505 results on '"Aaron I. Vinik"'
Search Results
2. Calcitonin-Secreting Pancreatic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1
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Umer A. Ansari, BS, Christine L. Ramirez, MD, Eric C. Feliberti, MD, Aaron I. Vinik, MD, PhD, and Roger R. Perry, MD, MS
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ABSTRACT: Objective: To present a patient with multiple endocrine neoplasia type 1 (MEN1) syndrome recently diagnosed with a calcitonin-secreting pancreatic neuroendocrine tumor.Methods: Clinical and diagnostic evaluation, along with intervention, is presented. The relevant literature is reviewed.Results: The patient was a 52-year-old Caucasian man with a history of known MEN1 who had a right parathyroidectomy 10 years prior to admission, completion parathyroidectomy and total thyroidectomy for C cell hyperplasia 3 years prior, and removal of a pituitary adenoma 4 years prior. He was asymptomatic but had persistently elevated serum calcitonin levels. Venous sampling and positron emission tomography–computerized tomography indicated several lesions in the pancreas as the most likely cause of ectopic calcitonin secretion. The patient underwent pylorus-sparing pancreaticoduodenectomy (Whipple procedure). Several well-differentiated neuroendocrine lesions of the pancreas were noted, with lymphatic invasion and spread to a peripancreatic lymph node. Postoperatively, the patient's calcitonin levels returned to the normal range.Conclusion: Calcitonin-secreting pancreatic neuroendocrine tumors are relatively rare entities that are even more rare in familial syndromes such as MEN1. Due to the clinically silent nature of these lesions, they are often discovered incidentally and late in their clinical course. More data are needed in order to establish a consensus on ideal management. Calcitonin elevation even in MEN1 may herald non-thyroid malignancy, therefore demanding an aggressive approach to evaluation and treatment.Abbreviations: CT computerized tomography; MEN1 multiple endocrine neoplasia type 1; PNETs pancreatic neuroendocrine tumors; PP pancreatic polypeptide; VIP vasoactive intestinal peptide
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- 2017
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3. Expression of Hypoxia-Inducible Factors in Different Stages of Pancreatic Tumor Progression
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Jung Hwa Jung, Danuta Sosnowska, Jessica Weaver, Henri K. Parson, Carolina M. Casellini, and Aaron I. Vinik
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hypoxia ,pancreatic adenocarcinoma ,neuroendocrine tumor ,pancreatic intraepithelial neoplasia ,intraductal papillary mucinous neoplasm ,Medicine (General) ,R5-920 ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Background: Early diagnosis in pancreatic cancer is key for improving prognosis. Hypoxia plays a critical role in tumor progression. Thus, an evaluation of associations between pancreatic tumor progression and markers of hypoxia is needed. Methods: We assessed the expression of hypoxia-inducible factors (HIF-1α and HIF-2α) by immuno-histochemical staining from 29 subjects with the following: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumor (NET), and pancreatic ductal adenocarcinoma (PDAC) and compared it to the expression in non-tumor samples. Results: Expression of HIF-1α increased significantly from PanIN (3.01 ± 0.17) to IPMN (7.63 ± 0.18), NET (9.10 ± 0.23) and PDAC samples (11.06 ± 0.15, p < 0.0001). Similar findings were observed for HIF-2α (p < 0.0001)}. A strong correlation between HIF-1α and HIF-2α expression was demonstrated (R2 = 0.8408, p < 0.0001). Conclusions: This data suggest that HIF-1α and HIF-2α may play a role in the progression from PanIN through PDAC. Further studies are necessary to confirm these findings and determine the effect of HIFs abrogation on tumor progression that can lead to novel therapies.
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- 2020
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4. Cardiac Autonomic Neuropathy in Diabetes: A Predictor of Cardiometabolic Events
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Aaron I. Vinik, Carolina Casellini, Henri K. Parson, Sheri R. Colberg, and Marie-Laure Nevoret
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cardiac autonomic neuropathy ,sympathetic ,parasympathetic ,dopamine deficiency ,insulin resistance ,cardiovascular event prediction ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that lower blood glucose. Rather than intensifying diabetes control, a regimen tailored to the individual risk of autonomic imbalance should be implemented. New agents that may improve autonomic function, such as SGLT2 inhibitors, should be considered and the use of incretins monitored. One of the central mechanisms of dysfunction is disturbance of the hypothalamic cardiac clock, a consequence of dopamine deficiency that leads to sympathetic dominance, insulin resistance, and features of the metabolic syndrome. An improvement in ANS balance may be critical to reducing cardiovascular events, cardiac failure, and early mortality in the diabetic population.
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- 2018
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5. Improved Patient Outcomes by Normalizing Sympathovagal Balance: Differentiating Syncope—Precise Subtype Differentiation Leads to Improved Outcomes
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Nicholas L. DePace, Julie A. Bateman, Michael Yayac, John Oh, Mushfiqur Siddique, Cesar Acosta, Jeysel M. Pinales, Aaron I. Vinik, and Heather L. Bloom
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Syncope is difficult to definitively diagnose, even with tilt-table testing and beat-to-beat blood pressure measurements, the gold-standard. Both are qualitative, subjective assessments. There are subtypes of syncope associated with autonomic conditions for which tilt-table testing is not useful. Heart rate variability analyses also include too much ambiguity. Three subtypes of syncope are differentiated: vasovagal syncope (VVS) due to parasympathetic excess (VVS-PE), VVS with abnormal heart rate response (VVS-HR), and VVS without PE (VVS-PN). P&S monitoring (ANSAR, Inc., Philadelphia, PA) differentiates subtypes in 2727 cardiology patients (50.5% female; average age: 57 years; age range: 12–100 years), serially tested over four years (3.3 tests per patient, average). P&S monitoring noninvasively, independently, and simultaneously measures parasympathetic and sympathetic (P&S) activity, including the normal P-decrease followed by an S-increase with head-up postural change (standing). Syncope, as an S-excess (SE) with stand, is differentiated from orthostatic dysfunction (e.g., POTS) as S-withdrawal with stand. Upon standing, VVS-PE is further differentiated as SE with PE, VVS-HR as SE with abnormal HR, and VVS-PN as SE with normal P- and HR-responses. Improved understanding of the underlying pathophysiology by more accurate subtyping leads to more precise therapy and improved outcomes.
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- 2018
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6. Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral Neuropathy
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Gautam Ghatnekar, April Ann Cox, Yves Sagot, Gael Hedou, Christina Grek, Travis Wilkes, and Aaron I. Vinik
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diabetic peripheral neuropathy ,interleukin-6 ,nerve regeneration ,myokine ,neurocytokine ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Diabetic peripheral neuropathy (DPN) remains one of the most common and serious complications of diabetes. Currently, pharmacological agents are limited to treating the pain associated with DPN, and do not address the underlying pathological mechanisms driving nerve damage, thus leaving a significant unmet medical need. Interestingly, research conducted using exercise as a treatment for DPN has revealed interleukin-6 (IL-6) signaling to be associated with many positive benefits such as enhanced blood flow and lipid metabolism, decreased chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known solely as a pro-inflammatory cytokine, is now understood to signal as a multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory responses in a context-dependent fashion. IL-6 released from muscle in response to exercise signals as a myokine and as such has a unique kinetic profile, whereby levels are transiently elevated up to 100-fold and return to baseline levels within 4 h. Importantly, this kinetic profile is in stark contrast to long-term IL-6 elevation that is associated with pro-inflammatory states. Given exercise induces IL-6 myokine signaling, and exercise has been shown to elicit numerous beneficial effects for the treatment of DPN, a causal link has been suggested. Here, we discuss both the clinical and preclinical literature related to the application of IL-6 as a treatment strategy for DPN. In addition, we discuss how IL-6 may directly modulate Schwann and nerve cells to explore a mechanistic understanding of how this treatment elicits a neuroprotective and/or regenerative response. Collectively, studies suggest that IL-6, when administered in a low-dose pulsatile strategy to mimic the body’s natural response to exercise, may prove to be an effective treatment for the protection and/or restoration of peripheral nerve function in DPN. This review highlights the studies supporting this assertion and provides rationale for continued investigation of IL-6 for the treatment of DPN.
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- 2017
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7. A Comparison of Screening Tools for the Early Detection of Peripheral Neuropathy in Adults with and without Type 2 Diabetes
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Jennifer J. Brown, Shana L. Pribesh, Kimberly G. Baskette, Aaron I. Vinik, and Sheri R. Colberg
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN) questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN) in overweight, obese, and inactive (OOI) adults or those who have prediabetes (PD) or type 2 diabetes (T2D). Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1) were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D). Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP) and sural nerve conduction velocity (SNCV). All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.
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- 2017
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8. Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol) on parasympathetic and sympathetic activity: a comparison of measures
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Aaron I. Vinik, Heather L. Bloom, and Joe Colombo
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Beta-blocker ,Cardiac autonomic neuropathy ,Heart rate variability ,Patient outcomes ,Respiratory analysis ,Sympathovagal imbalance ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Cardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk. Specific and sensitive measures of CAN are needed for early identification and treatment to avoid complications, preferably in the preclinical state. Objectives In this first of two articles, the patient cohort is described and two measures of autonomic function are reviewed: the traditional heart rate variability (HRV)-alone method and the newer parasympathetic and sympathetic (P&S) Method. These systems are then evaluated against known effects of the alpha/beta-adrenergic blocker, Carvedilol, and the selective beta-adrenergic blocker, Metoprolol, on P&S activity. Methods Serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced, (2) discontinued or (3) continued without adjustment. Group 3 served as the control. HRV-alone parameters are computed according to standards. The P&S Method, which is a time–frequency analyses of concurrent respiratory activity and HRV, is elucidated, as developed at MIT and Harvard Medical School (1981). Results The HRV-alone demonstrated that introducing either medication increased low frequency (msec2) and standard deviation of the beat-to-beat (N-N) interval (msec), as expected. The other HRV parameter responses were not consistent with expectations. Similar inconsistencies occurred when either medication was discontinued. The P&S Method demonstrated that introducing or discontinuing either agent decreased or increased sympathetic activity, respectively, according to expectations. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. Conclusion Autonomic assessment fidelity was significantly higher with the P&S Method as validated by comparison with previously known physiology of the cardiovascular system.
