Publications by authors named "Eric Nylen"

49 Publications

Resolution of hyperthyroidism and thyroid antibodies following struma ovarii resection: an uncommon entity.

BMJ Case Rep 2021 Apr 15;14(4). Epub 2021 Apr 15.

Division of Endocrinology, Department of Medicine, The George Washington University, Washington, DC, USA

We report a case of 34-year-old clinically asymptomatic woman who had been followed for 6 years for hyperthyroidism with thyroid stimulating hormone <0.006 uIU/mL, free T4 1.98 ng/mL, free T3 5.3 pg/mL, elevated thyroid stimulating immunoglobulin 1.70 IU/L, thyroid peroxidase antibody 38 IU/mL and thyroglobulin antibody 9.3 IU/mL. Radioiodine thyroid scan showed minimal uptake in both thyroid lobes (24-hour uptake was 0.3%). She subsequently underwent evaluation for lower abdominal pain and menstrual irregularities, which revealed a large left ovarian cyst measuring 15.9 cm × 10.8 cm × 13.2 cm and right-sided ovarian cyst measuring 2.7 cm × 3.3 cm × 3.5 cm. Laparoscopic bilateral ovarian cystectomy was performed and the final pathology revealed struma ovarii of the left ovarian cyst with the entire ovarian tumour made up of benign thyroid tissue. Thyroid function tests performed 3 months after surgical removal of struma ovarii showed euthyroidism. We present a rare case with detailed laboratory and immunological data before and after ovarian extirpation with resolution of hyperthyroidism associated with functional struma ovarii.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-240924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054055PMC
April 2021

Rhabdomyolysis in Patients Hospitalized With COVID-19 Infection: Five Case Series.

J Investig Med High Impact Case Rep 2020 Jan-Dec;8:2324709620984603

Veterans Affairs Medical Center, Washington, DC, USA.

The novel SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) is now known to cause acute respiratory distress, cytokine storm, and coagulopathy. Multiple other manifestations have been published in recent literature. Rhabdomyolysis is a syndrome of muscle damage, with release of intracellular contents into circulation. It is characterized by marked elevations of creatinine kinase levels and myoglobinuria. In this article, we describe a series of 5 cases who were admitted with COVID-19 pneumonia and had severe muscle injury, as demonstrated by significant elevation (>5 times upper limit of normal) of creatinine kinase levels likely secondary to SARS-CoV-2 virus. The median age for these patients was 65 years, and most of them suffered from diabetes and hyperlipidemia. All patients were hypertensive males. Four out of 5 patients had preserved kidney function at baseline and were chronic kidney disease (CKD) stage 2 or better. However, most of them suffered significant kidney injury and at the time of discharge one patient was CKD stage 2 or better, 2 were CKD stage 3 or worse, and 2 patients had renal failure and died due to complications of SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2324709620984603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780065PMC
January 2021

Proadrenomedullin Predicts Severe Disease in Children with Suspected Community-Acquired Pneumonia.

Clin Infect Dis 2020 Aug 6. Epub 2020 Aug 6.

Divisions of Hospital Medicine and Infectious Diseases, Cincinnati Children's Hospital Medical Center & Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP.

Methods: We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department (ED). Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (e.g., hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (e.g., vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP.

Results: Among 369 children, median proADM increased with disease severity [mild: median 0.53 nmol/L (IQR:0.43, 0.73), mild-moderate: 0.56 nmol/L (IQR:0.45, 0.71), moderate-severe: 0.61 nmol/L (IQR:0.47, 0.77), severe: 0.70 nmol/L (IQR:0.55, 1.04) (p=.002)]. ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP odds ratio (OR) 1.68 [95% CI, 1.2, 2.36], radiographic CAP OR 2.11 [95% CI, 1.36, 3.38]) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an area under the ROC curve (AUC) of 0.64 (95%CI, 0.56,0.72) in those with suspected CAP and AUC 0.77 (95% CI, 0.68,0.87) in radiographic CAP.

Conclusions: ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1138DOI Listing
August 2020

Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer.

J Investig Med High Impact Case Rep 2019 Jan-Dec;7:2324709619890942

George Washington University Medical Faculty Associates, Washington, DC, USA.

. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. . We report a case of aggressive ATC with 5 sequence mutations: (mutation fraction [MF] 34%), (MF 37%), (MF 55%), (MF 60%), and (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. . We report a unique case of ATC with 2 new mutations of and . This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2324709619890942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880026PMC
July 2020

Endothelium-Derived Factors Influence Differentiation of Fat-Derived Stromal Cells Post-Exercise in Subjects with Prediabetes.

Metab Syndr Relat Disord 2019 Jul/Aug;17(6):314-322. Epub 2019 Apr 24.

1Department of Medicine and Endocrinology, The George Washington University, Washington, District of Columbia.

