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Background The International Myeloma Working Group has defined smoldering multiple myeloma (SMM) as the presence of 10%-60% plasma cells in the bone marrow and M-protein (IgG, IgA) ≥3 g/dL without end-organ damage (an increased calcium level, renal failure, anemia, and destructive bone lesions). Areas of uncertainty Patients considered to have SMM should not have any myeloma-defining events or amyloidosis. Different risks factors classify SMM into low-, intermediate-, or high-risk categories. The rate of progression from SMM to symptomatic myeloma is ∼10% per year during the first 5 years of diagnosis. SMM requires frequent follow-up ∼every 3 months during the first 5 years as compared to monoclonal gammopathy of undermined significance, which usually requires follow-up every 6-12 months after the first year of diagnosis. Data sources A literature search was performed from electronic bibliographic databases: MEDLINE (Ovid SP/PubMed), EMBASE, the Cochrane Library (Cochrane Database of Systematic Reviews), and Cochrane Central Register of Controlled Trials and from annual meeting abstracts from inception to May 2017. Therapeutic advances This review presents the literature and available data that support or do not support early treatment of high-risk SMM (HR-SMM) and provides evidence-based recommendations for management of SMM patients. Despite emerging data recommending early treatment of HR-SMM, we predict the SMM category may disappear in the near future and patients will be diagnosed with either multiple myeloma or monoclonal gammopathy of undermined significance. Conclusions Success with early therapy trials for HR-SMM is largely due to patients meeting current criteria for multiple myeloma that may have been classified as SMM and, therefore, benefitted from therapy. Based on current practices and the literature, SMM should be managed with close follow-up. Based on available data, we suggest SMM to only be treated in clinical trial settings.

Coronavirus disease 2019 (COVID-19) continues to pose an unprecedented challenge for the entire world and the healthcare system. Different theories have been proposed elucidating the pathophysiological mechanisms attributing to high mortality and morbidity in COVID-19 infection. Out of them, thrombosis and procoagulant state have managed to earn the maximum limelight. We conducted an observational study based on data from randomly selected 349 hospitalized patients with COVID-19 infection in a community-based hospital in New York City during the first wave of the COVID-19 viral surge in March 2020. The main objective of our study was to assess the risk and occurrence of thrombotic events (both venous and arterial) among the hospitalized patients including the intensive care unit (ICU) and non-ICU admissions with confirmed COVID-19 infection. The primary outcome in our study was defined as the thrombotic events that included myocardial infarction (MI), deep venous thrombosis (DVT), cerebrovascular accidents (CVA), and pulmonary embolism (PE). The study correlated the association of thrombotic events with the level of biomarkers of interest: D-dimer >1000 ng/ml, troponin-I >1 ng/ml, or both. The association of D-dimers and troponin-I with thrombotic events was measured using both univariate and multivariate Cox proportional hazard (PH) regression analysis. Out of a total of 349 patients, 78 patients (22.35%) were found to have elevated biomarkers (D-dimer >1000 ng/ml and/or troponin-I >1 ng/ml) and were categorized as a high-risk group. Eighty-nine patients developed thrombotic complications (evidence of more than one thrombotic event was found in several patients). Two-hundred seventy-one (77.65%) patients had no documentation of thrombosis. The incidence of thrombotic events included myocardial infarction (MI; N=45; 12.8%), cerebrovascular accidents (CVA; N=16; 4.5%), deep venous thrombosis (DVT; N=16; 4.5%), and pulmonary embolism (PE; N=9; 2.57%).

Background: Although diffuse alveolar damage and respiratory failure are the key features of coronavirus disease 2019 (COVID-19), the involvement of other organs such as the kidney has also been reported. The reports of the incidence of acute kidney injury (AKI) in COVID-19 patients vary widely. In this study, we report our unique experience with AKI in COVID-19 patients in a low socioeconomic and predominantly ethnic minority group and provide its incidence, risk factors, and prognosis to expand the current understanding of this complication. Methods: In this single-center, retrospective cohort study, we analyzed the data of 469 COVID-19 patients admitted to the Brookdale University Hospital in Brooklyn, NY, from March 18 through April 23, 2020. Information regarding demographics, comorbidities, medications, clinical and laboratory data, and outcomes was collected from the electronic medical records. Both univariate and multivariate analyses were performed to determine the association of AKI with in-hospital mortality. Results: The median age was 66 years (interquartile range [IQR] 25–75; range 19–101 years), and 268 (57.14%) patients were male. Estimated glomerular filtration rate (eGFR) as determined by the Modification of Diet in Renal Disease Study Equation was low (2) in 207 (44.1%) patients. During hospitalization, 128 (27.3%) patients developed AKI, and the incidence was significantly higher in those patients presenting with a low eGFR (N = 81, 39.1%; p < 0.001). Male sex, hypertension, the use of angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatories, hemodynamic instability, mechanical ventilation, acute respiratory distress syndrome, and admission elevated ferritin, creatinine kinase, brain natriuretic peptide, and troponin 1 were identified as the risk factors for in-hospital AKI. Ninety-seven (28.45%) patients died in the non-AKI group versus 91 (71.1%) in the AKI group (p < 0.001). The Cox proportional hazard model after adjusting for age, gender, comorbidities, hemodynamic status, and PF ratio (arterial oxygen partial pressure [PaO2]/fractional inspired oxygen [FiO2]) determined that on admission, an elevated blood urea nitrogen (hazard ratio [HR]: 1.75; 95% confidence interval [CI] 1.23–2.48), a low eGFR (HR 1.43; CI 1.1–2.03), AKI stage 1 (HR 1.14; CI 0.64–2.03), AKI stage 2 (HR 1.86; CI 1.03–3.56), and AKI stage 3 (HR 2.1; CI 1.3–2.81) were independent risk factors for in-hospital mortality. Renal replacement therapy (RRT) did not improve survival in stage III AKI. Conclusion: AKI in our hospitalized COVID-19 patients was common and carried a high mortality, especially in patients with AKI stage 3. RRT did not improve survival. Policy changes and planning for this high incidence of AKI in COVID-19 patients and its associated high mortality are necessary at the local and national levels.

