Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation.

AIM: Invasive aspergillosis occurs in 5-15% of allogeneic hematopoietic stem cell transplant (HSCT) recipients. Through the 1990s there has been an increase in the incidence of late aspergillosis (LA). We report on the incidence, risk factors, and attributable mortality of LA in a cohort of 398 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center from January 1999 through December 2003. METHODS: LA was defined as occurring > 40 days post HSCT. LA cases were identified by prospective surveillance and examination of a computerized database. Probable or definite aspergillosis was defined by standard EORTC/MSG criteria. Mortality was attributed to LA if it caused or significantly contributed to death. RESULTS: The overall incidence of LA in our cohort was 4.1%. Median time from stem cell infusion to diagnosis of LA was 164 days (range 68-677) after HSCT. The incidence of LA among unmodified, T-cell depleted, or reduced intensity HSCT was 2.2%, 4%, and 6.8%, respectively (P not significant). Risk factors for LA were grade II-IV acute graft-versus-host disease (GVHD) (P=0.002), chronic GVHD (P=0.01), secondary neutropenia (P=0.02), and reduced intensity conditioning containing alemtuzumab (P=0.01). LA was the immediate cause of death in 1 of 10 (10%) T-cell depleted, 2 of 2 (100%) unmodified, and 1 of 4 (25%) of reduced-intensity HSCT. CONCLUSIONS: LA developed a median 164 days post HSCT. All-cause 30-day mortality of LA was 56.3%. The majority of LA cases died of concurrent infections and not from invasive aspergillosis.

Effect of Perioperative ß-Blockers on Pulmonary Complications among Patients with Chronic Obstructive Pulmonary Disease Undergoing Lung Resection Surgery.

The aim of this study is to determine if COPD patients undergoing lung resection with perioperative ß-blocker use are more likely to suffer postoperative COPD exacerbations than those that did not receive perioperative ß-blockers. Methods. A historical cohort study of COPD patients, undergoing lung resection surgery at Memorial Sloan-Kettering Cancer Center between 2002 and 2006. Primary outcomes were the rate of postoperative COPD exacerbations, defined as any initiation or increase of glucocorticoids for documented bronchospasm. Results. 520 patients with COPD were identified who underwent lung resection. Of these, 205 (39%) received perioperative ß-blockers and 315 (61%) did not. COPD was mild among 361 patients (69% of all patients), moderate in 117 patients (23%), and severe in 42 patients (8%). COPD exacerbations occurred among 11 (5.4%) patients who received perioperative ß-blockers and among 20 (6.3%) patients who did not. Secondary outcomes, which included respiratory failure, 30-day mortality, and the presence or absence of any cardiovascular complication, ICU transfer, cardiovascular complication, or readmission within 30 days, did not differ in prevalence between the two groups. Conclusions. This study implies that perioperative ß-blockers use among COPD patients undergoing lung resection surgery does not impact the rate of exacerbations.