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Feline odontoclastic resorptive lesion (FORL) is a common chronic inflammatory condition whose aetiopathogenesis remains unclear. FORL affects 20-75% of cats and causes excruciating pain and tooth loss. The purpose of this study was to evaluate chronic inflammation in FORL by assessing differences in Toll-like receptor (TLR) and cytokine transcripts in gingival tissues between diseased and healthy cats. Gingival tissue samples were collected from 14 healthy cats with no known clinical signs of oral disease and 41 cats with FORL. Levels of mRNA encoding TLR2, TLR3, TLR4, TLR7, TLR9 and the cytokines interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-12, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) was evaluated using quantitative real-time PCR. Statistical significance of the results was assessed using non-parametric tests. Levels of TLR and cytokine transcripts were upregulated in gingival tissue from cats with FORL as compared with healthy gingival tissue: TLR2, TLR3 and TLR9, p ≤ 0.001; TLR4 and TLR7, p ≤ 0.01; IFN-γ, IL-4, IL-6, IL-10, IL-12, IL-1β and TNF-α, p ≤ 0.001). In conclusion, expression of TLR and both pro- and anti-inflammatory cytokines were significantly increased, confirming an ongoing chronic inflammatory response to the microbiome in FORL. It is likely that dysbiosis of the oral microbiota in cats with FORL activates the innate immune response, leading to active inflammation that results in tooth resorption.

Introduction. Feline odontoclastic resorptive lesion (FORL) is one of the most common and painful oral diseases of the cat. It is characterised by tooth resorption due to destructive activity of odontoclasts. FORL can result in tooth loss. While the aetiology of FORL is not clearly understood, it is thought to be multifactorial and bacteria are likely to play a major role. Hypothesis. Dysbiosis of the normal feline oral microbiota leads to an alteration in commensal bacteria populations, which results in the development of FORL. Aim. The purpose of the current study was to determine the composition of the microbiomes associated with feline oral health and FORL. Methodology. Supragingival plaque was collected from 25 cats with a healthy oral cavity and 40 cats with FORL. DNA was extracted from each sample, the V4 region of the 16S rRNA gene amplified by polymerase chain reaction and amplicons sequenced. Diversity and species richness analyses were performed, principal component analysis was used to explore differences between the oral microbiomes of healthy cats and those with FORL, and linear discriminant analysis effect size was used to assess differences between the groups. Results. The six most abundant bacterial genera identified were Bergeyella , Capnocytophaga, Lampropedia, Morexella, Porphyromonas and Treponema . Two-step cluster analysis of the data identified two FORL sub-groups (FORL-1, FORL-2). The FORL-2 sub-group was very similar to the healthy group, whilst the FORL-1 sub-group was clearly different from both the FORL-2 sub-group and the healthy groups. In this analysis, Capnocytophaga (P Lampropedia (P Porphyromonas at a slightly higher level in the FORL-1 sub-group compared to the healthy and FORL-2 sub-groups. Microbial diversity was found to be less in the FORL-1 sub-group than in the healthy group. Lampropedia sp., a phosphate-accumulating oral commensal species, was significantly lower in the FORL-1 sub-group. Conclusion. The oral microbiota associated with the FORL-1 sub-group is distinct from that found in the healthy group and FORL-2 sub-group. Lampropedia species may influence the local calcium-phosphate ratio, which could be a factor in tooth and bone resorption observed in FORL.