We investigated the effect of aerobic and resistance exercise on abdominal subcutaneous fat-derived stromal cells in middle-aged subjects with prediabetes, pre- and post-exercise to establish molecular mechanisms that drive the effect of exercise. Five subjects, aged between 40 and 60 years with a body mass index between 25 and 39.9 kg/m and with prediabetes, were enrolled in a 12-week exercise intervention program. Biophysical parameters were assessed pre- and post-exercise. Stromal cells were obtained from subcutaneous abdominal fat and cultured for 2-3 weeks. The stromal cells were then analyzed for mRNA analysis pre- and post-exercise. This was followed up with experiments where commercially obtained human fat-derived mesenchymal stromal cells (MSCs) were exposed to adipogenic media, and conditioned media from human endothelial conditioned media (ECM) cells were added to note if ECM addition altered adipogenesis. Subsequently, MSC differentiation was monitored by reverse transcription-polymerase chain reaction (RT-PCR). Post-exercise, subjects' cardiometabolic parameters improved. MSC obtained at post-exercise phase, from subcutaneous fat biopsies, on RT-PCR analysis, showed upregulation of antioxidant, mitochondrial, glucose transporter, and genes associated with osteogenesis compared with pre-exercise MSC mRNA. A concomitant increase in plasma osteocalcin levels was also noted post-exercise. , MSCs exposed to adipogenic differentiation media with the addition of ECM showed a significant reduction in expression of adipogenic marker genes and instead showed upregulation of genes associated with osteogenic differentiation. Exercise appears to prevent adipogenic differentiation of fat-derived stromal cells and promote osteogenic differentiation, in prediabetic middle-aged subjects. Interestingly, the addition of endothelium-derived factors to adipogenic media also appears to prevent adipogenic differentiation of commercially obtained fat-derived stromal cells and promotes osteogenic differentiation. Both and findings emphasize the paracrine effect of endothelium-derived factors on fat differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/met.2018.0121DOI Listing
May 2020

Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study.

Am J Med 2017 12 31;130(12):1465.e27-1465.e39. Epub 2017 Aug 31.

Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

Background: Early stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3).

Methods: Τwo co-primary composite cardiovascular outcomes were assessed. The first was the composite end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes; and the second was a composite of any of these events plus a revascularization procedure, or hospitalization for heart failure. Several secondary outcomes were prespecified, including microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers.

Results: Complete renal function data were available in 12,174 of 12,537 ORIGIN participants. A total of 8114 (67%) had no chronic kidney disease, while 4060 (33%) had chronic kidney disease stage 1-3. When compared with nonchronic kidney disease participants, the risk of developing the composite primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in those with mild to moderate chronic kidney disease was 87% higher; hazard ratio (HR) 1.87; 95% confidence interval (CI), 1.71-2.04 (P < .0001). The presence of chronic kidney disease 1-3 was also associated with a greater than twofold higher risk for both all-cause mortality (HR 2.17; 95% CI, 1.98-2.38; P < .0001) and cardiovascular mortality (HR 2.39; 95% CI, 2.13-2.69; P < .0001). Moreover, patients with mild to moderate chronic kidney disease had significantly higher risk for nonfatal myocardial infarction (50%), nonfatal stroke (68%), any stroke (84%), the above composite primary end point plus revascularization or heart failure requiring hospitalization (59%), or a major coronary artery disease event (56%). Furthermore, in patients with chronic kidney disease and early diabetes mellitus type 2, the primary end point occurred 83% more frequently as compared with nonchronic kidney disease participants (HR 1.83; 95% CI, 1.67-2.01; P < .001) and in patients with prediabetes and chronic kidney disease 67% more frequently (HR 1.67; 95% CI,1.25-2.24; P < .001).

Conclusions: In high-risk patients with dysglycemia (prediabetes and early diabetes), mild and moderate chronic kidney disease significantly increased cardiovascular events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2017.05.047DOI Listing
December 2017

Cardiorespiratory Fitness and Incidence of Type 2 Diabetes in United States Veterans on Statin Therapy.

Am J Med 2017 10 25;130(10):1192-1198. Epub 2017 May 25.

John Ochsner Heart and Vascular Institute, Department of Cardiovascular Diseases, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, La.

Background: Impact of cardiorespiratory fitness on statin-related incidence of type 2 diabetes has not been assessed. We assessed the cardiorespiratory fitness and diabetes incidence association in dyslipidemic patients on statins.

Methods: We identified dyslipidemic patients with a normal exercise test performed during 1986 and 2014 at the Veterans Affairs Medical Centers in Washington, DC or Palo Alto, Calif. The statin-treated patients (n = 4092; age = 58.8 ± 10.9 years) consisted of 2701 Blacks and 1391 Whites. None had evidence of type 2 diabetes prior to statin therapy. We formed 4 fitness categories based on age and peak metabolic equivalents achieved: Least-fit (n = 954), Low-fit (n = 1201), Moderate-fit (n = 1242), and High-fit (n = 695). The non-statin-treated cohort (n = 3001; age = 57.2 ± 11.2 years) with no evidence of type 2 diabetes prior to the exercise test served as controls.