Introduction Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma. Methods A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P Results Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I2 = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%. Conclusion Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.

This study aims to identify the baseline patient characteristics, clinical presentation, and response to treatment of 11 patients who were diagnosed with thrombotic thrombocytopenic purpura (TTP) between 2014 and 2020 at Brookdale University Hospital Medical Center, Brooklyn, NY. Laboratory and clinical parameters were recorded for 29 patients who received plasmapheresis in this time period. Of 29 patients, 11 had confirmed TTP and one was diagnosed with hereditary TTP. Young, black, and female patients made up the majority of our patient population. A high prevalence of obesity and drug abuse were seen among our patients. Five out of 11 were obese and four of them were morbidly obese; six out of 11 patients were positive for the drug screen including cannabinoids (3), opiates (2), benzodiazepines (1), PCP (1), and methadone (1). Four patients with a positive drug screen had acute kidney injury (AKI), and plasmapheresis helped them enhance their kidney function. We observed a high incidence of AKI and high TTP exacerbation rates in patients who were drug abusers and those who were morbidly obese. There is a paucity of data on the relationship of TTP with obesityor drug abuse and this needs further study.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Approximately 20-30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40-50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown promising results for the treatment of relapsed or refractory hematological malignancies. Best results have been reported in acute lymphoblastic leukemia patients with a complete response rate above 80%. Patients who received donor-derived CAR T cells for the relapsed malignancy after stem cell transplantation (allogenic hematopoietic stem cell transplant) were identified from the published trials. A total of 72 patients from seven studies were treated with donor-derived CAR T cells. Only five out of 72 patients (6.9%) developed graft versus host disease. Use of donor-derived CAR T cell for relapse prophylaxis, minimal residual disease clearance or salvage from relapse is therefore highly effective, and risk of graft versus host disease flare is very low. Side effects include cytokine release syndrome, tumor lysis syndrome, B-cell aplasia along with CNS toxicity.

Pancreas divisum is reported to occur in up to 14% of the population. The majority of patients with this congenital anomaly remain asymptomatic. Pancreas divisum can be associated with recurrent pancreatitis due to inadequate drainage of pancreatic secretions through the dorsal pancreatic duct and the minor papilla. We present a patient with a six-month history of recurrent acute pancreatitis due to an impacted pancreatic duct stone in the minor papilla and an unrecognized pancreas divisum. This situation has only been reported in two other cases in the literature.

Bilateral renal infarction is a rare phenomenon which can be difficult to diagnose because the symptoms may often mimic renal calculi, infection, muscle inflammation, genital diseases, myocardial infarction, or ischemia. We present the case of a 55-year-old male patient who presented with non-radiating, left-sided flank pain associated with nausea and vomiting. A computed tomography (CT) scan of the abdomen and pelvis with contrast demonstrated bilateral renal infarction. A thorough workup was initiated, and the thrombus formation due to left atrial enlargement from hypertrophic obstructive cardiomyopathy was considered as the cause of the bilateral renal infarction in this patient. The patient's renal function improved with treatment, and she was discharged on an anticoagulant, considering her left atrial enlargement and renal infarction.

Objectives: This systematic review and meta-analysis assesses the utility of trimetazidine (TMZ) to prevent contrast induced nephropathy (CIN) in patients with renal insufficiency undergoing coronary angiography and angioplasty. Materials and methods: This meta-analysis was formulated and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of databases was conducted by 2 researchers independently for clinical trials, comparing hydration plus TMZ vs conventional hydration alone for prevention of CIN through January 2020. All patients had renal insufficiency (defined as GFR < 89 ml/minute/1.73 m2) and the outcome of interest was the incidence of contrast induced acute kidney injury. The odds ratio (OR) was estimated with 95% confidence interval (CI). Heterogeneity was reported with the I2 statistic, using a fixed-effects model, and >50% of I2 was considered to be statistically significant. Results: Eleven studies, 1611 patients, met the inclusion/exclusion criteria: 797 patients comprised the TMZ plus hydration group and the remaining 814 patients comprised the control (hydration only) group. Heterogeneity was low I2 = 0%, P = .84, and the heterogeneity of each study was also low. The incidence of CIN in the TMZ plus hydration group was 6.6% (53/797), while the incidence of CIN in the control (hydration only) group was 20% (165/814). Pooled analysis of all studies showed TMZ reduced incidence of CIN compared to saline hydration alone (OR risk 0.30, 95% CI 0.21, 0.42, P