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- 2014
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9. Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol) on parasympathetic and sympathetic activity: a comparison of clinical results
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Heather L. Bloom, Aaron I. Vinik, and Joe Colombo
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Beta-blocker ,Cardiovascular autonomic neuropathy ,Heart rate variability ,Patient outcomes ,Respiratory analysis ,Sympathovagal imbalance ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Cardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk, correlating with risk of heart disease, silent myocardial ischemia or sudden cardiac death. Beta-blockers are often prescribed to minimize risk. Objectives In this second of two articles, the effects on parasympathetic and sympathetic activity of the alpha/beta-adrenergic blocker, Carvedilol, are compared with those of the selective beta-adrenergic blocker, Metoprolol. Methods Retrospective, serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced, (2) discontinued or (3) continued without adjustment. Group 3 served as the control. Results Introducing Carvedilol or Metoprolol decreased heart rate and blood pressure, and discontinuing them had the opposite effect. Parasympathetic activity increased with introducing Carvedilol. Sympathetic activity increased more after discontinuing Carvedilol, suggesting better sympathetic suppression. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. Conclusion Carvedilol has a more profound effect on sympathovagal balance than Metoprolol. While both suppress sympathetic activity, only Carvedilol increases parasympathetic activity. Increased parasympathetic activity may underlie the lower mortality risk with Carvedilol.
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- 2014
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10. Delay between Onset of Symptoms and Seeking Physician Intervention Increases Risk of Diabetic Foot Complications: Results of a Cross-Sectional Population-Based Survey
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Norina A. Gavan, Ioan A. Veresiu, Etta J. Vinik, Aaron I. Vinik, Bogdan Florea, and Cosmina I. Bondor
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
We present a post hoc analysis of 17,530 questionnaires collected as part of the 2012 screening for neuropathy using Norfolk Quality of Life tool in patients with diabetes in Romania, to assess the impact on foot complications of time between the onset of symptoms of diabetes/its complications and the physician visit. Odds ratios (ORs) for self-reporting neuropathy increased from 1.16 (95% CI: 1.07–1.25) in those who sought medical care in 1–6 months from symptoms of diabetes/its complications onset to 2.27 in those who sought medical care >2 years after symptoms onset. The ORs for having a history of foot ulcers were 1.43 (95% CI: 1.26–1.63) in those who sought medical care in 1–6 months and increased to 3.08 (95% CI: 2.59–3.66) in those who sought medical care after >2 years from symptoms of diabetes/its complications onset. The highest ORs for a history of gangrene (2.49 [95% CI: 1.90–3.26]) and amputations (2.18 [95% CI: 1.60–2.97]) were observed in those who sought medical care after >2 years following symptoms onset. In conclusion, we showed that waiting for >1 month after symptoms onset dramatically increases the risk of diabetic foot complications. These results show the need for accessible educational programs on diabetes and its chronic complications and the need to avoid delays in reporting.
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- 2016
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11. Epidemiology of Diabetic Foot Ulcers and Amputations in Romania: Results of a Cross-Sectional Quality of Life Questionnaire Based Survey
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Cosmina I. Bondor, Ioan A. Veresiu, Bogdan Florea, Etta J. Vinik, Aaron I. Vinik, and Norina A. Gavan
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
This is a post hoc analysis of quality of life in diabetic neuropathy patients in a cross-sectional survey performed in 2012 in Romania, using the Norfolk QOL-DN in which 21,756 patients with self-reported diabetes were enrolled. This current analysis aims to expand research on the diabetic foot and to provide an update on the number of foot ulcers found in Romania. Of the 21,174 patients included in this analysis, 14.85% reported a history of foot ulcers and 3.60% reported an amputation. The percentage of neuropathy patients with foot ulcers increased with age; the lowest percentage was observed in the 20–29-year age group (6.62%) and the highest in the 80–89-year age group (17.68%). The highest number of amputations was reported in the 70–79-year age group (largest group). Compared to patients without foot ulcers, those with foot ulcers had significantly higher scores for total DN and all its subdomains translating to worse QOL (p
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- 2016
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12. Cardiac and Sudomotor Autonomic Function in Subjects with Psoriasis With and Without Metabolic Syndrome
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Carolina M. Casellini, Henri K. Parson, Michael D. Bailey, Taylor Dyson, Abby S. Van Voorhees, Aaron I. Vinik, and Elias S. Siraj
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Metabolic Syndrome ,Cross-Sectional Studies ,Endocrinology, Diabetes and Metabolism ,Quality of Life ,Internal Medicine ,Humans ,Insulin ,Psoriasis - Published
- 2022
13. Radioligand Theranostics in the Management of Neuroendocrine Tumors
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M Sue OʼDorisio, Aaron I. Vinik, Alan G. Harris, and Thomas M OʼDorisio
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Pathology ,medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Neuroendocrine tumors ,Medical Oncology ,medicine.disease ,Multimodal Imaging ,Theranostic Nanomedicine ,Article ,Neuroendocrine Tumors ,Endocrinology ,Internal Medicine ,Radioligand ,Humans ,Medicine ,Nuclear Medicine ,Precision Medicine ,Radiopharmaceuticals ,business - Published
- 2020
14. Case-Control Study of Paresthesia Among World Trade Center-Exposed Community Members
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Alexander Allen, Marc Wilkenfeld, Aaron I. Vinik, Michael Marmor, Joan Reibman, Yongzhao Shao, Sujata Thawani, Maria Luisa Cotrina, Mark M. Stecker, Ericka S Wong, Etta J. Vinik, and Bin Wang
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Nerve fiber ,Disease ,complex mixtures ,Article ,Disasters ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Occupational Exposure ,Humans ,Medicine ,Paresthesia ,business.industry ,Public Health, Environmental and Occupational Health ,World trade center ,Case-control study ,Dust ,Middle Aged ,030210 environmental & occupational health ,humanities ,medicine.anatomical_structure ,Case-Control Studies ,Neurologic abnormalities ,Etiology ,Female ,New York City ,September 11 Terrorist Attacks ,business ,Sensory nerve - Abstract
Objective To investigate whether paresthesia of the lower extremities following exposure to the World Trade Center (WTC) disaster was associated with signs of neuropathy, metabolic abnormalities, or neurotoxin exposures. Methods Case-control study comparing WTC-exposed paresthesia cases with "clinic controls" (WTC-exposed subjects without paresthesias), and "community controls" (WTC-unexposed persons). Results Neurological histories and examination findings were significantly worse in cases than controls. Intraepidermal nerve fiber densities were below normal in 47% of cases and sural to radial sensory nerve amplitude ratios were less than 0.4 in 29.4%. Neurologic abnormalities were uncommon among WTC-unexposed community controls. Metabolic conditions and neurotoxin exposures did not differ among groups. Conclusions Paresthesias among WTC-exposed individuals were associated with signs of neuropathy, small and large fiber disease. The data support WTC-related exposures as risk factors for neuropathy, and do not support non-WTC etiologies.
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- 2020
15. A Patient-Reported Outcomes Analysis Of Lanreotide In The Treatment Of NETs Patients With Carcinoid Syndrome: Evidence From The ELECT Trial
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Beloo Mirakhur, Nilani Liyanage, K Blot, Benedicte Lescrauwaet, Aaron I. Vinik, Luc Duchateau, and David Ray
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medicine.medical_specialty ,business.industry ,030503 health policy & services ,Octreotide ,Neuroendocrine tumors ,Placebo ,medicine.disease ,Lanreotide ,humanities ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Quality of life ,030220 oncology & carcinogenesis ,Relative risk ,Internal medicine ,Post-hoc analysis ,medicine ,0305 other medical science ,business ,Carcinoid syndrome ,medicine.drug - Abstract
Purpose The purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT. Methods The post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis. Results The three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06). Conclusion The higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide. Trial registration ClinicalTrials.gov identifier: NCT00774930.
- Published
- 2019
16. Patterns of Care Among Real-World Patients with Metastatic Neuroendocrine Tumors
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David Ray, Andrew J Klink, Alexandria T. Phan, Hsing-Ting Yu, Sonia Pulgar, Bruce A. Feinberg, and Aaron I. Vinik
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Male ,Cancer Research ,medicine.medical_specialty ,Octreotide ,Neuroendocrine tumors ,Lanreotide ,Systemic therapy ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,Endocrinology ,0302 clinical medicine ,Internal medicine ,Health care ,medicine ,Humans ,Dosing ,Neoplasm Metastasis ,Retrospective Studies ,Patterns of care ,business.industry ,Middle Aged ,medicine.disease ,Confidence interval ,Neuroendocrine Tumors ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Background Although recent pivotal trials (PROMID, CLARINET) have established somatostatin analogs (SSAs) as first-line agents for neuroendocrine tumors (NETs), their use in clinical practice is largely unknown. We aimed to understand real-world management and treatment of gastroenteropancreatic (GEP) NETs. Materials and Methods Patients with metastatic GEP-NETs treated with SSAs, lanreotide depot or octreotide long-acting release (LAR), between January 1, 2015, and December 31, 2015, were identified from a U.S. claims database supplemented with chart review for a subset of patients. Descriptive statistics summarized patients’ demographics, clinical characteristics, treatment patterns, and healthcare resource use. Univariate and multivariate comparisons were made across SSA groups. Results Among 548 patients treated with an SSA for metastatic GEP-NET (lanreotide = 108; octreotide = 440), demographic and clinical characteristics were similar across groups, except more patients with pancreatic NETs were treated with lanreotide (38.7% vs. 6.3%, p < .01). More octreotide patients had a diagnosis of carcinoid syndrome compared with lanreotide patients (19.8% vs. 11.1%, p = .02). Approximately 1.1% of patients received lanreotide (>120 mg every 4 weeks [Q4W]) at a dose above label compared with 12.7% of octreotide patients (>30 mg Q4W; p < .01). At 1.5 years after SSA initiation, 85.7% (95% confidence interval, 74.3%–92.3%) were still on index SSA as reported by the physician. Variances between chart review and claims data were significant. Conclusion SSAs were common in first-line systemic intervention, but dose escalations and dosing deviations outside of label were noted. Variances between claims and chart review warrant additional research to compare methodologies. With an increasing focus on value-based care in oncology, it is critical to understand the use of, and outcomes with, these agents in community practices. Implications for Practice The aim of this study was to enhance understanding of real-world management and treatment of metastatic neuroendocrine tumors (NETs), with particular focus on systemic therapy with a somatostatin analog (SSA). As per published guidelines, SSAs are common in first-line systemic intervention, but dose escalations and dosing deviations outside of the label are noted for symptom control. Nevertheless, oncologists must weigh the implications of the use of above-label dosing of SSAs to manage and treat patients with metastatic NET within a value-based care framework.
