Analysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African Americans.

Although absolute neutrophil counts (ANC) below 1.5x103/uL are used to define neutropenia as a marker of increased susceptibility to infections, their relationship with survival has not been examined. Since low counts trigger extensive investigations, determining prognostic cutoffs especially for different ethnicities and races is critical.A multiethnic cohort of 27,760 subjects, 65 years old and above, was utilized to evaluate the association of neutropenia with overall survival in different ethnicities and races.The mean ANC was 4.6±1.51x103/uL in non-Hispanic whites, 3.6±1.57x103/uL in non-Hispanic blacks and 4.3±1.54x103/uL in Hispanics (p<0.001). An ANC below 1.5x103/uL was associated with significantly shorter overall survival among whites (HR 1.74; 95% CI 1.18 - 2.58; p<0.001), but not in blacks (HR 0.89; 95% CI 0.86 - 1.17; p=0.40) or Hispanics (HR 1.04; 95% CI 0.76 - 1.46; p=0.82), after adjustment for age, sex, comorbidities, anemia and thrombocytopenia. Using Cox regression multivariable models, an ANC below 1.1x103/uL in blacks was found to be associated with increased mortality (HR 1.86; 95%CI 1.21 - 2.87; p<0.01). We found no association between neutropenia and mortality at any ANC cutoff in elderly Hispanics. In conclusion, neutropenia was found to be an independent prognostic variable in the elderly, when determined in race-specific manner. Most importantly, a cutoff of 1.1x103 neutrophils/uL may be a more prognostically relevant marker in elderly blacks and could serve as a novel threshold for further evaluation and intervention in this population.

Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity.

Even though alterations in platelet counts are presumed to be detrimental, their impact on the survival of patients has not been studied in large cohorts. The prevalence of thrombocytopenia and thrombocytosis was examined in a large inner city outpatient population of 36,262 individuals aged ≥65 years old. A significant association with shorter overall survival was found for both thrombocytopenia (HR=1.45; 95% CI: 1.36-1.56) and thrombocytosis (HR=1.75; 95% CI: 1.56-1.97) when compared to the survival of patients with normal platelet counts. This effect persisted across all ethnic groups. However, African-Americans (non-Hispanic Blacks) with either thrombocytopenia or thrombocytosis were at significantly lower risk compared to non-Hispanic Caucasians (HR=0.82; 95% CI: 0.69-0.96 and HR=0.70; 95% CI: 0.53-0.94, respectively). Furthermore, Hispanics with thrombocytosis were found to have a lower mortality risk compared to non-Hispanic Caucasians with thrombocytosis (HR=0.60; 95% CI: 0.44-0.81). A value of <125,000 platelets per microliter was a better prognostic marker for non-Hispanic Blacks and these subjects with this platelet count had similar overall survival to that of Caucasians with a value of <150,000 per microliter. In conclusion, thrombocytosis and thrombocytopenia are independently associated with shorter overall survival in elderly subjects and this effect is modified by ethnicity. Using different thresholds to define the association of thrombocytopenia and thrombocytosis with overall mortality risk among non-Hispanic Blacks may, therefore, be warranted.

Multiplicative interaction between mean corpuscular volume and red cell distribution width in predicting mortality of elderly patients with and without anemia.

