A comparison of meningococcal carriage by pregnancy status

Neisseria meningitidis is the second leading cause of invasive meningitis. A prerequisite for infection is colonization of the nasopharynx, and asymptomatic carrier rates are widely reported in the range of 10-15%. Recent reports have indicated an increased likelihood that a pediatric admission for Neisseria meningitidis will have a mother who is pregnant in the home. We hypothesized that this association may relate to immunologic changes in pregnancy leading to higher carrier rates

A comprehensive review of the PARTNER trial

ObjectivePercutaneous transcatheter aortic valve replacement was introduced in 2002, but its effectiveness remained to be assessed.MethodsA prospective, randomized trial (the Placement of Aortic Transcatheter Valves, or PARTNER) was designed with 2 arms: PARTNER A (n = 699) for high-risk surgical patients (Society of Thoracic Surgeons score >10%, surgeon assessed risk of mortality >15%) and PARTNER B (n = 358, patients inoperable by assessment of 2 surgeons). PARTNER A patients were divided into femoral artery access transcatheter aortic valve replacement or none (n = 207), and then randomized to open aortic valve replacement (n = 351) or device (n = 348). Inclusion criteria included valve area <0.8 cm2, gradient >40 mm Hg or peak >64 mm Hg, and survival >1 year. The end point of the study was 1-year mortality.ResultsThirty-day mortality for PARTNER A was 3.4% for transcatheter aortic valve replacement and 6.5% for aortic valve replacement; 1-year mortality was 24.2% and 26.8%, respectively (P = .001 for noninferiority). The respective prevalence of stroke was 3.8% and 2.1% (P = .2), although for all neurologic events, the difference between transcatheter aortic valve replacement and aortic valve replacement was significant (P = .04), including 4.6% for femoral artery access transcatheter aortic valve replacement versus 1.4% for open aortic valve replacement (P = .05). For PARTNER B—transcatheter aortic valve replacement versus medical treatment—30-day mortality was 5.0% versus 2.8% (P = .41), and at 1 year, mortality was 30.7% versus 50.7% (P < .001), respectively. Hospitalization cost of transcatheter aortic valve replacement for PARTNER B was $78,542, or$50,200 per year of life gained. Analysis of PARTNER A strokes showed that hazard with transcatheter aortic valve replacement peaked early, but thereafter remained constant in relation to aortic valve replacement. Two-year PARTNER A data showed paravalvular regurgitation was associated with increased mortality, even when mild (P < .001). Continued access to transapical transcatheter aortic valve replacement (n = 853) showed a mortality of 8.2% and decline in strokes to 2.0%. Of the 1801 Cleveland Clinic patients reviewed to December 2010, 214 (12%) underwent transcatheter aortic valve replacement with a mortality of 1%; in 2011, 105 underwent transcatheter aortic valve replacement: 34 transapical aortic valve replacement, with no deaths, and 71 femoral artery access aortic valve replacement with 1 death.ConclusionsThe PARTNER A and B trials showed that survival has been remarkably good, but stroke and perivalvular leakage require further device development

Adverse events during reoperative cardiac surgery: Frequency, characterization, and rescue

ObjectivesTo (1) determine frequency of occurrence and risk factors for intraoperative adverse events (IAE) during reoperative cardiac surgery, (2) characterize them with respect to structure injured, timing, and use of preventive strategies, and (3) identify the impact on outcome in terms of successful and unsuccessful rescue and cost.MethodsOperative notes of 1847 patients undergoing reoperative cardiac surgery were reviewed to identify and characterize documented intraoperative adverse events. Logistic regression modeling was used to identify risk factors for intraoperative adverse events and outcomes. Expected versus observed poor outcomes (stroke, myocardial infarction, death) was used to measure rescue.ResultsAmong 127 patients, 145 (7%) intraoperative adverse events occurred. These included injuries to bypass grafts (n = 47), heart (n = 38), and great vessels (n = 28) and ischemia without graft injury (n = 22). Most occurred on opening (n = 34, 23%) and during prebypass dissection (n = 57, 39%). Risk incremented as reoperations increased. Seventy-seven patients experienced 1 or more lapses in preventive strategies. Patients with intraoperative adverse events had a greater number of poor outcomes (n = 24 [19%] vs n = 107 [6.2%]; P < .0001) and incurred higher direct technical intraoperative and postoperative costs (ratio 1.3). Twelve patients with intraoperative adverse events were predicted to have poor outcomes versus 24 who did (P < .0001), indicating 12 “failures to rescue.”ConclusionsAdverse events still occur regularly during cardiac reoperation, are related to complexity of the procedure, and occur particularly during dissection and often when preventive strategies have not been used. Compensatory rescue measures are not always successful. Adverse events lead to poor patient outcome and higher cost

Evolution in Cardiovascular Care for Elderly Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: Results From the CRUSADE National Quality Improvement Initiative

OBJECTIVES This study evaluated the impact of age on care and outcomes for non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND Recent clinical trials have expanded treatment options for NSTE ACS, now reflected in guidelines. Elderly patients are at highest risk, yet have previously been shown to receive less care than younger patients. METHODS In 56,963 patients with NSTE ACS at 443 U.S. hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) National Quality Improvement Initiative from January 2001 to June 2003, we compared use of guidelines-recommended care across four age groups: <65, 65 to 74, 75 to 84, and ≥85 years. A multivariate model tested for age-related differences in treatments and outcomes after adjusting for patient, provider, and hospital factors. RESULTS Of the study population, 35% were ≥75 years old, and 11% were ≥85 years old. Use of acute anti-platelet and anti-thrombin therapy within the first 24 h decreased with age. Elderly patients were also less likely to undergo early catheterization or revascularization. Whereas use of many discharge medications was similar in young and old patients, clopidogrel and lipid-lowering therapy remained less commonly prescribed in elderly patients. In-hospital mortality and complication rates increased with advancing age, but those receiving more recommended therapies had lower mortality even after adjustment than those who did not. CONCLUSIONS Age impacts use of guidelines-recommended care for newer agents and early in-hospital care. Further improvements in outcomes for elderly patients by optimizing the safe and early use of therapies are likely

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction)

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine

The writing committee conducted a comprehensive search of the medical and scientific literature through the use of PubMed/MEDLINE. Searches were limited to publications written in the English language. Compiled reports were reviewed and additional articles were provided by committee members. Specifically targeted searches were conducted on the following subtopics: acute aortic dissection, ankylosing spondylitis, aortic dissection and litigation, aortic neoplasm, aortic tumors, Behçet disease, bicuspid aortic valve, calcified aorta, chronic dissection, coarctation of the aorta, D-dimer, dissecting aneurysm, Ehlers-Danlos syndrome, endovascular and aortic aneurysms, medial degeneration, porcelain aorta, giant cell arteritis, imaging and thoracic aortic disease, inflammatory disease, intramural hematoma, Loeys-Dietz syndrome, Marfan syndrome, Noonan syndrome, penetrating aortic ulcer, polycystic kidney disease, thoracic and aortic aneurysms, thoracic aortic disease and patient care, thoracic aortic disease and surgery, thoracic aorta and Kawasaki disease, Takayasu arteritis, thoracoabdominal and aorta or aortic disease, and Turner syndrome. More than 850 references were reviewed, with 830 used as the primary evidence base for the final guideline. The ACCF/AHA Task Force on Practice Guidelines methodology processes were followed to write the text and recommendations. In general, published manuscripts appearing in journals listed in Index Medicus were used as the evidence base. Published abstracts were used only for emerging information but were not used in the formulation of recommendations