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BACKGROUND Lung transplantation (LTx) is a life-extending therapy for specific patients with terminal lung diseases. This study aimed to evaluate the associations and causes of 1-year mortality after lung transplantation at Strasbourg University Hospital, France, between 2012 and 2021. MATERIAL AND METHODS We carried out a retrospective analysis on 425 patients who underwent LTx at Strasbourg University Hospital between January 1, 2012, and December 31, 2021. Pre-transplant, perioperative, and postoperative data were collected from the electronic medical records. RESULTS Among all patients, 94.6% had a LTx, 4.0% a heart-lung transplantation, and 1.4% underwent pancreatic islet-lung transplantation. The median age at transplantation was 57 years, with 55.3% male patients. The main native lung disease leading to LTx was chronic obstructive pulmonary disease in 51.1% of patients; 16.2% needed super-urgent LTx. The 1-year mortality rate was 11.5%. Most deaths were either caused by multi-organ failure or septic shock. In our multivariate analysis, we identified 3 risk factors significantly related to 1-year mortality after LTx: body mass index (BMI) between 25 and 30 kg/m² vs BMI between 18.5 and 25 kg/m² (P=0.032), postoperative extracorporeal membrane oxygenation support (P=0.034), and intensive care unit length of stay after transplantation (P<0.001). Two other factors were associated with a significantly lower 1-year mortality risk: longer hospital stay after LTx (P=0.024) and tacrolimus prescription (P=0.004). CONCLUSIONS Our study reported a 1-year mortality rate of 11.5% after LTx. Although LTx candidates are carefully selected, additional data are required to improve understanding of the risk factors for post-LTx mortality.
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Trasplante de Pulmón , Humanos , Trasplante de Pulmón/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Francia/epidemiología , Estudios Retrospectivos , Adulto , Factores de Riesgo , Anciano , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/cirugía , Complicaciones Posoperatorias/mortalidadRESUMEN
INTRODUCTION: Due to the COVID-19 pandemic, France underwent several lockdown periods during 2020. Our aim was to evaluate its clinical and social impact on lung transplant (LT) patients treated at Strasbourg University Hospital, by comparing three periods: first lockdown (T1: March-May 2020), end of the first lockdown (T2: May-October 2020), and second lockdown (T3: November-December 2020) and the incidence of COVID-19 infections. A cohort of patients with rare lung disease (RLD) was also studied during T2. METHODS: We used clinical and paraclinical data collected during routine follow-up. A questionnaire was submitted to each patient at each period to assess their lifestyle, adherence to protective measures against COVID-19, contacts with their family and friends, and contagion risk. The incidence of new COVID-19 cases was also assessed. RESULTS: Overall, 283 LT and 57 RLD patients were included. We observed only eight COVID-19 cases over the three periods (n = 4 during T1, n = 0 during T2, and n = 4 during T3) in LT patients, with 37.5 % of patients hospitalized, no ICU transfers, and 100 % favorable outcomes. No case of COVID-19 was diagnosed in the RLD cohort. When comparing the three periods in the LT group, fewer patients limited their out-of-home activities during T2 (p < 0.0001). The frequency of these activities increased after the first lockdown, for the purchase of basic necessities (p < 0.0001), and professional activity continued (p = 0.008). We observed a significant increase in unscheduled medical consultations and in the prescription of anti-infective treatments during the end of the lockdown (p = 0.0002 and p = 0.005, respectively). Adherence to lockdown and to protective measures was high in both groups of patients. CONCLUSION: COVID-19 incidence remained low in both groups and there were significant lifestyle evolutions in LT patients and in those with RLD between first and second lockdown.
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COVID-19 , Enfermedades Pulmonares , Trasplante de Pulmón , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Francia/epidemiología , Adulto , Incidencia , Enfermedades Pulmonares/epidemiología , Enfermedades Raras/epidemiología , Anciano , Estudios de Cohortes , PandemiasRESUMEN
BACKGROUND: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers. METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers. RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24â months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7). CONCLUSIONS: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.