Results: Diabetes incidence was 24% higher in statin-treated compared with non-statin-treated patients (P <.001). In the statin-treated cohort, 1075 (26.3%) developed diabetes (average annual incidence rate of 30.6 events/1000 person-years). Compared with the Least-fit, adjusted risk decreased progressively with increasing fitness and was 34% lower for High-fit patients (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.53-0.82; P <.001). Compared with the nonstatin cohort, elevated risk was evident only in the Least-fit (HR 1.50; 95% CI, 1.30-1.73; P <.001) and Low-fit patients (HR 1.22; 95% CI, 1.06-1.41; P = .006).

Conclusions: Risk of diabetes in statin-treated dyslipidemic patients was inversely and independently associated with cardiorespiratory fitness. The increased risk was evident only in relatively low-fitness patients. Improving fitness may modulate the potential diabetogenic effects of statins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2017.04.042DOI Listing
October 2017

Effects of High Density Lipoprotein Raising Therapies on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus, with or without Renal Impairment: The Action to Control Cardiovascular Risk in Diabetes Study.

Am J Nephrol 2017 17;45(2):136-145. Epub 2016 Dec 17.

Veteran Affairs Medical Center and Georgetown University, Washington, DC, USA.

Background: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial.

Methods: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD. Differences in CV outcomes during follow-up between CKD and non-CKD subgroups were examined. In addition, the effect of fenofibrate as compared to placebo on CV outcomes was examined for both subgroups.

Results: All CV outcomes were 1.4-3 times higher among patients with CKD as compared to non-CKD patients. In patients with CKD, the addition of fenofibrate had no effect on any of the primary or secondary outcomes. In patients without CKD, however, the addition of fenofibrate was associated with a significant 36% reduction of CV mortality (hazards ratio [HR] 0.64; 95% CI 0.42-0.97; p value for treatment interaction <0.05) and 44% lower rate of fatal or non-fatal congestive heart failure (CHF; HR 0.56; 95% CI 0.37-0.84; p value treatment interaction <0.03).

Conclusions: For patients with type 2 diabetes at high CV risk but no CKD, fenofibrate therapy added to statin reduced the CV mortality and the rate of fatal and non-fatal CHF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000453626DOI Listing
January 2018

Pleural fluid procalcitonin to distinguish infectious from noninfectious etiologies of pleural effusions.

J Hosp Med 2016 05 28;11(5):363-5. Epub 2016 Jan 28.

Department of Diabetes, Endocrinology, and Metabolism, Veterans Affairs Medical Center, and George Washington University, Washington, DC.

In this study we investigate the diagnostic value of pleural fluid procalcitonin (PCT) in distinguishing infectious and noninfectious etiologies of pleural effusion. We reviewed the medical records of 75 hospitalized patients who underwent thoracentesis between 2011 and 2012. Data on pleural fluid lactate dehydrogenase (LDH), protein, albumin, cell count and differential, pH, Gram stain and culture, cytology, triglyceride, cholesterol, amylase, and PCT were collected. Data on serum LDH, protein, albumin, prothrombin time, normalized, and blood culture were also collected. Pleural effusions were classified into 2 groups, infectious and noninfectious. There were 18 infectious pleural effusions (IPE) and 57 noninfectious pleural effusions (NIPE). Median pleural fluid PCT was 1.088 ng/mL (0.312-2.940 ng/mL) in IPE and 0.123 ng/mL (0.05-0.263 ng/mL) in NIPE, with a P value < 0.0001. Pleural fluid PCT > 0.25 ng/mL had a sensitivity of 77.78% and specificity of 74.14% for diagnosing an IPE. A subgroup analysis of PCT in exudative infectious effusions versus exudative noninfectious malignant/paramalignant effusions showed higher levels in the former. PCT is a novel biomarker for diagnosing infectious pleural effusion, and it would be worthwhile to investigate the role of pleural PCT in assessing severity of illness, risk stratification, and antibiotic stewardship in hospitalized patients with pleural effusions. Journal of Hospital Medicine 2016;11:363-365. 2016 Society of Hospital Medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhm.2551DOI Listing
May 2016

New-Onset Diabetes Mellitus With Exposure to Ledipasvir and Sofosbuvir.

J Investig Med High Impact Case Rep 2015 Oct-Dec;3(4):2324709615623300. Epub 2015 Dec 29.

VA Medical Center, Washington, DC, USA.

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. Hence, clinicians should be cautious about worsening of glucose intolerance, and more studies are warranted to explore the underlying mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2324709615623300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710113PMC
January 2016

Commentary.

