Immunotherapy for the treatment of multiple myeloma

Publication date: Available online 27 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade. Genetically engineered T cells, such as chimeric antigen receptor T cells or T cell receptor-engineered T cells, have also shown encouraging results in recent clinical studies of patients with MM. In this paper, we discuss recent progress in immunotherapy for the treatment of MM.



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Serum and tissue markers in colorectal cancer: State of art

Publication date: Available online 27 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Massimiliano Berretta, Lara Alessandrini, Chiara De Divitiis, Guglielmo Nasti, Arben Lleshi, Raffaele Di Francia, Gaetano Facchini, Carla Cavaliere, Carlo Buonerba, Vincenzo Canzonieri
Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade, the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. bevacizumab, cetuximab, panitumab, aflibercept and regorafenib), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future, the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment. Moreover, molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long-term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of serum and tissue markers according to the recently published English literature. This paper is an extension of the article "Biological and clinical markers in colorectal cancer: state of art" by Cappellani A published in Jan 2010.



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Differential engagement of attention and visual working memory in the representation and evaluation of the number of relevant targets and their spatial relations: Evidence from the N2pc and SPCN

Publication date: Available online 27 January 2017
Source:Biological Psychology
Author(s): Manon Maheux, Pierre Jolicœur
We examined the role of attention and visual working memory in the evaluation of the number of target stimuli as well as their relative spatial position using the N2pc and the SPCN. Participants performed two tasks: a simple counting task in which they had to determine if a visual display contained one or two coloured items among grey fillers and one in which they had to identify a specific relation between two coloured items. The same stimuli were used for both tasks. Each task was designed to permit an easier evaluation of either the same-coloured or differently-coloured stimuli. We predicted a greater involvement of attention and visual working memory for more difficult stimulus-task pairings. The results confirmed these predictions and suggest that visuospatial configurations that require more time to evaluate induce a greater (and presumably longer) involvement of attention and visual working memory.



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Radiofrequency ablation vs. microwave ablation for patients with benign thyroid nodules: a propensity score matching study

Abstract

Purpose

To compare the efficacy and the safety of radiofrequency ablation and microwave ablation for treatment of benign thyroid nodules using a propensity score matching study design.

Methods

Two hundred and sixty patients with benign thyroid nodules were studied retrospectively, including 102 patients treated with radiofrequency ablation and 158 treated with microwave ablation. To reduce confounding bias due to retrospective assignment, propensity score matching was performed to balance the preablation data of the two groups. After matching, a total of 102 patient pairs (1:1) were created. The volume reduction ratio, therapeutic success rate, symptom and cosmetic score, and major complication were compared between the two groups at 1, 3, 6, and 12 months after treatment.

Results

Between the well-matched groups, no significant differences were found in all nodule volume-related end points at 6 months (volume reduction ratio: 79.4 vs. 77.2 %, P = 0.108; symptom score: 2.1 vs. 1.9, P = 0.456; cosmetic score: 2.1 vs. 2.3, P = 0.119; therapeutic success rate: 99 vs. 97 %, P = 0.621) and 12 months (volume reduction ratio: 83.6 vs. 81.6 %, P = 0.144; symptom score: 1.5 vs. 1.5, P = 0.869; cosmetic score: 1.6 vs. 1.7, P = 0.409; therapeutic success rate: 100 vs. 100 %, P > 0.99) after treatment. No major complications occurred in either group (P > 0.99).

Conclusions

With well-matched groups and consistent procedure design, our results demonstrated that the volume reduction ratio, therapeutic success rate, symptom and cosmetic score, and complications related to treatment for the two techniques are equivalent. Radiofrequency ablation and microwave ablation are both effective and safe methods in treating benign thyroid nodules.

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Cooling down inflammation in type 2 diabetes: how strong is the evidence for cardiometabolic benefit?

Abstract

Chronic inflammation is supposed to be an important mediator of cardiometabolic dysfunctions seen in type 2 diabetes. In this mini-review, we collected evidence (PubMed) from randomized controlled trials (through March 2016) evaluating the effect of anti-inflammatory drugs on indices of glycemic control and/or cardiovascular events in people with type 2 diabetes. Within the last 25 years, many anti-inflammatory drugs have been tested in type 2 diabetes, including hydroxychloroquine, anti-tumor necrosis factor therapies (etanercept and infliximab), salsalate, interleukin-1 antagonists (anakinra, canakinumab, gevokizumab, LY2189102), and CC-R2 antagonists. Despite being promising, the observed effects on HbA1c or glucose control remain rather modest in most clinical trials, especially with the new drugs. There are many trials underway with anti-inflammatory agents to see whether patients with cardiovascular diseases and/or type 2 diabetes may have clinical benefit from marked reductions in circulating inflammatory markers. Until now, a large trial with losmapimod (a p38 inhibitor) among patients with acute myocardial infarction, including one/third of diabetic patients, showed no reduction in the risk of major ischemic cardiovascular events. Further evidence is warranted in support of the concept that targeting inflammation pathways may ameliorate glycemic control and also reduce cardiovascular complications in type 2 diabetes.

