed that the pooled mean score of FoP for Chinese breast cancer patients was 33.84 [95% CI (31.91, 35.77)], prediction interval (21.57 ~ 46.11). The subgroup study found that FoP levels varied among breast cancer patients of different regions, ages, educational levels, marital statuses, residences, illness stages, and disease statuses. Conclusion: Breast cancer patients have higher FoP scores. Healthcare workers should be concerned. We expect that more relevant research will be undertaken and more effective interventions will be developed. Patients can manage their illness and improve their quality of life by reducing their fears. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023408914.

Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Correlation of serum albumin level on postoperative day 2 with hospital length of stay in patients undergoing emergency surgery for perforated peptic ulcer.

BACKGROUND: Perforated peptic ulcer (PPU) is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide. While advances in surgical techniques have improved outcomes for patients with PPU, many factors still affect postoperative hospital stay and overall prognosis. One potential factor is the serum albumin (SA) level, a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures. AIM: To clarify the correlation of SA level on postoperative day 2 with hospital length of stay (HLOS) in patients undergoing emergency surgery for perforated peptic ulcer (PPU). METHODS: We retrospectively collected and analyzed clinical baseline data, including blood routine and SA levels, of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021. Patients were grouped according to HLOS with 7 d as the cut-off value, and relevant indicators were analyzed using SPSS 26.0. RESULTS: Of the 37 patients undergoing emergency surgery for PPU referred to our department, 33 had gastric and 4 had duodenal ulcer perforation. The median HLOS was 10 d. There were 8 patients in the ≤ 7-d group (median HLOS: 7 d) and 29 patients in the > 7-d group (median HLOS: 10 d). The ≤ 7-d group had markedly higher SA on postoperative day 2 than the > 7-d group (37.7 g/L vs 32.6g/L; P < 0.05). The SA level on postoperative day 2 was a protective factor for patients with HLOS > 7 d (Odds ratio = 0.629, P = 0.015). The cut-off of SA on postoperative day 2 was 30.6g/L, with an area under the curve of 0.86 and a negative predictive value of 100% for the prediction of HLOS ≤ 7 d. CONCLUSION: The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU. The pre- and post-operative albumin levels should be monitored, and infusion of human SA should be considered in a timely manner.

Association of mechanical power during one-lung ventilation and post-operative pulmonary complications among patients undergoing lobectomy: a protocol for a prospective cohort study.

The association of intra-operative mechanical power (MP) with post-operative pulmonary complications (PPCs) has been described before, but it is uncertain whether the potential inherent bias can limit the use of this parameter, particularly in the context of one-lung ventilation. This single-center study aims to investigate the effect of MP during one-lung ventilation (OLV), and the risks of PPCs in patients undergoing thoracoscopic lobectomy. This prospective observational study is being conducted in an academic tertiary hospital in mainland China. Participants diagnosed with lung cancer, and aged 50 to 80 years are eligible. Video-assisted thoracoscopic surgery (VATS) lobectomy is performed for all patients. The primary outcome is the occurrence of PPCs over 5 consecutive days after the surgery, or until discharge from the hospital. Secondary outcomes include the composite conditions of PPCs, in-hospital stay, systematic inflammation tested by blood samples, and changes in aeration compartments in the ventilated lung as assessed by CT scans. We aim to evaluate the association of mean MP and the temporal patterns in the trend of MP during OLV with the occurrence of PPCs. A total of 120 patients will be enrolled in this study. The study protocol has received approval from the Ethics Committee of the affiliated hospital of Southwest Medical University, China (Reference number: KY2022162). The findings will be made available to the funder and researchers via scientific conferences and peer-reviewed publications. This controlled trial was approved by the Ethics Committee of Southwest Medical University(ChiCTR2200062173), and registered in the Chinese Clinical Trial Register website ( http://www.chictr.org.cn/edit.aspx?pid=172533&htm=4 , ChiCTR2200062173). A written consent was obtained from each patient.

Incidence of delirium after non-cardiac surgery in the Chinese elderly population: a systematic review and meta-analysis.