- Published
- 2019
17. Biochemical Responses in Symptomatic and Asymptomatic Patients with Neuroendocrine Tumors: Pooled Analysis of Two Phase 3 Trials
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George A. Fisher, Aaron I. Vinik, Christine Massien, Nilani Liyanage, Rodney F. Pommier, Susan Pitman Lowenthal, Marianne Pavel, Beloo Mirakhur, and Alexandria T. Phan
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Neuroendocrine tumors ,Lanreotide ,Asymptomatic ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,biology ,business.industry ,5-Hydroxyindoleacetic acid ,Chromogranin A ,General Medicine ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Biomarker (medicine) ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Carcinoid syndrome ,medicine.drug - Abstract
Objective: Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes. Methods: Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly. Results: Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a dec...
- Published
- 2018
18. Factors influencing the quality of life over a 4-year period of time in Romanian patients with diabetes mellitus
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Etta J. Vinik, Cosmina-Ioana Bondor, Andrei Ioan Veresiu, Diana Iulia Sima, Daniel‐Tudor Cosma, Camelia Larisa Vonica, Norina Alinta Gâvan, and Aaron I. Vinik
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Male ,medicine.medical_specialty ,Diabetic neuropathy ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Diabetes mellitus ,Surveys and Questionnaires ,Diabetes Mellitus ,Medicine ,Humans ,In patient ,030212 general & internal medicine ,Aged ,business.industry ,Romania ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,Cross-Sectional Studies ,Amputation ,Cohort ,Quality of Life ,business ,Follow-Up Studies - Abstract
AIM To evaluate the changes in quality of life (QOL), diabetic neuropathy (DN) and amputations over 4 years in patients with diabetes. METHODS In 2012, 25,000 Romanian-translated Norfolk QOL-DN self-administered questionnaires were distributed during a cross-sectional study. Between March-December 2016, all patients identified from the 2012 cohort and enrolled in this follow-up study completed the Norfolk QOL-DN questionnaire; amputations suffered since 2012 were recorded. The influence of age and duration of diabetes (DD) on delta QOL scores (defined as the differences between 2012 and 2016 scores) and of sex, age, diabetes type, DD and declared DN on amputations was explored using multivariate linear and logistic regression, respectively. RESULTS The mean (standard deviation) age of the 1865 participants was 60.6 (10.3) years. Mean total QOL-DN score increased from 2012 to 2016 by 4.39% (P = .079). Both DD (b = 0.39, 95% confidence interval [CI] 0.21-0.57, P
- Published
- 2020
19. Expression of Hypoxia-Inducible Factors in Different Stages of Pancreatic Tumor Progression
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Carolina Casellini, Jessica R. Weaver, Henri K. Parson, Aaron I. Vinik, Jung Hwa Jung, and Danuta Sosnowska
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0301 basic medicine ,Medicine (General) ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,Pancreatic Intraepithelial Neoplasia ,R895-920 ,03 medical and health sciences ,Medical physics. Medical radiology. Nuclear medicine ,0302 clinical medicine ,R5-920 ,Pancreatic tumor ,Pancreatic cancer ,pancreatic intraepithelial neoplasia ,medicine ,pancreatic adenocarcinoma ,Electrical and Electronic Engineering ,Intraductal papillary mucinous neoplasm ,business.industry ,hypoxia ,intraductal papillary mucinous neoplasm ,Hypoxia (medical) ,medicine.disease ,Atomic and Molecular Physics, and Optics ,030104 developmental biology ,Hypoxia-inducible factors ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,medicine.symptom ,business ,neuroendocrine tumor - Abstract
Background: Early diagnosis in pancreatic cancer is key for improving prognosis. Hypoxia plays a critical role in tumor progression. Thus, an evaluation of associations between pancreatic tumor progression and markers of hypoxia is needed. Methods: We assessed the expression of hypoxia-inducible factors (HIF-1&alpha, and HIF-2&alpha, ) by immuno-histochemical staining from 29 subjects with the following: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumor (NET), and pancreatic ductal adenocarcinoma (PDAC) and compared it to the expression in non-tumor samples. Results: Expression of HIF-1&alpha, increased significantly from PanIN (3.01 ±, 0.17) to IPMN (7.63 ±, 0.18), NET (9.10 ±, 0.23) and PDAC samples (11.06 ±, 0.15, p <, 0.0001). Similar findings were observed for HIF-2&alpha, (p <, 0.0001)}. A strong correlation between HIF-1&alpha, expression was demonstrated (R2 = 0.8408, p <, 0.0001). Conclusions: This data suggest that HIF-1&alpha, may play a role in the progression from PanIN through PDAC. Further studies are necessary to confirm these findings and determine the effect of HIFs abrogation on tumor progression that can lead to novel therapies.
- Published
- 2020
20. 2152-PUB: Cardiac Autonomic Dysfunction in Patients with Psoriasis and without Metabolic Syndrome
- Author
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Michael D. Bailey, Elias S. Siraj, Aaron I. Vinik, Abby S. Van Voorhees, Abby Barney, Carolina Casellini, and Henri K. Parson
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Disease ,medicine.disease ,Sudomotor ,Psoriatic arthritis ,Insulin resistance ,Psoriasis ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Medicine ,Metabolic syndrome ,business - Abstract
Background: Studies have shown a connection between psoriasis (PsO) and metabolic syndrome (MS), diabetes mellitus and cardiovascular disease. In addition, MS is associated with autonomic dysfunction (AD). AD has also been associated with chronic arthritis including psoriatic arthritis, but there is lack of similar evidence in patients with PsO. The aim of this study was to look for an association between PsO and AD, independent of the presence of MS. Methods: Cross-sectional study of subjects with PsO without MS; age, sex and BMI matched healthy controls (HC); and age and sex matched subjects with MS. Subjects underwent skin evaluation by dermatologist, blood work for HbA1c, insulin, glucose, and lipids, sudomotor function testing with SudoscanTM device (Impeto Medical-Paris, France) and cardiac autonomic function testing with ANSAR device (ANX 3.0; ANSAR Group, Inc. Philadelphia). Results: We included 47 subjects (13 PsO, 16 HC and 18 MS). PsO subjects had worse cardiac autonomic function compared to the other groups, although glucose and insulin parameters were similar to the HC group (Table 1). No differences were seen in sudomotor function between the groups. Conclusions: PsO seems to have an association with cardiac autonomic dysfunction, independent of its relationship with insulin resistance and MS. Further studies are needed to clarify the significance of these findings and how they relate to MS and diabetes. Disclosure C.M. Casellini: None. H. Parson: None. M.D. Bailey: None. A. Barney: None. A.S. Van Voorhees: Consultant; Self; Celgene. Other Relationship; Self; AbbVie Inc., Lilly Diabetes. A.I. Vinik: None. E.S. Siraj: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; Novo Nordisk Inc. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc.
- Published
- 2020
21. Diabetes and the Nervous System
- Author
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Serina A. Neumann, Carolina Casellini, and Aaron I. Vinik
- Subjects
Nervous system ,03 medical and health sciences ,medicine.anatomical_structure ,0302 clinical medicine ,business.industry ,Diabetes mellitus ,medicine ,030209 endocrinology & metabolism ,Bioinformatics ,business ,medicine.disease ,030217 neurology & neurosurgery - Published
- 2020
22. Effect of Lanreotide Depot/Autogel on Urinary 5-Hydroxyindoleacetic Acid and Plasma Chromogranin A Biomarkers in Nonfunctional Metastatic Enteropancreatic Neuroendocrine Tumors
- Author
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Alexandria T. Phan, Nilani Liyanage, Aaron I. Vinik, Beloo Mirakhur, Susan Pitman Lowenthal, Marianne Pavel, Edward M. Wolin, and George A. Fisher
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Urinary system ,Antineoplastic Agents ,030209 endocrinology & metabolism ,Neuroendocrine tumors ,Placebo ,Lanreotide ,Peptides, Cyclic ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Gastrointestinal Cancer ,Post-hoc analysis ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Gastrointestinal Neoplasms ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,Hazard ratio ,International Agencies ,Chromogranin A ,Hydroxyindoleacetic Acid ,Middle Aged ,Prognosis ,medicine.disease ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Somatostatin ,business ,Carcinoid syndrome ,Follow-Up Studies - Abstract
Background Urinary 5-hydroxyindoleacetic acid (5-HIAA) is an established biomarker in neuroendocrine tumors and carcinoid syndrome; however, its role in nonfunctional neuroendocrine tumors is not defined. We present post hoc data on urinary 5-HIAA and plasma chromogranin A (CgA) from the CLARINET study. Methods Patients with well- or moderately differentiated, nonfunctioning, locally advanced or metastatic enteropancreatic neuroendocrine tumors were randomized to deep subcutaneous lanreotide depot/autogel 120 mg or placebo once every 28 days for 96 weeks. Tumor response, evaluated centrally (RECIST 1.0), and progression-free survival (PFS) were assessed by treatment and biochemical response, defined as (a) baseline >upper limit of normal (ULN, 41.6 μmol per day 5-HIAA; 98.1 μg/L CgA) and (b) ≥50% decrease from baseline and to ≤ULN value on study. Results Forty-eight percent (82 of 171; lanreotide, n = 45; placebo, n = 37) and 66% (129 of 195; lanreotide, n = 65; placebo, n = 64) of randomized patients had 5-HIAA and CgA > ULN at baseline. Among patients with >ULN baseline values who did not progress after 96 weeks of treatment, significantly greater reductions in 5-HIAA and CgA were observed in lanreotide-treated versus placebo-treated patients throughout the study (all p < .05). PFS was significantly prolonged among 5-HIAA responders versus nonresponders (median not reached vs. 16.2 months, p < .0001; hazard ratio [HR] = 0.21, 95% confidence interval [CI], 0.09–0.48) and CgA responders versus nonresponders (median not reached vs. 16.2 months, p = .0070; HR = 0.30, 95% CI, 0.12–0.76), regardless of treatment arm. PFS was also significantly prolonged among lanreotide-treated 5-HIAA responders versus nonresponders (p = .0071) but was not significantly different among placebo-treated 5-HIAA responders versus nonresponders. There were no significant differences in PFS between lanreotide-treated CgA responders versus nonresponders or between placebo-treated CgA responders versus nonresponders. Conclusions The 5-HIAA findings are noteworthy because they occurred in patients with nonfunctioning enteropancreatic neuroendocrine tumors. Monitoring 5-HIAA and CgA may be useful when treating patients with nonfunctional neuroendocrine tumors. Implications for Practice Current guidelines focus only on the monitoring of 5-hydroxyindoleacetic acid (5-HIAA) in the diagnosis and management of functional neuroendocrine tumors with carcinoid syndrome. The current post hoc analysis of patients with nonfunctional enteropancreatic neuroendocrine tumors in the CLARINET study demonstrated that measuring and following both 5-HIAA and chromogranin A as biomarkers of disease progression may be useful in the management of patients with nonfunctional neuroendocrine tumors.