e20548 Background: Patients diagnosed with multiple myeloma (MM) frequently visit emergency departments (ED) with complications, commonly with kidney disease. However, data regarding the prevalence of acute kidney injury (AKI) and its effects on patient outcome, economic burden, length of hospital stay and mortality among these patients are lacking. Methods: From the Nationwide Emergency Department Sample, we obtained 7-year (2010-2016) data of myeloma patients who visited ED. Baseline characteristics of these patients with and without AKI were compared. The multivariable regression model was used to estimate hospital admission, length of stay, healthcare burden and in-hospital mortality in patients with and without AKI. Results: Between 2010-2016, 657,392 adult myeloma patients visited ED at an increased rate from 35 to 45 per 100,000 census population. The prevalence of AKI was 22.5% (n = 147,743) with a stable trend over the study period. AKI was more common in patients with relapsed MM (33.5%) than those in remission (18.6%) or never achieving remission (22.4%) (P < 0.001), male (24.1 vs 20.6% in female, P < 0.001), age ≥65 years (24.1%) vs 18-44 years (12.9%), or 45-64 years (19.3%)(P < 0.001) and urban (23.3%) vs non-urban residents (17.9%)(P < 0.001). The majority patients with AKI were hospitalized (96.5%) compared with those without AKI (69.6%) (P < 0.001). In multivariable analysis, odds of hospitalization was higher in patients with AKI (OR: 8.8, P < 0.001) after adjusting age, gender, co-morbidities and other demographics. Median hospital stay was longer in patients with AKI compared to those without (6 vs 4 days, P < 0.001). Median ED and total hospitalization charges were higher in patients with AKI (ED: $2,057; total: $45,414) vs without AKI (ED: $1,853; total: $29,299) (P < 0.001). In the multivariable adjusted-model, odds of in-hospital mortality was significantly higher in patients not in remission (OR: 1.8), patients with relapse (OR: 2.3), AKI (OR: 2.2), age ≥ 65 years (OR: 1.4), male (OR: 1.1) and urban residents (OR:1.2). Conclusions: In this largest national study of MM patients visiting ED, patients with AKI had higher in-hospital admission, ED and total charges, length of hospital stays, and mortality, both by univariate and multivariate analysis. Prevalence of AKI and mortality were highest in patients with MM relapse.

We report a case of a patient with relapsed Ewing’s sarcoma (ES). After receiving conventional chemotherapy (CC) and noticing chemosensitivity of the disease, we proceeded to give the patient two separate cycles of HDCT consisting of a melphalan/busulfan regimen in the first cycle and etoposide/melphalan in the second cycle. The patient proceeded to get an autologous stem cell transplant (ASCT) after each cycle of HDCT. Our patient, despite multiple poor prognostic factors, including advanced age and multiple sites of disease relapse, showed a one-year event-free survival. Relapsed ES is associated with a poor prognosis. No treatment regimen has yet been established as a standard of care in patients with relapsed ES. We conducted a focused literature review to assess the efficacy of high-dose chemotherapy (HDCT) followed by ASCT in patients with relapsed ES. Given the improved survival outcome with HDCT followed by ASCT in our patient, we propose that its role in relapsed ES needs further assessment through large prospective, randomized controlled studies.

Immunocompromised patients undergoing chemotherapy for hematologic malignancy and hematopoietic stem cell transplant (HSCT) recipients are at increased risk of Clostridium difficile (C. difficile) infection (CDI). The recurrence of infection and its associated morbidity and mortality are due to multiple risk factors. Diarrhea is common in HSCT recipients, but the diagnosis of diarrhea caused by CDI is a therapeutic challenge due to frequent Clostridium difficile colonization with diarrhea secondary to non-infectious causes. The high recurrence rate is a significant challenge in the treatment of immunocompromised patients. Close monitoring of the patients, timely diagnosis, preventive measures, treatment with antibiotics, and the removal of offending agents can help in the management and cure of the disease. We review the literature on management and describe a patient with acute lymphoblastic leukemia (ALL) with multiple recurrences of CDI during leukemia therapy and allogeneic stem cell transplantation for leukemia.

Background. Relapsed Ewing’s sarcoma (RES) is an aggressive malignancy with poor survival. Although high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) given after conventional chemotherapy (CC) has shown survival benefits, it is not generally used in the United States for RES. We performed a systemic review to evaluate the benefits of HDCT for RES. Methods. Literature search involved Medline, Embase, and Cochrane database. We included studies with RES patients treated with HDCT/ASCT. Results. Twenty-four studies with total of 345 reported RES patients that got HDCT were included in final analysis. Seventeen studies had patients with multiple malignancies including RES, while seven had only RES patients. At 2 and 3–5 years, event-free survival (EFS) in studies with only RES patients ranged 42–47% and 20–61% and overall survival (OS) ranged 50–66% and 33–77%, respectively. In studies with combined patients that reported outcomes of RES separately, the EFS at 1–3 and 4 years was 36–66% and 17–50%, respectively. The OS at 1-2 and 3-4 years was 40–60% and 50–70%. Conclusions. Most studies using HDCT/ASCT as consolidation regimen showed improved survival benefits compared to CC. Randomized controlled studies are needed to determine true clinical benefits of HDCT followed by ASCT in patients with RES.

