The therapeutic responses to I-131 ablation in patients of differentiated thyroid carcinoma complicated with nodular goiter

IntroductionWe applied the response to therapy reclassification system (RTRS) to evaluate the disease status after surgery and I-131 therapy in differentiated thyroid carcinoma (DTC) patients with nodular goiter (NG).Materials and methodsA total of 268 DTC complicated with NG patients who underwent the I-131 treatment and thyroidectomy between 2010 and 2018 were analyzed. The RTRS were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Logistic regression analysis were performed to evaluate the relevant clinicopathologic and laboratory variables in the prediction of non-ER (IDR, BIR and SIR).ResultsIn the logistic analysis, gender (OR: 3.543, P = 0.01), lateral cervical lymph node metastases (N1b) (OR: 6.646, P = 0.005), pre-ablation stimulated thyroglobulin (Ps-Tg) (OR: 0.859, P = 0.000), and anti-Tg antibody (TgAb) (OR: 64.546, P = 0.000) were predictor of non-ER. The cut-off value of ps-Tg for predicting the ER was 19.98 ng/mL with a sensitivity of 92.6% and specificity of 83.2%. The non-ER rate of N1b group was significantly higher than the central cervical LNM (N1a) group.ConclusionFor patients with DTC complicated with NG, the cut-off value of ps-Tg for predicting the ER was 19.98 ng/mL. N1b patients showed inferior responses to I-131 therapy compared to N1a patients.     

Evaluación de la efectividad del tratamiento con glucocorticoides intravenosos en la oftalmopatía de Graves

ObjectiveTo assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methodsPatients with GO treated with IV GCs from August 2007 to August 2011 at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulse prednisolone (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks.ResultsEighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in 11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment, 83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain (P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).ConclusionsIntravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status.     

Influence of forward leaning and incentive spirometry on inspired volumes and inspiratory electromyographic activity during breathing exercises in healthy subjects

Breathing exercises (BE), incentive spirometry and positioning are considered treatment modalities to achieve lung re-expansion. This study evaluated the influence of incentive spirometry and forward leaning on inspired tidal volumes (V_T) and electromyographic activity of inspiratory muscles during BE. Four modalities of exercises were investigated: deep breathing, spirometry using both flow and volume-oriented devices, and volume-oriented spirometry after modified verbal instruction. Twelve healthy subjects aged 22.7 ± 2.1 years were studied. Surface electromyography activity of diaphragm, external intercostals, sternocleidomastoid and scalenes was recorded. Comparisons among the three types of exercises, without considering spirometry after modified instruction, showed that electromyographic activity and V_T were lower during volume-oriented spirometry (p = 0.000, p = 0.054, respectively). Forward leaning resulted in a lower V_T when compared to upright sitting (p = 0.000), but electromyographic activity was not different (p = 0.606). Inspired V_T and electromyographic activity were higher during volume-oriented spirometry performed after modified instruction when compared with the flow-oriented device (p = 0.027, p = 0.052, respectively). In conclusion BE using volume-oriented spirometry before modified instruction resulted in a lower work of breathing as a result of a lower V_T and was not a consequence of the device type used. Forward leaning might not be assumed by healthy subjects during situations of augmented respiratory demand.     

Punto de corte de espesor de tejido adiposo epicárdico para predecir síndrome metabólico en población venezolana

ObjectiveTo define an echocardiographically-assessed cut-off point for epicardial adipose tissue (EAT) thickness associated to metabolic syndrome (MS) components in Venezuelan subjects.MethodsFifty-two subjects aged 20-65 years diagnosed with MS according to International Diabetes Federation criteria and 45 sex- and age-matched controls were selected. Blood glucose and plasma lipids were tested; EAT thickness and left ventricular mass were measured by echocardiography.ResultsNo significant age and sex differences were found between the two groups. Body weight, body mass index, waist circumference, and systolic and diastolic blood pressure were significantly higher (P = .0001) in the MS group. This group showed significantly higher levels of fasting blood glucose (P = .0001), total cholesterol (P = .002), LDL-C (P = .007), non-HDL-C (P = .0001), triglycerides (P = .0001), Tg-HDL-C ratio (P = .0001), and lower HDL-C levels (P = .0001) as compared to the control group. EAT thickness (P = .0001) and left ventricular mass (P = .017) were significantly higher in the MS group. The ROC curve showed an AUC of 0.852 (P = .0001) with a power of the test of 0.99. A 5-mm EAT thickness showed a sensitivity of 84.62% (95% CI: 71.9-93.1) and a specificity of 71.11% (95% CI: 55.7-83.6) for predicting MS. The odds ratio of this population for experiencing MS due to an EAT ≥ 5 mm was 8.25 (95% CI: 3.15-21.56; P = .0001).ConclusionAn EAT value ≥ 5 mm has good sensitivity and specificity for predicting MS in the Venezuelan population.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

