4DCT in Discordant Parathyroid Adenoma Scans: Case Series and Meta-Analysis.

OBJECTIVE: To evaluate the accuracy of four-dimensional computerized-tomography (4DCT) for localizing parathyroid adenomas (PTAs) in cases with discordant or non-localizing ultrasonography (US) and Technetium-99 sestamibi (MIBI) scans. DATA SOURCES: Retrospective case series and systematic review. REVIEW METHODS: A case series and meta-analysis of patients diagnosed with primary hyperparathyroidism and discordant US and MIBI scans who underwent 4DCT prior to surgery. A comprehensive search for all relevant publications in the English literature between December 2006 and March 2022 was conducted for the meta-analysis. Patients undergoing parathyroidectomy between January 2015 and December 2021 were identified from the institutional electronic database for the case series. All studies were analyzed for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 4DCT adenoma localization capabilities. RESULTS: Thirteen retrospective studies that included 379 patients and one case series that included 37 patients were identified and analyzed. A per-patient analysis revealed sensitivity for lateralization to the correct side (n = 181) ranging from 80% to 100% with a fixed effects model of 89% (95%confidence interval [CI]: 82%-93%) and a PPV for lateralization ranging from 63%-95% with a random effects model of 87% (95% CI: 77%-95%). Sensitivity of localization to the correct quadrant (n = 172) ranged from 53% to 100% with a random effects model of 90.4% (95% CI: 76%-99%), and the PPV for localization ranged from 52% to 100% with a random effects model of 82% (95% CI: 73%-89%). CONCLUSION: 4DCT enhances imaging capabilities of localizing PTAs in cases of discordant or non-localizing US and MIBI scans. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2198-2205, 2024.

A new metabolic syndrome prediction model for self-evaluation as a primary screening tool in an apparently MetS-free population.

BACKGROUND: Metabolic syndrome (MetS) is a growing global public health concern associated with increased morbidity and mortality. The study aimed to establish a simple self-evaluated prediction model to identify MetS. METHODS: A cross-sectional study based on the American National Health and Nutrition Examination Survey database was performed. Participants aged ≥20 in the 2009-2018 surveys, with no current pregnancy or major morbidities, were included. The model was built with data from 2009 to 2016 and validated using 2017-2018 data. MetS was defined according to AHA/NHLBI guidelines. Multivariable logistic regression was applied to build a prediction model. The area under the receiver operating characteristic curve (AUC) was used to assess the discrimination ability and the maximal Youden's index was used to identify the optimal cut-off value. RESULTS: The study included 4245 individuals (median age 37, IQR 28-49, 51.8% females) in the training group and 911 individuals (median age 37, IQR 28-52, 52.5% females) in the validation group. Older age, male gender, non-Black race, no postsecondary education, and higher BMI were significantly associated with increased risk of MetS. The final model included age, gender, race, education, and BMI, and showed good discrimination ability (AUC = 0.810, 95% CI 0.793-0.827, sensitivity 80.4%, specificity 66.2%, positive likelihood ratio 2.379, negative likelihood ratio 0.296, PPV 59.6% and NPV 84.5%). CONCLUSION: A new model for self-evaluation may serve as a primary, easy-to-use screening tool to identify MetS in an apparently MetS-free population. A simple application may serve for primary and secondary prevention, thus enabling risk reduction in the development of cardiovascular morbidity and health expenditure.

Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to multiorgan insufficiency and death, particularly among the older adults. Statins have been suggested as potentially protective drugs due to their pleotropic effects, but the actual benefit of statin use among the older population in this setting is not clear. This study aimed to evaluate the association between preadmission statin use and the presentation and clinical outcomes of hospitalized COVID-19 patients older than 70 years of age. METHODS: A historical cohort study of all patients above 70 years of age who were hospitalized with COVID-19 infection in a large academic hospital between March and August 2020 was performed. The association between preadmission statin use and patients' presentation and adverse outcome was studied. Adverse outcome was defined as any of the following: shock, invasive or non-invasive ventilation, organ insufficiency, myocardial infarction, cerebrovascular accident, in-hospital or 30-day post-admission mortality, hospital stay longer than the median length of stay of all COVID-19 patients, referral to nursing home or rehabilitation center. RESULTS: Seventy-two (44%) of the 163 studied patients (median age 82 years, 45% males) had been preadmission treated with statins. The statin-treated patients (STP) had a higher prevalence of diabetes (40% vs 24%, p = 0.028) and cardiovascular disease (58% vs. 34%, p = 0.002). Seventy two percent of the STP had adverse outcome, compared to 86% of the non-STP (p = 0.033). After adjustment for potential confounders, prior statin use was associated with decreased risk for an adverse outcome (odds ratio = 0.4, 95% confidence interval 0.18-0.92, p = 0.03). CONCLUSIONS: The preadmission use of statins was associated with a lower risk of adverse outcome in older adults hospitalized with COVID-19. Continuation of statin treatment might be implemented for risk reduction of adverse outcomes in the older population in the era of new SARS-CoV-2 variants and less effective vaccines.

