Global, regional, and national burden of cirrhosis and other chronic liver diseases due to alcohol use, 1990-2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: To date, no study has evaluated trends in the burden of alcohol-induced cirrhosis and other chronic liver diseases based on the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2019 study. Herein, we report on the global burden of alcohol-induced cirrhosis and other chronic liver diseases in terms of age, sex, and sociodemographic index (SDI) from 1990 to 2019, based on analysis of GBD 2019 data. METHODS: The estimated annual percentage change (EAPC) was calculated to determine the trends in the age-standardized incidence and mortality rates and disability-adjusted life years (DALYs) for alcohol-induced cirrhosis and other chronic liver diseases. RESULTS: From 1990 to 2019, the global age-standardized incidence rate showed an upward trend (EAPC = 0.10), whereas the global age-standardized mortality rate and DALYs showed a downward trend (EAPC = - 0.88 and - 0.89, respectively). Low-(187.08 in 2019) and low-middle (178.11 in 2019)SDI regions had much higher age-standardized DALYs. Eastern Europe saw the largest increases in the age-standardized mortality rate and DALYs. Lithuania had the largest increase in mortalities caused by alcohol-induced cirrhosis and other chronic liver diseases(EAPC = 4.61). The age-standardized mortality rates and DALYs were higher in men than in women. CONCLUSION: From 1990 to 2019, the age-standardized incidence rate of alcohol-induced cirrhosis and other chronic liver diseases increased globally; however, both the age-standardized mortality rate and DALYs caused by alcohol-induced cirrhosis and other chronic liver diseases showed decreasing trends. Future studies should devise preventive strategies for low and low-middle SDI regions, Eastern Europe, Lithuania, and other high-risk regions.

MCTS1 as a Novel Prognostic Biomarker and Its Correlation With Immune Infiltrates in Breast Cancer.

Multiple copies in T-cell lymphoma-1 (MCTS1) plays an important role in various cancers; however, its effects on patient prognosis and immune infiltration in breast cancer remain unclear. In this study, the expression profiles and clinical information of patients with breast cancer were obtained from the Cancer Genome Atlas (TCGA) database. Using the Wilcoxon rank-sum test, the MCTS1 expression levels were compared between breast cancer and normal breast tissues. Functional enrichment analyses were performed to explore the potential signaling pathways and biological functions that are involved. Immune cell infiltration was assessed using single-sample gene set enrichment analysis. The UALCAN and MethSurv databases were used to analyze the methylation status of the MCTS1. The Kaplan-Meier method and Cox regression analysis were used to identify the prognostic value of MCTS1. A nomogram was constructed to predict the overall survival (OS) rates at one-, three-, and five-years post-cancer diagnosis. MCTS1 was overexpressed in breast cancer and significantly associated with the M pathological stage, histological type, PAM50, and increased age. MCTS1 overexpression contributes to a significant decline in OS and disease-specific survival. Multivariate Cox analysis identified MCTS1 as an independent negative prognostic marker of OS. The OS nomogram was generated with a concordance index of 0.715. Similarly, the hypomethylation status of MCTS1 is also associated with poor prognosis. Functional enrichment analysis indicated that the enriched pathways included the reactive oxygen species signaling pathway, MYC targets, interferon alpha response, immune response regulating signaling pathway, and leukocyte migration. Moreover, the overexpression of MCTS1 was negatively correlated with the levels of immune cell infiltration of natural killer cells, CD8+ T cells, effector memory T cells, and plasmacytoid dendritic cells. Therefore, MCTS1 maybe a novel prognostic biomarker.

Apatinib for the treatment of metastatic or locoregionally recurrent nasopharyngeal carcinoma after failure of chemotherapy: A multicenter, single-arm, prospective phase 2 study.

