Open Forum Infectious Diseases
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Published By Oxford University Press


Kun Fu ◽  
Ming Lei ◽  
Li-Sha Wu ◽  
Jing-Cheng Shi ◽  
Si-Yu Yang ◽  

Abstract Background The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582 m) were determined by quantitative methylation specific PCR (qMSP) and expressed in ΔCp. Receiver-operating characteristic (ROC) curves were used to evaluate predictive accuracy. Results The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high grade squamous intraepithelial lesion (HSIL) and 39 (14.08%) were squamous cervical cancer (SCC). PAX1 m and ZNF582 m increased as lesions progressed from inflammation/LSIL, HSIL to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared to common screening strategies, whether individually or combined. ΔCpZNF582 ≥19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582 < 7.09). Conclusion DNA Methylation would be an alternative screening method to triage and predict the final outcome of conization of the CIN3 cases.

Karam Mounzer ◽  
Laurence Brunet ◽  
Jennifer S Fusco ◽  
Ian R Mcnicholl ◽  
Helena Diaz Cuervo ◽  

Abstract Background Approximately 20% of newly diagnosed people with HIV (PWH) in the U.S. have advanced HIV infection, yet literature on current antiretroviral therapy (ART) options is limited. Discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/μL). Methods ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)- or elvitegravir/cobicistat (EVG/c)-based three-drug regimen between 1JAN2018 and 31JUL2019 in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights. Results Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/μL over a 16 months median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV aHR: 2.65 [95% CI: 1.75, 4.02], DTG: 2.42 [1.75, 3.35], EVG/c: 3.52 [95% CI: 2.44, 5.07]). Compared to B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (0.72 [0.52, 0.99]) and <200 copies/mL (0.55 [0.43, 0.70]); no statistically significant difference was detected with DTG or EVG/c. Conclusions Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared to those on bDRV but not compared to those on other integrase inhibitors.

Ronald E Fisher ◽  
Ashley L Drews ◽  
Edwin L Palmer

Abstract Background Labeled white blood cell scintigraphy (WBCS) has been used for over 40 years to localize an infection source in patients with fever of unknown origin (FUO). It continues to be in widespread use for such patients in modern times, despite the tremendous advances in modern radiological imaging and laboratory medicine. Methods We critically evaluated the clinical contribution of WBCS performed in 132 patients with FUO at 7 hospitals from mid-2015 to the end of 2019. For each patient, all radiographic and laboratory results, and all electronic clinical notes, were carefully evaluated as many days prior to and following the scan as necessary to arrive at a final diagnosis. Results Although 50 WBCS (38%) showed positive findings, the majority of these were false positive (FP). Of the 19 true positive (TP) scans, most were already known or about to become known by tests already ordered at the time of the scan. Only 2 TP scans (1.5%) contributed to the final diagnosis, and these did so only indirectly. FP scans led to 7 unnecessary procedures. Conclusions In FUO patients for whom an infection source is not discovered following an appropriate radiographic and laboratory workup, WBCS is not a useful procedure.

Mark Okwir ◽  
Abigail Link ◽  
Joshua Rhein ◽  
John Stephen Obbo ◽  
James Okello ◽  

Abstract Background The impact of the "test-and-treat" program for HIV treatment in rural areas of Uganda on cryptococcal antigen (CrAg) screening or cryptococcal meningitis (CM) is poorly understood. Methods We retrospectively evaluated clinical factors in 212 HIV-infected patients diagnosed with CM from February of 2017 to November of 2019 at Lira Regional Referral Hospital (LRRH) in northern Uganda. Results Among 212 patients diagnosed with CM, 58.5% were male. Median age, CD4 count, and HIV viral load were 35 years, 86 cells/μL, and 9,463 copies/mL respectively. Only 10% of patients had a previous history of CM. We found that 190 of 209 (90.9%) patients were ART-experienced, and 19 (9.1%) were ART-naïve. Overall, 90 of 212 (42.5%) patients died while hospitalized with a median time to death of 14 days. Increased risk of death was associated with altered mental status (HR 6.6, 95% CI 2.411-18.219, p =<0.0001), and seizures (HR 5.23, 95% CI 1.245-21.991, p=0.024). Conclusion Current guidelines recommend CrAg screening based on low CD4 counts for ART-naïve patients and VL or clinical failure for ART-experienced patients. Using current guidelines for CrAg screening, some ART- experienced patients miss CrAg screening in resource limited settings, when CD4 or VL tests are unavailable. We found that the majority of HIV- infected patients with CM were ART- experienced (90.9%) at presentation. The high burden of CM in ART-experienced patients supports a need for improved CrAg screening of ART-exposed patients.

Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  

Abstract Background The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality. Methods We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed qPCR DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results We found that patients with CdtB, the pore forming component of CDT, detected in their stool by ELISA were more likely to have severe disease with a higher 90-day mortality. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI, with the detection of CDT-expressing strains valuable in identifying patients at risk of more severe disease.

