The addition of nimotuzumab during concurrent chemoradiotherapy improved survival outcomes in locally advanced nasopharyngeal carcinoma patients with optimal response to induction chemotherapy.

OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.

Lasso-Cox interpretable model of AFP-negative hepatocellular carcinoma.

BACKGROUND: In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. METHODS: We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. RESULTS: The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. CONCLUSION: The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.

Xerostomia: An easily ignored symptom induced by induction chemotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the prevalence and predictive factors of xerostomia during induction chemotherapy (IC) in patients with nasopharyngeal carcinoma (NPC). METHODS: We prospectively enrolled NPC patients who received IC between October 2020 and October 2021. The Visual Analogue Scale (VAS) and Xerostomia Inventory (XI) were used to evaluate the condition of xerostomia. The volume of the submandibular gland (SMG) was also calculated before and after IC. RESULTS: Fifty-two patients were enrolled in this study. Of these patients, 32.7% (n = 17) experienced xerostomia before IC. There were 32 (61.5%) patients suffered from xerostomia after IC, including 21 (40.4%) patients with newly diagnosed xerostomia after IC and 11 (21.1%) patients complained their xerostomia aggravated in those with xerostomia before IC. The median XI scores increased from 11 (standard deviation [SD], 2.930) to 18 (SD 3.995), 16 (SD 3.605), and 17 (SD 4.331) after the first, second, and third cycles of IC, respectively. The median score of VAS also increased from 0 to 4 during the following three cycles of IC. In those with IC-related xerostomia, the SMG volume after IC was significantly decreased compared with those without IC-related xerostomia (P = 0.001). The reduction of the SMG volume after IC was the independent risk factor for xerostomia (P = 0.002). CONCLUSION: Approximately two-thirds of NPC patients suffered from IC-related xerostomia and patients with a reduction of SMG volume after IC had a higher risk of xerostomia.

PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study.

Background: Whether intensity-modulated radiotherapy (IMRT) can enhance the efficacy of the programmed death (PD)-1 inhibitors combined with anti-angiogenic therapy for hepatocellular carcinoma (HCC) is unclear. Therefore, we conducted this multicenter retrospective study to investigate the efficacy of the combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT. Methods: From April 2019 to March 2022, a total of 197 patients with HCC [combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT (triple therapy group), 54; PD-1 inhibitors plus anti-angiogenic therapy (control group), 143] were included in our study. Propensity score matching (PSM) was applied to identify two groups with similar baselines. The objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) of the two groups were compared before and after matching. Results: Prior to PSM, the triple therapy group had higher ORR (42.6% vs 24.5%, P = 0.013) and more superior median OS (mOS) (20.1 vs 13.3 months, P = 0.009) and median PFS (mPFS) (8.7 vs 5.4 months, P = 0.001) than the control group. Following PSM, the triple therapy group still exhibited better mPFS (8.7 vs 5.4 months, P = 0.013) and mOS (18.5 vs 12.6 months, P = 0.043) than the control group. However, the ORR of the two groups was similar (40% vs 25%, P = 0.152). No significant difference was observed in the treatment-related adverse events between the two groups (P < 0.05 for all). Conclusions: The combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT for HCC is a promising regimen.

PD-L1 expression on circulating tumor cells can be a predictive biomarker to PD-1 inhibitors combined with radiotherapy and antiangiogenic therapy in advanced hepatocellular carcinoma.

Aim: A programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy. Methods: In this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China). Result: A total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1+ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1+ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1+ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1+ CTC counts at 1 month after treatment. Conclusions: Our study demonstrated that PD-L1+ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.

Heat-shock protein 90α is a potential prognostic and predictive biomarker in hepatocellular carcinoma: a large-scale and multicenter study.

BACKGROUND: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. METHODS: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. RESULTS: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS. CONCLUSIONS: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

Purpose: To assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis. Methods: Using linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazard model were used for analyses. Results: Among the 3,036 long-term NPC survivors, 1,432 survived for >5-10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years. Conclusions: The probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.

Gamma knife radiosurgery versus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study.

BACKGROUND: The optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT. METHODS: This retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS). RESULTS: Before PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p < 0.001). We followed the Cheng's classification for PVTT. In the subgroup analysis, GKR was associated with significantly longer mOS for patients with PVTT II-IV (17.5 vs. 8.7 months, p < 0.001; 17.2 vs. 7.8 months, p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p < 0.001). In the subgroup analysis, the GKR group demonstrated superior mOS for patients with PVTT II-IV (all p < 0.05) and comparable OS for patients with PVTT I. CONCLUSIONS: GKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV. CLINICAL TRIALS REGISTRATION: The study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.

