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BACKGROUND: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).
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Infección Irruptiva , Infecciones por VIH , Fallo Renal Crónico , Trasplante de Riñón , Donantes de Tejidos , Obtención de Tejidos y Órganos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección Irruptiva/epidemiología , Infección Irruptiva/inmunología , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Obtención de Tejidos y Órganos/métodos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapiaRESUMEN
The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.
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Trasplante de Hígado , Listas de Espera , Humanos , Trasplante de Hígado/normas , Estados Unidos , Cuidados Preoperatorios/normas , Cuidados Preoperatorios/métodos , Técnica Delphi , Indicadores de Calidad de la Atención de SaludRESUMEN
Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.
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Infecciones Comunitarias Adquiridas , Neumonía , Guías de Práctica Clínica como Asunto , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Humanos , Estados Unidos , Neumonía/diagnóstico , Neumonía/terapia , Neumonía/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
In this case, a 64-year-old male with a history of simultaneous orthotopic liver transplant and cadaveric renal transplant presented five years prior presented with persistent fevers two days after a positive SARS-CoV-2 nasal PCR. A CT scan of the chest on hospital day nine revealed innumerable 1-2 mm nodules in a miliary pattern throughout the lung. (1,3)-ß-D-glucan on hospital day 11 was 133 pg/mL. In this article, the approach, diagnostic and management strategies for patients with persistent fevers after diagnosis of COVID-19 in a transplant recipient are discussed.
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COVID-19 , Fiebre , Trasplante de Riñón , Trasplante de Hígado , SARS-CoV-2 , Humanos , Masculino , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , COVID-19/diagnóstico , COVID-19/complicaciones , Persona de Mediana Edad , Fiebre/etiología , Receptores de Trasplantes , Tomografía Computarizada por Rayos X , beta-Glucanos/sangre , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/virologíaRESUMEN
Transplant infectious disease (TID) clinicians are integral to the pre-transplantation evaluation. Pre-transplant evaluations allow clinicians to assess risk factors for latent infections and relevant exposures to potential pathogens, address immunizations, and optimize patients' health and understanding of life after transplant. However, there is not a standardized approach to the pre-transplant evaluation. This article reviews the details of performing successful pre-transplant evaluations, including updated recommendations on available vaccines and contemporary opinions on marijuana use. This resource can be used for teaching with trainees or for early career TID clinicians.
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Enfermedades Transmisibles , Trasplante de Órganos , Humanos , Trasplante de Órganos/efectos adversos , Factores de Riesgo , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/normasRESUMEN
BACKGROUND: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. METHODS: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T-cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre-defined criteria. A cost analysis of diagnostic testing was performed. RESULTS: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1-year post-transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. CONCLUSION: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings.
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Huésped Inmunocomprometido , Receptores de Trasplantes , Humanos , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Receptores de Trasplantes/estadística & datos numéricos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anciano , Trasplante de Órganos/efectos adversos , Incidencia , Mycoplasma pneumoniae/inmunología , Mycoplasma pneumoniae/aislamiento & purificación , Bordetella pertussis/inmunología , Bordetella pertussis/aislamiento & purificación , Chlamydophila pneumoniae/inmunología , Connecticut/epidemiologíaRESUMEN
BACKGROUND: Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear. METHODS: We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30-day mortality. RESULTS: Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5 vs. 65; p = .035) and longer duration between vaccination and symptom onset (114 vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9 vs. 42.5 h) and to resolution of fever (21.6 vs. 26.6 h). There were no differences in secondary outcomes. CONCLUSION: Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.
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Dibenzotiepinas , Gripe Humana , Morfolinas , Piridonas , Tiepinas , Triazinas , Adulto , Humanos , Oseltamivir/uso terapéutico , Gripe Humana/tratamiento farmacológico , Estudios Retrospectivos , Oxazinas/uso terapéutico , Piridinas/uso terapéutico , Tiepinas/efectos adversos , Antivirales/uso terapéutico , Huésped Inmunocomprometido , HipoxiaRESUMEN
PURPOSE: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. METHODS: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. RESULTS: Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. CONCLUSIONS: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.
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Suero Antilinfocítico , Rechazo de Injerto , Supervivencia de Injerto , Infecciones por VIH , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Adulto , Persona de Mediana Edad , Suero Antilinfocítico/uso terapéutico , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Antirretrovirales/uso terapéutico , Quimioterapia de Inducción/métodos , Receptores de Trasplantes/estadística & datos numéricos , Resultado del Tratamiento , Terapia de Inmunosupresión/métodosRESUMEN
The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.
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Infecciones por VIH , Seropositividad para VIH , Trasplante de Hígado , Humanos , Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/tratamiento farmacológico , Provirus , Carga Viral , Latencia del VirusRESUMEN
BACKGROUND: Testing and treatment for latent tuberculosis infection (LTBI) can mitigate risk of active tuberculosis (TB) post-liver transplant (LT). Testing and treatment completion rates have been reported low in this population. Our study aims to quantify the proportion of LT candidates who completed LTBI care cascade in our center. METHODS: A retrospective chart review was conducted on LT candidates from 2012 to 2021. Primary outcome was the proportion of patients who completed each cascade stage. Secondary outcome was an analysis of factors associated with positive and indeterminate LTBI testing. RESULTS: Of the 273 LT candidates, 265 (97.1%) were referred to transplant infectious disease (TID), 264 (96.7%) had orders for interferon-gamma release assay (IGRA), 262 (96%) underwent TID evaluation, and 259 (94.9%) completed IGRA. Twenty had LTBI, and 18 were treatment naïve and recommended for treatment. Of the 18, 15 (83.3%) agreed to therapy, 14 (77.8%) initiated treatment, and 12 (66.7%) completed treatment. No posttransplant TB reactivation occurred. Patients born in Asia, previous incarceration, past military service, and granuloma findings on chest imaging were likely to have positive IGRA (p < .05). Older age and travel to TB-endemic countries were likely to have indeterminate IGRA (p < .05). Indeterminate IGRAs were more common in QuantiFERON (QTF)-Gold Plus TB (15.3%) versus QTF-Gold TB (9.3%, p < .001). CONCLUSIONS: High rates of LTBI testing and treatment initiation and completion can be attributed to a standardized process that includes TID evaluation. Future studies in larger cohort are needed to better understand factors that can optimize the completion rates of LTBI treatment in LT candidates.
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Tuberculosis Latente , Trasplante de Hígado , Tuberculosis , Humanos , Tuberculosis Latente/epidemiología , Estudios Retrospectivos , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis/complicaciones , Oro , Prueba de TuberculinaRESUMEN
BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.
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Trasplante de Riñón , Pneumocystis carinii , Neumonía por Pneumocystis , Brotes de Enfermedades , Humanos , Trasplante de Riñón/efectos adversos , Tipificación de Secuencias Multilocus , Pneumocystis carinii/genética , Neumonía por Pneumocystis/microbiología , Receptores de Trasplantes , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.
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Infecciones por VIH , Seropositividad para VIH , Antirretrovirales/uso terapéutico , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Seropositividad para VIH/tratamiento farmacológico , Humanos , Integrasas , Estudios Prospectivos , Donantes de Tejidos , Estados Unidos/epidemiología , Carga ViralRESUMEN
INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.
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The SARS-CoV-2 pandemic continues to place a substantial burden on healthcare systems. Outpatient therapies for mild-to-moderate disease have reduced hospitalizations and deaths in clinical trials, but the real-world effectiveness of monoclonal antibodies and oral antiviral agents in solid organ transplant recipients (SOTR) with coronavirus disease-2019 (COVID-19) is largely uncharacterized. We conducted a single-center, retrospective review of 122 SOTR diagnosed with COVID-19 in the outpatient setting during the Omicron surge to address this knowledge gap. The mean age was 54 years, 57% were males, and 67% were kidney transplant recipients. The mean time from transplant to COVID-19 diagnosis was 75 months. Forty-nine (40%) received molnupiravir, 24 (20%) received sotrovimab, and 1 (0.8%) received nirmatrelvir/ritonavir. No outpatient therapy was administered in 48 (39%). All 122 SOTR had >30 days follow-up. Rates of hospitalization within 30 days of initiating therapy for molnupiravir, nirmatrelvir/ritonavir, and sotrovimab were 16% (8/49), 0% (0/1), and 8% (2/24), respectively, compared to 27% (13/48) in patients without outpatient therapy. There were no deaths in those who received any therapy versus 3 (6%) deaths in patients without outpatient therapy (p = .002). Overall, our experience suggests a role for monoclonal antibodies and oral antiviral agents in reducing COVID-19-related morbidity and mortality in SOTR.
