Zinc, copper, sirtuin 1 concentration, and glucose metabolism parameters in the blood of women with polycystic ovary syndrome.

The aim of this study was to assess concentration of zinc (Zn), copper (Cu), and sirtuin 1 (SIRT1) in serum of women with polycystic ovary syndrome (PCOS) and their relationships with glucose metabolism parameters. The study included 76 women with PCOS aged between 17 and 39 years old. The blood was collected according to the routine procedure during the follicular phase. Zn and Cu concentrations were performed by flame atomic absorption spectrometry (FAAS). Glucose concentration was estimated by colorimetric methods. Insulin (INs) concentration was determined by enzyme-linked immunosorbent assay. SIRT1 concentration was determined using commercial test. We found higher Cu concentration and Cu/Zn value in the serum of women with PCOS with overweight/obesity. Early stage of insulin resistance (IR) in the group of women with PCOS affected on higher Cu concentration and Cu/Zn value. However, increased value of body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance (HOMA-IR) was not associated with changes in Zn and SIRT1 concentration. Further disturbances in glucose metabolic parameters in the blood of women with PCOS were intensified by overweight/obesity and IR. Overweight/obesity and IR in the women with PCOS increase disorders in Cu homeostasis and glucose metabolism parameters.

Impact of genetic and clinical factors on dose requirements and quality of anticoagulation therapy in Polish patients receiving acenocoumarol: dosing calculation algorithm.

BACKGROUND: Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves. OBJECTIVE: The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm. MATERIALS AND METHODS: We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors. RESULTS: We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04). CONCLUSION: Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

Right ventricular-pulmonary artery coupling in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension occurs in a proportion of patients with prior acute pulmonary embolism and is characterised by breathlessness, persistently raised pulmonary pressures and right heart failure. Surgical pulmonary endarterectomy (PEA) offers significant prognostic and symptomatic benefits for patients with proximal disease distribution. For those with inoperable disease, management options include balloon pulmonary angioplasty (BPA) and medical therapy. Current clinical practice relies on the evaluation of pulmonary haemodynamics to assess disease severity, timing of and response to treatment. However, pulmonary haemodynamics correlate poorly with patient symptoms, which are influenced by right ventricular tolerance of the increased afterload. How best to manage symptomatic patients with chronic thromboembolic pulmonary disease (CTEPD) in the absence of pulmonary hypertension is not resolved.Right ventricular-pulmonary artery coupling (RV-PAC) describes the energy transfer within the whole cardiopulmonary unit. Thus, it can identify the earliest signs of decompensation even before pulmonary hypertension is overt. Invasive measurement of coupling using pressure volume loop technology is well established in research settings. The development of efficient and less invasive measurement methods has revived interest in coupling as a viable clinical tool. Significant improvement in RV-PAC has been demonstrated after both PEA and BPA. Further studies are required to understand its clinical utility and prognostic value, in particular, its potential to guide management in patients with CTEPD. Finally, given the reported differences in coupling between sexes in pulmonary arterial hypertension, further work is required to understand the applicability of proposed thresholds for decoupling in therapeutic decision making.

The cut-off value for HOMA-IR discriminating the insulin resistance based on the SHBG level in women with polycystic ovary syndrome.

Introduction: The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) level in women with polycystic ovary syndrome (PCOS). Materials and methods: Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics. Results: Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 [area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%]. Conclusions: Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).

Balloon pulmonary angioplasty outcomes in patients previously treated by pulmonary endarterectomy surgery are inferior to those of inoperable patients.

Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post-PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA-89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6-minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)-quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (-27.9 ± 20.2% vs. -13.9 ± 23.9%, p < 0.05) and ΔmPAP (-17.1 ± 14.4% vs. -8.5 ± 18.0%, p < 0.05). There was a negative correlation between pre-BPA PVR and TTTL (r = -0.47, p < 0.05) which persisted post-BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post-BPA in PP patients. BPA response was not related to TTTL terciles or CTPA-quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.

Prediction of Insulin Resistance and Impaired Fasting Glucose Based on Sex Hormone-Binding Globulin (SHBG) Levels in Polycystic Ovary Syndrome.

OBJECTIVE: Decreased synthesis of sex hormone-binding globulin (SHBG) related to hyperinsulinemia is one of the disturbances characteristic of polycystic ovary syndrome (PCOS). Hyperinsulinemia is a compensatory mechanism for liver insulin resistance (IR); thus, SHBG may be considered as a surrogate marker of liver IR. Therefore, this study aimed to assess the prediction of IR and impaired fasting glucose (IFG) based on SHBG levels in women with PCOS. METHODS: This analysis included data retrieved from medical records of 854 patients with PCOS hospitalized in the Gynecological Endocrinology Clinic from 2012 to 2019. Data including anthropometric parameters, fasting plasma glucose, insulin, and SHBG levels were analyzed. BMI and HOMA-IR were calculated with standard formulas. RESULTS: IFG and IR assessed based on HOMA-IR values > 2.0 were found in 19.5% and 47.8% of the study group, respectively. Empirical optimal cutoff values for SHBG levels were ≤41.5 nmol/L typical for IR (AUC 0.711, sensitivity 61.1%, specificity 71.6%, positive predictive value (PPV) 70.7%, and negative predictive value (NPV) 62.1%). The probability of insulin resistance occurrence for SHBG concentration 26.1 nmol/L (the lower normal range) was 61.6% (95% CI: 57.4%-65.8%). The SHBG concentration of 36.4 nmol/L and 8.1 nmol/L was related to a 10% and 20% probability of IFG, respectively. CONCLUSION: In conclusion, this is the first study estimating the probability of liver IR and IFG occurrence based on SHBG levels in women with PCOS. Despite the low sensitivity, SHBG level below 42 nmol/L should cause closer monitoring for the fatty liver and prediabetes.