Recent studies have shown that an elevated red cell distribution width (RDW) is an important predictor of adverse outcomes. However, the strength of this biomarker has not been tested in a large outpatient elderly population. Also since increased RDW can be due to a variety of etiologies, additional biomarkers are needed to refine the prognostic value of this variable. We assembled a cohort of 36,226 elderly (≥65yo) patients seen at an outpatient facility within the Einstein/Montefiore system from January 1st 1997 to May 1st 2008 who also had a complete blood count performed within 3 months of the initial visit. With a maximum follow-up of 10 years, we found that an elevated RDW (>16.6) was associated with increased risk of mortality in both non-anemic (HR = 3.66, p < 0.05) and anemic patients (HR = 1.87, p < 0.05). The effect of RDW on mortality is significantly increased in non-anemic patients with macrocytosis (HR = 5.22, p < 0.05) compared to those with normocytosis (HR = 3.86, p < 0.05) and microcytosis (HR = 2.46, p < 0.05). When comparing non-anemic patients with both an elevated RDW and macrocytosis to those with neither, we observed an elevated HR of 7.76 (higher than expected in an additive model). This multiplicative interaction was not observed in anemic patients (HR = 2.23). Lastly, we constructed Kaplan-Meier curves for each RDW/MCV subgroup and found worsened survival for those with macrocytosis and an elevated RDW in both anemia and non-anemic patients. Based on our results, the addition of MCV appears to improve the prognostic value of RDW as a predictor of overall survival in elderly patients.

Phase II study of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in advanced pancreatic carcinoma.

PURPOSE: To determine the efficacy and toxicity of the protein kinase C inhibitor bryostatin-1 plus paclitaxel in patients with advanced pancreatic carcinoma. METHODS: Each treatment cycle consisted of paclitaxel 90 mg/m by intravenous infusion over 1 hour on days 1, 8, and 16, plus bryostatin 25 mcg/m as a 1-hour intravenous infusion on days 2, 9, and 15, given every 28 days. Patients were evaluated for response after every 2 treatment cycles, and continued therapy until disease progression or prohibitive toxicity. The primary objective was to determine whether the combination produced a response rate of at least 30%. RESULTS: Nineteen patients with locally advanced or metastatic pancreatic adenocarcinoma received a total of 52 cycles of therapy (range: 1-10). Patients received the combination as first-line therapy for advanced disease (N = 5) or after prior chemotherapy used alone or in combination with local therapy. No patients had a confirmed objective response. The median time to treatment failure was 1.9 months (95% confidence intervals: 1.2, 2.6 months). Reasons for discontinuing therapy included progressive disease or death in 14 patients (74%) or because of adverse events or patient choice in 5 patients (26%). The most common grade 3 to 4 toxicities included leukopenia in 26%, anemia in 11%, myalgias in 11%, gastrointestinal bleeding in 11%, infection in 10%, and thrombosis in 10%. CONCLUSION: The combination of weekly paclitaxel and bryostatin-1 is not an effective therapy for patients with advanced pancreatic carcinoma.

Dysrhythmia of caloric nystagmus.

OBJECTIVES: Objectives of the study were 1) to determine the prevalence and characteristics of dysrhythmia, 2) to identify associations between dysrhythmia and other patient variables, and 3) to determine whether dysrhythmia is more a characteristic of individuals than simply a correlate of alertness or response intensity. STUDY DESIGN: Cross-sectional. METHODS: Review of records from 150 patients undergoing the caloric test. RESULTS: Dysrhythmia severe enough to interfere with accurate analysis of the caloric test was present in 40% of the cases. Individuals were entered into an "orderly" group (n = 67) or a "dysrhythmic" group (n = 83) and were 5.8 times more likely to remain in the same group on a second visit than to change groups. Stronger response scores were associated with less dysrhythmia. Higher caloric-induced vertigo scores were associated with both stronger response scores and lower dysrhythmia scores. Cases in the dysrhythmic group were 3.8 times more likely to have abnormal caloric test results than individuals in the orderly group. CONCLUSIONS: Dysrhythmia frequently interferes with valid and accurate interpretation of the caloric test. Current methods of "mental alerting" frequently fail to eliminate dysrhythmia. The presence of dysrhythmia appears to be a strong predictor of an abnormal caloric test result, and there is a moderate correlation between dysrhythmia and response intensity. Nevertheless, our results suggest that dysrhythmia is specific to individuals, rather than simply a manifestation of peripheral vestibular disease or a correlate of alertness or response intensity.