Background: POD places a heavy burden on the healthcare system as the number of elderly people undergoing surgery is increasing annually because of the aging population. As a large country with a severely aging population, China's elderly population has reached 267 million. There has been no summary analysis of the pooled incidence of POD in the elderly Chinese population. Methods: Systematic search databases included PubMed, Web of Science, EMBASE, Cochrane Library Databases, China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), WanFang Database, and Chinese Science and Technology Periodicals (VIP). The retrieval time ranged from the database's establishment to February 8, 2023. The pooled incidence of delirium after non-cardiac surgery was calculated using a random effects model. Meta-regression, subgroup, and sensitivity analyses were used to explore the source of heterogeneity. Results: A total of 52 studies met the inclusion criteria, involving 18,410 participants. The pooled incidence of delirium after non-cardiac surgery in the elderly Chinese population was 18.6% (95% CI: 16.4-20.8%). The meta-regression results revealed anesthesia method and year of publication as a source of heterogeneity. In the subgroup analysis, the gender subgroup revealed a POD incidence of 19.6% (95% CI: 16.9-22.3%) in males and 18.3% (95% CI: 15.7-20.9%) in females. The year of publication subgroup analysis revealed a POD incidence of 20.3% (95% CI: 17.4-23.3%) after 2018 and 14.6 (95% CI: 11.6-17.6%) in 2018 and before. In the subgroup of surgical types, the incidence of hip fracture surgery POD was 20.7% (95% CI: 17.6-24.3%), the incidence of non-cardiac surgery POD was 18.4% (95% CI: 11.8-25.1%), the incidence of orthopedic surgery POD was 16.6% (95% CI: 11.8-21.5%), the incidence of abdominal neoplasms surgery POD was 14.3% (95% CI: 7.6-21.1%); the incidence of abdominal surgery POD was 13.9% (95% CI: 6.4-21.4%). The anesthesia methods subgroup revealed a POD incidence of 21.5% (95% CI: 17.9-25.1%) for general anesthesia, 15.0% (95% CI: 10.6-19.3%) for intraspinal anesthesia, and 8.3% (95% CI: 10.6-19.3%) for regional anesthesia. The measurement tool subgroup revealed a POD incidence of 19.3% (95% CI: 16.7-21.9%) with CAM and 16.8% (95% CI: 12.6-21.0%) with DSM. The sample size subgroup revealed a POD incidence of 19.4% (95% CI: 16.8-22.1%) for patients ≤ 500 and 15.3% (95% CI: 11.0-19.7%) for patients > 500. The sensitivity analysis suggested that the pooled incidence of postoperative delirium in this study was stable. Conclusion: Our systematic review of the incidence of delirium after non-cardiac surgery in elderly Chinese patients revealed a high incidence of postoperative delirium. Except for cardiac surgery, the incidence of postoperative delirium was higher for hip fracture surgery than for other types of surgery. However, this finding must be further explored in future large-sample studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023397883.

Long-term outcomes of aortic root operations in the United States among Medicare beneficiaries.

OBJECTIVE: The best method of aortic root repair in older patients remains unknown given a lack of comparative effectiveness of long-term outcomes data. The objective of this study was to compare long-term outcomes of different surgical approaches for aortic root repair in Medicare patients using The Society of Thoracic Surgeons Adult Cardiac Surgery Database-Centers for Medicare & Medicaid Services-linked data. METHODS: A retrospective cohort study was performed by querying the Society of Thoracic Surgeons Adult Cardiac Surgery Database for patients aged 65 years or more who underwent elective aortic root repair with or without aortic valve replacement. Primary long-term end points were mortality, any stroke, and aortic valve reintervention. Short-term outcomes and long-term survival were compared among each root repair strategy. Additional risk factors for mortality after aortic root repair were assessed with a multivariable Cox proportional hazards model. RESULTS: A total of 4173 patients aged 65 years or more underwent elective aortic root repair. Patients were stratified by operative strategy: mechanical Bentall, stented bioprosthetic Bentall, stentless bioprosthetic Bentall, or valve-sparing root replacement. Mean follow-up was 5.0 (±4.6) years. Relative to mechanical Bentall, stented bioprosthetic Bentall (adjusted hazard ratio, 0.80; confidence interval, 0.66-0.97) and stentless bioprosthetic Bentall (adjusted hazard ratio, 0.70; confidence interval, 0.59-0.84) were associated with better long-term survival. In addition, stentless bioprosthetic Bentall (adjusted hazard ratio, 0.64; confidence interval, 0.47-0.80) and valve-sparing root replacement (adjusted hazard ratio, 0.51; confidence interval, 0.29-0.90) were associated with lower long-term risk of stroke. Aortic valve reintervention risk was 2-fold higher after valve-sparing root replacement compared with other operative strategies. CONCLUSIONS: In the Medicare population, there was poorer late survival and greater late stroke risk for patients undergoing mechanical Bentall and a higher rate of reintervention for valve-sparing root replacement. Bioprosthetic Bentall may be the procedure of choice in older patients undergoing aortic root repair, particularly in the era of transcatheter aortic valve replacement.

