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Analysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African Americans. - Oncotarget
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 4.6Â±1.51x103/uL in non-Hispanic whites, 3.6Â±1.57x103/uL in non-Hispanic blacks and 4.3Â±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.
Phase II Study of Pazopanib and Paclitaxel in Patients With Refractory Urothelial Cancer. - Clinical genitourinary cancer
Currently, no standard treatments are available for relapsed or refractory urothelial carcinoma (UC). Paclitaxel has demonstrated efficacy in the treatment of UC when used alone or combined with other cytotoxic therapies. We designed a phase II trial combining paclitaxel with pazopanib, a commonly used antiangiogenic agent with significant antitumor activity in various solid tumors.We enrolled 32 patients with refractory UC who had demonstrated disease progression after 2 previous chemotherapeutic regimens. The patients received paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle and oral pazopanib 800 mg daily. The primary endpoint was the overall response rate (ORR). The secondary endpoints included progression-free survival, overall survival, and a safety assessment of the combination.Of the 28 evaluable patients, a complete response was observed in 3 patients and a partial response in 12, with an ORR of 54% (95% confidence interval, 33.9-72.5). The median progression-free and overall survival was 6.2 and 10 months, respectively. The most frequent side effects noted (all grades) were fatigue (63%), diarrhea (44%), and nausea and vomiting (41%). Hematologic toxicities were common and included (all grades) anemia (69%), neutropenia (38%), and thrombocytopenia (47%). Growth factor support was required for 44% of the patients.The combination of paclitaxel and pazopanib resulted in a promising ORR of 54% in patients with advanced pretreated UC. This represents a greater response rate and median survival than found with other existing second-line regimens for UC and is worthy of further study.Copyright Â© 2016 Elsevier Inc. All rights reserved.
The short-term accommodation response to aniso-accommodative stimuli in isometropia. - Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)
There have been only a limited number of studies examining the accommodative response that occurs when the two eyes are provided with disparate accommodative stimuli, and the results from these studies to date have been equivocal. In this study, we therefore aimed to examine the capacity of the visual system to aniso-accommodate by objectively measuring the interocular difference in the accommodation response between fellow dominant and non-dominant eyes under controlled monocular and binocular viewing conditions during short-term exposure to aniso-accommodative stimuli.The accommodative response of each eye of 16 young isometropic adults (mean age 22 Â± 2 years) with normal binocular vision was measured using an open-field autorefractor during a range of testing conditions; monocularly (accommodative demands ranging from 1.97 to 2.90 D) and binocularly while altering the accommodation demand for each eye (aniso-accommodative stimuli ranging from 0.08 to 0.53 D) [Corrected].Under monocular viewing conditions, the dominant and non-dominant eyes displayed a highly symmetric accommodative response; mean interocular difference in spherical equivalent 0.01 Â± 0.06 D (relative) and 0.22 Â± 0.06 D (absolute) (p > 0.05). During binocular viewing, the dominant eye displayed a greater accommodative response (0.11 Â± 0.34 D relative and 0.24 Â± 0.26 D absolute) irrespective of whether the demand of the dominant or non-dominant eye was altered (p = 0.01). Astigmatic power vectors J0 and J45 did not vary between eyes or with increasing accommodation demands under monocular or binocular viewing conditions (p > 0.05).The dominant and non-dominant eyes of young isometropic individuals display a similar consensual lag of accommodation under both monocular and binocular viewing conditions, with the dominant eye showing a small but significantly greater (by 0.12-0.25 D) accommodative response. Evidence of short-term aniso-accommodation in response to asymmetric accommodation demands was not observed.Â© 2015 The Authors Ophthalmic & Physiological Optics Â© 2015 The College of Optometrists.
Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity. - Haematologica
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 â‰¥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. - American journal of hematology
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 (â‰¥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.Â© 2013 Wiley Periodicals, Inc.
