Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations.

BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.

Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded.

In vitro effects of fermented papaya (Carica papaya, L.) on platelets obtained from patients with type 2 diabetes.

BACKGROUND AND AIM: Oxidative stress is associated with insulin resistance pathogenesis, insulin secretion deficiency, and complication onset. Fermented papaya preparation (FPP), a dietary supplement obtained by fermentation of the papaya fruit, may be used as an antioxidant in the prevention of diabetic complications. METHODS AND RESULTS: Platelets from 30 patients with type 2 diabetes mellitus (DM 2) and 15 healthy subjects were analyzed to evaluate the in vitro effects of FPP incubation. Na(+)/K(+)-adenosine triphosphatase (ATPase) activity, membrane fluidity, total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, and conjugated diene levels were determined. In vitro FPP incubation improved platelet function, by enhancing Na(+)/K(+)-ATPase activity and membrane fluidity, and ameliorated the antioxidant system functionality, through an increase in TAC and SOD activity and a parallel decrease in conjugated diene levels in patients with DM 2. CONCLUSION: Our data suggest that the incubation with FPP may have a protective effect on platelets from patients with DM 2, by preventing the progression of oxidative damage associated with diabetes and its complications.

Role of BRAF molecular analysis in the management of papillary thyroid carcinoma: analysis of cytological and histological samples.

BACKGROUND: Although fine needle aspiration (FNA) is the standard diagnostic test for the characterization of a suspicious thyroid nodule, in some cases cytological evaluation is inconclusive. The aim of this study was to determine the role of BRAF mutation in aiding diagnosis and to verify whether archival cytological samples could be suitable for molecular analysis. METHODS: Eighty-five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56 subsequently underwent surgery. The usefulness of archival samples for molecular analysis was also studied in a second cohort of 42 patients with a confirmed diagnosis of papillary thyroid carcinoma for whom both archived paraffin-embedded histological samples and cytological smears were available. A further 15 patients with paired fresh FNA and archived cytological and histological samples were recruited. RESULTS: BRAF mutation was found in the fresh FNA samples from 10 of 56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3 and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and negative predictive value of 57% (26/46). There was absolute concordance between the BRAF results obtained with 42 histological and cytological archived samples. BRAF analysis on 15 archived cytological samples showed absolute concordance with histology, whereas there was one false negative on the matched fresh FNA. CONCLUSION: BRAF analysis is a highly specific test that can facilitate cytological diagnosis in some cases and can also be performed on archived cytological samples.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

Oxidative stress and psoriasis: the effect of antitumour necrosis factor-α inhibitor treatment.

BACKGROUND: Psoriasis is a chronic, inflammatory skin condition associated with a high frequency of cardiovascular events. Modifications of plasma lipids, and an increase in the levels of biochemical markers of inflammation and lipid peroxidation have been reported in subjects with psoriasis, suggesting a relationship between psoriasis, inflammation and oxidative damage. OBJECTIVES: To investigate whether modulation of inflammatory activity by tumour necrosis factor-α inhibitors in patients with psoriasis is associated with modification of lipid profiles, oxidative stress and paraoxonase (PON)1 activity. METHODS: The levels of plasma lipids and lipoprotein(a), and the levels of the markers of inflammation and lipid peroxidation were evaluated in subjects with psoriasis (n=23) before and after 24 weeks of treatment with etanercept. In the same subjects plasma total antioxidant capacity and the activity of PON1, an antioxidant and anti-inflammatory enzyme associated with the high-density lipoproteins (HDLs), were investigated. RESULTS: The results showed that clinical improvement in patients with psoriasis treated with etanercept is associated with a reduction in the levels of inflammatory markers [C-reactive protein (CRP)] and lipid peroxidation, and also with increased antioxidant capacity in the serum of patients with psoriasis. These modifications are associated with a significant increase in the activity of PON1. A significant increase in the PON1/CRP ratio has also been observed in patients with psoriasis after treatment. The significant inverse correlation between CRP and PON1 activity suggests a relationship between PON1 activity and inflammation. CONCLUSIONS: Treatment with etanercept is associated with a reduction in lipid peroxidation and an improvement in HDL antioxidant and anti-inflammatory properties.

Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: role of the enzyme paraoxonase-1.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease associated with abnormal plasma lipid metabolism and with a high frequency of cardiovascular events. Modifications of plasma lipids and an increase in the levels of biochemical markers of lipid peroxidation have been reported in subjects with psoriasis, suggesting a relationship between psoriasis, lipoproteins and oxidative damage. OBJECTIVES: To investigate further the relationship between lipoproteins and oxidative stress in psoriasis. METHOD: The levels of plasma lipids, lipoprotein(a) [Lp(a)] and markers of lipid peroxidation were evaluated in subjects with psoriasis (n=23) and in controls (n=25). In the same subjects, the activity of paraoxonase-1 (PON1), an antioxidant and an anti-inflammatory enzyme associated with high-density lipoproteins, was investigated. RESULTS: The results showed higher levels of Lp(a) in the serum of patients with psoriasis compared with controls (P<0·001). Higher levels of lipid hydroperoxides (P<0·001) and lower PON1 activity were observed in the serum of patients compared with healthy subjects, confirming that psoriasis is associated with oxidative stress. The imbalance between oxidative stress and antioxidant enzymes, and the increase of Lp(a) serum levels was related to the extent and severity of psoriasis. Finally, our results demonstrated that Lp(a) levels were positively correlated with markers of lipid peroxidation and negatively related to PON1 activity, suggesting that subjects with higher levels of Lp(a) are more exposed to oxidative damage. CONCLUSIONS: Our results provide further evidence that oxidative stress and impairment of the antioxidant system in the plasma of patients may play a role in pathogenesis and progression of psoriasis and related complications.

Effect of dietary lipids on paraoxonase-1 activity and gene expression.

AIMS: Aim of the paper was to summarize the literature about the effect of dietary lipids on activity of paraoxonase-1 (PON1), a multifunctional enzyme associated with high density lipoprotein (HDL). PON1 exerts a protective effect against oxidative damage of cells and lipoproteins and modulates the susceptibility of HDL and LDL to atherogenic modifications such as homocysteinylation. DATA SYNTHESIS: The present review shows evidence that the amount and the composition of dietary lipids are key factors in the modulation of PON1. The effect of dietary lipids is also modulated by PON1 polymorphisms. The molecular mechanisms involved include an effect on PON1 hepatic synthesis or secretion and/or modification of PON1 interactions with HDL. Changes of PON1 activity could also be related to dietary intake of oxidized lipids that behave as PON1 inhibitors. CONCLUSION: Dietary fatty acids by the modulation of PON1 gene expression and activity could constitute an useful approach for the prevention of human diseases associated with oxidative damage.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Magnetic resonance diagnosis of posterior horn tears of the lateral meniscus using a thin axial plane: the zip sign--a preliminary study.

OBJECTIVE: The "zip" sign is a newly described form of meniscal tear progressing from the distal insertion of menisco-femoral ligaments (MFLs) through the lateral meniscal wall; the tear occurs during anterior cruciate ligament (ACL) rupture. The purpose of this study was to evaluate the zip sign on knee MRI within the context of ACL injuries. METHODS: From a series of 261 MR examinations for acute knee injury, we selected 97 patients with both MR and arthroscopic data for a retrospective blinded review. The zip sign was defined on axial thin MR sections as a straight line from the distal insertion of MFLs in association with five sagittal images lateral to the posterior cruciate ligament (PCL) where the MFLs were identified. Sensitivity and specificity in detecting lateral meniscal tears before and after having defined the zip sign were calculated. RESULTS: Sensitivity in detecting the tears of the posterior horn of the lateral meniscus (PHLM) reached 87.5% (CI 0.68-0.97) after zip sign criteria were defined. The zip sign has excellent inter-observer agreement, К>0.90. CONCLUSION: The zip sign indicates a lesion at the insertion site of MFLs into the PHLM on thin axial images associated with sagittal MR sections that may improve MR sensitivity in detecting PHLM tears.

Dental examiners consistency in applying the ICDAS criteria for a caries prevention community trial.

AIM: To examine dental examiners' one-year consistency in utilizing the International Caries Detection and Assessment System (ICDAS) criteria after baseline training and calibration. METHODS: A total of three examiners received baseline training/calibration by a "gold standard" examiner, and one year later re-calibration was conducted. For the baseline training/calibration, subjects aged 8-16 years, and for the re-calibration subjects aged five to six years were recruited for the study. The ICDAS criteria were used to classify visual caries lesion severity (0-6 scale), lesion activity (active/inactive), and presence of filling material (0-9 scale) of all available tooth surfaces of permanent and primary teeth. The examination used a clinical light, mirror and air syringe. Kappa (weighted: Wkappa, unweighted: Kappa) statistics were used to determine inter-and intra-examiner reliability at baseline and re-calibration. RESULTS: For lesion severity and filling criteria, the baseline calibration on 35 subjects indicated an inter-rater Wkappa ranging from 0.69-0.92 and intra-rater Wkappa ranging from 0.81-0.92. Re-calibration on 22 subjects indicated an inter-rater Wkappa of 0.77-0.98 and intra-rater Wkappa ranged from 0.93-1.00. The Wkappa for filling was consistently in the excellent range, while lesion severity was in the good to excellent range. Activity kappa was in the poor to good range. All examiners improved with time. CONCLUSIONS: The baseline training/calibration in ICDAS was crucial to maintain the stability of the examiners reliability over a one year period. The ICDAS can be an effective assessment tool for community-based clinical trials.

Inter- and intraobserver consistency in assessing eligibility for bevacizumab (BVZ) in non-small-cell lung cancer (NSCLC) patients with centrally located tumors.

BACKGROUND: Bevacizumab (BVZ) combined with platinum-based therapy is registered for first-line treatment of nonsquamous non-small-cell lung cancer (NSCLC). Patients with centrally located tumors are stated ineligible for BVZ treatment. The goal of this study was to assess the consistency in evaluating eligibility of patients with central tumors for BVZ treatment. MATERIALS AND METHODS: The study group was composed of 150 NSCLC patients with centrally located tumors. Eligibility for BVZ was assessed by chest computed tomography (CT) scan. Eligibility was assessed independently using CT images reviewed on workstations. Inter- and intraobserver variations on 50 randomly extracted patients were estimated through a statistical modeling (multiple correspondence analysis). RESULTS: Discordance in eligibility was found for 82 patients (55%). The interobserver strength of agreement was fair to moderate (average kappa = 0.40). Contrarily, the intraobserver strength of agreement was good to very good (average kappa = 0.74). At multivariate analysis, the risk of discrepancy was essentially related to the assessment of the contact between the tumor and the vessels (odds ratio = 13.3, 95% confidence interval 2.8-62.6, P = 0.001). CONCLUSIONS: The consistency in evaluating eligibility of patients with central tumors for BVZ treatment is weak. The study group indicated more stringent criteria to help physicians in taking the best treatment choice that need however to be prospectively validated.

Imaging of tumors of the trachea and central bronchi.

Tumors of the trachea and central bronchi can be benign or malignant. Clinical presentation may be confusing, particularly in benign tumors that can be misdiagnosed as asthma or chronic bronchitis. Chest radiography has many limitations and is often considered unremarkable in patients with tumors of the central airways; therefore, multidetector CT (MDCT) has become the most useful noninvasive method for diagnosing and assessing the central airways. The purpose of this article is to provide a review of imaging of the tumors of the trachea and central bronchi. We emphasize the crucial role of MDCT and postprocessing techniques in assessing neoplasms of the central airways.

[Post treatment thoracic aorta: CT and MR imaging features]. / Comment je contrôle une aorte thoracique après traitement en scanner ou en IRM?

Follow-up after thoracic aortic repair relies on CT and MR imaging in order to detect complications from the treatment or underlying pathology. Following prosthetic repair of the ascending aorta, peri-prosthetic hematoma and anastomotic complications (leak, false aneurysm, peri-prosthetic circulation) should be excluded. Following treatment with a covered stent, the location of the prosthesis and its skeleton should be evaluated and endo-leaks and wall defects should be excluded. Following treatment of a dissection, there often is persistent flow in the false lumen. The entry points into the false lumen should be identified. The caliber of the aorta at different levels should be assessed. Signs of ischemia (static and dynamic) and acute complications should be excluded in patients with acute chest pain. Atherosclerosis and dysplastic conditions may affect other segments of the aorta (aneurysm, dissection, hematoma). Follow-up is performed with CT, if possible, when high-resolution evaluation is required, of with MRI in other cases. Follow-up is obtained on a yearly basis or twice a year when an evolutive process is identified. It is performed every two to five years when the risk is low. Follow-up should be suggested by the radiologist.

Artificial intelligence solution to classify pulmonary nodules on CT.

PURPOSE: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques. MATERIALS AND METHOD: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC). RESULTS: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%). CONCLUSION: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

Imaging of tumors of the trachea and central bronchi.

Tumors of the trachea and central bronchi can be benign or malignant. Clinical presentation may be confusing, particularly in benign tumors that can be misdiagnosed as asthma or chronic bronchitis. Chest radiography has many limitations and is often considered unremarkable in patients with tumors of the central airways; therefore, multidetector CT (MDCT) has become the most useful noninvasive method for diagnosing and assessing the central airways. The purpose of this article is to provide a review of imaging of the tumors of the trachea and central bronchi. We emphasize the crucial role of MDCT and postprocessing techniques in assessing neoplasms of the central airways.

Dramatic improvement in survival after lung transplantation over time: a single center experience.

Lung transplantation (LT) is a recognized procedure for selected patients with end-stage respiratory failure. We performed 123 LT, including 32 single lung, 84 double lung, and 7 heart-lung transplantations in 48 patients with chronic obstructive pulmonary disease (COPD), 13 patients with pulmonary hypertension (PH), 33 with cystic fibrosis (CF), and 29 with interstitial lung disease (ILD) between July 1990 and January 2008. Survival was compared for periods before and after December 2001. The mean age of patients was 44.4 years (range 16-66.5 years); 84 (69%) were men. Before LT, 1 second forced expiratory volume was 28.7% +/- 18.1% and PaCO(2) = 6.3 kPa. Fifty-five patients were on noninvasive ventilation. Cold ischemia time was 320 +/- 91 minutes. Cardiopulmonary bypass (CPB) was used in 77 patients (64%). There were 18 early surgical reinterventions, 8 extracorporeal membrane oxygenations, and 38 bronchial stent insertions among 206 at-risk bronchial sutures. Crude survivals were 69%, 58%, 41%, and 18% at 1, 2, 5, and 10 years, respectively. Comparing before (n = 70 with 15 CF) vs after December 2001 (n = 53 with 17 CF), survivals were 63% vs 78%, 51% vs 71%, and 33% vs 60% at 1, 2, and 5 years, respectively (P = .01) and for CF patients, 52% vs 100%, 52% vs 94%, and 25% vs 94% at 1, 2, and 5 years, respectively (P = .005). There was significant improvement in survival before and after 2001 in 123 LT and particularly among CF patients. Improvement in survival after LT may be related to the sum of numerous changes in our practice since December 2001, including the use of pulmonary rehabilitation pre-LT, extracellular pneumoplegia, statins, macrolides for chronic rejection, monitoring of Epstein-Barr blood load, changes in maintenance immunosuppressants, as well as position movement up the coordinator nurse and learning curve.