Perfil clínico y mortalidad a 90 días de los pacientes centenarios atendidos en servicios de urgencias hospitalarios

ObjectivesTo determine the clinical profile and to develop a model to predict 90-day mortality in centenarian patients attended in emergency departments (ED).MethodologyThis was an observational, retrospective, multicentre cohort study including patients > 99 years attended in 5 ED in the Community of Madrid from January to December 2012. Demographic variables were recorded, as well as, comorbidities, cognitive, functional, social basal status, geriatric syndromes, acute episode, and hospital and social resources use, and 90-day mortality.ResultsThe study included 209 patients aged 101 years (SD 1.7) of whom 161 (77.0%) were female. Sixty four (32.5%) had severe comorbidity (Charlson index ≥ 3), 101 (49.8%) on multiple medication, 100 (52.6%) had cognitive impairment, 82 (42.3%) had severe functional dependence, 85 (40.7%) were institutionalised, and 190 (94.5%) had a geriatric syndrome. Dyspnoea (26.8%), followed by falls (12.4%) were the most common causes of attendance. One hundred and eighteen (56.5%) were admitted, and 58 out of 174 (33.3%) died in the first 90 days. The model to predict 90-day overall mortality included male sex (OR 2.42 95% CI = 0.97-6.04; P = .059), emergency care in the previous 3 months (OR 4.08 95% CI = 1.26-13.16; P = .019) and the hospitalization by index event (OR 8.63 95% CI = 3.25-22.9; P < .001) and this model had an area under ROC curve of 0.776 (95% CI = 0.70-0.85; P < .001).ConclusionsCentenarian patients attended in ED had a significant frailty and one in three cases died in the first 90 days after being attended, and this was associated with male sex, emergency care in the previous 3 months, and hospitalisation.     

老年支气管哮喘患者血清MC-CP、Th17的表达及其与呼吸功能、肺功能的相关性分析

摘要 目的：探究老年支气管哮喘患者血清肥大细胞羧肽酶（MC-CP）、Th17表达及其与患者呼吸功能、肺功能的相关性。方法：选择2018年4月至2021年8月于中国人民解放军东部战区总医院接受治疗的120例老年支气管哮喘患者为研究组（SG）,另选同期于我院接受治疗的100例支气管炎患者为对照组（CG）,对比两组患者血清MC-CP、Th-17、呼气峰值流速（PEF）、第1秒用力呼气量（FEV₁）、血氧分压（PaO₂）、FEV₁占预计值的百分数（FEV₁/FVC）差异,就研究组患者MC-CP、Th-17水平与其呼吸功能、肺功能的相关性开展Spearman分析。结果：（1）研究组患者的MC-CP水平明显高于对照组,Th17百分比同样明显高于对照组（P<0.05）;（2）研究组患者的呼吸功能指标PEF、PaO₂,以及肺功能指标FEV₁、FEV₁/FVC均明显低于对照组（P<0.05）;（3）研究组患者MC-CP与PEF、PaO₂呈现明显负相关联系（r=-0.558、-0.700,P<0.001）,研究组患者Th17与PEF、PaO₂呈现明显负相关联系（r=-0.695、-0.774,P<0.001）;（4）研究组患者MC-CP与FEV₁、FEV₁/FVC呈现明显负相关联系（r=-0.609、-0.481,P<0.001）,研究组患者Th17与FEV₁、FEV₁/FVC呈现明显负相关联系（r=-0.622、-0.561,P<0.001）。结论：老年支气管哮喘患者血清MC-CP及Th17水平会出现异常升高状态,而呼吸功能与肺功能会出现降低,相关性分析显示此类患者血清MC-CP及Th17水平与其呼吸功能、肺功能均呈现负相关联系。     

EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell lung tumors: Initial clinical experience

PurposeEPID-based in vivo dosimetry (IVD) has been implemented for stereotactic body radiotherapy treatments of non-small cell lung cancer to check both isocenter dose and the treatment reproducibility comparing EPID portal images.Methods15 patients with lung tumors of small dimensions and treated with volumetric modulated arc therapy were enrolled for this initial experience. IVD tests supplied ratios R between in vivo reconstructed and planned isocenter doses. Moreover a γ-like analysis between daily EPID portal images and a reference one, in terms of percentage of points with γ-value smaller than 1, P_γ<1, and mean γ-values, γ_mean, using a local 3%–3 mm criteria, was adopted to check the treatment reproducibility. Tolerance levels of 5% for R ratio, P_γ<1 higher than 90% and γ_mean lower than 0.67 were adopted.ResultsA total of 160 EPID images, two images for each therapy session, were acquired during the treatment of the 15 patients. The overall mean of the R ratios was equal to 1.005 ± 0.014 (1 SD), with 96.9% of tests within ± 5%. The 2 D image γ-like analysis showed an overall γ_mean of 0.39 ± 0.12 with 96.1% of tests within the tolerance level, and an average P_γ<1 value equal to 96.4 ± 3.6% with 95.4% of tests with P_γ<1 > 90%. Paradigmatic discrepancies were observed in three patients: a set-up error and a patient morphological change were identified thanks to CBCT image analysis whereas the third discrepancy was not fully justified.ConclusionsThis procedure can provide improved patient safety as well as a first step to integrate IVD and CBCT dose recalculation.     

Protective effects of losartan in mice with chronic viral myocarditis induced by coxsackievirus B3

AimTo investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3).Main methodsThirty two male Balb/c mice were intraperitoneally injected with CVB3 (10 × TCID₅₀) to induce chronic viral myocarditis (CVM). Losartan at 12.5 mg/kg (n = 16) or normal saline (n = 16) were orally administered daily for 28 days to these mice. Uninfected mice (n = 6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-γ and TNF-α levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72 h post infection.Key findingsMice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P < 0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08 ± 2.17 to 4.15 ± 0.99, and necrosis and inflammatory scores from 3.33 ± 0.50 to 2.50 ± 0.65 (all P < 0.05), and increased ejection fractions from 55.80 ± 9.25 to 72.31 ± 12.15 (P < 0.05). Losartan significantly enhanced IL-4, and decreased IFN-γ, TNF-α and IL-17 (all P < 0.05). In the in vitro experiment, losartan had no influence on virus titers.SignificanceLosartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses.     

Recherche de facteurs de risque de la thrombopénie induite par le 177Lu-DOTATATE dans le bilan de suivi standard

PurposeThe thrombocytopenia induced by the ¹⁷⁷Lu-DOTATATE is one of its frequent, adverse effects. Its persistence causing problems in the subsequent management of patients, especially when the disease progression occurs, predicting it is a major issue. Due to the lack of knowledge about this subject, we searched to determine the existence of predisposing factors concerning the platelet toxicity in the standard follow-up.Material and methodsThis monocentric retrospective study included 20 patients with gastroenteropancreatic neuroendocrine tumors. Various parameters were analyzed, including: the standard blood analysis, the osteomedullary invasion factor, the spleen's volume and the estimated activity in the bone marrow or the spleen 24 hours post-injection.ResultsFour patients had a persistent grade 2 thrombocytopenia, one year after the last treatment. A decrease in platelet count after the first treatment above 30% and an osteomedullary invasion factor above 30% were highlighted as risk factors odds-ratio = ∞ (P = 0.0379) and odds-ratio = ∞ (P = 0.003) respectively. The initial platelet count, splenic length and estimated activity in the spleen after 24 h were correlated with platelet nadir value r = 0.5459 (P = 0.0128); r = − 0,8105 (P < 0,0001) and r = − 0.467; (P < 0.0001) respectively.ConclusionThis study has shown that the decrease of platelet's count after the first round of treatment and the scale of osteomedullary invasion are risk factors for thrombocytopenia and has brought to light that the spleen acts as a factor impacting the severity of this thrombocytopenia.     

Factores de riesgo de mortalidad en pacientes mayores de 65 años hospitalizados por COVID-19

Background and objectiveCOVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has caused a global pandemic that we are currently suffering from.Objectiveto identify factors associated with the death of patients aged 65 years or older hospitalized for COVID-19.Materials and methodsRetrospective cohort study. We included patients aged 65 years or older who were hospitalized for COVID-19 and dead o discharged between March 5 and 25, 2020. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.Results277 patients were included in this study. The bivariate analysis showed significant differences (p < 0.05) between survivors and non survivors: age, increased dependence and comorbidity, history of ischemic heart disease, renal failure and non-hematological neoplasms, heart failure during admission, leukocytosis, elevated creatinine, PCR, GOT and troponin Ic values, lymphopenia, and decreased blood pH and SatO2. Multivariate logistic regression revealed that age ≥ 65 years (OR: 4.23 (95% CI: 1.43-12.52; p = 0.009), lymphopenia < 1000/μL (OR: 2.36 (95% CI: 1.07-5.20; p = 0.033), creatinine > 1.2 mg/dL (OR: 3.08 (95% CI: 1.37-6.92; p = 0.006), SatO₂ < 90% (OR: 2.29 (95% CI: 1.01-5.21; p = 0.049) and troponin Ic > 11 ng/mL (OR: 2.32 (95% CI: 1.04-5.16; p = 0.040) were independently associated with higher hospital mortality.ConclusionsOlder age, lymphopenia, SatO₂ < 90%, elevated creatinine and troponin Ic values were independently associated with higher mortality in hospitalized patients with COVID-19, these factors could help clinicians to identify patients with poor prognosis.     

Percutaneous Laser Ablation in the Treatment of Toxic and Pretoxic Nodular Goiter

ObjectiveTo report data regarding treatment with use of percutaneous laser ablation (PLA) in autonomously functioning thyroid nodules (AFTN).MethodsWe treated 18 patients (10 women and 8 men, 31 to 80 years old) who presented with a single hyperfunctioning thyroid nodule (8 patients) or a multi-nodular goiter (10 patients) with clearly hyperfunctioning areas on a thyroid scintiscan. In 5 cases, free thyroxine (FT₄) and free triiodothyronine (FT₃) levels were high, and in these patients and a further 9 patients with cardiovascular symptoms, methimazole therapy was initiated to restore euthyroidism. The total number of PLA sessions ranged from 1 to 5 (median, 3). Thyroid-stimulating hormone, FT₄, FT₃, thyroglobulin, and antithyroglobulin and anti-thyroid peroxidase antibodies were measured by a commercial kit the day after PLA treatment, then weekly during the first month, and monthly thereafter. The Student t test was used for statistical analyses, and data are reported as mean values ± SE.ResultsAfter each PLA session, there was a transient and mild increase in FT₄ and FT₃—5.2% to 18.1% (mean, 11.1 ± 0.69%) (P < 0.001) in patients not treated with methimazole and 4.0% to 8.3% (mean, 5.9 ± 0.31%) (P < 0.001) in patients treated with methimazole—relative to values before treatment; however, these values never reached the range of hyperthyroidism. In addition, thyroglobulin showed a remarkable increase after 24 hours— 115% to 390% (mean, 266.0 ± 12.7%) (P < 0.001). Thyroid-stimulating hormone increased in all cases and reached normal values in all patients with single AFTN and in 5 patients (50%) with multinodular goiter within 3 months after PLA. At 1-year follow-up, the decrease in nodular volume was 24% to 72% (mean, 59.3 ± 8.2%; P < 0.001).ConclusionOur data show that PLA can be a useful treatment in AFTN and particularly in single toxic nodules. Possible elective indications are patients who refuse surgical or radioiodine treatment and patients with cardiovascular comorbidity who need rapid restoration of the euthyroid state and who cannot tolerate the discontinuation of antithyroid drugs for radioiodine treatment. (Endocr Pract. 2007;13:30-36)     

Efficacy and Safety of Linagliptin in Black/African American Patients with Type 2 Diabetes: A 6-Month,Randomized, Double-Blind,Placebo-Controlled Study

