Effect of metformin on proliferative markers in women with endometrial carcinoma: Systematic review and meta-analysis.

Objective: Endometrial carcinoma (EC) is the most common gynecologic malignancy in the USA and Western Europe. Surgery is the mainstay of both staging and treatment of EC. Fertility sparing medical therapies are often offered to young women who desire fertility. Metformin has been suggested to be an anti-cancer agent as evidenced by previous studies. It decreases Antigen Ki-67 (Ki-67) proliferation and expression which is associated with proliferative activity of malignant tumors. In this systematic review and meta-analysis, we assessed the efficacy of metformin on patients with EC. Materials and Methods: We searched PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS for relevant clinical trials and excluded observational studies. The quality appraisal was evaluated according to GRADE, and we assessed the risk of bias using Cochrane's risk of bias tool. We conducted the analysis of continuous data using mean difference (MD). We included the following outcomes: Ki-67 index, glucose, insulin, P-S6, body mass index (BMI), C-peptide, Insulin-like growth factor (IGF-1), leptin, and hemoglobin. Results: Nine studies were eligible for our meta-analysis. We found that compared to the control group, metformin is highly effective in reducing Ki-67 proliferation and expression [MD=-10.14 (-19.10, -1.17)], (p=0.03), P-S6 [MD=-1.82 (-3.17, -0.46)], (p=0.009), plasma glucose level [MD=-1.76 (-4.88, 1.37), p=0.27], and BMI [MD=-1.07 (-1.49, -0.65)], (p<0.001). Conclusion: We conclude that metformin administration is effective in patients with EC. It decreases Ki-67 proliferation and expression, serum glucose, and p-S6 significantly.

Efficacy of hyoscine in pain management during hysteroscopy: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis of relevant clinical trials from full-text, scientific journal archives to assess the efficacy of hyoscine for the management of pain during in-office hysteroscopy (OH) procedures. Cochrane CENTRAL, ClinicalTrials.Gov, MEDLINE, PubMed, SCOPUS and the Web of Science were searched for all clinical trials that matched our search criteria. A full assessment of bias was made using the Cochrane Group tool-set. The following outcomes were included: visual analogue scale (VAS) score for postoperative pain, postoperative need for analgesia, and procedure time. In the case of homogeneous data, the analysis was performed using a fixed effects system, and the random effects system was used with heterogeneous data. Inclusion criteria included only randomized clinical trials, and interventions that included patients receiving hyoscine-N-Butyl Bromide during OH, regardless of dose or mode of administration, and compared this with placebo. Three clinical trials were included. The actual mean difference (MD) of the VAS pain score showed no significant difference between hyoscine or placebo [MD: -0.28 (-1.08, 0.52), (p=0.49)]. For postoperative analgesia, the overall MD showed no significant difference between hyoscine or placebo [MD: 0.43 (0.16, 1.14), (p=0.09)]. For procedure time, the combined effect estimate failed to show any significant difference between hyoscine and placebo [MD: -0.66 (-2.77, 1.44) (p=0.54)]. Contrary to previously published data, our meta-analysis using the latest available RCTs fails to show hyoscine as being effective in reducing pain or the need for other forms of anesthesia in OH.

Systematic review of the safety and efficacy of tramadol during office hysteroscopy

Office hysteroscopy (OH) is a common procedure in gynecology. Pain is the most frequently reported problem in OH. In this study, we aimed to investigate the role of tramadol administration in relieving pain in women undergoing OH. We searched PubMed, the Cochrane Library, ClinicalTrials.gov, MEDLINE, Scopus, and Web of Science databases for relevant clinical trials based on our search terms. We included randomized controlled trials and included all published trials in all six searched databases from their inception until February 28th 2021. We included pain as the primary outcome, and the incidence of adverse events of tramadol as secondary outcomes. We performed the analysis of continuous data using mean difference (MD) and dichotomous data using risk ratio (RR). We found that tramadol led to significantly less pain during the actual procedure [MD=-1.27, 95% confidence interval (CI): (-1.66, -0.88); p<0.001], immediately after the procedure [MD=-1.03, 95% CI: (-1.40, -0.67); p<0.001], and 30 minutes after the procedure [MD=-0.74, 95% CI: (-1.06, -0.41); p<0.001]. Regarding safety endpoints, no significant difference was noted for dizziness [RR=1.88, 95% CI: (0.79, 4.47); p=0.16] or vomiting [RR=1.80, 95% CI: (0.40, 8.18); p=0.45]. Based on the available data, we conclude that tramadol administration seems to be both effective and safe for patients undergoing office hysteroscopy.

Case study-based systematic review of literature on lymphoma-associated cardiac tamponade.