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COVID-19 , Trasplante de Órganos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes , Antivirales/uso terapéutico , COVID-19/epidemiología , Prueba de COVID-19 , Citidina/análogos & derivados , Femenino , Humanos , Hidroxilaminas , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , Ritonavir , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
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COVID-19 , Trasplante de Órganos , Humanos , Trasplante de Órganos/efectos adversos , Pandemias , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
INTRODUCTION: The impact of SARS-CoV-2 in rare disease populations has been underreported. Gaucher disease (GD) is a prototype rare disease that shares with SARS-CoV-2 a disruption of the lysosomal pathway. MATERIALS-METHODS: Retrospective analysis of 11 patients with Type 1 GD who developed COVID-19 between March 2020 and March 2021. RESULTS: Seven male and 4 female patients with Type 1 GD developed COVID-19. One was a pediatric patient (8 years old) while the remainder were adults, median age of 44 years old (range 21 to 64 years old). Two patients required hospitalization though none required intensive care or intubation. All 11 patients recovered from COVID-19 and there were no reported deaths. CONCLUSIONS: Our case series suggests that GD patients acquired COVID-19 at a similar frequency as the general population, though experienced a milder overall course despite harboring underlying immune system dysfunction and other known co-morbidities that confer high risk of adverse outcomes from SARS-CoV-2 infection.
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COVID-19/inmunología , Enfermedad de Gaucher/inmunología , Enfermedad de Gaucher/virología , Sistema Inmunológico/inmunología , Enfermedades Raras/inmunología , SARS-CoV-2/inmunología , Adulto , COVID-19/virología , Niño , Comorbilidad , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Solid organ transplant recipients (SOTRs) are at disproportionate risk for severe Coronavirus Disease 2019 (COVID-19). Vaccination is a key preventative strategy but is associated with decreased humoral responses among SOTR. Whether dampened immune responses correlate with reduced clinical effectiveness is unclear. Our study was designed to evaluate the clinical effectiveness of SARS-CoV-2 vaccination in the early vaccine era. METHODS: We conducted a retrospective cohort study comparing SARS-CoV-2 infection rates between SOTRs who received two doses of mRNA or one dose of Ad26.Cov2.S vaccine and those not fully vaccinated (partially vaccinated and unvaccinated). To evaluate clinical effectiveness of vaccine, cause-specific Cox regression model and modified Poisson regression model were built using the propensity score-matched cohort. Additionally, the clinical outcomes of COVID-19 of fully vaccinated and not fully vaccinated SOTR were compared. RESULTS: Of 2705 SOTRs, 1668 were included in our final matched analysis, which showed a 73% reduction of SARS-CoV-2 infection and 76% reduction of all-cause-mortality among fully vaccinated patients. Thirty-nine SOTRs developed SARS-CoV-2 infection, including nine fully vaccinated and 30 not fully vaccinated. Among fully vaccinated patients, 22% had severe/critical COVID-19 and 0% mortality versus not fully vaccinated SOTRs, of whom 37% had severe/critical COVID-19 and 6.67% COVID-19-related mortality. CONCLUSION: In SOTRs, completion of primary vaccine series in the early vaccine era was associated with a significant reduction of COVID-19 and was protective against severe/critical disease and death. Further studies are needed to evaluate the clinical effectiveness of current vaccine recommendations for SOTR against emerging new variants.