Revisiting Age Criterion for Surgery in Asymptomatic Primary Hyperparathyroidism.

OBJECTIVE: To revisit the current age criterion (50 years) for surgical candidacy in patients diagnosed with asymptomatic primary hyperparathyroidism (PHPT). STUDY DESIGN: A predictive model relying on past publications using the electronic databases "PubMed," "Embase," "Medline," and "Google Scholar." SETTING: Hypothetical large cohort. METHODS: A Markov model was constructed, based on relevant literature, to compare 2 potential treatment algorithms for asymptomatic PHPT patients, parathyroidectomy (PTX), and observation. The various potential health states were characterized for the 2 treatment options and included potential surgical complications, end-organ deterioration, and death. A 1-way sensitivity analysis was performed to calculate the quality-adjusted life year (QALY) gains of both strategies. A Monte-Carlo simulation for 30,000 subjects was performed and cycled per annum. RESULTS: On the basis of the model's assumptions, the QALY value for the PTX strategy was 19.17 versus 17.82 for the observation strategy. The incremental QALY gains for various ages according to the sensitivity analyses for PTX in comparison to observation were: 2.84 QALY for 40-year-old patients, 2.2 QALY for 50-year-old patients, 1.81 QALY for 55-year-old patients, 1.35 QALY for 60-year-old patients, and 0.86 QALY for 65-year-old patients. The incremental QALY is below 0.5 after the age of 75 years. CONCLUSION: This study found PTX to be advantageous for asymptomatic PHPT patients older than the current age criterion of 50 years. The calculated QALY gains support a surgical approach for medically fit patients in their 50s. The current guidelines for the surgical treatment of young asymptomatic PHPT patients should be revisited by the next steering committee.

Lateral Neck Dissection for Well-Differentiated Thyroid Carcinoma: Is Prophylactic Level V Neck Dissection Necessary? A Retrospective Cohort Study.

OBJECTIVE: The presence of clinically detectable papillary thyroid carcinoma (PTC) metastases in the lateral neck is an indication for neck dissection (ND) and thyroidectomy. Although there is a consensus regarding the importance of therapeutic selective ND of involved levels II to IV in patients with clinically evident locoregional metastatic disease, the prognostic benefit of level V prophylactic ND remains debatable. METHODS: All patients who underwent thyroidectomy with ND for metastatic PTC between 2006 and 2019 were included in a single-institution retrospective study. Preoperative characteristics at initial presentation, imaging workup, intraoperative findings, and the final histopathological reports were retrieved from the institutional database. RESULTS: A total of 189 patients with locally advanced PTC were identified, of whom 22 (11.6%) patients underwent therapeutic selective ND at levels II to IV together with level V dissection due to clinical involvement. Comparison of the patients who were operated on level V to those who were not revealed no significant difference. The disease recurrence rate was 20.1% throughout an average follow-up of 5.1±3.1 years. No significant differences in recurrence rate were found between patients who underwent and those who did not undergo level V ND (22.7% vs 19.8%, P = .648). No recurrence at resected level V was detected during follow-up, while recurrence at level V was found in 4 (2.1%) patients who did not undergo level V dissection. Evidence of macroscopic and microscopic extrathyroidal extension was significant predictors of disease recurrence risk. CONCLUSION: There were no significant associations between level V dissection and risk for recurrence. Recurrence at level V was rare (4/189 patients, 2.1%). Our study's findings suggest a low prophylactic benefit of an elective level V ND. Elective level V ND should not be done routinely when lateral ND is indicated but should rather be considered after careful evaluation in high-risk patients.

Validation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes.

BACKGROUND: Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA. METHODS: Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland-Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin). RESULTS: The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland-Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p < 0.0001; mean difference -0.068, p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA. CONCLUSIONS: In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.

The Effect of the PCSK9 Inhibitor Evolocumab on Aldosterone Secretion among High Cardiovascular Risk Patients: A Pilot Study.

