Automated intensive care unit risk adjustment: results from a National Veterans Affairs study

CONTEXT: Comparison of outcome among intensive care units (ICUs) requires risk adjustment for differences in severity of illness and risk of death at admission to the ICU, historically obtained by costly chart review and manual data entry. OBJECTIVE: To accurately estimate patient risk of death in the ICU using data easily available in hospital electronic databases to permit automation. DESIGN AND SETTING: Cohort study to develop and validate a model to predict mortality at hospital discharge using multivariate logistic regression with a split derivation (17,731) and validation (11,646) sample formed from 29,377 consecutive first ICU admissions to medical, cardiac, and surgical ICUs in 17 Veterans' Health Administration hospitals between February 1996 and July 1997. MAIN OUTCOME MEASURES: Mortality at hospital discharge adjusted for age, laboratory data, diagnosis, source of ICU admission, and comorbid illness. RESULTS: The overall hospital death rate was 11.3%. In the validation sample, the model separated well between survivors and nonsurvivors (area under the receiver operating characteristic curve = 0.885). Examination of the observed vs. the predicted mortality across the range of mortality showed the model was well calibrated. CONCLUSIONS: Automation could broaden access to risk adjustment of ICU outcomes with only a small trade-off in discrimination. Broader use might promote valid evaluation of ICU outcomes, encouraging effective practices and improving ICU quality.     

抗CD20单抗（Rituximab）作为B细胞淋巴瘤老龄患者初始治疗的新标准

背景侵袭性B细胞淋巴瘤是目前最常见的非霍奇金淋巴瘤类型,主要包括弥漫大B细胞淋巴瘤(DLBCL)和套细胞淋巴瘤(MCL)。超过60%的患者被诊断出B细胞淋巴瘤时年龄都在60岁以上。在过去的30年间,CHOP方案(环磷酰胺、多柔比星、长春新碱、泼尼松)是治疗DLBCL的金标准。年龄较轻的患者     

Restoration of thrombolytic potential in plasminogen-deficient mice by bolus administration of plasminogen

Homozygous plasminogen-deficient (Plg-/-) mice had a significantly reduced thrombolytic capacity toward intravenously injected 125I-fibrin labeled plasma clots prepared from Plg-/- murine plasma (9% +/- 3% lysis after 8 hours; (mean +/- SEM, n = 6), as compared with 82% +/- 8% in wild-type mice; P < .0001). Bolus injection of 1 mg purified murine plasminogen in 10- to 17-week-old Plg-/- mice increased the plasminogen antigen and activity levels at 8 hours to normal levels (130 +/- 5 micrograms/mL). Plasminogen administration was associated with significant restoration of thrombolytic potential (64% +/- 7% spontaneous clot lysis; P < .0001 versus lysis without plasminogen injection). Bolus injection of 1 mg plasminogen in homozygous tissue- type plasminogen activator-deficient (t-PA-/-) mice doubled the plasminogen antigen and activity levels after 8 hours and increased 125I-fibrin clot lysis at 8 hours from 13% +/- 3% to 34% +/- 5% (P = .008). Fibrinogen, t-PA antigen and alpha 2-antiplasmin activity levels after 8 hours were not significantly different in the groups with or without plasminogen injection. Injection of plasminogen induced a variable increase (on average 7- to 10-fold) of PAI-1, but no correlation with the extent of spontaneous clot lysis was observed. Histopathologic examination at the end of the experiments revealed that fibrin deposition in the liver of Plg-/- mice was slightly reduced 8 hours after bolus plasminogen injection (P = .007) and markedly reduced after 24 hours (P < .0001). Plasminogen antigen levels in liver extracts were comparable with those found in wild-type mice at 8 hours (130 +/- 20 versus 110 +/- 15 ng/mg protein) and decreased to 25 +/- 3.2 ng/mg protein at 24 hours. Thus, restoration of normal plasminogen levels in Plg-/- mice normalized the thrombolytic potential toward experimentally induced pulmonary emboli, and resulted in removal of endogenous fibrin deposits within 24 hours.     

Immunotherapy in gastric cancer

Gastric cancer is the second most common of cancerrelated deaths worldwide.In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain poor.Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and melanoma.Here,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric cancer.Adaptive cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric cancer.However,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response.Here,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy.We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment.We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells.Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being.Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.     

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.     

Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder

BACKGROUND: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. METHODS: 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. RESULTS: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. LIMITATIONS: This is a cross-sectional analysis of acutely hospitalized veterans. CONCLUSIONS: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built "from the patient out."