Concomitant versus sequential therapy for the treatment of Helicobacter pylori infection: a Greek randomized prospective study

Objective: The objective of this study is to compare, in Greece, a region with >20% local resistance to clarithromycin, the efficacy rates of the concomitant versus the sequential H. pylori eradication therapy. Materials and methods: Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day concomitant or 10-day sequential therapy. Treatment outcome was assessed by C¹³-urea breath test at least 4 weeks after therapy. Intention to treat (ITT) and per protocol (PP) analysis of the eradication rates were performed. Secondary end points included patient compliance and safety. Results: The concomitant therapy group achieved statistically significant higher eradication rates when compared with the sequential treatment group, both in the ITT and in the PP analysis (84.6% versus 70.9%, p?=?0.002, and 90.6% versus 78.1%, p?=?0.001, respectively), after adjusting for age, gender, smoking status, and the presence or not of ulcer and/or non-ulcer dyspepsia. Both groups displayed excellent compliance rates (99.5% for the concomitant therapy group and 96.2% for the sequential therapy group, p?=?0.067). Regarding treatment safety, major adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the two groups (7.0% for the concomitant therapy group and 2.9% for the sequential therapy group). Conclusions: Concomitant therapy led to statistically significant higher eradication rates over sequential therapy. Both therapies showed excellent compliance and an acceptable safety profile. The 10-day quadruple concomitant scheme should be the adopted for first-line H. pylori eradication in Greece.     

A qualitative study of early childhood educators' beliefs and practices regarding children's socioemotional development

Existing research underscores the significance of early childhood experiences in the childcare context for the development of socioemotional skills and competencies. However, the practices adopted within childcare for the enhancement of children's socioemotional development and the factors mediating these practices are less adequately researched. The present study contributes to this understanding, through studying the perceptions of 34 educators working in childcare centres in Greece with regard to children's socioemotional development and its promotion. Results showed that although they acknowledged the significance of social and emotional competencies for children's adjustment, learning and well-being, they did not report consistent use of practices having as a goal the promotion of such skills. Explanations involve on the one hand the lack of formal policy and the existence of structural barriers and on the other hand a perception that socioemotional development is mostly affected by factors beyond their influence. Results are discussed in relation to prior research and in terms of their implications for designing interventions, curricula and staff training.     

Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor

Recent evidence indicates that growth hormone-releasing hormone (GHRH) functions as an autocrine/paracrine growth factor for various human cancers. A splice variant (SV) of the full-length receptor for GHRH (GHRHR) is widely expressed in various primary human cancers and established cancer cell lines and appears to mediate the proliferative effects of GHRH. To investigate in greater detail the role of SV1 in tumorigenesis, we have expressed the full-length GHRHR and its SV1 in MCF-7 human breast cancer cells that do not possess either GHRHR or SV1. In accordance with previous findings, the expression of both GHRHR and SV1 restored the sensitivity to GHRH-induced stimulation of cell proliferation, with SV1 being more potent than the GHRHR. Furthermore, MCF-7 cells transfected with SV1 proliferated more quickly than the controls, even in the absence of exogenously added GHRH, suggesting the existence of intrinsic, ligand-independent activity of SV1 after its transfection. In agreement with the stimulation of cell proliferation, the levels of proliferation markers cyclin D1, cyclin E, and proliferating cell nuclear antigen were elevated in MCF-7 cells treated with GHRH, cultured in both serum-free and serum-containing media. In addition, SV1 caused a considerable stimulation of the ability of MCF-7 cells to grow in semisolid medium, an assay considered diagnostic for cell transformation. Collectively, our findings show that the expression of SV1 confers oncogenic activity and provide further evidence that GHRH operates as a growth factor in breast cancer and probably other cancers as well.     

Eosinophilic infiltration in the nasal mucosa of rhinitis patients: is it affected by the presence of asthma or the allergic status of the patients?

