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Background: Bilateral inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary from ectopic adrenocorticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin (DDAVP) stimulation in localization of the source of ACTH excess.Method: Retrospective review of 20 patients with ACTH-dependent Cushing's syndrome who underwent IPSS with DDAVP stimulation. Baseline, DDAVP-stimulated, and prolactin-normalized ACTH IPS:P (inferior petrosal sinus to peripheral) ratios were calculated. Cut-off values for each test were obtained from receiver-operating characteristic (ROC) curve analysis.Results: Fifteen patients had Cushing disease (CD), and five were diagnosed with ectopic ACTH syndrome (EAS). For the baseline ACTH IPS:P ratio of ≥2, the diagnostic sensitivity (80%), specificity (100%), positive predictive value (PPV) (100%) and negative predictive value (NPV) (62.5%) were calculated. These values for DDAVP-stimulated IPS:P ACTH ratio ≥ 3, were 86.7%, 100%, 100% and 71.4%, respectively. The corresponding value for the prolactin-normalized ACTH IPS:P ratio ≥ 0.8 were 86.6%, 80%, 92.8% and 66.7%. The cut-off value for the baseline, DDAVP-stimulated and prolactin-normalized ACTH IPS:P ratios were 1.76, 3.9, and 0.33, respectively.Conclusion: Prolactin-normalized ACTH IPS:P ratio measurement showed comparable sensitivity and less specificity than baseline/DDAVP-stimulated IPS/P ACTH ratios. Moreover, when baseline and stimulated IPS/P ACTH tests were discordant, prolactin-normalized ACTH IPS: P ratio correctly localized the source of ACTH excess. The sensitivity of the test increased, applying a prolactin-normalized ACTH IPS: P ratio ≥0.33.

Purpose: To evaluate the effect of cabergoline treatment on metabolic parameters including the Triglyceride-glucose (TyG) index in newly diagnosed patients with prolactinoma.Methods: 71 consecutive non-diabetic patients with prolactinoma were enrolled. Body mass index (BMI), blood pressure, and laboratory tests including TyG index were measured for each patient. Then, treatment with cabergoline was started for each patient and continued for 6 months. Anthropometric and laboratory tests were repeated every 3 months to evaluate the effects of cabergoline treatment. Results: At the baseline examination, the mean (SD) age, BMI, waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of patients were 36.2 (10.5) years, 29.2 (5.0) kg/m2, 98.2 (13.7) cm, 115.3 (13.3) mmHg, and 71.4 (8.1) mmHg, respectively. Furthermore, men were older and had higher values for BMI, WC, SBP, and metabolic syndrome (MetS) prevalence compared to women. Cabergoline treatment significantly improved anthropometric and metabolic measures including BMI, WC, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid (only among women), TyG index, and hypogonadism, while no significant change was detected in SBP and DBP. No significant change was found in Mets syndrome prevalence among women whereas the declining trend from baseline to 3-month evaluation was significant among men. Conclusion: Short-term treatment with cabergoline can significantly improve cardiovascular risk factors except for blood pressure. Moreover, the TyG index as a surrogate marker of insulin resistance decreased significantly after the reduction of prolactin by treatment. Generally, results were similar among both genders.