Case report: A report of the complete pathological response of intrahepatic cholangiocarcinoma after conversion therapy.

Cholangiocarcinoma (CCA) is a rare disease with poor prognosis, and surgery remains the only curative treatment option. However, surgery is inappropriate for the majority of patients with CCA. Conversion therapy may provide opportunities for the surgical treatment of these patients. Herein, we describe a patient with intrahepatic CCA who was first treated with albumin-bound paclitaxel, cisplatin, and gemcitabine in combination with camrelizumab. The patient then successfully underwent surgery and achieved pathological complete remission. This report can serve as a reference for clinicians regarding conversion therapy for intrahepatic CCA.

Non-Digestible Carbohydrate and the Risk of Colorectal Neoplasia: A Systematic Review.

Non-digestible carbohydrate (NDC) is a fiber that can be fermented into short chain fatty acids (SCFAs) in gut, represented by resistant starch (RS) and inulin. Colorectal cancer (CRC) is one of the most common malignant cancer. Pre-clinical studies have reported that NDC can produce SCFAs to protect the gut epithelium, which is associated with prevention of CRC, but this role in clinical trails is controversial. In this review, we discusses whether RS and inulin should be offered to cancer/precancerous patients or healthy subjects to decrease their risk of CRC. A multiple database search was conducted for studies published on RS/inulin supplementation as a chemopreventive method from 1989 to 2019. The meta-analysis showed the total SCFAs and butyrate concentrations (P = 0.84; P = 0.79), and excretions (P = 0.55; P = 0.63) in feces did not increase significantly after RS/inulin supplementation. Only two studies reported that RS/inulin inhibit the proliferation of large bowel epithelial, whereas 15 studies showed that it does not decrease the risk of neoplasia. RS/inulin restored the promotion of tumor risk factors in two studies and did not in four studies. Notably, the other four studies showed that RS increases pro-tumorigenesis mechanisms. The clinical evidences consistently show that RS/inulin is ineffective for preventing colorectal neoplasia.

Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis.

BACKGROUND: Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). METHODS: The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. RESULTS: A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. CONCLUSION: We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

Resistant starch ameliorated insulin resistant in patients of type 2 diabetes with obesity: a systematic review and meta-analysis.

BACKGROUND: Resistant starch (RS) is a starch that can be fermented by the microbial flora within gut lumen. Insulin resistance (IR) is a pathophysiological condition related to diabetes and obesity. RS could reduce blood glucose and ameliorate IR in animals, but its effect in human population is controversial. OBJECTIVE: The authors conducted a systematic literature review to evaluate the effect of RS diet supplement on ameliorating IR in patients with T2DM and simple obesity. METHODS: Databases that supplemented with RS in ameliorating IR in T2DM and simple obesity were queried for studies on or before August 15, 2018. Parameters including fasting insulin, fasting glucose, body mass index (BMI), homeostatic model assessment (HOMA) etc. were extracted from studies to systemically evaluate effects of RS. RESULTS: The database search yielded 14 parallel or crossover studies that met the inclusion criteria. The results indicated that there was no significant difference in the amelioration of BMI, HOMA-%S and HOMA-%B in T2DM patients between RS and the non-RS supplementation. However, the fasting blood glucose, fasting insulin and HOMA-IR in T2DM with obesity who supplemented RS were lower than control group, and the subgroup analysis according to the dose of RS supplementation was inconsistency. There was no significant difference between RS and non-RS supplements in patients with simple obesity. CONCLUSION: RS supplementation can ameliorate IR in T2DM, especially for the patients of T2DM with obesity, but not in simple obesity.

Sodium butyrate alleviates high-glucose-induced renal glomerular endothelial cells damage via inhibiting pyroptosis.