- Published
- 2018
23. Repeat treatment with capsaicin 8% patch (179mg capsaicin cutaneous patch): Effects on pain, quality of life, and patient satisfaction in painful diabetic peripheral neuropathy: an open-label, randomized controlled clinical trial
- Author
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Enrique Ortega, Etta J. Vinik, Aaron I. Vinik, Ladislav Pazdera, Robert Snijder, Nathaniel P. Katz, Malcolm Stoker, and Serge Perrot
- Subjects
business.industry ,Pain quality ,medicine.disease ,law.invention ,Cutaneous patch ,Clinical trial ,chemistry.chemical_compound ,Patient satisfaction ,Peripheral neuropathy ,chemistry ,Quality of life ,Randomized controlled trial ,Capsaicin ,law ,Anesthesia ,medicine ,business - Abstract
Objective: To determine long-term safety and effectiveness of repeat treatments with a high concentration capsaicin patch. Methods: In this 52-week, open-label, randomized controlled study, patients with painful diabetic peripheral neuropathy (PDPN) received either capsaicin patch: (30- or 60-min; 1–7 treatments to the feet) plus SOC or SOC alone. Effectiveness was assessed, by changes from baseline to end of study (EoS), in average and severity of pain, pain interference with daily function (Brief Pain Inventory-Diabetic Neuropathy version), responder rates, Patient Global Impression of Change (PGIC), and EuroQol 5-dimension (EQ-5D) questionnaire. Results: 468 patients were randomized (n=156 and n=157, 30 and 60-min respectively; SOC alone, n=155). Safety data have been reported previously. Changes in average pain from baseline to EoS (mean percentage (SD)) were: 30-min, −37.5% (32.9); 60-min, −40.8% (39.7); SOC alone, −13.9% (74.6). The difference between groups increased progressively from −17.7% and −18.6% at Month 1 for 30- and 60-min., respectively, to −21.9% and −24% at Month 12. More 30% responders occurred in the capsaicin groups (30-min, 67.3%; 60-min, 67.5%) and more felt: very much or much improved” (30-min, 24.2%; 60-min, 24.5%), compared with SOC alone (40.6% and 9.5% respectively). A greater mean improvement in EQ-5D utility index and EQ-5D visual analog scale score, from baseline to Month 12, was observed with the 30-min (0.12) and 60-min (0.15) versus SOC alone (0.07) and mean (SD), 30–min (10.4 [18.5]) and 60-min (11.2 [21.4]) versus SOC alone (5.5 [18.1]) respectively. Conclusion: Capsaicin 8% patch showed differential effectiveness over SOC alone, further increasing with repeat treatments.
- Published
- 2019
24. Lanreotide Therapy in Carcinoid Syndrome: Prospective Analysis of Patient-Reported Symptoms in Patients Responsive To Prior Octreotide Therapy And Patients Naïve To Somatostatin Analogue Therapy in The Elect Phase 3 Study
- Author
-
Beloo Mirakhur, George A. Fisher, Nilani Liyanage, Aaron I. Vinik, Edward M. Wolin, Montaser Shaheen, Rodney F. Pommier, and Susan Pitman Lowenthal
- Subjects
Adult ,Male ,medicine.medical_specialty ,genetic structures ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Octreotide ,Phases of clinical research ,030209 endocrinology & metabolism ,Carcinoid Tumor ,Neuroendocrine tumors ,Lanreotide ,Peptides, Cyclic ,Gastroenterology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Neoadjuvant therapy ,Aged ,Malignant Carcinoid Syndrome ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Clinical trial ,Neuroendocrine Tumors ,Treatment Outcome ,chemistry ,Female ,Self Report ,Somatostatin ,business ,Carcinoid syndrome ,medicine.drug - Abstract
This ELECT prospective analysis examined lanreotide depot/autogel for carcinoid syndrome (CS) symptom control in patients with neuroendocrine tumors (NETs) who were responsive to prior octreotide (prior octreotide group) compared with patients who were naïve to prior somatostatin analogue treatment (de novo group).Adults with histopathologically confirmed NET and stable CS (diarrhea and/or flushing) were randomized to subcutaneous (SC) lanreotide 120 mg or placebo every 4 weeks for 16 weeks. Patients reported diarrhea and/or flushing symptom severity and frequency and short-acting SC octreotide rescue therapy daily using an Interactive Voice/Web Response System. To evaluate the efficacy of lanreotide compared with placebo, the novel primary endpoint of patient-determined use of SC octreotide rescue therapy for breakthrough symptoms was used as a surrogate for symptom control. Clinically meaningful patient-reported treatment benefit was examined using daily patient-reported symptoms of diarrhea and flushing.Of the 115 randomized patients, 51 (n = 26 lanreotide, n = 25 placebo) were octreotide-naïve (de novo) and 64 (n = 33 lanreotide; n = 31 placebo) received prior octreotide. Lanreotide versus placebo patients had a lower mean percentage of days of SC octreotide rescue therapy in de novo and prior octreotide groups (least squares [LS] mean difference -19.1, P = .0477 and -6.9, P = .4332, respectively). The mean percentage of days with moderate/severe diarrhea and/or flushing was lower in lanreotide versus placebo patients in de novo and prior octreotide groups (LS mean difference -14.6, P = .0140 and -10.9, P = .0746, respectively). The transition from octreotide to lanreotide was generally well-tolerated.Improvement in CS symptoms occurred with lanreotide treatment, regardless of prior octreotide use.CI = confidence interval CS = carcinoid syndrome DB = double blind ELECT = Evaluation of Lanreotide depot/autogel Efficacy and safety as a Carcinoid-syndrome Treatment IOL = initial open-label IVRS/IWRS = interactive voice/web response system LS = least square NET = neuroendocrine tumor OR = odds ratio SC = subcutaneous SSA = somatostatin analogue SSTR = somatostatin receptor TEAE = treatment-emergent adverse event.
- Published
- 2018
25. Improved Patient Outcomes by Normalizing Sympathovagal Balance: Differentiating Syncope—Precise Subtype Differentiation Leads to Improved Outcomes
- Author
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Cesar Acosta, Heather L. Bloom, Jeysel M Pinales, Michael Yayac, Aaron I. Vinik, Mushfiqur Siddique, Julie A Bateman, Nicholas L. DePace, and John Oh
- Subjects
lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Article Subject ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Orthostatic vital signs ,0302 clinical medicine ,Internal medicine ,medicine ,Heart rate variability ,Vasovagal syncope ,Balance (ability) ,biology ,business.industry ,Syncope (genus) ,Abnormal heart rate ,medicine.disease ,biology.organism_classification ,Pathophysiology ,Blood pressure ,lcsh:RC666-701 ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Syncope is difficult to definitively diagnose, even with tilt-table testing and beat-to-beat blood pressure measurements, the gold-standard. Both are qualitative, subjective assessments. There are subtypes of syncope associated with autonomic conditions for which tilt-table testing is not useful. Heart rate variability analyses also include too much ambiguity. Three subtypes of syncope are differentiated: vasovagal syncope (VVS) due to parasympathetic excess (VVS-PE), VVS with abnormal heart rate response (VVS-HR), and VVS without PE (VVS-PN). P&S monitoring (ANSAR, Inc., Philadelphia, PA) differentiates subtypes in 2727 cardiology patients (50.5% female; average age: 57 years; age range: 12–100 years), serially tested over four years (3.3 tests per patient, average). P&S monitoring noninvasively, independently, and simultaneously measures parasympathetic and sympathetic (P&S) activity, including the normal P-decrease followed by an S-increase with head-up postural change (standing). Syncope, as an S-excess (SE) with stand, is differentiated from orthostatic dysfunction (e.g., POTS) as S-withdrawal with stand. Upon standing, VVS-PE is further differentiated as SE with PE, VVS-HR as SE with abnormal HR, and VVS-PN as SE with normal P- and HR-responses. Improved understanding of the underlying pathophysiology by more accurate subtyping leads to more precise therapy and improved outcomes.
- Published
- 2018
26. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on Testing for Autonomic And Somatic Nerve Dysfunction
- Author
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Dan Ziegler, Vicenza Spallone, Richard I. Cook, S. Sethu K. Reddy, Solomon Tesfaye, Yehuda Handelsman, Aaron I. Vinik, Anne L Leddy, Pauline M. Camacho, Howard M. Lando, and Jaime A Davidson
- Subjects
Position statement ,medicine.medical_specialty ,Consensus ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,law.invention ,Diabetes Complications ,Diagnostic Techniques, Endocrine ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetic Neuropathies ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Somatic nerve ,Association (psychology) ,Societies, Medical ,business.industry ,General Medicine ,United States ,Clinical Practice ,Position (obstetrics) ,Endocrinologists ,Autonomic Nervous System Diseases ,Somatosensory Disorders ,business - Abstract
This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.