Development of standardized methods for assessing biocidal efficacy of contact lens care solutions against Acanthamoeba trophozoites and cysts. - Investigative ophthalmology & visual science
To investigate experimental variables in the development of standardized methods to assess the efficacy of contact lens disinfection systems against the trophozoite and cysts of Acanthamoeba spp.A. castellanii (ATCC 50370), A. polyphaga (ATCC 30461), and A. hatchetti (CDC: V573) were adapted to axenic culture and used to produce cysts either with Neff's encystment medium (NEM) or starvation on nonnutrient agar (NNA). Challenge test assays and a most probable number approach were used to compare the trophozoite and cysticidal efficacy of four multipurpose disinfectant solutions (MPDSs) and a one-step hydrogen peroxide system (with and without the neutralizing step).With trophozoites, four of four MPDSs and the one-step peroxide system gave â‰¥3 logâ‚â‚€ kill for all strains 6 hours, regardless of culture medium used. Greater resistance was found against cysts, with results for MPDSs varying by species and method of cyst production. Here, 1-3 logâ‚â‚€ kill was found with NEM cysts for three of four MPDSs compared with one of four for the NNA cysts at 6 hours (A. castellanii and A. polyphaga, only). The one-step peroxide system gave 1-1.9 logâ‚â‚€ kill with NEM cysts and 0.8-1.1 for NNA cysts. Only 3% hydrogen peroxide gave total kill (>3 logâ‚â‚€) of NNA cysts at 6 hours.A reproducible method for determining the susceptibility of Acanthamoeba trophozoites and cysts to contact lens care systems has been developed. This will facilitate assay standardization for assessing the efficacy of such products against the organism and aid development of improved disinfectant and therapeutic agents.
Resistance and growth of Fusarium species in contact lens disinfectant solutions. - Optometry and vision science : official publication of the American Academy of Optometry
To compare the biocidal efficacy of contact lens care solutions against clinical isolates and the American Type Culture Collection (ATCC) 36031 reference strain of Fusarium species and to determine the ability of the organism to survive and grow in such systems.The ISO 14729 reference method to assess biocidal efficacy was applied to the purified conidial form of 10 strains of Fusarium species. Six multipurpose disinfectant solutions (MPDSs), a one-step hydrogen peroxide (Per-1) system, a hydrogen peroxide-sodium chlorite (Per-2) system, and a one-step povidone iodine (PI) system were compared. Challenge organism viability was determined at various intervals, including the manufacturers' recommended disinfection time for the products (4 to 6 hours) and thereafter to 21 days.All MPDSs achieved a 3- to 4-log10 reduction in viability of ATCC 36031 within the recommended disinfection time of 6 hours. For the clinical strains, MPDS-1 (PQ-1 + alexidine) and MPDS-2 (PQ-1 + PHMB) produced 3 to 5 logâ‚â‚€ kill after 6 hours. Multipurpose disinfectant solution 3 (PQ-1 + Aldox 0.0006%), MPDS-4 (PQ-1 + Aldox 0.0005% + C-9 ED3A), and MPDS-5 (PQ-1 + Aldox 0.0005%) showed reduced efficacy for the same two strains, with 0.6 to 1.7 logâ‚â‚€ kill. Multipurpose disinfectant solution 6 (PHMB) gave 1.6 logâ‚â‚€ for one strain and 3 to 4 logâ‚â‚€ for the remainder. Growth in all the MPDS was not detected up to 21 days incubation. Per-1 showed less than 1 logâ‚â‚€ kill at 6 hours for six of 10 strains, including ATCC 36031, and growth (1.2 to 2.7 logâ‚â‚€) occurred with three of 10 strains by 7 days. Per-2 gave less than or equal to 0.5 logâ‚â‚€ kill after 6- or 24-hour exposure without growth. The PI system showed 4 to 5 logâ‚â‚€ kill for all strains tested by the first time point of 4 hours. However, with the exception of ATCC 36031, growth (1.7 to 4.0 logâ‚â‚€) occurred with all strains by 7 days in PI.All MPDSs were effective against the ATCC 36031 reference strain of Fusarium solani. However, reduced efficacy was found for some MPDSs against the clinical isolates. Unlike MPDSs, peroxide- and povidone iodine-based systems have no continued antimicrobial presence once neutralized, and this can allow growth of surviving Fusarium in the solution. Accordingly, lenses should be subject to fresh disinfection if stored in such solutions for extended periods.