Temporal trends and rural-urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey.

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

Granulimonas faecalis gen. nov., sp. nov., and Leptogranulimonas caecicola gen. nov., sp. nov., novel lactate-producing Atopobiaceae bacteria isolated from mouse intestines, and an emended description of the family Atopobiaceae.

Two strictly anaerobic, Gram-stain-positive, non-motile bacteria (strains OPF53T and TOC12T) were isolated from mouse intestines. Strains OPF53T and TOC12T grew at pH 5.5-9.0 and 5.0-9.0, respectively, and at temperatures of 30-45 °C. The cell morphologies of these strains were short rods and rods, respectively, and the cells possessed intracellular granules. The major cellular fatty acids of OPF53T were C18  :  1 cis 9 and C18  :  1 cis 9 dimethyl acetal, whereas those of TOC12T were C18  :  0 and C18  :  1 cis 9. In OPF53T, the main end-products of modified peptone-yeast extract-glucose (PYG) fermentation were lactate, formate and butyrate, whereas, in addition to these acids, TOC12T also produced hydrogen. The genomes of OPF53T and TOC12T were respectively 2.2 and 2.0 Mbp in size with a DNA G+C contents of 69.1 and 58.7 %. The 16S rRNA gene sequences of OPF53T and TOC12T showed the highest similarity to members of the family Atopobiaceae, namely, Olsenella phocaeensis Marseille-P2936T (94.3 %) and Olsenella umbonata KCTC 15140T (93.2 %), respectively. Phylogenetic analyses revealed that both isolates formed distinct lineages from other genera of the family Atopobiaceae. In addition, the two strains were characterized by relatively low 16S rRNA gene sequence similarity (93.4 %) and can be distinguished by their distinctive traits (including cell shape, DNA G+C content, and major fatty acids profiles). On the basis of their polyphasic taxonomic properties, these isolates represent two noel species of two novel genera within the family Atopobiaceae, for which the names Granulimonas faecalis gen. nov., sp. nov. (OPF53T=JCM 35015T=KCTC 25474T) and Leptogranulimonas caecicola gen. nov., sp. nov. (TOC12T=JCM 35017T=KCTC 25472T) are proposed.

Anticoagulation in new-onset postoperative atrial fibrillation: An analysis from the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Background: New-onset postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and is associated with increased long-term stroke and mortality. Anticoagulation has been suggested as a potential therapy, but data on safety and efficacy are scant. Objectives: To determine the association between anticoagulation for POAF and long-term outcomes. Methods: Adult patients with POAF after isolated coronary artery bypass surgery (CABG) were identified through the Society of Thoracic Surgeons Adult Cardiac Surgery Database and linked to the Medicare Database. Propensity-matched analyses were performed for all-cause mortality, stroke, myocardial infarction, and major bleeding for patients discharged with or without anticoagulation. Interaction between anticoagulation and CHA2DS2-VASc score was also assessed. Results: Of 38,936 patients, 9861 (25%) were discharged on oral anticoagulation. After propensity score matching, discharge anticoagulation was associated with increased mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.26). There was no difference in ischemic stroke between groups (HR 0.97, 95% CI 0.82-1.15), but there was significantly higher bleeding (HR 1.60, 95% CI 1.38-1.85) among those discharged on anticoagulation. Myocardial infarction was lower in the first 30 days for those discharged on anticoagulation, but this effect decreased over time. The incidence of all complications was higher for patients with CHA2DS2-VASc scores ≥5 compared to patients with scores of 2-4. Anticoagulation did not appear to benefit either subgroup. Conclusion: Anticoagulation is associated with increased mortality after new-onset POAF following CABG. There was no reduction in ischemic stroke among those discharged on anticoagulation regardless of CHA2DS2-VASc score.

Cerebral Oximetry During Adult Cardiac Surgery Is Associated With Improved Postoperative Outcomes.

