Glucagon-Like Peptide-1 Receptor Agonists and Sodium Glucose Cotransporter-2 Inhibitors and Cardiorespiratory Fitness Interaction.

INTRODUCTION: Cardiorespiratory fitness (CRF) is a stronger predictor of mortality than traditional risk factors and is a neglected vital sign of health. Enhanced fitness is a cornerstone in diabetes management and is most often delivered concurrently with pharmacological agents, which can have an opposing impact, as has been reported with metformin. Considering the rapid evolution of diabetes medications with improved cardiovascular outcomes, such as glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, it is of importance to consider the influence of these vis-a-vis effects on CRF. MATERIALS AND METHODS: Combining the words glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors with cardiorespiratory fitness, an online search was done using PubMed, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Cochrane. RESULTS: There were only a few randomized controlled studies that included CRF, and the results were mostly neutral. A handful of smaller studies detected improved CRF using sodium glucose cotransporter-2 inhibitors in patients with congestive heart failure. CONCLUSIONS: Since CRF is a superior prognosticator for cardiovascular outcomes and both medications can cause lean muscle mass loss, the current review highlights the paucity of relevant interactive analysis.

Pituitary Macroadenoma With Macronodular Adrenal Hyperplasia and Novel Armadillo Repeat-Containing Protein 5 (ARMC5) Mutation.

We present an unusual case of primary bilateral macronodular adrenal hyperplasia (PBMAH) in a 72-year-old African American man. The patient was found to harbor massively enlarged bilateral adrenal glands on imaging along with mild autonomous cortisol secretion. His workup for PBMAH included leukocyte analysis for the armadillo repeat-containing protein 5 (ARMC5) gene. The test revealed a novel heterozygous somatic ARMC5 mutation. The patient was initially managed conservatively. He subsequently presented with unprovoked bilateral pulmonary emboli. This was followed by the discovery of a nonsecreting pituitary macroadenoma, a hitherto unreported but putative association.

An Atypical Cause of Hoarseness in a Patient With Thyroid Nodules.

Hoarseness due to vocal fold paresis (VFP) has a multitude of etiologies including systemic lupus erythematosus (SLE). During a clinical evaluation of a 58-year-old woman with long-standing hoarseness, an incidental finding of thyroid nodules was found to have VFP. Direct laryngoscopy and vocal fold biopsy confirmed the source was an inflammatory process involving the cricoarytenoid joint of the right hemilarynx. A presumptive diagnosis of SLE was made 3 years before meeting the clinical criteria of overt SLE. The VFP debut of SLE is extremely rare, and a literature review includes a handful of case reports (4 of a total of 37) since 1959. Only partial recovery of laryngeal function using glucocorticoids and Plaquenil was accomplished in the current case.

Novel Therapeutics in Nonalcoholic Fatty Liver Disease: A Focus on Adult Stem Cells.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is associated with abnormal accumulation of fat in the liver, which can lead to a wide variety of pathological liver defects and associated insulin resistance (IR), obesity, hypertension, dyslipidemia, diabetes, and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Increased lipolysis and de novo hepatic lipid synthesis lead to oxidative stress induced by reactive oxygen species and inflammation. Both these two entities could be interrelated and be an important mechanistic pathway, which can lead to tissue injury and hepatic cell death. Mechanisms for worsening of NAFLD include mitochondrial abnormalities, downregulation of glutathione (GSH), decreased activity of GSH-dependent antioxidants, accumulation of activated macrophages, hepatic inflammation, systemic inflammation, IR, and poorly controlled type 2 diabetes mellitus. Although no specific therapy has been approved for NAFLD, we review the latest medical therapeutics with emphasis on stem cell-based possibilities based on the presumed pathophysiology of NAFLD.

Lipid Profile Changes Associated with SGLT-2 Inhibitors and GLP-1 Agonists in Diabetes and Metabolic Syndrome.

The introduction of sodium glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetes mellitus treatment has shown an unexpectedly significant improvement in heart disease outcome trials. Although they have very different modes of action, a portion of the salutary cardiovascular disease improvement may be related to their impact on diabetic dyslipidemia. As discussed in this focused review, the sodium glucose transporter-2 inhibitors as a class show a mild increase in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, while triglycerides (TG) decrease inconsistently. In particular, the rise in LDL appears to be related to the less atherogenic, large buoyant LDL particles. The glucagon-like peptide-1 receptor agonists show more of an impact on weight loss and improvement in the underlying low HDL and high TG dyslipidemia. The effect of sodium glucose transporter-2 inhibitors and glucagon-like peptide 1 receptor agonists when used in combination remains largely unknown. Also unexplored is difference in effect of these medications among various ethnicities and metabolic syndrome.

Urinary Proadrenomedullin and Disease Severity in Children With Suspected Community-acquired Pneumonia.

BACKGROUND: Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP. CONCLUSIONS: Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.

Proadrenomedullin Predicts Severe Disease in Children With Suspected Community-acquired Pneumonia.

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. Disease severity was defined as mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, 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 [IQR], 0.53 [0.43-0.73]; mild-moderate: 0.56 [0.45-0.71]; moderate-severe: 0.61 [0.47-0.77]; severe: 0.70 [0.55-1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: 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 AUC of 0.64 (95% CI, .56-.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68-.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.

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

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.

Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer.

Context. 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 BRAF V600E 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. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (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. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. 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.

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

Purpose: 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. Methods: Five subjects, aged between 40 and 60 years with a body mass index between 25 and 39.9 kg/m2 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 in vitro 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). Results: 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. In vitro, 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. Conclusions: 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 in vivo and in vitro findings emphasize the paracrine effect of endothelium-derived factors on fat differentiation.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.