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%–23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20–27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20–56 and 20–70 mg/m2 dose of CFZ vs standard 20–27 mg/m2 dose in NDMM and RRMM.

Background Recently, several deaths secondary to cardiac arrhythmias have been reported in association with substitutive use of loperamide. Therefore, we conducted a systematic review of all reported cases to overview the epidemiologic patterns and clinical outcomes to better elucidate loperamide-induced cardiac complications. Areas of uncertainty Association between substitutive use of loperamide and cardiac arrhythmias. Data sources A comprehensive literature search was conducted across 6 databases using variety of keywords to identify all reports of cardiac side effects associated with loperamide abuse. Only original case reports of cardiac toxicity or cardiac arrhythmias after loperamide abuse or overuse were included. Data were extracted by 2 authors independently using a structured template from the selected reports. Quality assessment of the reports was performed by using a high-quality evaluation tool. Results Thirteen reports describing 19 cases were included in our review. Except for coronary artery spasm in one case, cardiac arrhythmias were the major reported cardiac adverse event. The average age of patients was 31 years with majority being men (79%). The most common presentation was syncope (63%). All cases were reported in US except for 1 case. Three patients were concomitantly taking cimetidine, which is known to cause inhibition of CYP3A4 and CYP2C8 leading to increased levels of loperamide. Thirteen of 19 patients were successfully treated and discharged in a stable condition. Conclusions Our results indicate that measures such as restricting over-the-counter availability of loperamide and increasing awareness regarding loperamide's toxicity are imperative to prevent deaths associated with loperamide abuse.

Background Diabetic foot ulcers (DFUs) cause significant morbidity and put great economic burden on patient and healthcare facilities. Infection is the main driving force behind admissions related to DFU. Culture of soft tissue or bone is invaluable in diagnosing infection but is time consuming. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) are rapid, simple, and inexpensive laboratory tests that can aid in early diagnosis of diabetic foot infection (DFI) and monitor response to treatment. We did a meta-analysis to compare diagnostic performance of inflammatory markers for detecting DFI. Methods We searched PubMed, Embase, and Cochrane databases from their inception to December 2017. This meta-analysis was performed according to PRISMA guidelines. We included studies based on following inclusion criteria: (1) at least one of the biomarkers (ESR, CRP, PCT) was evaluated; (2) both sensitivity and specificity were measured as outcomes; and (3) sufficient data were available to construct 2 × 2 contingency table. We used bivariate random effect regression model to pool the sensitivity and specificity of the targeted biomarkers. Results A comprehensive literature search identified a total of 73 studies. Twelve studies met our inclusion criteria. Number of studies reporting data on each individual biomarker was as follows: 11 for ESR, seven for CRP, and five for PCT. Pooled sensitivity and specificity for ESR were calculated to be 0.84 (95% CI 0.76–0.89) and 0.82 (95% CI 0.73–0.89) with area under receiver operating characteristic curve (AUROC) of 0.90 (95% CI 0.87–0.92). Pooled sensitivity and specificity for CRP were found to be 0.64 (95% CI 0.46–0.80) and 0.87 (95% CI 0.75–0.93) with AUROC of 0.85 (95% CI0.82–0.88). Pooled sensitivity and specificity for PCT were 0.74 (95% CI 0.62–0.83) with AUROC of 0.84 (95% CI 0.81–0.87). Conclusion ESR could be beneficial in ruling out infection in persons who have low suspicion of disease. For those who have high suspicion of disease, PCT could be helpful in ruling in infection. Clinicians should avoid ordering both ESR and CRP because role of CRP is limited. All inflammatory markers need standardization of threshold levels for detecting infection. Disclosures All authors: No reported disclosures.

Aim: A sporadic incident of Clostridial disease that affected Holstein Friesian (HF) cross bred cows (n=8) at an organized dairy farm was investigated. Materials and Methods: Detailed clinical investigations and treatment were carried out on all the affected animals. Complete blood count (CBC) and plasma biochemistry were performed on survived animals (n=6). The needle biopsy samples were subjected to culture and identification of the organism by Gram staining. Results: Two cows were died before instituting the treatment in this clinical incident. The carcasses were seen with typical bloated appearance immediately after death, laying one side with affected leg stuck out. Post-mortem of the carcasses were not been carried out. Pertinent findings of the CBC were a relative neutrophilia whilst a normal total leucocyte count and lowered Hb. Plasma biochemical parameters revealed significant increase in the mean activity of aspartate aminotransferase while alanine aminotransferase levels were within limits. Gram's staining of the inoculated culture revealed the presence of small gram-positive rods with sub terminal spores. Clinical treatment of the cases was performed with administration of heavy dose of crystalline penicillin and non-steroidal anti-inflammatory drugs (NSAIDS). Clinical recoveries of the cases were good and cessation of spread within the herd confining itself as a sporadic clinical incident. Conclusion: Sporadic Clostridiosis (BQ) of eight cross bred dairy cows was dealt in the present case study by including the details of its alterations in hematological parameters, Plasma biochemical parameters, observation of characteristic clinical signs of the disease and employment of empirical treatment with Penicillin. [Vet World 2012; 5(12.000): 767-770]

