Publications by authors named "Prasanna Santhanam"

67 Publications

Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus.

J Am Heart Assoc 2021 Jun 10;10(12):e018998. Epub 2021 Jun 10.

Division of Endocrinology, Diabetes & Metabolism Johns Hopkins School of Medicine Baltimore MD.

Background Microvascular disease (MVD) is a potential contributor to the pathogenesis of diabetes mellitus-related cardiac dysfunction. However, there is a paucity of data on the link between MVD and incident heart failure (HF) in type 2 diabetes mellitus. We examined the association of MVD with incident HF in adults with type 2 diabetes mellitus. Methods and Results A total of 4095 participants with type 2 diabetes mellitus and free of HF were assessed for diabetes mellitus-related MVD including nephropathy, retinopathy, or neuropathy at baseline in the Look AHEAD (Action for Health in Diabetes) study. Incident HF events were prospectively assessed and adjudicated using hospital and death records. Cox models were used to generate hazard ratios and 95% CIs for HF. Of 4095 participants, 34.8% (n=1424) had MVD, defined as the presence of ≥1 of nephropathy, retinopathy, or neuropathy at baseline. Over a median of 9.7 years, there were 117 HF events. After adjusting for relevant confounders, participants with MVD had a 2.5-fold higher risk of incident HF than those without MVD (hazard ratio, 2.54; 95% CI, 1.73-3.75). This association remained significant after additional adjustment for interval development of coronary artery disease (hazard ratio, 2.42; 95% CI, 1.64-3.57). The hazard ratios for HF by type of MVD were 2.22 (95% CI, 1.51-3.27), 1.30 (95% CI, 0.72-2.36), and 1.33 (95% CI, 0.86-2.07) for nephropathy, retinopathy, and neuropathy, respectively. CONCLUSIONS MVD is associated with an excess HF risk in individuals with type 2 diabetes mellitus after adjusting for other known risk factors. Our findings underscore the contribution of MVD to the development of diabetes mellitus-related HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.
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http://dx.doi.org/10.1161/JAHA.120.018998DOI Listing
June 2021

Long-term variability of blood pressure and incidence of heart failure among individuals with Type 2 diabetes.

ESC Heart Fail 2021 May 25. Epub 2021 May 25.

Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, 21224, USA.

Aims: Data on the association of long-term variability of blood pressure (BP) with incident heart failure (HF) in individuals with Type 2 diabetes are scarce. We evaluated this association in a large community-based sample of adults with Type 2 diabetes.

Methods And Results: A total of 4200 participants with Type 2 diabetes who had available BP measurements at four visits (baseline and 12, 24, and 36 months) in the Look AHEAD (Action for Health in Diabetes) study were included. Variability of systolic BP (SBP) and diastolic BP (DBP) across the four visits was assessed using four metrics. Participants free of HF during the first 36 months were followed for HF events. Cox regression was used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for HF. Of the 4200 participants, the average age was 59 years [standard deviation (SD): 6.8]; 58.5% were women. Over a median follow-up of 6.7 years, 129 developed HF events. After adjusting for relevant confounders, the HR of incident HF for the highest vs. lowest quartile of SD of SBP was 1.77 (95% CI 1.01-3.09); the HR for the highest (vs. lowest) quartile of variability independent of the mean of SBP was 1.29 (95% CI 0.78-2.14). The adjusted HR for participants in the highest (compared with the lowest) quartile of SD of DBP was 1.61 (95% CI 1.01-2.59), and the adjusted HR for variability independent of the mean of DBP was 1.65 (95% CI 1.03-2.65).

Conclusions: A greater variability in SBP and DBP is independently associated with greater risk of incident HF in individuals with Type 2 diabetes.
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http://dx.doi.org/10.1002/ehf2.13385DOI Listing
May 2021

Microvascular disease and cardiovascular outcomes among individuals with type 2 diabetes.

Diabetes Res Clin Pract 2021 May 12;176:108859. Epub 2021 May 12.

Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA. Electronic address:

Aim: To evaluate the associations of microvascular disease (MVD) with incident cardiovascular disease (CVD) in individuals with type 2 diabetes.

Methods: A total of 4098 participants with type 2 diabetes and without CVD were assessed for MVD (diabetic kidney disease, retinopathy or neuropathy) in the Look AHEAD (Action for Health in Diabetes) study. Cox models were used to generate hazard ratios (HRs) for: (1) CVD composite (myocardial infarction, stroke, hospitalization for angina and/or death from cardiovascular causes), (2) coronary artery disease (CAD), (3) stroke, and (4) CVD-related deaths.

Results: Of 4098 participants, 34.7% (n = 1424) had MVD at baseline. Over a median of 9.5 years, 487 developed the CVD composite, 410 CAD events, 100  stroke, and 54 CVD-related deaths. After adjusting for relevant confounders, MVD was associated with increased risks of CVD composite (HR 1.34, 95% CI 1.11-1.61), CAD (HR 1.24, 95% CI 1.01-1.52), stroke (HR 1.55, 95% CI 1.03-2.33), and cardiovascular mortality (HR 1.26, 95% CI 0.72-2.22). HRs for CVD composite by type of MVD were 1.11 (95% CI 0.89-1.38), 1.63 (95% CI 1.22-2.17) and 1.16 (95% CI 0.92-1.46) for diabetic kidney disease, retinopathy, and neuropathy, respectively.

