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Mycoplasma hominis and Ureaplasma species are urogenital mollicutes that can cause serious donor-derived infections in lung transplant recipients. Best practices for mollicute screening remain unknown. We conducted a single-center prospective study analyzing lung transplants performed from October 5, 2020, to September 25, 2021, whereby donor and recipient bronchoalveolar lavage (BAL) samples obtained at time of transplant underwent mollicute screening via culture and polymerase chain reaction (PCR). Of 115 total lung transplants performed, 99 (86%) donors underwent combined mollicute BAL culture and PCR testing. The study cohort included these 99 donors and their matched recipients. In total, 18 (18%) of 99 donors screened positive via culture or PCR. Among recipients, 92 (93%) of 99 had perioperative BAL screening performed, and only 3 (3%) had positive results. After transplant, 9 (9%) recipients developed mollicute infection. Sensitivity of donor screening in predicting recipient mollicute infection was 67% (6/9) via culture and 56% (5/9) via PCR. Positive predictive value for donor culture was 75% (6/8), compared with 33% (5/15) for PCR. Donor screening via culture predicted all serious recipient mollicute infections and had better positive predictive value than PCR; however, neither screening test predicted all mollicute infections. Independent of screening results, clinicians should remain suspicious for posttransplant mollicute infection.
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Mollicute infections, caused by Mycoplasma and Ureaplasma species, are serious complications after lung transplantation; however, understanding of the epidemiology and outcomes of these infections remains limited. We conducted a single-center retrospective study of 1156 consecutive lung transplants performed from 2010-2019. We used log-binomial regression to identify risk factors for infection and analyzed clinical management and outcomes. In total, 27 (2.3%) recipients developed mollicute infection. Donor characteristics independently associated with recipient infection were age ≤40 years (prevalence rate ratio [PRR] 2.6, 95% CI 1.0-6.9), White race (PRR 3.1, 95% CI 1.1-8.8), and purulent secretions on donor bronchoscopy (PRR 2.3, 95% CI 1.1-5.0). Median time to diagnosis was 16 days posttransplant (IQR: 11-26 days). Mollicute-infected recipients were significantly more likely to require prolonged ventilatory support (66.7% vs 21.4%), undergo dialysis (44.4% vs 6.3%), and remain hospitalized ≥30 days (70.4% vs 27.4%) after transplant. One-year posttransplant mortality in mollicute-infected recipients was 12/27 (44%), compared to 148/1129 (13%) in those without infection (P <.0001). Hyperammonemia syndrome occurred in 5/27 (19%) mollicute-infected recipients, of whom 3 (60%) died within 10 weeks posttransplant. This study highlights the morbidity and mortality associated with mollicute infection after lung transplantation and the need for better screening and management protocols.
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Transplante de Pulmão , Mycoplasma , Infecções por Ureaplasma , Humanos , Adulto , Estudos Retrospectivos , Infecções por Ureaplasma/epidemiologia , Infecções por Ureaplasma/etiologia , Infecções por Ureaplasma/diagnóstico , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Fatores de RiscoRESUMO
OBJECTIVE: To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs. METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.