We recently found that Sodium butyrate (NaB) possesses anti-inflammatory effects in diabetic nephropathy (DN) mouse model and in high-glucose induced mouse glomerular mesangial cells. Pyroptosis is a programmed cell death accompanied with the release of pro-inflammatory factors. Gasdermin D (GSDMD) is a novel discovered pivotal executive protein of pyroptosis, which can be cleaved by inflammatory caspases. The aim of our study is to verify if NaB have some effects against high-glucose induces pyroptosis in renal Glomerular endothelial cells (GECs). For this aim, human GECs were cultured and exposed to high-glucose. Exogenous NaB, caspase 1 inhibitor Ac-YVAD-CMK (A-Y-C) or knockdown GSDMD by siRNA were used. We found high glucose could increase Propidium Iodide (PI) positive cells and elevate release of lactate dehydrogenase (LDH), Interleukin 1 beta (IL-1ß) and Interleukin 18 (IL-18); protein levels of GSDMD, GSDMD N-terminal domain (GSDMD-N) and cleaved-caspase-1 were also elevated. Effect of NaB on LDH release and PI positive cells was further enhanced by inhibiting caspase 1-GSDMD. In addition, high glucose-induced nuclear factor kappa-B (NF-κB)/NF-κB inhibitor α (IκB-α) signaling pathway was reversed by NaB or A-Y-C administration. In conclusion, NaB could ameliorate high-glucose induced GECs via caspase1-GSDMD canonical pyroptosis pathway; and NF-κB/IκB-α signaling pathway was involved in it.

Effect of Inulin-Type Carbohydrates on Insulin Resistance in Patients with Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Insulin resistance (IR) is a physiological condition related to type 2 diabetes mellitus (T2DM) and obesity, which is associated with high blood insulin and glucose. Inulin-type carbohydrate (ITC) is a kind of fermentable fructan that can reduce glucose and ameliorate IR in an animal model, but the effect in clinical trials is controversial. OBJECTIVE: The authors conducted a systematic literature review to evaluate the effect of ITC supplementation in ameliorating IR in T2DM and obese patients. METHODS: Multiple databases were queried for studies before December 25, 2018, which involved supplementation with ITC in ameliorating IR in T2DM and obese patients. Studies that involved meta-analysis of the body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FI), HbA1c, homeostatic model assessment IR (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) of T2DM subjects were included. HOMA-IR and QUICKI were identified as the primary outcomes. A systematic review was performed to evaluate the effect of ITC on IR in obese patients. RESULTS: The database search yielded 25 studies, which met the inclusion criteria; 11 articles were meta-analyzed, and 5 other articles on T2DM and 9 articles on simple obesity were systematically reviewed. Our results did not find ITC supplementation decrease postintervention and reduction data of BMI (P = 0.08). However, it can significantly decrease postintervention and reduction data of FPG, FI, HbA1c, and HOMA-IR. Heterogeneity was eliminated by subgroup analysis according to baseline BMI. There was no significant difference in the amelioration of QUICKI between the ITC and control groups. However, the difference was statistically significant and the heterogeneity was eliminated after subgroup analysis according to intakes of ITC. 14 articles for a systematic review found that the results of blood glucose, insulin, and HbA1c were controversial. Only one of the seven studies on simple obesity concluded that ITC intervention significantly ameliorated HOMA-IR, while the other six did not. CONCLUSION: Supplementation of ITC can ameliorate IR in T2DM, especially in obese T2DM patients, but the effects are controversial in obese patients.

Advances on Cell Autophagy and Its Potential Regulatory Factors in Renal Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury is a major reason for acute kidney injury and various kidney diseases. Autophagy plays an important role during renal ischemia-reperfusion injury (RIRI), but it remains controversial whether autophagy contributes to cell survival or ischemia-reperfusion-induced cell death. In the review, we summarized the function of autophagy in the progression of acute ischemic kidney injury, as well as its related molecular mechanisms. While analyzing the opposite roles of autophagy in RIRI, it was concluded that the protective or detrimental function of autophagy was depending on the timing and amount of the activation of cell autophagy. We also summarized the regulatory agents, including active compounds, proteins, or microRNAs (miRNAs), which regulated the cell autophagy during renal acute ischemic kidney injury process. This explained why the opposite conclusion occurred when cell autophagy was studied in the RIRI models from different researchers. Therefore, the article provided a hypothesis to control cell autophagy at the appropriate timing and intensity so as to alleviate renal injury and sustain cell survival of the renal cell.

Effects of metformin treatment on radiotherapy efficacy in patients with cancer and diabetes: a systematic review and meta-analysis.