ObjectiveAlthough black/African American individuals are disproportionately affected by type 2 diabetes, there is scant clinical trial information available on antidiabetes therapies in this group. We compared linagliptin with placebo in black/African American adults who were treatment-naïve or receiving one oral antidiabetes drug.MethodsOf 226 patients randomized to 24 weeks’ linagliptin 5 mg/day or placebo, 208 had baseline and at least one on-treatment glycated hemoglobin (HbA_1c) measurement. Mean baseline HbA_1c was 8.6% in the linagliptin group (n = 98) and 8.68% in the placebo group (n = 110). The primary outcome was change in HbA_1c from baseline to week 24.ResultsBy week 24, mean HbA_1c changes were − 0.84% with linagliptin and − 0.25% with placebo (treatment difference, − 0.58%; P < .001), and more patients in the linagliptin group achieved HbA_1c < 7.0% (26.8% vs. 8.3%; P = .001) or an HbA_1c reduction ≥ 0.5% (54.1% vs. 30.0%; P < .001). Mean weight loss was − 1.1 kg in both groups. During the treatment period, 8 of 98 linagliptingroup patients and 17 of 110 placebo-group patients required rescue therapy (odds ratio, 0.5; P = .14). For postprandial glucose, values were available for few patients (11 placebo, 10 linagliptin), and thus the between-group difference was associated with wide confidence intervals (CIs) (difference, − 1.97 mg/dL; 95% CI, − 53.80 to 49.86; P = .94). In the overall study population, a similar proportion of patients in both groups had adverse events (58.5% vs. 61.7%); most events were mild or moderate and considered unrelated to study drug. Investigator-defined hypoglycemia was rare (3 linagliptin-group patients and 1 placebogroup patient), with no severe events (requiring external assistance).ConclusionThis study confirms that linagliptin is efficacious and well tolerated in black/African American patients with type 2 diabetes. (Endocr Pract. 2014;20: 412-420)     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

Tasa de filtración glomerular estimada y mortalidad posterior al alta en una unidad geriátrica de agudos

ObjectiveTo determine the relationship between estimated glomerular filtration rate (eGFR) and mortality in a retrospective cohort of older adults admitted to an acute care for the elderly (ACE) unit.Materials and methodsThe study included 1,678 patients aged 60 years and over admitted to an AEC, in Cali, Colombia, from 2012 to 2015, and followed- up until 2016. The primary outcome was mortality. Renal function (eGFR) was estimated using Modification of Diet in Renal Disease Study (MDRD-4) equation. The renal function was grouped according to the eGFR (ml/min/1.73 m²) as follows: slightly decreased (≥ 60), moderately decreased (30-59), and severely decreased (< 30). Bivariate survival and multivariate Cox regression analyses were performed.ResultsIn the univariate analysis, patients with severely decreased eGFR had higher mortality than those with a higher eGFR (P = .046). In the group with severely decreased eGFR, survival was lower in the functionally dependent group (Barthel index [IB] < 60) than in the independent group (IB ≥ 60) (log rank test; P = .001). In the multivariate analysis, there was a significant increase in the risk of death in the elderly with severely decreased eGFR (< 30) compared with slightly decreased eGFR (≥ 60) (hazard ratio [HR], 1.44; 95% confidence interval [CI]; 1.02-2.05, P = .039). There was also a significant increase in the risk of death in the dependent elderly compared to the independent ones [HR 1.72; 95% CI; 1.26-2.34, P = .000], those who had the high morbidity (≥ 4) with low albumin (< 3.2 g/dL) compared with those with low morbidity (0-3) and high albumin (≥ 3.2) [HR 1.77; 95% CI; 1.18-2.65, P = .005], and in those with a high (16-102 mg/dL) C-reactive protein (CRP) compared with those with low CRP (0-15) [HR 1.42; 95% CI; 1.01-2.01, P = .043].ConclusionsThe risk of mortality after hospital admission to an AEC unit is greater in patients with eGFR < 30. Poor functional status performance, high comorbidity, low plasma albumin, and increased inflammation markers are additional prognostic factors to be taken into account. The improvement in the functional status could improve the survival after hospitalisation.     