Clin Chem 2015 Nov;61(11):1331

Department of Endocrinology, DC VA Medical Center; Department of Endocrinology, George Washington University, Washington, DC.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2015.240630DOI Listing
November 2015

Lithium as an Alternative Option in Graves Thyrotoxicosis.

Case Rep Endocrinol 2015 6;2015:869343. Epub 2015 Sep 6.

Department of Medicine, Division of Endocrinology & Metabolism, Medical Faculty Associates, The George Washington University, Washington, DC, USA.

A 67-year-old woman was admitted with signs and symptoms of Graves thyrotoxicosis. Biochemistry results were as follows: TSH was undetectable; FT4 was >6.99 ng/dL (0.7-1.8); FT3 was 18 pg/mL (3-5); TSI was 658% (0-139). Thyroid uptake and scan showed diffusely increased tracer uptake in the thyroid gland. The patient was started on methimazole 40 mg BID, but her LFTs elevated precipitously with features of fulminant hepatitis. Methimazole was determined to be the cause and was stopped. After weighing pros and cons, lithium was initiated to treat her persistent thyrotoxicosis. Lithium 300 mg was given daily with a goal to maintain between 0.4 and 0.6. High dose Hydrocortisone and propranolol were also administered concomitantly. Free thyroid hormone levels decreased and the patient reached a biochemical and clinical euthyroid state in about 8 days. Though definitive RAI was planned, the patient has been maintained on lithium for more than a month to control her hyperthyroidism. Trial removal of lithium results in reemergence of thyrotoxicosis within 24 hours. Patient was maintained on low dose lithium treatment with lithium level just below therapeutic range which was sufficient to maintain euthyroid state for more than a month. There were no signs of lithium toxicity within this time period. Conclusion. Lithium has a unique physiologic profile and can be used to treat thyrotoxicosis when thionamides cannot be used while awaiting elective radioablation. Lithium levels need to be monitored; however, levels even at subtherapeutic range may be sufficient to treat thyrotoxicosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/869343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575726PMC
October 2015

Commentary.

Clin Chem 2014 Oct;60(10):1271

Division of Endocrinology and Metabolism, Department of Medicine, George Washington School of Medicine and Health Sciences; Division of Endocrinology and Metabolism, Department of Medicine, VA Medical Center, Washington, DC.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2014.221390DOI Listing
October 2014

Chronic kidney disease and intensive glycemic control increase cardiovascular risk in patients with type 2 diabetes.

Kidney Int 2015 Mar 17;87(3):649-59. Epub 2014 Sep 17.

Veterans Affairs Medical Center, VA Clinical Center Network, Memphis, Tennessee, USA.

Results of the main Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial indicate that intensive glucose lowering increases cardiovascular and all-cause mortality. As the contribution of mild-to-moderate chronic kidney disease (CKD) to these risks is not known, we assessed the impact on cardiovascular outcomes in this population. Renal function data were available on 10,136 patients of the original ACCORD cohort. Of those, 6,506 were free of CKD at baseline and 3,636 met the criteria for CKD. Participants were randomly assigned to a treatment strategy of either intensive or standard glycemic goal. The primary outcome, all-cause and cardiovascular mortality, and prespecified secondary outcomes were evaluated. Risk for the primary outcome was 87% higher in patients with than in those without CKD (hazard ratio of 1.866; 95% CI: 1.651-2.110). All prespecified secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD. In patients with CKD, compared with standard therapy, intensive glucose lowering was significantly associated with both 31% higher all-cause mortality (1.306: 1.065-1.600) and 41% higher cardiovascular mortality (1.412: 1.052-1.892). No significant effects were found in patients without CKD. Thus, in high-risk patients with type II diabetes, mild and moderate CKD is associated with increased cardiovascular risk. Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ki.2014.296DOI Listing
March 2015

Procalcitonin beyond the acute phase: novel biomediator properties?

BMC Med 2013 Aug 28;11:189. Epub 2013 Aug 28.

Department Endocrinology, VAMC, and George Washington University School of Medicine, Washington, DC, USA.

Since inflammation has been linked to carcinogenic events, discovery of relevant biomarkers may have important preventative implications. Procalcitonin (ProCT) has been shown to be an important prognostic biomarker in severe inflammatory conditions, but there is no data regarding its biomarker role, if any, beyond the acute phase. In a recent study published in BMC Medicine, Cotoi et al. analyzed whether serum ProCT levels in healthy individuals are associated with mortality outcomes. The results are affirmative in that baseline ProCT was shown to be strongly and independently associated with all-cause and cancer mortality and with the incidence of colon cancer in men. By contrast, the study indicated that high sensitivity C-reactive protein was independently associated with cardiovascular mortality but not with cancer mortality in men. Thus, baseline levels of ProCT appear to have prognostic biomarker implications potentially related to its emerging biomediator action(s).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1741-7015-11-189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765476PMC
August 2013

Procalcitonin induced cytotoxicity and apoptosis in mesangial cells: implications for septic renal injury.