Objectives The aim of this study was to identify risk factors of in-hospital mortality among diabetic patients infected with COVID-19. Study design Retrospective cohort study. Methods Using logistic regression analysis, the independent association of potential prognostic factors and COVID-19 in-hospital mortality was investigated in three models. Model 1 included demographic data and patient history; model 2 consisted of model 1, plus vital signs and pulse oximetry measurements at hospital admission; and model 3 included model 2, laboratory test results at hospital admission. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported for each predictor in the different models. Moreover, to examine the discriminatory powers of the models, a corrected area under the receiver-operating characteristic curve (AUC) was calculated. Results Among 560 patients with diabetes (men = 291) who were hospitalised for COVID-19, the mean age of the study population was 61.8 (standard deviation [SD] 13.4) years. During a median length of hospitalisation of 6 days, 165 deaths (men = 93) were recorded. In model 1, age and a history of cognitive impairment were associated with higher mortality; however, taking statins, oral anti-diabetes drugs and beta-blockers were associated with a lower risk of mortality (AUC = 0.76). In model 2, adding the data for respiratory rate (OR 1.07 [95% CI 1.00–1.14]) and oxygen saturation (OR 0.95 [95% CI 0.92–0.98]) slightly increased the AUC to 0.80. In model 3, the data for platelet count (OR 0.99 [95% CI 0.99–1.00]), lactate dehydrogenase (OR 1.002 [1.001–1.003]), potassium (OR 2.02 (95% CI 1.33–3.08]) and fasting plasma glucose (OR 1.04 [1.02–1.07]) significantly improved the discriminatory power of the model to AUC 0.86 (95% CI 0.83–0.90). Conclusions Among patients with type 2 diabetes, a combination of past history and pulse oximetry data, with four non-expensive laboratory measures, was significantly associated with in-hospital COVID-19 mortality.

Background and aims We aimed at evaluating whether the presence of gestational diabetes mellitus (GDM) in mothers is associated with increased risk of incident cardiovascular disease (CVD) in both mothers and fathers. Methods In this population-based study, 4308 Iranian women, aged 18–64 years, with at least 1 live-birth delivery, and free of CVD at baseline, were followed. Corresponding spouses were identified in 2547 cases. The association between history of GDM and incident CVD was assessed using multivariate Cox's proportional hazard in 3 models: model 1, unadjusted; model 2, adjusted for age, body mass index, smoking (for men), maternal parity, miscarriage, physical activity, hypertension and hypercholesterolemia, and model 3, further adjusted for diabetes mellitus. Results After a median follow-up of 14.1 years, 314 mothers and 424 fathers experienced CVD. Women with history of GDM had an adjusted hazard ratio (HR), 95% CI of 1.85 (1.38–2.48) and 1.29 (0.96–1.75) for CVD in models 1 and 2, respectively. Furthermore, an independent association with CVD was observed in fathers with an adjusted HR of 1.35 (1.02–1.79) in the confounder adjusted model and even after further controlling for diabetes [1.36 (1.03–1.80)]. Moreover, all traditional risk factors, excluding BMI, showed an independent risk for CVD in both genders. Conclusions Women with prior GDM showed an increased risk of CVD that was not independent of important CVD risk factors. However, among men, spousal history of GDM was an independent risk factor for incident CVD, even after considering important traditional risk factors, including diabetes.

For patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), total body irradiation (TBI) has been particularly advocated as a part of the conditioning regimen in case of extramedullary involvement in sanctuary sites such as the central nervous system (CNS), to ensure greater tissue penetration. In resource-limited countries lacking TBI facilities; however, ALL patients undergo radiation-free myeloablative conditioning, though its impacts on post-HSCT outcomes of the patients with pre-HSCT CNS involvement have not been analyzed. In this 14-year series of 278 adult (> 18 y) ALL patients undergoing TBI-free busulfan/cyclophosphamide conditioning allo-HSCT, we found that the long-term probabilities of overall survival, disease free survival, relapse and non-relapse mortality were not significantly different between CNS-involved and CNS-spared patients. Moreover, there was no statistically significant difference in the incidence of post-HSCT CNS relapse between CNS-involved and CNS-spared patients. Pre-HSCT cranial radiation therapy (CRT) showed no significant preventive effect on the likelihood of post-HSCT CNS relapse. Through multivariable regression analysis, grade III-IV acute graft-versus-host disease (GvHD), extensive chronic GvHD and post-HSCT relapse were ascertained as independent determinants of mortality (Adj.R2 = 53.9 %, F(12,265) = 28.1, P

