Real-time and non-invasive acute lung rejection diagnosis using confocal LASER Endomicroscopy in lung transplant recipients: Results from the CELTICS study.

BACKGROUND AND OBJECTIVE: Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs. METHODS: Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results. RESULTS: From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC. CONCLUSION: Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.

[Bronchial thermoplasty for severe asthma]. / Place de thermoplastie bronchique dans la prise en charge de l'asthme sévère.

Bronchial thermoplasty has been developed over the past fifteen years and is the first endoscopic technique approved in the management of severe asthma. This procedure uses radiofrequency applied to the airway wall to target bronchial smooth muscle. Patients treated in randomized controlled trials have experienced significant decreases in the use of rescue medications, urgent care visits, and exacerbations rate. The lack of reliable predictive markers of response to this expensive, minimally-invasive technique currently makes it a last-line treatment option. We review the principles and supposed mechanisms of action of this treatment, the results from the main trials and clinical registry data and discuss the place of bronchial thermoplasty in the current management of severe asthma. We also discuss perspectives to better characterize the mechanisms of action and identify the responder phenotype, the main challenge of current studies.

Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

[Use of endobronchial ultrasound in the management of cryptogenic haemoptysis]. / Apport de l'échoendoscopie radiaire dans la prise en charge de l'hémoptysie cryptogénique.

Currently about 50% of cases of haemoptysis are thought to be cryptogenic. Haemorrhage from the pulmonary arterial system is rare and usually due to aneurysms or pseudoaneurysms, the radiological diagnosis of which is often difficult. We report here the case of a patient admitted with a heavy haemoptysis in whom the thoracic CT scan did not reveal the diagnosis. Bronchoscopy with endobronchial ultrasound showed a vascular malformation of a branch of the pulmonary artery allowing a radiological embolisation. This case underlines the importance of bronchoscopy and the role of ultrasound in the diagnosis of haemoptysis, considered ideopathic, complicating vascular malformations.

[An unusual mediastinal mass]. / Une masse médiastinale atypique.

INTRODUCTION: Primary mediastinal tumors are rare diseases including a broad spectrum of pathologies ranging from the well-known, such as lymphoma, thymoma or germ-line tumors to some very unusual presentations. CASE REPORT: We describe a solitary mediastinal mass compressing the bronchial and vascular system in a patient suffering from chronic dyspnea. Diagnosis, obtained by means of a CT-guided biopsy, was a melanoma without any sign of a primary cutaneous lesion which harbored the BRAF V600E mutation. CONCLUSIONS: An exclusive mediastinal presentation of a malignant melanoma is exceptional and, in the context of BRAF mutation needs to be considered and diagnosed given the potential therapeutic impact.

[An analysis of treatment delays of thoracic cancers: a prospective study]. / Analyse des délais de prise en charge des cancers thoraciques: étude prospective.

INTRODUCTION: Lung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor. MATERIAL AND METHODS: Our prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays. RESULTS: The median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients. CONCLUSION: Evaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases.

[Incidence and characteristics of bronchial colonisation in patient with lung cancer: a retrospective study of 388 cases]. / Incidence et caractéristiques des colonisations des voies respiratoires lors du diagnostic de cancer bronchique: étude rétrospective de 388 cas.

INTRODUCTION: Bronchial colonisation is frequently reported in patients with lung cancer. These colonisations could influence patient therapeutic management and prognosis. The aim of our study is refine incidence and nature of bronchial colonisations in patients presenting with lung cancer. METHODS: Three hundred and eighty-eight patients with lung cancer underwent a flexible bronchoscopy at the time of diagnosis. Among them, 216 patients had a bacteriological, mycobacteriological and fungal investigation. Type and frequency of these colonisations were analyzed. RESULTS: Potential pathogens were found in 39.8% of samples, including mainly 39.8% of Gram-negative bacilli (Haemophilus influenzae, Enterobacter sp., Escherichia coli). In addition, we found 0.9% of mycobacteria and 13.9% of Candida albicans. Among these 216 patients where microbiological analysis was performed, patient features and tumor stage were not significantly correlated to microbial colonisation. CONCLUSIONS: Colonisation of airways is frequently reported when a lung cancer is diagnosed. Our data suggest that bronchial colonisation should be prospectively collected due to its potential interest in the management of lung cancer patients.

