Glycemic variability leads to higher levels of auto-oxidized oxysterol species in patients with type 1 diabetes mellitus.

PURPOSE: Hyperglycemia and glycemic variability (GV) are associated with oxidative stress in patients with diabetes mellitus (DM). Oxysterol species, produced by the non-enzymatic oxidation of cholesterol, are potential biomarkers of oxidative stress. This study examined the relationship between auto-oxidized oxysterols and GV in patients with type 1 DM. METHODS: Thirty patients with type 1 DM using a continuous subcutaneous insulin infusion pump therapy and a healthy control group (n = 30) were included in this prospective study. A Continuous Glucose Monitoring System device was applied for 72 h. Blood samples were taken for oxysterols produced by non-enzymatic oxidation [7-ketocholesterol (7-KC) and cholestane-3ß, 5α, 6ß-triol (Chol-Triol)] levels at 72 h. Short-term glycemic variability parameters, mean amplitude of glycemic excursions (MAGE), the standard deviation of glucose measurements (Glucose-SD), and mean of daily differences (MODD) were calculated with continuous glucose monitoring data. HbA1c was used to evaluate glycemic control and HbA1c-SD (the SD of HbA1c over the past year) for long-term glycemic variability. RESULTS: 7-KC and Chol-triol levels were significantly higher in the study group than in the control group. Strong positive correlations were found between 7-KC with MAGE(24-48 h) and Glucose-SD(24-48 h). 7-KC was positively correlated with MAGE(0-72 h) and Glucose-SD(0-72 h). No significant correlation was found between HbA1c and HbA1c -SD with oxysterol levels. The regression models showed that SD(24-48 h) and MAGE(24-48 h) predicted 7-KC levels while HbA1c did not. CONCLUSIONS: Glycemic variability leads to higher levels of auto-oxidized oxysterol species in patients with type 1 DM independent of long-term glycemic control.

No association of anti-osteoporosis drugs with COVID-19-related outcomes in women: a nationwide cohort study.

This study was performed to evaluate whether the use of drugs in the treatment of osteoporosis in women is associated with COVID-19 outcomes. The results showed that the risk of hospitalization, intensive care unit admission, and mortality was not altered in individuals taking anti-osteoporosis drugs, suggesting no safety issues during a COVID-19 infection. INTRODUCTION: Whether patients with COVID-19 receiving anti-osteoporosis drugs have lower risk of worse outcomes has not been reported yet. The aim of this study was to evaluate the association of anti-osteoporosis drug use with COVID-19 outcomes in women. METHODS: Data obtained from a nationwide, multicenter, retrospective cohort of patients diagnosed with COVID-19 from March 11th to May 30th, 2020 was retrieved from the Turkish Ministry of Health Database. Women 50 years or older with confirmed COVID-19 who were receiving anti-osteoporosis drugs were compared with a 1:1 propensity score-matched COVID-19 positive women who were not receiving these drugs. The primary outcomes were hospitalization, ICU (intensive care unit) admission, and mortality. RESULTS: A total of 1997 women on anti-osteoporosis drugs and 1997 control patients were analyzed. In the treatment group, 1787 (89.5%) women were receiving bisphosphonates, 197 (9.9%) denosumab, and 17 (0.9%) teriparatide for the last 12 months. Hospitalization and mortality rates were similar between the treatment and control groups. ICU admission rate was lower in the treatment group (23.0% vs 27.0%, p = 0.013). However, multivariate analysis showed that anti-osteoporosis drug use was not an independent associate of any outcome. Hospitalization, ICU admission, and mortality rates were similar among bisphosphonate, denosumab, or teriparatide users. CONCLUSION: Results of this nationwide study showed that preexisting use of anti-osteoporosis drugs in women did not alter the COVID-19-related risk of hospitalization, ICU admission, and mortality. These results do not suggest discontinuation of these drugs during a COVID-19 infection.

Impact of proactive low-molecular weight heparin therapy on outcomes in COVID-1.

