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Background: Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis.Methods: The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects.Results: The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness.Conclusions: Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution. [ABSTRACT FROM AUTHOR]

Abstract: Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Hypothermia on admission is associated with increased mortality in preterm infants. Drugs administered to pregnant women is implicated in its occurrence. Since magnesium sulfate has a myorelaxant effect, we aimed evaluating the association of hypermagnesemia at birth and admission hypothermia (axillary temperature <36.5°C) in preterm infants., Methods: We performed a secondary analysis of a prospective cohort study database including inborn infants <34 weeks, without congenital malformations. Hypermagnesemia was considered if the umbilical magnesium level > 2.5 mEq/L. Maternal and neonatal variables were used to adjust the model, submitted to the multivariate hierarchical modelling process., Results: We evaluated 249 newborns with median birth weight and gestational age of 1375 (IQR 1020-1375) g and 31 (IQR 28-32) weeks, respectively. Hypermagnesemia occurred in 28.5% and admission hypothermia occurred in 28.9%. In the univariate analysis, the following variables were identified as being associated with admission hypothermia: hypermagnesemia (OR 3.71; CI 2.06-6.68), resuscitation (OR 2.39; CI 1.37-4.19), small to gestational age (OR 1.91; CI1.03-3.53), general anesthesia (OR 3.34; CI 1.37-8.13), birth weight (OR 0.998; CI 0.998-0.999) and gestational age (OR 0.806; CI 0.725-0.895). In the hierarchical regression model, hypermagnesemia remained independent associated with admission hypothermia (OR 3.20; CI 1.66-6.15), as well as birth weight (OR 0.999; CI 0.998-0.999) and tracheal intubation (3.83; CI 1.88-7.80)., Conclusion: Hypermagnesemia was associated with an increased risk of admission hypothermia, as did tracheal intubation and lower birth weight.

MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. They have been implicated in the pathogenesis of cancer and neurological, cardiovascular, and autoimmune diseases. Several recent studies have suggested that miRNAs are key players in regulating the differentiation, maturation, and activation of immune cells, thereby influencing the host immune response to infection. The resultant upregulation or downregulation of miRNAs from infection influences the protein expression of genes responsible for the immune response and can determine the risk of disease progression. Recently, miRNAs have been explored as diagnostic biomarkers and therapeutic targets in various infectious diseases. This review summarizes our current understanding of the role of miRNAs during viral, fungal, bacterial, and parasitic infections from a clinical perspective, including critical functional mechanisms and implications for their potential use as biomarkers and therapeutic targets., Competing Interests: The authors declare no conflict of interest.

Background: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side-effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported., Methods: In this single-center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs., Results: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21-91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs-nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8-253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry-sponsored clinical trials. All-cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co-infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups., Conclusion: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side-effect and drug-interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs., (© 2023 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Background: The optimal number of doses as well as the role for measurement of postvaccination titers after measles, mumps, rubella (MMR) vaccination in adult hematopoietic cell transplantation (HCT) recipients remains unknown., Methods: In the present study, we assessed humoral immunity against measles, mumps and rubella before and after MMR vaccination in 187 adults who received at least one dose of the MMR vaccine after HCT., Results: Among those with baseline titers, posttransplant prevaccination seroprotection rates were 56%, 30%, and 54% for measles, mumps, and rubella, respectively; and significantly lower in allogeneic versus autologous HCT recipients for measles (39% vs. 80%, p = .0001), mumps (22% vs. 41%; p = .02) and rubella (48% vs. 62%, p = .12). Among those who were seronegative at baseline, seroconversion rates after one dose of MMR were 69%, 56%, and 97% for measles, mumps, and rubella, respectively. Seronegative patients after one dose of MMR (i.e., nonresponders) seroconverted for measles and mumps after a second MMR vaccine dose., Conclusion: Our findings demonstrate successful restoration of protective immunity against measles, mumps, and rubella after vaccination in adult HCT recipients; one dose of MMR elicited protective titers in the majority of patients, and a second vaccine dose was immunogenic in nonresponders., (© 2023 Wiley Periodicals LLC.)

Objective: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS)., Methods: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated., Results: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93)., Conclusion: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

We report a case of an immunocompromised man with monkeypox who experienced disease progression despite timely initiation of tecovirimat and ultimately required utilization of cidofovir and VIGIV for treatment. In immunocompromised patients, monkeypox might present with a more severe course of disease requiring consideration of alternative treatment strategies., (© 2023 Wiley Periodicals LLC.)

Background: Data on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS-CoV-2-specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab-imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID-19) in HM/HCT patients., Methods: This was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID-19 who received casirivimab-imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS-CoV-2-specific mAbs., Results: We identified 59 HM/HCT patients with mild to moderate COVID-19 who received casirivimab-imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45-65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T-cell therapy. The median time from COVID-19 symptom onset to SARS-CoV-2-specific mAb administration was 4 (IQR: 3-6) days. Forty-six (78%) patients received SARS-CoV-2-specific mAbs as outpatients and 13 (22%) patients received SARS-CoV-2-specific mAbs during hospitalization. Among patients who received SARS-CoV-2-specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS-CoV-2-specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID-19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS-CoV-2-specific mAb administration; two of these three deaths were attributed to COVID-19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab-imdevimab use., Conclusion: During the alpha and delta variant surges, early administration of bamlanivimab or casirivimab-imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID-19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID-19 in this population are needed., (© 2023 Wiley Periodicals LLC.)

