Center variability in the prognostic value of a cumulative acute cellular rejection "A-score" for long-term lung transplant outcomes.

The acute rejection score (A-score) in lung transplant recipients, calculated as the average of acute cellular rejection A-grades across transbronchial biopsies, summarizes the cumulative burden of rejection over time. We assessed the association between A-score and transplant outcomes in 2 geographically distinct cohorts. The primary cohort included 772 double lung transplant recipients. The analysis was repeated in 300 patients from an independent comparison cohort. Time-dependent multivariable Cox models were constructed to evaluate the association between A-score and chronic lung allograft dysfunction or graft failure. Landmark analyses were performed with A-score calculated at 6 and 12 months posttransplant. In the primary cohort, no association was found between A-score and graft outcome. However, in the comparison cohort, time-dependent A-score was associated with chronic lung allograft dysfunction both as a time-dependent variable (hazard ratio, 1.51; P < .01) and when calculated at 6 months posttransplant (hazard ratio, 1.355; P = .031). The A-score can be a useful predictor of lung transplant outcomes in some settings but is not generalizable across all centers; its utility as a prognostication tool is therefore limited.

Bioinformatics analysis and experimental validation reveal the anti-ferroptosis effect of FZD7 in acute kidney injury.

BACKGROUND: Ferroptosis plays an important role in acute kidney injury (AKI), but the specific regulatory mechanism of ferroptosis in AKI remains unclear. This study is expected to analyze ferroptosis-related genes (FRGs) in AKI and explore their underlying mechanisms. RESULTS: A total of 479 differentially expressed genes (DEGs), including 196 up-regulated genes and 283 down-regulated genes were identified in the AKI chip GSE30718. 341 FRGs were obtained from the Genecard, OMIM and NCBI database. Totally 11 ferroptosis-related DEGs in AKI were found, in which 7 genes (CD44, TIGAR, RB1, LCN2, JUN, ARNTL, ACSL4) were up-regulated and 4 genes (FZD7, EP300, FOXC1, DLST) were down-regulated. Three core genes (FZD7, JUN, EP300) were obtained by PPI and KEGG analysis, among which the function of FZD7 in AKI is unclear. The WGCNA analysis found that FZD7 belongs to a module that was negatively correlated with AKI. Further basic experiments confirmed that FZD7 is down-regulated in mouse model of ischemia-reperfusion-AKI and cellular model of hypoxia-reoxygenation(H/R). In addition, knockdown of FZD7 could further aggravate the down-regulation of cell viability induced by H/R and Erastin, while overexpression of FZD7 can rescue its down-regulation to some extent. Furthermore, we verified that knockdown of FZD7 decreased the expression of GPX4 and overexpression of FZD7 increased the expression of GPX4, suggesting that FZD7 may inhibit ferroptosis by regulating the expression of GPX4 and plays a vital role in the onset and development of AKI. CONCLUSIONS: This article revealed the anti-ferroptosis effect of FZD7 in acute kidney injury through bioinformatics analysis and experimental validation, suggesting that FZD7 is a promising target for AKI and provided more evidence about the vital role of ferroptosis in AKI.

Impact of baseline proteinuria level on long-term outcomes in lupus nephritis.

OBJECTIVES: Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes. METHODS: We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate-level (>1 and <3 g/day, group 2; 90 patients), and high-level proteinuria (≥3 g/day, group 3; 97 patients). Outcomes included complete proteinuria recovery (CPR) at 1 year, an adverse composite outcome (ESKD, a sustained ≥40% decline in eGFR, or death), and LN flares. Cox proportional hazard models were used to examine the association between baseline characteristics and long-term outcomes. RESULTS: At baseline, the median [IQR] age was 33.2 [26.4, 42.4] years; median proteinuria level was 2.2 [1.0, 3.8] g/day. 177 (71%) patients had proliferative lesions on biopsy; 59.7% in group 1, 78.9% in group 2, and 71.4% in group 3.The rate of achievement of CPR at 1 year was highest for group 1 and lowest for group 3. For long-term outcomes (median follow-up 8.4 years), the frequency of the adverse composite outcome was 27.4%, 26.7%, and 48.5% in groups 1, 2, and 3, respectively; p= 0.003. The corresponding frequency of flares was 27.4%, 38.2%, and 61.9%, respectively; p< 0.001. In the multivariable model for factors associated with long-term outcomes, there was no significant difference between groups 1 and 2; group 3 was associated with the worst prognosis. CONCLUSIONS: Low-level proteinuria is commonly associated with proliferative LN and adverse long-term outcomes.

