Incidence, risk factors, and outcomes of the transition of HIPEC-induced acute kidney injury to acute kidney disease: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. METHODS: From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. RESULTS: AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). CONCLUSIONS: Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence.

A large-scale cancer-specific protein-DNA interaction network.

Cancer development and progression are generally associated with dysregulation of gene expression, often resulting from changes in transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network as well as an extensive promoter clone resource for future studies. Most highly connected TFs do not show a preference for binding to promoters of genes associated with either good or poor cancer prognosis, suggesting that emerging strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activator or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF estrogen receptor ɑ (ESR1) on DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study not only broadens our knowledge of TFs involved in the cancer gene regulatory network but also provides a valuable resource for future studies, laying a foundation for potential therapeutic strategies targeting TFs in cancer.

Radiological evidence of rapid growth acceleration of a small part solid nodule found to be large-cell carcinoma of the lung.

BACKGROUND: With the widespread use of low-dose computed tomography for lung cancer screening, the detection rate of pulmonary lesions manifesting as ground-glass opacities (GGOs) has been increasing dramatically. The volume doubling time (VDT) has been introduced in clinical practice to monitor the potential growth rate of GGOs during long-term follow-up periods. CASE PRESENTATION: A 72-year-old never-smoker female diagnosed with mixed GGO manifested abruptly accelerated growth with sudden decreased VDT from 400 to 36 days. A thoracoscopic left lower lobectomy with mediastinal lymph node dissection was performed, and the diagnosis was stage IB large-cell neuroendocrine carcinoma (LCNEC). Next-generation sequencing of the tumor highlights an EML4-ALK gene fusion. CONCLUSIONS: The LCNEC may present as GGO with longer VDT in the early stage. VDT should calculate by the whole size either on the entire tumor diameter or on consolidation diameter. It is recommended that meticulous long-term follow-up with dynamic VDT monitoring may help select high-risk GGOs performing timely semi-elective surgical resection in clinical practice.

Characteristics and risk factors for renal recovery after acute kidney injury in critically ill patients in cohorts of elderly and non-elderly: a multicenter retrospective cohort study.

BACKGROUND: The purpose of this study was to explore the risk factors for renal nonrecovery among elderly and nonelderly patients with acute kidney injury (AKI) in critically ill patients. METHODS: A multicenter retrospective cohort of 583 critically ill patients with AKI was examined. We found the best cutoff value for predicting renal recovery by age was 63 years old through logistic regression. All patients were divided into two cohorts, age <63 and age ≥63-years old; on the basis of renal recovery at 30 days after AKI, the two patient cohorts were further divided into a renal recovery group and a renal nonrecovery group. Multivariate logistic regression was used to analyze the risk factors affecting renal recovery in the two cohorts. RESULTS: The 30-day renal recovery rate of patients aged <63 years was 70.0% (198/283), multivariate analysis showed that the independent risk factors affecting renal nonrecovery in age <63 years old included AKI stage, blood lactate level and hemoglobin level. The 30-day renal recovery rate of patients aged ≥63 years was 28.7% (86/300), multivariate analysis showed that the independent risk factors for renal nonrecovery in age ≥63-years old included diabetes mellitus, surgery with general anesthesia, AKI stage, APACHE II score, eGFR, and hemoglobin level. CONCLUSIONS: The renal nonrecovery after AKI in critically ill patients in patients aged ≥63 years was more strongly affected by multiple risk factors, such as diabetes mellitus, surgery with general anesthesia, eGFR, and APACHE II score, in addition to hemoglobin and AKI stage.

Clinicopathological features and prognosis of colonic and rectal gastrointestinal stromal tumors: A propensity score matching analysis.

Background: Colonic gastrointestinal stromal tumor (cGIST) and rectal gastrointestinal stromal tumor (rGIST) are two rare subtypes of gastrointestinal stromal tumor (GIST). The view that colonic and rectal carcinoma are different is generally accepted; however, whether there is a difference between cGIST and rGIST is still unknown. Here, we aimed to provide evidence for future clinical management and research by comparing the differences between the two types of GIST in the above-mentioned aspects. Methods: Patients were enrolled from three medical centers in China and published literature was collected following the inclusion and exclusion criteria. Propensity score matching was used to eliminate differences between cohorts. Results: Between cGIST and rGIST patients, significant differences were observed in age, tumor size, mitotic index, NIH risk category, growth pattern, and symptoms. Adjuvant therapy is used in a high proportion of cGIST patients, and neoadjuvant therapy is used in a high proportion of rGIST patients. Although local resection is the main surgical method in both cohorts, the proportion is higher in cGIST patients. The overall survival of rGIST patients was better than that of the cGIST patients before propensity score matching (PSM). Interestingly, no significant differences in prognosis were observed after PSM. Conclusions: Although there were significant differences between cGIST and rGIST patients in baseline characteristics, clinicopathological features, treatment choice, and overall survival rate before PSM, no significant differences in long-term survival were observed between the two groups after PSM. In our study, there may be no differences in the tumor entity between cGIST and rGIST.

Research Trends and Emerging Hotspots of Lung Cancer Surgery during 2012-2021: A 10-Year Bibliometric and Network Analysis.