Feline odontoclastic resorptive lesion (FORL) and feline chronic gingivostomatitis (FCGS) are two of the most common diseases of the feline oral cavity. While evidence is emerging that FCGS is caused by gingival inflammation initiated and perpetuated by the oral microbiota, little is known in this regard for FORL. Feline calicivirus (FCV) has been associated with the presence of FCGS and is thought to play a role in the initiation of this disease. In this study, the incidence of FCV was investigated in cats with FORL and FCGS, and compared to unaffected controls. FCV was detected by viral culture. The incidence of FCV was as follows: 6 (24.0%) of 24 control cats, 9 (22.5%) of 40 cats with FORL and 15 (60.0%) of 25 cats with FCGS were positive for FCV. There was a significant difference in FCV incidence between all the groups (p = 0.003) but none between the control group and the FORL group. However, significant differences were observed in the incidence of FCV between control and FCGS (p = 0.010) and between FORL and FCGS (p = 0.006). It is concluded that although FCV may be associated with FCGS, it appears unlikely to play a role in FORL.

INTRODUCTION: High-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma. However, almost all patients eventually relapse possibly due to incomplete elimination of malignant plasma cells. For patients with an identical twin, syngeneic-HCT provides a tumor-free graft without the risk of graft vs. host disease. We hypothesized that syngeneic-HCT would result in better disease control than auto-HCT. METHODS : We identified 10 patients with multiple myeloma who underwent syngeneic-HCT at our institution from 1994 to 2014. Using a propensity score, we identified 48 controls that received auto-HCT during the same time interval. Matching was done for the year of transplant, age and disease status at auto-HCT (Table 1). Primary endpoint was progression-free survival (PFS). Secondary endpoints were complete remission (CR) rates and overall survival (OS). RESULTS: Baseline characteristics are shown in Table 1. The two groups were well matched, with no significant statistical differences in age, sex, race, stage at diagnosis, lines of therapy received, or disease status prior to transplant. At the time of transplant, 7 (70%) patients in the syngeneic cohort were in first remission, with 3 (30%) having relapsed disease. Similarly, 28 (58%) patients in the autologous cohort were in first remission, with 20 (41%) having relapsed disease (p value 0.49). Patient outcomes are summarized in Table 2. All patients engrafted, with a median time to engraftment of 11 and 10 days, for the syngeneic and auto-HCT cohorts respectively (p=0.22). There was no treatment related mortality in the first 100 days post-transplant in either of the cohorts. In the syngeneic group 8 (80%) patients achieved ≥ CR, 1 achieved very good partial remission (VGPR), and 1 achieved a partial remission (PR), with an overall response rate (ORR) of 100%. Amongst the control group, 18 (37%) achieved ≥ CR, 5 (10%) achieved ≥ VGPR, 21 (43%) achieved ≥PR, 3 (6%) had stable disease and 1 (2%) had disease progression, with an ORR of 91.6%. There was no significant difference in the ORR between the two groups (p=0.21). At the time of last follow-up, a total of 4 (40%) patients had relapsed in the syngeneic cohort, and 31 (65%) had relapsed in the autologous cohort (p=0.15). The median progression free survival (PFS) for the syngeneic cohort was 98.6 months (95% CI from 76-118 months), while the median PFS for auto-HCT cohort was 34.5 months (95% CI from 16-52 months) (p=0.05). Median overall survival (OS) for the syngeneic and auto-HCT cohorts were not reached and 131 months, respectively (p=0.15). The PFS difference was not due to a difference in maintenance therapy after transplant, as 6 (60%) syngeneic patients and 32 (66.7%) auto-HCT (p=0.69) received maintenance therapy respectively. CONCLUSION: Our study shows that patients with multiple myeloma who underwent syngeneic-HCT had a trend to a higher CR rate and longer PFS compared to a matched cohort that underwent auto-HCT. This benefit may be related to the absence of malignant plasma cells in the syngeneic graft, and a normal donor immune system. The efficacy of syngeneic transplants needs to be assessed in a larger number of patients to provide sufficient power to detect clinically meaningful differences with autologous transplants. Table 1 Pre-transplant variables for cases and controls. Table 1. Pre-transplant variables for cases and controls. Table 2 Transplant Outcomes Table 2. Transplant Outcomes Kaplan Maier Curves for Progression Free Survival and Overall Survival. Kaplan Maier Curves for Progression Free Survival and Overall Survival. Disclosures Bashir: Takeda: Consultancy; Spectrum: Consultancy; Takeda: Research Funding; Celgene: Research Funding. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