PURPOSE: Metformin is a key pharmaceutical for patients with diabetes mellitus (DM). Metformin also can enhance tumor radiosensitivity in vitro and in vivo. Some retrospective cohort studies have indicated that metformin can improve the efficacy of radiotherapy in patients with cancer and DM. The aim of this systematic review was to evaluate the radiotherapy efficacy of metformin in patients with cancer and DM. METHODS: Multiple databases were queried for studies that address the efficacy of metformin in radiotherapy of patients with cancer and DM. Studies were included that involved comparisons of the short-term tumor responses and long-term survival outcomes of these patients who were managed with or without metformin as well as of nondiabetic patients without metformin. The OR and HR with accompanying 95% CI were assessed in a random effects model. The main endpoints were 2-year and 5-year overall survival (2y-OS and 5y-OS, respectively). RESULTS: The database search yielded 17 cohort studies that met the inclusion criteria. The results indicated that the tumor response was higher in patients who also were treated with metformin than in those who were not (OR, 0.48; 95% CI, 0.22-1.07; P=0.07) and nondiabetic (OR, 0.27; 95% CI, 0.07-0.98; P=0.05). Moreover, patients who received metformin had survival benefits compared with patients not treated with metformin (2y-OS: OR, 0.48; 95% CI, 0.29-0.80; P=0.005; 5y-OS: OR, 0.38; 95% CI, 0.25-0.56; P<0.00001). The metformin-related HRs of OS values were not significantly different. CONCLUSION: Metformin appears to improve the tumor response to radiotherapy in patients with cancer and DM and partly yield survival benefits. Despite the apparent advantages provided by metformin treatment on 2y-OS and 5y-OS, these retrospective data are at risk of bias and should be interpreted with caution.

Distribution of metastatic disease in the brain in relation to the hippocampus: a retrospective single-center analysis of 6064 metastases in 632 patients.

This study aimed to investigate the patterns of brain metastasis and to explore the risk factors affecting hippocampus metastasis (HM). We retrospectively analyzed the clinical information of patients with metastatic disease in the brain. The associations between clinicopathologic variables with HM and peri-hippocampal metastasis (PHM) were evaluated in univariate and multivariate regression analyses. A total of 632 patients with 6064 metastatic lesions were recruited into the present study. Of these, 4.1% (26/632) of patients developed HM, and 5.5% (35/632) of patients developed PHM. Only 0.5% (31/6064) of metastatic lesions were located in the hippocampus and 0.6% (37/6064) were in the PHM. Age ≤60 years was an independent risk factor for HM (odds ratio [OR]: 2.602, 95% confidence interval [CI]: 1.115-6.076, P = 0.027) and PHM (OR: 2.555, 95%CI: 1.229-5.310, P = 0.012) in univariate and multivariate analyses. The hippocampus is a rare site of brain metastasis. Younger patients (age ≤60 years) had increased risk of developing HM and PHM. The current study provides the opportunity to investigate the clinical feasibility of hippocampal sparing whole brain radiation therapy, especially in older patients.

Left ventricular function during acute high-altitude exposure in a large group of healthy young Chinese men.

OBJECTIVE: The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males. METHODS: A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points. RESULTS: Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude. CONCLUSION: Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.

[The change of left ventricular function upon acute high altitude exposure and its relationship with acute mountain sickness].

OBJECTIVE: To investigate the changes of the cardiac hemodynamics after acute high altitude exposure in healthy young males and the relationship with acute mountain sickness(AMS). METHODS: Left ventricular function and oxyhemoglobin saturation (SaO2), heart rate (HR), blood pressure (BP) were measured in 218 healthy young males before and after high altitude exposure within 24 h respectively. According to the lake louise score criteria, the subjects were divided into two groups: acute mountain sickness group (AMS group) and non acute mountain sickness group (non-AMS group). RESULTS: HR, diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular ejection fraction (LVEF), stroke volume (SV), stroke index (SI) cardiac output (CO), cardiac index (CI) were significantly increased upon acute high altitude exposure (P < 0.05). Whereas SaO2 and end-systolic volume (ESV) were significantly decreased (P < 0.05). In addition, HR, systolic blood pressure (SBP) and MAP in AMS group were significantly higher than those in non-AMS group (P < 0.05). But stroke index (SI) and end-diastolic volume (EDV) in AMS group were significantly lower than those in non-AMS group (P < 0.05). CONCLUSION: Cardiac function in healthy young males upon acute high altitude exposure was enhanced. EDV, HR and SI might become the indexes of predicting the acute mountain sickness in the future.