OBJECTIVES: Low molecular weight heparin (LMWH) may provide beneficial effects on outcomes of COVID-19. We aimed to examine the impact of LMWH treatment on clinical outcomes (duration of hospitalization, admission to intensive care unit, the requirement for mechanical ventilation, and death) of COVID-19 patients with normal D-dimer levels at admission. BACKGROUND: Coronavirus disease-2019 (COVID-19) predisposes patients to arterial and venous thrombosis. METHODS: In this retrospective, multicentre and observational study we analysed the data of 308 confirmed COVID-19 patients with normal D-dimer levels at initial admission. After propensity score matching (PSM) patients were grouped; Group 1; patients who received LMWH with D-dimer ≤0.5 mg/L, Group 2; patients who received LMWH after D-dimer levels exceeded 0.5 mg/L, and Group 3; patients who did not receive LMWH. RESULTS: After PSM, each group comprised 40 patients. The patients in Group1 had the best clinical outcomes compared to the other groups. Group 3 had the worst clinical outcomes (p<0.005). The benefit of LMWH increased with early prophylactic therapy especially when started while the D-dimer levels were ≤0.5 mg/L. CONCLUSION: Our results strongly suggest that proactive LMWH therapy improves clinical outcomes in hospitalized COVID-19 patients even with normal D-dimer levels (≤ 0.5 mg/L) (Tab. 3, Fig. 2, Ref. 34).

Genetic Alterations in Differentiated Thyroid Cancer Patients with Acromegaly.

AIM: Acromegaly is associated with increased thyroid cancer risk. We aimed to analyze the frequency of point mutations of BRAF and RAS genes, and RET/PTC, PAX8/PPARγ gene rearrangements in patients with acromegaly having differentiated thyroid cancers (DTC) and their relation with clinical and histological features. MATERIALS AND METHODS: 14 acromegalic patients (8 male, 6 female) with DTC were included. BRAF V600E and NRAS codon 61 point mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ gene rearrangements were analyzed in thyroidectomy specimens. We selected 14 non-acromegalic patients with DTC as a control group. RESULTS: 2 patients (14.3%) were detected to have positive BRAF V600E and 3 patients (21.4%) were detected to have NRAS codon 61 mutation. NRAS codon 61 was the most frequent genetic alteration. Patients with positive mutation had aggressive histologic features more frequently than patients without mutations. Comparison of the acromegalic and non-acromegalic patients with DTC revealed that BRAF V600E mutation was more frequent in non-acromegalic patients with DTC (14.2% vs. 64.3%, p=0.02). RET/PTC 1/ 3, PAX8/PPARγ gene rearrangements were not detected in any patient. None of the patients including the patients with positive point mutations had recurrence, and local and/or distant metastasis. CONCLUSION: NRAS codon 61 is the most frequent genetic alteration in this acromegaly series with DTC. Since acromegalic patients have lower prevalance of BRAF V600E mutation, BRAF V600E mutation may not be a causative factor in development of DTC in acromegaly. Despite the relation of BRAF V600E and NRAS codon 61 mutations with aggresive histopathologic features, their impact on tumor prognosis remains to be defined in acromegaly in further studies.

Changing clinical characteristics of thyroid carcinoma at a single center from Turkey: before and after the Chernobyl disaster.

AIM: The aim of the study was to determine the possible role of Chernobyl disaster on changing clinical features of thyroid carcinoma (TC) in a moderately iodine deficient region. METHODS: We retrospectively reviewed demographical features, presenting symptoms, tumor size, histopathological diagnosis and distant metastates in 160 patients with TC diagnosed between 1990-2007. We compared our findings with the database of 118 TC patients diagnosed between 1970-1990 in the same center. RESULTS: There were 123 female (76.9%) and 37 (23.1%) male patients with a mean age of 44.89±14.84. Sex distribution and age at diagnosis were similar between 1970-1990 and 1990-2007 (P=0.77 and P=0.42, respectively). Histopathological diagnoses were papillary in 114 (73.1%), follicular in 22 (14.1%), medullary in 9 (5.8%), hurthle cell in 7 (4.5%) and anaplastic TC in 4 (2.6%) patients. We observed a marked increase in papillary TC (P<0.001) and marked decreases in follicular (P<0.001) and anaplastic TC (P=0.01) compared to the period between 1970-1990. Thyroid microcarcinomas accounted for 27.1% and 37.1% of carcinomas in 1970-1990 and 1990-2007, respectively (P<0.05). CONCLUSION: We showed that incidence of papillary TC increased and incidences of follicular and anaplastic TC decreased in a period that might be affected by Chernobyl fallout in a moderately iodine deficient area. Presenting symptoms of TC have changed and microcarcinomas are diagnosed more frequently compared to past. Further large scale trials are needed to find out whether Chernobyl disaster has role on changing characteristic of TC in countries that are not very near but also not very far from Chernobyl such as Turkey.