Introduction: Multiple Myeloma is a heterogeneous cancer that affects the bone marrow. Given this heterogeneity, we aimed to elucidate the role of gene expression profiling (GEP) in identifying different MM subtypes and explore their relationship to clinical outcomes in a standard of care setting. Methods: We retrospectively analyzed all NDMM patients with baseline GEP analysis. 55 patients from April 2014 until March 2016 were identified and included in our analysis. GEP was performed using CD138+ cells from bone marrow samples through MyPRS® (Signal Genetics, Little Rock, AR). Fisher's exact test was used to evaluate the associations between two categorical variables. The Wilcoxon rank sum test was used to evaluate the difference in continuous variables between patient groups. Kaplan-Meier method was used to estimate the time to event endpoints including relapse free survival (RFS) and overall survival. The log-rank test was used to evaluate the differences in the time to event endpoints between/among patient groups. Univariate Cox proportional hazards model was used to evaluate the association between a continuous variable and relapse free survival. Results: Median age was 61 (38-76). Patients presented with lytic lesions (80%), anemia (78%), kidney dysfunction (24%) and hypercalcemia (31%). One patient did not meet CRAB criteria, but had 60% plasma cells in the bone marrow and an involved/uninvolved sFLC ratio of 199. All patients were treated with bortezomib (88%) or carfilzomib (12%) initial therapy in combination with lenalidomide (83%) or cyclophosphamide (17%). All patients received triple therapy as initial treatment, with 60% of patients receiving an upfront autologous transplant. With median follow-up of 12 months (1.64-24.54 months) 75% of patients had not relapsed and median overall survival had not been reached. 13 (24%) patients were characterized as high risk (HR) by GEP. GEP risk category predicted RFS (p=0.0014) in this series of patients (Fig. 1). Table 1 shows GEP risk subtypes with clinical outcomes and association to FISH abnormalities. We previously reported that HR FISH abnormalities are present in GEP low risk (LR) patients. LR GEP patients with CKS1B gene gain by FISH (n=9, 23%) had 100% RFS at 21 months, while 60% of HR GEP patients with CKS1B gene gain had relapsed by 24 months (p=0.0297, Fig. 2). All patients with HR GEP and 17p deletion relapsed by 14 months whereas only one patient with LR GEP and 17p deletion died 1 year from diagnosis, with an unknown cause of death (p=0.18, Fig. 3). Conclusion: Cytogenetics and FISH are still the current standard of care to predict prognosis in NDMM, direct care and inclusion in clinical trials. This study in a standard of care setting shows that GEP further refines prognosis in patients with HR FISH abnormalities. Future studies in larger cohorts of patients are warranted to confirm our findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Although Indian healthcare is booming it faces huge challenges in the area of rural healthcare delivery. Both public and private healthcare providers have been trying different models to reach out to the rural areas for providing primary healthcare and one of the major initiatives in this direction has been telehealth. Though there were few successful models, telehealth initiatives in general faced many challenges from inadequate infrastructure, unskilled paramedics and a lack of sustainable economic and business model. This paper analyses a private healthcare providers experience in conducting 16,609 teleconsultations across rural India using Cisco's health presence and focuses on identifying specialists need in the rural area and methods to address those needs in an India specific context.

Nonperipartum group B streptococcus infection usually occurs in elderly persons and in patients with underlying systemic diseases (e.g., diabetes, malignancy, or alcoholism). Group B streptococcal infections in adults are often life threatening, and have been associated with a toxic shock-like syndrome. We present a case of fulminant group B streptococcal cellulitis in a patient with sarcoidosis who was receiving corticosteroid therapy and who became hypotensive as her cellulitis rapidly progressed to involve her entire right thigh.