Insertion of a biventricular assist device.

This video tutorial demonstrates the insertion of a temporary biventricular assist device as a bridge to a heart transplant in a patient with end-stage heart failure with decompensation and increasing pulmonary pressure . This technique utilizes cardiopulmonary bypass to maintain hemodynamic stability throughout the procedure. Transesophageal echocardiography is used to guide the correct positioning of the ventricular cannulae. The cannulation sites include the right ventricle and the pulmonary artery for the right ventricular assist device and the left ventricular apex and the ascending aorta for the left ventricular assist device. The patient is weaned off cardiopulmonary bypass as the biventricular assist device flows are increased to the desired level. Following chest closure, the patient can be ambulatory with the device in situ.

Lead-Sparing Tricuspid Valve Repair Damaged by Pacemaker Lead.

Permanent pacemaker lead may damage the tricuspid valve in various ways, causing severe tricuspid valve regurgitation. The perforation of posterior papillary muscle is an uncommon complication caused by the lead. We describe a lead-sparing tricuspid valve repair in which the lead extraction was not an option. The papillary muscle containing the lead was fully mobilized to release the adherent leaflets. The repair was completed by commissuroplasty as well as ring annuloplasty, leaving the lead inside the implanted ring.

Cardiopulmonary Exercise Testing and Prognosis in Hypertrophic Cardiomyopathy.

BACKGROUND: Exercise testing is performed in patients with hypertrophic cardiomyopathy to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown. METHODS AND RESULTS: Between 1998 and 2010, 1898 patients (age 47±15 years, range 16-86 years; 67% male) with hypertrophic cardiomyopathy underwent cardiopulmonary exercise testing. A total of 178 (9.4%) patients reached the primary end point of all-cause mortality or heart transplant (death/transplant) during a median follow-up of 5.6 years (interquartile range 2.6-8.9), giving an annual event rate of 1.6% per person year. Peak oxygen consumption (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.77-0.88, P<0.001), ventilatory efficiency (adjusted HR 1.10, 95% CI 1.00-1.22, P=0.049), and ventilatory anaerobic threshold (adjusted HR 0.82, 95% CI 0.70-0.96, P=0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, nonsustained ventricular tachycardia, and ejection fraction. The overall adjusted death/transplant estimates for patients in the lowest quartile with peak oxygen consumption ≤15.3 mL/kg/min were 14% at 5 years and 31% at 10 years. Peak oxygen consumption (HR 0.81, 95% CI 0.77-0.86, P<0.01) and ventilation to carbon dioxide production (HR 1.10, 95% CI 1.08-1.13, P<0.001) were predictors of death because of heart failure or transplantation but not sudden cardiac death or implantable cardioverter defibrillator shocks. CONCLUSIONS: Cardiopulmonary exercise testing provides prognostic information in patients with hypertrophic cardiomyopathy. Submaximal exercise parameters, such as ventilatory efficiency and anaerobic threshold, measured alone or in combination with peak oxygen consumption, predict death from heart failure.

Peptide Vaccine Therapy in Colorectal Cancer.

Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer) in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

Patient education and quality of home-based rehabilitation in patients older than 60 years after acute myocardial infarction.

PURPOSE: Because only one-third of eligible patients participate in formal cardiac rehabilitation, home-based programs constitute a suitable alternative. We examined effectiveness of a minimal educational intervention on patient fitness and activity levels through the use of simple motivational tools including verbal encouragement and the provision of a booklet containing exercise guidelines and exercise diary. METHODS: We enrolled 186 patients (age, 60 ­ 78 years; mean age, 69 years; 140 men) who were admitted to the outpatient clinic of Warsaw Institute of Cardiology in 2007-2009 after acute myocardial infarction. Of these, 61.3% had coronary angioplasty with stenting and 30.7% had coronary artery bypass. Patients were randomly assigned into an intervention group receiving minimal educational intervention or control. At baseline and 3 months, assessment was made of cardiopulmonary fitness and autonomic tone with exercise testing. Leisure-time physical activity and atherosclerosis risk factors were assessed at baseline and after 3 and 12 months. RESULTS: At baseline, exercise test results and leisure-time activity levels were not significantly different between groups. After 3 months, we noted statistically significant differences in exercise test responses between the intervention group versus control: peak workload 57.3 ± 2.3 versus 47.2 ± 2.2 kJ (P < .04) and heart rate recovery 26.5 3.3 versus 23.7 4.2 bpm (P < .001). Leisure-time activity was greater in the intervention group than in control, 3.9 versus 2.3 h/wk (P < .001). Improvement in atherosclerosis risk factors during the course of the study was similar between groups. CONCLUSION: Minimal educational intervention is an effective and safe form of promoting physical activity in older patients after myocardial infarction.

Laparoscopic treatment of Cushing's syndrome in a woman in late pregnancy - a case presentation.

Hypercortisolaemia during pregnancy constitutes a serious threat to life of the mother and fetus and may be associated with adrenocortical carcinoma. The objective of this study is to present the usefulness of laparoscopic procedures in treating adrenal tumours in such cases. One 21-year-old woman, 24 weeks pregnant, with hypertension and Cushing's syndrome due to a left adrenal tumour, underwent laparoscopic adrenalectomy followed by hydrocortisone replacement. Spontaneous delivery occurred at the 37/38(th) week of gestation. At 3 months postpartum the function of the remaining adrenal gland was found to be normal. Similarly, imaging tests, abdominal CT scan and chest X-ray revealed no abnormalities. Pregnancy is not a contraindication for performing complicated laparoscopic procedures unless they are planned in advance and done by an experienced team.