Admission of advanced lung cancer patients to intensive care unit: A retrospective study of 76 patients

<p>Abstract</p> <p>Background</p> <p>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.</p> <p>Methods</p> <p>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.</p> <p>Results</p> <p>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.</p> <p>Conclusions</p> <p>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.</p

APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells

Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the viral protein Vpx coded by members of the SIVSM/HIV-2 lineage provides partial protection from APOBEC3A during infection. Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells. The findings presented here open up new venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role of the cellular context in the regulation of the antiviral activities of members of the APOBEC3 family and more generally on the natural functions of APOBEC3A

Facteurs pronostiques et survie des patients atteints d'un cancer bronchique évolué en réanimation

Le pronostic des cancers bronchiques évolués est sombre, rendant la décision de réanimation difficile. Nous avons réalisé une étude rétrospective multicentrique sur les patients porteurs d un cancer bronchique non à petites cellules (CBNPC) stade IIIB et IV ou un cancer bronchique à petites cellules (CBPC) localisé et disséminé, hospitalisés en réanimation entre 1996 et 2006. L objectif était d identifier les patients pour qui l apport d une réanimation est bénéfique. Parmi les 76 patients inclus (âge moyen 62,9 +-9,9 ans), 29 étaient porteurs d un CBPC (dont 18 disséminés) et 49 d un CBNPC (20 stade IIIB, 29 stade IV).Ces patients ont été transférés en réanimation pour une pathologie liée au cancer dans 78,9% des cas : iatrogénie (n=30), progression du cancer (n=14), pathologie favorisée par le terrain néoplasique (n=17). L étiologie principale était infectieuse (n=41). Trente six patients sont décédés en réanimation (47,4%). Cinquante sept patients sont décédés à l hôpital (64,5%). Avant ajustement, les facteurs liés à la survenue du décès étaient : un traitement préalable par radiothérapie (p=0,03), une thrombopénie inférieure à 100000/mm3 (0,015), le nombre de défaillances viscérales (p=0,038), la cause infectieuse (p=0,002) en particulier l infection respiratoire (p=0,001), nécessité d une ventilation mécanique (p=0,001), le recours aux amines vasopressives (p<0,0001). A l inverse, la réanimation pour complication iatrogène apparaissait de meilleur pronostic : 56,5% de survivants vs 33,3% pour les autres causes (p=0,04). En analyse multivariée, la mortalité en réanimation restait indépendamment liée à la présence d une thrombopénie inférieure à 100000/mm3 (OR 6, p=0,018), au recours aux amines vasopressives (OR 5,5, p=0,012) et à la ventilation mécanique (OR 4,69, p=0,021). L admission en réanimation en rapport avec une complication du traitement du cancer semblait de moins mauvais pronostic (OR 0,234, p=0,023). En conclusion, la décision d admettre en réanimation un patient atteint d un cancer bronchique évolué reste difficile mais devrait être encouragée plus particulièrement chez les patients présentant une défaillance viscérale en rapport avec une complication du traitement anti-cancéreuxAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Characterization of an antibody panel for immunohistochemical analysis of canine muscle cells

Immunohistochemistry is an indispensable tool in the assessment and characterization of lineage-specific differentiation of grafted cells in cell-based-therapy. This strategy is under investigation for the treatment of many muscle disorders and different animals such as dogs are used as models to study the tissue regeneration. The aim of the present study was to characterize an antibody panel for the analysis of canine muscle cells, useful in routinely processed formalin-fixed paraffin-embedded tissues. Overall, 12 antibodies (8 mouse monoclonal and 4 goat polyclonal), validated for use on human tissues tested for cross-reactivity on canine smooth muscle (bladder, intestine, and uterus), skeletal muscle and heart. Specific staining was achieved with eight antibodies, of which six were cytoplasmic markers (desmin, HDAC8, MHC, SMA, Troponin I and Troponin T) and two were cardiac nuclear markers (GATA-4 and Nkx-2.5). This antibody panel may be useful not only for the evaluation of cell-based therapies in muscle disorders, but also for the evaluation of canine soft tissue neoplasms in veterinary pathology

The rising prevalence of chronic myeloid leukemia in France

Outcomes in chronic myeloid leukemia (CML) have been dramatically improved since the emergence of imatinib and the subsequent generation of tyrosine kinase inhibitors (TKI) in the early 2000s. Indeed, CML is now associated with near-normal life expectancy for the majority of patients, provided they adhere to lifelong TKI-based treatment. This paradigm, in which CML can be regarded as a chronic disease, has inherent consequences on the prevalence of the disease. Our objective was to study CML prevalence trend in the French population from 1960 to 2060. We used a cohort component-based model to forecast the prevalence of CML using projections of the French population, the estimated incidence rates by age and sex, and various hypotheses on the year-specific relative survival. CML prevalence in France is estimated at 2.5 per 100,000 inhabitants before the 1980s, with a progression up to 6 by 2002. Since 2002 this trend has increased further, with current and predicted prevalence reaching levels around 18 and 24 per 100,000 in 2018 and 2030 respectively. CM prevalence reaches 30 per 100,000 by 2050 when progression slows. Our simulations show that prevalence of CML is driven by both population aging and relative survival improvement.</p