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The association between inferior vena cava (IVC) filter presence and subsequent bloodstream infection (BSI) is unknown. We hypothesized among patients with a new diagnosis of venous thromboembolism (VTE), incidence of BSI after 1 year would be higher in patients who had presence of an IVC filter.We performed a retrospective cohort study of patients with newly diagnosed VTE but no IVC filter (N = 4,053) and patients with IVC filter (N = 635) admitted to a metropolitan hospital system from 2006 to 2009 comparing incidence of BSI within 1 year of inclusion. Multivariable regression modeling was used to evaluate the association of IVC filter placement with BSI 1 year after placement.Patients with an IVC filter placed were more likely to be older with higher Charlson co-morbidity score (median 4 vs 1; P.001). The incidence of BSI was not different between the group with IVC filter and the group without (10.7% vs 8.8%; P = .12). There was no association with IVC filter placement and BSI before or after multivariable adjustment.In patients newly diagnosed with VTE, we found no association between IVC filter placement and increased incidence of BSI after 1 year.

Background:While numerous investigations have described worse outcomes for patients undergoing emergent procedures at night, few studies have investigated the impact of nighttime on the outcomes of emergent endotracheal intubation (EEI). We hypothesized that for patients requiring EEI at night, the outcome of first pass success would be lower as compared to during the day.Methods:We performed a retrospective cohort study of all patients admitted to our institution between January 1st, 2016 and July 17st, 2019 who underwent EEI outside of an emergency department or operating room. Nighttime was defined as between 7:00 pm and 6:59 am. The primary outcome was the rate of first pass success. Logistic regression was utilized with adjustment for demographic, morbidity and procedure related covariables.Results:The final examined cohort included 1,674 EEI during the day and 1,229 EEI at night. The unadjusted rate of first pass success was not different between the day and night (77.5% vs. 74.6%, unadjusted odds ratio (OR): 0.85; 95% confidence interval (CI): 0.72, 1.0; P = 0.073 though following adjustment for prespecified covariables the odds of first pass success was lower at night (adjusted OR: 0.83, 95% CI: 0.69, 0.99; P = 0.042. Obesity was found to be an effect modifier on first pass success rate for day vs. night intubations. In obese patients, nighttime intubations had significantly lower odds of first pass success (adjusted OR: 0.71, 95% CI: 0.52, 0.98; P = 0.037).Discussion:After adjustment for patient and procedure related factors, we have found that the odds of first pass success is lower at night as compared to the day. This finding was, to some degree, driven by obesity which was found to be a significant effect modifier in this relationship.

Survival rates for pancreatic cancer remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops. Tumors deficient in deoxyribonucleic acid (DNA) damage repair mechanisms such as BRCA mutants show better responses to platinum based agents, however, such tumors can utilize the poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) pathway as a salvage mechanism. Therefore, inhibition of PARP pathway could lead to tumor destruction and synthetic lethality in presence of BRCA mutation. Various PARP inhibitors have been approved for treatment of patients with germline or somatic BRCA mutant breast and ovarian cancer. This provides basis of using PARP inhibitors in patients with pancreatic cancer that harbor BRCA mutation. A recent phase III Pancreas Cancer Olaparib Ongoing (POLO) study showed impressive results with near doubling of progression free survival compared to placebo (7.4 vs 3.8 months). These results highlight the importance of germline testing for all patients with pancreatic cancer and inclusion of additional deficiencies in homologous recombination repair (ATM and PALB2) including BRCA variants of uncertain significance should be further explored.

