Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation.

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.

Ovarian reserve in breast cancer: assessment with anti-Müllerian hormone.

Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context.

The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation.

INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Incidence of liver abnormalities in Fanconi anemia patients.

Patients with Fanconi anemia (FA) are prone to liver tumors, especially after androgen treatment, but other liver abnormalities have not been described for these patients. Here, we systematically reviewed liver manifestations in a cohort of 64 adult and pediatric patients with FA followed in a single center. "Significant biological liver abnormalities(SBLA)" in the absence of any androgen treatment were found in five patients, including two children, belonging to rare FA groups; these two patients presented with a very severe chronic cytolysis pattern which may be classified as a new FA phenotype. Liver radiological abnormalities, which include hepatic tumors (n 5 4), hepatomegaly(n 5 1), hyperechogenicity (n 5 2), and a previously undescribed biliary duct dilatation as demonstrated by magnetic resonance cholangiopancreatography(MRCP) (n 5 2), were found in eight patients who received androgen treatment or who had iron overload. Lastly, we found no correlation between cytolysis intensity and high levels of alpha-fetoprotein (AFP); this common finding in FA patients cannot therefore be explained by hepatocyte regeneration.

Renal resistive index better predicts the occurrence of acute kidney injury than cystatin C.

The objective of this study was to determine the predictive value of the renal resistive index (RI) and cystatin C values in serum (SCys) and urine (UCys) in the development of acute kidney injury (AKI) in critically ill patients with severe sepsis or polytrauma. This was a prospective, double-center, descriptive study. There were 58 patients with severe sepsis (n= 28) or polytrauma (n = 30). Renal resistive index, SCys, and UCys were measured within 12 h following admission (day 1 [D1]) to the intensive care unit. Renal function was assessed using the AKI network classification: On day 3 (D3), 40 patients were at stage 0 or 1, and 18 were at stage 2 or 3. Patients with AKI stage 2 or 3 had significantly higher RI (0.80 vs. 0.66, P < 0.0001), SCys (1.23 vs. 0.68 mg/L, P = 0.0002), and UCys (3.32 vs. 0.09 mg/L, P = 0.0008). They also had higher Simplified Acute Physiology Score II, arterial lactate level, and intensive care unit mortality. In multivariate analysis, an RI of greater than 0.707 on D1 was the only parameter predictive of the development of AKI stage 2 or 3 on D3 (P = 0.0004). In the subgroup of patients with AKI stage 2 or 3 on D1, RI remained the only parameter associated with persistent AKI on D3 (P = 0.016). In multivariate analysis comparing the predictive value of RI, SCys, and UCys, RI was the only parameter predictive of AKI stage 2 or 3 on D3. Renal resistive index seems to be a promising tool to assess the risk of AKI.