Anorectal Testing for Mpox Virus Infection in Men Who Have Sex With Men With and Without Proctitis.

We performed anorectal testing in 18 cis-gender men who have sex with men with symptoms consistent with mpox virus (MPXV) infection. We found rectal MPXV DNA in 9/9 with and 7/9 without proctitis. Future study of anorectal testing is needed and may inform the diagnosis and pathogenesis of MPXV disease.

The Role of Early Subspeciality Consultation in the Timing of Hemophagocytic Lymphohistiocytosis Diagnosis and Management.

OBJECTIVE: The aim of this study was to investigate the relation between timing of subspeciality consult and hemophagocytic lymphohistiocytosis (HLH) consideration, immunosuppression initiation, and in-hospital mortality in patients with HLH. METHODS: We conducted a medical records review study of patients 18 years or older with definite or probable HLH at Montefiore Medical Center between 2006 and 2019. Earlier subspeciality consultation (rheumatology, hematology, and infectious disease) was defined as consultation in less than or equal to 18 hours from time of admission. Demographic, clinical characteristics, and outcomes were compared between patients with early and later subspecialty consultation. RESULTS: A total of 28 patients were included. The median age was 40 years, and 61% of patients were male. Infection was identified as a cause of HLH in 13 patients (46%). Fifteen patients (54%) were classified as having an earlier subspeciality consultation with a median time (interquartile range) to HLH consideration of 1.0 day (0.3-4.2 days) compared with 7.9 days (3.1-9.9 days) for the later consultation group (p = 0.002). The median time (interquartile range) to immunosuppression initiation was 4.6 days (1.7-7.8 days) versus 10.9 days (5.1-13.4 days) (p = 0.01), respectively. Five patients (33%) had in-hospital deaths in the early consultation group compared with 7 patients (54%) in later consultation group (p = 0.27). Among the subset of patients who survived to discharge, the 90-day readmission rate was higher in the later consultation group (83% vs 30%, p = 0.12). CONCLUSIONS: In patients with HLH, earlier subspeciality consultation may play a role in earlier HLH consideration and treatment initiation.

Medical student remote eConsult participation during the COVID-19 pandemic.

BACKGROUND: Undergraduate medical education was severely impacted by the COVID-19 pandemic. As traditional clinical rotations were suspended, medical students quickly began alternative, novel educational experiences. Third-year medical students at an academic medical center were given the opportunity to join inpatient eConsult teams within the department of medicine. This study describes the development and implementation of this program as well as the experiences of student and faculty participants. METHODS: Student eConsult participation was rapidly developed and implemented within medical subspecialty teams in either infectious diseases (ID) or nephrology. Twelve third-year medical students and 15 subspecialty attendings participated in this program during an eight-week period from April 6 through May 29, 2020. Breadth of student clinical experience was assessed via review of clinical documentation and surveys. Participating students and attending physicians completed surveys to reflect upon their impressions of the program. Surveys were returned by nine students and eight faculty members. Survey responses were summarized with descriptive statistics. RESULTS: Over an eight-week period, student consultants wrote 126 notes on 100 patients; 74 of these patients (74%) were hospitalized with COVID-19. Student experiences were largely positive with most strongly agreeing that attendings promoted interactive and engaged learning (N = 8 of 8, 100%), that the experience helped to expand their knowledge about consultant roles (N = 6, 75%), and that they would participate in a remote eConsult program again if given the opportunity (N = 6, 75%). Faculty also were largely positive about the experience with most agreeing or strongly agreeing with the importance of teaching medical students about telehealth (N = 7 of 8, 88%) and eConsults (N = 6, 75%). In narrative responses, students and faculty agreed that teaching was a strength of the program whereas lack of in-person contact was a challenge. CONCLUSIONS: Rapid development of an inpatient eConsult-based educational experience for third-year medical students was feasible and successful. Student-consultants saw a range of pathology including COVID-19 and related complications. Students were satisfied with the program. They were able to develop a strong relationship with attendings while learning about the role of a consultant. Faculty agreed with the importance of teaching students about telehealth and eConsults specifically.

