Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy.

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4-5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MAActivator cutoff of ≤40 mm, WBAAA vs TPM MAAA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MAActivator >40 had poor correlation with an accuracy of 37.5%. Irrespective of MAActivator value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MAActivator ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin.

High Molecular Weight von Willebrand Factor Multimer Loss and Bleeding in Patients with Short-Term Mechanical Circulatory Support Devices: A Case Series.

Acquired von Willebrand syndrome (VWS) due to loss of high-molecular-weight multimers (HMWMs) has been reported with longer term mechanical devices and is associated with mucosal bleeding, a primary hemostasis type of bleeding. However, little is known whether a similar defect occurs in patients with short-term mechanical circulatory support (STMCS) devices. We reviewed von Willebrand factor (VWF) profiles in patients with STMCS devices who underwent VWS workup from December 2015 to March 2017 at an academic quaternary care hospital. There were a total of 18 patients (57.0 ± 12.7 years old; 83.3% male) including nine with mucosal bleeding and nine with decreasing hemoglobin. The STMCS devices included Impella (n = 11), Impella and right ventricular assist device (n = 2), and an extracorporeal membrane oxygenator (n = 5). The mean HMWM by quantitative VWF multimer analysis was 3.6% ± 1.3% (normal cutoff: 18-34%). In all 10 cases in which VWF activity, fibrinogen, factor VIII, or VWF antigen level were obtained, they were either normal or elevated. All cases demonstrated high normal or elevated levels of low molecular weight multimers (LMWMs). These findings are consistent with type 2 VWS (qualitative defect). This is the first study that quantitatively describes STMCS device-associated HMWM loss, which may contribute to mucosal bleeding. This finding may have implications for intraoperative management during implantation of longer term devices or heart transplantation or other surgery while on STMCS.

Covid-19 shelter-in-place, modified reopening orders, and order compliance impact on adolescent alcohol use and drinking contexts in California: A longitudinal analysis.

INTRODUCTION: This study evaluated how Shelter-in-Place (SIP), modified reopening orders, and self-reported compliance with these orders have affected adolescent alcohol frequency and quantity of use across contexts during the COVID-19 pandemic. MATERIALS AND METHODS: Differences-in-differences (DID) models and multi-level modeling analyses were conducted on longitudinal data collected as part of a larger study on alcohol use among adolescents in California. 1,350 adolescents at baseline contributed 7,467 observations for a baseline and 5 six-month follow-up surveys. Analytic samples ranged from 3,577-6,245 participant observations based on models. Alcohol use outcomes included participant frequency (days) and quantity (number of whole drinks) of alcohol use in past 1-month and past 6-month periods. Context-specific alcohol use outcomes included past 6-month frequency and quantity of use at: restaurants, bars/nightclubs, outside, one's own home, another's home, and fraternities/sororities. Participant self-reported compliance with orders in essential business/retail spaces and at outdoor/social settings were also assessed. RESULTS: Our DID results indicated that being under a modified reopening order was associated with decreases in past 6-month quantity of alcohol use (IRR = 0.72, CI = 0.56-0.93, p < 0.05). Higher self-reported compliance with SIP orders related to social outdoor/social settings was associated with decreases in overall drinking frequency and quantity as well as decreases in frequency and quantity of alcohol use in all contexts in the past six months. Compliance with SIP orders impacting essential businesses and retail spaces was associated with decreased frequency and quantity of use at other's home and outdoors. CONCLUSIONS: Results suggest that SIP and modified reopening policies may not directly affect adolescent alcohol use or drinking contexts, and that individual compliance with such orders may be a protective factor for alcohol use.

Diagnosing heparin-induced thrombocytopenia in mechanical circulatory support device patients.

