Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions

Diabetes Mellitus Type 2 as a Risk Factor and Outcome Modifier for Cryptococcosis in HIV Negative, Non-transplant Patients, a Propensity Score Match Analysis

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We queried a global research network to identify NHNT patients (n = 3280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients by DM status. We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR 1.6; 95% CI (1.1–2.3); P = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. Pulmonary cryptococcosis was the most common site of infection. Among 44 cryptococcosis patients with DM2 as the only identifiable risk factor for disease, the annual incidence of cryptococcosis was 0.001%, with a prevalence of 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase the risk of cryptococcosis in patients with DM2

Monkeypox – a description of the clinical progression of skin lesions: a case report from Colorado, USA

A rapidly emerging global outbreak of monkeypox virus infection (MPXV) in over 50 non-endemic countries was identified in May 2022. We report the case and images of a patient with MPXV presenting with genital lesions later complicated by superimposed cellulitis in Colorado, USA. MPXV lesions are susceptible to bacterial superinfection, and with the advent of new cases, the early identification of skin lesions and their evolution during MPXV are imperative for treating clinicians. Clinicians should consider MPXV in differential diagnoses of sexually transmitted diseases presenting with genital lesions

Characteristics and Outcomes of Cryptococcosis among Patients with and without COVID-19

The effect of COVID-19 on the risk and prognosis of cryptococcosis is unclear. We compared the characteristics and outcomes of cryptococcosis in patients with and without COVID-19. Patients 18 years and older with cryptococcosis were identified from TriNetX and separated into two cohorts based on a diagnosis of COVID-19 within 3 months of the index diagnosis of cryptococcosis. Differences examined between groups included comorbidities, immunosuppressive medications, ED visits, hospitalizations, ICU admissions, mechanical ventilation, and deaths. The propensity score matching was performed based on demographics and comorbidities. Of the 6998 patients with cryptococcosis included, 4.4% (n = 306) had COVID-19 prior to cryptococcosis. Mortality was higher in patients with COVID-19 compared to those without COVID-19 (14% vs. 11%, p = 0.032). Additionally, those with COVID-19 were older (55.2 ± 14.4 vs. 51.9 ± 15.2 years, p < 0.001) with higher rates of transplant (29% vs. 13%, p < 0.001), neoplastic disease (37% vs. 21%, p < 0.001), chronic kidney disease (42% vs. 18%, p < 0.001), or diabetes (35% vs. 19%, p < 0.001) but not HIV (30% vs. 31%, p = 0.618). Glucocorticoid use was more common in those with COVID-19 (52% vs. 27%, p < 0.001). More patients with COVID-19 required ED visits (29% vs. 23%, p = 0.025) and ICU admission (18% vs. 11%, p < 0.001). After propensity score matching, patients with COVID-19 had higher rates of neoplastic disease, heart failure, chronic kidney disease, and glucocorticoid use but did not experience worse outcomes compared to those without COVID-19. Patients with COVID-19 who developed cryptococcosis had independently higher rates of comorbidities and glucocorticoid use but similar outcomes, including death, versus those without COVID-19

Cryptococcosis among hospitalised patients with COVID‐19: A multicentre research network study

It is unclear if there is an association between COVID-19 and cryptococcosis. Therefore, this study aimed to describe the clinical features, risk factors, and outcomes associated with cryptococcosis in hospitalised patients with COVID-19. The objectives of this study were to determine the incidence of and examine factors associated with cryptococcosis after a diagnosis of COVID-19. We used TriNetX to identify and sort patients 18 years and older hospitalised with COVID-19 into two cohorts based on the presence or absence of a diagnosis of cryptococcosis following diagnosis of COVID-19. Outcomes of interest included the incidence of cryptococcosis following the diagnosis of COVID-19 as well as the proportion of patients in each group who had underlying comorbidities, received immunomodulatory therapy, required ICU admission or mechanical ventilation (MV), or died. Propensity score matching was used to adjust for confounding. Among 212,479 hospitalised patients with COVID-19, 65 developed cryptococcosis. The incidence of cryptococcosis following COVID-19 was 0.022%. Patients with cryptococcosis were more likely to be male and have underlying comorbidities. Among cases, 32% were people with HIV. Patients with cryptococcosis were more likely to have received tocilizumab (p < .0001) or baricitinib (p < .0001), but not dexamethasone (p = .0840). ICU admission (38% vs 29%), MV (23% vs 11%), and mortality (36% vs 14%) were significantly higher among patients with cryptococcosis. Mortality remained elevated after adjusted propensity score matching. Cryptococcosis occurred most often in hospitalised patients with COVID-19 who had traditional risk factors, comparable to findings in patients without COVID-19. Cryptococcosis was associated with increased ICU admission, MV, and mortality