Introduction Bortezomib, a proteasome inhibitor and lenalidomide (Len), an immunomodulatory drug are the backbone of established treatment regimens for newly diagnosed MM. Patients with dual-refractory (refractory to both bortezomib and lenalidomide) disease have a poor prognosis with overall survival estimated to be less than one year. Pomalidomide (Pom) has distinct anticancer, antiangiogenic and immunomodulatory properties and has demonstrated synergistic antiproliferative activity in combination regimens. The aim of our study is to compare different Pom based regimens to identify the most effective regimen for relapsed refractory multiple myeloma (RRMM) patients. Methods A comprehensive literature search was performed on PubMed, Cochrane library, Web of Science, Embase and AdisInsight databases on 03/29/2018 which identified a total of 1374 studies. We included phase II/III clinical trials on pomalidomide based regimens that have clearly documented efficacy outcomes. All statistical analyses were performed using Comprehensive Meta-analysis (CMA) Version 3. We used the Cochrane Q statistics (p0.05 or I2 >50%). Studies were classified into subgroups according to the therapeutic regimen: dual and triplet combinations. A separate stratified analysis of triplet regimens based on type of regimen was also performed. Results A total of 35 studies (n = 4623 patients) were included. The most commonly studied regimen was Pom + LoDex (Low dose dexamethasone) with a total of 16 studies on this regimen. All patients included in our study had ≥ 2 prior lines of therapy. Mean number of prior lines of therapy was 6. Most patients were lenalidomide refractory, with 10 patient cohorts of 100% refractoriness and 8 cohorts of ≥ 90% refractoriness. Pooled analysis showed an overall response rate (ORR) of 47.1% across all Pom regimens including both doublet and triplet regimens. An I2 value of 87.3 was found, indicating high heterogeneity across all Pom regimens. With Pom-LoDex, pooled ORR was found to be 35.7% and mean OS 14.37 months. With triplet regimens, pooled ORR was found to be 61.9%. In a separate stratified analysis of triplet regimens based on type of regimen, pooled ORRs with few selected regimens were as follows; Bort-Pom-LoDex (pooled ORR 83.5%, mean PFS 15.7 months [mos]), CFZ-Pom-LoDex (pooled ORR 77.1%, mean PFS 15.3 mos), Pom-LoDex-bendamustine (pooled ORR 74.2%), Pom-Dex-daratumumab (pooled ORR 64.5%), Pom-LoDex-cyclophosphamide (pooled ORR 59.4%, mean PFS 9.5 mos), Pom-LoDex-doxorubicin (pooled ORR 32%). Most frequently reported adverse event with Pom based regimens was myelosuppression. Mean incidences of grade ≥3 hematologic adverse events were neutropenia (47.6%), anemia (26.5%), and thrombocytopenia (20.8%). Mean incidences of grade ≥3 non-hematologic adverse events were infections (29.1%), pneumonia (13.8%) and fatigue (10%). Most of the studies used pomalidomide 4mg daily dosing. Lacy et al. suggested no advantage of 4mg pomalidomide over 2 mg daily dosing. Conclusion From results of pooled analysis, we can infer that triplet combinations of Pom yield almost double response rates (pooled ORR 61.9%) when compared to dual combination of Pom-LoDex (pooled ORR 35.7%). Among three drug combinations, Bort-Pom-LoDex (pooled ORR 83.5%) and CFZ-Pom-LoDex (pooled ORR 77.1%) seem to produce better outcomes. Our study provides useful insight into relative efficacy of various Pom regimens for treatment of RRMM patients. Several trials involving various MoAbs like nivolumab, daratumumab, elotuzumab, isatuximab and pembrolizumab in combination with Pom-LoDex are currently ongoing. Pomalidomide has an acceptable safety profile. Most common treatment emergent adverse events were myelotoxicity and infections that can be effectively managed with supportive care and dose modifications. Disclosures No relevant conflicts of interest to declare.

National Trends in Leukemia Related Emergency Department Visits, Health Care Burden and Disposition Rate in the United States, 2010-2014. Background: Recently emergency department (ED) utilization has been increasing for the management of acute conditions. Utilization of ED healthcare services by hematology and oncology patients have been documented previously. Cancer patients frequently visit the EDs with acute symptoms, that may require further assessment, management, and even hospitalization. Whether the incidence of leukemia related ED visits has altered is unknown. The aim of this study was to analyze the trend of leukemia related ED visits, healthcare cost associated with the visit and the discharge disposition from ED. Methods: We utilized Nationwide Emergency Department Sample (NEDS) dataset for this study. NEDS is a part of the Healthcare Cost and Utilization Project (HCUP) database and contains the information of more than 950 United States (US) hospitals that is weighted to the national estimates. We used five years of data from 2010 to 2014 to examine the trends in prevalence and rates of ED visits, cost, and disposition (such as admission, discharge and death in ED). We defined patients with leukemia (acute myeloid, chronic myeloid, acute lymphocytic, and chronic lymphocytic leukemias) by using the international classification of disease, 9th revision, clinical modification (ICD-9-CM) codes. Cochrane-Armitage test was used to assess the trend of leukemia ER visits over five years. We used estimated US census population to calculate the rate of leukemia related ED visits. Furthermore, we assessed the predictors of hospital admission by using multivariable logistic regression model. Results: Between 2010 to 2014, a nationally weighted estimate of 771,510 patients visited ED with leukemia. The frequency of leukemia related ED visits increased 21.7% from 138,038 to 167,935 during this period that accounted for 0.12% of all ED visits. The rate of leukemia related ED visits increased 20.5% from 44 to 53 per 100,000 census population, which was statistically significant (p=0.04) on a trend test. The total national cost of leukemia related visit increased by 81% from $544 million in 2010 to $984 million in 2014 (p-value0.05). In an adjusted multivariable logistic regression analysis, increasing age (OR 1.02 95% CI 1.024, 1.027), male gender (OR 1.15, 95% CI 1.114, 1.188), patient location in metropolitan area (OR 2.08, 95% CI 1.88, 2.22) and northeast location (OR 1.16, 95% CI 1.03, 1.32) were found to be significantly associated with the higher odds of in hospital admission following leukemia related ED visits. While few other variables like residents of higher income quartile and those holding Medicaid, insurance were also found to be positively associated with the hospitalization but were not statistically significant (OR>1.00, p>0.05). Conclusions: There is an increasing trend of leukemia related ED utilization and associated total and mean/median costs over time, while the rate of hospitalization for leukemia associated visit from ED have decreased. Oncology providers need to plan care accordingly to reduce ER visits and hospital admission for patients with leukemia. Disclosures No relevant conflicts of interest to declare.