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.

Unknown Subclinical Hypothyroidism and In-Hospital Outcomes and Short- and Long-Term All-Cause Mortality among ST Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

Subclinical hypothyroidism (SCH) is defined as an elevated serum thyroid-stimulating hormone (TSH) level with a normal serum-free thyroxine (FT4) level. SCH has been associated with an increased risk of adverse cardiovascular outcomes. We investigated possible associations of unknown SCH with in-hospital outcomes and short- and long-term all-cause mortality in a large cohort of patients with ST segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). This retrospective, single-center observational study evaluated the TSH and FT4 levels of 1593 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit and underwent PCI between 1/2008 and 8/2017. SCH was defined as TSH levels ≥ 5 mU/mL in the presence of normal FT4 levels. Unknown SCH was detected in 68/1593 (4.2%) STEMI patients. These patients had significantly worse in-hospital outcomes compared to patients without SCH, including higher rates of acute kidney injury (p = 0.003) and left ventricular ejection fraction ≤ 40% (p = 0.03). Moreover, 30-day mortality (p = 0.02) and long-term (mean 4.2 ± 2.3 years) mortality (p = 0.007) were also significantly higher in patients with SCH. The thyroid function of STEMI patients should be routinely tested before they undergo a planned PCI procedure.

Long-term all-cause mortality and its association with cardiovascular risk factors in thyroid cancer survivors: an Israeli population-based study.

BACKGROUND: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. METHODS: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. RESULTS: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5677 (10.2%) TC patients and 1235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR = 1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR = 1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P <  0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. CONCLUSIONS: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

Correction to: Total thyroidectomy with therapeutic level II-IV neck dissection for papillary thyroid carcinoma: level VI recurrence patterns.

The original article can be found online.

Total thyroidectomy with therapeutic level II-IV neck dissection for papillary thyroid carcinoma: level VI recurrence patterns.

OBJECTIVE: Lateral and central compartments cervical lymph nodes metastases are common among patients with papillary thyroid carcinoma (PTC). Elective level VI neck dissection during thyroidectomy and lateral neck dissection (LND) for the treatment of PTC with lateral compartment lymph node metastases is controversial because of the uncertain benefit in clinical outcomes and increased risks of surgical morbidity. We aimed to determine the potential benefit of elective level VI neck dissection in patients with cN1 papillary thyroid carcinoma (PTC) by investigating the rate and pattern of locoregional recurrence in PTC patients who underwent total thyroidectomy and therapeutic lateral node dissection (LND; levels II-IV) without elective level VI dissection. METHODS: A retrospective cohort study. Data on demographics, clinical presentation and workup, intraoperative and pathological report, postoperative course, adjuvant therapy, recurrence patterns, and overall survival were retrieved from the medical charts of patients who underwent thyroid surgery in our hospital between January 2006 and December 2017. RESULTS: A total of 1415 thyroidectomies were performed during the study period, of which 802 (56.67%) were for PTC. Of those PTC patients, 228 (28.42%) also underwent LND (levels II-VI) during the same thyroidectomy procedure. Thirty-four (14.91%) of those 228 patients, underwent total thyroidectomy with therapeutic lateral ND II-IV without elective level VI ND. During the follow-up period, five (14.7%) of the latter cohort were diagnosed with recurrence in central neck (level VI) lymph nodes, and four of them (11.7%) were diagnosed with ipsilateral recurrence at level VI. CONCLUSION: Our results revealed 11.7% rate of clinically significant recurrent disease in ipsilateral level VI which, in our opinion, does not justify routine prophylactic level VI ND dissection when the ipsilateral lateral neck is operated for metastases.

Components of metabolic syndrome in patients with multiple myeloma and smoldering multiple myeloma.

BACKGROUND: The prevalences of diabetes mellitus and hypertension, both of which are components of metabolic syndrome, are known to be increased among patients with multiple myeloma (MM), but remain undetermined among patients with smoldering MM (SMM). METHODS: Changes in various components of metabolic syndrome were investigated during the follow-up of patients with either MM or SMM compared to healthy controls. The data of 153 patients (105 with MM and 48 with SMM) and 138 controls were accessed from our medical center's records between 2008 and 2015. We analyzed the patients' data at diagnosis (baseline) and after 1, 3, and 5 years of follow-up. RESULTS: Patients with SMM had a significantly higher prevalence of diabetes, hypertension, and dyslipidemia at baseline compared to controls. A multivariate Cox regression analysis revealed a higher risk to develop dyslipidemia after 1, 3, and 5 years of follow-up among the SMM patients. The MM patients had a higher risk to develop diabetes after 1 year, hypertension after 5 years, and dyslipidemia after 1, 3, and 5 years of follow-up. CONCLUSIONS: These data demonstrate that patients with SMM and those with MM are more prone to develop various components of metabolic syndrome, and they stress the importance of following-up metabolic syndrome components in both groups of patients.