Inflamm Res 2013 Oct 20;62(10):887-94. Epub 2013 Jul 20.

Nephrology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Objective And Design: Immuno-neutralization of procalcitonin (ProCT) has been shown to ameliorate experimental sepsis as well as the renal complications of this disease. Accordingly, we investigated the direct effect of ProCT on mesangial cells (MCs).

Material: Primary culture of murine MCs.

Treatment: ProCT (0.5, 1.0, 2.5, 5.0 ng/ml) for 2, 4, 6 h.

Methods: MCs were exposed in vitro to ProCT. Expression levels of IL-6, iNOS and TNF-α were determined by real time RT-PCR, Inflammatory pathways, and a panel of cytokines and chemokines involved in the process were investigated by PCR array; apoptosis/viability were evaluated in a multiplex assay and actin cytoskeleton alterations were examined by immunofluorescence (IF).

Results: ProCT caused an early elevation in both IL-6 and iNOS mRNA (2-4 h), and a later rise (6 h) in TNF-α mRNA. ProCT upregulated genes of proinflammatory pathways 5- to 24-fold compared to control. IF images revealed disruption of the actin cytoskeleton and retraction of cell bodies with loss of typical stellate or spindle shape phenotype. ProCT decreased MCs viability by 36 % compared to control cells and induced significant apoptosis.

Conclusions: ProCT has direct cytotoxic properties and may play a role in septic acute kidney injury that is independent of endotoxemia or hemodynamic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00011-013-0646-8DOI Listing
October 2013

Statins modulate the mortality risk associated with obesity and cardiorespiratory fitness in diabetics.

J Clin Endocrinol Metab 2013 Aug 19;98(8):3394-401. Epub 2013 Jun 19.

Departments of Endocrinology, Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422, USA.

Context: Statins are commonly prescribed to avert cardiovascular disease in diabetics. Little information, however, exists about the interrelationship of obesity, fitness, and statin treatment on mortality.

Objective: Our objective was to evaluate the influence of statin therapy on body mass index (BMI), cardiorespiratory fitness, and all-cause mortality risk in diabetics.

Design: We gathered prospective observational data from Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California, on type 2 diabetic male veterans (n = 3775; mean age = 58.9 ± 9.9 years) who underwent an exercise tolerance test during the period of 1986 to 2011.

Results: There were 930 deaths during a mean follow-up period of 10.5 years (37 826 person-years), with an average annual mortality of 24.6 events per 1000 person-years of observation. Adjusted Cox proportional hazard analysis revealed that mortality risk was 34% lower (hazard ratio [HR] = 0.66; confidence interval [CI] = 0.57-0.77) for individuals treated with statins compared with those not on statins. There was a paradoxical BMI-mortality association, with the highest mortality in those with a BMI of 18.5 to 24.9 kg/m(2) (HR = 1.54; CI = 1.26-1.87, P < .0001) compared with obese subjects (BMI of 30-34.9 kg/m(2)). However, this paradoxical association was evident only in those not treated with statins (HR = 1.79; CI = 1.39-2.29; P < .001) vs those on statins (HR = 1.06; CI = 0.75-1.54; P = .70). When statin therapy and fitness status were combined, mortality risk was 44% higher (HR = 1.44; CI = 1.16-1.78) in the least-fit not treated with statins compared with the least-fit treated with statins. Mortality risk declined progressively with increased fitness to 60% lower (HR = 0.40; CI = 0.24-0.66) and 49% lower (HR = 0.51; CI = 0.38-0.68) for the most highly fit individuals (>9 metabolic equivalents) treated and not treated with statins, respectively.

Conclusion: Statin therapy was associated with increased survival in diabetic veterans, which was further enhanced when fitness and statin therapy were combined. In addition, statin therapy eliminated the increased mortality risk associated with BMI <25 kg/m(2). The presence of a paradoxical BMI-mortality risk association, which is modulated by statin therapy has novel clinically relevant implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2013-1431DOI Listing
August 2013

Bacterial complications of respiratory tract viral illness: a comprehensive evaluation.

J Infect Dis 2013 Aug 9;208(3):432-41. Epub 2013 May 9.

Rochester General Hospital, Rochester, NY, USA.

Background: Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied.

Methods: Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization.

Results: Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis.

Conclusions: Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jit190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699009PMC
August 2013

Can serum procalcitonin levels help interpret indeterminate chest radiographs in patients hospitalized with acute respiratory illness?

J Hosp Med 2013 Feb 19;8(2):61-7. Epub 2012 Oct 19.

Department of Medicine, University of Rochester, Rochester, NY, USA.

Background: Clinical diagnosis of pneumonia is difficult and chest radiographs often indeterminate, leading to incorrect diagnoses and antibiotic overuse.