Jovana Milic ◽  
Sara Barbieri ◽  
Licia Gozzi ◽  
Alberto Brigo ◽  
Bianca Beghé ◽  

Abstract Background Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (p<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

Leah Harvey ◽  
Jacqueline Boudreau ◽  
Samantha K Sliwinski ◽  
Judith Strymish ◽  
Allen L Gifford ◽  

Abstract Background Injection drug use-associated bacterial and viral infections are increasing. Expanding access to harm reduction services, such as safe injection education, are effective prevention strategies. However, these strategies have had limited uptake. New tools are needed to improve provider capacity to facilitate dissemination of these evidence-based interventions. Methods The “Six Moments of Harm Reduction” provider educational tool was developed using a global, rather than pathogen-specific, infection prevention framework, highlighting the prevention of invasive bacterial and fungal infections in additional to viral pathogens. The tool’s effectiveness was tested using a short, paired pre/post survey that assessed provider knowledge and attitudes about harm reduction. Results N=75 respondents completed the paired surveys. At baseline, 17 respondents (22.6%) indicated that they had received no prior training in harm reduction and 28 (37.3%) reported discomfort counseling patients who inject drugs (PWID). 60 respondents (80.0%) reported they had never referred a patient to a syringe service program (SSP) and, of those, 73.3% cited lack of knowledge regarding locations of SSPs and 40.0% reported not knowing where to access information regarding SSPs. After the training, 66 (88.0%) reported that they felt more comfortable educating PWID (p<0.0001), 65 respondents (86.6%) reported they planned to use the “Six Moments” model in their own practice, and 100% said they would consider referring patients to a SSP in the future. Conclusions The “Six Moments” model emphasizes the importance of a global approach to infection prevention and harm reduction. This educational intervention can be used as part of a bundle of implementation strategies to reduce morbidity and mortality in PWID.

Sophia Lewis ◽  
Stephen Y Liang ◽  
Evan S Schwarz ◽  
David B Liss ◽  
Rachel P Winograd ◽  

Abstract Background Persons who inject drugs (PWID) are frequently admitted for serious injection related infections (SIRI). Outcomes and adherence to oral antibiotics for PWID with patient directed discharge (PDD) remain understudied. Methods We conducted a prospective multicenter bundled quality improvement project of PWID with SIRI at 3 hospitals in Missouri. All PWID with SIRI were offered multidisciplinary care while inpatient, including the option of addiction medicine consultation and medications for opioid use disorder (MOUD). All patients were offered oral antibiotics in the event of a PDD either at discharge, or immediately after discharge through an ID telemedicine clinic. Additional support services included health coaches, therapist, case manager, free clinic follow up, and medications in an outpatient bridge program. Patient demographics, comorbidities, 90-day readmissions, and substance use disorder clinic follow up were compared between PWID with PDD on oral antibiotics and those that completed IV antibiotics, using an as treated approach. Results Of 166 PWID with SIRI, 61 completed IV antibiotics inpatient (37%) while 105 had a PDD on oral antibiotics (63%). There was no significant difference in 90-day readmission rates between groups (p=0.819). For PWID with a PDD on oral antibiotics, 7.6% had documented non-adherence to antibiotics, 67% had documented adherence and 23% were lost to follow-up. Factors protective against readmission included antibiotic and MOUD adherence, engagement with support team, and clinic follow up. Conclusions PWID with SIRI who experience a PDD should be provided with oral antibiotics. Multidisciplinary outpatient support services are needed for PWID with PDD on oral antibiotics.

Daniel S Dodson ◽  
Heather R Heizer ◽  
James T Gaensbauer

Abstract Introduction Streptococcus anginosus group is a common cause of pediatric intracranial infections but treatment recommendations, including use of oral therapy, are poorly defined. Methods We performed a retrospective review from 2004-2019 of all patients with Streptococcus anginosus group pyogenic intracranial infections at Children’s Hospital Colorado, highlighting patients transitioned to oral therapy. The primary endpoint was worsening infection necessitating intravenous antibiotics or a source control procedure after transition to oral therapy. Results Of 107 patients with Streptococcus anginosus intracranial infections, 61 were transitioned to exclusive oral therapy after a median intravenous duration of 37 days, overwhelmingly with a levofloxacin-based regimen. Only one failure was noted in a patient who did not fill their prescription. Patients with epidural infections were more likely to be transitioned to oral therapy within the first 28 days of treatment (defined as “early”). Patients with parenchymal infections, bacteremia, co-pathogens, higher inflammatory markers, and requiring >1 source control procedure were less likely to be transitioned early to oral therapy. Complications of a central catheter and/or intravenous medications contributed to 56% of oral transitions. Conclusions Levofloxacin-based oral regimens were effective and well-tolerated. Patients with less severe infections were more likely to be transitioned early to oral therapy. Criteria for transitioning patients to oral antibiotics for intracranial infections should be established to minimize risks inherent with central catheters.

Melisa M Shah ◽  
Mohammad Ata Ur Rasheed ◽  
Jennifer L Harcourt ◽  
Glen R Abedi ◽  
Megan M Stumpf ◽  

Abstract We quantify antibody and memory B cell responses to SARS-CoV-2 at 6- and 12-months post-infection among 7 unvaccinated U.S. COVID-19 cases. All had detectable S-specific memory B cells and IgG at both time points, with geometric mean titers of 117.2 BAU/ml and 84.0 BAU/ml at 6 and 12 months, respectively.

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