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Anticorpos Monoclonais , Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Administração Oral , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/tratamento farmacológico , Topiramato/administração & dosagem , Topiramato/farmacologia , Ácido Valproico/administração & dosagem , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: Flushing is a common dermatologic complaint and can be resistant to many treatments. As the utility of botulinum toxin continues to expand, recent data suggest that it may also be a therapeutic option for flushing. OBJECTIVE: To evaluate the efficacy of botulinum toxin for the treatment of cutaneous flushing. MATERIALS AND METHODS: A systematic search of Medline, Embase, Cochrane CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted to identify studies evaluating the effect of botulinum toxin on flushing 1 month after treatment. Prespecified outcome measures included a clinical flushing score, dermatology life quality index (DLQI), and erythema index (EI). Meta-analysis was performed to calculate the mean differences in these outcomes before and after treatment at 1-month follow-up. RESULTS: Nine studies (132 patients) were included in the analysis of this study (2 randomized controlled trials and 7 nonrandomized studies). All studies had a low risk of bias (high quality). The most frequent outcome reported was a clinical flushing score, which significantly decreased by 1.25 points overall (95% confidence interval [CI]: -2.47; -0.04) 1 month after treatment with botulinum toxin. Mean DLQI scores decreased (i.e., improved) by 9.02 points (95% CI: -19.81; 1.77) 1 month after botulinum toxin injections. The EI (measured by Mexameter) before and after botulinum toxin was evaluated in 2 studies; however, not enough statistical information was provided to analyze with meta-analytic techniques. CONCLUSION: Based on this meta-analysis, botulinum toxin significantly improves clinical flushing scores 1 month after treatment.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Humanos , Administração Cutânea , Eritema/tratamento farmacológico , Rubor/induzido quimicamente , Fármacos Neuromusculares/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Controlados não Aleatórios como AssuntoRESUMO
PURPOSE OF REVIEW: In the era of HIV treatment as prevention (TasP), more clarity is needed regarding whether people with HIV who use stimulants (i.e., methamphetamine, powder cocaine, and crack cocaine) display elevated HIV viral load and greater immune dysregulation. RECENT FINDINGS: Although rates of viral suppression have improved in the TasP era, stimulant use was independently associated with elevated viral load in 23 of 28 studies included in our review. In the 12 studies examining other HIV disease markers, there was preliminary evidence for stimulant-associated alterations in gut-immune dysfunction and cellular immunity despite effective HIV treatment. Studies generally focused on documenting the direct associations of stimulant use with biomarkers of HIV pathogenesis without placing these in the context of social determinants of health. Stimulant use is a key barrier to optimizing the effectiveness of TasP. Elucidating the microbiome-gut-brain axis pathways whereby stimulants alter neuroimmune functioning could identify viable targets for pharmacotherapies for stimulant use disorders. Examining interpersonal, neighborhood, and structural determinants that could modify the associations of stimulant use with biomarkers of HIV pathogenesis is critical to guiding the development of comprehensive, multi-level interventions.
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Estimulantes do Sistema Nervoso Central , Infecções por HIV , Humanos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Biomarcadores , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína Crack/efeitos adversos , Infecções por HIV/patologia , Metanfetamina/efeitos adversosRESUMO
BACKGROUND: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. METHODS: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94 IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. CONCLUSIONS: Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.
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Cirrose Hepática Biliar , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/efeitos adversos , Bezafibrato/efeitos adversos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Qualidade de Vida , Quimioterapia Combinada , Colagogos e Coleréticos/efeitos adversosRESUMO
We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.
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Lesão Pulmonar Aguda , Transplante de Pulmão , Pneumonia , Adulto , Humanos , Estudos Prospectivos , Prognóstico , Estudos Retrospectivos , Transplante de Pulmão/efeitos adversos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Pulmão , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/patologia , Fatores de Risco , Estudos de CoortesRESUMO
Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.
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Doença Enxerto-Hospedeiro , Transplante de Pulmão , Aloenxertos , Biomarcadores , Quimiocina CXCL10 , Quimiocina CXCL9 , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Estudos ProspectivosRESUMO
PURPOSE OF REVIEW: Patterns of sexualized drug use, including stimulants (e.g., methamphetamine) and chemsex drugs, are key drivers of HIV incidence among sexual minority men (SMM). Although pre-exposure prophylaxis (PrEP) mitigates HIV risk, there is no consensus regarding the associations of substance use with the PrEP care continuum. RECENT FINDINGS: SMM who use substances are as likely or more likely to use PrEP. Although SMM who use stimulants experience greater difficulties with daily oral PrEP adherence, some evidence shows that SMM who use stimulants or chemsex drugs may achieve better adherence in the context of recent condomless anal sex. Finally, SMM who use substances may experience greater difficulties with PrEP persistence (including retention in PrEP care). SMM who use stimulants and other substances would benefit from more comprehensive efforts to support PrEP re-uptake, adherence, and persistence, including delivering behavioral interventions, considering event-based dosing, and providing injectable PrEP.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Corrida , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Fármacos Anti-HIV/uso terapêutico , Continuidade da Assistência ao Paciente , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Comportamento SexualRESUMO
We present the case of a 41-year-old female who underwent bilateral lung transplantation after the donor lungs were placed on a normothermic ex vivo lung perfusion and ventilation device and flown nearly 5000 miles from Honolulu, Hawaii to Durham, North Carolina. The patient experienced no primary graft dysfunction. One year after transplantation she has remained rejection-free and exhibits excellent pulmonary function. This case highlights the challenge that active organ preservation systems pose to questions of organ allocation and geographic sharing.