Objective: To determine if serum procalcitonin (ProCT) could assist in managing patients with respiratory illness and indeterminate radiographs.

Design: Subjects were prospectively enrolled during 2 consecutive winters.

Setting: A 520-bed hospital in Rochester, NY.

Patients: Five hundred twenty-eight adults admitted with acute respiratory illness were enrolled.

Measurements: Serum ProCT, admission diagnoses, and chest radiographic findings were used to derive receiver operating characteristics curves to assess predictive accuracy of ProCT for the presence of infiltrates.

Results: Subjects with pneumonia had higher ProCT (median 0.27 ng/ml) than those with exacerbations of chronic obstructive pulmonary disease (0.08 ng/ml), acute bronchitis (0.09 ng/ml), or asthma (0.06 ng/ml). ProCT had moderate accuracy for the presence of infiltrates (area under curve [AUC] 0.72), when indeterminate radiographs were independently classified as infiltrates by a pulmonologist evaluating patients.

Conclusions: ProCT may be useful in diagnosing pneumonia when chest radiographs are indeterminate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhm.1984DOI Listing
February 2013

Utility of serum procalcitonin values in patients with acute exacerbations of chronic obstructive pulmonary disease: a cautionary note.

Int J Chron Obstruct Pulmon Dis 2012 23;7:127-35. Epub 2012 Feb 23.

Department of Medicine, University of Rochester, Rochester, NY, USA.

Background: Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD). However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking. Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes. Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.

Methods: Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens. Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month. Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared.

Results: In total, 224 subjects with COPD were admitted for 240 respiratory illnesses. Of these, 56 had pneumonia and 184 had AECOPD alone. A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection). Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD. However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor.

Conclusion: Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S29149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292390PMC
June 2012

BMI-mortality paradox and fitness in African American and Caucasian men with type 2 diabetes.

Diabetes Care 2012 May 7;35(5):1021-7. Epub 2012 Mar 7.

Cardiology Department, Veterans Affairs Medical Center, Washington, DC, USA.

Objective: To assess the association between BMI, fitness, and mortality in African American and Caucasian men with type 2 diabetes and to explore racial differences in this association.

Research Design And Methods: We used prospective observational data from Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Our cohort (N = 4,156; mean age 60 ± 10.3 years) consisted of 2,013 African Americans (mean age, 59.5 ± 9.9 years), 2,000 Caucasians (mean age, 60.8 ± 10.5 years), and 143 of unknown race/ethnicity. BMI, cardiac risk factors, medications, and peak exercise capacity in metabolic equivalents (METs) were assessed during 1986 and 2010. All-cause mortality was assessed across BMI and fitness categories.

Results: There were 1,074 deaths during a median follow-up period of 7.5 years. A paradoxic BMI-mortality association was observed, with significantly higher risk among those with a BMI between 18.5 and 24.9 kg/m(2) (hazard ratio [HR] 1.70 [95% CI 1.36-2.1]) compared with the obese category (BMI ≥ 35 kg/m(2)). This association was accentuated in African Americans (HR 1.95 [95% CI 1.44-2.63]) versus Caucasians (HR 1.53 [1.0-2.1]). The fitness-mortality risk association for the entire cohort and within BMI categories was inverse, independent, and graded. Mortality risks were 12% lower for each 1-MET increase in exercise capacity, and ~35-55% lower for those with an exercise capacity >5 METs compared with the least fit (≤ 5 METs). CONCLUSIONS A paradoxic BMI-mortality risk association was observed in African American and Caucasian patients with diabetes. The exercise capacity-mortality risk association was inverse, independent, and graded in all BMI categories but was more potent in those with a BMI ≥ 25 kg/m(2).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc11-2407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329828PMC
May 2012

Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome.

Crit Care Med 2012 Feb;40(2):495-501

Pulmonary Section, Veterans Affairs Medical Center, Washington, DC, USA.

Objective: Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome.

Design: Retrospective analysis.

Setting: Four intensive care units.

Subjects: Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial.

Interventions: Early methylprednisolone infusion (n = 55) compared with placebo (n = 24).

Measurements And Main Results: Interleukin-6, tumor necrosis factor α, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p = .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p ≤ .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy.

Conclusions: In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0b013e318232da5eDOI Listing
February 2012

Vitamin D deficiency is less common among HIV-infected African-American men than in a matched cohort.

AIDS 2011 Jun;25(9):1237-9

Section of Infectious Diseases, Veterans Affairs Medical Center, Washington, District of Columbia, USA.

The aim of this study was to compare the prevalence of vitamin D sufficiency and deficiency in a HIV-infected cohort of African-American men with that of a general population. We found median vitamin D concentrations were significantly greater in the HIV-infected cohort, 18 ng/ml as compared to the National Health and Nutrition Examination Survey cohort, 14 ng/ml (P ≤ 0.0001). Thus, factors other than measured vitamin D are likely to be responsible for higher rates of bone disease in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0b013e3283474ef9DOI Listing
June 2011

Exogenous procalcitonin evokes a pro-inflammatory cytokine response.