Background. Lung cancer remains the leading cause of death because of cancer globally in the past years. To inspire researchers with new targets and path-breaking directions for lung cancer research, this study is aimed at exploring the research trends and emerging hotspots in the lung cancer surgery literature in the recent decade.Methods. This cross-sectional study combined bibliometric and network analysis techniques to undertake a quantitative analysis of lung cancer surgery literature. Dimensions database was searched using keywords in a 10-year period (2012-2021). Publications were characterized by publication year, research countries, field citation ratio, cooperation status, research area, and emerging hotspots.Results. Overall, global scholarly outputs of lung cancer surgery had almost doubled during the recent decade, with China, Japan, and the United States leading the way, while Denmark and Belgium predominated in terms of scientific influence. Network analysis showed that international cooperation accounted for a relatively small portion in lung cancer surgery research, and the United States, China, and Europe were the prominent centers of international cooperation network. In the recent decade, research of lung cancer surgery majored in prevention, biomedical imaging, rehabilitation, and genetics, and the emerging research hotspots transformed into immunotherapy. Research on immunotherapy showed a considerable increase in scientific influence in the latest year.Conclusions. The study findings are expected to provide researchers and policymakers with interesting insights into the changing trends of lung cancer surgery research and further generate evidence to support decision-making in improving prognosis for patients with lung cancer.

Effect of micronutrient pack on micronutrient status and antioxidant capacities among institutional older adults in Shanghai, China.

BACKGROUND AND OBJECTIVES: Older adults are at increased risk of micronutrient deficiency, disrupting the balance of oxidation/antioxidation system and leading to serious health burdens. This study aimed to investigate the effect of micronutrient pack on micronutrient status and oxidative/antioxidative biomarkers in institutional older adults. METHODS AND STUDY DESIGN: Subjects aged 65-100 years were randomly assigned to either intervention group or control group (n=49 each), providing a package of micronutrient pack or placebo daily for three months. The concentrations of micronutrients, malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected both at baseline and at the end of the study. RESULTS: The changes in concentrations of serum folate (21.1±1.6 vs 0.6±0.5 nmol/L), vitamin B-1 (3.4±0.4 vs -0.2±0.3 nmol/L), vitamin B-2 (11.5±3.3 vs 2.3±1.4 nmol/L), vitamin B-12 (128.8±34.8 vs 13.3±16.0 pmol/L), 25-hydroxyvitamin D (17.8±1.3 vs -0.8±0.5 ng/mL) and plasma zinc (0.6±1.8 vs -9.6±1.9 µmol/L) over 3-months were significantly increased in the intervention group compared with the control group (all p<0.05). While the prevalence of folate, vitamin B-12 and vitamin D deficiencies were significantly decreased after 3-months intervention (all p<0.05). Moreover, changes in serum MDA level (-1.5±0.2 vs 0.2±0.3 nmol/mL) were remarkably reduced, and the activities of serum GSH-Px (1.3±0.3 vs 0.3±0.2 ng/mL) and plasma SOD (14.3±2.4 vs -2.1±2.4 U/mL) were increased in the intervention group than those of in the control group (all p<0.01). CONCLUSIONS: The micronutrient pack among institutional older adults was well-accepted with good compliance and tolerance. The 3-month intervention may improve micronutrient status and enhance antioxidative capacities.

Morroniside prevents H2O2 or Aß1-42-induced apoptosis via attenuating JNK and p38 MAPK phosphorylation.

Amyloid-ß peptide (Aß) plays a causal role in the development and progression of Alzheimer's disease (AD). Oxidative stress and activation of mitogen-activated protein kinase (MAPK) are involved in Aß-induced neurotoxicity. Morroniside, one active monomer of dry ripe sarcocarp of Cornus officinalis, has shown antioxidant properties in several cell lines. The present study investigated the protective actions of morroniside against the cytotoxicity produced by exposure to H2O2 or Aß1-42 in rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to 150 µM H2O2 or 20 µM Aß1-42 down-regulated anti-apoptotic protein expression (Bcl-2), up-regulated pro-apoptotic protein expression (Bax, cytochrome C, and cleaved caspase-3), increased JNK and p38 MAPK phosphorylation and finally caused significant cell death. This effect was reversed by pretreatment with morroniside in a dose-dependent manner. Among the selective inhibitors of MAPKs, the JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) showed steady preventive effect against H2O2 or Aß1-42-induced apoptosis. The results suggest that different from the selective inhibitors of MAPKs, morroniside can inhibit H2O2 or Aß1-42-induced apoptotic pathway activation through suppressing its upstream signaling components of JNK and p38 MAPK phosphorylation simultaneously.

Expression of ER-{alpha}36, a novel variant of estrogen receptor {alpha}, and resistance to tamoxifen treatment in breast cancer.

PURPOSE Recently, a 36-kDa variant of estrogen receptor alpha (ER-alpha66), ER-alpha36, has been identified and cloned. ER-alpha36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Here, we investigate the association between ER-alpha36 expression and tamoxifen resistance in patients with breast cancer. PATIENTS AND METHODS ER-alpha36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-alpha36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-alpha66-positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-alpha36 was not associated with survival in patients with ER-alpha66-positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-alpha66-negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-alpha36 was significantly associated with poorer DFS and DSS in 156 ER-alpha66-positive patients from this cohort, and ER-alpha36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). CONCLUSION Women with ER-alpha66-positive tumors that also express high levels of ER-alpha36 are less likely to benefit from tamoxifen treatment.