Selenium Nanoparticles Modulate Steroidogenesis-Related Genes and Improve Ovarian Functions via Regulating Androgen Receptors Expression in Polycystic Ovary Syndrome Rat Model.

Polycystic ovary syndrome (PCOS) occurs during the reproductive period in women and is characterized by reproductive, endocrine, and metabolic disorders. Androgen plays a decisive role in its pathogenesis due to the interaction between hyperandrogenism and insulin resistance, which might be improved by selenium nanoparticles (SeNPs). The present study aimed to clarify the effect of SeNPs on androgen synthesis and action in the PCOS model and the resulting effect on ovarian function. Fifty-five 7-week-old female albino rats (90-105 g) were divided equally into five groups: control (C), fed a standard diet for 11 weeks; high-fat diet (HFD) group, fed HFD for 11 weeks; HFD and letrozole (L) (HFD + L), fed HFD for 11 weeks and administrated orally with L, at a daily dose of 1 mg/kg BW, for three weeks from the 7th to 9th week of the trial; HFD + L + 0.1SeNPs and HFD + L + 0.2SeNPs groups, treated the same as HFD + L group and orally gavaged SeNPs at daily doses of 0.1 and 0.2 mg/kg BW, respectively, during the last 14 day of the experiment. Daily determination of estrous cycle was performed, and at the end of the experimental period, BMI, serum glucose, insulin, HOMA-IR, lipid profile, sex hormones, TNF-α, IL6, oxidative stress biomarkers, ovarian mRNA expression of different proteins and enzymes involved in steroidogenesis, pathological examination, and immunohistochemical staining for androgen receptor (AR) were evaluated. Treatment of SeNPs restored estrous cyclicity, decreased BMI, and insulin resistance, improved dyslipidemia, reduced serum testosterone, and improved ovarian histopathology in PCOS rats. Furthermore, the anti-inflammatory and antioxidant impacts of SeNPs were remarkably noticed. Administration of SeNPs decreased androgen synthesis and expression of ovarian AR protein by decreasing the mRNA expression of STAR, Cyp11A1, Cyp17A1, and HSD17B3 and increasing the expression of Cyp19α1. Conclusively, SeNPs decreased androgen synthesis and blocked the vicious circle initiated by excessive androgen secretion via decreased AR expression. Thus, it may effectively treat PCOS cases by eliminating its reproductive, endocrine, and metabolic dysfunctions.

Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals. METHODS: A comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4. RESULTS: We found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001). CONCLUSION: Cotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD: CRD42021257670 ).

Can Chemotherapy-Related Acute Care Visits Be Accurately Identified in Administrative Data?

PURPOSE: There is increasing interest in using administrative data to examine treatment-related complications that lead to emergency department (ED) visits or hospitalizations (H). The purpose of this study was to evaluate the reliability of billing codes for identifying chemotherapy-related acute care visits (CRVs) among women with early-stage breast cancer. MATERIALS AND METHODS: The cohort was identified by using deterministically linked health databases and consisted of women who were diagnosed with early-stage breast cancer who started adjuvant chemotherapy between 2007 and 2009 in Ontario, Canada. A random sample of 496 patient cases was chosen as the validation cohort. Sensitivity (SN) and specificity (SP) were calculated for three scenarios: chemotherapy-related ED visit, chemotherapy-related H, and febrile neutropenia (FN)-related visit. For FN-related visits, three definitions were considered: general, moderate, and strict. RESULTS: The administrative cohort consisted of 8,359 patients, 43.4% of whom had at least one ED or H, including 1,496 women who had multiple visits that resulted in 6,293 unique visits. Of these, 73.1% were considered CRVs. The algorithm performed well in identifying CRVs that included H either from ED (SN, 90%; SP, 100%) or directly from home (SN, 91%; SP, 93%), but less well for ED visits that did not result in H (SN, 65%; SP, 80%). Depending on which FN algorithm was used, 4.8% to 24% of visits were considered related. The moderate FN algorithm provided the best tradeoff between SN (69% to 97%) and SP (83% to 98%). CONCLUSION: Administrative data can be valuable in evaluating chemotherapy-related serious events. Algorithm validation in other cohorts is needed.

Role of parasites among chronic diarrheic patients.

