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1.
J Infect Dis ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848312

RESUMO

BACKGROUND: Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. METHODS: Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months post vaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/ml (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. RESULTS: In SHCS participants, baseline anti-spike antibody concentrations ≥1642 were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a five-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. CONCLUSIONS: Bivalent mRNA vaccination elicited a robust humoral response in individuals with HIV or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.

2.
Clin Infect Dis ; 78(1): 48-56, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37584344

RESUMO

BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Transplante de Órgãos , Adulto , Humanos , Influenza Humana/prevenção & controle , Suíça , Anticorpos Antivirais , Polissorbatos/efeitos adversos , Esqualeno/efeitos adversos , Adjuvantes Imunológicos , Testes de Inibição da Hemaglutinação , Transplante de Órgãos/efeitos adversos
3.
Med Mycol ; 62(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38242842

RESUMO

Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with either colonization or infection. Evolution from colonization into infection is difficult to predict and clinical management upon microbiological detection is complex. Microbiological samples from 2015 to 2021 were retrospectively analyzed in a single tertiary care center. Classification into colonization or infection was performed upon first microbiological detection. Clinical evolution was observed until July 2023. Further diagnostic procedures after initial detection were analyzed. Among 38 patients with microbiological detection of Scedosporium spp., 10 were diagnosed with an infection at the initial detection and two progressed from colonization to infection during the observation time. The main sites of infection were lung (5/12; 41.6%) followed by ocular sites (4/12; 33.3%). Imaging, bronchoscopy or biopsies upon detection were performed in a minority of patients. Overall mortality rate was similar in both groups initially classified as colonization or infection [30.7% and 33.3%, respectively (P = 1.0)]. In all patients where surgical debridement of site of infection was performed (5/12; 42%); no death was observed. Although death occurred more often in the group without eradication (3/4; 75%) compared with the group with successful eradication (1/8; 12.5%), statistical significance could not be reached (P = 0.053). As therapeutic management directly impacts patients' outcome, a multidisciplinary approach upon microbiological detection of Scedosporium spp. should be encouraged. Data from larger cohorts are warranted in order to analyze contributing factors favoring the evolution from colonization into infection.


Scedosporium is an environmental mould with a varied clinical relevance, as described in this cohort from a tertiary centre. Its microbiological detection represents a colonization or infection. An interdisciplinary approach is crucial for an optimal diagnostic strategy and patient outcome.


Assuntos
Scedosporium , Humanos , Estudos Retrospectivos , Antifúngicos/uso terapêutico , Relevância Clínica , Fatores de Risco
4.
J Clin Apher ; 39(3): e22128, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38829041

RESUMO

BACKGROUND: Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. METHODS: We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. RESULTS: Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). CONCLUSION: In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.


Assuntos
Transplante de Pulmão , Fotoferese , Humanos , Fotoferese/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Aloenxertos , Doença Crônica , Recidiva , Disfunção Primária do Enxerto/terapia , Disfunção Primária do Enxerto/mortalidade
5.
Eur Arch Otorhinolaryngol ; 280(10): 4501-4507, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37249595

RESUMO

BACKGROUND: Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available. OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery. STUDY DESIGN: Retrospective single-center study. METHODS: We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5 mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15 mg/l CRP) and severe infections (> 15 mg/l CRP). RESULTS: There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15 mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056). CONCLUSIONS: CF patients undergoing Ltx benefit from extended endoscopic sinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.


Assuntos
Aloenxertos , Fibrose Cística , Transplante de Pulmão , Humanos , Fibrose Cística/mortalidade , Fibrose Cística/cirurgia , Transplante de Pulmão/métodos , Transplantados , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
6.
Medicina (Kaunas) ; 59(8)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37629763

RESUMO

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019-29 February 2020) and the first year of the pandemic (1 March 2020-28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Transplantados , Suíça/epidemiologia , Estudos de Coortes , Pandemias , Estudos Retrospectivos , Higiene , Pulmão
7.
Medicina (Kaunas) ; 59(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36984489

RESUMO

Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.


Assuntos
Imunossupressores , Transplantados , Humanos , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Biomarcadores , Pulmão , Rejeição de Enxerto/prevenção & controle
8.
Medicina (Kaunas) ; 59(3)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36984618

RESUMO

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5-8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the RPM system deployment was proven by the rapid recruitment uptake, technical performance (i.e., low number of errors), favorable user experience questionnaires and detailed individual user feedback.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplantados , Dispositivos Eletrônicos Vestíveis , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Projetos Piloto , Vacinação , Transplante de Pulmão
9.
Clin Infect Dis ; 75(1): e585-e593, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35234868

RESUMO

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.