Verapamil stimulation test in hyperprolactinemia: loss of prolactin response in anatomic or functional stalk effect.

AIM: Verapamil stimulation test was previously investigated as a tool for differential diagnosis of hyperprolactinemia, but with conflicting results. Macroprolactinemia was never considered in those previous studies. Here, we aimed to re-investigate the diagnostic value of verapamil in a population who were all screened for macroprolactinemia. Prolactin responses to verapamil in 65 female patients (age: 29.9 +/- 8.1 years) with hyperprolactinemia were tested in a descriptive, matched case-control study. METHODS: Verapamil 80 mg, p.o. was administered, and then PRL levels were measured at 8th and 16th hours, by immunometric chemiluminescence. Verapamil responsiveness was determined by peak percent change in basal prolactin levels (PRL). RESULTS: Verapamil significantly increased PRL levels in healthy controls (N. 8, PRL: 183%), macroprolactinoma (N. 8, PRL: 7%), microprolactinoma (N. 19, PRL: 21%), macroprolactinemia (N. 23, PRL: 126%), but not in pseudoprolactinoma (N. 8, PRL: 0.8%), and risperidone-induced hyperprolactinemia (N. 7, PRL: 3%). ROC curve analysis revealed that unresponsiveness to verapamil defined as PRL <7%, discriminated anatomical or functional stalk effect (sensitivity: 74%, specificity: 73%, AUC: 0.855+/-0.04, P <0.001, CI: 0.768-0.942) associated with pseudoprolactinoma or risperidone-induced hyperprolactinemia, respectively. CONCLUSION: Verapamil responsiveness is not a reliable finding for the differential diagnosis of hyperprolactinemia. However, verapamil unresponsiveness discriminates stalk effect (i.e., anatomically or functionally inhibited dopaminergic tonus) from other causes of hyperprolactinemia with varying degrees of responsiveness.

Simultaneous triple organ specific autoantibody profiling in adult patients with type 1 diabetes mellitus and their first-degree relatives.

AIMS: We aimed to document prevalence and clinical presentations of seropositivities for glutamate decarboxylase (GAD)-antibody, celiac's disease (CD) and autoimmune thyroiditis (AIT) in adult patients with type 1 diabetes mellitus (T1DM), and their first-degree relatives. METHODS: Sixty-five patients with T1DM, 124 first-degree relatives and 65 healthy controls were screened for GAD-antibody, anti-thyroid peroxidase (ATPO), anti-thyroid stimulating hormone receptor (TSHR), anti-tissue transglutaminase and anti-gliadin antibodies in a matched case-control study. RESULTS: Prevalence of more than one seropositivity for CD-associated antibodies in T1DM-group is 6.0 times increased, compared with controls (p < 0.05). ATPO seropositivity is 5.3 times increased in T1DM group (p < 0.05), but TSHR antibody is comparable with controls (p > 0.05). Seropositivities for T1DM, AIT and CD are 4.3, 1.9 and 2.4 times more prevalent among first-degree relatives respectively, compared with controls (p < 0.05). Pathologically confirmed cases with CD among first-degree relatives were all identified at screening. In contrast, all of pathologically confirmed cases with CD in T1DM group, were either previously diagnosed or symptomatic at time of screening. In the group of patients with T1DM, 31% of seropositive cases for anti-ATPO were clinically latent for AIT, and 74% of ATPO (+) cases were identified at current screening study. Sixty-four per cent of ATPO (+) first-degree relatives were clinically latent for AIT, and 54% were identified at screening. CONCLUSION: Type 1 diabetes mellitus, CD and AIT represent a significant overlap in an adult population with already-diagnosed T1DM and their first-degree relatives. With regard to clinical presentations, CD was less likely to be clinically silent than AIT among patients with T1DM.