Introduction: Multiple myeloma is comparatively uncommon cancer, but among blood malignancies it is still the second most common cancer after non-Hodgkin lymphoma. Patients with complications of multiple myeloma (MM) frequently present to the emergency department. There is a lack of data about the health care burden and trends of utilization of emergency department services by MM patients. The objective of this study is to investigate the recent trends in resource utilization in the emergency departments for MM. Furthermore, we aimed to look for the demographic characteristics associated with the subsequent hospitalization of MM patients. We hypothesized that there has been an increase in the utilization of emergency department services for the management of MM patients in recent years. We further hypothesized that subsequent hospitalization rate may be decreasing with the availability of more efficacious and potentially less toxic drugs. Methods: For this study we obtained the data from United States National Emergency Department Sample (NEDS) years 2010-2014. For categorical variables, frequencies and proportions were generated and statistical significance was tested using a chi-squared test. Rate of myeloma associated emergency department visits were estimated by using US census population. Patients and hospital characteristics were entered in univariate analysis to predict in-patient admissions from the ED. Multivariable logistic regression was used to predict in-patient admissions for the variables that were found statistically significant in univariate analysis. All tests were two-sided with the statistical significance set at p < 0.05. All analyses were conducted using STATA 14.2v and no missing data was imputed. Results: Between 2010 to 2014, approximately 443,214 patients visited emergency departments (ED) with the diagnosis of MM, that accounted for 0.06 % of all emergency department visits. There was an absolute increase of 22% in MM related visits from 80,466 in 2010 to 98,279 in 2014. While the rate of emergency department service utilization by myeloma patient increased significantly by 19% (p=0.04). Overall 73% of myeloma related visits resulted in hospitalization, but over the study period trend of hospitalization decreased. The percentage of patients treated and discharged to home increased from 23% to 29% between 2010 to 2014. Total charges associated with myeloma related visits increased significantly from $315 million to $626 million during 2010 to 2014, with an annual increase in the rate (19.26%: p Conclusion: Multiple myeloma related emergency department service utilization and total charges are increasing over the observed time limit. While the incidence of hospitalization from emergency department is decreasing overtime. These findings can be explained on the basis of few facts. MM patients are living longer with the availability of newer drugs but remain uncured. Most patients will face relapse after the initial disease control, at which point they may need to utilize ED services more frequently. As better oral or intravenous drugs are available through oncology out-patient offices, limited MM drug choices are available in the hospital, majority of MM patients are discharged sooner from the hospitals resulting in reduced hospital admission rates as well as shorter hospital stay. Disclosures No relevant conflicts of interest to declare.

