Head and Neck Diseases by Alexandros G.Sfakianakis: 12/06/15

Κυριακή 6 Δεκεμβρίου 2015

Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries; it affects primarily older persons, with a median age at diagnosis of 72 years. Chlorambucil has been a standard first-line therapy in CLL, especially for older patients or those with coexisting…

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma

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Letter: management of post-operative Crohn's disease - thiopurines vs adalimumab– authors' reply

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Editors' declarations of interest

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Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma – authors' reply

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Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries; it affects primarily older persons, with a median age at diagnosis of 72 years. Chlorambucil has been a standard first-line therapy in CLL, especially for older patients or those with coexisting…

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Letter: wide variation in faecal calprotectin values according to the assay

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Letter: coffee consumption and gallstone disease – a cautionary note on the assignment of exposure values in dose–response meta-analyses. Authors' reply

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Editorial: what can be done when infliximab stops working in ulcerative colitis? Authors' reply

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Letter: management of post-operative Crohn's disease - thiopurines vs adalimumab

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Editorial: what can be done when infliximab stops working in ulcerative colitis?

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Letter: prostaglandin E1 therapy with alprostadil and risk reduction of early hepatic cellular carcinoma after liver transplantation – authors' reply

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ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma

Background:

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults and currently incurable. To specifically target natural killer (NK) cell activity to GBM, we employed NK-92/5.28.z cells that are continuously expanding human NK cells expressing an ErbB2-specific chimeric antigen receptor (CAR).

Methods:

ErbB2 expression in 56 primary tumors, four primary cell cultures, and seven established cell lines was assessed by immunohistochemistry and flow cytometry. Cell killing activity of NK-92/5.28.z cells was analyzed in in vitro cytotoxicity assays. In vivo antitumor activity was evaluated in NOD-SCID IL2R^null (NSG) mice carrying orthotopic human GBM xenografts (6 to 11 mice per group) and C57BL/6 mice carrying subcutaneous and orthotopic ErbB2-expressing murine GBM tumors (5 to 8 mice per group). Statistical tests were two-sided.

Results:

We found elevated ErbB2 protein expression in 41% of primary GBM samples and in the majority of GBM cell lines investigated. In in vitro assays, NK-92/5.28.z in contrast to untargeted NK-92 cells lysed all ErbB2-positive established and primary GBM cells analyzed. Potent in vivo antitumor activity of NK-92/5.28.z was observed in orthotopic GBM xenograft models in NSG mice, leading to a marked extension of symptom-free survival upon repeated stereotactic injection of CAR NK cells into the tumor area (median survival of 200.5 days upon treatment with NK-92/5.28.z vs 73 days upon treatment with parental NK-92 cells, P < .001). In immunocompetent mice, local therapy with NK-92/5.28.z cells resulted in cures of transplanted syngeneic GBM in four of five mice carrying subcutaneous tumors and five of eight mice carrying intracranial tumors, induction of endogenous antitumor immunity, and long-term protection against tumor rechallenge at distant sites.

Conclusions:

Our data demonstrate the potential of ErbB2-specific NK-92/5.28.z cells for adoptive immunotherapy of glioblastoma, justifying evaluation of this approach for the treatment of ErbB2-positive GBM in clinical studies.

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Changes in Receipt of Cancer Screening in Medicare Beneficiaries Following the Affordable Care Act

Background:

The Affordable Care Act (ACA) removed copayments for screening mammography and colonoscopy in Medicare beneficiaries, but its clinical impact is unknown.

Methods:

Using a 5% random sample of Medicare claims from 2009 through 2012 in individuals age 70 years or older who were due for screening, we examined claims for screening mammography and screening or surveillance colonoscopy for two years prior to ACA (2009–2010) and two years post-ACA (2011–2012). Receipt of the procedures at the patient level was compared across years using generalized estimating equations. Statistical tests were two-sided.

Results:

Compared with 2009, we found an increase in mammography uptake during the ACA coverage period, with multivariable odds ratios (MOR) of 1.22 (95% confidence interval [CI] = 1.20 to 1.25, P < .001) for 2011 and 1.17 (95% CI = 1.15 to 1.20, P < .001) for 2012 and less change in 2010 (OR = 1.03, 95% CI = 1.01 to 1.05, P = .01). In contrast to mammography, uptake of screening or surveillance colonoscopy decreased in 2012 (MOR = 0.95, 95% CI = 0.92 to 0.98, P = .002) compared with 2009, with no change in 2010 (MOR = 1.01, 95% CI = 0.99 to 1.04, P = .47) or 2011 (MOR = 1.01, 95% CI = 0.99 to 1.04, P = .34). Other factors associated with procedure receipt included younger age and prior preventive health visits. In an analysis restricted to patients age 70 to 74 years, colonoscopy use increased slightly in 2011 but was unchanged in 2012, and the findings by year for mammography were consistent with the main analysis.

Conclusions:

Following ACA implementation with concomitant reduction in out-of-pocket expenditures, there was a statistically significant increment in mammography uptake but not colonoscopy. This suggests that affordability is a necessary but not sufficient facilitator of preventive services.

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Prostaglandin E1 therapy with alprostadil and risk reduction in early hepatic cellular carcinoma after liver transplantation

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Letter: coffee consumption and gallstone disease – a cautionary note on the assignment of exposure values in dose–response meta-analyses

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Letter: factors determining liver fibrosis – more to come

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma

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Letter: management of post-operative Crohn's disease - thiopurines vs adalimumab– authors' reply

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Editors' declarations of interest

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Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma – authors' reply

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Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries; it affects primarily older persons, with a median age at diagnosis of 72 years. Chlorambucil has been a standard first-line therapy in CLL, especially for older patients or those with coexisting…

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Letter: wide variation in faecal calprotectin values according to the assay

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Letter: coffee consumption and gallstone disease – a cautionary note on the assignment of exposure values in dose–response meta-analyses. Authors' reply

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Editorial: what can be done when infliximab stops working in ulcerative colitis? Authors' reply

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Letter: management of post-operative Crohn's disease - thiopurines vs adalimumab

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Editorial: what can be done when infliximab stops working in ulcerative colitis?

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Letter: prostaglandin E1 therapy with alprostadil and risk reduction of early hepatic cellular carcinoma after liver transplantation – authors' reply

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ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma

Background:

Methods:

Results:

Conclusions:

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Changes in Receipt of Cancer Screening in Medicare Beneficiaries Following the Affordable Care Act

Background:

The Affordable Care Act (ACA) removed copayments for screening mammography and colonoscopy in Medicare beneficiaries, but its clinical impact is unknown.

Methods:

Results:

Conclusions:

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Prostaglandin E1 therapy with alprostadil and risk reduction in early hepatic cellular carcinoma after liver transplantation

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Letter: coffee consumption and gallstone disease – a cautionary note on the assignment of exposure values in dose–response meta-analyses

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Letter: factors determining liver fibrosis – more to come

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Κυριακή 6 Δεκεμβρίου 2015

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