Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study

We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60–64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m² was more frequent in the 60–64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3–4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60–64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60–64.     

Reproducibility of skin testing and serum venom specific IgE in Hymenoptera venom allergy.

BACKGROUND: The decision regarding an immunotherapy regimen for venom-allergic patients is based on the results of skin testing and serum venom specific IgE measurements. However, their reliability has been questioned, and their reproducibility has not been examined. OBJECTIVE: To evaluate the reproducibility and reliability of the results of skin testing and serum venom specific IgE measurement in venom-allergic patients. METHODS: Patients with a systemic reaction after an insect sting were evaluated twice, 2 to 6 weeks apart, by intradermal skin tests and by determination of serum venom specific IgE to Hymenoptera venoms. RESULTS: Thirty-five patients were evaluated 1 to 168 months (mean, 23 months) after the sting reaction. Reproducibility of skin test results for all venoms at the 2 sessions was found in 23 patients (66%). Reproducibility of venom specific IgE results for all venoms was found in 16 (59%) of 27 patients from whom 2 blood samples were available for evaluation. Concordance between skin test and venom specific IgE results for all venoms was found in 30 (51%) of 59 samples available for evaluation. CONCLUSIONS: The reproducibility of venom skin test and serum venom specific IgE results is relatively poor. It is common practice for therapeutic decisions regarding venom immunotherapy to be based on a single diagnostic evaluation. Consequently, many patients are either overtreated or undertreated. Better diagnostic methods are required in venom allergy.     

Increased rate and greater severity of allergic reactions to insect sting among schoolchildren with atopic diseases

The question of whether atopic diseases are a risk factor for allergic reactions to insect sting is still unresolved. The aim of this study was to evaluate the association between atopic diseases (asthma, allergic rhinitis, atopic eczema) and allergic reactions to insect stings among schoolchildren in Israel. A self‐report questionnaire of the International Study of Asthma and Allergies in Childhood was administered to a national sample of 13–14‐yr‐old schoolchildren. Questions regarding reactions to insect stings were added. A total of 10,021 questionnaires were available for analysis. Among the children who reported insect stings (56.3%), the prevalence of current asthma was 6.0%, of allergic rhinitis, 10.5%, and of atopic eczema, 8.7%, with no significant differences from the whole study population. Among children with any of the atopic diseases, 36.9% reported an allergic reaction to insect sting compared to 24.8% of the non‐atopic children (p < 0.0001). On multivariate analysis, asthma, allergic rhinitis, and atopic eczema were found to be significant risk factors for allergic reactions of any severity. Children in the atopic group had a significantly higher rate of severe allergic reactions than the non‐atopic children, and relatively higher rates of milder ones (p < 0.0001). Asthmatic patients with severe allergic reactions had more parameters of severe asthma than asthmatic patients with mild or no reactions. In conclusions, allergic diseases are associated with a higher rate and greater severity of allergic reactions to insect sting in children. The severity of the allergic reaction is related to the severity of the asthma symptoms.     

Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis

In response to physiological or psychological challenges, the brain activates behavioral and neuroendocrine systems linked to both metabolic and emotional outputs designed to adapt to the demand. However, dysregulation of integration of these physiological responses to challenge can have severe psychological and physiological consequences, and inappropriate regulation, disproportional intensity, or chronic or irreversible activation of the stress response is linked to the etiology and pathophysiology of mood and metabolic disorders. Using a transgenic mouse model and lentiviral approach, we demonstrate the involvement of the hypothalamic neuropeptide Urocortin-3, a specific ligand for the type-2 corticotropin-releasing factor receptor, in modulating septal and hypothalamic nuclei responsible for anxiety-like behaviors and metabolic functions, respectively. These results position Urocortin-3 as a neuromodulator linking stress-induced anxiety and energy homeostasis and pave the way toward better understanding of the mechanisms that mediate the reciprocal relationships between stress, mood and metabolic disorders.     

Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma

Aims: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non‐obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER‐2 overexpression (triple‐negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC‐NST). Methods and results: We report on a case comprising MGA, AMGA and a high‐grade IDC‐NST. The three components were separately microdissected and subjected to genetic analysis with high‐resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple‐negative phenotype and variable positivity for basal markers. Conclusions: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non‐obligate precursor of a subgroup of high‐grade triple‐negative and basal‐like breast carcinomas.     

A randomized prospective study on the effect of short and long Buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I—long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II—short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P<0.01). Cancellation rate was significantly lower in Group I than in Group II (P<0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos trans-ferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.     

The influence of transient hyperprolactinemia on hormonal parameters,oocyte recovery,and fertilization rates in in vitro fertilization

A detrimental effect of transient elevation of plasma prolactin (PRL) during in vitro fertilization (IVF) has not been proven; however, treatment with a dopamine agonist has been suggested. The present study was undertaken to determine if transient, midcycle hyperprolactinemia exerted a deleterious effect on the number of oocytes retrieved or on fertilization of oocytes in vitro. Fifty-three infertile patients with midcycle hyperprolactinemia (PRL>20 g/liter) during ovarian hyperstimulation for IVF were compared with 53 matched controls who remained normoprolactinemic. Mean (±SE) serum PRL levels on the day after hCG were significantly higher in the study group (29.5±1 g/liter) than in the control (13.1±0.5 g/liter) (P<0.0005), whereas the mean estradiol (E₂) concentrations on the same day were not significanily different (4822±287 and 4492±269 pmol/liters, respectively). Fertilization rates (72±4 and 70±4%, respectively) and the mean number of oocytes recovered (4.2±0.3 and 3.7±0.3, respectively) did not differ between the two groups. No correlation was observed between serum PRL and E₂ levels, fertilization rates, or the number of oocytes retrieved in either group. Eleven patients with elevated PRL levels as a result of ovarian hyperstimulation were treated with 2.5 mg bromocriptine daily during the next IVF cycle. Serum PRL levels were significantly lower in the treated (5.6±1.8 g/liter) than in the untreated cycles (35.6±3.1 g/liter) (P<0.0005), whereas serum E₂ concentrations did not differ. Although the mean number of oocytes recovered was significantly higher in the treated (6.2±1.1) than in the untreated (4.7±0.7) (P<0.02) cycles, the fertilization rates were significantly lower when the patients were treated with bromocriptine compared with the previous untreated cycle (55±8.0 and 76.5±7.0%, respectively;P<0.05). Our data demonstrate that a transient elevation of PRL during ovarian stimulation for IVF does not adversely affect the endocrine response, number of oocytes retrieved, or fertilization rates. No improvement in these parameters was observed in bromocriptine-treated cycles. These results do not support the treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.