Utility of Stool PCR for the Diagnosis of COVID-19: Comparison of Two Commercial Platforms.

The ability to detect SARS-CoV-2 in the upper respiratory tract ceases after 2 to 3 weeks post-symptom-onset in most patients. In contrast, SARS-CoV-2 can be detected in the stool of some patients for greater than 4 weeks, suggesting that stool may hold utility as an additional source for diagnosis. We validated the Cepheid Xpert Xpress SARS-CoV-2 and Hologic Panther Fusion real-time RT-PCR assays for detection of viral RNA in stool specimens and compared performance. We utilized remnant stool specimens (n = 79) from 77 patients with gastrointestinal symptoms. Forty-eight patients had PCR-confirmed COVID-19, and 29 either were nasopharyngeal/oropharyngeal PCR negative or presented for reasons unrelated to COVID-19 and were not tested. Positive percent agreement between the Cepheid and Hologic assays was 93% (95% confidence interval [CI]: 81.1% to 98.2%), and negative percent agreement was 96% (95% CI: 89% to 0.99%). Four discrepant specimens (Cepheid positive only, n = 2; Hologic positive only, n = 2) exhibited average cycle threshold (CT ) values of >37 for the targets detected. Of the 48 patients with PCR-confirmed COVID-19, 23 were positive by both assays (47.9%). For the negative patient group, 2/29 were positive by both assays (6.9%). The two stool PCR-positive, nasopharyngeal/oropharyngeal PCR-negative patients were SARS-CoV-2 IgG positive. Our results demonstrate acceptable agreement between two commercially available molecular assays and support the use of stool PCR to confirm diagnosis when SARS-CoV-2 is undetectable in the upper respiratory tract.

Performance Characteristics of a High-Throughput Automated Transcription-Mediated Amplification Test for SARS-CoV-2 Detection.

The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus has imposed severe challenges on laboratories in their effort to achieve sufficient diagnostic testing capability for identifying infected individuals. In this study, we report the analytical and clinical performance characteristics of a new, high-throughput, fully automated nucleic acid amplification test system for the detection of SARS-CoV-2. The assay utilizes target capture, transcription-mediated amplification, and acridinium ester-labeled probe chemistry on the automated Panther system to directly amplify and detect two separate target sequences in the open reading frame 1ab (ORF1ab) region of the SARS-CoV-2 RNA genome. The probit 95% limit of detection of the assay was determined to be 0.004 50% tissue culture infective dose (TCID50)/ml using inactivated virus and 25 copies/ml (c/ml) using synthetic in vitro transcript RNA targets. Analytical sensitivity (100% detection) was confirmed to be 83 to 194 c/ml using three commercially available SARS-CoV-2 nucleic acid controls. No cross-reactivity or interference was observed with testing of six related human coronaviruses, as well as 24 other viral, fungal, and bacterial pathogens, at high titers. Clinical nasopharyngeal swab specimen testing (n = 140) showed 100%, 98.7%, and 99.3% positive, negative, and overall agreement, respectively, with a validated reverse transcription-PCR nucleic acid amplification test (NAAT) for SARS-CoV-2 RNA. These results provide validation evidence for a sensitive and specific method for pandemic-scale automated molecular diagnostic testing for SARS-CoV-2.

Histoplasma Capsulatum: Mechanisms for Pathogenesis.

Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts can be clinically silent or it can lead to life-threatening systemic disease, which can occur in immunologically intact or deficient hosts, albeit severe disease is more likely in the setting of compromised cellular immunity. H. capsulatum yeast cells are highly adapted to the mammalian host as they can effectively survive within intracellular niches in select phagocytic cells. Understanding the biological response by both the host and H. capsulatum will facilitate improved approaches to prevent and/or modify disease. This review presents our current understanding of the major pathogenic mechanisms involved in histoplasmosis.

The Transcription Factor NFAT1 Participates in the Induction of CD4+ T Cell Functional Exhaustion during Plasmodium yoelii Infection.

Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and upregulate cell surface inhibitory molecules such as PD-1 and LAG-3. The molecular events that lead to the induction of this phenotype have, however, not been fully characterized. In T cells, members of the NFAT family of transcription factors not only are responsible for the expression of many activation-induced genes but also are crucial for the induction of transcriptional programs that inhibit T cell activation and maintain tolerance. Here we show that NFAT1-deficient CD4+ T cells maintain higher proliferative capacity and expression of effector cytokines following Plasmodium yoelii infection and are therefore more resistant to P. yoelii-induced exhaustion than their wild-type counterparts. Consequently, gene expression microarray analysis of CD4+ T cells following P. yoelii-induced exhaustion shows upregulation of effector T cell-associated genes in the absence of NFAT1 compared with wild-type exhausted T cells. Furthermore, adoptive transfer of NFAT1-deficient CD4+ T cells into mice infected with P. yoelii results in increased production of antibodies to cognate antigen. Our results support the idea that NFAT1 is necessary to fully suppress effector responses during Plasmodium-induced CD4+ T cell exhaustion.

Coronavirus Disease 2019 (COVID-19) Perinatal Outcomes Across the Pandemic at an Academic Medical Center in New York City.

OBJECTIVE: To investigate perinatal complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy in the four major waves of the coronavirus disease 2019 (COVID-19) pandemic in the Bronx, New York. METHODS: This retrospective cohort study included all patients who delivered at a single academic medical center between March 1, 2020, and February 13, 2022. SARS-CoV-2 positivity was defined as a positive SARS-CoV-2 test result during pregnancy. Primary outcomes were preterm birth, low birth weight, stillbirth, cesarean delivery, and preeclampsia associated with SARS-CoV-2 infection. Secondary analyses examined outcomes by predominant variant at the time of infection. Group differences in categorical variables were tested using χ 2 tests. RESULTS: Of the 8,983 patients who delivered, 638 (7.1%) tested positive for SARS-CoV-2 infection during pregnancy. Age, race, ethnicity, and major comorbidities did not differ significantly between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts ( P >.05). Primary outcomes did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts ( P >.05). There was a marked increase in positive SARS-CoV-2 test results in individuals who gave birth during the Omicron wave (140/449, 31.2%). However, among patients who tested positive for SARS-CoV-2 infection, the preterm birth rate during the Omicron wave (9.9%) was significantly lower than during the original wave (20.3%) and the Alpha (18.4%) wave ( P <.05). Vaccination rates were low before the Omicron wave and rose to 47.2% during the Omicron wave among individuals hospitalized with SARS-CoV-2 infection. Finally, second-trimester infection was significantly associated with worse perinatal outcomes compared with third-trimester infection ( P <.05). CONCLUSION: There was a general trend toward improvement in preterm birth rates across the pandemic among pregnant patients with SARS-CoV-2 infection. The Omicron variant was more infectious, but the preterm birth rate during the Omicron wave was low compared with that during the original wave and the Alpha wave.

Assessing a standardized decision-making algorithm for blood culture collection in the intensive care unit.

PURPOSE: Blood cultures are commonly ordered for patients with low risk of bacteremia. Indications for obtaining blood cultures are often broad and ill defined, and decision algorithms for appropriate blood cultures have not been comprehensively evaluated in critically-ill populations. METHODS: We conducted a retrospective analysis to assess the frequency of inappropriate blood cultures in the ICUs at Montefiore Medical Center based on an evidence-based guidance algorithm. Blood cultures were reviewed against this algorithm to determine their appropriateness. We calculated the prevalence of inappropriate blood culture and explored the reasons for these collected cultures. RESULTS: 300 patients were randomly selected from an initial cohort of 3370 patients. 294 patients were included and of these, 167 patients had at least 1 blood culture drawn. 125 patients had one or more inappropriate blood culture. 61.4% of blood cultures drawn were assessed to be inappropriate. The most common reason for inappropriate cultures was a culture drawn as a result of isolated fever or leukocytosis. CONCLUSION: In a cohort of critically-ill patients, inappropriate blood cultures were common. The indications for blood cultures are often not evidence-based, and evidence-based algorithms to guide the collection of blood cultures may offer a way to decrease inappropriate culture orders.

