Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin.

Background: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility. Methods: We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic regression to identify factors associated with a positive clinical impact. Results: Of the 72 patients identified, 62.5% were males with a median age of 56. All patients had a fever at the time of evaluation. At least one organism was identified in 65.3% of cases; most commonly were Epstein-Barr virus (13.9%), cytomegalovirus (12.5%), and Rickettsia typhi (11.1%). Of those determined to have an infectious etiology of their febrile syndrome, 89.5% (n = 34/38) had a positive mNGS. Consistency between the organism(s) on mNGS and the clinically determined infectious etiology was 82.4%. mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. Besides age, we did not identify other factors associated with a higher likelihood of positive clinical impact. Conclusion: In our review, mNGS had a positive clinical impact in a large proportion of adults with fever of undetermined origin, with minimal negative impact. However, mNGS results should be interpreted carefully given the high rate of detection of pathogens of unclear clinical significance. Randomized clinical trials are needed to assess the clinical utility of this novel diagnostic tool.

Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin In this study, we evaluated the use of a new diagnostic tool, namely, metagenomic next generation sequencing (mNGS), in hospitalized, non-immunocompromised, adult patients with a fever that was otherwise unexplained. We reviewed the clinical utility of this tool in 72 patients and found that at least one organism was found in 65.3% of cases, with the 2 most common organisms being viruses. In patients who were found to have an infection as the cause of their fever, 89.5% had a positive mNGS study. In 82.4% of cases, the infectious organism(s) found on mNGS was the organism thought to be the cause of the fever. Based on definitions from another study, mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. This study suggests that mNGS has minimal negative impact and can be a useful tool in identifying a causative infectious organism in patients with unexplained fevers. Additional studies are needed to identify patients and clinical conditions that would most benefit from this tool.

Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

Impact of gastrointestinal polymerase chain reaction panels on antibiotic utilization in hospitalized adult patients.

Multiplex stool polymerase chain reaction (PCR) panels offer rapid comprehensive testing for patients with infectious diarrhea. We compared antibiotic utilization among hospitalized patients with suspected infectious diarrhea who underwent diagnostic testing with either a stool culture or stool PCR panel. No significant differences in antibiotic utilization were identified.

Case Report: Molecular Diagnosis of Cystoisospora belli in a Severely Immunocompromised Patient with HIV and Kaposi Sarcoma.

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting trimethoprim-sulfamethoxazole, her diarrhea and eosinophilia improved, and she had undetectable Cystoisospora belli DNA on repeat stool quantitative polymerase chain reaction. This case highlights the importance of a thorough workup for diarrhea, including parasites, especially for immunocompromised patients. Antibiotic prophylaxis is recommended in patients with Cystoisospora belli and HIV/AIDS.

Cardiovascular disease and prevention among people living with HIV in South Florida.

ABSTRACT: Antiretroviral therapy (ART) has improved survival of patients living with HIV (PLWH); however, this has been accompanied by an increase in cardiovascular disease (CVD). Although preventative measures for CVD among the general population are well described, information is limited about CVD prevention among PLWH. The goal of this study was to characterize the prevalence of CVD in our population and to assess the use of primary and secondary prevention.We performed a retrospective review of PLWH receiving primary care at a large academic center in Miami, Florida. We characterized the prevalence of CVD, CVD risk, and the use of aspirin and statins for primary and secondary CVD prevention.A total of 985 charts were reviewed (45% women, 55% men). Average age was 52.2 years. Average CD4 count was 568 cells/microL. 92.9% were receiving ART, and 71% were virologically suppressed. The median 10-year ASCVD risk was 7.3%. The prevalence of CVD was 10.4% (N = 102). The odds of having CVD was lower in patients on ART (OR 0.47, 95% CI: 0.25-0.90, P = .02). The use of medications for primary and secondary prevention of CVD based on current guidelines was low: 15% and 37% for aspirin respectively, and 25% and 44% for statins.CVD risk and rates of CVD are high among PLWH and receiving ART could protect against CVD. However, the use of medications for primary and secondary prevention is low. Increased awareness of CVD risk-reduction strategies is needed among providers of PLWH to decrease the burden of CVD.

Drug resistant cells with very large proliferative potential grow exponentially in metastatic prostate cancer.

Most metastatic cancers develop drug resistance during treatment and continue to grow, driven by a subpopulation of cancer cells unresponsive to the therapy being administered. There is evidence that metastases are formed by phenotypically plastic cancer cells with stem-cell like properties. Currently the population structure and growth dynamics of the resulting metastatic tumors is unknown. Here, using scaling analysis of clinical data of tumor burden in patients with metastatic prostate cancer, we show that the drug resistant, metastasis-causing cells (MCC) are capable of producing drug resistant, exponentially growing tumors, responsible for tumor growth as a patient receives different treatments.

Excess mortality risk from sepsis in patients with HIV - A meta-analysis.

PURPOSE: Differences in HIV prevalence, access to antiretrovirals and ICU resources may result in wide variation in sepsis mortality in HIV patients. The aim of this study was to perform a meta-analysis to quantify the excess risk of sepsis mortality in HIV patients. MATERIALS AND METHODS: A systematic review was performed using three databases. The systemic inflammatory response syndrome criteria was used for the presumptive diagnosis of sepsis. We only included studies that stratified sepsis mortality by HIV serostatus. A meta-analysis was performed using random effects models, with subgroup analyses performed using country income, sepsis severity, and time periods. RESULTS: 17 studies were included, containing 82,905 patients. Sepsis mortality was found to be 28% higher in the HIV positive patients (95% CI 1.13-1.46, p < .01). Relative risk of mortality was higher in patients treated in low-income countries (RR 1.43 in low-income vs. 1.29 in high-income countries). Mortality was more pronounced in HIV patients with severe sepsis (RR 1.32 in severe sepsis vs. RR 1.15 in sepsis). CONCLUSIONS: HIV increases the risk of sepsis mortality compared to seronegative individuals across all time periods and geographic areas. We note that this effect is more pronounced in patients with organ dysfunction.

Acquired Factor VIII Inhibitor Presenting as Occult GI Bleeding.

An acquired coagulation factor deficiency is characterized by acquired autoantibodies against specific clotting factors in those without diagnosed hemophilia. It is a relatively rare condition with an incidence of approximately one case per million per year. We present a case report of an elderly male who initially presented with an occult GI bleed that was identified with a positive fecal occult blood test result. This is the first case reported to our knowledge of an acquired factor inhibitor deficiency presenting in this manner. We postulate the importance of acquired factor inhibitors in the setting of unexplained anemia given absence of overt clinical symptoms that could contribute to aggravate an established GI bleed, especially in the elderly population.