Multidisciplinary Approach to Improve Human Immunodeficiency Virus and Syphilis Testing Rates in Emergency Departments.

Background: Best practice guidelines recommend that patients at risk for sexually transmitted infections (STIs), such as gonorrhea (GC) and chlamydia, should also be tested for human immunodeficiency virus (HIV) and syphilis. This prospective quality assurance study aimed to increase HIV and syphilis testing rates in emergency departments (EDs) across the Cleveland Clinic Health System from January 1, 2020 through January 1, 2022. Methods: A multidisciplinary team of emergency medicine, infectious diseases, pharmacy, and microbiology personnel convened to identify barriers to HIV and syphilis testing during ED encounters at which GC/chlamydia were tested. The following interventions were implemented in response: rapid HIV testing with new a workflow for results follow-up, a standardized STI-screening order panel, and feedback to clinicians about ordering patterns. Results: There were 57 797 ED visits with GC/chlamydia testing completed during the study period. Human immunodeficiency virus testing was ordered at 5% of these encounters before the interventions were implemented and increased to 8%, 23%, and 36% after each successive intervention. Syphilis testing increased from 9% before the interventions to 12%, 28%, and 39% after each successive intervention. In multivariable analyses adjusted for age, gender, and location, the odds ratio for HIV and syphilis testing after all interventions was 11.72 (95% confidence interval [CI], 10.82-12.71; P ≤.001) and 6.79 (95% CI, 6.34-7.27; P ≤.001), respectively. Conclusions: The multidisciplinary intervention resulted in improved testing rates for HIV and syphilis.

COVID-19: a primer for the rheumatologist: management of patients and care settings.

PURPOSE OF REVIEW: There are currently many unanswered questions surrounding the management of patients with immune-mediated inflammatory diseases during the COVID-19 pandemic and several 'rapid' guidelines have been released, although are subject to be updated and changed in the near future. The purpose of this review is to discuss the approach to management of patients with immune-mediated diseases during the COVID-19 pandemic. RECENT FINDINGS: At present, there is little evidence to suggest an increased risk of COVID-19 infection or its complications in patients with immune-mediated diseases or associated with conventional or biologic disease modifying antirheumatic drugs; however, glucocorticoid use does appear to have negative associations. SUMMARY: Currently, conventional and biologic disease modifying antirheumatic drugs can be continued in the absence of SARS-CoV-2 exposure. In the case of exposure, with the exception of hydroxyhcloroquine and sulfasalazine, immunosuppression should be held for 2 weeks. Our recommendations and the guidelines we discuss here are based on C-level recommendations but help provide a framework for how to counsel our patients during this pandemic.

Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

BACKGROUND: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center. METHODS: Blood and tissue culture results collected between January 2005 and January 2018 and maintained in the microbiology laboratory database at the Cleveland Clinic were reviewed to identify those with C. septicum reported. Each was reviewed to determine radiographic or histopathologic correlation with aortic disease. RESULTS: Seven cases of C. septicum aortitis were reviewed. Underlying malignant disease was found in four cases and a history of remote malignant disease in one case. The most common location for infection was the infrarenal abdominal aorta. Vascular surgery had previously been performed in three of the cases. Five of the seven patients underwent operative repair. All patients were treated with ß-lactam antibiotics. The two patients who did not undergo an operation died, which is consistent with the 100% mortality described in the literature. Of the five patients who underwent an operation, there was only one documented survivor and one was lost to follow-up. CONCLUSIONS: In the largest reported case series, only a small percentage of patients with C. septicum-infected aortic aneurysms survived >1 year. In the patients described, those who did not receive an operation had 100% mortality. Earlier recognition and prompt operation with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.

A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase.

OBJECTIVE: Daptomycin has been associated with increased creatine phosphokinase (CPK) due to muscle injury leading to myalgias and muscle weakness. Statins have been proven to cause the same effects and it is recommended to discontinue the use of statins while on daptomycin. Evidence regarding this drug interaction is mixed. This study evaluated the risk of CPK elevation in concomitant use of daptomycin and statins compared to daptomycin alone. METHOD: This is a multisite retrospective case-control study of patients who received daptomycin therapy with monitoring of CPK. Rates of CPK elevations were compared in patients receiving daptomycin with a statin versus daptomycin alone. To estimate the association between CPK elevation and daptomycin therapy controlling for other risk factors, logistic regression was used to analyze data. Statistical significance was determined at ɑ of 0.05. RESULTS: A total of 3658 patients were included in the study, with 2787 on daptomycin therapy alone and 871 with concurrent statin use. The incidence of CPK elevation was 90 events (3.2%) in the daptomycin group and 26 events (3.0%) in the concurrent statin group. Patients who received daptomycin therapy in addition to statins had no statistically significant difference from patients on daptomycin alone (hazard ratio, 1.05; P = .85; 95% confidence interval, 0.61-1.84). After adjusting for potential risk factors, the hazards ratio remained almost the same. CONCLUSIONS: Concomitant use of daptomycin and statin did not show an increase risk of CPK elevation. Clinicians may consider concomitant use of daptomycin and statin therapy with weekly CPK monitoring.

Disseminated Metacestode Versteria Species Infection in Woman, Pennsylvania, USA1.

