There is no consensus on the effect of red blood cell transfusion on colorectal cancer (CRC). This study examined the impact of perioperative red blood cell transfusion on postoperative complications, recurrence, and mortality in patients with CRC.In this retrospective cohort study, 219 CRC patients admitted to Chongqing Emergency Medical Center, and Chongqing University Central Hospital from 2008 to 2019 were divided into transfusion (n = 75) and non-transfusion (n = 144) groups. Univariate and multivariate Logistic regression analysis were used to analyze the effects of blood transfusion on the severity of postoperative complications in patients with CRC, and univariate and multivariate Cox regression was performed to analyze the effects of blood transfusion on postoperative death and recurrence.Twenty-two (29.33%) patients in the transfusion group were intermediate or advanced severity of postoperative complications, 31 (41.33%) patients died in the transfusion group, and 55 (73.33%) patients occurred recurrence of the CRC, with the median follow-up time being 24.57(14.50,36.37) months. Our result showed that perioperative red blood cell transfusion was associated with an increased risk of intermediate or advanced severity of postoperative complications in CRC patients [odds ratio (OR) = 3.368, 95% CI, 1.146-9.901]. And perioperative red blood cell transfusion increased the risk of postoperative death [hazard ratio (HR) = 2.747, 95% CI, 1.048-7.205] and recurrence in patients with CRC (HR = 2.168, 95% CI, 1.192-3.943).Our finding demonstrated that perioperative red blood cell transfusion was associated with severity of complications, recurrence, and death in CRC patients. However, further studies are still needed to confirm the adverse effects of red blood cell transfusions in CRC patients.
Abstract Background Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Methods Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. Results We uncovered that LC-BrMs exhibited a significantly greater intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN , TP53 , MUC16 , LRP1B , RYR2 , and EGFR . In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic, and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry, and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids of LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Conclusions In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.
OBJECTIVE: The objective of this meta-analysis was to systematically assess the association between aortic calcification (AC) and fractures. METHOD: Relevant studies were identified through searching PubMed, EMBASE and Cochrane databases before August 2014. Two investigators extracted data independ ently from the included studies. A random-effects model was derived to composite the pooled HRs or ORs for association of aortic calcification with fractures. RESULTS: A total of 15 articles (21927 subjects) were included in the final meta-analyses. Comparing with non-calcification subjects, patients with aortic calcification were associated with increased risk of fractures (OR = 2.97, 95% CI: 1.98-4.42). Stratified analysis indicated that patients with aortic calcification showed a higher risk of fractures in hemodialysis patients (OR = 1.89, 95% CI: 1.33-2.67; I2 = 0.0%, p= 0.781) and general population (OR = 2.90, 95% CI: 1.80-4.80; I2 = 33.0%, p= 0.225), respectively. Similar significant association between severe aortic calcification and fractures were also observed. CONCLUSIONS: Patients with aortic calcification or severe aortic calcification were associated with higher risk of fractures.
Type 2 diabetes mellitus (T2DM) is associated with coronary artery calcification (CAC) which is an independent risk factor for cardiovascular events. Metformin is the first-line antidiabetic medication. We aimed to investigate the association between metformin use and CAC.We included 369 patients with T2DM in this cross-sectional study. CAC scores, clinical characteristics, and antidiabetic drug prescription information of the patients were acquired. Baseline parameters were balanced for metformin and nonmetformin users using the propensity score matching (PSM) strategy.Among the 369 subjects who met our inclusion criteria, 288 subjects were included for further analysis after PSM. Metformin prescription rather than other antidiabetic medications was related to lower CAC scores (OR [95% CI] = 0.55 [0.34-0.90]; P = 0.018). Further multivariable logistic regression analysis demonstrated that metformin was negatively associated with CAC severity (OR [95% CI] = 0.58 [0.34-0.99]; P = 0.048), which was independent of age, BMI, eGFR, gender, cigarette smoking, duration of diabetes, hypertension, statin prescription, and number of nonmetformin antidiabetic agents. A subgroup analysis revealed a significant association between metformin and CAC scores in smokers (OR [95% CI] = 0.38 [0.16-0.93]; P = 0.035), but the association was not observed in never-smokers (OR [95% CI] = 0.72 [0.34-1.51]; P = 0.383).Metformin usage was independently associated with lower CAC scores in T2DM patients. The negative correlation between CAC scores and metformin was most prominent in patients with a history of cigarette smoking.
Abstract Context Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. Objective To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients. Design From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol. Setting This study was conducted at Sun Yat-Sen University Cancer Center. Patients PitNET patients who were pathologically confirmed were enrolled in this study. Interventions Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed. Main Outcome Measures PDOs retained key genetic and morphological features of their parental tumors. Results PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs. Conclusion The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.
A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11C-N-methylspiperone and glucose metabolic agent 18F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ (P < 0.01 in each comparison), as well as significantly lower monoamine receptor activities detected in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex, and amygdale (P < 0.05 in each comparison). However, regarding the glucose metabolism, there was no significant difference found in patients with monotherapy or polytherapy (P > 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.
An increasing number of bicuspid aortic valve (BAV) patients are undergoing transcatheter aortic valve replacement (TAVR), but the risk of brain injury in diffusion-weighted magnetic resonance imaging (DW-MRI) is currently unknown.This study sought to evaluate the risk of brain injury in BAV patients following TAVR.A total of 204 consecutive severe aortic stenosis patients who underwent TAVR were enrolled. A total of 83 (40.7%) patients were BAV patients, and the other 121 patients were tricuspid aortic valve (TAV) patients. All patients received DW-MRI at baseline, and after TAVR.Median ages (76 years [interquartile range (IQR): 71 to 81 years] vs. 79 years [IQR: 74 to 83 years]; p = 0.004) and Society of Thoracic Surgeons scores (4.87 [IQR: 3.72 to 8.54] vs. 6.38 [IQR: 3.96 to 9.50]; p = 0.044) of the BAV and TAV patients were significantly different, while the overt stroke rates (2.4% vs. 1.7%; p = 0.704) were comparable between the 2 groups. BAV patients were associated with higher number of new lesions (4.0 [IQR: 1.0 to 8.0] vs. 2.0 [IQR: 1.0 to 5.0]; p = 0.008), total lesion volume (290 mm3 [IQR: 70 to 930 mm3] vs. 140 mm3 [IQR: 35 to 480 mm3]; p = 0.008), and the volume per lesion (70.0 mm3 [IQR: 45.0 to 115.0 mm3] vs. 57.5 mm3 [IQR: 24.5 to 93.0 mm3]; p = 0.037) in DW-MRI. Moreover, the proportion of patients with lesions larger than 1 cm3 (28.6% vs. 10.9%; p = 0.005) was higher in BAV patients than in TAV patients.BAV patients may encounter more severe brain injuries not only due to greater number of lesions, but also due to larger lesion size in the early phase after TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294).
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