Short and Long-Term Outcomes of Patients with Pure Membranous Lupus Nephritis Compared to Patients with Proliferative Disease.

OBJECTIVES: Membranous lupus nephritis (MLN) is thought to have a more benign course than proliferative lupus nephritis (PLN). We aimed to determine the differences in short and long-term outcomes between patients with MLN and PLN. METHODS: We included patients with first biopsy-proven MLN and PLN. Short-term outcomes included complete proteinuria recovery (CPR), complete renal response (CRR), and primary efficacy renal response (PERR). Long-term outcomes included a sustained ≥40% reduction in baseline estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), cardiovascular (CV) events, ≥2 increase in SDI, and death. Univariable and multivariable Cox proportional hazard models were used to examine the effect of baseline characteristics on long-term outcomes. RESULTS: Of 215 patients, 51 had pure MLN, and 164 had PLN. We found no significant differences between the two groups in achieving CPR, CRR, and PERR at 1 and 2 years. Median time to outcomes was slightly, but insignificantly, longer in the MLN group.For long-term outcomes, PLN was associated with worse renal and non-renal outcomes, but this was not statistically significant.In the multivariable Cox proportional hazard models, ESKD was associated with the following baseline variables: younger age (HR 0.92, 95% CI 0.87-0.97), higher creatinine (HR 1.01, 95% CI 1.01-1.02), low complement (HR 4.0, 95% CI 1.04-11.10), and higher chronicity index (HR 1.28, 95% CI 1.08-1.51). CONCLUSION: The resolution of proteinuria in LN is slow. MLN is not a benign disease and may be associated with deterioration of renal function, ESKD, damage, CV events, and death.

A cuproptosis score model and prognostic score model can evaluate clinical characteristics and immune microenvironment in NSCLC.

BACKGROUND: Cuproptosis-related genes (CRGs) are associated with lung adenocarcinoma. However, the links between CRGs and non-small-cell lung cancer (NSCLC) are not clear. In this study, we aimed to develop two cuproptosis models and investigate their correlation with NSCLC in terms of clinical features and tumor microenvironment. METHODS: CRG expression profiles and clinical data from NSCLC and normal tissues was obtained from GEO (GSE42127) and TCGA datasets. Molecular clusters were classified into three patterns based on CRGs and cuproptosis cluster-related specific differentially expressed genes (CRDEGs). Then, two clinical models were established. First, a prognostic score model based on CRDEGs was established using univariate/multivariate Cox analysis. Then, through principal component analysis, a cuproptosis score model was established based on prognosis-related genes acquired via univariate analysis of CRDEGs. NSCLC patients were divided into high/low risk groups. RESULTS: Eighteen CRGs were acquired, all upregulated in tumor tissues, 15 of which significantly (P < 0.05). Among the three CRG clusters, cluster B had the best prognosis. In the CRDEG clusters, cluster C had the best survival. In the prognostic score model, the high-risk group had worse prognosis, higher tumor mutation load, and lower immune infiltration while in the cuproptosis score model, a high score represented better survival, lower tumor mutation load, and high-level immune infiltration. CONCLUSIONS: The cuproptosis score model and prognostic score model may be associated with NSCLC prognosis and immune microenvironment. These novel findings on the progression and immune landscape of NSCLC may facilitate the provision of more personalized immunotherapy interventions for NSCLC patients.

A novel prognostic signature based on smoking-associated genes for predicting prognosis and immune microenvironment in NSCLC smokers.

BACKGROUND: As a highly heterogeneous tumor, non-small cell lung cancer (NSCLC) is famous for its high incidence and mortality worldwide. Smoking can cause genetic changes, which leading to the occurrence and progress of NSCLC. Nevertheless, the function of smoking-related genes in NSCLC needs more research. METHODS: We downloaded transcriptome data and clinicopathological parameters from Gene Expression Omnibus (GEO) databases, and screened smoking-related genes. Lasso regression were applied to establish the 7-gene signature. The associations between the 7-gene signature and immune microenvironment analysis, survival analysis, drug sensitivity analysis and enriched molecular pathways were studied. Ultimately, cell function experiments were conducted to research the function of FCGBP in NSCLC. RESULTS: Through 7-gene signature, NSCLC samples were classified into high-risk group (HRG) and low-risk group (LRG). Significant difference in overall survival (OS) between HRG and LRG was found. Nomograms and ROC curves indicated that the 7-gene signature has a stable ability in predicting prognosis. Through the analysis of immune microenvironment, we found that LRG patients had better tumor immune activation. FCGBP showed the highest mutation frequency among the seven prognostic smoking related genes (LRRC31, HPGD, FCGBP, SPINK5, CYP24A1, S100P and FGG), and was notable down-regulated in NSCLC smokers compared with non-smoking NSCLC patients. The cell experiments confirmed that FCGBP knockdown promoting proliferation, migration, and invasion in NSCLC cells. CONCLUSION: This smoking-related prognostic signature represents a promising tool for assessing prognosis and tumor microenvironment in smokers with NSCLC. The role of FCGBP in NSCLC was found by cell experiments, which can be served as diagnostic biomarker and immunotherapy target for NSCLC.