This work studied the role of parasitic infection among 85 chronic diarrheic patients in Delta region and cross-matched 20 normal controls. They were subjected to thorough history taking and clinical examination and stool examination by direct smear, formol-ether concentration, simple sedimentation, simple floatation and Kato-katz thick smear. Questionnaire sheet was obtained for each case included personal history, complaint, present as well as past history and family history. The results showed that 67.1% of patients suffered from parasites versus 20% in controls. They included giardiasis mixed with hymenolepiasis nana, ameobiasis, ascariaisis, S. mansoni, heterophyiasis, B. homninis, Taenia spp and enterobiasis respectively. Single infection represented 54.2 %, while mixed ones were 12.9% of total chronic diarrhea cases and non parasitic causes were responsible for 32.9%. Mixed infection was common in A. lumbricoides with E. histolytica (18.18%) and H. nana with G. lambia (27.28%). The diarrhea duration was longer in mixed infections (3 months), E. histolytica (2 months) and H. nana (1.5 months). Commonest symptom other than diarrhea was abdominal pain mainly in mixed parasitosis. Parasitic diarrhea was more common in males than females (1.28: 1). Chronic parasitic diarrhea was most prevalent among low social class (49 or 57.6%) followed by very low social class (20 or 23.5%), middle social class (10 or 11.7%) and finally high social class (6 or 7.1%) with significant increase in low social class as compared to high one, and most prevalent among positive cases in rural area than in urban area.

Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation.

Massive blood transfusion (MBT) remains a serious and common occurrence in liver transplantation surgery. This retrospective cohort study was undertaken to identify preoperative predictors of MBT and to develop a risk index for MBT in liver transplantation. Data were retrospectively collected on all liver transplantations carried out at a single institution between January 1998 and March 2004. Multivariable logistic regression analysis was used to identify independent predictor variables of MBT, defined as >/=6 units of red blood cell concentrate (RBC) in the first 24 hours of surgery. The model was internally validated by bootstrapping. Of the 460 liver transplant recipients, 193 (42%) received >/=6 units of RBC within 24 hours of surgery. Unadjusted analyses identified 12 preoperative predictors of MBT: age, height, gender, repeat transplantation, etiology of liver failure, and preoperative laboratory values (hemoglobin concentration, platelet count, international normalized ratio for prothrombin activity [INR], albumin, total bilirubin, and creatinine). In multivariable logistic regression, 7 independent predictors of MBT were identified: age (>40 years), hemoglobin concentration (2.0), platelet count (/=110 micromol/L for female subjects and >/=120 micromol/L for male subjects), albumin (< 28 g/L), and repeat transplantation. The area under the receiver-operating characteristic curve (ROC) for the model was 0.82. By using the regression beta coefficients to derive weights for each of these predictors, a risk index was developed that assigned each patient a score between 0 and 8. The ROC for this risk index was 0.79. MBT in liver transplantation surgery can be accurately predicted by 7 readily available preoperative predictors.

Prognostic value of postoperative proteinuria in cardiac surgery: a pilot study.

BACKGROUND: Proteinuria is a non-specific marker of inflammation that may reflect the glomerular component of systemic capillary leak. The objective of this pilot study was to determine if postoperative proteinuria is associated with adverse outcomes following cardiac surgery with cardiopulmonary bypass. METHODS: Eligible patients were individuals undergoing cardiac surgery with cardiopulmonary bypass who did not have severe pre-existing renal dysfunction. Urine was collected after induction of anesthesia (baseline) and two to four hours after arrival to the intensive care unit (ICU). Proteinuria was measured as random protein creatinine ratio in g.mol(-1). Adverse events were defined a priori as prolonged ICU stay (> or = 90th percentile) and organ dysfunction. The relationship between proteinuria and adverse events was assessed by bivariate (Chi-square or Fisher's exact tests) and multivariable (multiple logistic regression) analyses. RESULTS: The study included 197 (of 243 eligible) patients. Postoperative proteinuria (protein creatinine ratio > or = 30 g.mol(-1)) was associated with prolonged (> or = four days) ICU stay [odds ratio (OR) 7.0; 95% confidence interval (CI) 2.8-17.1] and organ dysfunction (OR 3.9; CI 1.9-8.1). After adjustment for confounders, proteinuria was associated with a 3.2-fold increase in the odds of both prolonged ICU stay (CI 1.1-9.7) and organ dysfunction (CI 1.4-7.0). CONCLUSIONS: Proteinuria two to four hours after cardiac surgery with cardiopulmonary bypass may be a useful marker for systemic capillary leak and adverse postoperative events. Large prospective studies are needed to confirm these findings.