Background: There has been limited investigation into the procedural outcomes of patients undergoing emergent endotracheal intubation (EEI) by a critical care medicine (CCM) specialist outside the intensive care unit (ICU). We hypothesized that EEI outside an ICU would be associated with lower rates of first pass success (FPS) as compared to inside an ICU. Methods: We performed a retrospective cohort study of all adult patients admitted to our academic medical center between January 1, 2016, and July 31, 2018, who underwent EEI by a CCM practitioner. The primary outcome of FPS was identified in the EEI procedure note. Secondary outcomes included difficult intubation (> 2 attempts at laryngoscopy) and mortality following EEI. Results: In total, 1958 patients (1035 [52.9%] inside ICU and 923 [47.1%]) outside an ICU) were included in the final cohort. Unadjusted rate of FPS was not different between patients intubated out of the ICU and patients intubated inside of the ICU (689 [74.7%] vs 775 [74.9%]; P = .91). There was also no difference in FPS between groups after adjusting for predictors of difficult intubation and baseline covariates (odds ratio: 0.95; 95% confidence interval, 0.75-1.2, P = .65). Mortality of patients undergoing EEI out of the ICU was higher at each examined time interval following EEI. Discussion: For EEI done by CCM practitioners, rate of FPS is not different between patients undergoing EEI outside an ICU as compared to inside an ICU. Despite the lack of difference between rates of procedural success, patient mortality following EEI outside an ICU is higher than EEI inside an ICU at all examined time points during hospitalization.

To measure the impact of staged implementation of full versus partial ABCDE bundle on mechanical ventilation duration, ICU and hospital lengths of stay, and cost.Prospective cohort study.Two medical ICUs within Montefiore Healthcare Center (Bronx, NY).One thousand eight hundred fifty-five mechanically ventilated patients admitted to ICUs between July 2011 and July 2014.At baseline, spontaneous (B)reathing trials (B) were ongoing in both ICUs; in period 1, (A)wakening and (D)elirium (AD) were implemented in both full and partial bundle ICUs; in period 2, (E)arly mobilization and structured bundle (C)oordination (EC) were implemented in the full bundle (B-AD-EC) but not the partial bundle ICU (B-AD).In the full bundle ICU, 95% patient days were spent in bed before EC (period 1). After EC was implemented (period 2), 65% of patients stood, 54% walked at least once during their ICU stay, and ICU-acquired pressure ulcers and physical restraint use decreased (period 1 vs 2: 39% vs 23% of patients; 30% vs 26% patient days, respectively; p0.001 for both). After adjustment for patient-level covariates, implementation of the full (B-AD-EC) versus partial (B-AD) bundle was associated with reduced mechanical ventilation duration (-22.3%; 95% CI, -22.5% to -22.0%; p0.001), ICU length of stay (-10.3%; 95% CI, -15.6% to -4.7%; p = 0.028), and hospital length of stay (-7.8%; 95% CI, -8.7% to -6.9%; p = 0.006). Total ICU and hospital cost were also reduced by 24.2% (95% CI, -41.4% to -2.0%; p = 0.03) and 30.2% (95% CI, -46.1% to -9.5%; p = 0.007), respectively.In a clinical practice setting, the addition of (E)arly mobilization and structured (C)oordination of ABCDE bundle components to a spontaneous (B)reathing, (A)wakening, and (D) elirium management background led to substantial reductions in the duration of mechanical ventilation, length of stay, and cost.

BackgroundA feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure.MethodsTo assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay, Eve Technologies), secondary infections, duration of supplemental oxygen support and hospitalization.FindingsPatients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65yrs age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and further to 146 pg/ml at Day 14/discharge. Significant declines in IFN-γ, TNFα, IL-27, CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unmodified. IL-6 levels declined sharply among patients with baseline levels >10 pg/ml. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006).InterpretationConsistent with a pathophysiological role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are required to formally assess mortality outcomes. Funding: National Center for Advancing Translational Sciences

Background:A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure.Methods:To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h. Secondary endpoints included 28-day mortality, dynamic cytokine profiles, secondary infections, duration of supplemental oxygen support, and hospitalization.Findings:Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 years, range 31–80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953 ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days; 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Three deaths were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant Day 3 declines in IFN-$\gamma $, TNFα, IL-27, CRP, and ferritin occurred. IP-10 and CXCL-9 declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearsonr: 0.98,P-value 0.0006).Interpretation:Infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19.