- Published
- 2017
27. Diabetic Microvascular Disease: An Endocrine Society Scientific Statement
- Author
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Donald W. Bowden, Aaron I. Vinik, Mogher Khamaisi, George L. King, Eugene J. Barrett, Timothy M. Hughes, Zhenqi Liu, Barry I. Freedman, Ronald Klein, Suzanne Craft, Barbara E.K. Klein, and Carolina Casellini
- Subjects
medicine.medical_specialty ,Statement (logic) ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Adipose tissue ,030209 endocrinology & metabolism ,Disease ,Type 2 diabetes ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Endocrine system ,Diabetic Nephropathies ,Diabetic Retinopathy ,business.industry ,Biochemistry (medical) ,medicine.disease ,Research findings ,Cerebrovascular Disorders ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Quality of Life ,Scientific Statement ,business ,Diabetic Angiopathies ,030217 neurology & neurosurgery - Abstract
Both type 1 and type 2 diabetes adversely affect the microvasculature in multiple organs. Our understanding of the genesis of this injury and of potential interventions to prevent, limit, or reverse injury/dysfunction is continuously evolving. This statement reviews biochemical/cellular pathways involved in facilitating and abrogating microvascular injury. The statement summarizes the types of injury/dysfunction that occur in the three classical diabetes microvascular target tissues, the eye, the kidney, and the peripheral nervous system; the statement also reviews information on the effects of diabetes and insulin resistance on the microvasculature of skin, brain, adipose tissue, and cardiac and skeletal muscle. Despite extensive and intensive research, it is disappointing that microvascular complications of diabetes continue to compromise the quantity and quality of life for patients with diabetes. Hopefully, by understanding and building on current research findings, we will discover new approaches for prevention and treatment that will be effective for future generations.
- Published
- 2017
28. Sarcopenia: An Endocrine Disorder?
- Author
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Alexis McKee, Alvin M. Matsumoto, Aaron I. Vinik, and John E. Morley
- Subjects
Sarcopenia ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Dehydroepiandrosterone ,Endocrine System Diseases ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Testosterone ,030212 general & internal medicine ,Receptor ,business.industry ,Hypogonadism ,General Medicine ,musculoskeletal system ,medicine.disease ,Ghrelin ,Androgen receptor ,business ,human activities ,030217 neurology & neurosurgery ,Hormone - Abstract
Sarcopenia is defined as low muscle function (walking speed or grip strength) in the presence of low muscle mass. A simple screening test—the SARC-F—is available to identify persons with sarcopenia. The major endocrine causes of sarcopenia are diabetes mellitus and male hypogonadism. Other causes are decreased physical activity, loss of motor neuron units, weight loss, inflammatory cytokines, reduced blood flow to muscles, very low 25(OH) vitamin D levels, and decreased growth hormone and insulin-like growth factor 1. Treatment for sarcopenia includes resistance and aerobic exercise, leucine-enriched essential amino acids, and vitamin D. In hypogonadal males, testosterone improves muscle mass, strength, and function. Selective androgen receptor molecules and anti-myostatin activin II receptor molecules are under development as possible treatments for sarcopenia. Abbreviations: COPD = chronic obstructive pulmonary disease; DHEA = dehydroepiandrosterone; IGF-1 = insulin-like growth factor 1; GH = growth hormone; mTOR = mammalian target of rapamycin; SARM = selective androgen receptor molecule
- Published
- 2017
29. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study
- Author
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Sandrine Faivre, Patricia Niccoli, Aaron I. Vinik, Peter Metrakos, C. Lombard-Bohas, D. Smith, Y.-J. Bang, K.J. Ishak, Pascal Hammel, Shem Patyna, Jean-Luc Raoul, E. Raymond, Jin-Shyr Chen, E. Van Cutsem, Ivan Borbath, Daniel Castellano, D. Lu, Juan W. Valle, J.F. Seitz, Philippe Ruszniewski, and Sang Hyub Lee
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Indoles ,Urology ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Neuroendocrine tumors ,Placebo ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Statistical significance ,Sunitinib ,medicine ,Humans ,Pyrroles ,Progression-free survival ,Proportional Hazards Models ,Manchester Cancer Research Centre ,Proportional hazards model ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Hematology ,medicine.disease ,Confidence interval ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,Cross-Sectional Studies ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
BACKGROUND: In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) versus placebo (11.4 vs. 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib.PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a 2-reader, 2-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan-Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses.RESULTS: Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval [CI]) PFS was 12.6 (11.1-20.6) months for sunitinib and 5.8 (3.8-7.2) months for placebo (HR, 0.32; 95% CI 0.18-0.55; P = 0.000015). Five years after study closure, median (95%CI) OS was 38.6 (25.6-56.4) months for sunitinib and 29.1 (16.4-36.8) months for placebo (HR, 0.73; 95% CI 0.50-1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib.CONCLUSIONS: BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib.TRIAL REGISTRATION NUMBER: NCT00428597.
- Published
- 2017
30. Calcitonin-Secreting Pancreatic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1
- Author
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Roger R. Perry, Christine L. Ramirez, Umer Ansari, Eric Feliberti, and Aaron I. Vinik
- Subjects
Parathyroidectomy ,Pathology ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Pancreaticoduodenectomy ,medicine.disease ,RC648-665 ,Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,C-Cell Hyperplasia ,medicine.anatomical_structure ,Calcitonin ,Pituitary adenoma ,030220 oncology & carcinogenesis ,medicine ,MEN1 ,business ,Multiple endocrine neoplasia ,Pancreas - Abstract
Objective: To present a patient with multiple endocrine neoplasia type 1 (MEN1) syndrome recently diagnosed with a calcitonin-secreting pancreatic neuroendocrine tumor.Methods: Clinical and diagnostic evaluation, along with intervention, is presented. The relevant literature is reviewed.Results: The patient was a 52-year-old Caucasian man with a history of known MEN1 who had a right parathyroidectomy 10 years prior to admission, completion parathyroidectomy and total thyroidectomy for C cell hyperplasia 3 years prior, and removal of a pituitary adenoma 4 years prior. He was asymptomatic but had persistently elevated serum calcitonin levels. Venous sampling and positron emission tomography–computerized tomography indicated several lesions in the pancreas as the most likely cause of ectopic calcitonin secretion. The patient underwent pylorus-sparing pancreaticoduodenectomy (Whipple procedure). Several well-differentiated neuroendocrine lesions of the pancreas were noted, with lymphatic invasion and spread to a peripancreatic lymph node. Postoperatively, the patient's calcitonin levels returned to the normal range.Conclusion: Calcitonin-secreting pancreatic neuroendocrine tumors are relatively rare entities that are even more rare in familial syndromes such as MEN1. Due to the clinically silent nature of these lesions, they are often discovered incidentally and late in their clinical course. More data are needed in order to establish a consensus on ideal management. Calcitonin elevation even in MEN1 may herald non-thyroid malignancy, therefore demanding an aggressive approach to evaluation and treatment.Abbreviations: CT computerized tomography; MEN1 multiple endocrine neoplasia type 1; PNETs pancreatic neuroendocrine tumors; PP pancreatic polypeptide; VIP vasoactive intestinal peptide
- Published
- 2017
31. Content validity of symptom-based measures for diabetic, chemotherapy, and HIV peripheral neuropathy
- Author
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Bryce B. Reeve, Shannon M. Smith, Justin C. McArthur, A. Gordon Smith, Tony D. Gover, James W. Russell, Jennifer S. Gewandter, Roy Freeman, Bob A. Rappaport, Dennis C. Turk, Aaron I. Vinik, Robert H. Dworkin, Guido Cavaletti, David N. Herrmann, Laurie B. Burke, Michael P. McDermott, and Christopher H. Gibbons
- Subjects
medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Content validity ,medicine ,Chemotherapy ,business.industry ,Outcome measures ,medicine.disease ,Peripheral ,Allodynia ,Peripheral neuropathy ,030220 oncology & carcinogenesis ,Physical therapy ,Etiology ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Introduction: No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. Methods: This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Results: Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Conclusions: Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366–372, 2017
- Published
- 2016
32. Clinical measures in transthyretin familial amyloid polyneuropathy
- Author
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Jeff Packman, Donna R. Grogan, Tara Tripp, Etta J. Vinik, Teresa Coelho, and Aaron I. Vinik
- Subjects
medicine.medical_specialty ,biology ,Physiology ,Cross-sectional study ,business.industry ,Amyloidosis ,Disease ,030204 cardiovascular system & hematology ,medicine.disease ,Surgery ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Transthyretin ,0302 clinical medicine ,Quality of life ,Physiology (medical) ,Internal medicine ,Severity of illness ,medicine ,biology.protein ,Neurology (clinical) ,Young adult ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
Introduction: This observational, cross-sectional, single-center study aimed to identify instruments capable of measuring disease progression in transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods: The relationship between disease stage and Neuropathy Impairment Score-Lower Limbs (NIS-LL) and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOLDN) total score was assessed in 61 (stage 1–stage 3) patients with TTR-FAP (V30M variant) and 16 healthy controls. Composite measures of large- and small-nerve fiber function, and modified body mass index (mBMI) were also assessed. Results: Ordinal-based NIS-LL and Norfolk QOL-DN scores discriminated between disease stages (P
- Published
- 2016
33. Electrochemical skin conductance to measure sudomotor function: the importance of not misinterpreting the evidence
- Author
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Aaron I. Vinik, Carolina Casellini, and Henri K. Parson
- Subjects
Endocrine and Autonomic Systems ,business.industry ,Measure (physics) ,030204 cardiovascular system & hematology ,Sudomotor ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Medicine ,Neurology (clinical) ,Skin conductance ,Autonomic neuropathy ,business ,030217 neurology & neurosurgery - Published
- 2018
34. Development and Validation of the Norfolk Quality of Life Fatigue Tool (QOL-F): A New Measure of Perception of Fatigue
- Author
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Sheri R. Colberg, Aaron I. Vinik, Henri K. Parson, Richard W. Handel, Ying-Chuen Lai, Carolina Casellini, Etta J. Vinik, James F. Paulson, Kim Hodges, Joshua Edwards, Steven Morrison, Serina A. Neumann, and Rajan Lamichhane
- Subjects
Adult ,Male ,Activities of daily living ,Psychometrics ,Psychological intervention ,Article ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Cronbach's alpha ,Surveys and Questionnaires ,Activities of Daily Living ,Medicine ,Humans ,030212 general & internal medicine ,General Nursing ,Fatigue ,Balance (ability) ,Aged ,Aged, 80 and over ,business.industry ,Health Policy ,Reproducibility of Results ,Cognition ,General Medicine ,Middle Aged ,Confirmatory factor analysis ,Quality of Life ,Anxiety ,Female ,Perception ,Geriatrics and Gerontology ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Objectives To design a questionnaire to evaluate and distinguish between cognitive and physical aspects of fatigue in different age groups of “nondiseased” people and guide appropriate prevention and interventions for the impact of frailty occurring in normative aging. Study design and participants The Norfolk QOL-Fatigue (QOL-F) with items of cognitive and physical fatigue, anxiety, and depression from validated questionnaires including items from the Patient-Reported Outcomes Measure Information System (PROMIS) databank was developed. The preliminary QOL-F was administered to 409 healthy multiethnic local participants (30-80 years old) in 5 age groups. Methods The authors distilled the item pool using exploratory (EFA) and confirmatory factor analysis (CFA). EFA identified 5 latent groups as possible factors related to problems due to fatigue, subjective fatigue, reduced activities, impaired activities of daily living (ADL), and depression. Results CFA demonstrated good overall fit [χ2(172) = 1094.23, P 0.617 and strong interfactor correlations (0.69-0.83), suggesting that fatigue in each domain is closely related to other domains and to the overall scale except for ADL. The 5-factor solution displayed good internal consistency (Cronbach α = 0.78-0.94). Total and domain scores were fairly equivalent in all age groups except for the 40 to 49-year-old group with better overall scores. In addition, 70 to 79-year-olds had better ADL scores. In item response analysis, factor scores in different age groups were similar, so age may not be a significant driver of fatigue scores. Fatigue scores were significantly higher in females than in males (P Conclusions and clinical implications The developed Norfolk QOL-F tool demonstrated fatigue as a perceived cognitive phenomenon rather than an objective physical measure, suggesting mandatory inclusion of cognitive as well as physical measures in the evaluation of people as they age. QOL-F is able to distinguish QOL-F domain scores unique to different age groups, proposing clinical benefits from physical, balance, and cognitive interventions tailored to impact frailty occurring in normative aging.