A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass may result in excessive fibrinolysis and platelet (PLT) dysfunction, resulting in impaired hemostasis and excessive blood loss. Prophylactic use of the antifibrinolytic drugs aprotinin and tranexamic acid is thought to prevent these hemostatic defects. Their relative clinical utility and safety in high-transfusion-risk cardiac surgery, however, is not known. STUDY DESIGN AND METHODS: Using propensity scores, 449 patients who received aprotinin for high-transfusion-risk cardiac surgery were matched to 449 patients who received tranexamic acid from a pool of 10,870 consecutive patients who underwent cardiac surgery at a single center, 586 of whom received aprotinin and the remainder of whom received tranexamic acid. RESULTS: The two matched groups were well balanced in terms of measured perioperative variables. Blood product transfusion rates were similar in the aprotinin and tranexamic acid groups: red blood cells, 79 percent versus 76 percent (p = 0.3); PLTs, 56 percent versus 50 percent (p = 0.06); and plasma, 66 percent versus 61 percent (p = 0.1). Adverse events rates were comparable in the two groups, except for renal dysfunction (defined as a greater than 50% increase in creatinine concentration during the first postoperative week to >100 micromol/L in women and >110 micromol/L in men or a new requirement for dialysis support), which occurred in 24 percent (107/449) of aprotinin patients and 17 percent (75/449) of tranexamic acid patients (p = 0.01). CONCLUSIONS: Aprotinin and tranexamic acid have similar hemostatic effectiveness in high-transfusion-risk cardiac surgery. Within the confines of propensity score matching, our results suggest that aprotinin may be associated with renal dysfunction.

Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia.

PURPOSE: To determine if early recovery from severe post-operative anemia is accelerated by iv iron therapy alone or in combination with recombinant erythropoietin (EPO). METHODS: In this double-blinded, placebo-controlled randomized study, consenting adult patients without preoperative anemia whose hemoglobin concentration (Hb) was 70 to 90 g x L(-1) on the first day after cardiac or orthopedic surgery (POD 1) were assigned to one of three groups: control, iv iron alone (200 mg of iron sucrose on POD 1, 2, and 3) or in combination with EPO (600 U x kg(-1) on POD 1 and 3). The primary outcome was increase in Hb (adjusted for red blood cell transfusions) from POD 1 to 7. Analysis was by intention-to-treat in patients for whom the primary outcome was available. Group effect was analyzed by the ANOVA test, and between-group differences were specified with a Duncan multiple-range test. RESULTS: The primary outcome was available in 31 of 38 randomized patients. The average POD 1 Hb was 84 +/- 4 g x L(-1). There were no between-group differences in outcomes except for higher reticulocyte counts on POD-7 in the combination group. The average adjusted one-week increases in Hb were 7 +/- 8 g x L(-1) in the control group (n = 10), 9 +/- 9 g x L(-1) in the iv iron group (n = 11), and 10 +/- 14 g x L(-1) in the combination group (n = 10). The average adjusted six-week increases in Hb were 37 +/- 14 g x L(-1) in the control group, 40 +/- 7 g x L(-1) in the iv iron group, and 45 +/- 12 g x L(-1) in the combination group. CONCLUSION: Early postoperative treatment with iv iron alone or in combination with EPO does not appear to accelerate early recovery from postoperative anemia.

Erythropoietin is an effective clinical modality for reducing RBC transfusion in joint surgery.