Background For patients with novel coronavirus 2019 (COVID-19) who undergo emergency endotracheal intubation, there is limited data regarding the practice, outcomes and complications of this procedure. Research Question For COVID-19 patients requiring emergency endotracheal intubation, how do the procedural techniques, the incidence of first pass success and the complications associated with the procedure compare with intubations on critically ill patients prior to the COVID-19 pandemic? Study Design and Methods We conducted a retrospective study of adult COVID-19 patients at Montefiore Medical Center who underwent first-time endotracheal intubation by critical care physicians between July 19, 2019 and May 1, 2020. The first COVID-19 patient was admitted to our institution on March 11, 2020, before which patients were designated as the pre-pandemic cohort. Descriptive statistics was used to compare groups. A Fischer’s exact test was used to compare categorical variables. A two-tailed Student’s t-test for parametric variables or a Wilcoxon rank sum test for nonparametric variables were utilized for continuous variables. Results 1,260 intubations met inclusion criteria (782 pre-pandemic, 478 pandemic). Patients during the pandemic were more likely to be intubated for hypoxemic respiratory failure (72.6% vs 28.1%; P

Communication and teamwork are essential during inpatient emergencies such as cardiac arrest and rapid response (RR) codes. We investigated whether wearing numbered jerseys affect directed commands, teamwork, and performance during simulated codes. Eight teams of 6 residents participated in 64 simulations. Four teams were randomized to the experimental group wearing numbered jerseys, and four to the control group wearing work attire. The experimental group used more directed commands (49% vs. 31%, p < .001) and had higher teamwork score (25 vs. 18, p < .001) compared with control group. There was no difference in time to initiation of chest compression, bag-valve-mask ventilation, and correct medications. Time to defibrillation was longer in the experimental group (190 vs. 140 seconds, p = .035). Using numbered jerseys during simulations was associated with increased use of directed commands and better teamwork. Time to performance of clinical actions was similar except for longer time to defibrillation in the jersey group.

For critically ill patients with acute respiratory failure (ARF), lung ultrasound (LUS) has emerged as an indispensable tool to facilitate diagnosis and rapid therapeutic management. In ARF, there is now evidence to support the use of LUS to diagnose pneumothorax, acute respiratory distress syndrome, cardiogenic pulmonary edema, pneumonia, and acute pulmonary embolism. In addition, the utility of LUS has expanded in recent years to aid in the ongoing management of critically ill patients with ARF, providing guidance in volume status and fluid administration, titration of positive end-expiratory pressure, and ventilator liberation. The aims of this review are to examine the basic foundational concepts regarding the performance and interpretation of LUS, and to appraise the current literature supporting the use of this technique in the diagnosis and continued management of patients with ARF.

Background Evidence-based timeliness benchmarks have been established to assess quality of breast cancer care, as delays in treatment are associated with poor clinical outcomes. However, few studies have evaluated how current breast cancer care meets these benchmarks and what factors may delay the timely initiation of treatment. Patients and Methods Demographic and disease characteristics of 377 newly diagnosed patients with breast cancer who initiated treatment at Tufts Medical Center (2009-2015) were extracted from electronic medical records. Time from diagnosis to initial surgery and time from diagnosis to initiation of hormone therapy were estimated with Kaplan-Meier curves. Multivariable regression analysis was used to identify factors associated with treatment delays. Thematic analysis was performed to categorize reasons for delay. Results Of 319 patients who had surgery recommended as the first treatment, 248 (78%) met the 45-day benchmark (median, 28 days; 25th-75th %, 19-43). After adjusting for potential confounders, multivariable regression analysis revealed that negative hormone receptor status (odds ratio, 3.48; 95% confidence interval, 1.44-8.43) and mastectomy (odds ratio, 4.07; 95% confidence interval, 2.10-8.06) were significantly associated with delays in surgery. Delays were mostly owing to clinical complexity or logistical/financial reasons. Of 241 patients eligible for hormone therapy initiation, 232 (96%) met the 1-year benchmark (median, 147 days; 25th-75th %, 79-217). Conclusion Most patients met timeliness guidelines for surgery and initiation of hormone therapy, although risk factors for delay were identified. Knowledge of reasons for breast cancer treatment delay, including clinical complexity and logistical/financial issues, may allow targeting interventions for patients at greatest risk of care delays.