Inflamm Res 2011 Feb 17;60(2):203-7. Epub 2010 Oct 17.

Medical Service and Section of Infectious Diseases, Veterans Affairs Medical Center, 50 Irving Street, NW 4A155, Washington, DC, USA.

Objective And Design: Procalcitonin (ProCT) is increased in serum of septic patients and those with systemic inflammation. Endogenous levels of ProCT might influence the response of polymorphonuclear leukocytes (PMNs), independently of endotoxin, in clinical disease.

Subjects: Healthy human volunteers.

Treatment: Recombinant human ProCT (rhProCT).

Methods: Whole blood and PMNs were exposed in vitro to exogenous rhProCT. Interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNFα), IL-1β, and macrophage inflammatory protein (MIP)-1β (pg/ml) were measured by multiplex suspension bead-array immunoassay, and migration and phagocytosis were measured in PMNs.

Results: In a whole-blood model, a dose-dependent increase in IL-6, TNFα, and IL-1β of the cell-free supernatant was noted. Pre-incubation with ProCT, at doses consistent with clinical sepsis, resulted in a decrease in PMN migration without alteration in phagocytosis of Staphylococcus aureus or indirect measurements of bacterial killing.

Conclusion: Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00011-010-0255-8DOI Listing
February 2011

Prognostic effect of exercise capacity on mortality in older adults with diabetes mellitus.

J Am Geriatr Soc 2010 Oct;58(10):1850-4

Department of Endocrinology, Veterans Affairs Medical Center, Washington, DC 20422, USA.

Objectives: To investigate the prognostic effect of exercise capacity in older individuals with diabetes mellitus.

Design: Retrospective data review in a clinic-based cohort.

Setting: Veterans Affairs Medical Centers in Washington, District of Columbia, and Palo Alto, California.

Participants: Two thousand eight hundred sixty-seven men aged 50 to 87 with type 2 diabetes mellitus.

Measurements: Exercise tolerance testing with fitness categories based on peak metabolic equivalents of task (METs) achieved adjusted for age. All-cause mortality in age groups 50 to 65 (Group 1; n=1,658) and older than 65 (Group 2; n=1,209) was analyzed using adjusted Cox proportional hazards models.

Results: After a mean ± standard deviation follow-up period of 7.8 ± 5.1 years, there were 324 deaths in Group 1 (20%) and 464 in Group 2 (38%). For each 1-MET increase in exercise capacity, mortality was 18% lower for the entire cohort (hazard ratio (HR)=0.82, 95% confidence interval (CI)=0.79-0.86), 23% lower for Group 1 (HR=0.77, 95% CI=0.73-0.82), and 16% lower for Group 2 (HR=0.84, 95% CI=0.8-0.89). When fitness categories were considered, the mortality risk was 30% to 80% lower for those who achieved more than 4 METs in both age groups.

Conclusion: Augmented exercise capacity is associated with lower risk of mortality in people with type 2 diabetes mellitus aged 50 to 65 as well as in those older than 65. Thus, physical fitness, as represented by exercise capacity, lowers mortality risk in people with diabetes mellitus irrespective of age. These findings suggest that healthcare providers should be cognizant of the level of exercise capacity in individual patients and encourage a physically active lifestyle regardless of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1532-5415.2010.03068.xDOI Listing
October 2010

Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.

Pancreas 2010 Oct;39(7):1064-9

Department of Surgery, Manchester Royal Infirmary, Manchester, United Kingdom.

Objectives: This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients.

Methods: A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially.

Results: Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002).

Conclusions: Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0b013e3181da8d51DOI Listing
October 2010

Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target.

Br J Pharmacol 2010 Jan 27;159(2):253-64. Epub 2009 Nov 27.

George Washington University and Veterans Affairs Medical Center, Washington, DC 20422, USA.

The worldwide yearly mortality from sepsis is substantial, greater than that of cancer of the lung and breast combined. Moreover, its incidence is increasing, and its response to therapy has not appreciably improved. In this condition, the secretion of procalcitonin (ProCT), the prohormone of calcitonin, is augmented greatly, attaining levels up to thousands of fold of normal. This hypersecretion emanates from multiple tissues throughout the body that are not traditionally viewed as being endocrine. The serum values of ProCT correlate with the severity of sepsis; they recede with its improvement and worsen with exacerbation. Accordingly, as highlighted in this review, serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions. It is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement. Moreover, it has been demonstrated that the administration of ProCT to septic animals greatly increases mortality, and several toxic effects of ProCT have been elucidated by in vitro experimental studies. Antibodies have been developed that neutralize the harmful effects of ProCT, and their use markedly decreases the symptomatology and mortality of animals that harbour a highly virulent sepsis analogous to that occurring in humans. This therapy is facilitated by the long duration of serum ProCT elevation, which allows for a broad window of therapeutic opportunity. An experimental groundwork has been established that suggests a potential applicability of such therapy in septic humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1476-5381.2009.00433.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825349PMC
January 2010

Diagnostic accuracy of chromogranin A and calcitonin precursors measurements for the discrimination of ectopic ACTH secretion from Cushing's disease.

