Jennifer K. L. Chow

Cytomegalovirus immune globulin (CMVIG) reduces severe Cytomegalovirus (CMV) associated disease in liver transplant recipients (LTR). Because CMV viral loads (VL) were not available when the original prophylaxis trial was conducted, we retrospectively assessed CMV disease severity and CMV VL patterns in moderate and low‐risk LTR receiving CMVIG prophylaxis. CMV VLs were measured using a quantitative PCR assay (Eurofins Viracor) in stored serial serum specimens from 96 LTR (D‐/R‐ and R +). CMV‐associated disease was classified according to original trial definitions and stratified by CMV disease severity. CMV outcomes and VL parameters were compared between CMVIG and placebo groups. 96 patients out of the original 146 study subjects had available serum samples for analysis. 67 (70%) had at least 1 detectable CMV VL. Severe CMV disease (vs. CMV syndrome/asymptomatic CMV disease) was associated with higher peak CMV VLs ( p < 0.0001), shorter times to first detectable CMV VL ( p = 0.01), and increased mortality ( p = 0.003). Compared to placebo, CMVIG recipients had longer times to peak CMV VL (median days 38 vs. 35; log‐rank p = 0.049), lower rates of CMV pneumonitis (0% vs. 17.6%, p = 0.01) and fewer cases of severe CMV disease (3% vs. 17.6%, p = 0.04). Using specimens from studies preceding the antiviral prophylaxis era, among moderate‐ and low‐risk LTR, CMVIG prophylaxis was associated with attenuated CMV disease severity and delayed progression of CMV viremia. These findings suggest that CMVIG may offer both clinical and limited antiviral benefits in this population, particularly in settings where standard antiviral prophylaxis cannot be used.

Background.: The combined effects of age and sex impact important posttransplant outcomes. Despite key physiologic differences in metabolic and immune function, older women are often indiscriminately grouped with either young women or older men. We examined sex- and age-based differences in clinical markers of immunity in heart and kidney recipients, with specific attention to those of postmenopausal women. Methods.: Blood was prospectively collected before transplantation, and at 1 and 6 mo posttransplantation, alongside 12 mo of clinical data. Patients were stratified by age, biological sex, and menopause status. Absolute lymphocyte count (ALC), CD4⁺ and CD8⁺ lymphocyte subsets, total IgG, 4 selected cytokines, estradiol and progesterone, and cumulative incidence of infection were quantified within groups. The relationship between menopause category (premenopausal women, postmenopausal women, men) and 6-mo ALC was tested by linear regression, controlling for multiple confounding variables. Results.: The cohort included 40 heart, 23 kidney, and 3 heart-kidney recipients categorized as 10 women older than 50 y, 12 women 50 y and younger, 26 men older than 50 y, and 18 men 50 y and younger. At 6 mo posttransplant, mean ALC among older women (0.59 K/µL) fell to a far lower range of lymphopenia than in young women (0.9 K/µL), older men (0.85 K/µL), and younger men (0.82 K/µL). Postmenopausal women had significantly lower ALC compared with premenopausal women (P = 0.03) and men (P = 0.05). Women older than 50 y also had the greatest cumulative incidence of infection by 1 y compared with other groups. Conclusions.: These findings support the concern for increased risk of infection in postmenopausal organ transplant recipients.

Background.: Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y. Methods.: A retrospective cohort study of HT recipients (2000–2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application. Results.: Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 10³cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated. Conclusion.: This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.

Background: The aim of our survey was to analyze the current attitudes toward antimicrobial prophylaxis in heart transplanting centers worldwide.Methods: The survey was composed of a total of 50 questions, it consisted of four different sections as follows. The first section collected physicians’ personal data and centers’ general characteristics, second assessed the approach to patients colonized with multidrug‐resistant organisms (MDROs), while the third consisted of the infection risk related to cardiovascular devices, and antimicrobial treatment data, the last focused on donor's colonization.Results: A total of 56 answers from 26 different countries were collected, mostly from Europe (n = 30) and the USA (n = 16). A first‐generation cephalosporin (58.9%) or a combination therapy with vancomycin (10.7%) were the most frequently prescribed antimicrobial prophylaxis. Roughly 30% of the centers used different antimicrobial prophylaxis,mostly including Gram negative bacteria coverage. The frequency of screening for multidrug resistant Gram‐negative bacteria was higher in Europe, where the percentage of centers providing screening for extended spectrum beta‐lactamase (46.7%) and carbapenem‐resistant Enterobacteriaceae (CRE) (53.3%) was higher than in other geographic area (p = .019; p = .013, respectively).Conclusion: This survey highlights a heterogeneity of clinical practice concerning antimicrobial prophylaxis at transplant. The concern for potential Gram‐negative bacteria infection was responsible for broader antimicrobial coverage in 30% of centers. image

Global economies depend on the use of fossil‐fuel‐based polymers with 360–400 million metric tons of synthetic polymers being produced per year. Unfortunately, an estimated 60% of the global production is disposed into the environment. Within this framework, microbiologists have tried to identify plastic‐active enzymes over the past decade. Until now, this research has largely failed to deliver functional biocatalysts acting on the commodity polymers such as polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), ether‐based polyurethane (PUR), polyamide (PA), polystyrene (PS) and synthetic rubber (SR). However, few enzymes are known to act on low‐density and low‐crystalline (amorphous) polyethylene terephthalate (PET) and ester‐based PUR. These above‐mentioned polymers represent >95% of all synthetic plastics produced. Therefore, the main challenge microbiologists are currently facing is in finding polymer‐active enzymes targeting the majority of fossil‐fuel‐based plastics. However, identifying plastic‐active enzymes either to implement them in biotechnological processes or to understand their potential role in nature is an emerging research field. The application of these enzymes is still in its infancy. Here, we summarize the current knowledge on microbial plastic‐active enzymes, their global distribution and potential impact on plastic degradation in industrial processes and nature. We further outline major challenges in finding novel plastic‐active enzymes, optimizing known ones by synthetic approaches and problems arising through falsely annotated and unfiltered use of database entries. Finally, we highlight potential biotechnological applications and possible re‐ and upcycling concepts using microorganisms.