Integrative analysis of aging-related genes reveals CEBPA as a novel therapeutic target in non-small cell lung cancer.

BACKGROUND: To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. METHODS: Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. RESULTS: Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. CONCLUSIONS: The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.

Efficacy of Telitacicept in a systemic lupus erythematosus patient with suboptimal response to Belimumab: A case report.

As a therapeutic treatment for systemic lupus erythematosus (SLE), Belimumab reduces disease relapses and minimizes organ damage. Clinical practice, however, shows that the treatment is ineffective for a number of patients. Treatments for such cases are still lacking. As a biologic agent that targets both BLys and APRIL, Telitacicept inhibits both B cells and plasma cells. This case report describes a 35-year-old female with lupus nephritis (LN) who had previously undergone 10 cycles of Belimumab treatment but remained poorly controlled. Despite this, her condition improved significantly after switching to Telitacicept. This is the first report on the efficacy of Telitacicept in an SLE patient with suboptimal response to Belimumab. Telitacicept's role in this scenario needs more investigation and attention.

Identification of Plasma hsa_circ_0001230 and hsa_circ_0023879 as Potential Novel Biomarkers for Focal Segmental Glomerulosclerosis and circRNA-miRNA-mRNA Network Analysis.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with an unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. METHODS: The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by the receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U test. RESULTS: A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of the two-circRNA panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. CONCLUSION: hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.

MR-CT image fusion method of intracranial tumors based on Res2Net.

BACKGROUND: Information complementarity can be achieved by fusing MR and CT images, and fusion images have abundant soft tissue and bone information, facilitating accurate auxiliary diagnosis and tumor target delineation. PURPOSE: The purpose of this study was to construct high-quality fusion images based on the MR and CT images of intracranial tumors by using the Residual-Residual Network (Res2Net) method. METHODS: This paper proposes an MR and CT image fusion method based on Res2Net. The method comprises three components: feature extractor, fusion layer, and reconstructor. The feature extractor utilizes the Res2Net framework to extract multiscale features from source images. The fusion layer incorporates a fusion strategy based on spatial mean attention, adaptively adjusting fusion weights for feature maps at each position to preserve fine details from the source images. Finally, fused features are input into the feature reconstructor to reconstruct a fused image. RESULTS: Qualitative results indicate that the proposed fusion method exhibits clear boundary contours and accurate localization of tumor regions. Quantitative results show that the method achieves average gradient, spatial frequency, entropy, and visual information fidelity for fusion metrics of 4.6771, 13.2055, 1.8663, and 0.5176, respectively. Comprehensive experimental results demonstrate that the proposed method preserves more texture details and structural information in fused images than advanced fusion algorithms, reducing spectral artifacts and information loss and performing better in terms of visual quality and objective metrics. CONCLUSION: The proposed method effectively combines MR and CT image information, allowing the precise localization of tumor region boundaries, assisting clinicians in clinical diagnosis.

Inferior vena cava ultrasound to predict hypotension after general anesthesia induction: a systematic review and meta-analysis of observational studies.