Relation of Subclinical Hypothyroidism to Acute Kidney Injury Among ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Data suggest that subclinical hypothyroidism (SCH) is associated with progression of chronic renal disease; however, no study to date has assessed the possible relation between SCH and acute deterioration of renal function. OBJECTIVES: To investigate the possible relation between SCH and acute kidney injury (AKI) in a large cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary coronary intervention (PCI). METHODS: We evaluated thyroid stimulating hormone (TSH) and free T4 levels of 1591 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit (October 2007-August 2017). The presence of SCH was defined as TSH levels ≥ 5 mU/ml in the presence of normal free T4 levels. Patients were assessed for development of AKI ( 0.3 mg/dl increase in serum creatinine, according to the KDIGO criteria). RESULTS: The presence of SCH was demonstrated in 68/1593 (4.2%) STEMI patients. Patients presenting with SCH had more AKI complications during the course of STEMI (20.6% vs. 9.6 %; P = 0.003) and had significantly higher serum creatinine change throughout hospitalization (0.19 mg/dl vs. 0.08 mg/dl, P = 0.04). No significant difference was present in groups regarding baseline renal function and the amount of contrast volume delivered during coronary angiography. In multivariate logistic regression model, SCH was independently associated with AKI (odds ratio = 2.19, 95% confidence interval 1.05-4.54, P =0.04). CONCLUSIONS: Among STEMI patients treated with PCI, the presence of SCH is common and may serve as a significant marker for AKI.

Body Composition, Resting Energy Expenditure, and Metabolic Changes in Women Diagnosed with Differentiated Thyroid Carcinoma.

Background: Thyroid hormones heavily impact energy expenditure, body mass, and body composition. Their role in the state of exogenous subclinical hyperthyroidism in differentiated thyroid carcinoma (DTC) patients, however, is less well defined. The first aim of this study was to assess changes in body weight, body composition, resting energy expenditure (REE), respiratory quotient (RQ), and metabolic parameters in female DTC patients, starting from the phase of a euthyroid state before total thyroidectomy through the subsequent year after thyrotropin (TSH) suppression. The second aim was to assess the relationship between these variables and thyroid function parameters. Methods: This observational case series analyzed changes in body composition, calorimetric, and metabolic parameters of 15 DTC female patients at 5 time points: (1) at initial DTC diagnosis (euthyroid state), (2) at 2-3 weeks after thyroidectomy (hypothyroid state), (3) at 2-3 months of levothyroxine (LT4) treatment (exogenous euthyroid state), (4) after 6-9 months, and (5) after 1 year of TSH suppressive LT4 therapy (exogenous subclinical hyperthyroid state). A generalized estimating equation (GEE) analysis was performed to estimate the longitudinal correlations of the total triiodothyronine (TT3)/free thyroxine (fT4) ratio (as an independent variable) with body composition, metabolic, and calorimetric parameter changes (as dependent variables). Results: REE, REE per kilogram of lean body mass (REE/LBM), pulse, and systolic and diastolic blood pressure were significantly higher after TSH suppressive LT4 therapy. The GEE analysis revealed longitudinal negative correlations between the TT3/fT4 ratio and systolic blood pressure, fasting blood glucose, body mass index, android (abdominal wall and visceral mesentery) fat distribution, trunk, and arm fat distribution, REE, and REE/LBM. There was a positive correlation with RQ. Conclusions: REE, REE/LBM, pulse, and systolic and diastolic blood pressure were significantly higher after thyroidectomy, radioiodine and TSH suppressive therapy in female DTC patients, while no changes were observed in body weight or body composition. A lower TT3/fT4 ratio longitudinally correlated with increases in REE, REE/LBM, abdominal fat distribution, systolic blood pressure, and fasting blood glucose, as well as with decreased RQ. These findings highlight the importance of judicial balancing of the benefits and detriments of TSH suppression with subsequent decreased TT3/fT4 ratios for female DTC patients.

Long-term cardiovascular and cerebrovascular morbidity in Israeli thyroid cancer survivors.