Background: Elotuzumab (elo) is a humanized monoclonal antibody, which has been approved by the FDA for use in combination with lenalidomide (lena) and dexamethasone (dexa) in patients (pts) with relapsed and refractory multiple myeloma (RRMM). Elotuzumab is effective as a single agent, as well as in combination for multiple myeloma treatments, supporting the use of elo in pts with RRMM and newly diagnosed multiple myeloma (NDMM) pts. Method: After review of literature using database searches was done on 6/27/18 (Pubmed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov), 9 prospective and 1 retrospective study with 1128 enrolled pts met the inclusion criteria to date in RRMM and 2 clinical trials including 123 pts in NDMM (Table 1). CMA software v.3 was used for meta-analysis. A random-effect model was applied. Result: Regimens used in RRMM: Based on pooled analysis (95% CI), an overall response rate (ORR) of 66% (54-76.2) was calculated in 685 evaluable pts treated with elo based regimens in RRMM (Figure 1). Most common grade (G) ≥ 3 hematological adverse events (HAE) and non-hematological adverse events (NHAE) based on regimen were calculated using pooled analysis in RRMM pts (Table 2). Anemia was noted in 12.1% ( 7.7-18.6) in 559 pts, while neutropenia in 14.5% (7.5-26.4) out of 591 pts and thrombocytopenia (tcp) in 11.9% (7.9-17.4) in 198 evaluable pts. Diarrhea 5.5% (3.6-8.3), pyrexia 2.4% (1.5-4), peripheral neuropathy (PN) 8.4% (3.8-17.8) were measured in 626, 668 and 143 pts respectively. Elotuzumab as monotherapy: 1 study (n=34) evaluated the efficacy of elo as single agent in RRMM. The median age, time from diagnosis and number of prior therapies were 64.5 years (y) (46-87), 4.4 y (0.9-12.8) and 4.5 y (2-10) respectively. It produced an ORR of 1.4% (0.1-19.1 95% CI) in 34 evaluable pts. Adverse events recorded were pyrexia and fatigue in 17.6% and 8.8% pts respectively. Elotuzumab in two drug regimen: In RRMM, 2 clinical trials (n=49) evaluated the efficacy (95% CI) of elo, ORR of 25% (4.1-72.3) was calculated. The best PFS (progression free survival) produced was in combination of elo 20 mg with bortezumib (bort) 1.3mg/m2 of 9.46 months as compared to 1.8 months when elo10mg/kg + dexamethasone (dexa) 28mg was used. In our analysis for safety, common G≥ 3 HAE calculated were, thrombocytopenia 8.7% (3.3-21.1) n=49, neutropenia 10.7 % (3.5-28.4) n=28 pts and anemia 7.1% (1.8-24.5) n=28 pts. NHAE included diarrhea 1.7% (0.1-22.3), PN 10.7% (3.5-28.4), pyrexia 1.7% (0.1-22.3) in 28 evaluable pts each. Elotuzumab in three drug regimen: In RRMM, 10 clinical trials including 602 pts evaluated the efficacy of elo as a part of triple drug regimen, producing an ORR of 72.2% (54-76.2). The best results were produced with the combination of elo 10-20mg/kg + lenalidomide (lena) 25mg + dexa 40mg producing a PFS of 32.2 mo and 28.62 mo in its phase I and II cohorts respectively. Based on pooled analysis (95% CI) common HAE calculated were neutropenia 17.5% (7.6-35.4) in n=563, thrombocytopenia 12.7% (8.2-19.4) in n=149 and anemia 13% (8-20.5) in n=531 pts. Common G ≥ 3 NHAE estimated were diarrhea 5.7% (3.7-8.6), PN 6.6% (2-19.2), pyrexia 2.5% (1.5-4.1) in 598, 115 and 640 pts respectively. Elotuzumab based regimen in NDMM: A currently ongoing clinical trial NCT02272803 has produced promising results in NDMM pts. As a part of three drug regimen with dose of elo 10mg/kg-20mg/kg, lena 25mg, dexa 20mg in 40 pts produced an ORR of 87.5% (73.2-95.8) versus control group of lena 25mg plus dexa 40mg in 42 pts with an ORR of 73.8% (58-86.1). The PFS rate recorded at 1 year was 93% (79-98%) and 91% (73-97%) respectively. The HAE G ≥ 3 included, neutropenia 18% and leukopenia 15%. In another study with 41 pts, elo was used in combination with lena, bort and dexa producing an ORR of 100% and greater than grade 3 adverse events including Tcp 15%, PN 2%. Conclusion: Results produced in our study suggest that elotuzumab is highly effective when used in pts with RRMM and NDMM. Combination regimens for elo produces an ORR ranging from 79-83% with elo + lena+ dexa, proving that the best results were produced by three drug regimens. Large prospective studies are required to evaluate efficacy and safety of elotuzumab in combination therapies. Disclosures No relevant conflicts of interest to declare.