PURPOSE: Hypotension after induction of general anesthesia is common and is associated with significant adverse events. Identification of patients at high risk can inform the use of preoperative mitigation strategies. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the inferior vena cava collapsibility index (IVC-CI) and maximal diameter (dIVCmax) in predicting postinduction hypotension and to identify their predictive performance across different threshold ranges. METHODS: We searched MEDLINE, PubMed®, and Embase from inception to March 2023 for prospective observational studies exploring the performance of IVC-CI and dIVCmax in predicting postinduction hypotension in adults presenting for elective surgery under general anesthesia. We excluded studies reporting on IVC parameters predicting postinduction hypotension in the obstetric patient population or exclusively in patients with obesity. Trials screening and data extraction were conducted independently. We performed meta-analyses to identify the performance of IVC parameters in predicting postinduction hypotension, followed by subgroup analyses that sought the IVC-CI range with the highest hierarchical summary receiver-operating characteristic area under the curve (HSROC-AUC). We used a bivariate random effects model to calculate summary estimates. We evaluated study quality using Newcastle-Ottawa scores and certainty of evidence using the GRADE framework. RESULTS: We included 14 studies involving 1,166 patients. Pooled sensitivity and specificity of the IVC-CI to predict postinduction hypotension was 0.68 (95% confidence interval [CI], 0.55 to 0.79; coverage probability, 0.91) and 0.78 (95% CI, 0.69 to 0.85; coverage probability, 0.9), respectively, with an HSROC-AUC of 0.80 (95% CI, 0.68 to 0.85, high quality of evidence). An IVC-CI threshold range of 40-45% had an HSROC-AUC of 0.86 (95% CI, 0.69 to 0.93, high quality of evidence). CONCLUSIONS: Preoperative IVC-CI is a strong predictor of postinduction hypotension. We recommend that future studies use an IVC-CI threshold of 40-45% (low certainty of evidence). Future studies are needed to establish whether ultrasound-guided preoperative optimization improves outcomes in high-risk patients. STUDY REGISTRATION: PROSPERO ( CRD42022316140 ); first submitted 10 March 2022.

RéSUMé: OBJECTIF: L'hypotension après l'induction de l'anesthésie générale est fréquente et est associée à des effets indésirables importants. L'identification des patient•es à haut risque peut éclairer l'utilisation de stratégies préopératoires d'atténuation. Nous avons réalisé une revue systématique et une méta-analyse pour évaluer la précision diagnostique de l'indice de collapsibilité de la veine cave inférieure (IC-VCI) et du diamètre maximal (dVCImax) pour prédire l'hypotension post-induction et identifier leurs performances prédictives dans différentes plages de seuils. MéTHODE: Nous avons fait des recherches dans les bases de données MEDLINE, PubMed® et Embase de leur création jusqu'en mars 2023 pour en extraire les études observationnelles prospectives explorant les performances de l'IC-VCI et du dVCImax pour la prédiction de l'hypotension post-induction chez des adultes se présentant pour une chirurgie non urgente sous anesthésie générale. Nous avons exclu les études rapportant des paramètres de VCI prédisant l'hypotension post-induction dans la population obstétricale ou exclusivement chez des personnes obèses. Le tri des études et l'extraction des données ont été menés indépendamment. Nous avons réalisé des méta-analyses pour identifier la performance des paramètres de VCI dans la prédiction de l'hypotension post-induction, suivies d'analyses de sous-groupes qui ont recherché la plage d'IC-VCI avec le plus haut niveau de hiérarchie de l'aire sous la courbe de la courbe ROC (HSROC-AUC). Nous avons utilisé un modèle bivarié à effets aléatoires pour calculer des estimations sommaires. Nous avons évalué la qualité des études à l'aide des scores de Newcastle-Ottawa et la certitude des données probantes à l'aide de l'outil GRADE. RéSULTATS: Quatorze études portant sur 1166 patient·es ont été incluses. La sensibilité et la spécificité combinées de l'IC-VCI pour prédire l'hypotension post-induction étaient de 0,68 (intervalle de confiance [IC] à 95 %, 0,55 à 0,79; probabilité de couverture, 0,91) et 0,78 (IC 95 %, 0,69 à 0,85; probabilité de couverture, 0,9), respectivement, avec une HSROC-AUC de 0,80 (IC 95 %, 0,68 à 0,85, données probantes de haute qualité). Une plage de seuils d'IC-VCI de 40 à 45 % avait une HSROC-AUC de 0,86 (IC 95 %, 0,69 à 0,93, haute qualité des données probantes). CONCLUSION: L'IC-VCI préopératoire est un bon prédicteur de l'hypotension post-induction. Nous recommandons que les études futures utilisent un seuil d'IC-VCI de 40 à 45 % (faible certitude des données probantes). De futures études sont nécessaires pour déterminer si l'optimisation préopératoire échoguidée améliore les devenirs chez la patientèle à risque élevé. ENREGISTREMENT DE L'éTUDE: PROSPERO ( CRD42022316140 ); première soumission le 10 mars 2022.

Outcomes after flow cytometry crossmatch-positive lung transplants managed with perioperative desensitization.

Our program previously reported successful outcomes following virtual crossmatch (VXM)-positive lung transplants managed with perioperative desensitization, but our ability to stratify their immunologic risk was limited without flow cytometry crossmatch (FCXM) data before 2014. The aim of this study was to determine allograft and chronic lung allograft dysfunction (CLAD)-free survival following VXM-positive/FCXM-positive lung transplants, which are performed at a minority of programs due to the high immunologic risk and lack of data on outcomes. All first-time lung transplant recipients between January 2014 and December 2019 were divided into 3 cohorts: VXM-negative (n = 764), VXM-positive/FCXM-negative (n = 64), and VXM-positive/FCXM-positive (n = 74). Allograft and CLAD-free survival were compared using Kaplan-Meier and multivariable Cox proportional hazards models. Five-year allograft survival was 53% in the VXM-negative cohort, 64% in the VXM-positive/FCXM-negative cohort, and 57% in the VXM-positive/FCXM-positive cohort (P = .7171). Five-year CLAD-free survival was 53% in the VXM-negative cohort, 60% in the VXM-positive/FCXM-negative cohort, and 63% in the VXM-positive/FCXM-positive cohort (P = .8509). This study confirms that allograft and CLAD-free survival of patients who undergo VXM-positive/FCXM-positive lung transplants with the use of our protocol does not differ from those of other lung transplant recipients. Our protocol for VXM-positive lung transplants improves access to transplant for sensitized candidates and mitigates even high immunologic risk.

Cuproptosis in lung cancer: mechanisms and therapeutic potential.

Cuproptosis, a recently identified form of cell death that differs from other forms, is induced by the disruption of the binding of copper to mitochondrial respiratory acylation components. Inducing cell cuproptosis and targeting cell copper death pathways are considered potential directions for treating tumor diseases. We have provided a detailed introduction to the metabolic process of copper. In addition, this study attempts to clarify and summarize the relationships between cuproptosis and therapeutic targets and signaling pathways of lung cancer. This review aims to summarize the theoretical achievements for translating the results of lung cancer and cuproptosis experiments into clinical treatment.

Association Between the FRAIL Scale and Postoperative Complications in Older Surgical Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Several frailty screening tools have been shown to predict mortality and complications after surgery. However, these tools were developed for in-person evaluation and cannot be used during virtual assessments before surgery. The FRAIL (fatigue, resistance, ambulation, illness, and loss of weight) scale is a brief assessment that can potentially be conducted virtually or self-administered, but its association with postoperative outcomes in older surgical patients is unknown. The objective of this systematic review and meta-analysis (SRMA) was to determine whether the FRAIL scale is associated with mortality and postoperative outcomes in older surgical patients. METHODS: Systematic searches were conducted of multiple literature databases from January 1, 2008, to December 17, 2022, to identify English language studies using the FRAIL scale in surgical patients and reporting mortality and postoperative outcomes, including postoperative complications, postoperative delirium, length of stay, and functional recovery. These databases included Medline, Medline ePubs/In-process citations, Embase, APA (American Psychological Association) PsycInfo, Ovid Emcare Nursing, (all via the Ovid platform), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EbscoHost, the Web of Science (Clarivate Analytics), and Scopus (Elsevier). The risk of bias was assessed using the quality in prognosis studies tool. RESULTS: A total of 18 studies with 4479 patients were included. Eleven studies reported mortality at varying time points. Eight studies were included in the meta-analysis of mortality. The pooled odds ratio (OR) of 30-day, 6-month, and 1-year mortality for frail patients was 6.62 (95% confidence interval [CI], 2.80-15.61; P < .01), 2.97 (95% CI, 1.54-5.72; P < .01), and 1.54 (95% CI, 0.91-2.58; P = .11), respectively. Frailty was associated with postoperative complications and postoperative delirium, with an OR of 3.11 (95% CI, 2.06-4.68; P < .01) and 2.65 (95% CI, 1.85-3.80; P < .01), respectively. The risk of bias was low in 16 of 18 studies. CONCLUSIONS: As measured by the FRAIL scale, frailty was associated with 30-day mortality, 6-month mortality, postoperative complications, and postoperative delirium.

Pelvic floor symptoms in cisgender women with Ehlers-Danlos syndrome: an international survey study.