Conclusions: Our findings underscore the relevance of MVD in CVD risk assessment in type 2 diabetes.
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http://dx.doi.org/10.1016/j.diabres.2021.108859DOI Listing
May 2021

Long-Term Variability of Blood Pressure, Cardiovascular Outcomes, and Mortality: The Look AHEAD Study.

Am J Hypertens 2021 Apr 2. Epub 2021 Apr 2.

Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: We evaluated the associations of visit-to-visit blood pressure (BP) variability with incident cardiovascular disease (CVD) and deaths in adults with type 2 diabetes.

Methods: We analyzed 4,152 participants in Look AHEAD (Action for Health in Diabetes) free of CVD events and deaths during the first 36 months of follow-up. Variability of systolic BP (SBP) and diastolic BP (DBP) across 4 annual visits was assessed using the intraindividual SD, variation independent of the mean, and coefficient of variation. Cox regression was used to generate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD (myocardial infarction [MI], stroke, or CVD-related deaths) and mortality.

Results: Over a median of 6.6 years, there were 220 MIs, 105 stroke cases, 62 CVD-related deaths, and 236 deaths. After adjustment for confounders including average BP, the aHRs for the highest (vs. lowest) tertile of SD of SBP were 1.98 (95% CI 1.01-3.92), 1.25 (95% CI 0.90-1.72), 1.26 (95% CI 0.96-1.64), 1.05 (95% CI 0.75-1.46), and 1.64 (95% CI 0.99-2.72) for CVD mortality, all-cause mortality, CVD, MI, and stroke, respectively. The equivalent aHRs for SD of DBP were 1.84 (95% CI 0.98-3.48), 1.43 (95% CI 1.03-1.98), 1.19 (95% CI 0.91-1.56), 1.14 (95% CI 0.82-1.58), and 0.97 (95% CI 0.58-1.60), respectively.

Conclusions: In a large sample of individuals with type 2 diabetes, a greater variability in SBP was associated with higher cardiovascular mortality and CVD events; a higher variability in DBP was linked to increased overall and cardiovascular mortality.
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http://dx.doi.org/10.1093/ajh/hpaa210DOI Listing
April 2021

Body fat predicts exercise capacity in persons with Type 2 Diabetes Mellitus: A machine learning approach.

PLoS One 2021 31;16(3):e0248039. Epub 2021 Mar 31.

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.

Diabetes mellitus is associated with increased cardiovascular disease (CVD) related morbidity, mortality and death. Exercise capacity in persons with type 2 diabetes has been shown to be predictive of cardiovascular events. In this study, we used the data from the prospective randomized LOOK AHEAD study and used machine learning algorithms to help predict exercise capacity (measured in Mets) from the baseline data that included cardiovascular history, medications, blood pressure, demographic information, anthropometric and Dual-energy X-Ray Absorptiometry (DXA) measured body composition metrics. We excluded variables with high collinearity and included DXA obtained Subtotal (total minus head) fat percentage and Subtotal lean mass (gms). Thereafter, we used different machine learning methods to predict maximum exercise capacity. The different machine learning models showed a strong predictive performance for both females and males. Our study shows that using baseline data from a large prospective cohort, we can predict maximum exercise capacity in persons with diabetes mellitus. We show that subtotal fat percentage is the most important feature for predicting the exercise capacity for males and females after accounting for other important variables. Until now, BMI and waist circumference were commonly used surrogates for adiposity and there was a relative under-appreciation of body composition metrics for understanding the pathophysiology of CVD. The recognition of body fat percentage as an important marker in determining CVD risk has prognostic implications with respect to cardiovascular morbidity and mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248039PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011752PMC
March 2021

Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings From the Look AHEAD Study.

J Am Heart Assoc 2021 Apr 17;10(7):e016947. Epub 2021 Mar 17.

Division of Endocrinology, Diabetes & Metabolism Department of Medicine Johns Hopkins School of Medicine Baltimore MD.

Background Metabolic dyslipidemia (high triglyceride) and low high-density lipoprotein cholesterol (HDL-C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus-related abnormalities in the triglyceride-HDL-C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL-C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL-C at baseline (2001-2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow-up of 9.5 years (interquartile range, 8.7-10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL-C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12-1.64 [=0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18-1.81 [=0.001]) but not stroke (HR, 1.38; 95% CI, 0.90-2.11 [=0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03-1.63 [=0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14-1.93 [=0.003]) but not stroke (HR, 1.23; 95% CI, 0.74-2.05 [=0.420]). Conclusions In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial.org; Unique identifier: NCT00017953.
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http://dx.doi.org/10.1161/JAHA.120.016947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174364PMC
April 2021

Aggressive Differentiated Thyroid Cancer due to EML4e13-ALKe20 Fusion: A Case Presentation and Review of the Literature.

Case Rep Endocrinol 2021 15;2021:8837399. Epub 2021 Feb 15.