Abstract 2951 Introduction: Everolimus (RAD001) is an inhibitor of MTORC1, a component of the Akt-MTOR pathway which regulates growth and survival of lymphoplasmacytic cells in Waldenstrom's Macroglobulinemia (WM). Everolimus also exhibits activity in WM patients with relapsed/refractory disease (Ghobrial et al, JCO 2010; 28 :1408–14). We therefore initiated this multicenter, prospective study to delineate the efficacy and tolerability of Everolimus as primary therapy in WM. Patients and Methods: WM patients with symptomatic disease, adequate organ function, who were not previously treated, and who did not have symptomatic hyperviscosity were eligible for this study. Intended therapy consisted of 10 mg of oral Everolimus administered daily, with sequential dose de-escalation to 7.5 mg daily, 5 mg daily, and 5 mg every other day permitted for toxicity. Patients were treated until progression or unacceptable toxicity. Patients were encouraged to use 5 mL of an oral dexamethasone solution (0.5 mg/5mL) to swish and spit up to 4 times daily for prevention of oral ulcerations associated with Everolimus. Study participants were assessed monthly for the first 3 months, and thereafter every 3 months which included a physical examination, complete blood counts, chemistries, and serum IgM monitoring. Bone marrow biopsies and aspirations were performed at baseline, at months 6 and 12, and as required for response assessment. Results: Thirty-three patients were enrolled on this prospective, multicenter study and are evaluable for response. Median baseline characteristics for all patients are as follows: Age 62 (range 41–80 years); Hematocrit 31.3% (range 24.5–45.7%); Hemoglobin 10.8 (range 7.8–15.7 g/dL); serum IgM 4, 440 (range 959–10, 256 mg/dL), with 23 (69.7%) patients demonstrating an IgM level ≥3, 000 mg/dL; serum M-protein 2.60 g/dL (range 0.31–5.31 g/dL), B2M 3.0 mg/L (1.6–6.7 mg/L). The median baseline bone marrow disease burden was 70% (range 7.5–95%), and 21 patients (63.6%) demonstrated adenopathy or splenomegaly by CT scans at baseline. At best response, serum IgM levels declined from 4, 440 to 1, 925 (p Conclusions: Everolimus is active in the primary therapy of WM, with rapid reductions observed in serum IgM levels in most patients. Serum IgM discordance to underlying bone marrow disease burden is common, and serial bone marrow assessments are important for response monitoring in WM patients receiving Everolimus. Disclosures: Treon: Millennium: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria. Eradat:Millennium: Speakers Bureau; Genentech, A Roche Company: Speakers Bureau. Matous:Seattle Genetics, Inc.: Research Funding; Celgene: Speakers Bureau; Cephalon: Speakers Bureau; Millennium: Speakers Bureau. Anderson:Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Acetylon: Equity Ownership. Ghobrial:Noxxon: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Abstract 1395 Poster Board I-417 Background: Multiple myeloma accounts for approximately 10% of hematologic malignancies diagnosed annually in the U.S. It is well documented that the African-American population is disproportionately affected by multiple myeloma in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African-American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplant (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutics is an evolving question. Methods: We performed a retrospective review of 170 African-American multiple myeloma patients and 170 age and gender-matched Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results: Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 53%, 28% and 19% respectively. The percentage of stage I, II and III patients in the Caucasian group was 40%, 30% and 29% respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic (thalidomide, lenalidomide or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African-American and Caucasian patients who received high dose chemotherapy and ASCT (65% and 76%, respectively, p=0.04). There was no difference observed in the number of second transplants performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1. There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between black and white patients (p =0.1) Conclusions: In this single-center, retrospective study of multiple myeloma patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African-American and Caucasian patients. To our knowledge, this is the largest number of African-American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African-American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African-American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African-American patients on clinical trials to validate this observation prospectively. Disclosures: No relevant conflicts of interest to declare.