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Transplante de Pulmão , Disfunção Primária do Enxerto , Obtenção de Tecidos e Órgãos , Adulto , Feminino , Humanos , Pulmão , North Carolina , Preservação de Órgãos , Perfusão , Doadores de TecidosRESUMO
The histopathologic diagnosis of acute allograft injury is prognostically important in lung transplantation with evidence demonstrating a strong and consistent association between acute rejection (AR), acute lung injury (ALI), and the subsequent development of chronic lung allograft dysfunction (CLAD). The pathogenesis of these allograft injuries, however, remains poorly understood. CXCL9 and CXCL10 are CXC chemokines induced by interferon-γ and act as potent chemoattractants of mononuclear cells. We hypothesized that these chemokines are involved in the mononuclear cell recruitment associated with AR and ALI. We further hypothesized that the increased activity of these chemokines could be quantified as increased levels in the bronchoalveolar lavage fluid. In this prospective multicenter study, we evaluate the incidence of histopathologic allograft injury development during the first-year post-transplant and measure bronchoalveolar CXCL9 and CXCL10 levels at the time of the biopsy. In multivariable models, CXCL9 levels were 1.7-fold and 2.1-fold higher during AR and ALI compared with "normal" biopsies without histopathology. Similarly, CXCL10 levels were 1.6-fold and 2.2-fold higher during these histopathologies, respectively. These findings support the association of CXCL9 and CXCL10 with episodes of AR and ALI and provide potential insight into the pathogenesis of these deleterious events.
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Quimiocina CXCL10 , Rejeição de Enxerto , Aloenxertos , Quimiocina CXCL9 , Rejeição de Enxerto/etiologia , Pulmão , Estudos ProspectivosRESUMO
BACKGROUND: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods. METHODS: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis. RESULTS: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1). CONCLUSIONS: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.
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Crowdsourcing , Estudos Transversais , Humanos , Programas de Rastreamento , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
Rationale: Acute rejection, manifesting as lymphocytic inflammation in a perivascular (acute perivascular rejection [AR]) or peribronchiolar (lymphocytic bronchiolitis [LB]) distribution, is common in lung transplant recipients and increases the risk for chronic graft dysfunction.Objectives: To evaluate clinical factors associated with biopsy-proven acute rejection during the first post-transplant year in a present-day, five-center lung transplant cohort.Methods: We analyzed prospective diagnoses of AR and LB from over 2,000 lung biopsies in 400 newly transplanted adult lung recipients. Because LB without simultaneous AR was rare, our analyses focused on risk factors for AR. Multivariable Cox proportional hazards models were used to assess donor and recipient factors associated with the time to the first AR occurrence.Measurements and Main Results: During the first post-transplant year, 53.3% of patients experienced at least one AR episode. Multivariable proportional hazards analyses accounting for enrolling center effects identified four or more HLA mismatches (hazard ratio [HR], 2.06; P ≤ 0.01) as associated with increased AR hazards, whereas bilateral transplantation (HR, 0.57; P ≤ 0.01) was associated with protection from AR. In addition, Wilcoxon rank-sum analyses demonstrated bilateral (vs. single) lung recipients, and those with fewer than four (vs. more than four) HLA mismatches demonstrated reduced AR frequency and/or severity during the first post-transplant year.Conclusions: We found a high incidence of AR in a contemporary multicenter lung transplant cohort undergoing consistent biopsy sampling. Although not previously recognized, the finding of reduced AR in bilateral lung recipients is intriguing, warranting replication and mechanistic exploration.
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Bronquiolite/epidemiologia , Rejeição de Enxerto/epidemiologia , Transplante de Pulmão , Complicações Pós-Operatórias/epidemiologia , Doença Aguda , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. METHODS: We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007-October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. RESULTS: In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4-21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2-13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9-10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16-56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40-121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. CONCLUSIONS: Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.