PURPOSE: Efficacy trials of preoperative erythropoietin therapy (PET) recommend a dosing schedule that cannot always be adhered to in everyday clinical practice. Consequently, we instituted a flexible dosing schedule and routinely offered it to anemic patients [hemoglobin (Hb)] < or = 130 g x L(-1)) undergoing total joint arthroplasty (TJA). The purpose of this observational, cohort study was to assess the effectiveness of this practice in reducing red blood cell (RBC) transfusion. METHODS: After obtaining Institutional Ethics Board approval, data were collected prospectively on all patients who underwent TJA at our institution from July 1999 to June 2003. Patients with baseline Hb < or = 130 g x L(-1) were offered PET as follows: one to three sc injections (20,000 IU for those < or = 70 kg, and 40,000 IU for those > 70 kg) every three to seven days before surgery. Since treatment was not randomly assigned, multivariable logistic regression analysis and propensity score case-control matching were used to adjust for baseline differences in patient demographics and perioperative risk factors for RBC transfusion. The adjusted relationship between PET and RBC transfusion was then determined. RESULTS: Of the 1,782 patients that underwent TJA during the study period, 770 (47.9%) had a Hb < 130 g x L(-1). Of these patients, 214 received PET and their RBC transfusion rate was 16.4%, whereas the transfusion rate was 56.1% in those who did not receive PET (P < 0.0001). The adjusted odds ratio of RBC transfusion with PET was 0.33 (95% confidence interval = 0.21-0.49). CONCLUSION: PET, used as part of routine clinical practice, is an effective blood conservation modality.

Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score-matched case-control analysis.

BACKGROUND: Cardiac surgery is occasionally complicated by massive blood loss that is refractory to standard hemostatic interventions. Recombinant factor VIIa (rF-VIIa) is being increasingly used as rescue therapy in such cases, but little information is available on its safety and efficacy for this indication. STUDY DESIGN AND METHODS: The outcomes of the first 51 cardiac surgery patients who received rF-VIIa for intractable blood loss (from November 2002 to February 2004) at a single institution according to a standardized clinical guideline were compared to 51 matched control patients, with the control patients identified from a large database and matched based on the propensity for massive blood loss. RESULTS: Blood loss and blood product usage were significantly decreased after 2.4 to 4.8 mg of rF-VIIa. In those treated after sternal closure (n = 32), there was a significant reduction in blood loss from the hour before to the hour after treatment: 100 (70, 285) mL (median [25th, 75th percentiles]; p < 0.0001). Except for a slower postoperative recovery and higher incidence of acute renal dysfunction, the adverse event rates were similar between the rF-VIIa-treated patients and their matched controls. CONCLUSIONS: These results suggest that rF-VIIa may be an effective rescue therapy for patients with intractable hemorrhage after cardiac surgery. A clinically important risk of stroke or other major thrombotic complications could not be ruled out by our study. Controlled clinical trials with adequate power to detect the impact of rF-VIIa therapy on morbidity and mortality therefore are necessary before one can recommend its routine use in patients undergoing cardiac surgery who have excessive bleeding.

The independent association of massive blood loss with mortality in cardiac surgery.

BACKGROUND: Although the association between massive perioperative blood loss (MBL) and adverse outcomes is well recognized, it is unclear whether MBL is an independent risk factor or, instead, simply a marker for other adverse events or severity of illness. The objective of this cohort study was to quantify the independent association of MBL in cardiac surgery with all-cause in-hospital mortality. STUDY DESIGN AND METHODS: Data were prospectively collected on consecutive patients who underwent cardiac surgery with cardiopulmonary bypass at a quaternary-care academic center from 1999 to 2003. The number of red blood cell (RBC) units transfused within 1 day of surgery was used as a surrogate measure of perioperative blood loss. Receiver-operating characteristic curve analyses were employed to identify the most appropriate cutoff for defining MBL. The independent association of MBL with mortality was determined with multivariable logistic regression analyses. Bootstrapping and sensitivity analyses were used to confirm the validity of the results. RESULTS: MBL was defined as receiving at least 5 units of RBCs within 1 day of surgery. Of 9215 patients analyzed, 1.8 percent (n = 169) died and 9.7 percent (n = 890) had MBL. After adjusting for multiple potential confounders (including perioperative adverse events), MBL was associated with an 8.1-fold (95% confidence interval, 3.9-17.0) increase in the odds of death. This risk estimate was stable across different modeling conditions as well as in bootstrap sampling. CONCLUSION: MBL after cardiac surgery has a strong, independent association with in-hospital mortality.