OBJECTIVE: Thyroid cancer (TC) survivors may be at risk of subsequent cardiovascular and cerebrovascular (CaV&CeV) morbidity. The 2009 American Thyroid Association (ATA) guidelines recommended less aggressive treatment for low-risk TC patients. The aim of this study was to assess the atherosclerotic CaV&CeV outcome of Israeli TC survivors compared to individuals with no thyroid disease, and the atherosclerotic CaV&CeV outcome before (2000-2008) and after (2009-2011) implementation of the 2009 ATA guidelines. METHODS: All members of the largest Israeli healthcare organization who were diagnosed with TC from 1/2000 to 12/2014 (study group) and age- and sex-matched members with no thyroid disease (controls) were included. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models. RESULTS: The mean follow-up was 7.6 ± 4.2 and 7.8 ± 4.1 years for the study (n = 5,677, 79% women) and control (n = 23,962) groups, respectively. The former had an increased risk of new atherosclerotic CaV&CeV events (adjusted HR 1.26, 95% CI 1.15-1.39). The 5-year incidence of CaV&CeV was lower (adjusted HR 0.49, 95% CI 0.38-0.62) from 2009 to 2011 compared to 2000 to 2008, but remained higher in the study group than in the control group (adjusted HR 1.5, 95% CI 1.14-1.69). CONCLUSIONS: This large Israeli population-based cohort study showed greater atherosclerotic CaV&CeV morbidity in TC survivors compared to individuals with no thyroid diseases. There was a trend toward a decreased 5-year incidence of atherosclerotic CaV&CeV events among TC survivors following the implementation of the 2009 ATA guidelines, but it remained higher compared to the general population.

Prolonged Hyperglycemia and Renal Failure after Primary Percutaneous Coronary Intervention.

BACKGROUND: There are limited data regarding the effect of long-standing hyperglycemia on the occurrence of acute kidney injury (AKI) in ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: We retrospectively studied 723 STEMI patients undergoing primary PCI. Patients were stratified into two groups according to glycated hemoglobin (HbA1c) levels as a marker of prolonged hyperglycemia: those with HbA1c < 7% and those with HbA1c ≥7%. Medical records were reviewed for the occurrence of AKI. RESULTS: HbA1c levels ≥7% were found in 225/723 (31%) of patients. The occurrence of AKI was significantly higher among patients with HbA1c levels ≥7% (32/225, 14%) compared to patients with HbA1c levels < 7% (32/498, 6%; p = 0.001). Patients with chronic kidney disease (CKD) and HbA1c ≥7% had an eight-fold increase in the incidence of AKI compared to patients with HbA1c < 7% and no CKD (32 vs. 4%). In a multivariable regression model, HbA1c ≥7% was independently associated with AKI (OR 1.92, 95% CI 1.09-3.36, p = 0.02). CONCLUSION: HbA1c ≥7% was associated with a higher likelihood of AKI in STEMI patients treated with primary PCI.

Severe central obesity or diabetes can replace weight loss in the detection of frailty in obese younger elderly - a preliminary study.

PURPOSE: Unwanted weight loss is one of the established criteria for the diagnosis of frailty. However, the relevance of this criterion to detect frailty in obese older adults has not been assessed. In particular, with the exception of malignancy, unwanted weight loss is not commonly seen in older obese subjects. Therefore, we tested the possibility that some obesity phenotypes and/or diabetes might be more useful in the detection of frailty in this setting. PATIENTS AND METHODS: A preliminary cross-sectional study of 50 consecutive subjects was conducted at The Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center. Inclusion criteria were: young elderly (aged 65-75 years), with general and/or abdominal obesity, without cancer. Frailty was assessed directly using the Fried model, the five-item fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale. Eventually, in the assessment of frailty, the weight loss criterion was replaced by one or several of obesity/diabetes-related variables each time: severity of obesity by body mass index, waist circumference (and their interaction), body fat, and diabetes. The receiver operating characteristic curves for functional impairment indices were plotted to compare the usefulness of the frailty accepted and adjusted models. RESULTS: The prevalence of frailty and pre-frailty in this cohort were 7/50 (14%) and 27/50 (54%), respectively, but unwanted weight loss was seen in three subjects (6%) only. The level of abdominal obesity had the strongest correlation with functional score (r=0.292, P<0.05). Frailty models which included either severe abdominal obesity or diabetes in lieu of unwanted weight loss had good sensitivity rates per each frailty score as compared with the original Fried model. CONCLUSION: For detecting and/or screening for the frailty syndrome in obese young elderly, the level of abdominal obesity or diabetes may provide a useful marker.