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Vacunas contra la COVID-19 , COVID-19 , Trasplante de Órganos , Ad26COVS1 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Trasplante de Órganos/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , SARS-CoV-2 , Receptores de Trasplantes , Resultado del Tratamiento , Vacunas ViralesRESUMEN
In this inaugural clinicopathological conference, the invited experts discussed the diagnostic approach to central nervous system infections in immunocompromised hosts. The case presented involved a pancreas-kidney transplant recipient with multiple brain abscesses caused by Bartonella henselae. CSF metagenomic next-generation sequencing played a significant role in the diagnosis. Bartonella henselae is a gram-negative zoonotic pathogen that causes cat-scratch disease, which can be transmitted to humans through cat bites or scratches. Symptoms can vary in severity, correlating with the patient's immune status. Visceral organ involvement, ocular involvement, and neurological manifestations have been reported in immunocompromised patients, but brain abscesses are rare.
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Bartonella henselae , Enfermedad por Rasguño de Gato , Bartonella henselae/genética , Encéfalo/diagnóstico por imagen , Enfermedad por Rasguño de Gato/diagnóstico , Humanos , Huésped InmunocomprometidoRESUMEN
INTRODUCTION: Candidiasis is the most common invasive fungal infection in solid organ transplant recipients, and liver transplant (LT) recipients are at heightened risk. We hypothesized that pre-transplant screening for azole non-susceptible Candida (ANSC) allows for tailored antifungal prophylaxis to reduce the incidence of post-LT ANSC infection. METHODS: We performed a retrospective chart review of adult (age ≥18 years) patients who underwent LT at Yale New Haven Hospital from April 2019 to March 2021. Screening for ANSC, defined as Candida glabrata or Candida krusei, was performed using a rectal swab prior to or at the time of LT. RESULTS: During the study period, ANSC screening was performed in 47 patients who underwent a total of 48 LTs, with 46/48 (96%) primary LTs and two re-transplantations. Ten of 48 screened cases (21%) had ANSC-positive rectal swabs. Only seven of 10 ANSC-colonized patients received appropriate antifungal prophylaxis (i.e., anidulafungin), and one of these seven patients developed candidemia within 30 days of LT. The median number of candidiasis risk factors was one, and 29% of the cohort had two or more risk factors. DISCUSSION: Routine ANSC screening of LT candidates may assist in selecting appropriate antifungal prophylaxis but may be insufficient to prevent infection in those with multiple risk factors for Candida infection.
Asunto(s)
Candida , Trasplante de Hígado , Adolescente , Adulto , Antifúngicos/uso terapéutico , Azoles/uso terapéutico , Humanos , Trasplante de Hígado/efectos adversos , Estudios RetrospectivosRESUMEN
Mycobacterium tuberculosis can be transmitted via organ donation and result in severe outcomes. To better understand donor-derived tuberculosis (DDTB), all potential transmissions reported to the Organ Procurement and Transplantation Network (OPTN) Ad Hoc Disease Transmission Advisory Committee between 2008 and 2018 were analyzed. Among 51 total reports, nine (17%) (9 donors/35 recipients) had ≥ 1 recipient with proven/probable disease transmission. Of these, eight were reported due to recipient disease, and one was reported due to a positive donor result. Proven/probable DDTB transmissions were reported in six lung and five nonlung recipients. The median time to diagnosis was 104 days posttransplant (range 0-165 days). Pulmonary TB, extrapulmonary TB, pulmonary plus extrapulmonary TB, and asymptomatic TB infection with positive interferon-gamma release assay were present in five, three, one, and two recipients, respectively. All recipients received treatment and survived except for one whose death was not attributed to TB. All donors associated with proven/probable DDTB had ≥ 1 TB risk factor. Six were born in a TB-endemic country, five had traveled to a TB-endemic country, three had been incarcerated, and three had latent TB infection. These cases highlight the importance of evaluating donors for TB based on risk factors. Early posttransplant TB in organ recipients of donors with TB risk factors requires prompt reporting to OPTN to identify other potential affected recipients and implement timely treatment interventions.