Recombinant human erythropoietin in very elderly patients with myelodysplastic syndromes: results from a retrospective study

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged ≥80 years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80–99.1) with a median hemoglobin (Hb) level of 9 g/dl (range 6–10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000 IU/week or epoetin beta 30,000 IU/week) in 59 (63.4 %) pa-tients or high in 34 (36.6 %) (epoetin alpha 80,000 IU/week) patients. We observed an erythroid response (ER) in 59 (63.4 %) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p?=?0.004), ferritin <200 ng/ml (p?=?0.017), Hb >8 g/dl (p?=?0.034), and a high-dose rHuEPO treatment (p?=?0.032). Median OS from rHuEPO start was 49.3 months (95 % CI 27.5–68.4) in responders versus 30.6 months (95 % CI 7.3–53.8) in resistant patients (p?=?0.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients.     

Heterozygous TREM2 mutations in frontotemporal dementia

A causative association was recently demonstrated between homozygous TREM2 mutations and frontotemporal dementia (FTD)-like syndrome and between heterozygous TREM2 exon2 genetic variations and late-onset Alzheimer's disease (AD). The objective of this study was to evaluate whether heterozygous TREM2 genetic variations might be associated to the risk of FTD. TREM2 exon 2 was sequenced in a group of 1030 subjects—namely, 352 patients fulfilling clinical criteria for FTD, 484 healthy control subjects (HCs), and 194 patients with AD. The mutation frequency and the associated clinical characteristics were analyzed. We identified 8 missense and nonsense mutations in TREM2 exon 2 in 24 subjects. These mutations were more frequent in patients with FTD than in HCs (4.0% vs. 1.0%, p = 0.005). In particular, TREM2 Q33X, R47H, T66M, and S116C mutations were found in FTD and were absent in HCs. These mutations were associated with either the semantic variant of primary progressive aphasia or the behavioral variant FTD phenotypes. The FTD and AD groups were not significantly different with regard to TREM2 genetic variation frequency (AD: 2.6%, p = 0.39). Heterozygous TREM2 mutations modulate the risk of FTD in addition to increasing susceptibility to AD. Additional studies are warranted to investigate the possible role of these mutations in the pathogenesis of neurodegenerative disorders.     

Prevalence of diabetes and pre‐diabetes in a cohort of Italian young adults with Williams syndrome

Williams syndrome (WS) is a rare, multisystemic genomic disorder showing a high prevalence of impaired glucose metabolism in adulthood. The reason for this association is unknown, though hemizygosity for genes mapping to the WS chromosome region has been implicated. Twenty‐two Italian young adults with WS (13 females, 9 males) were studied. A 75 g oral glucose tolerance test (OGTT) was performed and β‐cell function was estimated with Homeostasis Model Assessment (HOMA)‐B%, Insulinogenic Index, and corrected insulin response whereas insulin sensitivity was assessed with HOMA‐Insulin Resistance Index, Quantitative Insulin Check Index, and composite Insulin Sensitivity Index. One patient had known diabetes mellitus (DM), whereas impaired glucose tolerance (IGT) was diagnosed in 12 patients and DM in one (63.6% prevalence of impaired glucose metabolism). IGT patients were more insulin resistant than those with normal glucose tolerance (NGT), whereas β‐cell function was unchanged or increased. Islet autoimmunity was absent. Logistic regression showed that impaired glucose metabolism was not associated with age, body mass index (BMI), or family history of DM. β‐cell function, insulin sensitivity, and post‐load insulin levels did not differ between WS patients with NGT and healthy controls comparable for gender, age, and BMI, though WS–NGT patients had higher post‐load glucose values. These data confirm the high prevalence of impaired glucose metabolism in WS young adults, thus suggesting the need for screening these patients with OGTT. IGT is associated with reduced insulin sensitivity, but not with impaired β‐cell function, islet autoimmunity, and traditional risk factors for type 2 DM. © 2013 Wiley Periodicals, Inc.     

Satisfaction,quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants

Journal of Thrombosis and Thrombolysis - Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed...     

Fragile X premutation with atypical symptoms at onset

OBJECTIVE: To evaluate the presence of carriers of the fragile X premutation among male patients with sporadic ataxia without expansion into known spinocerebellar ataxia genes. DESIGN: Clinical and genetic examinations were performed on patients with sporadic pure ataxia and patients with ataxia associated with extracerebellar features such as pyramidal and extrapyramidal signs, dementia, or peripheral neuropathy. SETTING: University department of neurology. PATIENTS: One hundred forty-two Italian men with sporadic ataxia with onset at age 30 to 84 years. INTERVENTIONS: The CGG repeat size of the FMR1 gene was evaluated with fluorescent polymerase chain reaction. Premutated allele lengths were confirmed with Southern blot analysis. RESULTS: FMR1 premutation alleles with a repeat number greater than 55 were detected in 3 probands (2.1%) from a total of 142 male subjects initially referred to our university medical center for evaluation of sporadic ataxia. Two patients had typical fragile X syndrome with associated tremor or ataxia, and the third patient had spastic paraparesis without clear symptoms of cerebellar ataxia and without the common signs seen at magnetic resonance imaging. CONCLUSIONS: Genetic analysis of the FMR1 gene could provide a reliable diagnostic tool for the definitive diagnosis of late-onset ataxias. Additional studies are needed to clarify the importance of premutation screening in patients with movement disorders or other associated atypical features at onset, such as paraparesis.     

Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.     

Cow's milk allergic children can present sensitisation to probiotics

Aim: To evaluate sensitivity to different probiotics in children with cow's milk allergy.
Methods: Eighty-five patients (age range: 4 months –12 years) presenting atopic dermatitis (AD) were enrolled. Skin prick test (SPT) responses to three different probiotics preparations (Fiorilac®, Dicoflor® and Reuterin®) were evaluated in addition to relevant food allergens.
Results: Thirty-nine patients out of 85 (45.8%) had a positive skin response to prick test for cow's milk (3 with reaction <3 mm). Of the thirty-six patients with a cow's milk weal reaction >3 mm, twenty-eight (77.8%) had a skin response to Fiorilac®, four patients (11%) to Dicoflor® and four (11%) to Reuterin®. The proportion of SPT reaction to all the investigated probiotics preparations was significantly lower than cow's milk (r = 9.406; p = 0.002). A significantly higher sensitization was observed for Fiorilac® versus Dicoflor® (r = 30.916; p < 0.001) and versus Reuterin® (r = 34.133; p < 0.001).
Conclusion: Probiotic use in patients with cow's milk allergy has to be limited to products that do not contain milk. This should be clearly reported in the label. In selected patients, it is advisable to perform a screening SPT with the product to evaluate its potential contamination with milk.