INTRODUCTION AND HYPOTHESIS: Ehlers-Danlos Syndrome (EDS) is a group of inherited connective tissue disorders associated with abnormal collagen, and is more prevalent in women than in men. The aim of this cross-sectional study was to characterize pelvic floor symptoms in cisgender women with EDS and to describe their impact on quality of life. METHODS: An online questionnaire on obstetric and gynecological experiences of cisgender women with EDS was disseminated through EDS patient societies and social media. This study was a sub-analysis of the broader questionnaire and focused on pelvic floor disorders, whereby self-reported symptoms and validated questionnaires were used to assess pelvic floor symptom severity (Pelvic Floor Distress Inventory, PFDI-20), impact on quality of life (Pelvic Floor Impact Questionnaire, PFIQ-7), and sexual function (Female Sexual Function Index, FSFI-6). Groups based on age and EDS type were compared using Kruskal-Wallis and Chi-squared tests. RESULTS: A total of 1,303 participants were included in the analysis. Pelvic floor symptom prevalence included: stress urinary incontinence in 60%, urgency urinary incontinence in 54%, fecal incontinence in 24%, and pelvic organ prolapse in 21%. Bladder symptoms were reported to be the most bothersome. The impact of prolapse symptoms on quality of life was higher in women under age 40 than in older participants (p<0.001). Pelvic pain was reported in 71%. Pain ratings were highest for dysmenorrhea, muscle and joint pain, and backache (median 7 out of 10 for each). Almost half of participants screened positive for possible sexual dysfunction and 36% reported dyspareunia more than half the time. CONCLUSIONS: This large, observational study demonstrated that cisgender women with EDS report a high prevalence of pelvic floor symptoms that appear to be more severe than in the general population.

Secondary infections in critically ill patients with viral pneumonia due to COVID-19 and influenza: a historical cohort study.

PURPOSE: To compare the incidence and nature of secondary infections (SI) between critically ill patients with viral pneumonia due to COVID-19 and seasonal influenza and explore the association between SI and clinical outcomes. METHODS: We conducted a historical cohort study of patients admitted to the intensive care unit (ICU) at two tertiary care centers during the first wave of the COVID-19 pandemic and patients admitted with influenza during the 2018-2019 season. The primary outcome was the rate of SI. Secondary outcomes included rates of ICU and in-hospital mortality, organ-support-dependent disease, and length of ICU and hospital stay. RESULTS: Secondary infections developed in 55% of 95 COVID-19 patients and 51% of 47 influenza patients (unadjusted odds ratio [OR], 1.16; 95% confidence interval [CI], 0.57 to 2.33). After adjusting for baseline differences between cohorts, there were no significant differences between the COVID-19 cohort and the influenza cohort (adjusted OR, 1.00; 95% CI, 0.41 to 2.44). COVID-19 patients with SI had longer ICU and hospital stays and duration of mechanical ventilation. The SI incidence was higher in COVID-19 patients treated with steroids than in those not treated with steroids (15/20, 75% vs 37/75, 49%). CONCLUSION: Secondary infections were common among critically ill patients with viral pneumonia including COVID-19. We found no difference in the incidence of SI between COVID-19 and influenza in our cohort study, but SI in patients with COVID-19 were associated with worse clinical outcomes and increased healthcare resource use. The small cohort size precludes any causal inferences but may provide a basis for future research.

RéSUMé: OBJECTIF: Comparer l'incidence et la nature des infections secondaires entre les patients gravement malades atteints de pneumonie virale due à la COVID-19 et ceux atteints de la grippe saisonnière et explorer l'association entre les infections secondaires et les issues cliniques. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients admis à l'unité de soins intensifs (USI) dans deux centres de soins tertiaires pendant la première vague de la pandémie de COVID-19 et de patients admis pour la grippe au cours de la saison 2018-2019. Le critère d'évaluation principal était le taux d'infections secondaires. Les critères d'évaluation secondaires comprenaient les taux de mortalité à l'USI et à l'hôpital, les maladies nécessitant un support d'organes et la durée du séjour à l'USI et à l'hôpital. RéSULTATS: Des infections secondaires se sont développées chez 55 % des 95 patients atteints de COVID-19 et 51 % des 47 patients grippaux (rapport des cotes [RC] non ajusté, 1,16; intervalle de confiance [IC] à 95 %, 0,57 à 2,33). Après ajustement pour tenir compte des différences initiales entre les cohortes, aucune différence significative n'a été observée entre la cohorte de COVID-19 et la cohorte de grippe (RC ajusté, 1,00; IC 95 %, 0,41 à 2,44). Les patients atteints de COVID-19 atteints d'infections secondaires ont séjourné plus longtemps aux soins intensifs et à l'hôpital et la durée de la ventilation mécanique était plus longue pour ces patients. L'incidence d'infections secondaires était plus élevée chez les patients atteints de COVID-19 traités par stéroïdes que chez ceux non traités par stéroïdes (15/20, 75 % vs 37/75, 49 %). CONCLUSION: Les infections secondaires étaient fréquentes chez les patients gravement malades atteints de pneumonie virale, y compris de COVID-19. Nous n'avons observé aucune différence dans l'incidence d'infections secondaires entre les patients atteints de COVID-19 et ceux atteints de grippe dans notre étude de cohorte, mais les infections secondaires chez les patients atteints de COVID-19 étaient associées à de moins bonnes issues cliniques et à une utilisation accrue des ressources de soins de santé. La petite taille de la cohorte exclut toute inférence causale, mais peut fournir une base pour les recherches futures.