Previous corticosteroid exposure associates with an increased pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study

Background: HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality. Objective: We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality. Methods: We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis ( n  = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis. Results: 1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p  < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p  = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p  = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 10 3 cells/µl, p  < 0.0001) and hypoxia (SatO 2 : 86.7% versus 91.6%, p  < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p  < 0.001) or prednisone (49% versus 29%, p  < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5–9.2, p  = 0.004) and 1 year (HR: 4.5, CI: 2.0–10.4, p  < 0.0001) among HIV-negative patients with previous corticosteroid exposure. Conclusion: Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses

Previous corticosteroid exposure associates with an increased Pneumocystis jirovecii pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study

BackgroundHIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality.ObjectiveWe aim to characterize the role of prior corticosteroid exposure in PJP-related mortality.MethodsWe queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis (n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis.Results1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p &lt; 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p &lt; 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p &lt; 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p &lt; 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p &lt; 0.001) or prednisone (49% versus 29%, p &lt; 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5-9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0-10.4, p &lt; 0.0001) among HIV-negative patients with previous corticosteroid exposure.ConclusionPreceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses

The global prevalence of human fascioliasis: a systematic review and meta-analysis

Background: Fascioliasis is a parasitic zoonosis that can infect humans and be a source of significant morbidity. The World Health Organization lists human fascioliasis as a neglected tropical disease, but the worldwide prevalence of fascioliasis data is unknown. Objective: We aimed to estimate the global prevalence of human fascioliasis. Data sources and methods: We performed a systematic review and prevalence meta-analysis. We used the following inclusion criteria: articles published in the English, Portuguese, or Spanish languages from December 1985 to October 2022 and studies assessing the prevalence of Fasciola in the general population with an appropriate diagnostic methodology, including longitudinal studies, prospective and retrospective cohorts, case series, and randomized clinical trials (RCTs). We excluded animal studies. Two reviewers independently reviewed the selected studies for methodological quality, performing critical standard measures from JBI SUMARI. A random-effects model was conducted of the summary extracted data on the prevalence proportions. We reported the estimates according to the GATHER statement. Results: In all, 5617 studies were screened for eligibility. Fifty-five studies from 15 countries were selected, including 154,697 patients and 3987 cases. The meta-analysis revealed a pooled prevalence of 4.5% [95% confidence interval (CI): 3.1–6.1; I 2  = 99.4%; T 2  = 0.07]. The prevalence in South America, Africa, and Asia was 9.0%, 4.8%, and 2.0%, respectively. The highest prevalence was found in Bolivia (21%), Peru (11%), and Egypt (6%). Subgroup analysis showed higher prevalence estimates in children, in studies from South America, and when Fas2-enzyme-linked immunosorbent assay (ELISA) was used as a diagnostic method. A larger study sample size ( p  = 0.027) and an increase in female percentage ( p  = 0.043) correlated with a decrease in prevalence. Multiple meta-regression showed a higher prevalence for hyperendemic than hypoendemic ( p  = 0.002) or mesoendemic ( p  = 0.013) regions. Conclusion: The estimated prevalence and projected disease burden of human fascioliasis are high. Study findings support that fascioliasis continues to be a globally neglected tropical disease. Strengthening epidemiological surveillance and implementing measures to control and treat fascioliasis is imperative in the most affected areas

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN