Citations

BACKGROUND: An increasing number of patients require prolonged mechanical ventilation (PMV), which is associated with high morbidity and poor long-term survival, but there are few data regarding the incidence and outcome of PMV patients from a community perspective. METHODS: We retrospectively reviewed the electronic medical records of adult Olmsted county, Minnesota, residents admitted to the intensive care units at the 2 Mayo Clinic Rochester hospitals from January 1, 2003, to December 31, 2007, who underwent tracheostomy for PMV. RESULTS: Sixty-five patients, median age 68 years (interquartile range [IQR] 49–80 y), 39 male, underwent tracheostomy for PMV, resulting in an age-adjusted incidence of 13 (95% CI 10–17) per 100,000 patient-years at risk. The median number of days on mechanical ventilation was 24 days (IQR 18–37 d). Forty-six patients (71%) survived to hospital discharge, and 36 (55%) were alive at 1-year follow-up. After adjusting for age and baseline severity of illness, the presence of COPD was independently associated with 1-year mortality (hazard ratio 3.4, 95% CI 1.4–8.2%). CONCLUSIONS: There was a considerable incidence of tracheostomy for PMV. The presence of COPD was an independent predictor of 1-year mortality.

Abstract Deficiencies in transmembrane activator and CAML interactor (TACI) result in common variable immune deficiency, a syndrome marked by recurrent infections with encapsulated microorganisms, impaired production of antibodies, and lymphoproliferation. How TACI promotes antibody production and inhibits lymphoproliferation is not understood. To answer this question, we studied the generation of immunity to protein antigens in both TACI-deficient and TACI-proficient mice. We show that TACI promotes sustained Blimp-1 expression by B cells responding to antigen, which in turn limits B-cell clonal expansion and facilitates differentiation of long-lived antibody-secreting cells. Short-term IgG secretion occurs independently of TACI as DNA double-strand breaks associated with isotype class switching induce Blimp-1 transiently, independently of TACI. Our results showing that TACI induces and maintains Blimp-1 provide, for the first time, a unified molecular and cellular mechanism explaining the primary features of common variable immune deficiency, exquisite vulnerability to infection with encapsulated organisms, lymphoproliferation, and hypogammaglobulinemia.

BACKGROUND We analyzed serial data in patients with clinically stable monoclonal gammopathy to determine the total variation of serum M-spikes [measured with serum protein electrophoresis (SPEP)], urine M-spikes [measured with urine protein electrophoresis (UPEP)], and monoclonal serum free light chain (FLC) concentrations measured with immunoassay. METHODS Patients to be studied were identified by (a) no treatment during the study interval, (b) no change in diagnosis and <5 g/L change in serum M-spike over the course of observation; (c) performance of all 3 tests (SPEP, UPEP, FLC immunoassay) in at least 3 serial samples that were obtained 9 months to 5 years apart; (d) serum M-spike ≥10 g/L, urine M-spike ≥200 mg/24 h, or clonal FLC ≥100 mg/L. The total CV was calculated for each method. RESULTS Among the cohort of 158 patients, 90 had measurable serum M-spikes, 25 had urine M-spikes, and 52 had measurable serum FLC abnormalities. The CVs were calculated for serial SPEP M-spikes (8.1%), UPEP M-spikes (35.8%), and serum FLC concentrations (28.4%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-spike (7.8%), urine M-spike (35.5%), and serum FLC concentration (27.8%). CONCLUSIONS The variations in urine M-spike and serum FLC measurements during patient monitoring are similar and are larger than those for serum M-spikes. In addition, in this group of stable patients, a measurable serum FLC concentration was available twice as often as a measurable urine M-spike.

Background— The impact of incomplete revascularization (IR) on adverse outcomes after percutaneous coronary intervention remains inconclusive, and few studies have examined mortality during follow-ups longer than 5 years. The objective of this study is to test the hypothesis that IR is associated with higher risk of long-term (8-year) mortality after stenting for multivessel coronary disease. Methods and Results— A total of 13 016 patients with multivessel disease who had undergone stenting procedures with bare metal stents in 1999 to 2000 were identified in the New York State's Percutaneous Coronary Intervention Reporting System. A logistic regression model was fit to predict the probability of achieving complete revascularization (CR) in these patients using baseline risk factors; then, the CR patients were matched to the IR patients with similar likelihoods of achieving CR. Each patient's vital status was followed through 2007 using the National Death Index, and the difference in long-term mortality between IR and CR was compared. It was found that CR was achieved in 29.2% (3803) of the patients. For the 3803 pair-matched patients, the respective 8-year survival rates were 80.8% and 78.5% for CR and IR ( P =0.04), respectively. The risk of death was marginally significantly higher for IR (hazard ratio=1.12; 95% confidence interval, 1.01–1.26, P =0.04). The 95% bootstrap confidence interval for the hazard ratio was 0.98 to 1.32. Conclusions— IR may be associated with higher risk of long-term mortality after stenting with BMS in patients with multivessel disease. More prospective studies are needed to further test this association.

Purpose: To describe technical tips for recanalization of long-segment flush superior mesenteric artery (SMA) occlusions. Technique: Ultrasound-guided left brachial artery access was gained in 2 patients with a 7F 90-cm sheath being advanced to the supraceliac aorta. The SMA stump was visualized using a selective inferior mesenteric artery (IMA) catheterization via femoral approach. A combination of a 7F 100-cm Multipurpose (MPA) guide and a 5F 125-cm MPA catheter was utilized to provide support for selective catheterization. Subsequently, a 0.018-inch wire and catheter were advanced crossing the area of occlusion. Predilatation was performed, followed by placement of covered stent. Both patients had uncomplicated course and resolution of symptoms. Conclusion: Flush SMA occlusions are challenging lesions but may be treated by antegrade percutaneous recanalization with good results. Technical aspects that facilitate recanalization include brachial approach, use of a stiff system (sheath, guide, and catheter) and concomitant injection to facilitate visualization of the SMA stump.

Background—Current clinical diagnosis of long-QT syndrome (LQTS) includes genetic testing of family members of mutation-positive patients. The present study was designed to assess the clinical course of individuals who are found negative for the LQTS-causing mutation in their families.Methods and Results—Multivariate Cox proportional hazards model was used to assess the risk for cardiac events (comprising syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) from birth through age 40 years among 1828 subjects from the LQTS Registry who were found negative for their family LQTS-causing mutation. The median QTc of study subjects was 423 ms (interquartile range, 402–442 ms). The cumulative probability of a first syncope through age 40 years was 15%. However, only 2 patients (0.1%) had ACA, and none died suddenly during follow-up. Independent risk factors for syncope in genotype-negative subjects included female sex (hazard ratio [HR], 1.60;P=0.002), prolonged QTc (HR=1.63 per 100 ms increment,P=0.02), family history of ACA or SCD (HR=1.89,P=0.002), and LQT2 versus LQT1 family mutation (HR=1.41,P=0.03). Subgroup analysis showed that the presence of theK897Tpolymorphism in the LQT2 gene in an affected family was associated with an 11-fold (P=0.001) increase in the risk of recurrent syncope in genotype-negative subjects.Conclusions—Our findings suggest that cardiac events among genotype-negative family members of LQTS patients are dominated by nonfatal syncopal episodes without occurrence of sudden cardiac death. The risk for nonfatal events in this population may be mediated by the presence of common polymorphisms in LQTS genes.