A hood shield reduces postdoffing contamination during simulated COVID-19 airway management: an exploratory, simulation-based randomized study.

PURPOSE: SARS-CoV-2 poses a significant occupational health threat to health care workers performing aerosol-generating medical procedures, with a threefold increased risk of a positive test and predicted infection compared with the general population. Nevertheless, the personal protective equipment (PPE) configuration that provides better protection with lower contamination rates is still unknown. METHODS: We enrolled 40 practitioners with airway management training (anesthesiologists, anesthesia assistants/nurses) in an exploratory, simulation-based randomized study. We evaluated the performance of a novel, locally designed hood (n = 20) in terms of protection from surrogate contamination using an ultraviolet (UV) marker during a standardized urgent intubation procedure and a simulated episode of coughing in a high-fidelity simulation setting compared with standard PPE (n = 20). The primary outcome was the presence of residual UV fluorescent contamination on any base clothing or exposed skin of the upper body after doffing PPE assessed by a blinded evaluator. RESULTS: The proportion of participants with residual contamination on any base clothing or exposed skin of the upper body after doffing was less than half in the hood PPE group compared with the standard PPE group (8/20 [40%] vs 18/20 [90%], respectively; P = 0.002). CONCLUSIONS: Compared with standard PPE, enhanced PPE with a locally designed prototype hood was associated with reduced contamination of the upper torso and fewer body areas being exposed to droplets after a simulated aerosol-generating scenario without designed airflow. STUDY REGISTRATION: ClinicalTrials.gov (NCT04373096); registered 4 May 2020.

RéSUMé: OBJECTIF: Le SRAS-CoV-2 représente une menace importante pour la santé au travail des travailleurs de la santé réalisant des interventions médicales générant des aérosols, avec un risque trois fois plus élevé de test positif au SRAS-CoV-2 et d'infection prédite au SRAS-CoV-2 par rapport à la population générale. Néanmoins, la configuration optimale des équipements de protection individuelle (EPI) offrant la meilleure protection avec des taux de contamination plus faibles est encore inconnue. MéTHODE: Nous avons recruté 40 praticiens ayant une formation en prise en charge des voies aériennes (anesthésiologistes, assistants en anesthésie/personnel infirmier) dans le cadre d'une étude exploratoire randomisée de simulation. Nous avons évalué la performance d'un nouveau capuchon conçu localement (n = 20) par rapport aux EPI standards (n = 20) en termes de protection contre la contamination de substitution à l'aide d'un marqueur ultraviolet (UV) au cours d'une procédure d'intubation urgente normalisée et d'un épisode simulé de toux dans un environnement de simulation haute fidélité. Le critère d'évaluation principal était la présence d'une contamination résiduelle par fluorescence UV sur les vêtements de base ou la peau exposée du haut du corps après le retrait des EPI telle qu'évaluée par un évaluateur en aveugle. RéSULTATS: La proportion de participants présentant une contamination résiduelle sur les vêtements de base ou la peau exposée du haut du corps après le retrait des équipements de protection était de moins de la moitié dans le groupe ayant porté le capuchon par rapport au groupe EPI standard (8/20 [40 %] vs 18/20 [90 %], respectivement; P = 0,002). CONCLUSION: Par rapport aux EPI standards, les EPI améliorés avec un prototype de capuchon conçu localement étaient associés à une contamination réduite du haut du torse et à moins de zones du corps exposées aux gouttelettes après une mise en situation simulée de génération d'aérosols sans flux d'air préconçu. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04373096); enregistrée le 4 mai 2020.

Recurrence of locally invasive retroperitoneal dedifferentiated liposarcoma shortly after surgery: A case report and literature review.