Objectives: This study aimed to compare the analgesic effect between carprofen and grapiprant every 12 or 24 h on postoperative pain in cats undergoing ovariohysterectomy, in addition to the effects on the hematological, biochemical and urinalysis variables., Methods: A total of 32 female cats were randomly divided into three groups, according to the treatment administered with the first dose given orally 90 mins before surgery, as follows: CAR (cats received 4 mg/kg carprofen, n = 11); GRA1 (cats received 2 mg/kg grapiprant, n = 10); and GRA2 (cats received 2 mg/kg grapiprant q12h, n = 11). Pain was assessed by UNESP-Botucatu Multidimensional Composite Pain Scale (UNESP) and Glasgow Feline Composite Measure Pain Scale (GLASGOW) for cats preoperatively (baseline) and at 1, 3, 6, 8, 12 and 24 h after extubation. Venous blood was collected at baseline, and 12 and 24 h after the administration of carprofen or grapiprant to perform a complete blood count (CBC), the percentage of Heinz bodies and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, creatinine and urea). Urinalysis was performed at baseline and 24 h after extubation. Glucose levels were evaluated at baseline and 1 h postoperatively., Results: Pain scores were not significantly different among groups in both scales, although pain was higher at 3 h in comparison with 24 h in all groups. In the GRA1 and GRA2 groups, 67% (14/21) of cats needed rescue analgesia compared with 18% (2/11) in the CAR group. Glucose increased from baseline to 1 h in the GRA1 and GRA2 groups. None of the CBC, serum biochemistry and urinalysis variables differed among groups., Conclusions and Relevance: Grapiprant did not promote adequate analgesia during the first 3 h postoperatively in cats undergoing ovariohysterectomy compared with carprofen, and no benefits were observed by administering grapiprant every 12 h.

We evaluated the microbial diversity and metabolome profile of an uncommon hypersaline elastic microbial mat from Cuatro Ciénegas Basin (CCB) in the Chihuahuan Desert of Coahuila, México. We collected ten samples on a small scale transect (1.5-m) and described its microbial diversity through NGS-based ITS and 16S rDNA gene sequencing. A very low number of taxa comprised a considerable proportion of the mat and were shared across all sampling points, whereas the rare biosphere was more phylogenetically diverse (Faith's Phylogenetic Diversity (FPD) index) and phylogenetically disperse (using a null model distribution of Phylogenetic Species Clustering (nmdPSC)) than the abundant (high read count) taxa for both analyzed libraries. We also found a distinctive metabolome profile for each sample and were able to tentatively annotate several classes of compounds with relevant biological properties., Competing Interests: Luis E. Eguiarte and Valeria Souza are Academic Editors for PeerJ., (© 2022 Espinosa-Asuar et al.)

Background: Mycobacterium abscessus is increasingly recognized as a human pathogen causing life-threatening infections in immunocompromised patients. There is a paucity of data around this topic in solid organ transplant (SOT) recipients., Methods: This work was a single-center retrospective cohort study of all SOT recipients with a positive culture for M abscessus between 2013 and 2018., Results: A total of 20 patients (55% female) met inclusion criteria, including 1 kidney recipient (5.0%), 2 liver recipients (10.0%), 12 lung recipients (60.0%), 1 heart recipient (5.0%), and 4 combined organ recipients (20.0%). The median time from SOT to infection was 100 days (range, 30-431 days). Thirteen (65.0%) patients (1 kidney, 1 heart, 7 lung, 1 liver, 1 intestine, and 2 multivisceral) were treated with a median duration of 185 antibiotic days (range, 20-523 days). Among them, M abscessus was isolated from respiratory samples in 8 and nonrespiratory samples in 5; 4 of 13 (30.8%) patients had treatment failure and 3 of 13 (23.1%) had unrelated deaths within 1 year after diagnosis. Seven patients (5 lung transplant recipients) with the organism isolated from respiratory samples were not treated as their cultures represented airway colonization or contamination; of those, 2 (28.6%) died (unrelated to infection) and 5 (71.4%) were alive without the infection after 1 year of follow-up., Conclusions: Mycobacterium abscessus infections affect SOT recipients with a high proportion of clinical failures. However, in lung recipients, not all positive cultures correlated with infection, and without treatment some patients had good clinical outcomes. Thus, differentiating colonization from infection is important, and infection prevention measures and novel therapeutic agents are needed for SOT recipients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The occurrence of laryngeal paralysis following endotracheal intubation in dogs is rare. A one-year-old canine was presented with aspiration pneumonia in the postoperative period following general anesthesia for acetabular denervation surgery. After a month of treatment for aspiration pneumonia, the patient had inspiratory stridor and dyspnea, and the diagnosis of unilateral laryngeal paralysis was made through laryngoscopy. Along with the benefits of endotracheal intubation come many risks. Laryngeal paralysis can be a serious complication, predisposing the patient to aspiration. This report is the second in veterinary medicine to describe laryngeal paralysis as a possible complication after endotracheal intubation in a dog., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Invasive aspergillosis is the most common invasive mold infection following a hematopoietic cell transplant. Widespread use of antifungal prophylaxis has led to the increasing incidence of cryptic Aspergillus species. Aspergillus calidoustus is one of those emerging species and is notorious for multidrug resistance to antifungals. Here, we report a case of disseminated A. calidoustus infection in a hematopoietic stem cell transplant recipient who was successfully treated with combination therapy that included a novel antifungal.

