Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Clinical impact of amotosalen-ultraviolet A pathogen-inactivated platelets stored for up to 7 days.

BACKGROUND: Universal pathogen inactivation of platelet concentrates (PCs) using amotosalen/ultraviolet A with 7-day storage was implemented in Switzerland in 2011. Routine-use data were analyzed at the University Hospital Basel, Switzerland. STUDY DESIGN: A retrospective two-cohort study of patient and PC characteristics, component usage, patient outcomes, count increments (CIs), and adverse events were analyzed for two consecutive 5-year periods with either 0- to 5-day-old conventional PC (C-PC) (n = 14,181) or 0- to 7-day-old pathogen-inactivated PC (PI-PC) (n = 22,579). RESULTS: In both periods, PCs were issued for transfusion on a "first in, first out" basis. With 7-day PI-PC, wastage was reduced from 8.7% to 1.5%; 16.6% of transfused PI-PCs were more than 5 days old. Transfusion of PI-PC more than 5 days old compared with 5 days old or less did not increase platelet and RBC use on the same or next day as an indirect measure of hemostasis and did not increase transfusion reactions. Mean corrected count increments (CCIs) for PI-PC stored for 5 days or less were 22.6% lower than for C-PC (p < 0.001), and declined with increasing storage duration for both, although the correlation was weak (r2 = 0.005-0.014). Mean number of PCs used per patient and duration of PC support were not different for hematology/oncology, allogeneic and autologous hematopoietic stem cell transplant (HSCT), and general medical/surgical patients, who used the majority (~92.0%) of PI-PCs. Five-year treatment-related mortality in allogeneic HSCT was unchanged in the PI-PC period. CONCLUSIONS: PI-PCs with 7-day storage reduced wastage and did not increase PC or red blood cell utilization or adverse reactions compared with fresh PI-PC or a historical control group, demonstrating preserved efficacy and safety.

Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR.

Incremental value of copeptin for rapid rule out of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). BACKGROUND: The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. METHODS: In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. RESULTS: The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T < or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. CONCLUSIONS: The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).