J Clin Endocrinol Metab 2009 Aug 26;94(8):2962-5. Epub 2009 May 26.

The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1109, USA.

Context: Inferior petrosal sinus sampling (IPSS) best discriminates between the two causes of ACTH-dependent Cushing's syndrome, Cushing's disease (CD) and ectopic ACTH secretion (EAS). However, when sampling is not available, adjunctive diagnostic tests might be helpful. Neuroendocrine tumors may secrete chromogranin A (CgA), calcitonin (CT), procalcitonin (ProCT), a fragment of the amino terminus of procalcitonin (NProCT), and/or ACTH.

Objective: The aim of the study was to evaluate the ability of serum CgA, CT, ProCT, or NProCT values to distinguish CD from EAS.

Design And Setting: We conducted a prospective pilot study at a clinical research center.

Subjects And Methods: Serum ProCT, NProCT, and CgA were measured in six patients with occult EAS diagnosed by IPSS, 25 CD patients, and 11 patients with histologically proven EAS.

Results: Nine EAS patients (53%) had at least one value above the reference range, including CgA alone (n = 4), ProCT alone (n = 3), CgA and ProCT (n = 1), and NProCT and ProCT (n = 1). Of nine (36%) CD patients with one or two abnormal values, seven had increased ProCT only, one had increased NProCT only, and one had increased CgA and ProCT. CgA had a positive predictive value of 83% and a negative predictive value of 70% for the diagnosis of EAS; other markers showed less discrimination. On pituitary magnetic resonance imaging, no EAS patient had an abnormality, whereas 21 of 25 patients with CD had a mass.

Conclusion: These preliminary results suggest that an abnormal CgA and normal pituitary magnetic resonance imaging favor the diagnosis of EAS, but normal tumor markers do not exclude the diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2009-0604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730869PMC
August 2009

Exercise capacity and all-cause mortality in African American and Caucasian men with type 2 diabetes.

Diabetes Care 2009 Apr 5;32(4):623-8. Epub 2009 Feb 5.

Veterans Affairs Medical Center, Washington, DC, USA.

Objective: The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship.

Research Design And Methods: African American (n = 1,703; aged 60 +/- 10 years) and Caucasian (n = 1,445; aged 62 +/- 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 +/- 4.7 years.

Results: The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1-1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P < 0.001) and among race and fitness categories (P < 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P < 0.001). Similarly, the risk was 43% lower (0.57 [0.44-0.73]) for moderate-fit and 67% lower (0.33 [0.22-0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55-0.80]) and 46% (0.54 [0.39-0.73]), respectively.

Conclusions: Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc08-1876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660444PMC
April 2009

Procalcitonin levels in febrile infants after recent immunization.

Pediatrics 2008 Nov;122(5):e1119-22

Divisions of Endocrinology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.

Background: Procalcitonin has been identified as a useful blood marker of serious bacterial infection in febrile infants. Many infants present with a febrile reaction after receiving immunizations. The effects of immunization on procalcitonin have not been investigated.

Methods: We performed a prospective observational cohort study at a large, urban pediatric emergency department. Infants or=38 degrees C were enrolled. Subjects were divided into 3 groups: infants with serious bacterial infection; subjects without serious bacterial infection who received recent (<48 hours) immunizations; and subjects without serious bacterial infection who did not recently receive immunizations. Procalcitonin was measured by using a quantitative immunometric assay.

Results: Over 13 months, procalcitonin was measured for 271 infants. There were 44 (16%) patients with serious bacterial infection, 35 in the recent-immunization group, and 192 in the no-recent-immunization group. The median procalcitonin level for serious bacterial infection was 0.53 ng/mL, for recent immunization was 0.29 ng/mL, and for no recent immunizations was 0.17 ng/mL. Procalcitonin values were elevated for patients with serious bacterial infection compared with patients both with and without recent immunizations. Compared with patients who had no recent immunizations, procalcitonin levels were elevated in patients with recent immunization. Using a cut point of 0.12 ng/mL, the sensitivity of procalcitonin for serious bacterial infection was 96%, specificity was 23%, and negative predictive value was 96%. Two patients with recent immunization who had serious bacterial infection were identified with this cut point.

Conclusions: Among febrile infants with recent immunization, procalcitonin levels are increased compared with patients with fever and no identified bacterial infection. Despite this increase, procalcitonin can still reliably discriminate infants with serious bacterial infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2008-1884DOI Listing
November 2008
-->