Endovascular stent-graft treatment of type A dissection: case report and review of literature.

We report a successful endovascular stent-graft treatment of a patient with type A dissection with primary entry tear at the ascending aorta. Simultaneous coronary stenting was performed. A literature review was performed and the possible use of endovascular treatment for ascending aortic dissections is discussed.

Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times.

The aim of the study is to investigate whether platelet activity is increased by hyperprolactinemia during pregnancy as reflected by beta-thromboglobulin level. Forty-eight healthy, pregnant, and 30 healthy, non-pregnant women were investigated with respect to platelet count, collagen/ADP and collagen/epinephrine closure times, beta-thromboglobulin and prolactin levels. The comparison of the variables between the two groups was made by Mann-Whitney U test. The correlation analyses were performed by Spearman's rank correlation test. Our results revealed that platelet counts, collagen/ADP and collagen/epinephrine closure times and beta-thromboglobulin showed no statistically significant differences between pregnant and non-pregnant women. We found no significant correlation between prolactin and collagen/ADP closure time (r = 0.175), between prolactin and collagen/epinephrine closure time (r = -0.112) and between prolactin and beta-thromboglobulin (r = 0.220) in pregnant women. Our findings suggest that platelet activity is comparable during pregnant and non-pregnant states and there is no significant effect of prolactin on platelet function in vivo as reflected by beta-thromboglobulin level.

Follow-up of pregnancy in acromegalic women: different presentations and outcomes.

Pregnancy in acromegaly is a rather rare event since the fertility is reduced in acromegalic women. Besides, metabolic complications of acromegaly are harmful to both mother and fetus. Little is known about the outcome of pregnancy in acromegalic women. Here, we report seven cases of pregnancy out of 48 acromegalic women followed for 16 years. At diagnosis, five patients had macroadenoma, one patient had microadenoma and the size of the tumor was not documented in one patient. In one patient, acromegaly was initially diagnosed during pregnancy at 29 weeks. When she was 33 weeks, she developed pituitary apoplexy and had an emergency transsphenoidal resection of her macroadenoma during which she also had a cesarian section and delivered a healthy baby girl. In the remaining six patients, pregnancy occurred 6 to 64.5 months after the adenoma resection. Three patients received radiotherapy before getting pregnant. In three patients, pregnancy occurred during bromocriptine treatment and the drug was withdrawn. In one patient, pregnancy occurred during chronic octreotide treatment and therapeutic abortion was performed. In another patient, therapeutic abortion was performed because of uncontrolled disease. In the remaining four patients, there were neither worsening of symptoms nor tumor growth. All four patients gave birth to full-term healthy infants. Out of our seven patients, two developed gestational diabetes mellitus which was controlled with diet. None of the patients had coronary artery disease, hypertension or dyslipidemia. These cases show that pregnancy might be uneventful in acromegalic women when the disease is controlled with prior surgery and radiotherapy.

EuroSCORE overestimates the cardiac operative risk.

INTRODUCTION: It was the purpose of our study to assess the validity of EuroSCORE (European system for cardiac operative risk evaluation) in our patient population. MATERIALS AND METHODS: Between March 1999 and August 2001, information on risk factors and mortality was collected for 1123 consecutive adult patients undergoing heart surgery with cardiopulmonary bypass. EuroSCORE was used for risk stratification. Mean age +/- standard deviation was 58.6 +/- 10.9 and 29.1% of the patients were female. The area under the receiver operating characteristic (ROC) curve was calculated as an index for the predictive value of the scoring system. RESULTS: The area under the ROC curve was 0.824 for all patients and 0.828 for the isolated CABG subgroup which shows an excellent predictive ability. When the scoring system was applied in low, medium, and high risk groups, there was no overlap between 95% confidence intervals of observed and expected mortality in all three groups both for the isolated CABG cases and for all patients. Decreased left ventricular ejection fraction, emergent operation, and preoperative unstable angina requiring i.v. nitrate treatment were significant predictive variables for early mortality. CONCLUSION: EuroSCORE is a simple and objective system for predicting the risk of heart surgery. The predictive power of the EuroSCORE is excellent, however it seems that mortality is considerably overestimated by this score.

The effect of lipoprotein-a on thrombolytic therapy and spontaneous reperfusion in acute myocardial infarction. A comparative study.