[Pneumocystis jiroveci infection associated with organizing pneumonia in a kidney transplant patient]. / Infection à Pneumocystis jiroveci associée à une pneumopathie organisée chez une patiente transplantée rénale.

The authors report the association of organizing pneumonia (OP) and a Pneumocystis jiroveci infection in a woman who benefited from a kidney transplant 13 years before and was under corticoids, cyclosporine and mycophenolate mofetil. The diagnosis was based on progressive dyspnoea with fever with an alteration in the general state associated with diffuse micronodular pneumopathy suggesting bronchiolitis. The conformation was obtained by the analysis of the alveolar bronchial washings and the histological examination of the distal biopsies revealing endo-alveolar vegetant fibromas. Transbronchial biopsies may be used for the diagnosis and thereby, avoid an invasive surgical pulmonary biopsy. The aetiology of OP may be related to the immunosuppressant treatment or infection by Pneumocystis jiroveci. The evolution in this case was favourable with trimethoprime and sulfamethoxazole associated with a transient increase in the corticoid treatment. This association is rarely described in patients undergoing solid organ transplants.

The Idefix enhancer-blocking insulator also harbors barrier activity.

Chromatin insulators are cis-regulatory sequences participating in the regulation of gene expression. Their presence within the genome is associated with two main functions. One of them is an enhancer-blocking function that blocks enhancer-promoter communication when the insulator is located in between. The second is a boundary or barrier function that insulates independent units of transcription. This latter is observed when two insulators flanking a gene and its regulatory sequences block the regulatory influences of surrounding chromatin. Some years ago, we reported the presence of an insulator within the retrotransposon Idefix from Drosophila melanogaster. This insulator displays an enhancer-blocking activity toward an enhancer located within a second retrotransposon called ZAM. Here, we show that this insulator is not specific to the ZAM enhancer but has the capacity to interfere in the communication established between a broad range of cis-regulatory enhancer and a promoter. Furthermore, we show that, if it is placed on both sides of a transgene, this insulator acts as a barrier able to isolate the transgene from its repressive or enhancing environment. Thus, the Idefix insulator carries both an enhancer-blocking and a barrier activity. According to these properties, the Idefix insulator might prove to be a useful tool to isolate artificial transgenes from positive or negative influences from their integration sites.

[Diagnostic flexible bronchoscopy. Recommendations of the Endoscopy Working Group of the French Society of Pulmonary Medicine]. / Les bonnes pratiques de la bronchoscopie souple diagnostique, en 2007.

These guidelines on flexible bronchoscopy depict important clues to be known and taken into account while practicing flexible bronchoscopy, in adult, except in emergency situations. This is a practical clarification. Safety conditions, complications, anesthesia, infectious risks, cleaning and disinfection are detailed from a review of the literature. Intensive care practice of bronchoscopy requires more attention due to higher risks patients and is discussed extensively. Standards and performances of the various sampling techniques complete this work. Indications for bronchoscopy, therapeutic and paediatric bronchoscopy are not covered in these guidelines.

[Intra-vascular lymphoma presenting with respiratory symptoms]. / Lymphome intravasculaire à présentation pulmonaire.

INTRODUCTION: Intra-vascular large cell lymphoma is a rare disease characterised by the proliferation of malignant cells within small blood vessels. CASE REPORT: We report a case of intra-vascular lymphoma presenting with unexplained dyspnoea, hypoxaemia and associated neurological symptom. The diagnosis was made by liver biopsy but the patient ultimately died. CONCLUSIONS: Earlier diagnosis with transbronchial biopsy might have improved the prognosis by allowing more prompt treatment.

Management of diabetes in French prisons: a cross-sectional study.

AIMS: To assess by a survey the management of prisoners with diabetes treated with insulin in French prisons. METHODS: A questionnaire was sent to the head of healthcare services for prisoners of every French prison. Information was obtained on prevalence of insulin-treated diabetes prisoners and diabetes care in prison. The number of episides of ketoacidosis and hypoglycaemia needing hospital admissions were evaluated during the past year. RESULTS: Among the 163 questionnaires sent, 115 were returned, giving an overall response rate of 69%. At the time of the study the prison population was 38 175 people. One hundred and sixty-nine prisoners were treated by insulin (0.4%). Self-monitoring of blood glucose was available only for 94 (55.6%) insulin-treated prisoners. A total of 130 (76.9%) prisoners performed two insulin injections daily or less, 105 (62.1%) prisoners were not allowed to keep their insulin delivery systems with them. Of the prisoners who treated themselves, 14 (12.1%) used syringes and 42 (36.5%) used pen devices. Ninety-two (55.1%) prisoners had had access to a diabetes specialist during the previous year. Diabetic diets were available in only 65 (60.7%) prisons. From June 1998 to June 1999, there were 20 hospital admissions for a diabetic ketoacidosis and 14 for hypoglycaemia. CONCLUSIONS: This study shows that prison decreases the autonomy of diabetic prisoners who often cannot self-inject or test their blood. Access to visiting consultant diabetologists and specialist nurses to educate both prisoners with diabetes and prison staff could improve diabetic care.

[Acquired right-to-left shunt with normal right heart pressure]. / Shunts intra-cardiaques droits-gauches acquis à pressions cardiaques droites normales.

Intracardiac right-to-left shunting through a patent ovale foramen (POF) despite normal right-sided pressures is an uncommon cause of dyspnea with posture worsening in adults. We report herein 6 cases which sum up etiological circumstances, diagnostic workup and management of this syndrome. The main reported etiopathologic mechanism is consistent with a change in the internal configuration of the right atria leading to preferential blood flow from inferior vena cava through patent foramen ovale. The treatment lies on surgical closure of the septal defect, which can now be performed using a noninvasive percutaneous procedure.

[Pulmonary hypertension in patient with beta-thalassemia major]. / Hypertension artérielle pulmonaire chez un patient porteur d'une bêta-thalassémie majeure.

We report a case of pulmonary hypertension (PH) in a 35-year old patient with beta-thalassemia major; he had commenced blood transfusions after the age of 4 years and had been splenectomised at the age of 6 years. PH clinical presentation was not uncommon. Hemodynamic study revealed precapillary PH with high cardiac output; vasodilators agents led to significant pulmonary responsiveness. In beta-thalassemia, whereas congestive heart failure is common and due to cardiac hemosiderin deposition, PH appears to be non rare but its etiopathogenic mechanism remain unclear and probably non univoqual. Hypoxemia as well as hemodynamic changes related to chronic anemia including increased pulmonary flow might play an important role. Management should include blood transfusions to correct anemia, the indication and the choice of vasodilator agents need to be evaluated.

[Pulmonary embolism in patients using estrogen-progestagen contraceptives]. / Embolies pulmonaires sous contraception estro-progestative.

OBJECTIVES: The risk of thromboembolism in patients taking estrogen-progestagen oral contraceptive drugs has apparently increased since the introduction of third-generation progestagens (desogestrel, gestodene). We examined the clinical features, risk factors and outcome of pulmonary embolism in this context. PATIENTS AND METHODS: We reviewed 11 cases of thromboembolism in patients on oral contraception and hospitalized in emergency situations in 1995 and 1996 for pulmonary embolism in order to determine the gravity of the thromboembolic event, risk factors and type of drug used. RESULTS: Early clinical signs had preceded the onset of embolism by 2 to 164 days. PaO2 was below 70 mmHg in 4 patients. Diagnosis was achieved with pulmonary scintigraphy (11 cases), spiral CT (3 cases) and angiopneumography (2 cases). Duplex Doppler visualized the phlebitis in 7 patients. Given heparin (with fibrinolysis in 3 cases) then anti-vitamin K, and after withdrawal of the oral contraceptive, outcome was favorable in all cases. There were no recurrences. The nature of the oral contraceptive varied. Five patients were taking third-generation progestagens. In two cases, embolism had occurred following a change from a second-generation to a third-generation progestagen. Family history of phlebitis and/or abnormal laboratory findings were observed in 6 patients: resistance to activated protein C (2 patients), protein C deficiency (2 patients), anticardiolipin (2 patients) and low-titre antinuclear antibodies (2 patients). CONCLUSION: Pulmonary embolism in patients on oral contraceptives persists despite changes in the hormone content of the drugs. Diagnosis is often delayed. Family history of thrombosis or biological risk factors are often found.

[Pulmonary artery hypertension in HIV seropositive drug addicts. Apropos of 10 cases]. / Hypertension artérielle pulmonaire chez le toxicomane VIH+. A propos de 10 cas.

Pulmonary hypertension (PH) is a classic complication associated with intravenous drug addiction. Various pathogenic mechanisms may be involved but HIV infection now appears to be the main etiologic factor. We report herein 10 case of PH occurred in HIV+ intravenous drug abusers. Each patient had several pathogenic factors: HIV infection, pills crushed and intravenously injected (6 cases), heavy and repeated consumption of amphetamines and cocaine (6 cases), cirrhosis with portal hypertension (2 cases), anticardiolipid antibodies (2 cases). The clinical findings were similar to those reported for PH in HIV seronegative patients; however, in 5 cases, opiates could have alleviated dyspnea, which became perceptible only at the time of drug withdrawal. Because drug addicts usually exhibit a weak support for medical prescriptions, long term therapy needing regular follow-up such as anticoagulation appears to be hazardous and even dangerous. The prognosis remains poor, since the progression of PH led to the death of one third patients within the year following the diagnosis.

Relation between unbound plasma concentrations and toxicity in a prolonged oral etoposide schedule.

OBJECTIVE: This study was undertaken in order to evaluate the impact of pharmacokinetics on the toxicity of oral etoposide administered daily for 21 days. METHODS: The daily dose was 50 mg/m2. Thirty-two patients 24 males and eight females, 36 76 years old, treated for various tumour types), were evaluated. Blood samples were obtained on day 1 for all patients, and on day 21 for 16 patients. Plasma etoposide concentrations were determined by high-performance liquid chromatography, and etoposide plasma protein binding by equilibrium dialysis. RESULTS: On day 1, the mean value (with coefficient of variation for interindividual variability) for the unbound fraction (fu), area under the concentration versus time curve (AUC), and unbound AUC was 9.8% (59%), 34 mg x h/l (39%), and 3.5 mg x h/l (92%), respectively. The ratio between AUC on day 1 and day 21 ranged between 0.5 and 1.8 (mean 0.9, with CV 33%). The plasma trough unbound concentrations and the unbound AUCs both corresponding to the first administration were significantly higher in the 11 patients who had a severe neutropenia than in the 21 patients who had no or moderate toxicity. However, total etoposide concentrations did not differ between these two groups. A limited sampling strategy using the NONMEM program and a database of 89 patients previously studied was performed. The optimal sampling schedule (i.e. 1, 4, and 24 h after oral etoposide administration) allowed to obtain the AUC accurately on day 1. CONCLUSION: Individual adjustment of oral etoposide based on unbound pharmacokinetics after the first administration appears relevant and feasible.

Pulmonary veno-occlusive disease in a HIV-infected intravenous drug abuser.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Its origin remains unknown but in some cases a viral aetiology has been suggested. Recently primary pulmonary hypertension has been increasingly observed in patients with human immunodeficiency virus (HIV) infection, but only one case of pulmonary veno-occlusive disease has so far been described. We report the case of a 27 year old male intravenous drug abuser with HIV infection and pulmonary hypertension. Open lung biopsy led to the diagnosis of pulmonary veno-occlusive disease. This second case of pulmonary veno-occlusive disease raises the question of a relationship between HIV infection and lesions involving the pulmonary veins. However, the pathogenesis of vascular changes remains to be elucidated.

[Disseminated aspergillosis with pulmonary and cardiac localization in an HIV-infected patient]. / Aspergillose disséminée avec localisations pulmonaires et cardiaques chez un sujet infecté par le VIH.

The authors report a case of invasive aspergillosis with pulmonary and cardiac involvement revealed by a pericarditis in a seropositive patient (VIH1). Clinical findings, differential diagnosis and outcome underly the issues encountered in the management of aspergillosis in AIDS patients. Indeed, the low prevalence of aspergillosis in AIDS and the insidious features of aspergillosis locations make the early diagnosis difficult. It is though essential for a favourable outcome under specific treatment. The risk factors, clinical characteristics and diagnostic procedures are mentioned as well as the various available treatments.