Marshall University, School of Medicine, Huntington, WV, USA.

Background: Differentiated thyroid cancer (DTC) is an indolent malignancy. It rarely presents with aggressive local invasion and/or distant metastatic disease. . We describe a case of a 30-year-old man with a locally aggressive form of papillary thyroid cancer with fusion (: echinoderm microtubule-associated protein-like 4; : anaplastic lymphoma kinase). He presented with right-side cervical lymphadenopathy with a highly suspicious right-side thyroid nodule. Total thyroidectomy and level IV lymph node resection showed extensive bilateral disease, with extrathyroidal and extranodal extension. FDG-PET CT scan following surgery confirmed the presence of significant residual disease in the neck area. He underwent bilateral lateral lymph node dissection followed by radioactive iodine treatment. Somatic mutation testing showed fusion. . This case represents an aggressive form of DTC with fusion. The rapid progression of clinical signs and symptoms and the local extension beyond the thyroid and lymph nodes with the persistence of high-volume local disease after thyroidectomy highlight the aggressive nature of this mutation and the importance of performing genetic analysis to guide future treatments and determine prognosis.

Conclusion: This case highlights the importance of using molecular diagnostics in patient care, especially if the presentation is unusual for DTC. A thorough evaluation of the tumor pathology and the somatic mutational profile analysis are important for obtaining vital therapeutic and prognostic guidance.
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http://dx.doi.org/10.1155/2021/8837399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899757PMC
February 2021

RFA and benign thyroid nodules: Review of the current literature.

Laryngoscope Investig Otolaryngol 2021 Feb 9;6(1):155-165. Epub 2021 Jan 9.

Department of Surgery, Section of Endocrine Surgery Columbia University Medical Center New York New York USA.

Benign thyroid nodules (BTNs) are commonly found in the general population. They are usually asymptomatic and their incidence has increased as a result of wide-spread use of ultrasound. Benign nodules are typically monitored clinically until they increase in size, resulting in compressive symptoms warranting surgery. However, although surgery is generally well-tolerated and of low-risk, it is associated with a small risk for several complications including hypothyroidism, nerve injury, hematoma, injury to other structures and wound infection. Recently, newer image-guided ablation techniques including radiofrequency ablation (RFA) have been introduced. RFA has a similar safety profile when compared to surgery and has shown promising results in challenging surgical candidates. Though several studies have been published in Asian and European countries on the efficacy of RFA, limited data is available on the North American population. The aim of the study is to review the current literature establishing the clinical outcomes and safety of RFA for benign nodules.

Level Of Evidence: V.
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http://dx.doi.org/10.1002/lio2.517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883624PMC
February 2021

Cardiorespiratory Fitness and Atherosclerotic Cardiovascular Outcomes by Levels of Baseline-Predicted Cardiovascular Risk: The Look AHEAD Study.

Am J Med 2021 06 17;134(6):769-776.e1. Epub 2021 Feb 17.

Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins School of Medicine, Baltimore, Md. Electronic address:

Background: We evaluated the associations of cardiorespiratory fitness with atherosclerotic cardiovascular disease (ASCVD) by levels of baseline-predicted ASCVD risk among adults with type 2 diabetes.

Methods: We analyzed data from 4203 adults with type 2 diabetes in the Look AHEAD (Action for Health in Diabetes) study. Cardiorespiratory fitness was assessed using maximal exercise testing and categorized into low, moderate, and high; baseline-predicted. ASCVD risk was calculated using the American College of Cardiology/American Heart Association Pooled Cohort Equation. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ASCVD events (fatal and nonfatal myocardial infarction and stroke).

Results: Over a median of 9.6 years, there were 295 ASCVD events. The effect of fitness on outcomes was different across levels of 10-year predicted ASCVD risk (P for interaction < .001). Among participants with a baseline-predicted risk of 7.5% to 20%, the HR of low (vs high) fitness group was 1.94 (95% CI, 1.12-3.35) for ASCVD events. Fitness was not significantly associated with ASCVD events in the groups with baseline-predicted risk <7.5% (HR 1.53; 95% CI, 0.49-4.76) or ≥20% (HR 1.40; 95% CI, 0.88-2.24). A similar pattern was observed for myocardial infarction and stroke separately.

Conclusions: In a large sample of type 2 diabetes individuals, the association of low fitness with incident ASCVD was modified by the baseline-predicted 10-year ASCVD risk. Our findings suggest the utility of assessing fitness in ASCVD risk stratification in type 2 diabetes, especially among those with intermediate predicted 10-year risk of ASCVD.
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http://dx.doi.org/10.1016/j.amjmed.2021.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176653PMC
June 2021

A systematic review of imaging studies of human brown adipose tissue.

Ann N Y Acad Sci 2021 Feb 18. Epub 2021 Feb 18.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, Maryland.