A patient in Pennsylvania, USA, with common variable immunodeficiency sought care for fever, cough, and abdominal pain. Imaging revealed lesions involving multiple organs. Liver resection demonstrated necrotizing granulomas, recognizable tegument, and calcareous corpuscles indicative of an invasive cestode infection. Sequencing revealed 98% identity to a Versteria species of cestode found in mink.

Chronic laryngitis caused by Mycobacterium Kansasii in a traveler.

Chronic laryngitis commonly presents with dysphonia, and infectious causes include tuberculosis and endemic mycoses. We present a 58-year-old female with laryngitis for 5 years, fevers, chills, fatigue, malaise, myalgias, anterior neck pain, and night sweats after multicontinent exposure. Bronchoscopy cultures were negative. Bilateral microflap excision of vocal fold lesions demonstrated thickened epithelium and a deep vocal fold mass. Biopsy showed necrotizing granulomatous inflammation with acid-fast bacilli. Mycobacterium kansasii was identified. Treatment led to improvement in dysphonia, systemic symptoms, and vocal fold irritation. To our knowledge, this is the first case of isolated nontuberculous mycobacterial vocal fold infection. Laryngoscope, 129:2534-2536, 2019.

Quantitative Thresholds Enable Accurate Identification of Clostridium difficile Infection by the Luminex xTAG Gastrointestinal Pathogen Panel.

Clostridium difficile colonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion for C. difficile is low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) for C. difficile infection. Analysis of cotested liquid stool samples (n = 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of ≥1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (n = 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of ≥150 (standard), MFI cutoff of ≥1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of ≥150) and high specificity for active infection (MFI of ≥1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (n = 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting of C. difficile for 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing.

Validation of a rodent model of Barrett's esophagus using quantitative gene expression profiling.

BACKGROUND: A rodent model of gastroduodenal-esophageal reflux can result in replacement of squamous esophageal mucosa with intestinal-type columnar mucosa and carcinoma. The validity of this model is debated, as it is unproven whether this mucosa is intestinal metaplasia due to reflux or represents migration of adjacent jejunal mucosa above the anastomosis. The aim of this study was to evaluate the esophageal intestinal-type mucosa in these animals by measuring expression of trefoil factor genes (TFF-1, -2, -3) and comparing it with adjacent jejunum in order to determine its etiology. METHODS: Twenty-five rats underwent esophagojejunostomy at the ligament of Treitz to induce reflux of gastric and duodenal contents. The animals were sacrificed at 16 weeks (n = 14) and 30 weeks (n = 11). After sacrifice, the distal esophagus, jejunum, and colon were obtained. RNA was isolated, reverse transcribed, and messenger RNA (mRNA) expression of TFF-1, -2, and -3 was measured with real-time polymerase chain reaction (PCR). Linear discriminant analysis classified samples based on gene expression. RESULTS: Esophageal intestinal-type mucosa was present at sacrifice in 18 animals. Compared to jejunum, the expression of TFF-1 and TFF-2 mRNA in the intestinal mucosa of the distal esophagus was increased (p = 0.0007 and p < 0.0001, respectively). Expression of TFF-3 was also increased in esophageal intestinal mucosa compared with jejunum (p = 0.0002), but there was significant overlap in expression between these tissues for this gene. Linear discriminant analysis misclassified esophageal intestinal-type mucosa as jejunum in only one case. In no cases was jejunum misclassified as esophageal intestinal-type mucosa. CONCLUSION: The gene expression profile of esophageal intestinal-type mucosa following surgically induced reflux in a rodent model indicates that this represents intestinal metaplasia, not proximal migration of jejunum. This validates this model for studying the pathogenesis of Barrett's esophagus. Use of this model has potential for assessment of the impact of various therapies on the natural history of reflux disease.

Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients.

Thymidylate synthase (TS) is known to have polymorphisms in the 5' and 3' untranslated region (UTR). These polymorphisms have been reported to be associated with high TS expression and chemoresistance to 5-FU. The aim of this study was to examine the prognostic roles of the 5'-UTR and 3'-UTR TS polymorphisms in esophageal adenocarcinoma patients, as well as their relation with TS mRNA expression. Eighty-three patients with esophageal adenocarcinoma were assessed. Thirty-four had received 5-FU containing chemotherapy and 49 were treated with surgery alone. Surgically resected tumor tissues were analyzed for TS genotype and TS mRNA expression using a quantitative real-time RT-PCR method. No survival difference was seen between the patients with 3RG allele (3RG group) and non-3RG group among surgery-alone patients. However, among patients with a history of 5-FU-based chemotherapy, the non-3RG group showed significantly better overall survival compared to the 3RG group (p=0.02). Moreover, whereas chemotherapy produced a significant increase in survival for the non-3RG group patients, those in the 3RG group obtained no survival benefit from chemotherapy. When patients were classified by low or high TS mRNA expression levels, low TS expressers obtained survival benefit from chemotherapy while high TS expressers did not, although there was no difference of median TS mRNA levels between 3RG and non-3RG group. The 3'-UTR polymorphism was not associated with overall survival. These results suggest that the status of the TS 5'-UTR polymorphism and TS mRNA expression are independent predictive markers for survival benefit from 5-FU-based therapy.