Elucidating the role of procalcitonin as a biomarker in hospitalized COVID-19 patients.

Our objectives were to evaluate the role of procalcitonin in identifying bacterial co-infections in hospitalized COVID-19 patients and quantify antibiotic prescribing during the 2020 pandemic surge. Hospitalized COVID-19 patients with both a procalcitonin test and blood or respiratory culture sent on admission were included in this retrospective study. Confirmed co-infection was determined by an infectious diseases specialist. In total, 819 patients were included; 335 (41%) had an elevated procalcitonin (>0.5 ng/mL) and of these, 42 (13%) had an initial bacterial co-infection. Positive predictive value of elevated procalcitonin for co-infection was 13% while the negative predictive value was 94%. Ninety-six percent of patients with an elevated procalcitonin received antibiotics (median 6 days of therapy), compared to 82% with low procalcitonin (median 4 days of therapy) (adjusted OR:3.3, P < 0.001). We observed elevated initial procalcitonin in many COVID patients without concurrent bacterial co-infections which potentially contributed to antibiotic over-prescribing.

Rapid implementation of Inpatient eConsult Programme addresses new challenges for patient care during COVID-19 pandemic.

INTRODUCTION: At the early epicentre of the COVID-19 crisis in the USA, our institution saw a surge in the demand for inpatient consultations for areas impacted by COVID-19 (eg, infectious diseases, nephrology, palliative care) and shortages in personal protective equipment (PPE). We aimed to provide timely specialist input for consult requests during the COVID-19 pandemic by implementing an Inpatient eConsult Programme. METHODS: We used the reach, effectiveness, adoption, implementation and maintenance implementation science framework and run chart analysis to evaluate the reach, adoption and maintenance of the Inpatient eConsult Programme compared with traditional in-person consults. We solicited qualitative feedback from frontline physicians and specialists for programme improvements. RESULTS: During the study period, there were 46 available in-person consult orders and 21 new eConsult orders. At the peak of utilisation, 42% of all consult requests were eConsults, and by the end of the study period, utilisation fell to 20%. Qualitative feedback revealed subspecialties best suited for eConsults (infectious diseases, nephrology, haematology, endocrinology) and influenced improvements to the ordering workflow, documentation, billing and education regarding use. DISCUSSION: When offered inpatient eConsult requests as an alternative to in-person consults in the context of a surge in patients with COVID-19, frontline physicians used eConsult requests and decreased use of in-person consults. As the demand for consults decreased and PPE shortages were no longer a major concern, eConsult utilisation decreased, revealing a preference for in-person consultations when possible. CONCLUSIONS: Lessons learnt can be used to develop and implement inpatient eConsults to meet context-specific challenges at other institutions.

Evaluation of Clinical Outcomes After Introduction of a Dedicated Infectious Diseases-Critical Care Medicine Service in Critical Care Units.

BACKGROUND: Infection is a leading cause of admission to intensive care units (ICUs), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-critical care medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. METHODS: In this single-site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during the postintervention period from January 1 to December 31, 2017, and compared it to antibiotic utilization in the same ICUs during the preintervention period from January 1 to December 31, 2015. RESULTS: Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam, and cefepime during the intervention period. When compared to the preintervention period there was no difference in-hospital mortality, hospital length of stay, and readmission. CONCLUSIONS: With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

Approaching the Interpretation of Discordances in SARS-CoV-2 Testing.