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Neoplasias Pulmonares , Proteína A Asociada a Surfactante Pulmonar , Proteína C Asociada a Surfactante Pulmonar , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Transversales , Proteína C Asociada a Surfactante Pulmonar/genética , Proteína A Asociada a Surfactante Pulmonar/genética , Adulto , Factor Nuclear Tiroideo 1/genética , Transportadoras de Casetes de Unión a ATP/genética , Factores de Riesgo , Predisposición Genética a la Enfermedad , Enfermedades Pulmonares Intersticiales/genética , Heterocigoto , Proteínas Asociadas a Surfactante Pulmonar/genéticaRESUMEN
BACKGROUND: Antifibrotic agents (AFAs) are now standard-of-care for idiopathic pulmonary fibrosis (IPF). Concerns have arisen about the safety of these drugs in patients undergoing lung transplantation (LTx). METHODS: We performed a multi-centre, nationwide, retrospective, observational study of French IPF patients undergoing LTx between 2011 and 2018 to determine whether maintaining AFAs in the peri-operative period leads to increased bronchial anastomoses issues, delay in skin healing and haemorrhagic complications. We compared the incidence of post-operative complications and the survival of patients according to AFA exposure. RESULTS: Among 205 patients who underwent LTx for IPF during the study period, 58 (28%) had received AFAs within 4 weeks before LTx (AFA group): pirfenidone in 37 (18.0%) and nintedanib in 21 (10.2%). The median duration of AFA treatment before LTx was 13.8 (5.6-24) months. The AFA and control groups did not significantly differ in airway, bleeding or skin healing complications (p = 0.91, p = 0.12 and p = 0.70, respectively). Primary graft dysfunction was less frequent in the AFA than control group (26% vs. 43%, p = 0.02), and the 90-day mortality was lower (7% vs. 18%, p = 0.046). CONCLUSIONS: AFA therapy did not increase airway, bleeding or wound post-operative complications after LTx and could be associated with reduced rates of primary graft dysfunction and 90-day mortality.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Antifibróticos , Estudios Retrospectivos , Disfunción Primaria del Injerto/tratamiento farmacológico , Disfunción Primaria del Injerto/etiología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Piridonas/efectos adversos , Resultado del TratamientoRESUMEN
Background: Interstitial lung disease associated with genetic disorders of the surfactant system is a rare entity in adults that can lead to lung transplantation. Our objective was to describe the outcome of these patients after lung transplantation. Methods: We conducted a retrospective, multicentre study, on adults who underwent lung transplantation for such disease in the French lung transplant centres network, from 1997 to 2018. Results: 20 patients carrying mutations in SFTPA1 (n=5), SFTPA2 (n=7) or SFTPC (n=8) were included. Median interquartile range (IQR) age at diagnosis was 45 (40-48) years, and median (IQR) age at lung transplantation was 51 (45-54) years. Median overall survival after transplantation was 8.6â years. Two patients had a pre-transplant history of lung cancer, and two developed post-transplant lung cancer. Female gender and a body mass index <25â kg·m-2 were significantly associated with a better prognosis, whereas transplantation in high emergency was associated with a worst prognosis. Conclusions: Lung transplantation in adults with interstitial lung disease associated with genetic disorders of surfactant system may be a valid therapeutic option. Our data suggest that these patients may have a good prognosis. Immunosuppressive protocol was not changed for these patients, and close lung cancer screening is needed before and after transplantation.
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BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the main limitation to long-term survival following lung transplantation. Several studies generated promising results regarding the efficacy of extracorporeal photopheresis (ECP) in BOS management. We aimed to compare FEV1 evolution in ECP-treated versus non-ECP treated patients among BOS recipients. METHODS: Overall, 25 BOS patients were included after receiving optimized treatment. Data were collected retrospectively. Twelve patients with moderate and refractory BOS received ECP treatment. RESULTS: Among non-ECP treated control patients (n = 13), six experienced persistent decline without undergoing ECP for various reasons. ECP stabilized pre-ECP lung function during the subsequent 6 to 24 months (repeated measures one-way Anova, p = 0.002), without any significant impact observed by either FEV1 decline speed prior to ECP or time between BOS diagnosis and ECP onset. ECP-treated patients displayed a similar risk of an additional permanent 20% or higher drop in FEV1 after BOS onset compared to controls, but a lower risk compared to control decliners (p = 0.05). ECP quickly stabilized FEV1 decline in refractory BOS patients compared to non-treated decliners. CONCLUSIONS: We confirmed that this therapeutic option against refractory BOS can be managed in a medium-size LTx center, with a satisfactory efficacy and an acceptable tolerance.
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Bronquiolitis Obliterante , Trasplante de Pulmón , Fotoféresis , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/terapia , Humanos , Trasplante de Pulmón/efectos adversos , Fotoféresis/efectos adversos , Fotoféresis/métodos , Estudios Retrospectivos , SíndromeRESUMEN
BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.
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Glucocorticoides , Fibrosis Pulmonar Idiopática , Adulto , Ciclofosfamida/efectos adversos , Método Doble Ciego , Glucocorticoides/efectos adversos , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. METHODS: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). RESULTS: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. CONCLUSION: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.
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Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium/epidemiología , Infecciones por Mycobacterium/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Francia/epidemiología , Adhesión a Directriz/estadística & datos numéricos , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/terapia , Masculino , Persona de Mediana Edad , Mycobacterium/aislamiento & purificación , Infecciones por Mycobacterium/diagnóstico por imagen , Infecciones por Mycobacterium/terapia , Pronóstico , Estudios Retrospectivos , Distribución por Sexo , Adulto JovenRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the posttransplant setting. Treatment is based on chemotherapy; surgery is still debated and should be performed in very select cases. METHODS: We observed 2 patients out of 300 who underwent lung transplantation in the Nouvel Hopital Civil between 2013 and 2019 with primary hepatic lymphoma. Chemotherapy with a rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone protocol was performed in all patients. Mycophenolate mofetil was interrupted before treatment, and everolimus was introduced after chemotherapy by associating tacrolimus withdrawal. RESULTS: One patient showed complete remission; after 7 years, no recurrence has been noticed. The second is still undergoing chemotherapy with no signs of disease progression. CONCLUSIONS: DLBCL risk is higher in solid organ transplant recipients than in the general population. Primary hepatic lymphoma diagnosis is often difficult and based on histologic findings after initial clinical and radiological suspicion of primary or secondary liver neoplasia. Diagnosis is challenging because no clinical, radiological, or biological features exist. Biopsy is always indicated for histologic confirmation. Chemotherapy is the mainstay of therapy, but surgery may be indicated in very select patients.
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Neoplasias Hepáticas/etiología , Trasplante de Pulmón/efectos adversos , Linfoma de Células B Grandes Difuso/etiología , Adulto , Anciano , Humanos , Huésped Inmunocomprometido , Masculino , Inducción de RemisiónRESUMEN
The clinical and social impacts of the COVID-19 epidemic on lung transplant (LTx) recipients remain poorly known. We aimed to evaluate its social, clinical, and behavioral consequences on the LTx patients followed in Strasbourg university hospital. A questionnaire was used to collect details concerning patients' lifestyles, their protection methods used to avoid COVID-19 contamination, and clinical infection-related information for March 2020. A specific score was created to quantify patients' contacts and the associated risk of infectious contagion. Data were collected from 322 patients (91.2%). A majority reported a higher application than usual of social distancing and barrier measures. 43.8% described infectious-related symptoms and 15.8% needed an anti-infective treatment. There was no difference in symptom onset according to age, native lung disease, diabetes, or obesity. Nineteen patients were tested for COVID-19, and four were diagnosed positive, all with a favorable outcome. The infection risk contact score was higher for symptomatic patients (p: 0.007), those needing extra-medical appointments (p < .001), and those receiving anti-infective treatments (p = .02). LTx patients reported a careful lifestyle and did not seem at higher risk for COVID-19. Our score showed encouraging preliminary results and could become a useful tool for the usual infection-related follow-up of the LTx patients.
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COVID-19/etiología , Conductas Relacionadas con la Salud , Trasplante de Pulmón , Complicaciones Posoperatorias , Determinantes Sociales de la Salud , Receptores de Trasplantes/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , Trazado de Contacto , Epidemias , Femenino , Francia/epidemiología , Hospitales Universitarios , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Cooperación del Paciente/psicología , Cooperación del Paciente/estadística & datos numéricos , Distanciamiento Físico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/psicología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Lung transplantation (LT) is an identified risk factor for Pneumocystis pneumonia (PCP). However, PCP management and outcomes remain poorly described in LT recipients and PCP incidence is rarely documented in this population. METHODS: PCP episodes that occurred in 9 French LT centers between January 2010 and October 2017 were included in this analysis. PCP was defined as compatible clinical and radiologic findings associated with fungal identification. RESULTS: Forty-seven PCP were included. The annual incidence rate of PCP was 2.7/1000 patients/year. Patients had a mean age of 53 ± 14 years. Median time from LT was 2.4 ± 3.0 years. Sixty-five percent of patients were not on prophylaxis at the time of PCP while all patients were receiving steroids at the time of PCP. Diagnosis was obtained by bronchoalveolar lavage in 91% (direct examination: 47%, PCR: 62%). The majority of patients were treated with trimethoprim-sulfamethoxazole (78%). Fifty-five percent of patients were hospitalized in ICU for organ failure (for which non-invasive ventilation was used for 21% and mechanical ventilation for 23%). Mortality rate was 15% at day 28 and reached 23% at day 90. Mortality was associated with decreased FEV1, everolimus treatment, Pseudomonas aeruginosa coinfection, fungal coinfection (especially Aspergillus sp.), mechanical ventilation and vasopressors. PCP primary prophylaxis, steroid modification during PCP and the number of immunosuppressive molecules were not associated with mortality. CONCLUSION: PCP is associated with a high mortality in LT. Our data suggest the need for a lifetime PCP prophylaxis in LT recipients. The benefit of adjuvant steroids remains unclear.
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Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/mortalidad , Neumonía por Pneumocystis , Complicaciones Posoperatorias , Adulto , Anciano , Estudios de Cohortes , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/prevención & control , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Factores de Tiempo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
OBJECTIVE: To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. MATERIAL AND METHODS: Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. RESULTS: DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. CONCLUSIONS: Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.
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Glucemia/análisis , Diabetes Mellitus/sangre , Hemoglobina Glucada/análisis , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias/sangre , Adulto , Diabetes Mellitus/etiología , Diabetes Mellitus/mortalidad , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND Although central airway stenosis (CAS) is a common complication after lung transplantation, its consequences have been poorly evaluated. The objective of our study was to evaluate the impact of CAS on lung function after lung transplantation. MATERIAL AND METHODS All lung transplant recipients from June 2009 to August 2014 in a single center (Strasbourg, France) were retrospectively reviewed. RESULTS A total of 191 lung transplantations were performed: 175 bilateral, 15 single, and 1 heart-lung transplantation. Of the 161 bilateral lung-transplanted patients who survived >3 months, 22 (13.6%) developed CAS requiring endobronchial treatment. All these patients were treated by endoscopic balloon dilatation, and 9 additionally needed endobronchial stents. Respiratory function tests demonstrated persistent obstructive ventilatory pattern despite endoscopic treatment in recipients with CAS compared to those without CAS at 6, 12, and 18 months post-transplant. At 18 months, CAS patients had significantly lower post-transplant FEV1 (1.96±0.60 L versus 2.57±0.76 L, p=0.001) and FEV1/FVC (61±14% versus 81±13%, p<0.001). The percentage of patients hospitalized for respiratory infections and number of hospital days were significantly increased in recipients with CAS (20 [91%] versus 92 [66%] p=0.036, and 144±110 days versus 103±83 days p=0.042, respectively). Survival in transplant recipients did not significantly differ between those with CAS and those without. CONCLUSIONS CAS after lung transplantation was not associated with worse survival, but it did have a significant and persistent effect on lung function, and was associated with increased rate of respiratory infection.
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Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Trasplante de Pulmón/efectos adversos , Insuficiencia Respiratoria/etiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Insuficiencia Respiratoria/fisiopatología , Estudios RetrospectivosRESUMEN
Regulator of telomere length 1 (RTEL1) mutations have been evidenced in 5-9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1â years (range 28.0-80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2â months and 45.3â months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts.
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ADN Helicasas/genética , Regulación de la Expresión Génica , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares/metabolismo , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Exoma , Femenino , Estudios de Seguimiento , Heterocigoto , Humanos , Enfermedades Pulmonares/genética , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Análisis de Secuencia de ADN , Telomerasa/genética , Capacidad VitalRESUMEN
BACKGROUND: The aim of our study was to describe the lung cancer characteristics in lung transplant recipients at our institution. METHODS: Between January 1, 1992, and August 15, 2017, 463 patients underwent lung transplantation. RESULTS: We found a total of 19 lung cancers (4.10%). Eight patients had lung cancer in the explanted lung, 8 in the native remaining lung, and 3 in the transplanted lung. Histopathological findings were: adenocarcinoma in 10, SCC in 8 patients, and 1 was undetermined. Among lung cancers in the explanted lungs, there were 6 stage I, 1 stage III, 1 stage IV. Among patients with a lung cancer in the remaining native lung, 3 had early stage disease and 5 had stage IV disease. Among lung cancers in the transplanted lung, there were: 1 stage I, 1 stage II and 1 stage IV. Overall median survival in lung transplant recipients without lung cancer was 8.77 ± 0.74 years compared to 6.19 ± 1.4 years in recipients with lung cancer. CONCLUSION: Lung cancer following lung transplantation was uncommon. Early stage lung cancer discovered in the explanted lungs had no impact on survival. Lung cancer occurring in the transplanted or in the native remaining lung had a poor prognosis.
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Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiología , Trasplante de Pulmón/efectos adversos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Cladophialophora bantiana brain abscesses are rare, but are frequently and quickly lethal in transplanted patients. We report the case of a 63-year-old man who had undergone lung transplantation for chronic obstructive pulmonary disease and presented with headaches and a neurological deficit. Magnetic resonance imaging revealed multiple brain abscesses. C. bantiana was identified by DNA sequencing performed directly on cerebral tissue obtained by surgical biopsy. After 6 months of antifungal treatment, the brain abscesses were replaced by ischemic sequelae. The patient died suddenly 2 months later from a pulmonary bacterial infection. This is the second reported case of C. bantiana brain abscesses in a lung transplant recipient, to our knowledge, who experienced a long survival period with medical antifungal treatment alone. We review the literature and discuss our treatment.
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Ascomicetos/aislamiento & purificación , Absceso Encefálico/microbiología , Trasplante de Pulmón/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Antifúngicos/uso terapéutico , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Absceso Encefálico/diagnóstico por imagen , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/patología , Infecciones Fúngicas del Sistema Nervioso Central , Resultado Fatal , Humanos , Hifa/aislamiento & purificación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. METHODS: After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.
Asunto(s)
Lesión Pulmonar Aguda/diagnóstico , Agua Pulmonar Extravascular/metabolismo , Trasplante de Pulmón/efectos adversos , Pulmón/metabolismo , Oxígeno/sangre , Disfunción Primaria del Injerto/diagnóstico , Edema Pulmonar/diagnóstico , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/fisiopatología , Adulto , Área Bajo la Curva , Teorema de Bayes , Biomarcadores/sangre , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Presión Parcial , Valor Predictivo de las Pruebas , Disfunción Primaria del Injerto/sangre , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/fisiopatología , Proteoglicanos/sangre , Edema Pulmonar/sangre , Edema Pulmonar/etiología , Edema Pulmonar/fisiopatología , Curva ROC , Receptor para Productos Finales de Glicación Avanzada/sangre , Índice de Severidad de la Enfermedad , Termodilución , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Arthrographis kalrae is a hyalin fungus. It is a saprophyte of the environment, mainly found in soil and compost. In recent years, cases of opportunistic infections attributed to this pathogen have been described. Our patient was a 19-year-old woman with cystic fibrosis. She presented a bacterial and fungal pulmonary colonization with Aspergillus fumigatus and Arthrographis. kalrae. After her lung transplantation, she developed an A. kalrae fungemia, treated with caspofungin 50 mg/day associated to liposomal amphotericin B i.v. 3 mg/kg/day. The patient died 8 months after her transplantation as the result of a bacterial septic shock.
Asunto(s)
Aspergilosis/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Cardiopatías/dietoterapia , Imagen por Resonancia Cinemagnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , RadiofármacosRESUMEN
PURPOSE: To describe tracheal rupture after orotracheal intubation assisted by a tracheal tube introducer. CLINICAL FEATURES: A 73-yr-old morbidly obese female patient with a history of hypertension underwent a total knee replacement. There were no anticipated signs of difficult intubation. Orotracheal intubation was attempted twice by direct laryngoscopy, and a Boussignac bougie was used as a tube exchanger for the second attempt. Seven hours after tracheal extubation, the patient became dyspneic and showed a large subcutaneous emphysema. A chest x-ray and computerized tomography scan revealed rupture of the posterior tracheal wall. The distal part of the injury was 26.5 cm from the patient's teeth and 0.5 cm from the carina (i.e., beyond the normal location of the tracheal tube tip) and extended to the origin of the right main bronchus, where the tip of the Boussignac bougie was probably pushed. Formation of an endotracheal sac occurred during the first two weeks after intubation, accompanied by dyspnea and alveolar hypoventilation, but symptoms resolved favourably with conservative management. CONCLUSION: The tracheal rupture was attributed to airway manipulations, and the distal location of the lesion suggests that the cause was the Boussignac bougie rather than the tracheal tube. Long-term healing of the injury was satisfactory, although the patient continued to complain of dyspnea one year after the rupture.