Background Outcomes in primary amyloid renal patients are of interest as the era of monoclonal antibody therapies begins. Patients and Methods We studied 77 consecutive primary amyloid renal patients (58% men) for renal progression (end stage renal disease [ESRD]), renal response (RR), and overall survival (OS). Results At diagnosis median age was 63 (range, 35-81) years, estimated glomerular filtration rate 70 mL/min (range, 5-114), difference between involved and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2 and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR. Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months, respectively. Median OS was not reached in this cohort and was not reached from onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR. In those without ESRD at diagnosis, baseline creatinine and absent RR predicted progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR predicted RR. In multivariate Cox regression analysis, cardiac stage and achievement of CR/VGPR predicted OS, enabling construction of a prognostic model. Conclusion Anti-plasma cell therapies provide a definite albeit limited benefit and new approaches to amyloid-related organ dysfunction are needed.

Pulmonary hypertension (PH) due to chronic respiratory disease and/or hypoxia is classified as World Health Organization (WHO) Group III pulmonary hypertension. The patients most commonly encountered in clinical practice with group III PH include those with chronic obstructive lung disease (COPD), diffuse parenchymal lung disease, and sleep-disordered breathing. The purpose of this review is to outline the variable clinical significance of pulmonary hypertension in the most common pulmonary disease states and how a clinician may approach the management of these patients.

Background Treprostinil is an intravenous prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH). Few studies have compared the pharmacodynamics and effectiveness of treprostinil and epoprostenol in patients with high-risk PAH . Methods Case series of patients with PAH admitted to a Medical Intensive Care Unit for transition from epoprostenol to intravenous treprostinil for refractory class III–IV functional symptoms or right heart failure . Mixed linear models were used for comparisons between repeated hemodynamic measurements. Results Five of fourteen patients treated with intravenous treprostinil during the study period underwent transition to epoprostenol. Two had PAH associated with systemic sclerosis , three had idiopathic PAH. Pulmonary arterial pressures (PAP) and pulmonary vascular resistance significantly increased within 1 h after discontinuation of treprostinil in all subjects. Mean PAPs immediately prior to discontinuation of treprostinil (53.4 ± 7.5 mmHg) were significantly lower than the values 1 h after discontinuation (63.6 ± 9.6 mmHg, p = 0.026), but were significantly higher than the values following transition to epoprostenol (45.4 ± 5.5, p = 0.0493); 4/5 subjects had short-term clinical follow-up data available; all improved in functional class. No subject experienced adverse events during the transition. Conclusions High-risk PAH patients with an inadequate response to treprostinil may have significant clinical and hemodynamic response to epoprostenol. Following discontinuation of treprostinil in these patients, the hemodynamic effects of discontinuation were seen in substantially shorter time than what is known to be the pharmacokinetic terminal half-life.

e18637Background: Delays in breast cancer treatment lead to poor clinical outcomes. Evidence-based timeliness benchmarks have been established to assess quality of care. However, few studies have e...

To assess understanding of numerical concepts in asthma self-management instructions, a 4-item Asthma Numeracy Questionnaire (ANQ) was developed and read to 73 adults with persistent asthma. Participants completed the Short Test of Functional Health Literacy in Adults (STOFHLA), 12(16%) answered all 4 numeracy items correctly; 6(8%) answered none correctly. Participants were least likely to understand items involving risk and percentages. Low numeracy but not STOFHLA score was associated with a history of hospitalization for asthma. At higher STOFHLA levels there was a wide range of the total number of correct numeracy responses. Numeracy is a unique and important component of health literacy.

