Citations

Background— The relationship between neutrophils and outcomes post–myocardial infarction (MI) is not completely characterized. We examined the associations of neutrophil count with mortality and post-MI heart failure (HF) and their incremental value for risk discrimination in the community. Methods and Results— MI was diagnosed with cardiac pain, biomarkers, and Minnesota coding of the ECG. Neutrophil count at presentation, reported as counts ×10 9 /L, was categorized by tertiles (lower tertile, <5.7; middle tertile, 5.7 to 8.5; upper tertile, >8.5). From 1979 to 2002, 2047 incident MIs occurred in Olmsted County, Minn (mean age, 68±14 years; 44% women). Median (25th to 75th percentile) neutrophil count was 7.0 (5.1 to 9.5). Within 3 years post-MI, 577 patients died, and 770 developed HF. Overall survival and survival free of HF decreased with increased neutrophil tertile ( P <0.001). Compared with the lower tertile, the age and sex adjusted hazard ratio for death was 1.44 (95% CI, 1.14 to 1.81) for the middle tertile and 2.60 (95% CI, 2.10 to 3.22) for the upper tertile ( P <0.001). Similarly, for HF, the hazard ratio was 1.32 (95% CI, 1.09 to 1.59) for the middle and 2.12 (95% CI, 1.77 to 2.53) for the upper tertile ( P <0.001). These associations persisted after adjustment for risk factors, comorbidities, Killip class, revascularization, and ejection fraction. Neutrophil count improved risk discrimination as indicated by increases in the area under the receiver operating characteristic curves (all P <0.05) and by the integrated discrimination improvement analysis (all P <0.001). Conclusions— In the community, the neutrophil count was strongly and independently associated with death and HF post-MI and improved risk discrimination over traditional predictors.

Background— The risk of syncope occurring while driving has obvious implications for personal and public safety. We aimed to define the clinical characteristics, causes, and prognosis of syncope while driving. Methods and Results— In this case-control study of consecutive patients evaluated for syncope from 1996 through 1998 at an academic medical center, we documented causes, clinical characteristics, and recurrence of syncope while driving. Of 3877 patients identified, 381 (9.8%) had syncope while driving (driving group). Compared with the 3496 patients (90.2%) who did not have syncope while driving, the driving group was younger ( P =0.01) and had higher percentages of male patients ( P <0.001) and patients with a history of any cardiovascular disease ( P =0.01) and stroke ( P =0.02). Syncope while driving was commonly caused by neurally mediated syncope (37.3%) and cardiac arrhythmias (11.8%). Long-term survival in the driving group was comparable to that of an age- and sex-matched cohort from the Minnesota population ( P =0.15). Among the driving group, syncope recurred in 72 patients, 35 of whom (48.6%) had recurrence >6 months after the initial evaluation. Recurrences during driving happened in 10 patients in the driving group, 7 of which (70%) were >12 months after the initial evaluation. Conclusions— In our study, neurally mediated syncope was the most common type of syncope while driving. The causes of syncope, the late recurrences of syncope (during ≥6 months of follow-up), and the overall low incidence of recurrent syncope while driving provide useful information to supplement current recommendations on driving for these patients.

Purpose Thalidomide and lenalidomide are immunomodulatory drugs (IMiDs) that produce high remission rates in the treatment of multiple myeloma. Pomalidomide is a new IMiD with high in vitro potency. We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma. Patients and Methods Pomalidomide was administered orally at a dose of 2 mg daily on days 1 through 28 of a 28-day cycle. Dexamethasone 40 mg daily was administered orally on days 1, 8, 15, and 22 of each cycle. Responses were recorded using the criteria of the International Myeloma Working Group. Results Sixty patients were enrolled. Thirty-eight patients (63%) achieved confirmed response including complete response in three patients (5%), very good partial response in 17 patients (28%), and partial response in 18 patients (30%). Responses were seen in 40% of lenalidomide-refractory patients, 37% of thalidomide-refractory patients, and 60% of bortezomib-refractory patients. Responses were seen in 74% of patients with high-risk cytogenetic or molecular markers. Toxicity consisted primarily of myelosuppression. Grade 3 or 4 hematologic toxicity consisted of anemia (5%), thrombocytopenia (3%), and neutropenia (32%). One patient (1.6%) had a thromboembolic event. The median progression-free survival time was 11.6 months and was not significantly different in patients with high-risk disease compared with patients with standard-risk disease. Conclusion The combination of pomalidomide and low-dose dexamethasone is extremely active in the treatment of relapsed multiple myeloma, including high response rates in patients refractory to other novel agents.

Purpose This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients. Patients and Methods This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 μg/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 μg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until ≥ 5 × 10 6 CD34+ cells/kg were collected. The primary end point was the percentage of patients who collected ≥ 5 × 10 6 CD34+ cells/kg in 4 or fewer apheresis days. Results This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions. Conclusion Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34+ cell target for transplantation in fewer apheresis days, compared with G-CSF alone.

The technical evolution of extracorporeal membrane oxygenation (ECMO) coincides with the vast improvement in intensive care medicine of the past 4 decades. Extracorporeal circulatory technology substitutes for acutely failed cardiac or pulmonary function until these organs regain sustainable function through goal-oriented intensive care practice. The technology has been validated to improve survival in select patients who would otherwise have 100% mortality. This is by far the most complex life-sustaining technology employed and thus can contribute significant risks such that the decision to institute ECMO requires prompt risk and benefit analysis. Delaying the institution of ECMO may cause irreversible pulmonary and cardiac injuries in addition to other organs. Therefore, the optimal time of initiating ECMO support is crucial to the survival of a critically ill patient.

Though much has been surveyed and written about the equipment aspects of extracorporeal life support (ECLS) in the past 10 years, there is value in reviewing the use and nonuse of multiple safety devices and techniques. Minimally equipped ECLS circuits for adult and pediatric bridge to decision during cardiac and respiratory failure are rapidly gaining popularity to maintain simplicity and portability. ECLS circuits employed for long-term therapy are outfitted differently and should include more safety devices. The purpose of this review is to compare and contrast the spectrum of minimally equipped ECLS circuits to circuits with maximum flexibility and safety device protection. Due to the lack of high-level, well-controlled scientific studies regarding ECLS equipment and safety devices, this study reviews the basis for how we use ECLS circuits and devices in our institution to provide safe patient support.

ABSTRACT Members of the Streptococcus bovis group are important causes of endocarditis. However, factors associated with their pathogenicity, such as adhesins, remain uncharacterized. We recently demonstrated that endocarditis-derived Streptococcus gallolyticus subsp. gallolyticus isolates frequently adhere to extracellular matrix (ECM) proteins. Here, we generated a draft genome sequence of an ECM protein-adherent S. gallolyticus subsp. gallolyticus strain and found, by genome-wide analyses, 11 predicted LPXTG-type cell wall-anchored proteins with characteristics of MSCRAMMs, including a modular architecture of domains predicted to adopt immunoglobulin (Ig)-like folding. A recombinant segment of one of these, Acb, showed high-affinity binding to immobilized collagen, and cell surface expression of Acb correlated with the presence of acb and collagen adherence of isolates. Three of the 11 proteins have similarities to major pilus subunits and are organized in separate clusters, each including a second Ig-fold-containing MSCRAMM and a class C sortase, suggesting that the sequenced strain encodes three distinct types of pili. Reverse transcription-PCR demonstrated that all three genes of one cluster, acb - sbs7 - srtC1 , are cotranscribed, consistent with pilus operons of other gram-positive bacteria. Further analysis detected expression of all 11 genes in cells grown to mid to late exponential growth phases. Wide distribution of 9 of the 11 genes was observed among S. gallolyticus subsp. gallolyticus isolates with fewer genes present in other S. bovis group species/subspecies. The high prevalence of genes encoding putative MSCRAMMs and pili, including a collagen-binding MSCRAMM, among S. gallolyticus subsp. gallolyticus isolates may play an important role in the predominance of this subspecies in S. bovis endocarditis.