Assuntos
COVID-19 , Vacinas Virais , Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Estudos de Coortes , Humanos , Hospedeiro Imunocomprometido , SARS-CoV-2 , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
10.
Transpl Int ; 35: 10451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845547

RESUMO

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992-2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection.


Assuntos
Insuficiência Cardíaca , Transplante de Pulmão , Disfunção Primária do Enxerto , Adulto , Aloenxertos , Comorbidade , Sobrevivência de Enxerto , Insuficiência Cardíaca/etiologia , Humanos , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
11.
Am J Transplant ; 20(10): 2876-2882, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32412159

RESUMO

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, comprehensive data of SARS-CoV-2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS-CoV-2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety-five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow-up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS-CoV-2 infection in middle-aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Transplante de Órgãos/métodos , Pneumonia Viral/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Transplantados , Idoso , COVID-19 , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Taxa de Sobrevida/tendências , Suíça/epidemiologia
12.
Clin Transplant ; 32(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194767

RESUMO

Calcineurin inhibitor (CNI) toxicity leads to end-stage renal disease in almost half of long-term survivors after lung transplantation, some of them receiving kidney transplants. Little is known about the outcomes of kidney and lung allograft function following kidney after lung transplantation (KALTPL) in the modern era. We retrospectively analyzed a group of 13 consecutive patients who received a KALTPL with respect to their renal and pulmonary function and immunological evolution over 2 years. We documented a stable evolution of forced expiratory volume in 1 second (FEV1) after KALTPL in most patients as well as an excellent kidney graft during the 2-year follow-up period. In our small cohort, living donations showed a significantly higher estimated glomerular filtration rate compared to deceased donation (75.7 compared to 41.6 mL/min). Patients who received a preemptive KALTPL were more likely to improve their lung function after KALTPL. Four patients developed de novo donor-specific antibodies (DSA) against the kidney graft. There were no DSA against shared antigens from the lung allograft. De novo DSA did not lead to graft loss in any patient. All 13 patients survived the first 24 months after KALTPL.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Rim/fisiopatologia , Fígado/fisiopatologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias , Adulto , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Falência Renal Crônica/etiologia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Transplante Homólogo
13.
Transpl Infect Dis ; 20(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29044831

RESUMO

Scedosporium species are fungal pathogens increasingly recognized in cystic fibrosis (CF). They can cause multiresistant, life-threatening infections that are of particular concern in CF patients undergoing lung transplantation, as optimal treatment remains unclear. Here, we describe our Zurich experience of CF patients with Scedosporium infection. Disseminated infection occurred in one patient after transplantation and was successfully treated. We propose a step-by-step approach to treat candidates with colonization, and discuss our cases in the context of the current literature.


Assuntos
Transplante de Pulmão/efeitos adversos , Micoses/epidemiologia , Scedosporium/isolamento & purificação , Transplantados , Adulto , Antifúngicos/uso terapêutico , Fibrose Cística/microbiologia , Feminino , Humanos , Masculino , Micetoma/tratamento farmacológico , Micoses/microbiologia , Suíça/epidemiologia , Voriconazol/uso terapêutico , Adulto Jovem
14.
Pediatr Transplant ; 22(3): e13145, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29380491

RESUMO

ECP is an established "second-line" treatment for CLAD/BOS. Recently, ECP was used for the first time in an adolescent CF patient as a "second-line" treatment therapy in life-threatening primary graft dysfunction following lung transplantation who deteriorated despite extensive treatment including ECMO and ATG. Within 10 days after initiation of ECP twice weekly, allograft function and clinical status improved significantly and the patient was weaned from mechanical ventilation support. ECP has been continued every 2 weeks since. Two hundred days after lung transplantation, the patient has an acceptable allograft function (FEV1 67%) and no signs of allograft rejection. We advocate that use of ECP and its immunomodulatory effects should be evaluated in the early period following lung transplantation.


Assuntos
Transplante de Pulmão , Fotoferese/métodos , Disfunção Primária do Enxerto/terapia , Feminino , Humanos , Adulto Jovem
15.
Respir Res ; 18(1): 151, 2017 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-28784117

RESUMO

The role of differential cytology patterns in peripheral blood and bronchoalveolar lavage samples is increasingly investigated as a potential adjunct to diagnose acute and chronic allograft dysfunction after lung transplantation. While these profiles might facilitate the diagnosis of acute cellular rejection, low sensitivity and specificity of these patterns limit direct translation in a clinical setting. In this context, the identification of other biomarkers is needed. This review article gives an overview of cytokine profiles of plasma and bronchoalveolar lavage samples during acute cellular rejection. The value of these cytokines in supporting the diagnosis of acute cellular rejection is discussed. Current findings on the topic are highlighted and experimental settings for future research projects are identified.