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Candidíase , Infecções Fúngicas Invasivas , Transplante de Pulmão , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Transplante de Pulmão/efeitos adversos , MicafunginaRESUMO
In the United States, an overall national decline in organ transplants has accompanied the substantial burden of COVID-19. Amidst significant regional variations in COVID-19, lung transplantation (LTx) remains a critical life-saving operation. Our LTx practice during the early pandemic may provide a blueprint for managing LTx in an era of continued community prevalence. Patients who underwent LTx at our institution between March 1 and May 20, 2020 were included. Recipient, operative, and donor characteristics were compared to those from our program in 2019, and COVID-19 testing practices were evaluated for March, April, and May to understand how our practice adapted to the pandemic. Our program performed 36 LTx, 33% more than the same period in 2019. Recipient, operative, and donor characteristics during COVID-19 were similar to those in 2019. By April 1, all donors and recipients underwent pretransplant COVID-19 testing, all returning negative results. To date, no recipients have developed posttransplant COVID-19. At our institution, pretransplant COVID-19 testing, use of local donor lungs, and avoidance of donors from areas of increased community penetration supported a safe and effective LTx practice during the early COVID-19 pandemic. Continued follow-up is required to ensure the long-term safety of these newly transplanted patients.
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COVID-19/epidemiologia , Transplante de Pulmão/métodos , Pandemias , SARS-CoV-2 , Doadores de Tecidos/provisão & distribuição , Transplantados , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Long-term survival after lung transplant lags behind that of other commonly transplanted organs, reflecting the current incomplete understanding of the mechanisms involved in the development of posttransplant lung injury, rejection, infection, and chronic allograft dysfunction. To address this unmet need, 2 ongoing National Institute of Allergy and Infectious Disease funded studies through the Clinical Trials in Organ Transplant Consortium (CTOT) CTOT-20 and CTOT-22 were dedicated to understanding the clinical factors and biological mechanisms that drive chronic lung allograft dysfunction and those that maintain cytomegalovirus polyfunctional protective immunity. The CTOT-20 and CTOT-22 studies enrolled 800 lung transplant recipients at 5 North American centers over 3 years. Given the number and complexity of subjects included, CTOT-20 and CTOT-22 utilized innovative data transfers and capitalized on patient-entered data collection to minimize site manual data entry. The data were coupled with an extensive biosample collection strategy that included DNA, RNA, plasma, serum, bronchoalveolar lavage fluid, and bronchoalveolar lavage cell pellet. This Special Article describes the CTOT-20 and CTOT-22 protocols, data and biosample strategy, initial results, and lessons learned through study execution.
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Transplante de Pulmão , Transplante de Órgãos , Líquido da Lavagem Broncoalveolar , Citomegalovirus , Rejeição de Enxerto/etiologia , Humanos , Transplante de Pulmão/efeitos adversos , Transplante de Órgãos/efeitos adversos , TransplantadosRESUMO
OBJECTIVE. The purpose of this study was to assess the image quality and resource utilization of single-injection, split-bolus, dual-enhancement abdominopelvic CT angiography (hereafter referred to as dual-enhancement CTA) performed for combined vascular and solid organ assessment compared with those of single-injection, single-enhancement abdominopelvic CT angiography (hereafter referred to as single-enhancement CTA) for vascular assessment in combination with additional examinations (CT, MRI, and US) performed to assess for malignancy in lung transplant candidates. MATERIALS AND METHODS. We retrospectively reviewed 100 patients who underwent abdominopelvic CTA examinations before lung transplant. Cohort A (n = 50) underwent dual-enhancement CTA and cohort B (n = 50) underwent single-enhancement CTA. Contrast opacification of the vasculature was assessed along the abdominal aorta through the right femoral artery. Solid organ enhancement was assessed in the right lobe of the liver and the right renal cortex. Measurements of mean radiation dose, contrast exposure, and cost of the studies (in U.S. dollars) were compared. RESULTS. Mean (± SD) vascular enhancement on dual-enhancement CTA and single-enhancement CTA was 334.2 ± 26.5 HU (coefficient of variation, 8.3%) and 340.0 ± 21.6 HU (coefficient of variation, 6.5%) (p = 0.23), respectively. For dual-enhancement CTA and single-enhancement CTA, mean liver enhancement was 125.8 ± 30.5 HU and 60.4 ± 6.9 HU (p < 0.01), respectively, whereas mean renal cortical enhancement was 260.3 ± 62.2 HU and 133.4 ± 38.6 HU (p < 0.01), respectively. The mean IV contrast volume was 150 mL for dual-enhancement CTA and 75 mL for single-enhancement CTA. Cohort A underwent six additional imaging studies (one of which was a CT colonography study with an effective dose of 19.0 mSv) at a total cost of $9840 per patient. Cohort B underwent 44 additional imaging studies (mean effective dose, 12.7 ± 6.5 mSv) at a total cost of $12,846 per patient (resulting in a 30.6% reduction in cost for dual-enhancement CTA studies; p < 0.0001). CONCLUSION. Dual-enhancement abdominopelvic CTA allows combined vascular and abdominopelvic solid organ assessment with improved image quality and a lower cost compared with traditional imaging pathways.