Brown adipose tissue (BAT) is involved in energy dissipation and has been linked to weight loss, insulin sensitivity, and reduced risk of atherosclerotic disease. BAT is found most often in the supraclavicular region, as well as mediastinal and paravertebral areas, and it is predominantly seen in young persons. BAT is activated by cold temperature and the sympathetic nervous system. In humans, BAT was initially detected via 2-deoxy-2-[ F]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), a high-resolution molecular imaging modality used to identify and stage malignancies. Recent studies have shown that BAT can be localized using conventional imaging modalities, such as CT or magnetic resonance imaging, as well as radiotracers used for single-photon emission CT. In this systematic review, we have summarized the evidence for BAT detection in humans using various imaging techniques.
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http://dx.doi.org/10.1111/nyas.14579DOI Listing
February 2021

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size.

Endocr Pract 2020 Jul 24;26(7):754-760. Epub 2020 Nov 24.

Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baltimore, Maryland. Electronic address:

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.

Methods: Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.

Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.

Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.

Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.
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http://dx.doi.org/10.4158/EP-2019-0473DOI Listing
July 2020

Radiofrequency ablation and thyroid nodules: updated systematic review.

Endocrine 2021 Jun 15;72(3):619-632. Epub 2021 Jan 15.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Purpose: In the thyroid gland, radiofrequency ablation (RFA) is being applied to both benign nodules and cancers internationally, while interest is also growing in the West. Benign thyroid nodules (BTNs) may be candidates for intervention when symptoms develop. For differentiated thyroid cancers (DTC), surgery is currently the first-line treatment. However, for candidates with high surgical risk or those who refuse to undergo repeated surgery, newer techniques such as RFA are an option. Surgery is associated with complications including hypothyroidism, voice change, hypocalcemia, and a scar. RFA has been used in Asian and European institutions as an alternative to surgery, but is relatively new in North America. Although RFA is not associated with significant complications, few randomized control trials have assessed its efficacy. The studies to date suggest a low rate of severe complications and a small need for thyroid hormone replacement following RFA. Further large-scale studies focusing on a Western population are needed. The aim of this review is to evaluate the evidence with respect to the current studies and data about the safety and efficacy of radiofrequency ablation for the management of BTNs and DTC.

Methods: We systematically searched the PubMed/MEDLINE, EMBASE, Clinical Queries, and Web of Science databases, for articles published up to April 30th, 2020.

Results: Total of 75 studies that met the inclusion criteria were included in the review. Thirty-five studies focused on RFA use for solid nodules, 12 studies on predominantly cystic nodules, 10 for autonomously functioning thyroid nodules, and 18 studied were published on differentiated thyroid cancer.

Conclusions: RFA seems to be an effective and safe alternative to surgery in high-risk surgical patients with thyroid cancers and for selected BTNs. Additional trials with longer follow-up in North American patients are needed to validate its full role in the armamentarium of thyroid ologists.
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http://dx.doi.org/10.1007/s12020-020-02598-6DOI Listing
June 2021

Long-term variability of glycemic markers and risk of all-cause mortality in type 2 diabetes: the Look AHEAD study.

BMJ Open Diabetes Res Care 2020 11;8(2)

Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Introduction: Glycemic variability may predict poor outcomes in type 2 diabetes. We evaluated the associations of long-term variability in glycosylated hemoglobin (HbA) and fasting plasma glucose (FPG) with cardiovascular disease (CVD) and death among individuals with type 2 diabetes.

Research Design And Methods: We conducted a secondary, prospective cohort analysis of the Look AHEAD (Action for Health in Diabetes) data, including 3560 participants who attended four visits (baseline, 12 months, 24 months, and 36 months) at the outset. Variability of HbA and FPG was assessed using four indices across measurements from four study visits. Participants without CVD during the first 36 months were followed for incident outcomes including a CVD composite (myocardial infarction, stroke, hospitalization for angina, and CVD-related deaths), heart failure (HF), and deaths.

Results: Over a median follow-up of 6.8 years, there were 164 deaths from any cause, 33 CVD-related deaths, 91 HF events, and 340 participants experienced the CVD composite. Adjusted HRs comparing the highest to lowest quartile of SD of HbA were 2.10 (95% CI 1.26 to 3.51), 3.43 (95% CI 0.95 to 12.38), 1.01 (95% CI 0.69 to 1.46), and 1.71 (95% CI 0.69 to 4.24) for all-cause mortality, CVD mortality, CVD composite and HF, respectively. The equivalent HRs for highest versus lowest quartile of SD of FPG were 1.66 (95% CI 0.96 to 2.85), 2.20 (95% CI 0.67 to 7.25), 0.94 (95% CI 0.65 to 1.35), and 2.05 (95% CI 0.80 to 5.31), respectively.

Conclusions: A greater variability in HbA was associated with elevated risk of mortality. Our findings underscore the need to achieve normal and consistent glycemic control to improve clinical outcomes among individuals with type 2 diabetes.
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http://dx.doi.org/10.1136/bmjdrc-2020-001753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705503PMC
November 2020

The prostate-specific membrane antigen (PSMA)-targeted radiotracer F-DCFPyL detects tumor neovasculature in metastatic, advanced, radioiodine-refractory, differentiated thyroid cancer.

Med Oncol 2020 Oct 9;37(11):98. Epub 2020 Oct 9.

Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Prostate-specific membrane antigen (PSMA; also termed glutamate carboxypeptidase II (GCP II)) is abundantly expressed in prostate cancer. It has been shown recently that PSMA is expressed in neovasculature of differentiated thyroid cancer. In this study, we show that F-DCFPyl might detect neovasculature in advanced, metastatic differentiated thyroid cancer (DTC). We first stained the preserved lymph node samples of three patients with DTC who had undergone total thyroidectomy and neck dissection for cervical lymph node metastatic disease to identify PSMA expression, with the PSMA antibody (DAKO Monoclonal). Then, we performed F-DCFPyl imaging in two other advanced DTC patients with elevated serum thyroglobulin (Tg), indicative of residual disease. We compared the findings with contemporaneous FDG PET/CT scan, conventional Imaging (CT,MRI) and whole-body scan performed with I/I. All the three lymph node samples stained positive for PSMA expression in the neovasculature. In the first imaged patient, F-DCFPyl detected activity within the retropharyngeal CT contrast-enhancing lymph node. Compared to FDG PET/CT, the F-DCFPyl scan showed a greater SUV (3.1 vs 1.8). In the second imaged patient, F-DCFPyl showed intense uptake in the L3 vertebra (not seen on the post treatment I scan or the F-FDG PET/CT). MRI of the lumbar spine confirmed the presence of sclerotic-lytic lesion at the location, consistent with metastatic disease. Our exploratory study is proof of principle, that the prostate cancer imaging agent F-DCFPyl may prove useful for the localization of metastases, in patients with metastatic RAI-refractory DTC by detecting neoangiogenesis within the tumor.
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http://dx.doi.org/10.1007/s12032-020-01427-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759157PMC
October 2020

C-metomidate PET in the diagnosis of adrenal masses and primary aldosteronism: a review of the literature.

Endocrine 2020 12 4;70(3):479-487. Epub 2020 Sep 4.

Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Adrenal masses are commonly encountered in clinical practice, many of whom are incidental. Identifying malignancy, and excess hormone production is essential for appropriate management. Biochemical workup and imaging tests (dedicated adrenal CT and/or MRI) are used to determine the likelihood of excessive hormone function and malignancy, respectively. However, imaging cannot provide information about function and biochemical workup cannot localize the source. Furthermore, in primary aldosteronism, adrenal vein sampling, the gold standard for lateralization, has important limitations such as the technical expertise required, the elevated costs, and potential complications. Over the last decades, there has been a renewed interest in alternative noninvasive imaging techniques that provide information about adrenal function without the need for invasive procedures. In this review, we will evaluate the evidence and the potential role of C-metomidate as a promising positron emission tomography (PET) tracer in clinical practice.

Methods: A review of the English literature for articles describing the use of the tracer C-metomidate in adrenal disorders.

Results: A total of 12 studies were included in the systematic review, which altogether addressed the use of C-metomidate in adrenal masses and the application of this tracer in primary aldosteronism.

Conclusions: C-metomidate, a selective inhibitor of 11-β-hydroxylase, demonstrated a high specificity for adrenocortical tissue. In addition, C-metomidate is correlated with this enzyme activity making it a potentially useful PET tracer for the identification primary aldosteronism, in addition to detection of adrenocortical masses.
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http://dx.doi.org/10.1007/s12020-020-02474-3DOI Listing
December 2020

Misdiagnosis of Paraganglioma by I-mIBG Without Stable Iodine Blockade of Thyroidal Radioiodine Uptake.

J Endocr Soc 2020 Sep 17;4(9):bvaa099. Epub 2020 Jul 17.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Iodine-123/iodine-131 (I/I)-metaiodobenzylguanidine (mIBG) scan is an established tool for the localization and treatment of neuroendocrine tumors such as paragangliomas (PGL). To minimize thyroid irradiation by the radioactive iodine in the mIBG preparation, blockade of thyroidal iodine uptake with high doses of stable iodine used to be given routinely as part of all mIBG protocols. As I is now more frequently utilized than I, concern about thyroid radiation has lessened and thyroid blockade is often considered unnecessary. However, in certain situations, the lack of thyroid blockade can significantly impact treatment decisions. This report describes 2 patients who had mediastinal masses incidentally discovered on CT scans, and on further evaluation were found to have symptoms suggesting catecholamine excess with mildly elevated plasma normetanephrine levels. I-mIBG scans were performed without thyroid blockade, which demonstrated accumulation of tracer in the masses that were therefore deemed positive for PGL. Both patients underwent surgical resection of the masses with their surgical pathology revealing ectopic thyroid tissue (ETT). These cases illustrate that if appropriate thyroid blockade is not performed, ETT concentrating radioiodine from mIBG can lead to falsely positive mIBG scans and unnecessary surgical procedures. We conclude that in the setting of a mass suspicious for PGL in a location potentially representing ETT, such as the mediastinum, thyroid blockade should be employed for mIBG protocols to avoid false positive scans caused by ETT.
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http://dx.doi.org/10.1210/jendso/bvaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414919PMC
September 2020

DXA measured body composition predicts blood pressure using machine learning methods.

J Clin Hypertens (Greenwich) 2020 06 4;22(6):1098-1100. Epub 2020 Jun 4.

Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1111/jch.13914DOI Listing
June 2020

Artificial intelligence may offer insight into factors determining individual TSH level.

PLoS One 2020 20;15(5):e0233336. Epub 2020 May 20.

Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

The factors that determine Serum Thyrotropin (TSH) levels have been examined through different methods, using different covariates. However, the use of machine learning methods has so far not been studied in population databases like NHANES (National Health and Nutritional Examination Survey) to predict TSH. In this study, we performed a comparative analysis of different machine learning methods like Linear regression, Random forest, Support vector machine, multilayer perceptron and stacking regression to predict TSH and classify individuals with normal, low and high TSH levels. We considered Free T4, Anti-TPO antibodies, T3, Body Mass Index (BMI), Age and Ethnicity as the predictor variables. A total of 9818 subjects were included in this comparative analysis. We used coefficient of determination (r2) value to compare the results for predicting the TSH and show that the Random Forest, Gradient Boosting and Stacking Regression perform equally well in predicting TSH and achieve the highest r2 value = 0.13, with mean absolute error of 0.78. Moreover, we found that Anti-TPO is the most important feature in predicting TSH followed by Age, BMI, T3 and Free-T4 for the regression analysis. While classifying TSH into normal, high or low levels, our comparative analysis also shows that Random forest performs the best in the classification study, performed with individuals with normal, high and low levels of TSH. We found the following Areas Under Curve (AUC); for low TSH, AUC = 0.61, normal TSH, AUC = 0.61 and elevated TSH AUC = 0.69. Additionally, we found that Anti-TPO was the most important feature in classifying TSH. In this study, we suggest that artificial intelligence and machine learning methods might offer an insight into the complex hypothalamic-pituitary -thyroid axis and may be an invaluable tool that guides us in making appropriate therapeutic decisions (thyroid hormone dosing) for the individual patient.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233336PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239447PMC
August 2020

Machine learning and blood pressure.

J Clin Hypertens (Greenwich) 2019 11 19;21(11):1735-1737. Epub 2019 Sep 19.

Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Machine learning (ML) is a type of artificial intelligence (AI) based on pattern recognition. There are different forms of supervised and unsupervised learning algorithms that are being used to identify and predict blood pressure (BP) and other measures of cardiovascular risk. Since 1999, starting with neural network methods, ML has been used to gauge the relationship between BP and pulse wave forms. Since then, the scope of the research has expanded to using different cardiometabolic risk factors like BMI, waist circumference, waist-to-hip ratio in concert with BP and its various pharmaceutical agents to estimate biochemical measures (like HDL cholesterol, LDL and total cholesterol, fibrinogen, and uric acid) as well as effectiveness of anti-hypertensive regimens. Data from large clinical trials like the SPRINT are being re-analyzed by ML methods to unearth new findings and identify unique relationships between predictors and outcomes. In summary, AI and ML methods are gaining immense attention in the management of chronic disease. Elevated BP is a very important early metric for the risk of development of cardiovascular and renal injury; therefore, advances in AI and ML will aid in early disease prediction and intervention.
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http://dx.doi.org/10.1111/jch.13700DOI Listing
November 2019

Relationship between DXA measured metrics of adiposity and glucose homeostasis; An analysis of the NHANES data.

PLoS One 2019 22;14(5):e0216900. Epub 2019 May 22.

Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.

Introduction: Obesity is associated with insulin resistance and type 2 diabetes. Dual-energy X-ray absorptiometry (DXA) is a means of determining body composition and body fat distribution at different sites including whole body and trunk-locations where there tends to be high correlation at an individual level.

Methods: We performed an analysis of DXA-derived metrics of adiposity (truncal fat %,subtotal fat % and total fat %) from the NHANES database and then correlated the findings with markers of insulin resistance. We analyzed the data from DXA scans in NHANES 1999-2004. Homeostatic model assessment-insulin resistance and HOMA-β (beta-cell function) were estimated. Spearman correlation coefficients were calculated (ρ) between HOMA-IR,HOMA-β and different measures of obesity (Waist circumference(in cm), Body Mass Index (kg/m2), truncal fat %, subtotal fat % as well as total fat %) to gauge the relationship between markers of glucose homeostasis and DXA derived metrics of obesity. We also performed logarithmic transformation of HOMA-IR as well as HOMA-β to ensure normality of distribution and to meet the criteria for regression analysis. A forward selection model (by outcome and gender) was performed to predict log transformed insulin resistance (log HOMA-IR) as well as log transformed HOMA-β (log HOMA-β,measure of beta cell function) from age, serum triglycerides, HDL, trunk fat % and the SBP (in both males and females separately), after reviewing the spearman correlation coefficients.

