Intensive care in patients with lung cancer: a multinational study.

BACKGROUND: Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS: Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS: Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS: ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

[Severe hemoptysis in the onco-hematology patient]. / Hémoptysies sévères du patient d'onco-hématologie.

In France, even though it occurs only exceptionally in cases of hemopathy, severe hemoptysis in cancer is the leading cause of hemoptysis. Without adequate treatment, in-hospital mortality exceeds 60%, even reaching 100% at 6 months. The management of severe hemoptysis should be discussed with the oncologist. Aside from situations of threatening hemoptysis, in which bronchoscopy should be performed immediately, CT angiography is an essential means of localizing the bleeding and determining the causes and the vascular mechanisms involved. In more than 90% of cases, hemoptysis is linked to systemic bronchial or non-bronchial hypervascularization, whereas in fewer than 5%, it is associated with pulmonary arterial origin or, exceptionally, with damage to the alveolar-capillary barrier. The most severely ill patients must be treated in intensive care in centers equipped with interventional radiology, thoracic surgery and, ideally, with interventional bronchoscopy. Interventional radiology is the first-line symptomatic treatment. In over 80% of cases, bronchial arteriography with embolization allows immediate control. Emergency surgery should be avoided, as it is associated with significant mortality. Appropriate and adequate care reduces hospital mortality to 30%, enabling patients to benefit from the most recent, survival-prolonging treatments.

[Hereditary hemorrhagic telangiectasia]. / La maladie de Rendu-Osler (télangiectasie hémorragique héréditaire).

Hereditary hemorrhagic telangiectasia, also known as Rendu-Osler - Weber disease, is a rare, autosomal dominant vascular disease, with prevalence of 1/5,000. The condition is characterized by muco-cutaneous telangiectasias, which are responsible for a hemorrhagic syndrome of variable severity, as well as arteriovenous malformations (AVMs) appearing in the lungs, the liver, and the nervous system. They can be the source of shunts, which may be associated with high morbidity (neurological ischemic stroke, brain abscess, high-output heart failure, biliary ischemia…). It is therefore crucial to establish a clinical diagnosis using the Curaçao criteria or molecular diagnosis based on genetic analysis of the ENG, ACVRL1, SMAD4 and GDF2 genes. In most cases, multidisciplinary management allows patients to have normal life expectancy. Advances in interventional radiology and better understanding of the pathophysiology of angiogenesis have resulted in improved therapeutic management. Anti-angiogenic treatments, such as bevacizumab (BVZ, an anti-VEGF antibody), have proven to be effective in cases involving bleeding complications and severe liver damage with cardiac repercussions. Other anti-angiogenic agents are currently being investigated, including tyrosine kinase inhibitors.

Successful rituximab therapy in a lupus patient with diffuse alveolar haemorrhage.

Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Specific therapy is based on a heavy immunosuppressive treatment that usually associates corticosteroid and cyclophosphamide boluses and plasma exchange. Despite this treatment, an early mortality rate of 20-50% is reported in the literature. Immunosuppression-related complications are responsible for further mortality and morbidity. Rituximab, a specific anti-CD20 antigen B-cell antibody, has been used with success for the treatment of several refractory autoimmune disorders, but rarely for SLE-induced DAH. We report here the first case of SLE-induced DAH treated successfully with rituximab without cyclophosphamide administration in a patient intolerant to cyclophosphamide. We review the two other cases of SLE-induced DAH managed with rituximab as a part of the immunosuppressive regimen.

Daily multidisciplinary COVID-19 meeting: Experiences from a French university hospital.

OBJECTIVES: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic. In absence of official recommendations, implementing daily multidisciplinary team (MDT) COVID-19 meetings was urgently needed. Our aim was to describe our initial institutional standard operating procedures for implementing these meetings, and their impact on daily practice. METHODS: All consecutive patients who were hospitalized in our institution due to COVID 19, from March 31 to April 15, 2020, were included. Criteria to be presented at MDT meetings were defined as a proven COVID-19 by PCR or strongly suspected on CT scan, requiring hospitalization and treatment not included in the standard of care. Three investigators identified the patients who met the predefined criteria and compared the treatment and outcomes of patients with predefined criteria that were presented during MDT meeting with those not presented during MDT meeting. COVID-19 MDT meeting implementation and adhesion were also assessed by a hospital medical staff survey. RESULTS: In all, 318 patients with confirmed or suspected COVID-19 were examined in our hospital. Of these, 230 (87%) were hospitalized in a COVID-19 unit, 91 (40%) of whom met predefined MDT meeting criteria. Fifty (55%) patients were presented at a MDT meeting versus 41 (45%) were not. Complementary exploration and inclusion in the CorImmuno cohort were higher in MDT meeting group (respectively 35 vs. 15%, P=0.03 and 80 versus 49%, P=0.0007). Prescription of hydrocortisone hemisuccinate was higher in group of patients not presented during MDT meeting (24 vs. 51%, P=0.007). Almost half of the patients fulfilling the inclusion criteria were not presented at MDT meeting, which can be partly explained by technical software issues. CONCLUSIONS: Multidisciplinary COVID-19 meetings helped implementing a single standard of care, avoided using treatments that were untested or currently being tested, and facilitated the inclusion of patients in prospective cohorts and therapeutic trials.

Diffuse alveolar haemorrhage: factors associated with in-hospital and long-term mortality.

Diffuse alveolar haemorrhage (DAH) is a feature of several immune and nonimmune disorders. Reported prognosis is poor, with in-hospital mortality ranging from 20% to 100%. Early identification of prognostic factors may be useful in the initiation of appropriate treatment. We retrospectively analysed the charts of all patients referred to a university hospital for DAH between 1980 and 2008. Variables associated with in-hospital and long-term mortality were determined using a logistic regression model and the Kaplan-Meier method, respectively. Immunosuppressed patients were excluded. Overall, 97 patients were included in the study. In-hospital mortality was 24.7%. Factors associated with in-hospital mortality were shock (OR 77.5, 95% CI 8.9-677.2), glomerular filtration rate <60 mL x min(-1) (OR 11.2, 95% CI 1.8-68.4) and plasmatic lactate dehydrogenase level more than twice the normal value (OR 12.1, 95% CI 1.7-84.3). Mortality among discharged patients was 16.4% with a median follow-up duration of 34 months. Factors associated with increased long-term mortality in univariate analysis were age over 60 yrs (p = 0.026), cardiovascular comorbidity (p = 0.027) and end-stage renal failure with dependence on haemodialysis (p = 0.026). Patients with immune and nonimmune DAH had similar outcomes. Early outcome depended on nonpulmonary organ failures. Conversely, late outcome was related to age, cardiac comorbidities and the need for haemodialysis.

[Normal and abnormal systemic pulmonary circulation: CT imaging features]. / Vascularisation systémique normale et pathologique du poumon: sémiologie tomodensitométrique.

In most cases, treatment of life-threatening hemoptysis requires systemic arterial embolization, bronchial or not. Knowledge of the normal and pathological features of this systemic arterial network as depicted on multidetector row CTA, is an essential key because this examination has become the main imaging study prior to any interventional procedure. This article will review the indications for chest CTA, technical considerations and protocol in the evaluation of the systemic pulmonary circulation, as well as the imaging features of this circulation with emphasis on the normal and pathological imaging features to better correlate with the clinical presentation.

The 3rd degree of biomimetism: associating the cavity effect, ZnII coordination and internal base assistance for guest binding and activation.

The synthesis and characterization of a resorcinarene-based tetra(imidazole) ligand is reported. The properties of the corresponding ZnII complex are studied in depth, notably by NMR spectroscopy. In MeCN, acid-base titration reveals that one out of the four imidazole arms is hemi-labile and can be selectively protonated, thereby opening a coordination site in the exo position. Quite remarkably, the 4th imidazole arm promotes binding of an acidic molecule (a carboxylic acid, a ß-diketone or acetamide), by acting as an internal base, which allows guest binding as an anion to the metal center in the endo position. Most importantly, the presence of this labile imidazole arm makes the ZnII complex active for the catalyzed hydration of acetonitrile. It is proposed that it acts as a general base for activating a water molecule in the vicinity of the metal center during its nucleophilic attack to the endo-bound MeCN substrate. This system presents a unique degree of biomimetism when considering zinc enzymes: a pocket for guest binding, a similar first coordination sphere, a coordination site available for water activation in the cis position relative to the substrate and finally an internal imidazole residue that plays the role of a general base.

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs).

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.

Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis.

Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV) proteins have been analyzed in lymphoid organs from seropositive patients. Indeed, an active HIV replication coexists with a major CD8+ lymphocytic infiltration in these organs. We have shown in a previous report that HIV-seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins. The primary NEF-specific CTL responses were further characterized by epitope mapping. Determination of epitope-specific CTL frequencies were performed by limiting dilution analysis. Our results indicated that, in addition to the central region of NEF (AA66-148), a new immunodominant region is recognized by CTL. This region corresponds to the carboxyl-terminal domain of NEF (amino acids 182-206). AA182-206 is recognized in association with at least two common human histocompatibility leukocyte antigen (HLA) molecules (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic lymphocytes. Our data indicate that lymphoid organs may represent a major reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl-terminal domain of NEF was found to be conserved among several HIV strains. Therefore, our finding is of interest for further HIV vaccines development.

[Management of severe hemoptysis: experience in a specialized center]. / Prise en charge des hémoptysies graves: expérience d'un centre spécialisé

Bronchiectasis, cancer and tuberculosis account for the majority of haemoptysis requiring intensive care unit admission. Bedside evaluation (volume and bronchoscopic active bleeding) is safe to screen patients for arteriography and bronchial artery embolisation (BAE). First-line interventional arteriography should be favour over surgery in patients with non traumatic life-threatening hemoptysis. Surgery must be reserved in cases of failure or recurrence of bleeding after BAE.

[Immune mediated intra-alveolar haemorrhage in the adult]. / Hémorragies intra-alvéolaires de l'adulte d'origine immunitaire.

INTRODUCTION: The diagnosis of diffuse intra-alveolar haemorrhage (DAH) is suggested by the combination of haemoptysis, anaemia and pulmonary infiltrates. Broncho-alveolar lavage produces macroscopically haemorrhagic fluid and/or haemosiderin laden macrophages. The diagnostic approach should allow distinction between immune mediated and other causes on account of the therapeutic implications. BACKGROUND: The main immunological causes are small and medium vessel vasculitis (Wegener's granulomatosis, microscopic polyangeitis), lupus and Goodpasture's syndrome. Other immune disorders are only rarely involved. The association of DAH with an acute glomerulonephritis, indicating the pulmonary-renal syndrome, extra-thoracic involvement and immunological abnormalities suggest an immune aetiology. Immunosuppressant treatment should be started as soon as possible with corticosteroids often combined with intravenous cyclophosphamide. Plasmapharesis is indicated for Goodpasture's syndrome and poorly responding lupus. Aggravating factors such as hypervolaemia and disorders of haemostasis should be searched for and treated. Hospital mortality is close to 20%. VIEWPOINT AND CONCLUSION: Immune mediated DAH is a disorder whose rarity justifies the establishment of a national registry with the aim of developing standardised diagnostic and therapeutic strategies.

[Haemoptysis after anesthesia]. / Hémoptysie au réveil anesthésique.

Postobstructive pulmonary oedema is a complication after extubation that occurs rarely . It can be associated with haemoptysis. We report two cases of haemoptysis occuring in ASA 1 otherwise healthy patients who underwent uncomplicated anaesthesia. Understanding of the mechanism and prompt treatment lead to rapid recovery of this dramatic complication.

[Critical evaluation and predictive value of clinical presentation in out-patients with acute community-acquired pneumonia]. / 07--analyse critique et valeurs prédictives des signes de pneumonies aiguës communautaires en médecine ambulatoire.

Diagnostic probability of community-acquired pneumonia (CAP) depends on data related to age and clinical and radiological findings. The critical evaluation of data in the literature leads to the following conclusions: 1) the prevalence of CAP in a given population with acute respiratory disease is 5% in outpatients and 10% in an emergency care unit. This could be as low as 2% in young people and even higher than 40% in hospitalized elderly patients; 2) the collection of clinical data is linked to the way the patient is examined and to the expertise of the clinician. The absolute lack of "vital signs" has a good negative predictive value in CAP; presence of unilateral crackles has a good positive predictive value; 3) there is a wide range of X-ray abnormalities: localized alveolar opacities; interstitial opacities, limited of diffused. The greatest radiological difficulties are encountered in old people with disorders including chronic respiratory or cardiac opacities and as a consequence of the high prevalence of bronchopneumonia episodes at this age; 4) among patients with lower respiratory tract (LRT) infections, the blood levels of leukocytes, CRP and procalcitonine are higher in CAP patients, mainly when their disease has a bacterial origin. Since you have not a threshold value reliably demonstrated in large populations with LRT infections or acute respiratory disease, presence or absence of these parameters could only be taken as a slight hint for a CAP diagnosis.

[Spontaneous hemothorax: a rare but serious complication of intralobular pulmonary sequestration]. / Un hémothorax spontané: complication rare mais grave d'une séquestration pulmonaire intra-lobaire.

Pulmonary sequestration is a rare congenital malformation characterized by a non-functional portion of pulmonary parenchyma devoid of any connection with the bronchial tree and pulmonary artery. If not identified antenatally or at birth, the sequestration may not be discovered until complications, mainly repeated infections, arise. Hemorrhage is another but much rarer complication which is generally severe. We report a new case of intralobular pulmonary sequestration revealed by hemoptysis then massive hemothroax with shock requiring emergency thoracotomy for hemostasis.

[Intra-alveolar hemorrhage revealing pheochromocytoma]. / Hémorragie intra-alvéolaire révélatrice d'un phéochromocytome.

We report a case of pheochromocytoma revealed by alveolar hemorrhage in a 51-year-old woman. Pheochromocytomas are rare tumors deriving from the chromaffin tissue, and which clinical manifestations are highly variable, mostly unspecific, and very rarely concern the lung. Therefore, the diagnosis is often missed or delayed. However, without correct diagnosis and subsequently adapted treatment, the disease may be fatal. Thus, clinicians should be aware of the possible diagnosis of pheochromocytoma in patients presenting hemoptysis of an unknown origin.

[Acute forms of diffuse interstitial hypoxemic pneumonia in immunocompetent patients]. / Les formes aiguës des pneumopathies infiltrantes diffuses hypoxémiantes de l'immunocompétent.

The large majority of patients with acute respiratory failure present diffuse pulmonary opacities resulting from pulmonary embolism, intra-alveolar hemorrhage, or a classical cause of ARDS. In a small number of patients however, these opacities correspond to diffuse interstitial pneumonia. This should be suspected in light of the context, the time of formation, and the unusual respiratory and/or extrarespiratory signs. If there is a clinical doubt, thoracic scan and bronchoalveolar lavage should be performed together with infectious and immunology tests. Treatment depends on the cause and/or the type of lesion.

[Alveolar hemorrhage]. / Hémorragie intra-alvéolaire.

Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority.

Severe hemoptysis: From diagnosis to embolization.

Severe hemoptysis is life-threatening to patients because of the asphyxia it causes. The diagnosis and treatment are therefore urgent and chest imaging is essential. Multidetector CT-angiography provides an exhaustive non-invasive assessment which includes localization, mechanisms, causes and severity of the hemoptysis. It is an invaluable step in preparation for endovascular treatment which is the first line invasive therapy, particularly with bronchial arteriography embolization in the majority of cases (over 90%) and erosion or rupture of the pulmonary artery in less than 10% of cases. Hemoptysis control is achieved in 65 to 92% of cases depending on the cause.