The use of haploidentical or HLA-mismatched unrelated donors (MMUD) allows allogeneic hematopoietic cell transplantation in individuals without suitable matched donors. Post-transplantation cyclophosphamide (PTCy) is used routinely for prevention of graft-versus-host disease in recipients of haploidentical transplants, and its use has been recently explored in MMUD transplantation. We compared the incidence of cytomegalovirus (CMV) reactivation and rate of lymphocyte recovery between PTCy MMUD and alternative transplantation modalities. Single-center retrospective study of 22 consecutive PTCy MMUD recipients transplanted between April 2017 and January 2019. Patients undergoing anti-thymocyte globulin (ATG) MMUD (n = 37) and PTCy haploidentical transplantation (n = 19) between January 2015 and July 2018 served as historical controls. We assessed the incidence of CMV (any viremia) and clinically significant CMV reactivation (cs-CMVi; defined as CMV disease or CMV viremia leading to preemptive treatment) in these 3 groups. Immune reconstitution was assessed by absolute lymphocyte count (ALC) at days 30, 90, 180, and 360 after transplantation. Statistical analyses included Kaplan-Meier plots with a log-rank test, Kruskal-Wallis test, and Fisher's exact test where appropriate, and logistic regression analyses. For PTCy MMUD, PTCy haploidentical and ATG MMUD groups, the 100-day and 200-day incidence of CMV (any viremia) were 41%, 63%, and 77% (P = .02), and 64%, 68%, and 86% (P = .049), respectively. The rate of cs-CMVi was also lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (14% versus 53% and 54% at day 100 [P = .01] and 25% versus 53% and 58% at day 200 [P = .03]). There was a trend toward lower 200-day incidence of cs-CMVi in PTCy MMUD compared to ATG MMUD, even after excluding letermovir-treated patients from the analysis (25% versus 58% [P = .06]). The association between PTCy MMUD and lower risk of cs-CMVi remained significant even after adjusting for letermovir prophylaxis (odds ratio = 0.23, 95% confidence interval, 0.07-0.81 [P = .02]). Day 30 ALC was lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (0.14, 0.33, 0.44 × 10 9 /L, respectively [P = .005) but similar across groups at other time points. PTCy MMUD transplantation was associated with lower incidence of CMV events, independent of the use of CMV prophylaxis. Larger studies are needed., Competing Interests: Conflict of interest statement J.F.C. has served as consultant and received honoraria from Merck. K.V.K. has served as an ad hoc consultant to Kite/Gilead, Novartis, Celgene, Atara, Kiadis, Kadmon, Incyte, Gamida Cell, Iovance, Genentech/Roche and Takeda. M.I.M. is a consultant in the medical advisory board of Viracor Eurofins and has received research funding from Merck., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Adenovirus (AdV) is a serious infection following hematopoietic cell transplantation (HCT). Little is known about AdV viral kinetics and optimal threshold for initiation of pre-emptive therapy., Methods: Single-center retrospective study of 16 consecutive adult HCT recipients with detectable AdV identified over a 5-year period., Results: Median time to AdV reactivation after HCT was 176 days (IQR 86-408). Nine patients received cidofovir, although 14/16 had no tissue-invasive disease. Among treated patients, median duration of viremia was shorter when initiating treatment at viral loads < 10,000 copies/ml (28 vs. 52 days). All-cause mortality in this cohort was 44%. All six patients (five of which were untreated) with peak viral loads < 10,000 copies/ml survived; whereas only 30% (3/10) of patients with peak viral loads greater than this threshold survived, despite most (n = 8; 80%) of them receiving cidofovir (P = .01). Three-month survival following diagnosis of AdV viremia was significantly lower with peak viremia > 10,000 copies/ml (100 vs. 17%; P = .005)., Conclusion: AdV is associated with high all-cause mortality, especially for viremia > 10,000 copies/ml. Delaying therapy until viremia reaches AdV levels ≥10,000 copies/ml was associated with more protracted infection and poor outcomes. Larger studies are needed., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To analyze the incidence, complications, and hospital discharge status in newborns with ≥35 weeks of gestational age with early neonatal sepsis., Methods: This is a cross-sectional, retrospective study. Cases of early-onset sepsis registered from January 2016 to December 2019 in neonates with gestational age of 35 weeks or more were reviewed in a level III neonatal unit. The diagnoses were performed based on the criteria by the Brazilian Health Regulatory Agency (Anvisa), and the episodes were classified according to microbiological classification and site of infection. The following complications were evaluated: shock, coagulation disorders, and sequelae of the central nervous system. The conditions at hospital discharge were also assessed. The collected data were analyzed with the descriptive analysis., Results: In the period, early neonatal sepsis occurred in 46 newborns, corresponding to 1.8% of all newborns admitted to the neonatal unit, with a prevalence of 4/1,000 live births. Culture confirmed sepsis ocurred in three patients (0.3/1,000 live births), with the following agents: S. pneumoniae, S. epidermidis and S. agalactiae. As to site of infection, there were 35 cases of primary bloodstream infection, seven cases of pneumonia and four cases of meningitis. Most patients (78.3%) had at least one risk factor for sepsis, and all were symptomatic at admission. There were no deaths. Complications occurred in 28.2% of the cases, especially shock (10 cases - 21.7%)., Conclusions: The prevalence of proven early neonatal sepsis was low. Despite the common occurrence of complications, there were no deaths.

Problem: The utility of the polymerase chain reaction (PCR) cycle threshold (C t ) values in the management of patients with coronavirus disease 2019 (COVID-19) remains controversial., Methods: We assessed the correlation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) C t values in nasopharyngeal swab samples with the oxygen requirements at the time of sample collection. Specimens were tested with the Simplexa PCR platform, which targets the SARS-CoV-2 ORF1ab and S genes., Results: We identified 23 COVID-19 patients with 49 C t values available. While C t values from ORF1ab and S genes were highly correlated for a given specimen, there was no correlation between C t values for any of these target genes and the oxygen requirements of the patient at the time of sample collection. We found no differences in the initial nor the nadir C t values between survivors and non-survivors or mild/moderate versus severe/critical illness at the maximum point of illness., Conclusion: SARS-CoV-2 C t values have limited value in the management of COVID-19., (© 2021 Wiley Periodicals LLC.)

Background: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited., Methods: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Results: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88). Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively. Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01)., Conclusions: Mortality in COVID-19 HCT patients is higher than that of the age-comparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression., (© 2021 Wiley Periodicals LLC.)

Two patients receiving oral etoposide therapy developed Pneumocystis jirovecii pneumonia during chemotherapy with significant lymphopenia without corticosteroid use. In this commentary we discuss cellular mechanisms by which etoposide induced CD4+ T lymphocyte dysfunction and reduced survival may lead to predisposition to P. jirovecii infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

SARS-CoV-2 emerged as a worldwide pandemic in late 2019 and initially was described as a primary respiratory illness. The clinical manifestations of COVID-19 are now known to encompass nearly all organ systems, including the central nervous system. We present a case of an allogeneic hematopoietic stem cell transplant recipient who recovered from documented SARS-CoV-2 infection and later presented with symptoms of meningitis. While cerebrospinal fluid analysis did not reveal any bacterial or viral etiologies, evidence of an inflammatory state, including ophthalmologic findings of episcleritis, indicate what is likely the first reported case of aseptic meningitis associated with SARS-CoV-2 infection after initial clinical recovery., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1 st t October 9 th , 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no competing conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: Coronavirus 2019 (COVID-19) pandemic has resulted in more than 350 000 deaths worldwide. The number of kidney transplants has declined during the pandemic. We describe our deceased donor kidney transplantation (DDKT) experience during the pandemic., Methods: A retrospective study was conducted to evaluate the safety of DDKT during the COVID-19 pandemic. Multiple preventive measures were implemented. Adult patients that underwent DDKT from 3/1/20 to 4/30/20 were included. COVID-19 clinical manifestations from donors and recipients, and post-transplant outcomes (COVID-19 infections, readmissions, allograft rejection, and mortality) were obtained. The kidney transplant (KT) recipients were followed until 5/31/20., Results: Seventy-six patients received kidneys from 57 donors. Fever, dyspnea, and cough were reported in 1, 2, and 1 donor, respectively. Thirty-eight (66.6%) donors were tested for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) prior to donation (mainly by nasopharyngeal or bronchoalveolar lavage polymerase chain reaction [PCR]) and 36 (47.3%) KT recipients were tested at the time of DDKT by nasopharyngeal PCR; all of these were negative. Our recipients were followed for a median of 63 (range: 33-91) days. A total of 42 (55.3%) recipients were tested post-transplant for SARS-CoV2 by nasopharyngeal PCR including 12 patients that became symptomatic; all tests were negative except for one that was inconclusive, but it was repeated and came back negative. Forty (52.6%) KT recipients were readmitted, and 7 (9.2%) had biopsy-proven rejection during the follow-up. None of the KT recipients transplanted during this period died., Conclusions: Our cohort demonstrated that DDKT can be safely performed during the COVID-19 pandemic when preventive measures are implemented., (© 2020 Wiley Periodicals LLC.)