Cardiac stage and depth of hematologic remission are major predictors of survival for AL amyloidosis patients (Wechalekar et al., Blood, 2013; Dispenzieri et al., JCO, 2004; Palladini et al., JCO, 2012). Renal staging in AL amyloidosis (AL) has been studied in the context of renal survival (Palladini et al., Blood 2014). Influences on survival for renal patients have yet to be fully defined. We performed a retrospective study of all AL patients with renal involvement diagnosed at our center between 7/1/08 and 6/30/15. In this cohort of consecutive patients (n=80) median age was 63 (IQR 55-70) and 56% were men. Eighty-eight percent had lambda plasma cell disease and median involved FLC was 140mg/L (69-485). Thirty-nine percent were renal stage 1, 44% stage 2, and 16% stage 3. Median 24-hour proteinuria and serum creatinine were 6.23 g (3.47-10.70) and 1.03 mg/dL (0.80-1.80) respectively, and median eGFR was 72 mL/min (41-90). Fifty-eight percent had cardiac involvement, of whom 11% were cardiac stage 1, 54% stage 2, and 34% stage 3, while 18% had GI and 9% peripheral nerve involvement. As first-line therapy, 70% received bortezomib-based regimens and 25% melphalan-based autologous stem cell transplant. By intention-to-treat, at 6 months after beginning therapy, 54% of patients had a hematologic response of PR or better, and renal and cardiac responses occurred in 13% and 14% of patients respectively, while renal progression occurred in 6%. Median overall survival (OS) for this cohort (n=80) was 67 months. Those with cardiac involvement (n=45) had a median OS of 41 months and, while median OS was not reached for cardiac stage ≤ 2, it was 31 months for those who were stage 3 (P In conclusion, for AL patients with renal involvement, both cardiac stage and depth of hematologic response are important contributors to overall survival. Furthermore, as this real world intention-to-treat analysis demonstrates, there is a continuing need for better therapies for both the hematologic disease and the organ damage associated with AL. Figure. Figure. Disclosures Oliver: Prothena Biosciences, Inc.: Employment, Equity Ownership. Guthrie:Prothena: Employment, Equity Ownership, Other: Leadership. Comenzo:Takeda: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Karyopharm: Research Funding; Janssen: Consultancy, Research Funding.

Abstract 3150 Background: AL is a plasma cell dyscrasia characterized by the pathologic production of monoclonal light chains which misfold, deposit in various organs, including the heart, and can cause early death. High dose melphalan with stem cell transplant (SCT) results in high hematologic response rates and is a standard treatment for eligible patients. Achieving a complete hematologic response (CR) to SCT results in extended event-free and overall survival (OS), up to 8 and 13 years respectively in one large series. (Blood 2011; 118:4346) We have studied the addition of novel agents as consolidation following risk-adapted SCT (RA-SCT) in order to improve hematologic response (HR) rates and therefore outcomes. (Br J Haem 2007;139:224; Amyloid 2010;17:80a) In this report we examine the long-term outcomes of patients who received initial therapy with RA-SCT followed by consolidation for hematologic response less than CR (HR < CR). Methods: We performed a retrospective study to assess the HR rates, incidence of hematologic progression and overall survival (OS) of AL patients enrolled at diagnosis on two consecutive phase II trials using RA-SCT with consolidation for HR < CR (NCT01527032 and NCT00458822). OS was calculated from date of transplant to date of death or last follow up. Median event free survival (EFS) and OS were estimated by the method of Kaplan Meier. Cumulative incidence function was used to estimate the incidence of progression and death. Results: Between 2002 and 2011, 83 patients were enrolled and underwent RA-SCT on these trials and, following RA-SCT, those with HR < CR received consolidation with thalidomide and dexamethasone (TD) in the first and bortezomib and dexamethasone (BD) in the second trial. Thirty-six patients had cardiac involvement (43%) and all patients had free light chain measurements employed to score hematologic response and progression using consensus criteria (Am J Hematol 2005;79:319; Blood 2010;116:1364a). The frequency of CR following SCT was 24% and increased to 48% with post-SCT consolidation. The CR rates increased at 1 year compared to 3 months post-SCT from 21% to 36% with TD and from 28% to 62% with BD. With a median follow up of 5.1 years, the EFS is 4.5 years (95% CI: 2.6 to not reached) and the OS of all patients has not been reached (Figure 1). Sixteen patients died prior to hematologic progression and 26 patients have progressed with a cumulative incidence of hematologic progression of 8%, 18%, and 29% at 1, 2 and 3 years, respectively (Figure 2). Thirty-one percent (8/26) of relapsed patients have not required second-line therapy while among those who have, 78% (14/18) have responded including 44% (8/18) with CR. The median OS following hematologic progression was 5 years (95% CI: 2.6–5.8). Conclusions: Half of the AL patients on initial therapy trials employing RA-SCT and consolidation for HR < CR achieved CR with 36% of pts on the TD and 62% on the BD consolidation trial in CR at 1 year post-SCT respectively. At 3 years post-SCT the cumulative incidence of relapse was 29% and a third of relapsed patients did not require therapy, likely due to the very sensitive serum free light chain assay that detects low level hematologic progression in the absence of organ progression. Almost 80% of patients requiring second-line therapy responded, over half with CR, and median OS after relapse was 5 years. These results indicate that initial therapy with RA-SCT and consolidation is an effective initial treatment strategy for patients with AL in the era of novel agents. With over 5 years of follow up the median OS has not been reached. Disclosures: Comenzo: Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Use of the investigational agent MLN9708, an oral proteasome inhibitor, in the treatment of relapsed or refractory light-chain amyloidosis. Hassoun:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Giralt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. Landau:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding.