The coronavirus disease 2019 pandemic has upended life throughout the globe. Appropriate emphasis has been placed on developing effective therapies and vaccines to curb the pandemic. While awaiting such countermeasures, mitigation efforts coupled with robust testing remain essential to controlling spread of the disease. In particular, serological testing plays a critical role in providing important diagnostic, prognostic, and therapeutic information. However, this information is only useful if the results can be accurately interpreted. This pandemic placed clinical testing laboratories and requesting physicians in a precarious position because we are actively learning about the disease and how to interpret serological results. Having developed robust assays to detect antibodies generated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and serving the hardest-hit areas within the New York City epicenter, we found 3 types of discordances in SARS-CoV-2 test results that challenge interpretation. Using representative clinical vignettes, these interpretation dilemmas are highlighted, along with suggested approaches to resolve such cases.

Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6-7 days, and 79% had received prior antibiotics. Metallo-ß-lactamase-producing E. cloacae coinfections occurred in 5 patients.

Analysis of catheter utilization, central line associated bloodstream infections, and costs associated with an inpatient critical care-driven vascular access model.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) carry serious risks for patients and financial consequences for hospitals. Avoiding unnecessary temporary central venous catheters (CVC) can reduce CLABSI. Critical Care Medicine (CCM) is often consulted to insert CVC when alternatives are unavailable. We aim to describe clinical and financial implications of a CCM-driven vascular access model. METHODS: In this retrospective, observational cohort study, all CLABSI and a sample of CCM consults for CVC insertion on adult medical-surgical inpatient units were reviewed in 2019. Assessment of CVC appropriateness and financial analysis of labor, reimbursement, and attributable CLABSI cost was conducted. RESULTS: Of 554 CCM consult requests, 75 (13.5%) were for CVC and 36 (48.0%) resulted in CVC insertion; 6 (16.7%) CVC were avoidable. Three CLABSI occurred in avoidable CVC with estimated annual attributable cost of $165,099. Estimated annual CCM consultant cost for CVC was $78,094 generating $110,733 in reimbursement. Overall estimated annual loss was $132,460. DISCUSSION: Reliance on CCM for intravenous access resulted in avoidable CVC, CLABSI, inefficient physician effort, and financial losses; nurse-driven vascular access models offer potential cost savings and risk reduction. CONCLUSIONS: CCM-driven vascular access models may not be cost-effective; alternatives should be considered for utilization reduction, CLABSI prevention, and financial viability.

Treatment of severe COVID-19 with convalescent plasma in Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.

Treatment of Severe COVID-19 with Convalescent Plasma in the Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients <65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients <65 years, but data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy.

Early Infectious Disease Consultation Is Associated With Lower Mortality in Patients With Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle.

OBJECTIVE: Severe sepsis and septic shock (SS/SS) treatment bundles reduce mortality, and early infectious diseases (ID) consultation also improves patient outcomes. We retrospectively examined whether early ID consultation further improves outcomes in Emergency Department (ED) patients with SS/SS who complete the sepsis bundle. METHOD: We included 248 adult ED patients with SS/SS who completed the 3-hour bundle. Patients with ID consultation within 12 hours of ED triage (n = 111; early ID) were compared with patients who received standard care (n = 137) for in-hospital mortality, 30-day readmission, length of hospital stay (LOS), and antibiotic management. A competing risk survival analysis model compared risks of in-hospital mortality and discharge alive between groups. RESULTS: In-hospital mortality was lower in the early ID group unadjusted (24.3% vs 38.0%, P = .02) and adjusted for covariates (odds ratio, 0.47; 95% confidence interval (CI), 0.25-0.89; P = .02). There was no significant difference in 30-day readmission (22.6% vs 23.5%, P = .89) or median LOS (10.2 vs 12.1 days, P = .15) among patients who survived. A trend toward shorter time to antibiotic de-escalation in the early ID group (log-rank test P = .07) was observed. Early ID consultation was protective of in-hospital mortality (adjusted subdistribution hazard ratio (asHR), 0.60; 95% CI 0.36-1.00, P = .0497) and predictive of discharge alive (asHR 1.58, 95% CI, 1.11-2.23; P-value .01) after adjustment. CONCLUSIONS: Among patients receiving the SS/SS bundle, early ID consultation was associated with a 40% risk reduction for in-hospital mortality. The impact of team-based care and de-escalation on SS/SS outcomes warrants further study.