Severe acute respiratory syndrome coronavirus 2 is associated with severe disease in patients with hematologic malignancy. We report a series of patients with underlying hematologic malignancy and coronavirus disease of 2019 with discrepancy between radiographic findings and molecular testing. Initial chest x-ray findings should raise suspicion in immunosuppressed patients with typical clinical presentation even with negative initial testing., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: The burden of urinary tract infections (UTIs) and risk factors for developing infections with multidrug resistant organisms (MDROs) post-kidney transplantation (KT) are poorly understood., Methods: Single-center retrospective cohort study (January 2015-December 2017) evaluating first and recurrent episodes of bacteriuria and subsequent analysis of episodes caused by MDROs up to 6 months post-KT. Donor and recipient variables were reviewed., Results: A total of 743 adults underwent single KT during the study period, and 106 patients were hospitalized with bacteriuria. 45% were asymptomatic in their first episode. 73.6% had a single episode, and 26.4% had 2 or more episodes. A total of 28 patients had recurrent episodes; 64.3% had an MDRO on the first episode and 78.6% on the second episode. Escherichia coli was the most common organism isolated, 88.5% were resistant to trimethoprim-sulfamethoxazole (TMP-SMX), 9.3% were extended-spectrum beta-lactamase (ESBL) producers, and 38.1% were MDROs. Body mass index ≥30 was significantly associated with the presence of MDROs in both univariate and multivariate analyses (RR 1.37, 95% CI 1.01-1.88; OR 3.26, CI 1.29-8.25). A total of 12 donors had bacteremia or bacteriuria and 6 (50%) with E coli. A total of 10 KT recipients received antibiotic prophylaxis to prevent donor-derived infections., Conclusions: Our results suggest that a significant proportion of patients develop recurrent bacteriuria post-transplantation; of those, more than half caused by MDROs. There is a possible association between obesity and MDROs in KT recipients that merits further investigation. With the global crisis in antimicrobial resistance, innovative strategies are needed to prevent and treat UTIs in KT patients., (© 2020 Wiley Periodicals LLC.)

Asthma epidemics have been shown to be related to where soybeans are loaded and handled, but data are scarce in the literature. This pilot study evaluated the levels of Gly m 1 in dust samples collected in Maringá, Brazil, a city with high soy production and processing. A dust impactor was used to collect seven isolated samples during 2015 and 2016. Samples were analyzed by an ELISA (enzyme-linked immunosorbent assay) detection method. Gly m 1 was found in all samples, ranging from 0.82-24.38 ng/m 3 (median 2.41), regardless of the month or year evaluated. The levels of Gly m 1 were considered low, but the concentrations required to cause sensitization and symptoms are uncertain.

Progressive multifocal leukoencephalopathy (PML) remains a life-threatening central nervous system infection in immunocompromised patients. Although outcomes have improved in cases that immune reconstitution is feasible with anti-retroviral therapy (ART) in HIV + patients or natalizumab removal in those with multiple sclerosis, in individuals with hematological malignancies, the prognosis is usually dismal. Anti-viral treatments have been largely ineffective, but immunotherapy-based approaches with checkpoint inhibitors and adoptive virus-specific T cells' transfer are currently explored in clinical trials. PML has not been described as a cause of encephalopathy after CAR T therapy. We report the first case of PML 7 months after lymphodepleting chemotherapy with fludarabine/cyclophosphamide and anti-CD19-directed CAR T therapy in a patient with relapsed diffuse large B-cell lymphoma who relapsed fast after a previous autologous hematopoietic stem cell transplant. She remains alive 12 months after diagnosis with stabilization of her symptoms with a combination of therapies targeting viral replication and immunotherapy.

Aim: This study relates the average number of nucleolar organizing regions (NORs) obtained in a series of cases of oral leukoplakia, with three methods of histopathological classification of such lesion., Materials and Methods: This is a histopathological-histochemical laboratory cross-sectional study. The 18 cases of leukoplakia analyzed were filed at Pathology Service of the Biological Sciences Institute of the University of Passo Fundo, Rio Grande do Sul, Brazil (SDH/ICB/UPF) (2017 and 2018), from which epidemiological data were extracted. New histological sections were performed for impregnation by the argyrophilic nucleolar organizer regions (AgNOR) technique. The histopathological slides were analyzed by photon microscopy (1,000×), and the nuclei of 100 epithelial cells were photographed to count the number of NORs. Three methods were used for the lesions' histopathological classification [World Health Organization (WHO), Brothwell, and binary system]. The means of NORs were compared with the three histopathological classifications by means of the t or analysis of variance (ANOVA) statistical tests, at a significance level of 5%., Results: According to the WHO classification method, most cases (11-61.1%) had a moderate classification. Evaluations by the Brothwell method showed moderate and mild classification in 50 and 38.9% of cases, respectively. According to the binary system, most cases (10-55.6%) had low risk. The average NORs found in 100 nuclei of each of the 18 lesions ranged from 2 to 4. When crossing the average NORs with the histopathological classification methods of the lesions by means of the t test or ANOVA, no significant relationship was noted., Conclusion: The average of NORs is not associated with the histological classifications of leukoplakias. Thus, the AgNOR method should be used with caution when differentiating different histological grades of leukoplakias., Clinical Significance: The AgNOR method should be used with caution to determine the clinical treatment of oral leukoplakias, since no agreement was observed between this method and the histopathological classifications available for such lesion.

Background: Treatment data for latent tuberculosis infection (LTBI) among potential living kidney donors are scarce., Methods: This retrospective study was performed to evaluate the prevalence of positive QuantiFERON-TB Gold In-Tube (QFT-GIT) among potential living kidney donors that were screened from 2009 to 2017. We investigated if there was any difference in the time to donation between QFT-GIT-positive and QFT-GIT-negative donors. We assessed the regimens used to treat LTBI and whether the recipients of QFT-GIT-positive donors developed active tuberculosis (TB)., Results: Forty out of 427 (9%) potential living kidney donors had a positive QFT-GIT. QFT-GIT-positive donors were as likely as negative donors to undergo donation (30 [75%] vs 315 [81%], P = .33). The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors (median 221 days [range: 4-1139] vs 86 days [range: 3-1887], P = .001). Twelve-week rifapentine (RPT)/Isoniazid (INH) was the most common treatment used and was not associated with significant adverse reactions. There was a trend toward longer time to donation among QFT-GIT-positive donors who were treated for LTBI compared with QFT-GIT-positive donors who were not (252 days [range: 88-1139] vs 95 days [range: 4-802], P = .05). Twenty-nine recipients of QFT-GIT-positive living kidney donors were evaluated. Eleven of these recipients received kidneys from donors that were not treated for LTBI. Two of these recipients were treated with INH post-transplantation., Conclusions: The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors. The short-course regimens appear to be excellent options for LTBI treatment among living kidney donors and avoid delaying organ donation further., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Invasive aspergillosis (IA) is the most common invasive fungal infection following a hematopoietic cell transplant, with emerging cryptic species exhibiting resistance to commonly used antifungals such as azoles. These species have been increasingly found after the introduction of anti-mold prophylaxis. We report a case of a 56-year-old female with primary myelofibrosis whose allogeneic hematopoietic cell transplant was complicated by disseminated fungal infection (skin, lung) due to Aspergillus calidoustus, a cryptic specie. Treatment of Aspergillus species remains challenging as these cryptic species are usually resistant to azoles including voriconazole which is the first line of treatment of IA. Infection was successfully treated with surgical excision and combination antifungal therapy based on in vitro susceptibility and synergy testing. Therapy included isavuconazole, a drug that has been shown to be non-inferior to voriconazole in the treatment of invasive mold infections.

Background: The use of preemptive antimicrobial therapy for recipients of donors with microbial growth on pre-transplant urine cultures remains poorly studied., Methods: Single-center retrospective study of kidney transplant recipients of allografts from deceased donors with urine-only (ie, in absence of donor bacteremia) positive cultures (September 2011 to August 2015). Transplant outcomes, including donor-derived infections (DDI) within the first three months post transplant, were analyzed., Results: Of the 970 kidney transplants performed during the study period, urine cultures were obtained from all donors, and of these, 27 (2.8%) yielded growth. Twenty-nine (73%) recipients were treated preemptively after transplantation. All of the recipients of donors with urine cultures positive for Enterococcus, Pseudomonas, or Candida spp. received therapy whereas only one of seven recipients with urine cultures positive for Escherichia coli was treated (P < .0001). All E coli isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), which was given to all patients for Pneumocystis pneumonia (PCP) prophylaxis. Infection within 3 months was evident in 16 (40%) patients: 10 out of 29 (35%) in the preemptive group and 6 out of 11 (55%) in the not-treatment group (P = .29). Evidence of DDI occurred in two recipients, one in each group. There were no differences in one-year graft and patient survival between groups., Conclusion: Preemptive antibiotic therapy did not seem to impact transmission events and transplant outcomes in this small cohort. Low transmission rates might have been influenced by administration of PCP prophylaxis and universal preemptive therapy for positive donor urine cultures with virulent organisms. Larger studies are needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: HIV-positive (HIV+) kidney transplant recipients exhibit a 2- to 3-fold increased risk of allograft rejection. Dysregulated immune activation in HIV infection persists despite successful antiretroviral therapy and is associated with non-AIDS morbidity, including renal disease. We hypothesized that the pathological levels of inflammation and immune activation associated with chronic HIV infection could have clinical utility in the prediction of rejection in HIV+ kidney recipients., Methods: Prospective cohort study of 22 HIV-negative (HIV-; donor) to HIV+ (recipient) kidney transplant recipients who underwent biomarker assessment pretransplant and were subsequently followed for development of acute rejection. Plasma levels of markers of inflammation (soluble tumor necrosis factor receptor 1 [sTNF-R1] and C-reactive protein [CRP]) and microbial translocation (soluble CD14 and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay or chromogenic endpoint assay. Levels of activated (CD38+HLADR+) CD4+ and CD8+ T cells, and T regulatory cells (CD4+CD25highFoxP3+) were measured by flow cytometry., Results: Among the biomarkers evaluated, only the pretransplant levels of sTNF-R1, CRP, and frequencies of CD38+HLADR+ CD8 T cells, were found to be at significantly higher levels among patients who experienced biopsy-proven acute rejection. Confirming our hypothesis, patients with high pretransplant levels of sTNF-R1 or activated CD8+ T cells had a significantly increased 200-day cumulative incidence of biopsy-proven acute rejection (0 vs. 38% for both; P  = 0.01). Similarly, pretransplant CRP levels higher than 5 μg/ml were associated with increased risk of acute rejection within the first 6 months post-transplant (0 vs. 43%; P  = 0.01)., Conclusion: Biomarker-based identification of HIV+ recipients at increased risk for rejection might facilitate individualized induction immunosuppression regimens in this vulnerable patient population., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)

Background: Cell-free DNA (cfDNA) sequencing has emerged as an effective laboratory method for rapid and noninvasive diagnosis in prenatal screening testing, organ transplant rejection screening, and oncology liquid biopsies.  Methods: Here we report our experience using next-generation sequencing (NGS) for detection of microbial cfDNA in a cohort of ten immunocompromised patients with febrile neutropenia or deep-seated infection.  Results: Among five hematological malignancy patients, for whom a microbiological diagnosis was established, pathogen identification by cfDNA NGS demonstrated 100% positive agreement with conventional diagnostic laboratory methods. Further, cfDNA identified the etiological agent in two patients with culture negative sepsis who had undergone hematopoietic stem cell transplant. Conclusion: These data support the clinical utility of measurement of microbial cfDNA sequencing from peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts. Larger studies are needed., Competing Interests: Competing interests: Karius, Inc. ran the tests on the clinical specimens for these 10 patients at no charge to our institution., (Copyright: © 2019 Camargo JF et al.)

Background: Vancomycin-resistant enterococci are an important cause of healthcare-associated infections and are inherently resistant to many commonly used antibiotics. Linezolid is the only drug currently approved by the US Food and Drug Administration to treat vancomycin-resistant enterococci; however, resistance to this antibiotic appears to be increasing. Although outbreaks of linezolid- and vancomycin-resistant Enterococcus faecium (LR-VRE) in solid organ transplant recipients remain uncommon, they represent a major challenge for infection control and hospital epidemiology., Methods: We describe a cluster of 4 LR-VRE infections among a group of liver and multivisceral transplant recipients in a single intensive care unit. Failure of treatment with linezolid in 2 cases led to a review of standard clinical laboratory methods for susceptibility determination. Testing by alternative methods including whole genome sequencing (WGS) and a comprehensive outbreak investigation including sampling of staff members and surfaces was performed., Results: Review of laboratory testing methods revealed a limitation in the VITEK 2 system with regard to reporting resistance to linezolid. Linezolid resistance in all cases was confirmed by E-test method. The use of WGS identified a resistant subpopulation with the G2376C mutation in the 23S ribosomal RNA. Sampling of staff members' dominant hands as well as sampling of surfaces in the unit identified no contaminated sources for transmission., Conclusions: This cluster of LR-VRE in transplant recipients highlights the possible shortcomings of standard microbiology laboratory methods and underscores the importance of WGS to identify resistance mechanisms that can inform patient care, as well as infection control and antibiotic stewardship measures., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Data on bloodstream infection (BSI) due to enteric organisms are scarce., Methods: This retrospective study (1/2009-5/2017) was aimed to evaluate the incidence of BSI episodes due to enteric organisms during the first 6 months after intestinal transplant (ITx). Differences between the first (2009-2012) and second period (2013-2017) were evaluated as they differed from each other in the perioperative fungal prophylaxis and immunosuppressive regimen., Results: Fifty-five adult patients were analyzed. Twenty-eight (51%) patients developed a total of 51 episodes of BSI. Mean time from transplant to BSI was 85.5 ± 58.8 days. The most common organisms were Klebsiella pneumoniae (33%), Enterococcus spp (31%), and Candida spp (18%). Twenty-three (45%) were multidrug resistant. The most common sources were gut translocation (35%), central line infection (20%), and intra-abdominal abscess (14%). Biopsy-proven rejection was associated with 16 (31%) of the BSI episodes. Patients during the first period were more likely to develop BSI (79% vs 41%, P = 0.03). There were more episodes of rejection associated with BSI in the first period (45% vs 14%, P = 0.03). The rate of reoperation into the abdominal cavity within 2 weeks after ITx was higher and the transplant hospital stay was longer among those who developed BSI (P = 0.04 for both)., Conclusions: Half of our patients developed BSI (typically during the first 3 months). Gut translocation was the most common source of BSI. Patients with rejection and/or enteritis should be monitored closely for BSI., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Previous studies have demonstrated inferior patient and graft survival following kidney transplant (KT) in HIV+/HCV+ coinfected patients compared to HIV+/HCV- recipients. However, these studies were conducted prior to the availability of direct-acting antiviral (DAA) agents and data in the modern era are lacking., Methods: Single center retrospective study of HIV+/HCV+ coinfected KT recipients (2007-2017). Outcomes were assessed for the pre-DAA and post-DAA (ie, after December 2013) eras including 