- Published
- 2019
35. Countering the Modern Metabolic Disease Rampage With Ancestral Endocannabinoid System Alignment
- Author
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Ian Pepper, Anca D. Dobrian, Aaron I. Vinik, Frank A. Lattanzio, and William McPheat
- Subjects
0301 basic medicine ,obesity ,Endocrinology, Diabetes and Metabolism ,Lineage (evolution) ,030209 endocrinology & metabolism ,Comparative biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,cannabinoids ,0302 clinical medicine ,Endocrinology ,biology.animal ,Hypothesis and Theory ,NAFLD ,evolution ,lcsh:RC648-665 ,biology ,Mechanism (biology) ,Vertebrate ,Evolutionary medicine ,Endocannabinoid system ,energy balance ,030104 developmental biology ,type 2 diabetes ,Neuroscience ,Developmental biology ,Function (biology) - Abstract
When primitive vertebrates evolved from ancestral members of the animal kingdom and acquired complex locomotive and neurological toolsets, a constant supply of energy became necessary for their continued survival. To help fulfill this need, the endocannabinoid (eCB) system transformed drastically with the addition of the cannabinoid-1 receptor (CB1R) to its gene repertoire. This established an eCB/CB1R signaling mechanism responsible for governing the whole organism's energy balance, with its activation triggering a shift toward energy intake and storage in the brain and the peripheral organs (i.e., liver and adipose). Although this function was of primal importance for humans during their pre-historic existence as hunter-gatherers, it became expendable following the successive lifestyle shifts of the Agricultural and Industrial Revolutions. Modernization of the world has further increased food availability and decreased energy expenditure, thus shifting the eCB/CB1R system into a state of hyperactive deregulated signaling that contributes to the 21st century metabolic disease pandemic. Studies from the literature supporting this perspective come from a variety of disciplines, including biochemistry, human medicine, evolutionary/comparative biology, anthropology, and developmental biology. Consideration of both biological and cultural evolution justifies the design of improved pharmacological treatments for obesity and Type 2 diabetes (T2D) that focus on peripheral CB1R antagonism. Blockade of peripheral CB1Rs, which universally promote energy conservation across the vertebrate lineage, represents an evolutionary medicine strategy for clinical management of present-day metabolic disorders.
- Published
- 2019
36. Diabetic Neuropathy: New Insights to Early Diagnosis and Treatments
- Author
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Nigel A. Calcutt, Soroku Yagihashi, Mark A. Yorek, Aaron I. Vinik, and Rayaz A. Malik
- Subjects
Diabetic neuropathy ,Article Subject ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Bioinformatics ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Text mining ,Diabetic Neuropathies ,Surveys and Questionnaires ,medicine ,Animals ,Humans ,Mass Screening ,lcsh:RC648-665 ,business.industry ,Disease progression ,medicine.disease ,Editorial ,Early Diagnosis ,Disease Progression ,business - Published
- 2018
37. Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function
- Author
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Jaakko Tuomilehto, A. Gordon Smith, Frédéric Roche, B. Bauduceau, Barry I. Freedman, Brian C. Callaghan, Lyse Bordier, Aaron I. Vinik, and J. Robinson Singleton
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Pathology ,Endocrinology, Diabetes and Metabolism ,Ethnic group ,030209 endocrinology & metabolism ,Autonomic Nervous System ,Body Mass Index ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Asian People ,Reference Values ,Diabetes mellitus ,Internal medicine ,Ethnicity ,medicine ,Humans ,Young adult ,Aged ,Glycemic ,Aged, 80 and over ,Sex Characteristics ,business.industry ,Galvanic Skin Response ,Middle Aged ,medicine.disease ,Healthy Volunteers ,Sweat Glands ,Black or African American ,Sudomotor ,Medical Laboratory Technology ,Female ,business ,Body mass index ,030217 neurology & neurosurgery ,Sex characteristics ,Cohort study - Abstract
Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan™ (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology.Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants.Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P 0.0001). No participant discomfort or safety concern was reported in 1,376 tests. No significant difference in ESC was observed between women and men at the hands (75 [57-87] vs. 76 [56-89] μS; P = 0.35) or feet (83.5 [71-90] vs. 82.5 [70-91] μS; P = 0.12). The coefficient of correlation between right and left side ESC was r = 0.96, P 0.0001 for hands and r = 0.97, P 0.0001 for feet. A significant but weak correlation was observed between ESC and age: for hands, r = -0.17, P 0.0001; for feet, r = -0.19, P 0.0001.A normative reference range was established in whites showing that there was no effect of sex or body mass index and a slight decrease in ESC with age. Ethnicity influenced ESC scores, but additional studies are necessary to validate this effect and determine its mechanism and impact on nerve function.
- Published
- 2016
38. Diabetic Sensory and Motor Neuropathy
- Author
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Aaron I. Vinik
- Subjects
Weakness ,medicine.medical_specialty ,Gabapentin ,Proprioception ,business.industry ,Pregabalin ,030209 endocrinology & metabolism ,Sensory loss ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Diabetes mellitus ,Sensation ,Physical therapy ,Medicine ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Stabbing Pain ,medicine.drug - Abstract
Key Clinical PointsDiabetic Sensory and Motor Neuropathy Symptoms of distal symmetric motor and sensory polyneuropathy may be “positive” (manifested as sensations of tingling, burning, or stabbing pain) or “negative” (manifested as sensory loss, weakness, or numbness). These symptoms occur in one third of patients with type 1 or 2 diabetes. Decreased sensation confers a predisposition to painless foot ulcers and to amputations. Proprioceptive impairment leads to imbalance and unsteadiness in gait and to an increased likelihood of falls and serious traumatic injury. Laboratory testing should be used to rule out other causes of neuropathy, including vitamin B12 deficiency, which may occur with metformin use. Lifestyle interventions (diet and exercise) may restore nerve fibers, and exercises that improve strength and balance may reduce the risk of falls. Medications most commonly used in pain management include anticonvulsants (particularly gabapentin and pregabalin), tricyclic antidepressants, and serotonin...
- Published
- 2016
39. Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4years in the NATHAN 1 trial
- Author
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Dan Ziegler, Aaron I. Vinik, H. J. Tritschler, Phillip A. Low, and Roy Freeman
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Placebo ,Antioxidants ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetic Neuropathies ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Heart rate ,Internal Medicine ,medicine ,Humans ,Thioctic Acid ,business.industry ,Insulin ,Remission Induction ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Treatment Outcome ,Blood pressure ,Diabetes Mellitus, Type 2 ,ACE inhibitor ,Disease Progression ,Female ,business ,Polyneuropathy ,030217 neurology & neurosurgery ,Follow-Up Studies ,medicine.drug - Abstract
Aims We aimed to analyze the impact of baseline factors on the efficacy of α-lipoic acid (ALA) over 4 years in the NATHAN 1 trial. Methods This was a post-hoc analysis of the NATHAN 1 trial, a 4-year randomized study including 460 diabetic patients with mild-to-moderate polyneuropathy using ALA 600 mg qd or placebo. Amongst others, efficacy measures were the Neuropathy Impairment Score of the lower limbs (NIS-LL) and heart rate during deep breathing (HRDB). Results Improvement and prevention of progression of NIS-LL (ΔNIS-LL ≥ 2 points) with ALA vs. placebo after 4 years was predicted by higher age, lower BMI, male sex, normal blood pressure, history of cardiovascular disease (CVD), insulin treatment, longer duration of diabetes and neuropathy, and higher neuropathy stage. Participants treated with ALA who received ACE inhibitors showed a better outcome in HRDB after 4 years. Conclusions Better outcome in neuropathic impairments following 4-year treatment with α-lipoic acid was predicted by normal BMI and blood pressure and higher burden due to CVD, diabetes, and neuropathy, while improvement in cardiac autonomic function was predicted by ACE inhibitor treatment. Thus, optimal control of CVD risk factors could contribute to improved efficacy of α-lipoic acid in patients with higher disease burden.