Expression of the Androgen Receptor,pAkt, and pPTEN in Breast Cancer and Their Potential in Prognostication

BACKGROUNDImportance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.METHODSThis study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82).RESULTSExpression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P < .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR⁺ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR^? tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR⁺ /pAkt⁺ /pPTEN^? tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR^?/pAkt⁺/pPTEN^? tumors (Mean OS = 5.1 ± 0.738 years).CONCLUSIONAR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.     

Delayed treatment with GnRH agonist,hCG and progesterone and reduced embryonic mortality in buffaloes

The present study examined the effect of delayed treatment with tropic hormones and progesterone (P₄) on embryonic mortality in buffaloes. Buffaloes with a conceptus on Day 25 after AI were assigned to the following treatments: Control (n = 41), i.m. physiological saline; GnRH agonist (n = 36), i.m. 12 μg buserelin acetate; hCG (n = 33), i.m. 1500 IU hCG; P₄ (n = 38), i.m. 341 mg P₄ every 4 days on three occasions. Control buffaloes had an embryonic mortality of 41.4% (17/41) between Days 25 and 45, and this was reduced (P < 0.01) by treatment with GnRH agonist (11.1%, 4/36), hCG (9.0%, 3/33) and P₄ (13.1%, 5/38). On Day 45, buffaloes treated with hCG and which ovulated had greater (P < 0.05) concentrations of P₄ in whey (453 ± 41 pg/ml) than buffaloes in the same treatment that did not ovulate (297 ± 32 pg/ml). A similar but non-significant trend was observed for buffaloes treated with GnRH agonist. It was concluded from the findings that the treatment of buffaloes on Day 25 after AI with tropic hormones or P₄ is beneficial to processes associated with embryonic implantation.     

Preadmission Glycemic Control and Changes to Diabetes Mellitus Treatment Regimen After Hospitalization

ObjectiveTo evaluate treatment patterns associated with diabetes medication regimen changes after hospitalization on the basis on preadmission hemoglobin A_1c levels.MethodsIn this retrospective database analysis, patients with a diabetes diagnosis, hospitalization, and documented hemoglobin A_1c level within the 90 days leading up to hospital admission were identified in an administrative claims database. Treatment regimens were assessed before and after hospitalization. The proportion of patients who had progression, reduction, or no change in therapy was compared across hemoglobin A_1c subgroups: hemoglobin A_1c < 7.0%, hemoglobin A_1c 7.0%-7.9%, and hemoglobin A_1c ≥ 8.0%.ResultsFour hundred patients were included (192 in hemoglobin A_1c < 7.0% group, 94 in hemoglobin A_1c 7.0% 7.9% group, and 114 in hemoglobin A_1c ≥ 8.0% group). Demographically, hemoglobin A_1c subgroups did not differ significantly (mean age, 57 years; 47.5% male). With respect to therapeutic regimen overall, 28%, 24%, and 48% of patients experienced progression, reduction, and no change, respectively. Across hemoglobin A_1c subgroups, 37.7% of patients in the hemoglobin A_1c ≥ 8.0% subgroup had therapy progression compared with 26% and 20.2% in the hemoglobin A_1c < 7.0% and hemoglobin A_1c 7.0%-7.9% subgroups, respectively (P = .032 and P = .006, respectively). Within the progression category, progression via insulin initiation was significantly higher in the hemoglobin A_1c ≥ 8.0% subgroup (55.8%) than in the hemoglobin A_1c < 7.0% subgroup (16%, P < .001), but not significantly higher than in the hemoglobin A_1c 7.0%-7.9% subgroup (36.8%, P = .084). In the hemoglobin A_1c ≥ 8.0% subgroup, a lower percentage of patients, 35.1%, experienced no therapy change than in both the hemoglobin A_1c < 7.0% subgroup (52.6%) and the hemoglobin A_1c 7.0%-7.9% subgroup (54.3%) (P = .003 and P = .006, respectively). There was no difference between subgroups in reduction of therapy.ConclusionsA higher proportion of patients with a hemoglobin A_1c level ≥ 8.0% had progression of their antidiabetes therapy after hospitalization and fewer patients had no change in therapy than those in lower hemoglobin A_1c subgroups. These data suggest that clinicians may be using hemoglobin A_1c measurements to guide discharge planning treatment decisions. (Endocr Pract. 2012;18:371-375)