1-year patient survival, death-censored graft survival, and acute rejection; and serious infections (defined as infections requiring admission to the intensive care unit during initial transplant hospitalization or re-admission to the hospital after discharge) within the first 6 months post-transplant., Results: A total of 13 consecutive HIV+/HCV+ recipients were identified. Median time of post-transplant follow-up was 722 days. Seven patients were transplanted in the DAA era; five of them had anti-HCV Ab+ donors, with two donors being HCV NAT positive; all received DAA therapy, six of them post-transplant (median time from KT to DAA: 83 days; IQR, 54-300). All the patients in the pre-DAA era were on a protease inhibitor-containing ART regimen. One-year patient and death-censored graft survivals were 83% and 67%, respectively, for the patients transplanted in the pre-DAA era, and 100% for both outcomes in the subgroup of patients transplanted in the post-DAA era (P > 0.05). Compared to patients in the post-DAA era, those in the pre-DAA era had higher incidence of serious infections (0 vs 67%; P = 0.02). Acute rejection exclusively occurred in the pre-DAA group (n = 1; 17%)., Conclusions: Outcomes of HIV+/HCV+ KT recipients, including HIV-/HCV+ to HIV+/HCV+ transplants, in the DAA era were excellent in this small cohort. Larger studies are needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Strongyloides stercoralis infects 100 million people worldwide. Mortality rates in hyperinfection syndrome exceed 50%. Donor-derived Strongyloides infection has occurred after heart, kidney, kidney-pancreas and liver transplantation; yet, only 10% of the US organ procurement organizations currently screen donors for strongyloidiasis., Methods: We report a fatal case of donor-derived disseminated Strongyloides infection in a liver transplant recipient. Following this case, we implemented universal screening and treatment of donors and recipients. We reviewed our local epidemiology and outcomes after protocol implementation., Results: From a total of 355 deceased donors accepted at our center between January 2016, and March 2018, 14 (3.9%) had positive Strongyloides serology. Except for the index case, all other recipients of Strongyloides antibody-positive donors within that period (including 10 kidneys, 3 livers, one combined liver/kidney, and one kidney/pancreas from eight seropositive donors) received post-transplant prophylaxis with ivermectin, and to date are alive and doing well without signs of infection. Between October 2015, and September 2016, a total of 441 deceased donor solid organ transplants were performed at our center. 220 of these recipients had pretransplant Strongyloides serology available, and 23 of them were seropositive (10.5%). Within the first two years after the implementation of universal screening and treatment of donors and recipients, we had no cases of Strongyloides reactivation in our center., Conclusions: Implementation of a Strongyloides screening and treatment protocol in our center was an effective strategy to prevent both recipient- and donor-derived strongyloidiasis. Transplant centers should consider implementation of Strongyloides preventive strategies., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cytomegalovirus (CMV) infection is the most common infection following hematopoietic cell transplantation (HCT). Preemptive antiviral therapy is highly effective at halting viral replication and preventing CMV disease; however, recurrence rates after clearance of CMV DNAemia are high (50-70%). Current treatment guidelines recommend maintenance therapy after initial clearance. Yet, the effectiveness of this intervention to prevent recurrence is not well defined., Objectives: We aimed to assess the impact of maintenance therapy on the probability of recurrent CMV in allogeneic HCT recipients with early CMV reactivation., Study Design: Sixty-six patients with an initial episode of early CMV reactivation who achieved viral clearance in response to preemptive therapy were included. We compared the incidence of recurrent CMV DNAemia in patients who received maintenance therapy vs those who underwent early discontinuation of antiviral therapy., Results: Recurrence occurred in 47/64 (73%) patients, including 11/14 (79%) patients without maintenance therapy and 36/50 (72%) of patients who received maintenance therapy (P = 0.74). The propensity score adjusted risk ratio for the effect of maintenance therapy on recurrence was 0.89 (95% CI 0.64-1.25; P = 0.41). In a time to event analysis using the unweighted cohort, the 90-day probability of CMV recurrence was similar between patient groups independent of maintenance therapy administration (54% vs 64% for maintenance vs non-maintenance groups, respectively; log-rank P = 0.37)., Conclusion: These data suggest that maintenance antiviral therapy does not reduce the incidence of CMV recurrence while off therapy and is of limited value in HCT recipients who have successfully eradicated CMV DNAemia in response to preemptive therapy. Larger studies in this area are needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)