Background: To assess the association between fasting plasma glucose (FPG) and 2-h post challenge plasma glucose (2h-PCPG) as continuous or categorical variables with risk of recurrent cardiovascular disease (CVD) and incident diabetes among subjects with history of previous CVD. Methods: In a prospective population-based cohort, a total of 335 Iranians aged ≥30 years, with history of CVD and free of known diabetes were included. Prediabetes was defined as impaired fasting glucose (IFG) according to the criteria of the American Diabetes Association (ADA) [IFG-ADA; FPG: 5.6-6.9 mmol/L], the World Health Organization (WHO) expert group (IFG-WHO; FPG: 6.1-6.9 mmol/L) and impaired glucose tolerance [IGT: 2h-PCPG: 7.8-11.0 mmol/L]. Cox’s proportional hazard models adjusted for traditional risk factors were used to estimate the hazard ratio (HR) with 95% confidence interval (CI) of different glucose intolerance for outcomes of interest. Results: During a median follow-up of 15.8 (IQR, 10.7-16.5) years, 178 CVD (hard event including death, myocardial infarction and stroke=69) events occurred. Regarding FPG, only IFG-ADA was associated with significant higher risk of hard CVD in the fully adjusted model (HR, 1.73, 95% CI: 1.04-2.89). Moreover, newly diagnosed diabetes (FPG≥7 mmol/L) was an independent risk of CVD (2.11: 1.22-3.66). Focusing on 2h-PCPG, subjects with newly diagnosed diabetes (2h-PCPG ≥ 11.1 mmol/L) had moderately increased risk of hard coronary heart disease (2.02:0.91-4.47, P=0.08). The multivariate HRs (95% CI) associated with 1 SD increase in FPG and 2h-PCPG was 1.16 (1.01–1.33) and 1.19 (1.02–1.38) for CVD, respectively. Among population free of diabetes at baseline (n=270), IFG-ADA, IFG-WHO and IGT were significantly associated with incident diabetes in multivariate analysis (all HRs > 4, P< 0.001); significant associations were also found for FPG and 2h-PCPG as continuous variables (all HRs for 1-SD increase > 2, all P < 0.001). Conclusions: Among subjects with stable CVD, both FPG and 2h-PCPG as continuous variables was associated with higher risk of recurrent CVD. However, only IFG-ADA was independent predictor of hard CVD events. Also, newly diagnosed diabetes, using FPG criteria, was associated with a significant risk of CVD. IFG-ADA, IFG-WHO and IGT were all significant predictors of incident diabetes.

ObjectivesTo investigate the association of alkaline phosphatase (ALP) levels with the risk of the composite end point of cardiovascular disease (CVD), and all-cause mortality as well as each of them separately.DesignProspective cohort study.SettingWithin the framework of the Tehran Lipid and Glucose Study (TLGS) cohort, participants were followed from baseline examination (1999–2001) until March 2014.ParticipantsA total of 2578 participants, aged ≥30 years free of prevalent CVD at baseline examination.Primary outcomeThe main outcome measures were composite end point of coronary heart disease (CHD), stroke, all-cause mortality and each per se.ResultsDuring a median follow-up of 11.3 years, 369, 68, 420, 170 and 495 participants experienced CHD, stroke, CVD, all-cause mortality and the composite outcome, respectively. In the multivariable Cox regression models, the adjusted HRs (95% CI) for mentioned events per one SD increase in ALP level after full adjustment were 1.11 (1.01 to 1.22), 1.20 (0.97 to 1.49, p=0.058), 1.10 (1.01 to 1.21), 1.16 (1.01 to 1.33) and 1.11 (1.02 to 1.21), respectively. Furthermore, participants with ALP levels in the highest tertile had significant adjusted HRs (95% CI) for stroke (1.88 (1.00 to 3.61)), CVD (1.30 (1.01 to 1.68)) and composite outcome (1.27 (1.00 to 1.61)). The cut-off value of ALP ≥199 IU/L for predicting composite outcome was derived using Youden’s index, based on which this cut-off point was associated with significant risk of 80%, 26%, 43% and 26% for incident stroke, CVD, all-cause mortality and composite outcome. Additionally, no improvement was seen in the predictive ability of traditional risk factors models after adding ALP values, considering the levels of Akaike information criterion, C-index and Net Reclassification Index.ConclusionIndependent associations between ALP levels and the risks of CVD and mortality events were shown, despite the fact that adding the data of ALP to known risk factors did not improve the prediction of these events.