RATIONALE: Retroperitoneal dedifferentiated liposarcoma (RPDDL) is an uncommon malignancy, which often remains undetected for many years due to having adequate space in the retroperitoneal cavity and lacking clinical manifestations in the early stage of the disease. Surgical procedure is usually used as the first choice for treatment. However, it is prone to local recurrence after the operation, resulting in an unfavorable prognosis. Our aim is to draw useful lessons from the new case and provide some experience for management of the disease. PATIENT CONCERNS: We describe a 55-year-old male patient who was admitted for a 3-week history of persistent dull ache of the left waist. A large mass of the left upper abdomen was palpated in physical examination. Moreover, the imaging examination revealed that the diameter of the mass was about 21 cm, and some adjacent vital organs were invaded, which brought great challenges to complete surgical resection. DIAGNOSIS: The postoperative pathological results confirmed that the mass was RPDDL with invasion of the surrounding vital structures including pancreas, spleen, left adrenal gland, left kidney, and vasculature with tumor emboli. INTERVENTIONS: Surgical resection of the mass was performed by our multidisciplinary team. The patient received chemotherapy 1 month after surgery. OUTCOMES: The effect of chemotherapy seemed to be unsatisfactory. Local multifocal recurrence of the tumor was considered about 2 months after surgery. Finally, he gave up any treatments and died of the disease. LESSONS: Regular physical examination and ultrasound screening may detect the disease as early as possible, especially for high-risk group aged 60 to 70, which should be popularized. Incomplete resection, vascular invasion, and interruption of postoperative treatment may lead to an unfavorable prognosis. Therefore, we think that patients with the disease may benefit from complete surgical resection and uninterrupted adjuvant therapy.

A cuproptosis-related prognostic signature for guiding clinical diagnosis and treatment in uveal melanoma patients.

Background: Cuproptosis, one of the most recently discovered forms of cell death, is induced by the disruption of copper binding to the mitochondrial respiratory acylation components. However, the mechanism underlying cuproptosis in uveal melanoma (UM) has not yet been adequately studied. Methods: RNA and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed cuproptosis-related genes were identified by R software. A prognostic signature was constructed by applying LASSO regression and Cox regression models. The associations between the signature and the immune microenvironment, overall survival, and drug sensitivity were studied. In addition, qPCR and Western blotting were performed on UM cells and RPE cell lines to verify the expression levels of the genes encoding dihydrolipoamide dehydrogenase (DLD) and dihydrolipoamide S-succinyltransferase (DLST) in UM cases. Results: Using a cuproptosis-related prognostic signature, UM samples were classified into high- and low-risk groups. A significant difference in overall survival between the two risk groups was evident. Receiver operating characteristic curves demonstrated that the signature is a reliable predictor of prognosis. Immune cell infiltration, drug sensitivity, and immune checkpoint expression were analysed. Significant immune difference between the two high-risk groups was found, and the high expression of immune checkpoints in high-risk groups suggests significant immunotherapy potential. In addition, drug sensitivity analysis experiments suggest that erlotinib may be a potential treatment for high-risk patients. The results of in vitro experiments confirmed that DLD and DLST had higher expression levels in UM cell lines. Conclusions: The prognostic signature developed in this study is a reliable biomarker for predicting the prognosis of UM and may serve as a tool for personalised treatment of patients with UM.

CMAF-Net: a cross-modal attention fusion-based deep neural network for incomplete multi-modal brain tumor segmentation.

Background: The information between multimodal magnetic resonance imaging (MRI) is complementary. Combining multiple modalities for brain tumor image segmentation can improve segmentation accuracy, which has great significance for disease diagnosis and treatment. However, different degrees of missing modality data often occur in clinical practice, which may lead to serious performance degradation or even failure of brain tumor segmentation methods relying on full-modality sequences to complete the segmentation task. To solve the above problems, this study aimed to design a new deep learning network for incomplete multimodal brain tumor segmentation. Methods: We propose a novel cross-modal attention fusion-based deep neural network (CMAF-Net) for incomplete multimodal brain tumor segmentation, which is based on a three-dimensional (3D) U-Net architecture with encoding and decoding structure, a 3D Swin block, and a cross-modal attention fusion (CMAF) block. A convolutional encoder is initially used to extract the specific features from different modalities, and an effective 3D Swin block is constructed to model the long-range dependencies to obtain richer information for brain tumor segmentation. Then, a cross-attention based CMAF module is proposed that can deal with different missing modality situations by fusing features between different modalities to learn the shared representations of the tumor regions. Finally, the fused latent representation is decoded to obtain the final segmentation result. Additionally, channel attention module (CAM) and spatial attention module (SAM) are incorporated into the network to further improve the robustness of the model; the CAM to help focus on important feature channels, and the SAM to learn the importance of different spatial regions. Results: Evaluation experiments on the widely-used BraTS 2018 and BraTS 2020 datasets demonstrated the effectiveness of the proposed CMAF-Net which achieved average Dice scores of 87.9%, 81.8%, and 64.3%, as well as Hausdorff distances of 4.21, 5.35, and 4.02 for whole tumor, tumor core, and enhancing tumor on the BraTS 2020 dataset, respectively, outperforming several state-of-the-art segmentation methods in missing modalities situations. Conclusions: The experimental results show that the proposed CMAF-Net can achieve accurate brain tumor segmentation in the case of missing modalities with promising application potential.