Background: Multiple Myeloma (MM) is the second most common hematologic malignancy in the United States. African Americans have among the highest risks of MM and MGUS with several distinct features compared to existing literature. Furthermore, the prevalence of MM is even higher in the Afro-Caribbean population. Cytogenetic and molecular genetic abnormalities predict outcome in patients with MM. Hyperdiploid MM (H-MM) generally has a better prognosis than nonhyperdiploid MM (NH-MM). In addition, patients with additional chromosome 1 abnormalities, loss of chromosome 13, translocation t(14;16) and t(4;14) tend to have a worse survival while patients with translocations t(11;14) are associated with improved survival. In our patient population, the most common cytogenetic abnormalities and their effect on survival remain unknown. Objective: This study was performed to establish a profile of Afro-Caribbean patients with newly diagnosed Multiple Myeloma in order to gain further insight into unique cytogenetic abnormalities and their effects on survival. Methods: Patients with Multiple Myeloma at Kings County Hospital Center and University Hospital at Brooklyn from 2000-2013 were identified by our tumor registries (n=311). We included all the newly diagnosed patients from 2000-2013 who underwent a bone marrow biopsy and conventional cytogenetic by chromosome banding and FISH (n= 173). Patients who did not have a cytogenetic analysis were excluded. Data was collected at the time of initial presentation to include demographics and cytogenetic abnormalities. Survival data was obtained from Social Security Death Index. Differences in frequency of each cytogenetic abnormality by mortality status were examined using Chi-Square or Fisher’s Exact Tests. Two sets of age-adjusted logistic regression models were used to examine potential cytogenetic correlates of both poor (less than two years) and good (4 years or more) survival. Data analysis was performed using SPSS Advanced Statistics. Results: The median age at the time of diagnosis was 65 (Range 36-90). Chromosome banding and FISH showed abnormal cytogenetics in 46% of our patients (n=79). These patients were also found to have multiple abnormal clones. NH-MM was found in 24% (n=19) and H-MM was found in 39% (n=31) of the 79 patients. The most commonly affected abnormalities were trisomiesof odd-numbered chromosomes; +1 (47%), +3 (19%), +5 (21%), +7 (24%), +9 (47%), +11 (42%), +15 (44%), +17 (9%) and +19 (29%). Thirty five percent of 173 patients have expired (n=60). The median survival in the deceased patients was 6.2 years (Range 0.34-12.9). When we examined all patients who lived greater than four years post-diagnosis (n=152), we found significant abnormalities including +5 (p=0.052), NH-MM (p=0.009) and t(11;14) (p=0.03) (See Table 1). Indicators of poor prognosis including 1q gain (p=0.13), loss of chromosome 13 (p=0.21) and del17 (p=0.08) were not significant. In patients who are living, 19% (n=29) have not yet reached the four-year post-diagnosis survival. Less than ten percent underwent autologous stem cell transplantation. Excludes patients who lived less than 3 months post diagnosis August 5 2014 | Chromosome abnormality ( + gain, - loss) | Age-Adjusted Odds Ratio (95% CI) N=152 | P -value | | ------------------------------------------------ | ---------------------------------------------- | -------- | | 1+ | 0.77 (0.26, 2.29) | 0.63 | | 1- | 2.91 (0.58, 14.57) | 0.19 | | 3+ | 1.05 (0.35, 3.17) | 0.93 | | 5+ | 0.47 (0.22, 1.00) | 0.052 | | 7+ | 0.39 (0.14, 1.10) | 0.08 | | 11+ | 0.80 (0.36, 1.75) | 0.57 | | 14+ | 2.07 (0.62, 6.91) | 0.24 | | 15+ | 0.74 (0.34,1.60) | 0.44 | | 19+ | 1.20 (0.46, 3.13) | 0.71 | | X- | 0.42 (0.11, 1.50) | 0.18 | | Y- | 0.40 (0.13, 1.26) | 0.12 | | Hyperdiploidy | 0.88 (0.39, 2.00) | 0.88 | | Nonhyperdiplody | 0.24 (0.08, 0.70) | 0.009 | | t(4;14) | 0.76 (0.27, 2.15) | 0.60 | | t(11;14) | 0.18 (0.04, 0.86) | 0.03 | Table 1: Age-Adjusted Logistic Regression Models Predicting Good Survival (lived 4 years or more post-diagnosis) Conclusion: In this group of Afro-Caribbean patients, median survival (6 years) was higher than Surveillance, Epidemiology, and End Results (SEER) data and more recent review of literature. Gain of chromosome 5 and t(11;14) are consistent with existing data for good prognosis. However, NH-MM which is usually an indicator of poor prognosis was also highly significant in the four-year post-diagnosis survival. This further supports the notion that prognostic value of cytogenetic analysis in this population requires further exploration. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma (MM), a plasma-cell neoplasia characterized by bone marrow (BM) infiltration, monoclonal protein production, and end organ dysfunction, is the most common hematologic neoplasm in blacks. The subclinical syndrome monoclonal gammopathy of undetermined significance (MGUS) precedes MM, and SEER data as well as more recent reports show that blacks have a 2-3-fold higher risk of developing MGUS and MM suggesting a genetic predisposition that causes the marked racial disparity in the incidence of both conditions. In addition, the recent rate of survival improvement observed in Caucasian patients has not been observed in blacks implying that the clinical course and development of resistance are varied between black and Caucasian MM patients. We have recently reported that in our inner-city, largely Caribbean-African patients MM occurs more frequently in women and at a younger age compared to literature. In this report we present cytogenetic information on 146 of these newly-diagnosed MM patients and their survival data. Patients were identified by tumor registries at UH and Kings County Hospital based on tumor histopathology. Data were collected from hospital records of patients treated between 2001-2011 (n=242).Downstate’s inner-city MM patients in Brooklyn, NY are largely Caribbean-African individuals and descendants. Demographics, disease indicators, and vital statistics were collected. In 146 patients, baseline cytogenetics by chromosome banding studies were available. In 63 of these patients baseline FISH used locus-specific probes del13 (13q14), IGH translocation (14q32), del17 and t(11;14)(q13;q32). Patients were treated with standard combination therapies. 146 patients had active, advanced newly-diagnosed MM. Median age=66 (range 36-91), male/female= 0.8, and evidence for the degree of tumor burden included: median % infiltration with CD138-positive cells within BM=50% (range 7%-99%), median serum M protein 3.3 g/dL (range 0.2-9.1). International Staging System level: Stage II: 28%, Stage III: 72%; median serum creatinine=2 mg/dL (range 0.38-14), median serum beta-2 microglobulin= 5.8 mg/dl (range 0.96-20.2). Further, 58% of patients with cytogenetic information had diffuse skeletal involvement with multiple lytic lesions (48%) and fractures (10%). Contrary to expectations from patients with advanced MM, chromosome banding and FISH showed abnormal cytogenetics (AC) in only 26% (n=38). At present, 50% of the patients have expired in both the normal cytogenetics (NC) and AC groups. In the AC group who expired, average time with MM was 2 years (range 0.5-5.6), whereas in the NC patients, average survival was 3.4 years (range, 0.6-5.2). Frequency of trisomies 5 and 9 indicative of hyperdiploidy, were twice as common in patients who are surviving with AC. In these latter patients as well as in surviving patients with NC, average survival time with MM is 4 years (range 0.4-15). In addition, IGH translocation was twice as common in AC patients who expired compared to the NC group. Other AC findings including hypodiploidy, del13, chr1 loss, and trisomies involving chromosomes 1, 7, 11, 19, and 21 were equally frequent in expired and living patients with AC. Using clinically available methods we found IGH translocation, trisomy 5 and trisomy 9 to be prognostically significant in this cohort of 145 inner-city, largely Carribean-African patients. Subtle presentation of cytogenetic abnormalities suggest that genome-wide analyses are needed to asses this patient populations’ MM biology.Cytogenetic Abnormality (frequency)Alive (n)Expired (n)Mean Survival in Years of Expired Patients with AC (Range)del 13 (12.3%)8101.2 (0.1-3.6)IGH translocation (13.0%)7121.7 (0.1-4.1)Chr 1 gain (8.2%)571.1 (0.1-2.4)Chr 1 loss (4.8%)342.3 (0.5-4.1)Hyperdiploidy (19.9%)15141.8 (0.1-5.6)Hypodiploidy (8.9%)761.7 (0.1-4.1)Trisomy 5 (12.3%)1261.7 (0.1-5.6)Trisomy 7 (6.9%)641.2 (0.5-2.3)Trisomy 9 (15.1%)1482.1 (0.1-5.6)Trisomy 11 (12.3%)992.0 (0.1-5.6)Trisomy 15 (11.6%)1161.5 (0.1-5.6)Trisomy 19 (13.7%)1371.7 (0.1-4.1) Disclosures: No relevant conflicts of interest to declare.

