Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).
Over the period 1980-2009, there were 58 documented hyperthermia deaths of American-style football players in the United States. This study examines the geography, timing, and meteorological conditions present during the onset of hyperthermia, using the most complete dataset available. Deaths are concentrated in the eastern quadrant of the United States and are most common during August. Over half the deaths occurred during morning practices when high humidity levels were common. The athletes were typically large (79% with a body mass index >30) and mostly (86%) played linemen positions. Meteorological conditions were atypically hot and humid by local standards on most days with fatalities. Further, all deaths occurred under conditions defined as high or extreme by the American College of Sports Medicine using the wet bulb globe temperature (WBGT), but under lower threat levels using the heat index (HI). Football-specific thresholds based on clothing (full football uniform, practice uniform, or shorts) were also examined. The thresholds matched well with data from athletes wearing practice uniforms but poorly for those in shorts only. Too few cases of athletes in full pads were available to draw any broad conclusions. We recommend that coaches carefully monitor players, particularly large linemen, early in the pre-season on days with wet bulb globe temperatures that are categorized as high or extreme. Also, as most of the deaths were among young athletes, longer acclimatization periods may be needed.
Rituximab is used for in vivo tumor cell purging for non-Hodgkin's lymphoma (NHL) patients prior to autologous peripheral blood stem cell transplantation (PBSCT). However, its effects on PBSC mobilization and function are poorly understood. We compared the mobilization characteristics and engraftment kinetics of 13 NHL patients receiving and 34 NHL patients not receiving rituximab 6 months before PBSC mobilization. In the rituximab group, there was a significantly longer time to neutrophil engraftment (P=0.0466), a trend toward the need for BM harvest to supplement low-yield PBSC collections (31 vs 9%, P=0.08) and a significantly increased rate of bacteremia episodes (62 vs 26%, P=0.025). Median progression-free survival (PFS) and overall survival (OS) were significantly longer in the rituximab compared to the nonrituximab patients (P=0.049 and 0.042, respectively). However, patients in the nonrituximab group were at high risk for recurrence and expected to have shorter survival. Rituximab used within 6 months prior to collection may have a detrimental effect on PBSC mobilization and engraftment. However, rituximab is a major therapeutic breakthrough for NHL treatment and this negative effect may be offset by improved survival. Further studies are warranted in larger populations to determine the impact of rituximab on engraftment, PFS and OS.
Werner's syndrome is an autosomal recessive disorder resulting in premature aging. Most patients die in their fifth decade from malignancies or heart disease. The gene for Werner's syndrome (WRN) encodes a recQ helicase. Cells from patients with Werner's syndrome have increased sensitivity to DNA-damaging drugs in vitro. Here we present a patient with Werner's syndrome who developed severe chemotherapy-induced toxicity during treatment for acute myelogenous leukemia. We propose that lack of WRN resulted in increased sensitivity of the patient's cells to the toxicity of chemotherapy.
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