BACKGROUND: Mechanical circulatory support device (MCSD) patients with positive heparin-induced thrombocytopenia (HIT) screening pose a unique challenge, as clinicians must make rapid decisions about their anticoagulation and whether they can safely undergo cardiopulmonary bypass. We identified screening practices at our institution and other institutions nationwide that differed from American Society of Hematology (ASH) guidelines. This discovery prompted a data review to confirm the applicability of guidelines to this unique population and to highlight complications of "gestalt" screening. METHODS: Our study included MCSD patients with HIT testing from April 2014 to August 2020. We evaluated 510 PF4 IgG ELISA results. RESULTS: HIT was confirmed in 4.2% of patients. There was an increased prevalence of HIT in patients with nondurable (5.3%) vs durable devices (2.9%) or those in the preimplantation setting (1.3%), however this difference was not statistically significant (p = 0.26). None of the patients with a low probability 4T Score had HIT. All patients with a high probability 4T Score and PF4 immunoassay OD >2.0 had HIT. False positive results occurred in 22% of assays ordered for patients with a low probability 4T Score. Twelve patients with a low probability 4T Score and a false positive immunoassay were switched to a direct thrombin inhibitor (DTI) while awaiting confirmatory results. Two patients experienced clinically significant bleeding after conversion to a DTI. An organ was refused in one patient with false positive HIT screening. CONCLUSIONS: Our findings demonstrate that an opportunity exists to improve clinical outcomes by re-emphasizing the utility of established guidelines and highlighting their safe use in the MCSD patient population.

Clinical and virological characterization of persistent human infection with simian foamy viruses.

Persons occupationally exposed to nonhuman primates (NHPs) can be persistently infected with simian foamy virus (SFV). The clinical significance and person-to-person transmissibility of zoonotic SFV infection is unclear. Seven SFV-infected men responded to annual structured interviews and provided whole blood, oral, and urogenital specimens for study. Wives were tested for SFV infection. Proviral DNA was consistently detected by PCR in PBMCs of infected men and inconsistently in oral or urogenital samples. SFV was infrequently cultured from their PBMCs and throat swabs. Despite this and a long period of intimate exposure (median 20 years), wives were SFV negative. Most participants reported nonspecific symptoms and diseases common to aging. However, one of two persons with mild thrombocytopenia had clinically asymptomatic nonprogressive, monoclonal natural killer cell lymphocytosis of unclear relationship to SFV. All participants worked with NHPs before 1988 using mucocutaneous protection inconsistently; 57% described percutaneous injuries involving the infecting NHP species. SFV likely transmits to humans through both percutaneous and mucocutaneous exposures to NHP body fluids. Limited follow-up has not identified SFV-associated illness and secondary transmission among humans.

Role of Thromboelastography Platelet Mapping and International Normalized Ratio in Defining "Normocoagulability" During Anticoagulation for Mechanical Circulatory Support Devices: A Pilot Retrospective Study.

Thromboembolic (TE) events and hemorrhagic complications continue to remain as frequent adverse events and causes of death after mechanical circulatory support device (MCSD) implantation. To counterbalance this postimplant multifactorial hypercoagulable state, antithrombotic therapy given postimplant must be individually tailored to keep patient adequately anticoagulated yet normocoagulable. Prior studies describing different anticoagulation protocols do not define normocoagulability for patients on MCSDs. We evaluated the role of thromboelastography platelet mapping (TEG PM) in defining "normocoagulability" for MCS patients on anticoagulant (warfarin) and antiplatelet agents. Ninety-eight MCSD patients who underwent TEG PM assay at our institution from 2012 to 2014 were included for retrospective analysis. Eleven (11.2%) subjects developed at least one TE event during the study period. Of the 13 TE events, 8 occurred in patients with total artificial heart (TAH). TEG parameters closest to the event or when patient was clinically adequately anticoagulated and corresponding international normalized ratio (INR) were measured. Thromboelastography coagulation index (CI) appears to be the single most statistically significant parameter that can be used to designate a patient as normocoagulable. Based on our results, patients with HeartMate II (HM II) and Heart Ware (HW) devices should be maintained at a CI value of less than or equal to 1.5 whereas patients with TAH devices should be maintained at a CI less than or equal to 1.2. The CI should be correlated with the degree of Vitamin K-dependent coagulation factor inhibition that is achieved using device-specific goal INR ranges. A recent modification, TEG PM assesses the effects of antiplatelet drug. Maximal amplitude arachidonic acid (MA-AA) < 50 and maximal amplitude adenosine diphosphate (MA-ADP) < 50 are desired for normocoagulable state.