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Angiografia por Tomografia Computadorizada/métodos , Transplante de Pulmão , Radiografia Abdominal/métodos , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Iopamidol , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos RetrospectivosRESUMO
OBJECTIVE: Posttransplant depression has been linked to increased risk for adverse outcomes in lung transplant patients. Maintaining target serum immunosuppressant levels is also essential for optimal lung transplant clinical outcome and may be a crucial predictor of outcomes. Because depression could affect medication nonadherence, resulting in out-of-range immunosuppressant levels, we examined the relationship between posttransplant depression, immunosuppressant medication trough level variability, indexed by out-of-range values on clinical outcomes and coefficient of variability, and clinical outcomes. METHOD: A consecutive series of 236 lung transplant recipients completed the Center for Epidemiological Studies-Depression two-month posttransplant. Immunosuppressant trough levels (i.e., tacrolimus or cyclosporine) within the range of individualized immunosuppressant targets were obtained at three-, six-, nine-month follow-up clinic visits. Clinical outcomes including hospitalizations and mortality were obtained from medical records. RESULTS: Fourteen percent of patients were classified as depressed (Center for Epidemiological Studies-Depression ≥16), 144 (61%) of patients had at least 25% out-of-range immunosuppressant values, and the average coefficient of variability was 36%. Over a median of 2.6 years (interquartile range = 1.2), 32 participants died (14%) and 144 (61%) had at least one unplanned, transplant-related hospitalization. Both depression (hazard ratio = 1.45 (1.19, 1.76), p < . 01) and immunosuppressant variation (immunosuppressant out-of-range: hazard ratio = 1.41 (1.10, 1.81), p < .01) independently predicted more frequent hospitalizations and higher mortality. CONCLUSIONS: Early posttransplant depression was associated with significantly worse clinical outcomes. While immunosuppressant level variability is also related to adverse outcomes, such variability does not account for increased risk observed with depression.
Assuntos
Depressão/psicologia , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Pulmão/psicologia , Adesão à Medicação/psicologia , Transplantados , Adulto , Idoso , Depressão/sangue , Feminino , Humanos , Imunossupressores/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
CONTEXT: A significant contribution to the success of lung transplantation is the recipient's ability to self-manage a multidrug regimen and follow complex instructions. Effective education has always been an integral component of the process of preparing patients to care for themselves post lung transplant. Impaired cognition, anxiety, and psychological distress, however, can decrease the retention of posttransplant care information provided during education sessions. OBJECTIVE: This quality improvement project evaluated whether a multimedia education method compared to standard education method improves posttransplant care knowledge, anxiety, and satisfaction with the education experience in lung transplant patients and their caregivers. METHODS: Two education methods groups, comprised of transplant patients and their primary caregivers, were compared: (1) historic control group who received the standard education (n = 19 dyads) and (2) multimedia group who received the new multimedia education (n = 18 dyads). Knowledge of posttransplant care was evaluated in both groups before and after receiving the education. A satisfaction survey was administered at the end of the education program. RESULTS: A significantly higher percentage of patients receiving the multimedia method reported gains in posttransplant care knowledge ( P = .05), less anxiety about the transplant surgery ( P = .02), and satisfaction with the education method ( P = .02) when compared to those receiving the standard method. Caregivers and transplant team member also indicated that the multimedia method was more effective than the standard method. CONCLUSION: Multimedia methods decrease anxiety and increase satisfaction with the education experience when preparing patients for lung transplantation.
Assuntos
Ansiedade/prevenção & controle , Transplante de Pulmão/psicologia , Multimídia , Educação de Pacientes como Assunto/métodos , Transplantados/educação , Transplantados/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. METHODS: Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. RESULTS: The incidence rate of M. abscessus increased from 0.7 cases per 10000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. CONCLUSIONS: We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection.