Circovirus Hepatitis Infection in Heart-Lung Transplant Patient, France.

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection.

We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD). METHODS: We retrospectively reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for Aspergillus was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD. RESULTS: During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for Aspergillus; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1-44). Median time from transplantation to first Aspergillus-positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively. Aspergillus fumigatus (n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval [CI], 1.61-8.73; P < 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively (P < 0.01, logrank test). CONCLUSIONS: Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.

Outcomes of patients with cancer and sarcoid-like granulomatosis associated with immune checkpoint inhibitors: A case-control study.

PURPOSE: Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy. PATIENTS AND METHODS: Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort. RESULTS: The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7-75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p < 0.001) and more often received combined therapies of anti-programmed cell death 1 plus anti-cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086-0.630) (p = 0.002). CONCLUSION: Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

Lung transplantation for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by relentlessly progressive lung function impairment that is consistently fatal in the absence of lung transplantation, as no curative pharmacological treatment exists. The pace of progression varies across patients, and acute life-threatening exacerbations occur unpredictably, causing further sharp drops in lung function. Recently introduced antifibrotic agents slow the pace of disease progression and may improve survival but fail to stop the fibrotic process. Moreover, the magnitude and kinetics of the response to these drugs cannot be predicted in the individual patient. These characteristics require that lung transplantation be considered early in the course of the disease. However, given the shortage of donor lungs, lung transplantation must be carefully targeted to those patients most likely to benefit. Current guidelines for lung transplantation listing may need reappraisal in the light of recent treatment advances. Patients with IPF often have multiple comorbidities such as coronary heart disease, frailty, and gastro-oesophageal reflux disease (GERD). Consequently, extensive screening for and effective treatment of concomitant conditions is crucial to appropriate candidate selection and outcome optimisation. A multidisciplinary approach is mandatory. Pulmonologists with expertise in IPF must work closely with lung transplant teams. Careful consideration must be given to preoperative optimisation, surgical technique, and pulmonary rehabilitation to produce the best post-transplantation outcomes.

Characteristics and outcome of patients set up on high-flow oxygen therapy at home.

BACKGROUND: High-flow oxygen therapy (HFOT) is increasingly used for acute respiratory failure. Few data support its use at home for the treatment of chronic respiratory failure. Our aim was to report the pattern of the use of long-term HFOT in our center and the outcome of patients setup on long-term HFOT. METHODS: A retrospective monocentric study including all patients setup on long-term HFOT between January 2011 and April 2018 in Rouen University Hospital was carried out. Patients were divided into two groups, patients with hypoxemic respiratory failure treated with nasal HFOT (nHFOT) and tracheotomized patients treated with tracheal HFOT (tHFOT). RESULTS: A total of 71 patients were established on long-term HFOT. Out of these 43 (61%) were included in the nHFOT group and 28 (39%) were included in the tHFOT group. In the nHFOT group, underlying respiratory diseases were interstitial lung disease (n = 15, 35%), pulmonary hypertension (n = 12, 28%), lung cancer (n = 9, 21%), and chronic airway disease (n = 7, 16%). In the tHFOT group, the number of admissions for exacerbation decreased by -0.78 per year (-2 to 0) (p = 0.045). In total, 51 (72%) patients were discharged to their homes and 20 (28%) went to a post-acute re-enablement facility. Median survival following HFOT was 7.5 months. Survival was significantly lower in the nHFOT group with a median survival of 3.6 months whereas median survival was not reached in the tHFOT group (p < 0.001). Monthly costs associated with home delivery of HFOT were €476 (296-533) with significant differences in costs between the nHFOT group of €520 (408-628) and costs in the tHFOT group of €296 (261-475) (p < 0.001). CONCLUSIONS: The use of long-term HFOT allows very severe patients to be discharged at a reasonable cost from acute care facilities. The reviews of this paper are available via the supplementary material section.