BACKGROUND: To evaluate the role of serum lipoprotein-a (Lp-a) levels on the success of thrombolytic therapy (TT) in patients with acute myocardial infarction (MI). PATIENTS: 56 patients randomly allocated into 2 groups (A and B) with an approximately 1 to 2 ratio. Group A consisted of 18 patients who received 1,5 million IU streptokinase. Group B: 38 patients receiving 100 mg t-PA totally and Group C: 22 patients who did not received any TT as controls. All patients had undergone coronary angiography in the first 7 days and the degree of TIMI flow was determined in the infarct related artery with TIMI-0 and I being considered as unsuccessful perfusion, whereas TIMI-II and III as successful. Lp-a level gs;30 mg/dl was considered as high Lp-a level. RESULTS: Patency rates were similar in Group A and B, in cases with high or low Lp-a levels (p>0.05 for both). In Group C patency rate was found significantly higher in patients with high Lp-a level compared to patients with low Lp-a (p<0.01). Lp-a level in Group C was similar with Group A and B (p>0.05). The time interval for coronary angiography was similar in all groups (p>0.05 for all). CONCLUSIONS: Lp-a level does not effect the reperfusion outcome of TT in patients with MI. However in those patients who not received TT, spontaneous reperfusion rate was found significantly higher in patients with low Lp-a level compared to those with high Lp-a level.

Estimation of left ventricular end-diastolic pressure by color M-mode Doppler echocardiography and tissue Doppler imaging.

OBJECTIVES: The aim of this study was to estimate left ventricular end-diastolic pressure (LVEDP) noninvasively by tissue Doppler imaging and color M-mode echocardiography. MATERIAL AND METHODS: We studied 3 groups of patients who were proven by angiography to be free of significant coronary artery lesions (<40% stenosis) with an LVEDP < 10 mm Hg (group A: n = 24; 16 men, 18 women; mean age +/- SD = 55 +/- 13 years), an LVEDP of 10 to 15 mm Hg (group B: n = 21; 17 men, 4 women; mean age 56 +/- 11 years), or an LVEDP > 15 mm Hg (group C: n = 35; 20 men, 15 women; mean age 58 +/- 9 years). Tissue Doppler imaging of the lateral mitral annulus and color M-mode imaging of the mitral valve in the apical 4-chamber view were obtained with an echocardiographic system. Early and late diastolic velocities (Em and Am, respectively), Em deceleration time (EmDT), Am time (Am-t), and mitral propagation velocity time delay (VpDT) were measured in each patient. RESULTS: In group A, sensitivity and specificity for EmDT < or = 100 ms, Am-t < or = 90 ms, Em/Am > or = 1, and VpDT < or = 45 ms were found to be 0.57 and 0.89, 0.66 and 0.88, 0.86 and 0.92, and 0.73 and 0.89, respectively. In group B, sensitivity and specificity for EmDT 100 to 120 ms, Am-t 90 to 110 ms, Em/Am 1 to 0.5, and VpDT 45 to 60 ms were found to be 0.57 and 0.84, 0.69 and 0.82, 0.66 and 0.75, and 0.55 and 0.83, respectively. In group C, sensitivity and specificity for EmDT > 120 ms, Am-t > 110 ms, Em/Am < 0.5, and VpDT > 60 ms were found to be 0.88 and 0.81, 0.71 and 0.80, 0.86 and 0.72, and 0.78 and 0.86, respectively. CONCLUSION: The EmDT, Am-t, Em/Am, and VpDT measurements obtained noninvasively by left ventricular tissue Doppler imaging and mitral flow propagation velocity were found to be useful in the estimation of LVEDP.

Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications of cardiac surgery. Magnesium, like several other pharmacologic agents, has been used in the prophylaxis of postoperative AF with varying degrees of success. However, the dose and the timing of magnesium prophylaxis need to be clarified. The purpose of this study was to assess the effect of intermittent magnesium infusion on postoperative AF. METHODS: A total of 200 consecutive patients who had elective, isolated, first-time coronary artery bypass grafting were prospectively randomized to two groups. Patients in the magnesium group (n = 100) received 6 mmol MgSO4 infusion in 100 mL 0.9% NaCl solution (25 mL/h) the day before surgery, just after cardiopulmonary bypass, and once daily for 4 days after surgery. Patients in the control group (n = 100) received only 100 mL 0.9% NaCl solution (25 mL/h) at the same time points. RESULTS: Postoperative AF occurred in 2 (2%) patients in the magnesium group and in 21 (21%) patients in the control group (p < 0.001). Atrial fibrillation started, on average, 49.4 +/- 16.8 hours postoperatively. The postoperative length of hospital stay was not significantly different in patients with AF (7.4 +/- 8.0 days) compared with patients without AF (5.4 +/- 1.1 days; p = 0.236). CONCLUSIONS: The use of magnesium in the preoperative and early postoperative periods is highly effective in reducing the incidence of AF after coronary artery bypass grafting.

Resolution of a spontaneous coronary artery thrombus with a new antiplatelet agent.

A thrombus was observed in the left anterior descending coronary artery in a 47 year-old woman who presented with acute anterior myocardial infarction. On a coronary angiogram in the right oblique cranial position, the thrombus appeared as an eccentric, solid and homogeneous mass with a 22 mm maximal length and 1.9 mm maximal diameter. The thrombotic segment and the rest of the coronary tree was free of atherosclerosis. Due to the inappropriate coronary structure and length of the thrombus, coronary angioplasty and/or stent procedures were not performed. The patient refused coronary artery by-pass. She was given the glycoprotein IIb/IIIa inhibitor tirofiban 0.4 microg x kg(-1) x min(-1) bolus over 30 minutes followed by 0.1 microg x kg(-1) x min(-1) for 24 hours, orally acetylsalicylic acid 300 mg per day, nytroglicerin 40 mg per day and warfarine with INR being in a range of 2-2.5 times. A control coronary angiography performed two months later showed total dissolution of the coronary thrombus and clearance of the culprit vessel.

The response of the myocardial metabolism to atrial pacing in patients with coronary slow flow.

The pathophysiology of angina pectoris is not precisely known yet in patients who have no coronary lesion but slow coronary flow by angiography. In this study we aim to display metabolic ischemia via atrial pacing to determine the difference of lactate production and arterio-venous O2 content difference (AVO2). Thirty-four patients with slow coronary flow detected by coronary angiography via the TIMI 'frame count' method were included in this study. The resting and stress images from the patients undergoing myocardial perfusion tomography were recorded, pre and postpacing lactate extraction and AVO2 content difference values were calculated. Patients were classified according to their metabolic responses to atrial pacing stress. Group I consisted of 28 patients (18 male, 10 female, mean age 54.42 +/- 9.61) who did not demonstrate metabolic ischemia and group II consisted of six patients (four male, two female, mean age 60 +/- 5.76) who had metabolic ischemia after the procedure. There was no statistically significant difference between prepacing AVO2 content difference in group I (57.38+/-2.05%) and group II (58.23 +/- 2.11%) (P = NS). However postpacing AVO2 content difference of group I and group II was statistically significant (respectively, 57.96+/-2.65 vs. 68.35 +/- 2.15%, P < 0.001). In other words, postpacing AVO2 content difference was unchanged from the basal AVO2 content difference level in group I (respectively, 57.38 +/- 2.05 vs. 57.96 +/- 2.65%; P = NS) in contrast to the postpacing AVO2 content difference which increased significantly in group II (58.23 +/- 2.11 vs. 68.35 +/- 2.15%; P < 0.028). Although basal lactate extraction rates were similar in groups I and II (respectively, 0.24 +/- 0.1 vs. 0.23 +/- 0.18; P = NS), postpacing lactate extraction rates were decreased significantly in the two groups, prominently in group II (0.154 +/- 0.15 vs. -0.471 +/- 0.27; P < 0.0001) which indicated that lactate extraction converted to lactate production. Metabolic ischemia was detected in only 17.6% of patients included in this study and 83.4% of these six patients with proven metabolic ischemia had perfusion defects in scintigraphy. Our data confirmed that angina pectoris was not originated from myocardial ischemia in most of the patients with slow coronary flow. We conclude that perfusion scintigraphy is a reliable and accurate method for detection of true ischemia in this group of patients.