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Cytotoxic and Apoptotic Effects of Ethyl Acetate Extract of Elephantopus mollis Kunth. in Human Liver Carcinoma HepG2 Cells Through Caspase-3 Activation.

Previous cytotoxic (anticancer) evaluations ofElephantopus molliswere mainly focused on its elephantopin derivatives neglecting the combined effect of the phytochemicals in its traditionally used extracts. In this study, the cytotoxic mechanism of its extracts was investigated using methylene blue assay. The cytotoxic screening results revealed the ethyl acetate extract as the most potent extract by displaying prominent dose-dependent and time-dependent growth inhibitions in human liver carcinoma HepG2 cells with the lowest EC50value of 9.38 ± 0.43 µg/mL after 72 hours of treatment. Acute exposure of the HepG2 cells to the ethyl acetate extract produced a significant regulation of caspase-3 with the peak expression at 8 hours of treatment (P< .05). DNA fragmentation indicated by DeadEnd Apoptosis Detection System-labeled nuclei cells confirmed that the extract induced apoptotic cell death through caspase-3-dependent pathway in HepG2 cells.

Estimating aminoglycoside clearance and creatinine clearance in underweight patients.

PURPOSE: An adjustment factor (AF) was developed and evaluated to determine the best method for estimating aminoglycoside clearance (CL(amino)) and creatinine clearance (CL(cr)) in underweight patients. METHODS: This study was a retrospective, multicenter, chart analysis of aminoglycoside pharmacokinetic data obtained between January 2000 and August 2006 at the University of Southern California University Hospital and Cedars-Sinai Medical Center. Adult patients were included in this study if they had received inpatient aminoglycoside therapy, were at least 60 inches tall, and were at least 10% below their ideal body weight (IBW). CL(cr) and CL(amino) were estimated and compared to actual CL(amino) using the Cockcroft-Gault equation with actual serum creatinine (SCr) (CG(SCr)), Cockcroft-Gault equation with SCr rounded to 1 mg/dL (CG(rnd)), and Cockcroft-Gault equation multiplied by an AF (CG(AF)). Results An AF of 0.69 was determined from 52 patients and tested in 53 separate patients. The CG(AF) method was more precise and less biased than the CG(SCr) equation; the CG(rnd) equation was less biased than the CG(SCr) equation; the CG(AF) method was more precise and less biased than the CG(rnd) equation, but this difference was not statistically significant. In underweight patients with an SCr concentration of > or = 1 mg/dL, the CG(AF) method had less bias compared with the CG(SCr) equation. CONCLUSION: Both the CG(rnd) and CG(AF) methods of predicting CL(amino) in underweight patients were superior to the CG(SCr) equation. The CG(AF) method was more accurate in patients exhibiting greater differences between IBW and actual body weight.

A North American multilaboratory study of CD4 counts using flow cytometric panLeukogating (PLG): a NIAID-DAIDS Immunology Quality Assessment Program Study.

BACKGROUND: The global HIV/AIDS pandemic and guidelines for initiating anti-retroviral therapy (ART) and opportunistic infection prophylaxis demand affordable, reliable, and accurate CD4 testing. A simple innovative approach applicable to existing technology that has been successfully applied in resource-challenged settings, PanLeukogated CD4 (PLG), could offer solutions for cost saving and improved precision. METHODS: Day-old whole blood from 99 HIV+ donors was simultaneously studied in five North-American laboratories to compare the performance of their predicate methods with the dual-platform PLG method. The predicate technology included varying 4-color CD45/CD3/CD4/CD8 protocols on different flow cytometers. Each laboratory also assayed eight replicate specimens of day-old blood from 10 to 14 local donors. Bias and precision of predicate and PLG methods was studied between- and within-participating laboratories. RESULTS: Significantly (P < 0.0001) improved between-laboratory precision/coefficient of variation (CV%) was noted using the PLG method (overall median 9.3% vs. predicate median CV 13.1%). Within-laboratory precision was also significantly (P < 0.0001) better overall using PLG (median 4.6% vs. predicate median CV 6.2%) and in 3 of the 5 laboratories. PLG counts tended to be 11% smaller than predicate methods (P < 0.0001) for shipped (median of predicate-PLG = 31) and local specimens (median of predicate-PLG = 23), both overall and in 4 of 5 laboratories (median decreases of 4, 16, 20, and 21% in shipped specimens); the other laboratory had a median increase of 5%. CONCLUSION: Laboratories using predicate CD4 methods similar to those in this study could improve their between-laboratory and their within-laboratory precision, and reduce costs, by switching to the PLG method after adequate training, if a change (usually, a decrease) in CD4 counts is acceptable to their health systems.