A sorafenib-sparing effect in the treatment of thyroid carcinoma cells attained by co-treatment with a novel isoflavone derivative and 1,25 dihydroxyvitamin D3.

BACKGROUND: Sorafenib improves progression-free survival in patients with progressive radioactive iodine-refractory differentiated thyroid carcinoma, but causes severe side effects. Estrogens may accelerate thyroid carcinoma cell growth. Our group recently reported that isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine (cD-tboc), a novel anti-estrogenic compound, retards the growth of both thyroid carcinoma cell lines and cultured human carcinoma cells. Vitamin D receptor (VDR) is expressed in malignant cells and responds to 1,25 dihydroxyvitamin D3 (1.25D) by decreased proliferative activity in vitro. The purpose of this study was to examine the effects of vitamin D metabolites (VDM) on the expression of estrogen receptors (ERs), VDR, and 1OHase mRNA, and to evaluate the inhibitory effect of low doses of sorafenib in combination with cDtboc and VDM on cell proliferation in cultured human papillary thyroid carcinoma (PTC). METHODS: In 19 cultured PTC specimens and 19 normal thyroid specimens, harvested during thyroidectomies from the same patients, expression levels of ERα, ERß, VDR, and 1 alpha-hydroxylase (1OHase) mRNA (by quantitative real-time PCR) were determined at baseline and after treatment with VMD. Cell proliferation was determined by measurement of 3[H] thymidine incorporation after treatment with sorafenib alone, sorafenib with added 1.25D or cD-tboc, and sorafenib with both 1.25D and cD-tboc added. RESULTS: 1,25D increased mRNA expression of all tested genes in the malignant and normal thyroid cells, while the ERα mRNA of the normal cells was unaffected. 1.25D dose-dependently inhibited cell proliferation in the malignant cells. The inhibitory effect of sorafenib on cell proliferation in the malignant cells was amplified after the addition of cDtboc and 1.25D, such that the maximal inhibition was not only greater, but also had been attained at a 10-fold lower concentration of sorafenib (20 µg/ml). This inhibition was similar to that of the generally used concentration of sorafenib (200 µg/ml) alone. CONCLUSIONS: The demonstration that low concentrations of cDtboc and 1.25D markedly amplify the inhibitory effect of sorafenib on the growth of human PTC supports the use of a 10-fold lower concentration of sorafenib. The findings may promote a new combination treatment for progressive radioactive iodine-refractory PTC.

Trends of Second Primary Malignancy in Patients with Thyroid Cancer: A Population-Based Cohort Study in Israel.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy. TC patients have a good prognosis and a low disease-related mortality rate. Since such patients are often young, they may be at a higher risk for a second primary malignancy (SPM). This study sought to determine the incidence, risk, and types of SPM between 1980 and 2011, and to assess SPM trends over time among Israeli TC patients. METHODS: Data were derived from the Israel National Cancer Registry. Primary TC patients diagnosed during 1980-2009 were followed up for SPM incidence until December 31, 2011. Standardized incidence ratios (SIRs) of observed to expected SPM (based on the general population rates) were calculated using Poisson regression. Analyses were stratified by time period of initial TC diagnosis (1980-1995 and 1996-2009). RESULTS: A total of 11,538 TC patients were identified. After exclusion of 107 duplicate cases, records of 1032 patients with SPM were analyzed (an SPM incidence of 8.9%). SIRs for all-site SPMs were 1.23 [confidence interval 1.08-1.35] for males and 1.19 [confidence interval 1.10-1.27] for females. SIRs for tumors of the urinary system and prostate were significantly elevated in males, as were SIRs for tumors of the brain, urinary system, breast, and lung in females. Variables associated with increased risk of developing SPMs included a younger age at TC diagnosis, a shorter latency period, being born in Asia/Africa for both sexes, and being born in Israel for females. Compared with the general population, a subanalysis by TC diagnosis during 1980-1995 and 1996-2009 disclosed a higher SPM incidence for the latter time period in males and for both time periods, with a slightly higher SIR for the latter time period in females. CONCLUSIONS: The overall risk of SPM in Israeli TC patients was significantly greater for both sexes compared with the general population, thus identifying TC patients as a high-risk group and calling for caretakers to apply specific follow-up guidelines.

Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors.

PURPOSE: Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function. METHODS: Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD). RESULTS: IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = -0.44, p = 0.02). CONCLUSIONS: Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.