- Published
- 2016
40. Effectiveness of Metanx Prescription Medical Food on Small Nerve Fibers and Monofilament Sensation in Patients with Diabetic Peripheral Polyneuropathy
- Author
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Lori Barrentine, Victor F. McNamara, Edward B. De Vol, and Aaron I. Vinik
- Subjects
Medical food ,education.field_of_study ,Diabetic neuropathy ,business.industry ,Population ,030209 endocrinology & metabolism ,Nerve fiber ,Type 2 diabetes ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Peripheral neuropathy ,medicine.anatomical_structure ,Anesthesia ,Neuropathic pain ,Sensation ,medicine ,education ,business ,030217 neurology & neurosurgery - Abstract
Purpose: Diabetic peripheral neuropathy (DPN) is prevalent among the population with type 2 diabetes, and treatment approaches are limited. The combination of L-methylfolate-methylcobalamin-pyridoxal-5-phospate (LMF-MC-PP, Metanx?) is a prescription medical food that has demonstrated significant improvements in sensory perception and quality of life as well as reduced neuropathic pain in patients with DPN. The present study examined the effects of LMF-MC-PP on sensory perception and epidermal nerve fiber density (ENFD) among patients with confirmed DPN. Methods: Patients with type 2 diabetes and diagnosed with diabetic peripheral polyneuropathy, based on loss of vibratory perception, warm-cold discrimination or monofilament sensation, underwent bilateral lower extremity ENFD assessments via skin punch biopsy and were started on LMF-MC-PP. ENFD and monofilament testing were repeated at 6 months. Findings: Of 123 patients evaluated, all had monofilament testing at baseline and 6 months and 122 had assessments at both time points. A significant (p
- Published
- 2016
41. Change in Patient-Reported Symptom Control in Patients With Neuroendocrine Tumors Treated With Lanreotide Depot
- Author
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Beloo Mirakhur, Edward M. Wolin, George A. Fisher, Susan Pitman Lowenthal, Montaser Shaheen, Aaron I. Vinik, Nilani Liyanage, and Rodney F. Pommier
- Subjects
Oncology ,medicine.medical_specialty ,Hepatology ,Depot ,business.industry ,Gastroenterology ,Neuroendocrine tumors ,medicine.disease ,Lanreotide ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Symptom control ,In patient ,business - Published
- 2017
42. The efficacy of pregabalin for treating pain associated with diabetic peripheral neuropathy in subjects with type 1 or type 2 diabetes mellitus
- Author
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Chunming Li, Bruce Parsons, Birol Emir, and Aaron I. Vinik
- Subjects
Male ,medicine.medical_specialty ,endocrine system diseases ,Pregabalin ,030209 endocrinology & metabolism ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Diabetic Neuropathies ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Adverse effect ,Pain Measurement ,Randomized Controlled Trials as Topic ,Sleep disorder ,Analgesics ,business.industry ,nutritional and metabolic diseases ,Repeated measures design ,General Medicine ,Middle Aged ,medicine.disease ,Dyssomnias ,Peripheral neuropathy ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Neuropathic pain ,Female ,Drug Monitoring ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
OBJECTIVE: To assess efficacy of pregabalin using pooled data on diabetic peripheral neuropathy (DPN)-associated pain with type 1 (T1DM) or 2 diabetes mellitus (T2DM). BACKGROUND: The US Food and Drug Administration has approved pregabalin for DPN-associated pain treatment. However, the efficacy of pregabalin has not been compared between T1DM and T2DM patients. DESIGN/METHODS: DPN-associated pain and sleep data (10 pooled trials) were evaluated in T1DM and T2DM. Change from baseline (CFB) pain and sleep disturbance were analyzed weekly through Week 12 using mixed model repeated measures (MMRM). Adverse events (AEs) were recorded. RESULTS: Enrolled patients (placebo; pregabalin, respectively) had T1DM (n=92; n=156) and T2DM (n=868; n=1632). Baseline characteristics (placebo & pregabalin, respectively) included: *age (median [range] years; T1DM: 51 [26-76] & 50 [20-78]; T2DM: 61 [26-86] & 60 [29-89]); *females (n [[percnt]]; T1DM: 39 [42.4] & 72 [46.2]; T2DM: 380 [43.8] & 700 [42.9]); *pain scores (mean±SD; T1DM: 6.5±1.6 & 6.2±1.4; T2DM: 6.4±1.5 & 6.5±1.5); *sleep scores (mean±SD; T1DM: 5.2±2.7 & 5.2±2.4; T2DM: 5.1±2.5 & 5.3±2.5). With respect to pain, mean [95[percnt] CI] CFB score differences (pregabalin minus placebo) were significant every treatment week for both diabetes types (at Week 12, T1DM: -0.91 [-1.52, -0.29], P=0.004; T2DM: -0.75 [-0.93, -0.57], P
- Published
- 2018
43. BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS
- Author
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Beloo, Mirakhur, Marianne E, Pavel, Rodney F, Pommier, George A, Fisher, Alexandria T, Phan, Christine, Massien, Nilani, Liyanage, Susan Pitman, Lowenthal, and Aaron I, Vinik
- Abstract
Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes.Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly.Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P.0001). A large proportion (87%) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48%ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50% decrease from baseline) achieved greater symptom control.This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control.5-HIAA = 5-hydroxyindoleacetic acid; CgA = chromogranin A; CI = confidence interval; CLARINET = Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors; CS = carcinoid syndrome; ELECT = Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment; HR = hazard ratio; ITT = intention-to-treat; NET = neuroendocrine tumor; PanNET = pancreatic NET; PFS = progression-free survival; PPI = proton pump inhibitor; SSA = somatostatin analogue; ULN = upper limit of normal.
- Published
- 2018
44. Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world
- Author
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George Dailey, Aaron I. Vinik, Mélanie Groleau, William Stager, Harpreet S. Bajaj, and Terry Dex
- Subjects
Blood Glucose ,Male ,safety ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,efficacy ,Insulin Glargine ,Type 2 diabetes ,Hypoglycemia ,iGlarLixi ,Lixisenatide ,chemistry.chemical_compound ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Glycemic ,Aged ,Glycated Hemoglobin ,business.industry ,Insulin glargine ,Emerging Technologies, Pharmacology and Therapeutics ,Middle Aged ,medicine.disease ,Drug Combinations ,Postprandial ,chemistry ,Diabetes Mellitus, Type 2 ,North America ,Female ,Glycated hemoglobin ,business ,Peptides ,medicine.drug - Abstract
ObjectiveTo assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW).Research design and methodsPost hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O (NCT02058147; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L (NCT02058160; inadequately controlled patients on basal insulin; NA, n=196; RoW, n=535). Efficacy outcomes were: change from baseline to Week 30 in glycated hemoglobin (HbA1c), postprandial glucose (PPG), PPG excursions, fasting plasma glucose (FPG) and body weight; proportion of patients achieving HbA1c ResultsSignificantly larger reductions (p≤0.003) in HbA1c from baseline to Week 30 were achieved with iGlarLixi, compared with iGlar or lixisenatide, in NA and RoW patients in LixiLan-O (iGlarLixi vs iGlar: −0.31 and −0.29, respectively; iGlarLixi vs lixisenatide: −0.84 and −0.69, respectively) and in LixiLan-L (iGlarLixi vs iGlar: −0.5 and −0.51, respectively). Documented symptomatic hypoglycemia was similar between NA and RoW patients. iGlarLixi resulted in significant weight benefits versus iGlar (change from baseline –1.58 and –1.29 kg for NA and RoW patients, respectively; p<0.001). GI adverse events were similar for iGlarLixi and iGlar, but significantly higher for lixisenatide.ConclusionsiGlarLixi improved glycemic parameters versus iGlar or lixisenatide alone in both NA and RoW patients, with beneficial weight effects versus iGlar. iGlarLixi treatment responses, hypoglycemia risk and GI adverse events in NA patients were comparable with patients in the RoW.Trial registryClinicaltrials.govNCT02058147andNCT02058160.
- Published
- 2018
45. Muscarinic Receptor Antagonist Improves Nerve Fiber Function in Subjects with Type 2 Diabetes and Peripheral Neuropathy
- Author
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Nigel A. Calcutt, Michael D. Bailey, Katie E. Frizzi, Jessica R. Weaver, Paul Fernyhough, Joshua Edwards, Lindsey B. Cundra, Carolina Casellini, Henri K. Parson, and Aaron I. Vinik
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Urology ,Antagonist ,Nerve fiber ,Type 2 diabetes ,Placebo ,medicine.disease ,Neuroprotection ,medicine.anatomical_structure ,Peripheral neuropathy ,Muscarinic acetylcholine receptor ,Internal Medicine ,medicine ,Oxybutynin ,business ,medicine.drug - Abstract
Degeneration of nerve fibers due to diabetic peripheral neuropathy (DPN) has been linked to mitochondrial dysfunction. Manipulation of mitochondrial dysfunction through antagonism of muscarinic receptors (MR) promotes neurite outgrowth in adult sensory neurons in vitro and provides neuroprotection in rodent models of DPN. The aim of the study was to assess the efficacy of MR antagonist topical 3% oxybutynin in structural and functional measures of nerve fiber function in subjects with type 2 diabetes (T2DM) and DPN. Pilot, randomized, placebo-controlled, double-blinded study in 40 subjects assessed at baseline and after 20 weeks of treatment with oxybutynin or placebo with the following: intraepidermal nerve fiber density (IENFD) on proximal and distal leg; neuropathy scores and quality of life (Norfolk QoL DN) questionnaire. Baseline demographic characteristics were similar between the treatment groups. IENFD improved significantly after 20 weeks for the treatment group. Neuropathy scores and Norfolk QoL DN also improved significantly in the treatment group (Table 1). No improvements were seen in the placebo group. In this study, oxybutynin proves to be efficacious in improving structural and functional measures of small fiber function, and quality of life in T2DM subjects. These results offer a promising novel therapeutic approach for DPN that needs to be explored further. Disclosure A.I. Vinik: None. N.A. Calcutt: Stock/Shareholder; Self; WinSanTor, Inc.. J.F. Edwards: None. J.R. Weaver: None. M.D. Bailey: None. P. Fernyhough: Stock/Shareholder; Self; WinSanTor, Inc.. L.B. Cundra: None. K.E. Frizzi: None. H. Parson: None. C.M. Casellini: None.