Prevalence of HIV in the US household population: the National Health and Nutrition Examination Surveys, 1988 to 2002.

To examine trends in HIV prevalence in the US household population, serum or urine samples from 2 National Health and Nutrition Examinations Surveys (NHANES) (1988-1994 and 1999-2002), were tested for HIV antibody. In the 1999 to 2002 survey, data on risk behaviors, CD4 T lymphocytes, and antiretroviral therapy (ART) were also available. In the 1988 to 1994 survey, there were 59 positive individuals of 11,203 tested. In NHANES 1999 to 2002, there were 32 positive individuals of 5926 tested. The prevalence of HIV infection among those aged 18 to 39 years in NHANES 1988 to 1994 was 0.38% (95% confidence interval [CI]: 0.22-0.68) as compared with 0.37% (95% CI: 0.17 to 0.80) in 1999 to 2002. Prevalence did not change significantly between surveys in any race and/or ethnic or gender group among 18- to 39-year-old participants. HIV prevalence was 3.58% (95% CI: 1.88 to 6.71) among non-Hispanic blacks in the 40- to 49-year-old age group in 1999 to 2002, but the age range available in NHANES 1988 to 1994 was 18 to 59 years and does not allow direct comparison of prevalence. Cocaine use and the presence of herpes simplex virus-2 antibody were the only significant risk factors for HIV infection for non-Hispanic blacks. Fifty-eight percent of infected individuals not reporting ART had CD4 T-lymphocyte counts < 200 cells/mm3 compared with 18.2% on therapy and 12.5% of participants newly informed of their HIV status.

Comparison of serologic responses between Kaposi's sarcoma-positive and -negative men who were seropositive for both human herpesvirus 8 and human immunodeficiency virus.

Although the introduction of HAART decreased substantially the incidence of Kaposi's sarcoma (KS), KS remains the most common cancer among individuals infected with human immunodeficiency virus (HIV). To define markers for progression to KS from the asymptomatic infection of human herpesvirus 8 (HHV-8), serologic responses against HHV-8 were compared between KS-negative and -positive men who were seropositive for both HIV and HHV-8. There was no difference in prevalence of detectable neutralizing antibodies between the two groups. The prevalence of anti-ORF73 antibodies among the dual seropositive patients increased in proportion to their risk of KS. In specimens obtained from 11 HIV+ patients at different intervals over a period of 4-12 years, increase of anti-ORF73 antibody titers was observed in the patients who developed KS but not in the patients who did not develop KS. These results suggest that there is a difference in serologic response against ORF73 between the HIV patients with and without KS.

Highly sensitive assay for human herpesvirus 8 antibodies that uses a multiple antigenic peptide derived from open reading frame K8.1.

The immunodominant region of the human herpesvirus 8 (HHV-8), the antibody-binding site of glycoprotein K8.1A, was mapped to the N-terminal region by using overlapping peptides and a residue replacement method. The main epitope was located within residues 44 to 56 (GQVYQDWL----C). Based on this information, we developed an enzyme immunoassay to detect HHV-8 antibodies in human sera using a four-branch multiple antigenic peptide as the antigen. The sensitivity and specificity of the assay were 96 and 99.4%, respectively. This assay should be useful for population-based, epidemiological studies of HHV-8 infection.