Results: There were a total of 6147 men and 6369 women who were part of the study cohort. There was a positive correlation between markers of adiposity and log HOMA-IR and log HOMA-β in both males and females.Truncal fat % had the highest nonparametric correlation coefficent with log HOMA-IR among the DXA derived fat% (0.54 in males and 048 in females). In the multivariate analysis, truncal fat % was an independent predictor of logHOMA-IR as well as logHOMA-β. In males, the significant predictors of log HOMA-IR were; age, truncal fat % and HDL cholesterol (Adjusted R square of 0.325 (±0.66), F(3,207) = 34.63, p < .01). In females, the significant predictors of log HOMA-IR were; age, truncal fat %, SBP, Serum triglyceride and HDL cholesterol (Adjusted R square of 0.307 (±0.65),F(5,198) = 18.9, p < .01). In both males and females, the significant predictors of log HOMA-β were; age, and truncal fat % (Males; adjusted R square of 0.25 (±0.63), F (2,208) = 36.4, p < .01, Females; adjusted R square of 0.27 (±0.62), F (2,201) = 38.4, p < .01).

Conclusions: Body fat % on DXA is an imaging biomarker for insulin resistance. Incorporating this important information into DXA acquisitions and reporting frameworks may allow for this information to be available to providers who refer patients for these imaging studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216900PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530894PMC
January 2020

Detection rate of unknown primary tumour by using somatostatin receptor PET/CT in patients with metastatic neuroendocrine tumours: a meta-analysis.

Endocrine 2019 06 19;64(3):456-468. Epub 2019 Apr 19.

Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Bellinzona, Switzerland.

Purpose: The high diagnostic performance of somatostatin receptor positron emission tomography with computed tomography (PET/CT) in neuroendocrine tumours (NETs) was demonstrated by several articles. However, only some studies evaluated the detection rate (DR) of this imaging method in patients with metastatic NETs and unknown primary tumours (CUP-NETs). Therefore, we aimed to perform a meta-analysis to add evidence-based data in this setting.

Methods: A comprehensive computer literature search of studies listed in PubMed/MEDLINE, EMBASE, and Cochrane library databases through December 2018 and regarding the use of somatostatin receptor PET/CT in patients with CUP-NETs was carried out. Pooled DR of CUP-NETs by using somatostatin receptor PET/CT was calculated. A pooled analysis evaluating the percentage of change of management by using somatostatin receptor PET/CT in these patients was also performed.

Results: Twelve studies on the use of somatostatin receptor PET/CT in detecting CUP-NETs in 383 metastatic patients were included. The meta-analysis of all these studies provided the following DR on a per patient-based analysis: 56% (95% confidence interval (95% CI): 48-63%). Moderate heterogeneity among the selected studies was found (I = 50%), whereas a significant publication bias was excluded by Egger's test (p = 0.45). The most common primary tumour sites were the bowel and the pancreas. A change of management by using somatostatin receptor PET/CT was demonstrated in 20% (95% CI: 10-33%) of patients with CUP-NET.

Conclusions: Somatostatin receptor PET/CT is very useful in detecting CUP-NETs in patients with metastatic disease. More studies on the change of management by using this imaging method in this setting are needed.
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http://dx.doi.org/10.1007/s12020-019-01934-9DOI Listing
June 2019

Relationship between lean body mass indices, physical activity, and systolic BP: Analysis of 1999-2006 NHANES data.

J Clin Hypertens (Greenwich) 2019 05 20;21(5):692-693. Epub 2019 Mar 20.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1111/jch.13516DOI Listing
May 2019

Surveillance for Differentiated Thyroid Cancer Recurrence.

Endocrinol Metab Clin North Am 2019 03;48(1):239-252

Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, MD 21287, USA.

Serum thyroglobulin monitoring along with anatomic and functional imaging play key roles in the surveillance of patients with differentiated thyroid cancer after initial treatment. Among patients with a disease stage justifying thyroid remnant ablation or with suspected metastatic disease, radioiodine whole-body scans are essential in the months after surgery. For patients with low to moderate-risk cancers, ultrasonography of the neck (with measurement of serum thyroglobulin on thyroid hormone replacement) are the best initial diagnostic modalities, and are often the only tests required. In individuals suspected of having distant metastases, CT, MRI, and 18F-FDG PET can make important contributions in localizing residual disease and monitoring its progression and responses to therapy, provided they are used in the appropriate setting.
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http://dx.doi.org/10.1016/j.ecl.2018.11.008DOI Listing
March 2019

Differences in blood pressure among ethnicities presenting for catecholamine-secreting tumor evaluation.

J Clin Hypertens (Greenwich) 2019 02 5;21(2):338. Epub 2018 Dec 5.

Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1111/jch.13454DOI Listing
February 2019

Adding value to myocardial perfusion SPECT/CT studies that include coronary calcium CT: Detection of incidental pulmonary arterial dilatation.

Medicine (Baltimore) 2018 Aug;97(32):e11359

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD.

The aim of the present study was to evaluate the incidence of undiagnosed pulmonary arterial dilatation using the gated computed tomography (CT) images acquired in patients with an otherwise normal Tc-sestamibi single-photon-emission CT (SPECT)/CT myocardial perfusion study.This was a retrospective review of 200 consecutive patients (100 men, mean age 58.7 years) who underwent a myocardial perfusion Tc-sestamibi SPECT/CT study with normal perfusion and with gated CT images acquired for coronary calcium scoring. The CT images were reviewed using a previously validated mean main pulmonary artery diameter (mPAD) measurement method which has been correlated with pulmonary arterial hypertension (PAH). Clinical information on multiple comorbidities was also retrieved. Previously reported mPAD cutoffs (>29.5 and >31.5 mm) were used to stratify patients.Indications for the study included dyspnea on exertion (58.9%), preoperative workup (22.3%), and chest pain (13.9%). The mean mPAD measurement was 26.3 mm (±0.5). There was a significant correlation between body mass index and mPAD (correlation coefficient [ρ]: 0.28; P < .001). About 23% (46/200) of patients had mPAD > 29.5 mm and 15.0% (30/200) of patients had mPAD > 31.5 mm. From previous work, these cutoffs have a sensitivity and specificity for PAH of 70.8%, 79.4% and 52.0%, 90.2%, respectively. Among patients undergoing a preoperative myocardial perfusion study, 35.6% (16/45) patients had mPAD > 29.5 mm and 26.7% (12/45) patients had mPAD > 31.5 mm. There was a higher prevalence of congestive heart failure (62.5% vs 19.6%; P < .001) and hypertension (78.3% vs 21.7%; P < .02) in patients with mPAD > 29.5 mm. Similarly, there was a high prevalence of congestive heart failure (P < .001), hyperlipidemia (P < .04), and hypertension (P < .04) in patients with mPAD > 31.5 mm.Incidental pulmonary arterial dilatation (mPAD ≥ 29.5 mm) can be detected in a large number of patients with normal myocardial perfusion scintigraphy and correlates with multiple different comorbidities. The mPAD can be measured in all patients undergoing gated imaging as part of a myocardial perfusion study, and PAH may be considered as an alternative explanation for symptoms in some patients without perfusion deficits. The data to make this potential diagnosis is already being acquired and represents an opportunity to add value to the interpretations of otherwise negative myocardial perfusion studies.
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http://dx.doi.org/10.1097/MD.0000000000011359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133560PMC
August 2018

Brown Adipose Tissue (BAT) detection by F-FDG PET and thyroid hormone level(s)-a systematic review.

Endocrine 2018 11 31;62(2):496-500. Epub 2018 Jul 31.

Clinic of Nuclear Medicine and PET/CT Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

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http://dx.doi.org/10.1007/s12020-018-1698-xDOI Listing
November 2018

Body mass index, dual-energy X-ray absorptiometry fat indices and systolic hypertension in NHANES 2000-2006.

J Clin Hypertens (Greenwich) 2018 Jun 12. Epub 2018 Jun 12.

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1111/jch.13318DOI Listing
June 2018

Detection of brown adipose tissue by F-FDG PET/CT in pheochromocytoma/paraganglioma: A systematic review.

J Clin Hypertens (Greenwich) 2018 03 14;20(3):615. Epub 2018 Feb 14.

Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1111/jch.13228DOI Listing
March 2018

Systematic review of nephrotoxicity of drugs of abuse, 2005-2016.

BMC Nephrol 2017 12 29;18(1):379. Epub 2017 Dec 29.

Joan C. Edwards School of Medicine, Marshall University, 1690 Medical Center Drive, Huntington, WV, 25701, USA.

Background: The United States is faced with an unprecedented epidemic of drug abuse. Every year thousands of Americans visit the emergency departments all over the country with illicit drug related complaints. These drugs have been known to be associated with a range of renal pathologies, from reversible acute kidney injuries to debilitating irreversible conditions like renal infarction. So far, no comprehensive study or systematic review has been published that includes the commonly used street drugs and designer drugs with potential nephrotoxic outcomes.

Methods: We conducted a systematic review of published case reports, case series, and cross sectional studies of nephrotoxicities related to drugs of abuse. Literature review was conducted using PubMed/Medline from January 1, 2005 -December 31, 2016 to search for publications related to drug abuse with a defined renal outcome. Publications which reported renal injury in relation to the use of illicit drugs were selected, specifically those cases with raised creatinine levels, clinically symptomatic patients, for instance those with oliguria and proven renal biopsies.

Results: A total of 4798 publications were reviewed during the search process and PRISMA flow chart and Moose protocol regarding systematic reviews were followed. 110 articles were shortlisted for the review. A total of 169 cases from case reports and case series, and 14 case studies were analyzed. Renal manifestations of specific illicit drug abuse were included in this review.

Conclusion: Based on the evidence presented, a wide range of renal manifestations were found to be associated with drug abuse. If the trend of increasing use of illicit drug use continues, it will put a significant percentage of the population at an elevated risk for poor renal outcomes. This study is limited by the nature of the literature reviewed being primarily case reports and case series.
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http://dx.doi.org/10.1186/s12882-017-0794-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747941PMC
December 2017

Correction to: Molecular imaging of advanced thyroid cancer: iodinated radiotracers and beyond.

Med Oncol 2017 12 12;35(1):10. Epub 2017 Dec 12.

Section of Nuclear Medicine, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

The original version of this article unfortunately contained a mistake. The middle name of the author Steven B. Rowe is incorrect. The corrected name is Steven P. Rowe.
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http://dx.doi.org/10.1007/s12032-017-1063-6DOI Listing
December 2017