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The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy‐proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy; (2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x‐ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3‐[3H] glucose); (5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3‐[3H] glucose infusion × FPI) and adipose tissue (fasting FFA × FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 ± 2% vs. 24 ± 2%, p = 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis. Conclusion: When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long‐term studies are needed to define their risk of disease progression. (HEPATOLOGY 2011;)

Objective To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. Methods A C. trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C. trachomatis infection. Results Thirteen immunodominant antigens reacted with 50% or more sera from all women (N=73). Six C. trachomatis antigens were uniquely recognized by women diagnosed with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.91–1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C. trachomatis-exposed women with a detection sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.95–1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. Conclusion A sequential screening of antibodies against panels of C. trachomatis antigens can be used to identify women with tubal factor infertility and acute C. trachomatis infection.

The impact of antiretroviral therapy (ART) on opportunistic conditions in HIV patients continues to evolve. We specifically studied the changing epidemiology of oropharyngeal candidiasis (OPC) in 215 HIV/AIDS patients. Status of yeast colonization was assessed from oral rinse samples, and preliminary yeast identification was made using CHROMagar Candida and confirmed with standard microbiological techniques and/or molecular sequencing. Susceptibility to fluconazole was determined by CHROMagar Candida agar dilution screening and CLSI broth microdilution. 176 (82%) patients were colonized and 59 (27%) patients had symptomatic OPC. Candida albicans was the most prevalent species, though C. glabrata and C. dubliniensis were detected in 29% of isolates. Decreased fluconazole susceptibility occurred in 10% of isolates. Previous ART reduced the risk of OPC, while smoking increased the risk of colonization. Oral yeast colonization and symptomatic infection remain common even with advances in HIV therapy. C. albicans is the most common species, but other yeasts are prevalent and may have decreased susceptibility to fluconazole.

Background/Aim: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers. Patients and Methods: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV). Results: We identified 33 protein biomarkers and developed a classifier using Random Forest. Our test detected early-stage Non-Small Cell Lung Cancer (NSCLC) with a 90% accuracy, 80% sensitivity, and 95% specificity in the validation set using the 33 markers. Conclusion: A specific, noninvasive, early-detection test, in combination with low-dose computed tomography, could increase survival rates and reduce false positives from screenings.According to the American Cancer Society, on a global scale, lung cancer is the leading cause of cancer-related incidence and death at 2.09 million cases and 1.76 million deaths in 2018 (1). By 2016, in the US, an estimated 538,243 living individuals were diagnosed with lung and bronchus cancer (2). An additional 228,150 new cases with an estimated 142,670 deaths are expected in 2019 (3).Lung cancer originates in the lungs, but can metastasize to other organs in the body. It is classified based on the histological profile of the tumor cell and predominantly falls into two major categories: i) small cell lung cancer (SCLC, 13%) and ii) non-small cell lung cancer (NSCLC, 84%) (3). Detection at Stage I or II for NSCLC can offer good prognosis. Symptoms and detection.Current methods of detecting lung cancer include a chest x-ray (CXR), computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, sputum analysis, and lung biopsy. Despite the advancement in technology and the extensive cancer research, 57% of lung cancer patients are diagnosed only after a tumor has metastasized to a different location. Under these circumstances, there is little chance of a cure, and the 5-year survival rate is less than 6% (2). Late diagnosis of lung cancer can be attributed to: i) primarily the lack of symptoms at early-stage lung cancer (4) ii) misdiagnosis of the disease since early symptoms (persistent cough, shortness of breath, chest pain, wheezing, and hemoptysis) are often misinterpreted (5) iii) the lack of proven benefit for lung cancer screening until recently (6), and iv) cost effect and limited access to state-of-the-art detection methods in indigent populations (7).It is evident that the sooner lung cancer is diagnosed, the better the prognosis for the patient. However, only 16% of patients were diagnosed when the disease was still restricted to the lungs and even for these, only 57.4% survived 5 years (8). Based on the 2016 Cancer Statistics Review by SEER (8), the 5-year survival rate decreased to 30....

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Background: Community-acquired respiratory distress syndrome (CARDS) toxin is a unique Mycoplasma pneumoniae virulence factor. Molecular assays targeting this toxin are more sensitive than existing diagnostics, but these assays have not been used to investigate the role of M pneumoniae as a nosocomial infection in critical illness. We sought to determine the incidence of M pneumoniae among mechanically ventilated subjects using these novel assays and to investigate the impact of this pathogen on pulmonary outcomes. Methods: We conducted a prospective observational study enrolling subjects with suspected ventilator-associated pneumonia (VAP) undergoing BAL in the surgical trauma ICU at a level I trauma center. Lavage fl uid and serum samples were tested for M pneumoniae using assays to detect CARDS toxin gene sequences, protein, or antitoxin antibodies. Results: We collected samples from 37 subjects, with 41% (15 of 37) testing positive using these assays. The positive and negative groups did not differ signifi cantly in baseline demographic characteristics, including age, sex, injury severity, or number of ventilator days before bronchoscopy. The positive group had signifi cantly fewer ventilator-free days ( P 5 .04) and lower average oxygenation ( P 5 .02). These differences were most pronounced among subjects with ARDS. Conclusions: Evidence is provided that M pneumoniae is present in a substantial number of subjects with suspected VAP. Subjects testing positive experience a signifi cantly longer ventilator course and worse oxygenation compared with subjects testing negative. CHEST 2011; 139(2):305-310Abbreviations: APACHE 5 Acute Physiology and Chronic Health Evaluation; CARDS 5 community-acquired respiratory distress syndrome; ELISA 5 enzyme-linked immunosorbent assay; PCR 5 polymerase chain reaction; P:F ratio 5 ratio of Pa o 2 to F io 2 ; VAP 5 ventilator-associated pneumonia; VFD 5 ventilator-free day

Background/Aim: Alterations of plasma membrane fluidity are characteristic of many diseases but the intentional modulation of membrane fluidity with drugs has been less studied. We examined the therapeutic potential of the membrane fluidizer diethyl azelate (DEA) and related azelates. Materials and Methods: The effects of azelates on plasma membrane fluidity and cell signaling were examined in primary human and murine cells and in vivo. Endpoints were queried using single target and multiplexed immunoassays. Results: Unique membrane-fluidizing properties and biomarker signatures suggest that azelates are not prodrugs. DEA decreased cytokine signaling from pattern recognition receptors in human dendritic cells, disabled membrane attack of cholera toxin in vitro, and prevented immunosuppression by anthrax lethal toxin in vitro and in vivo. In the murine sepsis model, DEA increased survival and reduced organ damage. Conclusion: Azelates represent a new class of drugs, membrane active immunomodulators, which target an innate homeostatic mechanism, adaptive membrane fluidity modulation.