OBJECTIVE: To examine the association/effect of intraoperative cerebral oximetry (CeOx) on major organ morbidity and mortality (MOMM) after adult cardiac surgery. DESIGN: A retrospective, multicenter cohort study. SETTING: Patients treated at any hospital within the Society of Thoracic Surgeons Adult Cardiac Surgery Database between July 1, 2011, and December 31, 2016, with a 30-day postoperative follow-up. PARTICIPANTS: Individuals ≥18 years old undergoing isolated coronary artery bypass graft (CABG) or valve repair or replacement, or any combination of procedures with cardiopulmonary bypass. INTERVENTIONS: Intraoperative CeOx. MEASUREMENTS AND MAIN RESULTS: MOMM includes operative mortality, stroke, renal failure, prolonged mechanical ventilation, deep sternal wound infection, or reoperation for any reason within 30 days. Of 1.19 million patients who met inclusion criteria within 1,180 facilities, ∼30% (n = 361,124) received CeOx versus nonrecipients (n = 838,675) with similar baseline patient characteristics. Using a propensity score-based 1:1 greedy matching method, 99.7% of CeOx recipients (n = 360,285) were matched with nonrecipients. The rates of MOMM were lower with versus without CeOx. The absolute risk reduction translated to a number needed to treat of 227 patients (95% CI: 166-363, p < 0.0001). In sensitivity analyses of prespecified subgroups, the benefit was strongest among patients undergoing aortic valve repair or replacement ± CABG (more than 7 fewer MOMM events per 1,000, p < 0.0001). However, intensive care unit stay >72 hours was higher with CeOx. CONCLUSION: Intraoperative cerebral oximetry is associated with less major organ morbidity and mortality after adult cardiac surgery. A large-scale clinical trial is warranted, given that desaturation is common and correctable.

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy.

Purpose: The aim of this study was to investigate whether 11q loss of heterozygosity (LOH) aberration would impact the response of the primary tumor to neoadjuvant chemotherapy or to the degree of surgical resection in neuroblastoma (NB) patients with MYCN amplification. Methods: The clinical data of 42 NB patients with MYCN amplification who were newly diagnosed and received treatments at our hospital from 2011 to 2020 were retrospectively analyzed. According to the results of the segmental chromosome aberration analysis, the patients enrolled were assigned to an 11qLOH positive group and an 11qLOH negative group. Results: There was no significant difference in the mean number of chemotherapy courses completed before surgery between the 11qLOH positive and 11qLOH negative groups (p = 0.242). Each of the 42 patients had metaiodobenzylguanidine (MIBG) scans both before and after neoadjuvant chemotherapy. The percentage of patients who had a clinical MIBG change in the 11qLOH positive group was lower than the percentage in the 11qLOH negative group (27.27 vs. 66.67%, p = 0.030). The 11qLOH negative group seemed to have a higher rate of surgical resection (≥90%); however, the difference between the two groups was not statistically significant (p = 0.088). Furthermore, the 11qLOH negative group did not show significantly superior event-free survival and overall survival rates compared with the 11qLOH positive group. Conclusions: This study showed that patients with NB and MYCN amplification in combination with 11qLOH might be less likely to respond to neoadjuvant chemotherapy when compared with patients with NB and MYCN amplification without 11qLOH.

Evaluation of dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted imaging for predicting muscular hyperplasia/hypertrophy in Crohn's disease.

OBJECTIVES: The existence of smooth muscle alteration in Crohn's disease (CD) is often neglected. It has been found that muscular hyperplasia/hypertrophy rather than fibrosis was the primary component of bowel wall thickening. This study aimed to assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging for the characterization of histopathologic tissue composition of CD, particularly smooth muscle hypertrophy, as well as inflammation and fibrosis. METHODS: The study included patients diagnosed with CD who received MRI examination 30 days before resection from August 2016 to December 2020. A semiquantitative histological grading scheme was employed to evaluate the pathological tissues. Resected sections were matched with MRI according to pathological marks. Parameters evaluated included: mural thickness, T2 ratio, apparent diffusion coefficient value; and maximum enhancement, initial slope of increase, perfusion parameters of DCE-MRI and enhancement pattern. These parameters were compared with location-matched histopathological grade. RESULTS: Ninety-one sections were enrolled in this retrospective study. When active inflammation is moderate or severe, volume transfer coefficient (Ktrans), maximum enhancement (ME) and initial slope of increase (ISI) are lower, mural thickness is higher when a certain degree of smooth muscle alteration is present. When active inflammation is absent or mild, ME, mural thickness and ISI can differentiate the presence of predominant muscular alteration. By combining ME and thickness comparisons against their cutoff values to create a combined ordinal parameter, the area under the curve value for whether significant muscular alteration coexists with moderate or severe active inflammation was found to be 0.953. CONCLUSIONS: MRI predicts the degree of inflammation, and can distinguish the degree of muscular alteration coexists with moderate or severe active inflammation with reasonable accuracy.