Treatments for Burning Mouth Syndrome: A Network Meta-analysis.

The aim of this systematic review and network meta-analysis (NMA) of randomized controlled trials was to evaluate the effectiveness of treatments for pain relief of burning mouth syndrome (BMS). Five databases and gray literature were searched. Independent reviewers selected studies, extracted data, and assessed the risk of bias. The primary outcome was pain relief or burning sensation, and the secondary outcomes were side effects, quality of life, salivary flow, and TNF-α and interleukin 6 levels. Four comparable interventions were grouped into different network geometries to ensure the transitivity assumption for pain: photobiomodulation therapy, alpha-lipoic acid, phytotherapics, and anxiolytics/antidepressants. Mean difference (MD) and 95% CI were calculated for continuous outcomes. The minimal important difference to consider a therapy beneficial against placebo was an MD of at least -1 for relief of pain. To interpret the results, the GRADE approach for NMA was used with a minimally contextualized framework and the magnitude of the effect. Forty-four trials were included (24 in the NMA). The anxiolytic (clonazepam) probably reduces the pain of BMS when compared with placebo (MD, -1.88; 95% CI, -2.61 to -1.16; moderate certainty). Photobiomodulation therapy (MD, -1.90; 95% CI, -3.58 to -0.21) and pregabalin (MD, -2.40; 95% CI, -3.49 to -1.32) achieved the minimal important difference of a beneficial effect with low or very low certainty. Among all tested treatments, only clonazepam is likely to reduce the pain of BMS when compared with placebo. The majority of the other treatments had low and very low certainty, mainly due to imprecision, indirectness, and intransitivity. More randomized controlled trials comparing treatments against placebo are encouraged to confirm the evidence and test possible alternative treatments (PROSPERO CRD42021255039).

Tumor microenvironment and its clinicopathological and prognostic associations in surgically resected cutaneous angiosarcoma.

PURPOSE: Cutaneous angiosarcoma (CAS) is a rare but typically aggressive malignant vascular neoplasm of the skin. Tumor microenvironment (TME) of CAS and its associations with baseline clinicopathological features and patient outcomes are very important, especially when considering the recent advances in understanding of the tumor biology. METHODS/PATIENTS: We retrospectively reviewed medical records of patients who underwent surgical resection for CAS at a tertiary Hospital. The pretreated specimens were evaluated by immunohistochemistry for programmed cell death protein 1 (PD-1) and its ligand (PD-L1), densities of tumor infiltrative lymphocytes (TILs) (CD3+, CD4+, CD8+, CD45RO+, FoxP3+), as well as c-MYC and Ki-67 expressions. Overall survival (OS) was estimated by Kaplan-Meier method and compared with Log-rank test. RESULTS: A total of 21 CAS patients were identified. Median age was 67 (ranges: 20-81) years, 14 (66.7%) were male, and over 50% had lesions of scalp. Histopathological examination showed a predominantly spindle cell type (57.1%). All patients underwent surgery, 16 (76.2%) were treated further. PD-L1 was positively stained (> 1%) in tumor cells (42.9%) and TILs (23.8%). PD-1 expression (> 1%) was identified in TILs of 11 (52.4%) cases. PD-1/PD-L1 expressions were significantly associated with the higher densities of CD3+, CD4+, CD8+, CD45RO+, and Foxp3+ TILs, but not with patient characteristics or c-MYC or Ki-67 expression. Median OS was 18.5 months (95% CI 6.0-35.9), although no prognostic significance was observed with respect to any clinicopathological features. CONCLUSION: We characterized TME and its clinical and prognostic association in CAS. PD-1/PD-L1 expressions were significantly associated with TILs subtypes but not with OS.

Hepatic phosphoenolpyruvate carboxykinase expression after gastric bypass surgery in rats with type 2 diabetes mellitus.

The objective of this study was to investigate the mRNA expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) after gastric bypass surgery (GBS) in rats with type 2 diabetic mellitus (T2DM). Thirty-six male Goto-Kakizaki rats, aged 12 weeks, were randomly divided into the GBS, sham operation with diet restriction (SO), and sham operation alone (control) groups (N = 12 per group). Liver specimens from all rats were obtained during the operation and 8 weeks after operation. Blood lipid levels were measured before and 8 weeks after operation. Fasting blood glucose (FBG), food intake, and body weight were recorded at weekly time points after operation. The blood glucose area under the curve (AUC) was calculated, and insulin sensitivity indices (ISI) were assessed. The expression PEPCK mRNA and protein were measured by real-time polymerase chain reaction and western blot. Compared with those of the SO and control groups, the blood lipid levels and the FBG in the GBS group was significantly decreased (P < 0.05), as was the AUC (P < 0.05), whereas the ISI was significantly increased (P < 0.05). PEPCK mRNA and protein levels in the GBS group were lower than those in the control group, whereas those in the SO group were significantly higher than those in controls (P < 0.05). In conclusion, GBS can reduce blood glucose in T2DM rats while improving glucose tolerance and hyperglycemia, and the mechanism appears to be associated with a decrease of hepatic PEPCK mRNA and protein expression.