An adrenal incidentaloma is a mass lesion greater than 1 cm in diameter, serendipitously discovered by radiologic examination. Extramedullary hematopoiesis presenting as adrenal mass is not a common entity but foci of Extramedullary Hematopoiesis (EMH) may occur in almost any organ.

(Table1). All donor sources were included: 63 matched sibling (MSD), 95 10/10 MUD, 11 9/10 MUD, 18 cord blood (CB), and 13 haploidentical (Haplo). Results: The majority of pts received myeloablative conditioning (n1⁄4170; busulfan-based n1⁄4148). Disease status at AlloSCT was: CR1 (n1⁄499), CR2 (n1⁄420), CR with incomplete count recovery or hypoplasticmarrowor CR3 (CRi; n1⁄431), and active disease (AD; n1⁄450). Thirty percent of pts received a FLT3 inhibitorbeforeAlloSCT.After amedian follow-upof27mo, the 2-year (2Y) OS and PFS rates were 43% and 41%, respectively. Relapse-related mortality was the main cause of death (68%). Remission and FLT3 status at the time of AlloSCT were significantly associated with PFS. Compared to CR1 pts, PFS was not different inCR2 [HR1.5, p1⁄40.3], but itwasworse inCRi (HR3.9, p 4 [HR 1.6, p1⁄40.05], and unrelated donor source [HR 1.6, p1⁄40.05]. No difference in PFS was found between Haplo and MSD donor sources (HR1⁄40.9, p1⁄40.9). No significant association was identified by age, conditioning intensity or use of a FLT3 inhibitor prior to transplant. Post-transplant FLT3 status was available for 105 of 190 evaluable pts by day 30. Among them, 7ptshaddetectable FLT3PCR and5/7 pts (71%) relapsed. Conclusion: Morphologic remission and FLT3 PCR status at the time of transplant are key predictors of relapse risk in pts with FLT3+ AML. Patients who achieved a morphologic CR with an undetectable FLT3 by PCR at the time of SCT had the best outcomes and should undergo an AlloSCTwithout delay. Although the experience is limited, Haplo transplants had similar outcomes to MSD transplants. Prospective clinical trials with FLT3 inhibitors post-transplant are warranted at least for pts with AD or persistent FLT3+ on PCR at transplant.

A 12-year-old boy was admitted to the hospital because of fever, chills, sweats, productive cough, nausea, and vomiting. He had been subject to recurrent pneumonias since the age of 5 years.

Mucocutaneous manifestations are common among patients on hemodialysis (HD). This study was undertaken to determine the prevalence of mucocutaneous manifestations in patients with end-stage renal disease (ESRD) who are on HD. In this cross-sectional, descriptive and analytic study conducted in 2009, 100 patients on HD at the Five Azar Hospital in Gorgan city were randomly selected. All the patients underwent detailed examination by a dermatologist to look for lesions in the skin, hair, nail and mucous membranes; if felt necessary, biopsy was obtained from the lesions. The findings were statistically analyzed using SPSS-13 software. For evaluation of normality of distribution, Kolmogorov-Smirnov was used, for quantitative variables Mann-Whitney and T-test (abnormal distribution) were used and for qualitative variables, Chi-2 and Fisher were used. In this study, P-value less than 0.05 was considered significant. Fifty-one males and 49 females were enrolled. The mean age was 49 ± 12 years. Diabetes was the most common cause of ESRD. In 95% of the patients, at least one mucocutaneous manifestation was present. Xerosis (78.3%) was the most common lesion, followed by pruritus (39.1%), lentigo (34.8%), skin discoloration (32.6%), leukonychia (32%) and thinning of the nail bed (24%). Xerosis, scaling, lentigo, folliculitis, idiopathic guttate hypopigmentation, leukonychia and half and half nail were associated with age. A significant relationship was seen between duration on dialysis and skin discoloration and leukonychia. Clubbing had a significant association with calcium-phosphorus product (Ca × P). There was a significant association between serum ferritin level and pruritus and tinea versicolor lesions. Our study shows that mucocutaneous manifestations are common among patients with ESRD. Identification of these manifestations and their association with causative factors are useful for preventing the lesions.