Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma.

Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches.

An in vitro comparison of incisal preparation design on load-to-failure of ceramic veneers.

Introduction: This in vitro study aimed to compare the load-to-failure values of two different ceramic veneers (IPS e.max Press [Ivoclar Vivadent] and Vintage lithium disilicate [LD] press [Shofu]) with incisal preparation designs under standardized conditions. Materials and Methods: Twenty-two intact extracted maxillary incisors were selected and divided randomly into two groups (n = 11). The veneer tooth preparation was standardized in both groups where a butt joint incisal preparation was done along with chamfer margin. Group 1 included veneers made from IPS e.max Press (Ivoclar Vivadent) and Group 2 included veneers fabricated from Vintage LD Press (Shofu). Veneers were luted to their respective abutment teeth using standardized bonding protocols and resin cement for both groups. Later, every specimen was loaded to failure utilizing a universal testing machine, and the outcomes were noted in Newtons (N). Results: The mean load-to-failure value obtained for Group 1 (IPS e.max Press) was 1386.46 N while that obtained for Group 2 was 1777.07 N. Statistically significant difference was found in this intergroup comparison (P = 0.006). Conclusion: The load-to-failure value of Vintage LD Press veneers (Shofu) was greater than that of IPS e.max Press veneers (Ivoclar Vivadent).

The Role of Shared Epitope in Rheumatoid Arthritis Prognosis in Relation to Anti-Citrullinated Protein Antibody Positivity.

INTRODUCTION: Shared epitope (SE) is present in high proportions of anti-citrullinated protein antibody (ACPA) + patients with rheumatoid arthritis (RA) and is associated with poor prognosis. We assessed the role of SE in RA prognosis, in relation to ACPA positivity. METHODS: Patients enrolled in the Brigham and Women's RA Sequential Study were included. Changes from baseline in disease activity (Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI]) to 1 year were assessed. Baseline characteristics were compared by SE and ACPA status (±; chi-squared, Kruskal-Wallis). Association between number of SE alleles and ACPA status (logistic regression models), relationships between baseline characteristics and changes in disease activity (adjusted linear regression model), and effect of ACPA on the association between SE and changes in disease activity (mediation analysis) were studied. RESULTS: Nine hundred twenty-six patients were included. SE + versus SE - patients had significantly longer disease duration and higher disease activity scores and were more likely to have erosive disease, have higher comorbidity burden, and be RF + (all p < 0.05). Among patients with one or two SE alleles (vs. 0), odds of being ACPA + were 1.97 (p = 0.0003) and 3.82 (p < 0.0001), respectively. SE + versus SE - patients had worse disease activity scores as indicated by mean increases in DAS28 (CRP) of 0.22, CDAI of 2.07, and SDAI of 2.43 over 1 year (all p < 0.05). Direct effect of SE + accounted for 76.4-80.1% of total effect in disease activity increases. CONCLUSIONS: SE is strongly associated with ACPA positivity and higher disease activity in patients with RA. SE was associated with greater increases in disease activity over 1 year, which was partially mediated by the presence of ACPA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01793103; registration date: February 15, 2013, retrospectively registered.

Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease where proteins called autoantibodies in the blood of patients with RA target the patient's own joint tissue and organs by mistake. This causes inflammation. Patients with certain autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), may experience worse symptoms. There are certain genetic risk factors that may mean a person is more likely to develop RA. One example of a genetic risk factor is having the shared epitope (SE).Our study looked at almost 1000 patients with RA in the general population. It explored the impact of having SE and ACPAs on changes in RA disease activity. Patients with SE had RA for a longer time, had more severe disease, and were more likely to have other diseases compared with patients without SE. Patients with SE were also more likely to have ACPAs. Over the course of one year, patients with SE had larger increases in RA disease activity than those patients without SE, even though they were taking the same treatments. These results suggest that patients with the genetic risk factor, SE often have RA that is harder to treat. Doctors should take this into account when selecting treatment for RA.

Dopamine levels in human tear fluid.

PURPOSE: To determine the levels of dopamine in tear fluid and demonstrate the use of tear fluid as a non-invasive source for dopamine measurements in humans. METHODS: The study cohort included 30 clinically healthy individuals without any pre-existing ocular or systemic conditions. Matched tear fluid (using Schirmer's strips and capillary tubes) and plasma were collected from the subjects. Dopamine levels were evaluated using direct competitive chemiluminescent enzyme-linked immunosorbent assay (ELISA), dopamine kit (Cloud Clone Corp, TX, USA). RESULTS: Significantly higher dopamine levels were found in the tear fluid compared to plasma in the study subjects. The level of dopamine was 97.2 ± 11.80 pg/ml (mean ± SEM), 279 ± 14.8 pg/ml (mean ± SEM), and 470.4 ± 37.64 pg/ml (mean ± SEM) in the plasma and in the tears collected using Schirmer's strips and capillary tubes, respectively. CONCLUSION: Dopamine was detectable in all the tear fluid samples tested and was also found to be at a higher concentration than in plasma samples. Tear fluid can be used as a non-invasive sample source to monitor dopamine levels.

Eruptive disseminated Spitz naevus (EDSN) in a young girl of Indian origin.

Eruptive disseminated Spitz naevus (EDSN) is a rare entity and has never been documented in a South-east Asian individual (of Indian origin) previously. We report an adolescent with this condition which, to our knowledge, has only been previously reported a few times.

TEN-like eruption in setting of EBV positive T-cell lymphoproliferative disease with HLH, in a child.

Haemophagocytic lymphohistiocytosis complicating Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood is a rare and life-threatening entity. We report a child with this condition presenting with a toxic epidermal necrolysis-like eruption.

Non-melanoma skin cancer in Australia.

OBJECTIVES: To report the burden and cost of non-melanoma skin cancer (NMSC) treatments in Australia and to project estimates of numbers and costs to 2015. DESIGN AND SETTING: Retrospective study of data obtained from Medicare Australia for NMSC treated by excision, curettage, laser or cryotherapy between 1 January 1997 and 31 December 2010, by year, sex, age group and state or territory. MAIN OUTCOME MEASURES: Total number, total Medicare Benefits Schedule (MBS) benefit and total cost in Australian dollars of NMSC treatments. RESULTS: The total number of NMSC treatments increased from 412 493 in 1997 to 767 347 in 2010, and we estimated that the number of treatments would increase to 938 991 (95% CI, 901 047-976 934) by 2015. The total MBS benefit for NMSC treatments in 2010 was $93.5 million, and we estimated that this will increase to $109.8 million (95% CI, $105.9-$113.7 million) by 2015, whereas the total cost with inflation (ie, cost which includes diagnosis, treatment and pathology) was $511.0 million in 2010, estimated to increase to $703.0 million (95% CI, $674.6-$731.4 million) by 2015. CONCLUSION: NMSC treatments increased by 86% between 1997 and 2010. We anticipate that the number and the total cost without inflation of NMSC treatments will increase by a further 22% between 2010 and 2015. NMSC will remain the most costly cancer and place an increasing burden on the Australian health care system.