This study aimed to compile all the relevant studies of patients presenting with pericardial tamponade before or after diagnosis of lymphoma, describe the clinical presentations of patients with lymphoma and cardiac tamponade, and assess the difference in overall survival based on the timing of cardiac tamponade diagnosis. A comprehensive search strategy was conducted in the following databases: PubMed and Cochrane Library, using the following keywords: Lymphoma AND Cardiac Tamponade. The criteria for eligibility included cases with a confirmed diagnosis of lymphoma and cardiac tamponade, human studies, and publications in English language. The statistical analysis was performed using IBM Statistical Package for Social Sciences (SPSS) version 20. We included 48 research articles (n = 52 cases) with adequate reporting of measured outcomes. The median age of the patients was 52 (9-94) years. Only 6 patients were noted to have primary cardiac lymphoma, while the majority of cases were considered to have secondary cardiac lymphoma (88.5%). According to the data on the type of lymphoma reported through cytology and immunohistochemistry, 49 patients were diagnosed with non-Hodgkin lymphoma, and of these cases the most common subtype was large B-cell lymphoma (42.9%). Overall, the average duration of illness was 14 ± 23 days. A total of 13 patients had distant heart sounds, 12 cases were noted to be hypotensive, and 13 subjects were found to have increased jugular venous pressure. Our retrospective study demonstrated that most patients presented with pericardial tamponade after lymphoma diagnosis, and those were mostly secondary cardiac lymphoma of the non-Hodgkin type with large B-cell as the most common subtype. Dyspnoea, oedema, and constitutional symptoms were the most common presenting signs. The median overall survival of patients with lymphoma and cardiac tamponade is 4 months, with no significant difference in mortality in the presentation timing before and after the diagnosis of lymphoma.

Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials.

Our objective was to assess and rank different pharmacological interventions for relieving endometriosis-related pain. We conducted an online bibliographic search in different databases from their inception until March 2019. We included randomized controlled trials (RCTs) that assessed different medical therapies in the management of endometriosis-related pain. We applied this network meta-analysis (NMA) based on the frequentist approach using statistical package "netmeta" (version 1.0-1) in R software. Our main outcomes were the change in severity of pelvic pain, dysmenorrhea score, non-menstrual pelvic pain score, and dyspareunia score. Overall, 36 RCTs were included in this study (patients no. = 7942). Dienogest (0.94), combined hormonal contraceptives (CHCs) (0.782), and elagolix (0.38) were the highest-ranked interventions for reducing the severity of pelvic pain at three months, while at six months, gonadotropin-releasing hormone (GnRH) analogues (0.75), levonorgestrel-releasing intrauterine system (LNG-IUS) (0.73), and dienogest (0.65) were linked to more reduction in pelvic pain. The ranking p-score showed that GnRH analogues was the highest-ranked treatment for reducing dysmenorrhea at 3 months (1.00), while CHCs were the highest-ranked treatment at 6 months (0.97), followed by GnRH analogues (0.89). GnRH analogues (0.63) and elagolix (0.54) at three months while desogestrel (0.94) and CHCs (0.91) at six months were the highest-ranked treatment to reduce non-menstrual pelvic pain. GnRH analogues and elagolix were the highest-ranked pharmacologic therapies for reducing dyspareunia. In conclusion, CHCs, GnRH analogues, progesterone, and elagolix were the best approaches in reducing the pain of endometriosis.

Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.

Melanoma stem cells (MSCs) are characterized by their unique cell surface proteins and aberrant signaling pathways. These stemness properties are either in a causal or consequential relationship to melanoma progression, treatment resistance and recurrence. The functional analysis of CD133+ and CD133- cells in vitro and in vivo revealed that melanoma progression and treatment resistance are the consequences of CD133 signal to PI3K pathway. CD133 signal to PI3K pathway drives two downstream pathways, the PI3K/Akt/MDM2 and the PI3K/Akt/MKP-1 pathways. Activation of PI3K/Akt/MDM2 pathway results in the destabilization of p53 protein, while the activation of PI3K/Akt/MKP-1 pathway results in the inhibition of mitogen-activated protein kinases (MAPKs) JNK and p38. Activation of both pathways leads to the inhibition of fotemustine-induced apoptosis. Thus, the disruption of CD133 signal to PI3K pathway is essential to overcome Melanoma resistance to fotemustine. The pre-clinical verification of in vitro data using xenograft mouse model of MSCs confirmed the clinical relevance of CD133 signal as a therapeutic target for melanoma treatment. In conclusion, our study provides an insight into the mechanisms regulating MSCs growth and chemo-resistance and suggested a clinically relevant approach for melanoma treatment.