BACKGROUND: The authors aimed to investigate the efficacy and safety of apatinib in patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma (NPC). METHODS: A multicenter, single-arm, prospective phase 2 study was conducted on patients (18-70 years of age) with metastatic or recurrent NPC who had failed chemotherapy. Patients with recurrent disease involving vascular structure invasion were excluded. All enrolled patients received apatinib (500 mg daily) in continuous 4-week cycles until disease progression or development of unacceptable toxicity. The primary end point of this study was objective response rate (ORR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. This study was registered with ClinicalTrials.gov (NCT03130270). RESULTS: Between January 2017 and June 2018, 33 patients were enrolled. At the end of the data collection (May 20, 2020), the 33 patients had completed a total of 261.2 cycles of apatinib. Although 12 patients achieved a partial response, no patient achieved a complete response; thus, the ORR in the 33 patients was 36.4% (95% CI, 19.0%-53.7%). At the end of follow-up (median, 30 months; 95% CI, 24.9-35.1), median OS and median PFS were 16 months (95% CI, 14.6-17.4 months) and 5.0 months (95% CI, 3.6-6.4 months), respectively. The most common adverse events (grade 1/2) were hand-foot syndrome (18 [54.5%]), hypertension (14 [42.4%]), oral ulcer (8 [24.2%]), and proteinuria (4 [12.1%]). Two patients (1 with diabetes and 1 with hypertension) developed cerebral infarction. Grade 3/4 toxicities were uncommon. CONCLUSIONS: Apatinib shows promising activity, with manageable toxicities, in patients with metastatic or locoregionally recurrent NPC. Further evaluation of apatinib in large-scale studies is warranted. LAY SUMMARY: Clinical studies on vascular endothelial growth factor receptor (VEGFR)-targeted therapy for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. A recent preclinical study that evaluated apatinib in models of NPC showed a high objective response rate and a favorable safety profile. Our data further confirmed good efficacy in patients with lung metastasis. Further studies of the efficacy and safety of apatinib combined with immune checkpoint inhibitors or chemotherapy in NPC is warranted.

Positive effect of HPV status on prognostic value of blood lymphocyte-to-monocyte ratio in advanced cervical carcinoma.

BACKGROUND: This retrospective study aimed to investigate the prognostic significance of pretreatment lymphocyte-to-monocyte ratio (LMR) in locally advanced cervical cancer and its effect on overall survival. METHODS: The usual blood routine test was quantitatively performed to detect LMR. Signal strengths of human papilloma virus (HPV) type DNA in detected cervical cancer samples using hybrid capture 2 were analyzed in relative light units (RLU) compared with 1 pg/mL of HPV type 16 DNA-positive control (RLU/PC) samples. A total of 1.0 RLU/PC (~1 pg/mL) was used as the threshold for a positive result. The HPV-positive specimens were typed using reverse-hybridization line probe assay. RESULTS: The LMR and HPV DNA were found to be independent prognostic markers for 5-year overall survival (OS) and progression-free survival, respectively. Their joint detection may further enhance the predictive value for OS. In the positive HR (high risk)-HPV DNA status subgroup, LMR had a positive effect on improved OS but not in the non-HR HPV DNA status subgroup. CONCLUSIONS: The LMR and HR-HPV DNA status can be identified as independent prognostic factors. The different influences of LMR in combined chemoradiotherapy on survival may be related to HR-HPV DNA status. The combined detection of LMR and HR-HPV DNA status may contribute to screening prognosis.

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma : A matched-pair multicenter analysis of outcomes.

PURPOSE: The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. METHODS: Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. RESULTS: Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). CONCLUSION: Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC.

[CT perfusion study of acute local cerebral infarction in rhesus monkeys].

OBJECTIVE: To explore the value of CT perfusion in early diagnosis and management of superacute local cerebral infarction in rhesus monkeys. METHOD: Acute local cerebral infarction was induced in the rhesus monkeys during digital subtraction angiography (DSA) by introduction of pale thrombus prepared from autologous blood into the M1 branch of the middle cerebral artery (MCA). Plain CT scan and CT perfusion scanning were performed at different time points before and after DSA operation, and the results were analyzed in conjunction with the pathologic changes. RESULTS: Ischemic lesions were displayed on CT perfusion images, which showed local hypoperfusion, reduced cerebral blood flow and volume, and mean transit time delay in the compromised area. Local hypointense infarct area was identified in plain CT scan 24 h after the DSA operation, and the results were in good agreement with pathological examination during autopsy. CONCLUSION: CT perfusion imaging of the brain can accurately capture the cerebral perfusion deficits in acute ischemic stroke before morphologic changes take place, and therefore provides good means for thrombolytic treatment evaluation of stroke.