Safety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver Transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141779/1/phar2036.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141779/2/phar2036_am.pd

Safety and efficacy of direct- acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single- center cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/1/tri13599.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/2/tri13599_am.pd

Development of a novel inhalational model of invasive pulmonary aspergillosis in rats and comparative evaluation of three biomarkers for its diagnosis.

Aspergillus fumigatus, a thermotolerant fungus, is the main causative agent of invasive pulmonary aspergillosis (IPA) in immunocompromised patients that is associated with high mortality rates. Early diagnosis of IPA is crucial for mortality reduction and improved prognosis. An experimental inhalational model of IPA was developed in rats and the efficacy of three biomarkers, namely β-D-glucan (BDG), a panfungal marker, galactomannan (GM), a genus-specific marker, and A. fumigatus DNA, a species-specific marker was evaluated in serum and bronchoalveolar lavage (BAL) specimens at different time points postinfection for early diagnosis of IPA. BDG and GM were detected by using commercial Fungitell and Platelia Aspergillus EIA kits, respectively. A. fumigatus DNA was detected by developing a sensitive, single-step PCR assay. IPA was successfully developed in immunosuppressed rats and all animals until 5 days post-infection were positive for A. fumigatus by culture and KOH-calcofluor microscopy also showed A. fumigatus in 19 of 24 (79%) lung tissue samples. Fourteen of 30 (47%) and 27 of 30 (90%) serum and BAL specimens, respectively, were positive for all three biomarkers with 100% specificity (none of sera or BAL specimens of 12 control rats was positive for biomarkers). Our data show that BAL is a superior specimen than serum and combined detection of BDG, GM and A. fumigatus DNA provide a sensitive diagnosis of IPA in an experimental animal model. Moreover, combined detection of GM and DNA in BAL and detection of either GM or DNA in serum was also positive in 27 of 30 (90%) animals. For economic reasons and considering that the positive predictive value of BDG is low, the detection of GM and/or DNA in serum and BAL samples has the potential to serve as an integral component of the diagnostic-driven strategy in high-risk patients suspected for IPA

Exposure chamber used for infection of immunosuppressed rats with <i>A. fumigatus</i>.

<p>The figure shows the chamber (<b>a</b>) where the rats were kept, <i>A. fumigatus</i> culture flask (<b>b</b>) that was connected directly to the chamber and the pump (<b>c</b>) that was used to manually transfer conidia of <i>A. fumigatus</i> to the chamber for exposing immunosuppressed rats.</p

KOH-calcoflour mounts and histopathology of lung tissue sections.

<p>The KOH-calcoflour mounts (<b>a</b> and <b>b</b>), and histopathology (<b>c</b> and <b>d</b>) of lung tissue sections obtained from 4 immunosuppressed rats sacrificed on Day 3 postinfection showing abundant growth of <i>A. fumigatus</i>.</p

Comparative results of culture and KOH-calcofluor microscopy of lung tissue samples from <i>A. fumigatus</i>-infected rats.

<p>*Kappa (κ)  = 0.67 (no value could be obtained for κ for other time points since all lung tissue samples were positive for culture).</p

The Efficacy of Antioxidant Oral Supplements on the Progression of COVID-19 in Non-Critically Ill Patients: A Randomized Controlled Trial

Modulation of cytokine production using immunonutrition is a relatively novel concept to improve outcomes among patients with SARS-CoV-2 infection and is now hypothesized to help manage COVID-19, however, clinical evidence is lacking. This prospective, double-blinded, randomized parallel-controlled interventional clinical trial investigated the effect of antioxidant supplements on inflammatory cytokines and disease progression in non-critically ill patients. A total of 87 hospitalized COVID-19 patients were randomized using computer-generated-randomization into the supplement group (n = 18) and the placebo group (n = 16) for 10 days. Baseline and final nutritional screening via nutrition risk screening (NRS-2002) and subjective global assessment (SGA), as well as the recording of anthropometric, clinical, biochemical, and functional parameters, were done. Serum ferritin level, cytokine storm parameters such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1(MCP-1), C-reactive protein, total leukocyte count, lymphocytic count, and neutrophil-to-lymphocyte ratio were measured. Anthropometric and clinical parameters showed nonsignificant differences between groups. The hematology profile showed improvement in lymphocyte count in the supplement group. However, levels of alkaline phosphatase, IL-6, TNF-α, and MCP-1 were significantly lower in the supplement group. In conclusion, antioxidant oral supplementation significantly reduced the cytokine storm and led to partial improvements in clinical parameters among patients with non-critical COVID-19

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes