Screening for colorectal cancer: a guidance statement from the American College of Physicians

DESCRIPTION: Colorectal cancer is the second leading cause of cancer-related deaths for men and women in the United States. The American College of Physicians (ACP) developed this guidance statement for clinicians by assessing the current guidelines developed by other organizations on screening for colorectal cancer. When multiple guidelines are available on a topic or when existing guidelines conflict, ACP believes that it is more valuable to provide clinicians with a rigorous review of the available guidelines rather than develop a new guideline on the same topic. METHODS: The authors searched the National Guideline Clearinghouse to identify guidelines developed in the United States. Four guidelines met the inclusion criteria: a joint guideline developed by the American Cancer Society, the U.S. Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology and individual guidelines developed by the Institute for Clinical Systems Improvement, the U.S. Preventive Services Task Force, and the American College of Radiology. GUIDANCE STATEMENT 1: ACP recommends that clinicians perform individualized assessment of risk for colorectal cancer in all adults. GUIDANCE STATEMENT 2: ACP recommends that clinicians screen for colorectal cancer in average-risk adults starting at the age of 50 years and in high-risk adults starting at the age of 40 years or 10 years younger than the age at which the youngest affected relative was diagnosed with colorectal cancer. GUIDANCE STATEMENT 3: ACP recommends using a stool-based test, flexible sigmoidoscopy, or optical colonoscopy as a screening test in patients who are at average risk. ACP recommends using optical colonoscopy as a screening test in patients who are at high risk. Clinicians should select the test based on the benefits and harms of the screening test, availability of the screening test, and patient preferences. GUIDANCE STATEMENT 4: ACP recommends that clinicians stop screening for colorectal cancer in adults over the age of 75 years or in adults with a life expectancy of less than 10 years.     

Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications. METHODS: This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).     

On relaxations and aging of various glasses

Slow relaxation occurs in many physical and biological systems. "Creep" is an example from everyday life. When stretching a rubber band, for example, the recovery to its equilibrium length is not, as one might think, exponential: The relaxation is slow, in many cases logarithmic, and can still be observed after many hours. The form of the relaxation also depends on the duration of the stretching, the "waiting time." This ubiquitous phenomenon is called aging, and is abundant both in natural and technological applications. Here, we suggest a general mechanism for slow relaxations and aging, which predicts logarithmic relaxations, and a particular aging dependence on the waiting time. We demonstrate the generality of the approach by comparing our predictions to experimental data on a diverse range of physical phenomena, from conductance in granular metals to disordered insulators and dirty semiconductors, to the low temperature dielectric properties of glasses.     

Mortality of patients with pulmonary embolism

BACKGROUND: Pulmonary embolism (PE) is a potentially fatal disorder with highly varying mortality rates. To provide information that is more precise for prospective intervention studies, we analysed the data of our patients with PE, defining clinically relevant subgroups with respect to their individual mortality rates. METHODS: We studied 283 consecutive patients with confirmed PE diagnosis, with respect to demographic data, risk factors for thromboembolic disease and clinical signs. In addition, diagnostic and therapeutic interventions such as blood gas analysis (BGA), lactate and D-dimer determination, electrocardiography (ECG), echocardiography, spiral computer tomography (Spiral CT), ventilation/perfusion lung scintigraphy (V/Q-Scan), thrombolytic therapy, mechanical ventilation, and cardiopulmonary resuscitation (CPR), were accounted for. Study endpoint was mortality rates on day three. RESULTS: Overall, mortality rate was 15% (42 of 283). Mortality rates differed considerably; 95% of patients with cardiac arrest on arrival (21 of 22), 85% of patients with cardiac arrest--not in hospital (28 of 33), 80% of patients receiving mechanical ventilation (40 of 50), 77% of patients needing cardiopulmonary resuscitation within the first 24 hours (37 of 48), 37% of patients with syncope (18 of 49), 30% of patients receiving thrombolytic treatment (25 of 87), 26% of patients on whom lactate measurement was performed (36 of 139), 18% of patients on whom blood gas analysis was done (35 of 197), 17% of patients on whom echocardiography was performed (34 of 195), 8% of patients with twelve complete lead ECG recordings (21 of 262) and D-Dimer determination (12 of 148), 2% of patients tested on Spiral CT (5 of 226) and 1% where a V/Q-Scan was performed (1 of 74). CONCLUSION: Patients with PE who received mechanical ventilation, cardiopulmonary resuscitation, and thrombolytic treatment had very high mortality rates of 80, 77 and 30% respectively. However, patients stable enough for diagnostic procedures as Spiral CTs and V/Q-Scans had mortality rates of 1 to 2%. These facts are to be considered when planning pulmonary embolism intervention trials in which reduction of mortality is a defined endpoint.     

Variant antigenic peptide promotes cytotoxic T lymphocyte adhesion to target cells without cytotoxicity

Timelapse video microscopy has been used to record the motility and dynamic interactions between an H-2D^b-restricted murine cytotoxic T lymphocyte clone (F5) and D^b-transfected L929 mouse fibroblasts (LD^b) presenting normal or variant antigenic peptides from human influenza nucleoprotein. F5 cells will kill LD^b target cells presenting specific antigen (peptide NP68: ASNENMDAM) after “browsing” their surfaces for between 8 min and many hours. Cell death is characterized by abrupt cellular rounding followed by zeiosis (vigorous “boiling” of the cytoplasm and blebbing of the plasma membrane) for 10–20 min, with subsequent cessation of all activity. Departure of cytotoxic T lymphocytes from unkilled target cells is rare, whereas serial killing is sometimes observed. In the absence of antigenic peptide, cytotoxic T lymphocytes browse target cells for much shorter periods, and readily leave to encounter other targets, while never causing target cell death. Two variant antigenic peptides, differing in nonamer position 7 or 8, also act as antigens, albeit with lower efficiency. A third variant peptide NP34 (ASNENMETM), which differs from NP68 in both positions and yet still binds D^b, does not stimulate F5 cytotoxicity. Nevertheless, timelapse video analysis shows that NP34 leads to a significant modification of cell behavior, by up-regulating F5–LD^b adhesive interactions. These data extend recent studies showing that partial agonists may elicit a subset of the T cell responses associated with full antigen stimulation, by demonstrating that TCR interaction with variant peptide antigens can trigger target cell adhesion and surface exploration without activating the signaling pathway that results in cytotoxicity.     

Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique

Background.?Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria. Methods.?HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status. Results.?HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P?相似文献   

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.     

Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing

Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5?years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.     

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza‐Rev and cryopreserved. Subsequent stem cell mobilization was followed by high‐dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up‐regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)‐specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.     

Routine Coronary Arteriography Following Thrombolytic Therapy for Acute Myocardial Infarction: An Unsettled Controversy

Although coronary artery disease remains the leading cause of death in industrialized countries, the management of patients recovering from acute myocardial infarction varies significantly. The issue of routine arteriography and revascularization following thrombolytic therapy remains controversial despite substantial evidence associating infarct-related artery patency with improved cardiac function and survival. Randomized trials of routine intervention after myocardial infarction have generally failed to demonstrate advantages of this invasive approach but methodological problems limit their application to current practice. High-risk patients should be referred for arteriography. While awaiting definitive trials addressing the influence of routine arteriography on patient survival and its cost effectiveness, the management of other patient groups must be individualized.