BACKGROUND: Asthma and rhinitis often coexist, and there is evidence to suggest that they have similar histopathologic features. OBJECTIVE: To examine whether the inflammatory infiltration in the nasal mucosa in rhinitis is affected by the presence of asthma and allergy. METHODS: Nasal mucosa biopsy samples were collected from 44 individuals: 18 with rhinitis and asthma (9 allergic and 9 nonallergic), 16 with rhinitis and no asthma (8 allergic and 8 nonallergic), and 10 nonallergic control subjects. The alkaline phosphatase-anti-alkaline phosphatase method was applied to 6-microm-thick cryostat sections using monoclonal antibodies against T cells (CD4 and CD8) and eosinophils (EG2). Slides were counted blindly, and results are expressed as cells per high-power field. RESULTS: Eosinophil counts were higher in the nasal mucosa of rhinitic patients vs controls. No differences in cellular infiltration were detected between rhinitic patients with and without asthma or between allergic and nonallergic patients. A trend toward higher CD4+ T-cell counts in the nasal mucosa of rhinitic patients was observed, whereas no differences were noted in CD8+ T-cell infiltration among the groups. CONCLUSION: Inflammatory infiltration, characterized by the presence of eosinophils and CD4+ T cells, was similar in the nasal mucosa in noninfectious rhinitis irrespective of the presence of asthma or the allergic status of the patient.     

Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in childhood acute leukaemia

It has been reported that the cyclin-dependent kinase inhibitor (CDKI) gene p15INK4B is frequently inactivated by genetic alterations and may be responsible for various malignant tumours. Another way of inactivation of this CDKI is by hypermethylation of 5'CpG islands in the promoter region of the p15INK4B gene and this inactivation seems to be a frequent event in various haematological malignancies. In the present study, we investigated the methylation status of the p151NK4B gene to clarify its role in the pathogenesis of childhood acute myeloid (AML) and acute lymphoblastic leukaemia (ALL). The study included 23 cases of B-cell origin ALL, 13 cases of T-cell origin ALL, 32 cases of AML, and 10 apparently healthy controls. Hypermethylation was studied by methylation-specific polymerase chain reaction. Hypermethylation of the p15INK4B gene was more frequent in cases with T-cell origin ALL (46.2%), but similar among children with B-cell origin ALL (13.0%) and AML (18.8%). Hypermethylation of p15INK4B may be involved in the pathogenesis of T-cell origin ALL, but not in that of AML or B-cell origin ALL.     

Long‐term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty‐six patients received full‐dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low‐dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full‐dose bortezomib/dexamethasone, in 22% of lenalidomide‐treated patients but only in 4.5% of patients treated with risk‐adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide‐based regimens. However, risk adjusted‐bortezomib/dexamethasone was associated with improved 1‐year survival vs. full‐dose bortezomib/dexamethasone or lenalidomide‐based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk‐adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators.Am. J. Hematol. 90:E60–E65, 2015. © 2015 Wiley Periodicals, Inc.     

Periodic Therapeutic Plasma Exchange in Patients With Moderate to Severe Chronic Myasthenia Gravis Non‐Responsive to Immunosuppressive Agents: An Eight Year Follow‐Up

Few patients with moderate or severe myasthenia gravis (MG) do not respond to immunosuppressive treatment. We present our experience with periodic therapeutic plasma exchange (TPE), in 11 patients with MG resistant to intravenous immunoglobulin (IVIg) therapy, who had frequent relapses even whilst on high doses of immunosuppressive drugs, over a period of 8 years. All patients underwent TPE until control of their symptoms was achieved, and afterwards TPE sessions were continued periodically in an attempt to achieve remission of the disease, without immunosuppressant therapy. Two of the patients were progressively weaned off immunosuppressive agents, as well as TPE, and they are now symptom free. The other nine patients are still under a periodic TPE regime. Seven of them were weaned off all medications and required an average of 3.7 TPE sessions per year during the last 5 years. In the other two patients, those with the most severe form of the disease, the immunosuppressant dosage has been decreased and a TPE session every 2–3 weeks is required in order to control their symptoms. Through all these years TPE has been well tolerated and only minor side‐effects were observed in two patients. Finally, during this 8 year follow‐up period, nine of the patients treated with periodic TPE have been in good control of their symptoms over the last 5 years, and the other two patients live a normal life without any treatment in the last 3 years. Our results suggest that periodic TPE is safe and effective in the control of symptoms in patients with moderate to severe MG who do not respond to immunosuppressive therapies.     

Euglycaemic diabetic ketoacidosis as a complication of SGLT-2 inhibitors: epidemiology,pathophysiology, and treatment

ABSTRACT

Introduction

Sodium-glucose co-transporters 2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 Diabetes Mellitus, which lower plasma glucose by inhibiting glucose reabsorption in the proximal renal tubule. Apart from their hypoglycemic action, recent data suggest these agents have additional major cardioprotective and nephroprotective properties.