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New insights for male infertility revealed by alterations in spermatic function and differential testicular expression of thyroid-related genes

Abstract

The impact of thyroid hormone (TH) disorders on male reproductive biology has been a controversial issue for many years. Recently, we reported that hypothyroid male rats have a disruption of the seminiferous epithelium, which may compromise spermatogenesis. To improve the understanding of the reproductive pathogenesis of hypothyroidism and hyperthyroidism, male Wistar rats that developed these dysfunctions in adulthood were used as an experimental model. We evaluated the sperm production, reserves, transit time, morphology, and functionality (acrosome integrity, plasma membrane integrity, and mitochondrial activity), and the testicular expression of the TH receptors (Thra1 and Thra2, Thrb1, and Thrb2), deiodinases (Dio2 and Dio3), and the Mct8 transporter (Slc16a2) were assessed by reverse transcription followed by real-time quantitative PCR (RT-qPCR). The results were evaluated statistically by ANOVA and Tukey HSD test (P < 0.05). Hypothyroidism decreased the total and daily sperm productions and increased the sperm transit time through the epididymis, while the sperm functionality was reduced in both thyroid dysfunctions. Regarding the modulation of gene expression in the testis, hypothyroidism increased the expression of Thra1 and decreased the expression of Dio3, and hyperthyroidism increased the expression of Slc16a2. The observed alterations in spermatic production and function and in the expression of the TH receptor, deiodinase, and the TH transporter are suggestive of TH participation in spermatogenesis in adulthood.

http://ift.tt/2kuSGfj

Improving care and outcomes of inpatients with syndrome of inappropriate antidiuresis (SIAD): a prospective intervention study of intensive endocrine input vs. routine care

Abstract

Purpose:

The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an endocrine input is superior to routine care in correcting hyponatraemia and can improve patient outcomes.

Methods:

This single-centre prospective-controlled intervention study included inpatients admitted at a UK teaching hospital, with serum sodium ≤ 127 mmol/l, due to syndrome of inappropriate antidiuresis over a 6-month period. The prospective intervention group (18 subjects with mean serum sodium 120.7 mmol/l) received prompt endocrine input, while the historical control group (23 patients with mean serum sodium 124.1 mmol/l) received routine care. The time needed for serum sodium increase ≥ 5 mmol/l was the primary endpoint.

Results:

The intervention group achieved serum sodium rise by ≥5 mmol/l in 3.5 vs. 7.1 days in the control group (P = 0.005). In the intervention group, the mean total serum sodium increase was 12 mmol/l with only 5.8 % of patients discharged with serum sodium < 130 vs. 6.3 mmol/l increase (P < 0.001) and 42.1 % of the subjects discharged with serum sodium < 130 mmol/l in the control group (P = 0.012). The mean length of hospital stay in the intervention group (10.9 days) was significantly shorter than in the control group (14.5 days; P = 0.004).The inpatient mortality rate was 5.5 % in intervention arm vs. 17.4 % in control arm, but this difference was not statistically significant.

Conclusions:

Since the endocrine input improved time for correction of hyponatraemia and shortened length of hospitalisation, widespread provision of endocrine input should be considered.

http://ift.tt/2kuUMfh

New year, new resolution

British Dental Journal 222, 133 (2017). doi:10.1038/sj.bdj.2017.81

http://ift.tt/2jngT5s

Oral health: OHRQoL in systemic sclerosis

British Dental Journal 222, 67 (2017). doi:10.1038/sj.bdj.2017.51

Authors: A. Curto, D. Curto & J. Sanchez

http://ift.tt/2jnkWih

Health impacts of Facebook usage and mobile texting among undergraduate dental students: it's time to understand the difference between usage and an excessive use

British Dental Journal 222, 92 (2017). doi:10.1038/sj.bdj.2017.73

http://ift.tt/2jna4kg

Pharmacology: Discontinuation of bisphosphonates

British Dental Journal 222, 67 (2017). doi:10.1038/sj.bdj.2017.52

Authors: N. Malden & S. Loh

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Focusing on the keystones of modern dentistry

British Dental Journal 222, 135 (2017). doi:10.1038/sj.bdj.2017.89

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Oral surgery: Mutilation following MDMA

British Dental Journal 222, 68 (2017). doi:10.1038/sj.bdj.2017.53

Authors: G. Nugent, S. Basyuni, D. McAnerney & M. Cameron

http://ift.tt/2jnj9d5

The perceptions of dental practitioners of their role as clinical teachers in a UK outreach dental clinic

British Dental Journal 222, 107 (2017). doi:10.1038/sj.bdj.2017.77

Authors: L. Parrott, A. Lee & S. Markless

http://ift.tt/2jnaw25

Oral medicine: A waste of paper

British Dental Journal 222, 68 (2017). doi:10.1038/sj.bdj.2017.54

Author: R. Raeburn

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Protecting your toothbrush from contamination

British Dental Journal 222, 134 (2017). doi:10.1038/sj.bdj.2017.85

http://ift.tt/2jnlGnl

Social media: Professionalism

British Dental Journal 222, 68 (2017). doi:10.1038/sj.bdj.2017.55

Author: P. Affleck

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Change

British Dental Journal 222, 65 (2017). doi:10.1038/sj.bdj.2017.50

Author: Stephen Hancocks

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Law and ethics: Out of context

British Dental Journal 222, 69 (2017). doi:10.1038/sj.bdj.2017.56

Author: P. Singh

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Laypeople's perceptions of frontal smile esthetics: a systematic review

British Dental Journal 222, 92 (2017). doi:10.1038/sj.bdj.2017.75

http://ift.tt/2jnkTD7