Adolescents and Young Adults Living With an Uncertain or Poor Cancer Prognosis:The "New" Lost Tribe

Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a "lost tribe" without a medical "home"; neither pediatric nor adult oncology services were able to provide ageappropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of longterm disease control, AYA care programs should address the unique palliative care needs of this "new" lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group

Diagnosis, prognostic factors and assessment of ALL in adults: 2023 ELN recommendations from a European Expert Panel

Working groups of the European Leukemia Net (ELN) have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors and risk stratification as well as definitions of endpoints and outcomes. Aspects of treatment, management of subgroups and specific situations, aftercare and supportive care are covered in a separate publication. The present recommendation intends to provide guidance for the initial management of adult ALL patients and to define principles as a basis for future collaborative research

Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury during severe infection. To review the cross-talk between coagulation and inflammation that may affect this response. DATA SOURCES: Published articles on experimental and clinical studies of coagulation and fibrinolysis during infection, inflammation, acute lung injury, and evolving acute respiratory distress syndrome. CONCLUSIONS: Fibrin deposition is an important feature of pulmonary infection or severe inflammation. The mechanisms that contribute to this fibrin deposition are bronchoalveolar tissue factor-mediated thrombin generation and localized depression of urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines. Rather than being a unidirectional relationship, the interaction between inflammation and coagulation involves significant cross-talk. Coagulation and fibrinolytic proteins may have an additional role beyond fibrin turnover and inflammation, e.g., in mechanisms mediating cell recruitment and migratio

Anti-tumor necrosis factor antibody impairs the therapeutic effect of ceftriaxone in murine pneumococcal pneumonia

Treatments aimed at inhibition of tumor necrosis factor (TNF) in patients with sepsis have been unsuccessful. Up to 50% of such patients suffer from pneumonia. To determine the effect that treatment with anti-TNF has on pneumococcal pneumonia, mice were intranasally inoculated with Streptococcus pneumoniae and, 25 h later, treated with 1 of the following: (1) control antibody, (2) anti-TNF, (3) ceftriaxone (CEF) with control antibody, or (4) CEF with anti-TNF. In the absence of treatment with CEF, mice displayed high bacterial loads in lungs, and all of these mice died within 5 days after inoculation. Anti-TNF did not influence these outcomes. In contrast, 60% of mice treated with CEF alone survived. Anti-TNF administered together with CEF reduced survival to 40% and was associated with enhanced bacterial outgrowth. These data suggest that treatment with anti-TNF impairs the therapeutic efficacy of CEF during pneumococcal pneumoni

Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia

Cell recruitment is a multistep process regulated by cytokines, chemokines, and growth factors. Previous work has indicated that the urokinase plasminogen activator receptor (uPAR) may also play a role in this mechanism, presumably by an interaction with the beta(2) integrin CD11b/CD18. Indeed, an essential role of uPAR in neutrophil recruitment during pulmonary infection has been demonstrated for beta(2) integrin-dependent respiratory pathogens. We investigated the role of uPAR and urokinase plasminogen activator (uPA) during pneumonia caused by a beta(2) integrin-independent respiratory pathogen, Streptococcus pneumoniae. uPAR-deficient (uPAR(-/-)), uPA-deficient (uPA(-/-)), and wild-type (Wt) mice were intranasally inoculated with 10(5) CFU S. pneumoniae. uPAR(-/-) mice showed reduced granulocyte accumulation in alveoli and lungs when compared with Wt mice, which was associated with more S. pneumoniae CFU in lungs, enhanced dissemination of the infection, and a reduced survival. In contrast, uPA(-/-) mice showed enhanced host defense, with more neutrophil influx and less pneumococci in the lungs compared with Wt mice. These data suggest that uPAR is necessary for adequate recruitment of neutrophils into the alveoli and lungs during pneumonia caused by S. pneumoniae, a pathogen eliciting a beta(2) integrin-independent inflammatory response. This function is even more pronounced when uPAR is unoccupied by uP