- Published
- 2018
46. Low blood pressure levels for fall injuries in older adults: the Health, Aging and Body Composition Study
- Author
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Jane A. Cauley, Tamara B. Harris, Suzanne Satterfield, Elsa S. Strotmeyer, Anne B. Newman, Robert M. Boudreau, Zachary A. Marcum, Ann V. Schwartz, Aaron I. Vinik, Joseph T. Hanlon, Celia O'Hare, Steven M. Albert, and Naoko Sagawa
- Subjects
Polypharmacy ,medicine.medical_specialty ,Health (social science) ,Proportional hazards model ,Fall injury ,business.industry ,Public health ,Diastole ,030204 cardiovascular system & hematology ,medicine.disease ,Comorbidity ,03 medical and health sciences ,0302 clinical medicine ,Blood pressure ,Internal medicine ,medicine ,030212 general & internal medicine ,Geriatrics and Gerontology ,business ,Body mass index ,Original Investigation - Abstract
Fall injuries cause morbidity and mortality in older adults. We assessed if low blood pressure (BP) is associated with fall injuries, including sensitivity analyses stratified by antihypertensive medications, in community-dwelling adults from the Health, Aging and Body Composition Study (N = 1819; age 76.6 ± 2.9 years; 53% women; 37% black). Incident fall injuries (N = 570 in 3.8 ± 2.4 years) were the first Medicare claims event from clinic visit (7/00–6/01) to 12/31/08 with an ICD-9 fall code and non-fracture injury code, or fracture code with/without a fall code. Participants without fall injuries (N = 1249) were censored over 6.9 ± 2.1 years. Cox regression models for fall injuries with clinically relevant systolic BP (SBP; ≤ 120, ≤ 130, ≤ 140, > 150 mmHg) and diastolic BP (DBP; ≤ 60, ≤ 70, ≤ 80, > 90 mmHg) were adjusted for demographics, body mass index, lifestyle factors, comorbidity, and number and type of medications. Participants with versus without fall injuries had lower DBP (70.5 ± 11.2 vs. 71.8 ± 10.7 mmHg) and used more medications (3.8 ± 2.9 vs. 3.3 ± 2.7); all P
- Published
- 2018
47. Detection of undisclosed neuropathy and assessment of its impact on quality of life: a survey in 25,000 Romanian patients with diabetes
- Author
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Andrei Ioan Veresiu, Etta J. Vinik, Cosmina Ioana Bondor, Bogdan Florea, Aaron I. Vinik, and Norina Alinta Gâvan
- Subjects
Male ,medicine.medical_specialty ,Delayed Diagnosis ,Diabetic neuropathy ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,Severity of Illness Index ,Amputation, Surgical ,Gangrene ,Endocrinology ,Cost of Illness ,Quality of life ,Internal medicine ,Diabetes mellitus ,Prevalence ,Internal Medicine ,medicine ,Humans ,Mass Screening ,Diabetic Nephropathies ,Screening tool ,education ,Ulcer ,Aged ,education.field_of_study ,Romania ,business.industry ,Middle Aged ,medicine.disease ,Health Surveys ,humanities ,Cross-Sectional Studies ,Amputation ,Quality of Life ,Physical therapy ,Female ,Self Report ,business - Abstract
The objective of this cross-sectional survey was to capture undiagnosed neuropathy in Romanian patients with self-reported diabetes using Norfolk QoL-DN as a screening tool and to assess its impact on quality of life (QoL).25,000 Romanian-translated, validated Norfolk QoL-DN questionnaires were distributed between June and December 2012. 21,261 patients who self-reported diabetes and answered questions related to neuropathy, ulceration, gangrene and amputation were included in the analysis.52% of diabetic patients (n = 6615) who answered "no" to the question "Do you have neuropathy?" had total QoL scores above the cut-off, suggesting the presence of diabetic neuropathy. 13,854 (65.2%) patients answered "yes" to the question "Do you have neuropathy?" and 3,150 (14.8%) reported at least one episode of ulceration, gangrene or amputation. Total QoL score was 3-fold higher (worse) for patients who answered "yes" to the question "Do you have neuropathy?" than for those who answered "no" (38.39 vs. 13.71; p0.001) and 1.4-fold worse for patients who reported ulceration, gangrene or amputation than for those who did not report any of these (50.38 vs. 34.87; p0.001).We found a high prevalence of undisclosed diabetic neuropathy in this population and showed that neuropathy severity has an increasing impact on total QoL and its domains.
- Published
- 2015
48. Aace/Ace Disease State Clinical Review: Diagnosis and Management of Midgut Carcinoids
- Author
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Aaron I. Vinik, Carmen C. Solorzano, Laurence Katznelson, Richard J. Wong, Gregory W. Randolph, and Eric H. Liu
- Subjects
Diagnostic Imaging ,Diarrhea ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Carcinoid tumors ,Carcinoid Heart Disease ,Octreotide ,Carcinoid Tumor ,Neuroendocrine tumors ,Lanreotide ,Peptides, Cyclic ,Gastroenterology ,Article ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Intestinal Neoplasms ,Intestine, Small ,Biomarkers, Tumor ,Flushing ,medicine ,Humans ,Cholecystectomy ,Mesentery ,business.industry ,Liver Neoplasms ,General Medicine ,medicine.disease ,Abdominal Pain ,Review article ,Somatostatin ,chemistry ,Lymphatic Metastasis ,Quality of Life ,Lymph Node Excision ,Biomarker (medicine) ,Interdisciplinary Communication ,business ,medicine.drug - Abstract
Neuroendocrine tumors (NETs) are a collection of complex tumors that arise from the diffuse endocrine system, primarily from the digestive tract. Carcinoid tumors most commonly originate from the small intestine. These tumors are either referred to as small intestinal neuroendocrine tumors or midgut carcinoids (MGCs). The purpose of this review article is to survey the diagnostic and therapeutic pathways for patients with MGC and provide an overview of the complex multidisciplinary care involved in improving their quality of life, treatment outcomes, and survival.The current literature regarding the diagnosis and management of MGCs was reviewed.Dry flushing and secretory diarrhea are the hallmarks of the clinical syndrome of MGC. Managing MGC requires attention to the overall symptom complex, including the physical effects of the tumor and biomarker levels. The somatostatin analogs (SAs) octreotide and lanreotide are highly efficacious for symptomatic improvement. MGCs require resection to encompass the primary tumor and mesenteric lymph node metastases and should include cholecystectomy if the patient is likely to receive SA therapy. Debulking of liver metastasis by resection in combination with ablative therapies and other liver-directed modalities may help palliate symptoms and hormonal overproduction in carefully selected patients. Quality of life is an important measure of patients' perception of the burden of their disease and impact of treatment modalities and may be a useful guide in deciding changes in therapy to alter apparent health status.MGC is a challenging malignancy that requires the input of a multidisciplinary team to develop the best treatment plan. Consultation with expert centers that specialize in NETs may also be indicated for complex cases. With expert care, patients can be cured or live with the disease and enjoy good quality of life.
- Published
- 2015
49. American Association of Clinical Endocrinologists and American College of Endocrinology – Clinical Practice Guidelines for Developing A Diabetes Mellitus Comprehensive Care Plan – 2015 — Executive Summary
- Author
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Aaron I. Vinik, W. Timothy Garvey, George A. Bray, Etie S. Moghissi, George Grunberger, Irl B. Hirsch, Jorge H. Mestman, Daniel Einhorn, Alan J. Garber, Timothy S. Bailey, Lois Jovanovič, Robert R. Henry, Jaime A. Davidson, Derek LeRoith, Paul D. Rosenblit, Rachel Pessah-Pollack, Edward S. Horton, Guillermo E. Umpierrez, Yehuda Handelsman, Kathleen Wyne, Philip T. Levy, Om P. Ganda, Paul S. Jellinger, A. Jay Cohen, Lawrence Blonde, Farhad Zangeneh, Daniel L. Hurley, Janet B. McGill, Eric A. Orzeck, Harold E. Lebovitz, Samuel Dagogo-Jack, Jeffrey I. Mechanick, Zachary T. Bloomgarden, and Robert S. Zimmerman
- Subjects
medicine.medical_specialty ,Health professionals ,business.industry ,Endocrinology, Diabetes and Metabolism ,education ,MEDLINE ,Alternative medicine ,General Medicine ,Medical decision making ,Clinical judgment ,Article ,Clinical Practice ,Endocrinology ,Care plan ,Internal medicine ,medicine ,Association (psychology) ,business - Abstract
The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascu...
- Published
- 2015
50. American Association Of Clinical Endocrinologists And American College Of Endocrinology -Clinical Practice Guidelines For Developing A Diabetes Mellitus Comprehensive Care Plan – 2015
- Author
-
Yehuda Handelsman, Zachary T. Bloomgarden, George Grunberger, Guillermo Umpierrez, Robert S. Zimmerman, Timothy S. Bailey, Lawrence Blonde, George A. Bray, A. Jay Cohen, Samuel Dagogo-Jack, Jaime A. Davidson, Daniel Einhorn, Om P. Ganda, Alan J. Garber, W. Timothy Garvey, Robert R. Henry, Irl B. Hirsch, Edward S. Horton, Daniel L. Hurley, Paul S. Jellinger, Lois Jovanovič, Harold E. Lebovitz, Derek LeRoith, Philip Levy, Janet B. McGill, Jeffrey I. Mechanick, Jorge H. Mestman, Etie S. Moghissi, Eric A. Orzeck, Rachel Pessah-Pollack, Paul D. Rosenblit, Aaron I. Vinik, Kathleen Wyne, and Farhad Zangeneh
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism ,General Medicine - Published
- 2015
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