Assuntos
Aloenxertos/metabolismo , Líquido da Lavagem Broncoalveolar , Citocinas/fisiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Transplante de Pulmão/efeitos adversos , Animais , Biomarcadores/metabolismo , Lavagem Broncoalveolar/métodos , Humanos , Transplante de Pulmão/tendências
16.
Clin Transplant ; 31(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28653398

RESUMO

Extracorporeal photophoresis (ECP) is an increasingly used therapy to address chronic lung allograft dysfunction (CLAD) following lung transplantation. In 2008, we reported the first single-center experience showing that ECP not only reduces lung function decline in patients with bronchiolitis obliterans syndrome (BOS) but results in stabilization of patients with recurrent acute cellular rejection (ACR). In this study, the original cohort was followed up further 5 years. In addition, patients with CLAD were retrospectively classified according to recently published phenotypes. The current cohort included 21 of the original 24 patients, of which nine were initially treated for CLAD, 12 were initially treated for recurrent ACR. Our results show that survival of patients treated with ECP for CLAD was inferior to patients treated for recurrent ACR (66% vs. 82% survival rate). Long-term survivors in the CLAD subgroup were mostly classified as BOS 1 at time of ECP initiation. These long-term data show that patients started on ECP at early BOS stages have better long-term outcome. The subgroup of ECP patients with recurrent ACR has an overall superior survival. To assist prediction of therapy response, we agree with other authors that patients with CLAD should be aimed to be phenotyped and evaluated for an early treatment with ECP.


Assuntos
Bronquiolite Obliterante/terapia , Transplante de Pulmão/métodos , Fotoferese/métodos , Adolescente , Adulto , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplantados , Adulto Jovem
18.
Respir Res ; 17(1): 74, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27323950

RESUMO

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.


Assuntos
Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Transplante de Pulmão/efeitos adversos , Pulmão/metabolismo , Doença Aguda , Aloenxertos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Rejeição de Enxerto/sangue , Rejeição de Enxerto/patologia , Humanos , Leucócitos/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Valor Preditivo dos Testes , Prognóstico
19.
Clin Transplant ; 30(10): 1264-1270, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27448095

RESUMO

BACKGROUND: We aim to assess the incidence, current treatment, and outcome of diverticulitis in highly immunosuppressed lung transplant recipients. METHODS: Retrospective analysis of a prospective database of 403 lung transplant recipients transplanted between 1992 and 2013 with a mean follow-up of 100 months (SD 58.0). RESULTS: 4.46% of lung transplant recipients (n=18) developed diverticulitis. Eight lung transplant recipients developed uncomplicated diverticulitis, which were all treated successfully with antibiotics. Three patients (37.5%) underwent elective sigmoid resection with severe Grade 3b complications after two of five (40%) surgical procedures. Diverticulitis recurrence occurred in five patients (60%). In total, 10 lung transplant recipients presented with 11 episodes of perforated diverticulitis with a 30-day mortality rate of 9.1%. Hartmann procedure was performed in eight lung transplant recipients. Sigmoid resection with primary anastomosis and protective ileostomy was performed in three patients with Hinchey I. Two of these patients developed anastomotic leakage with a secondary Hartmann procedure. CONCLUSION: Due to high leakage rate after resection with primary anastomosis and protective ileostomy in our cohort of lung transplant recipients with perforated diverticulitis, the Hartmann procedure seems to be the safer option. In contrast, in uncomplicated diverticulitis, non-operative treatment can be considered as a safe and highly successful treatment option, even for recurrences.


Assuntos
Antibacterianos/uso terapêutico , Doença Diverticular do Colo/tratamento farmacológico , Transplante de Pulmão , Complicações Pós-Operatórias/tratamento farmacológico , Doenças do Colo Sigmoide/tratamento farmacológico , Adulto , Idoso , Colectomia , Colostomia , Doença Diverticular do Colo/epidemiologia , Doença Diverticular do Colo/etiologia , Doença Diverticular do Colo/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/prevenção & controle , Humanos , Ileostomia , Imunossupressores/uso terapêutico , Incidência , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Doenças do Colo Sigmoide/epidemiologia , Doenças do Colo Sigmoide/etiologia , Doenças do Colo Sigmoide/cirurgia , Resultado do Tratamento
20.
Clin Transplant ; 30(8): 857-63, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27219076

RESUMO

In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome.


Assuntos
Infecções por Bactérias Gram-Negativas/microbiologia , Doenças Pulmonares Intersticiais/diagnóstico , Transplante de Pulmão , Pulmão/microbiologia , Stenotrophomonas maltophilia/isolamento & purificação , Transplantados , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adulto , Idoso , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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