Infections and neutrophils in the pathogenesis of bronchiolitis obliterans syndrome in children after allogeneic stem cell transplantation

It is plausible that infections post‐hematopoietic SCT play a role in the pathogenesis of BOS. A prospective study for children with history, questionnaire, examination, PFTs, and blood counts at one, three, six, nine, 12, 18, and 24 months post‐SCT was conducted. Between September 2009 and September 2011 (n = 39), six developed BOS at 200 days (range 94–282), three patients had probable clinical respiratory infection, and all six had higher neutrophil count compared to non‐BOS patients (4.7 vs. 2.4 at three months and 6.3 vs. 2.9 at six months ×10⁹/L, p = 0.03). Contribution of clinical and subclinical infection needs to be considered in the pathogenesis of BOS.     

Risk of Positive Nonsentinel Nodes in Women with 1–2 Positive Sentinel Nodes Related to Age and Molecular Subtype Approximated by Receptor Status

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1–2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1‐2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1–10) and 14 (range 6–37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.     

Socioeconomic status,access to triple therapy,and survival from HIV-disease since 1996

BACKGROUND: In the era before highly active antiretroviral therapy (HAART), socioeconomic status was associated with survival from HIV disease. We have explored socioeconomic status, access to triple therapy (HAART), and mortality in the context of a universal healthcare system. METHODS: We evaluated 1408 individuals who initiated double or triple therapy between 1 August 1996 and 31 December 1999, and were followed until 31 March 2000. Cumulative HIV-related mortality rates were estimated using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: In the overall Cox model, we found that adherence [risk ratio (RR) 0.83; per 10% increase], CD4 cell count (RR 1.53; per 100 cell decrease), and lower socioeconomic status (RR 2.19; high versus low), were associated with HIV-related mortality. However, socioeconomic status was not significant among patients prescribed triple therapy in a stratified analysis, or in a sub-analysis restricted to patients prescribed HAART in the initial regimen. When we investigated if inequitable access to HAART by socio-economic status could explain the discrepancy, we found that persons in the lower socio-economic strata were less likely to be prescribed triple therapy even after adjustment for clinical characteristics. CONCLUSION: In a universal healthcare system, socioeconomic status was strongly associated with HIV-related mortality. When we investigated possible explanations for this association, we found that individuals of lower socioeconomic status were less likely to receive triple therapy after adjustment for clinical characteristics. Our findings highlight the need for the monitoring of therapeutic guidelines to ensure equitable access, as treatment strategies are updated.     

13C NMR quantitation of polymer in deoxyhemoglobin S gels.

13C/1H magnetic double-resonance spectroscopy has been used to quantitate the amount of polymerized hemoglobin S in deoxygenated gels at 30 degrees C, for samples whose hemoglobin concentration range from 21 to 32 g/dl. Scalar- and dipolar-decoupled spectra and a 13C proton-enhanced dipolar-decoupled spectrum were recorded for each sample as was a scalar-decoupled spectrum for a matching oxyhemoglobin S control. The difference between the oxyhemoglobin S and deoxyhemoglobin S scalar-decoupled spectra was used to determine the polymer fraction, and this value was compared with the polymer fraction determined by using ultracentrifugation sedimentation on the same sample (assuming a two-phase model). The polymer fraction value determined by uncorrected sedimentation averaged 0.15 more than the value obtained from NMR. The discrepancy between the two techniques was largely removed when the analysis of the sedimentation data included a correction for depletion of hemoglobin in the supernatant or sol phase due to sedimentation of free molecules. The best fit to both the sedimentation and NMR data was obtained by using a solubility of deoxyhemoglobin S at 30 degrees C of 17.3 +/- 1 g/dl. These results indicate that the NMR techniques, which do not require separation of the sample into a sol phase and a pellet phase, provide quantitative information about the deoxyhemoglobin S polymer and will be useful for studies of sickle erythrocytes.