The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis. - British journal of haematology
The prevalence and prognostic value of a concomitant diagnosis of symptomatic or asymptomatic multiple myeloma (MM), as defined by the current International Myeloma Working Group (IMWG) criteria, in patients with immunoglobulin light chain amyloidosis (AL), are unknown. We studied 46 consecutive patients with AL who underwent quantification of serum M-protein and clonal bone marrow plasma cells, as well as a comprehensive evaluation for end organ damage by MM. Using standard morphology and CD138 immunohistochemical staining, 57% and 80% of patients were found to have concomitant MM, respectively. Nine patients exhibited end organ damage consistent with a diagnosis of symptomatic MM. While overall survival was similar between AL patients with or without concurrent myeloma (1-year overall survival 68% vs. 87%; P = 0.27), a diagnosis of symptomatic myeloma was associated with inferior outcome (1-year overall survival 39% vs. 81%; P = 0.005). Quantification of bone marrow plasma cells by both standard morphology and CD138 immunohistochemistry identified a much higher prevalence of concurrent MM in patients with AL than previously reported. Evaluation of bone marrow plasma cell infiltration and presence of myeloma associated end organ damage could be clinically useful for prognostication of patients with AL.Â© 2013 Blackwell Publishing Ltd.
Antimicrobial efficacy of multi-purpose contact lens disinfectant solutions following evaporation. - Contact lens & anterior eye : the journal of the British Contact Lens Association
Non-compliance is a significant factor in contact lens related microbial keratitis and includes solution reuse and failure to recap the lens storage case resulting in evaporation effects. To address this, impact of partial evaporation on the antimicrobial efficacy of multipurpose contact lens care solutions was investigated.Solutions were evaporated under a stream of air to 2Ã— and 4Ã— concentration and challenged with Fusarium solani (ATCC 36031), Candida albicans (ATCC 10231) and Acanthamoeba castellanii (ATCC 50370). The level of organism kill at 6h was compared to the non-evaporated product.ReNu with MoistureLoc(Â®) (RML) lost 90-100% of biocidal activity against C. albicans on evaporation, 75-99% for F. solani and 29-33% with A. castellanii at 2Ã— or 4Ã— concentration, respectively. OPTI-FREE(Â®) RepleniSH(Â®) lost 72-90% efficacy against C. albicans and F. solani, and 61% at 2Ã— and 10% at 4Ã— concentration with A. castellanii. ReNu(Â®) MultiPlus, AQuify(Â®) Multi-Purpose and Biotrueâ„¢ showed only loss in efficacy with C. albicans at 4Ã— concentration giving 79%, 34.5% and 48% reduction, respectively. No loss in biocidal activity on evaporation was obtained with Complete(Â®) Revitalens for all organisms.Partial evaporation can affect biocidal efficacy of multi-purpose solutions and may have been a significant factor in an outbreak of Fusarium keratitis cases associated with RML. Evaporation results in increased binding of cationic disinfectants to counter-ions in the formulation, reducing ability to attach and rupture anionic microbial cell walls. Interaction may also occur between the biocidal ingredient and other components, such as surfactants, resulting in sequestration of activity through micelle formation.Copyright Â© 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Phase II study of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in advanced pancreatic carcinoma. - American journal of clinical oncology
To determine the efficacy and toxicity of the protein kinase C inhibitor bryostatin-1 plus paclitaxel in patients with advanced pancreatic carcinoma.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%.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%.The combination of weekly paclitaxel and bryostatin-1 is not an effective therapy for patients with advanced pancreatic carcinoma.
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