Prognostic and predictive value of plasma D-dimer in advanced non-small cell lung cancer patients undergoing first-line chemotherapy.

PURPOSE: Previous studies have demonstrated that plasma D-dimer, a degradation product of cross-linked fibrin, correlated with tumor stage and prognosis in cancer patients. The aim of this study is to examine whether plasma D-dimer levels before and during chemotherapy predict tumor response and survival in advanced NSCLC patients undergoing first line chemotherapy. METHODS: Plasma D-dimer levels before (B0), and after one (B1) and two (B2) cycles of chemotherapy in 82 patients with advanced NSCLC were measured and correlated with treatment response, clinical features, progression-free survival (PFS) and overall survival. RESULTS: A significant correlation was identified between changes in D-dimer levels before and after two chemotherapy cycles and treatment response. In addition, there were significant correlations between D-dimer positivity at B0, B1 and B2 time points and tumor stage, number of metastatic sites and treatment response. Patients with positivity of D-dimer at B0, B1 and B2 had significantly shorter PFS compared with those with negativity. Notably, positivity of D-dimer at B1 and B2 time points was an independent predictive factor for unfavorable PFS. CONCLUSIONS: The positivity of D-dimer before and during chemotherapy is a predictor of treatment response and worse PFS in patients with advanced NSCLC. D-dimer levels provide prognostic information in addition to that of imaging studies.

Predictive role of RRM1 and BRCA1 mRNA expression on the clinical outcome of advanced non-small cell lung cancer.

This study aimed to evaluate the association between RRM1 and BRCA1 expressions and the therapeutic efficacy of platinum-based chemotherapy in non-small cell lung cancer patients in terms of their response and prognosis. In total, 377 patients agreed to participate in our study, and all of them received platinum-based combination chemotherapy between January 2008 and January 2009. The relative cDNA quantitation for RRM1 and BRCA1 was conducted using a fluorescence-based, real-time detection method, using ß-actin as a reference gene. The average age of the 377 patients was 64.6 years (range: 25.5-86.4 years), including 269 men and 108 women. Patients with high RRM1 expression benefited more from a platinum-containing regimen, and patients with high BRCA1 expression showed a high response rate to a platinum-containing regimen and reduced disease progression. Patients with high RRM1 expression were associated with a longer progression-free survival (PFS) and overall survival (OS) than those with low expression, and the hazard ratios (HRs) (95% confidence interval (CI)) were 0.67 (0.32-0.91) and 0.54 (0.30-0.95), respectively. Patients with high BRCA1 expression showed longer PFS and OS compared to those with low expression, and the HRs (95%CI) were 0.54 (0.30-0.95) and 0.62 (0.32-0.93), respectively. These results could be used in personalized chemotherapy decisions and to increase the response rate and prolonged survival, and could encourage exploration of the predictive value of other genes.

Gene diagnosis of micrometastases in regional lymph nodes of patients with stage I non-small cell lung cancer: impact on staging and prognosis.

PURPOSE: The long-term survival of patients with completely resected stage I non-small cell lung cancer (NSCLC) is not optimal because of undetected lymph node micrometastasis at the time of surgery. The aim of this study is to evaluate the role of survivin and livin mRNA expression in histopathologically negative lymph nodes of stage I NSCLC patients as markers of micrometastasis. METHODS: Clinical data and tissue samples of primary tumor and lymph nodes were collected from 44 patients with stage I NSCLC. Reverse-transcriptase-PCR (RT-PCR) was used to detect survivin and livin mRNA expression in these tumor and lymph node samples. RESULTS: Survivin mRNA was detected in all tumors, and livin mRNA was detectable in 39 of the 44 primary tumors. The cut-off values of survivin and livin mRNA levels for diagnosing micrometastasis in lymph nodes were set up according to the expression of survivin and livin mRNA in control lymph nodes. Fifteen (34.1 %) of 44 stage I NSCCL patients had micrometastasis in lymph nodes by survivin and/or livin mRNA positive expression. Survival analysis showed higher rate of cancer recurrences and tumor-related death in patients with lymph node micrometastasis (P < 0.001 and P = 0.001, respectively). Tumor-free survival and overall survival were significantly worse in patients with lymph node micrometastasis compared with those without such micrometastasis (P = 0.007 and P = 0.01, respectively). CONCLUSION: RT-RCR assay for survivin and livin mRNA can be considered as useful diagnostic tool for the detection of lymph node micrometastasis for stage I NSCLC patients.