8594 Background: Multiple myeloma (MM) is the most common hematologic neoplasm in blacks in the US. Based on SEER data of all Americans, the disease is more common in men, has a median diagnosis age of 70 and median survival of 3-6 years. The subclinical syndrome MGUS precedes MM, and blacks have a 2-3-fold higher risk of developing MGUS and MM. Further, recent improvements in survival observed for white patients are not observed in blacks. To gain new insight into pathogenesis and to optimize patient care, we characterized our inner city, largely Caribbean-African population in Brooklyn, NY, in terms of disease presentation and course. Methods: MM patients were identified by tumor registries based on histopathology. Data including survival were collected from records of patients diagnosed between 2001-2011 (n=242). Data analysis was performed using SPSS Advanced Statistics. Results: Median age was 64 (range 35-91), male: female ratio was 0.70. The most common presenting pathology was the presence of multiple skeletal lesions with fractures (67% of patients). Spinal cord compression and spinal compression fractures occurred in 33% and 32% of patients, respectively. Renal disease was present in 26%, indicated by serum creatinine >2 mg/dL. Consistent with advanced stage and renal failure, median serum beta-2 microglobulin was 4.25 (range 0.96-82.8). Chromosome banding and FISH was available on 133 patients and showed no cytogenetic abnormalities in 53%; hyperdiploidy (30.4%). Common trisomies included chr 1, 5, 15 and 19. Other abnormalities were del 13 (13%) and chr 14 translocations (11%). Comorbidities include hypertension (65%), diabetes (35%) and obesity (BMI over 30 in 24%). While recent improvements in acquiring health insurance have improved access, less than 10% of patients received HDCT and ASCT. As of October 1, 2012, 36% of all patients are living. Survival analyses are underway. Conclusions: MM presents at an advanced stage and affects younger AA’s in the Downstate community. Strategies for identifying and treating patients with progressive MGUS and at earlier disease stages may enhance survival.