Background - Acute myeloid leukemia (AML) in elderly patients (>65 years) is associated with poor prognosis with median overall survival (mOS) of 6 months. Hypomethylating agents (Azacytidine (Aza) and Decitabine) are used in elderly patients who are not candidates for intensive chemotherapy. Aza has resulted in complete remission/complete remission with incomplete hematologic recovery (CR/CRi) of 18-27.8% and mOS of 10.4-24.5 months. Decitabine resulted in CR/CRi of 18-47% and mOS of 7.7-8 months. We conducted a systemic review to assess survival benefit of novel combination drug regimens (CDR) involving hypomethylating agent (HMA) in elderly patients with newly diagnosed AML. Methods - Comprehensive literature search was conducted in Medline, Embase and Cochrane database. We included phase I/II studies only that used CDR involving HMA. Results - Initial database search (since inception) lead to 975 studies. After exclusion (duplicates, case reports, relapsed/refractory AML) final analysis included 17 studies(n=540) Ten phase I/II CDR studies involving Aza (n=334) were included. The various drugs used in combination included valproic acid/all trans retinoic acid (n= 42 ,CR/CRi=26.2% mOS= 18.1 m), thalidomide (n= 14,CR/CRi= 29%, mOS= 13.2 m ), gemtuzumab ozogamicin (GO) (n= 142,CR/CRi = 35-44%, mOS= 11 m), lenalidomide (n= 45,CR/CRi=28-44% , mOS= 3-8.2 m), panobinostat (n=38,CR/CRi=10-22.4%, mOS= 8 m), midostaurin (n=12,CR/CRi=25%, mOS=6 m) , entinostat (n=18 ,CR/CRi=0% ,mOS= 6 m ), Seven phase I/II CDR studies(n=206) involving decitabine were included. Drugs used in combination included low dose cytarabine and aclarubicin (n= 85 ,CR/CRi = 64.7% , mOS= 10-12 m ), tosedostat (n=17 ,CR/CRi= 59% mOS= 11.5 m ), bexarotene(n= 4 ,CR/CRi= 0% mOS= 9.2 m), valproic acid(n= 62 ,CR/CRi= 9% mOS= 7.4m) , GO (n= 40,CR/CRi= 45% , mOS= 7m ),bortezomib (n= 10,CR/CRi= 50% ), vorinostat(n = 31,CR/CRi= 30%). Seven studies reported outcomes for patients with adverse cytogenetics separately. Of these, Aza with lenalidomide (n= 11) had a mOS of 9.5 months and with panobinostat (n=12) the overall response rate was 25% and mOS of 7 months. Similarly, decitabine with vorinostat (n = 8) and tosedostat(n =12) resulted in CR/CRi of 25% and 43% respectively. Long term outcomes for these CDR with decitabine were not reported. In two additional studies, valproic acid/all trans retinoic acid given with AZA and low dose cytarabine & aclarubicin with decitabine(p=0.023) showed poor outcome through multivariable cox model analysis. Five studies reported response rates for subgroup of patients with secondary AML using HMA. Of these, Aza with lenalidomide (n= 16) had a CR/CRi = 27% with median response duration of 21.3 weeks, a CR/CRi of 0% with entinostat (n= 18) and CR/CRi of 22% with thalidomide(n=9). Decitabine given with tosadostat (n= 10) had CR/CRi of 60% and with bortezomib(n=3) the CR/CRi was 66%. The long term outcomes were not reported for these patients. Conclusion - Novel combinations involving Aza with valproic acid/all trans retinoic acid, thalidomide, or GO showed similar CR/CRi and mOS compared to Aza alone. Tosedostat, low dose cytarabine, and aclarubicin given in combination with decitabine showed best results with superior CR/CRi and mOS compared to decitabine alone. Bexarotene with decitabine also improved mOS over decitabine alone despite lower CR/CRi. In patients with adverse cytogenetics, Aza with lenalidomide or panobinostat showed superior CR/CRi and mOS. Decitabine given with vorinostat and tosedostat also showed superior CR/CRi. In patients with secondary AML, Aza in combination with lenalidomide or thalidomide and decitabine with tosedostat or bortezomib showed superior CR/CRi. These CDR for patients with adverse cytogenetics and secondary AML need further testing in studies designed with this specific patient population in which long term outcomes are also measured. These CDR need to be evaluated in large, randomized, prospective studies to assess definitive benefit. Disclosures No relevant conflicts of interest to declare.

Background: Chimeric antigen receptor (CAR) modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. CD19 and CD20 targeted CAR constructs from several different institutions have demonstrated consistently high anti-tumor efficacy in children and adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL). We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 CAR-T therapy for B-cell hematologic malignancies. Methods: Literature search was performed using MEDLINE (Ovid SP and PubMed), EMBASE, The Cochrane Library, Scopus and Web of Science. We conducted meta-analysis using random effects model using Comprehensive Metaanalysis 3.0. Heterogeneity was assessed using Q-statistic and it was quantified using I2statistic. Results: After a comprehensive literature search 4476 studies were identified and finally 15 eligible studies involving 121 patients were included in the final systematic review. The infused CAR T-cell dose was in the range of 0.76 x 106 to 3 x 107 cells/kg in seven trials and in the range of 0.8 x 107 cells to 3.3 x 109 cells/m2in 6 trials. Among 106 patients, the overall response to treatment after CAR T-cell infusion were 33% complete remission (CR), 30 % partial remission (PR), 21% stable disease (SD), and 8% progressive disease (PD). Three studies described response to immunotherapy as minimal residual disease negative (MRD-) and as no evidence of disease (NED) and after including it, the overall CR was 38%. Major adverse events included fever (38%), hypotension (23%), chills (29%), rigor (28%), fatigue 17% and dyspnea 10%. One patient died from cytokine release syndrome, which is potentially serious complication. Neurological symptoms require prompt recognition and management. Conclusion: CAR T cell therapy is a promising treatment for refractory and relapsed hematological malignancies. The durable responses of CAR T cell therapy help integrate it in standard treatment protocols. Patients who are refractory to standard salvage chemotherapy or relapse after allo - HSCT have overall poor prognosis and can potentially achieve remission again with CAR T cell therapy. Disclosures McBride: Sanofi: Research Funding. Anwer:Seattle Genetics: Other: Advisory Board Participant; Incyte: Speakers Bureau.

Chemotherapy-induced cardiomyopathy is one of the major possible hazards that can result from potential cardiotoxic agents while treating cancer. Prognostic risk factors include the rate of drug administration, history of hypertension, female gender, extremes of age, previous history of mediastinal irradiation, cumulative dose and pre-existing heart disease. Close monitoring of the patients, timely diagnosis, use of well-known biomarkers including cardiac troponins, NT-ProBNP and imaging studies like 2D Echo or cardiac MRI are essential. Emerging biomarkers include carbonyl reductases (CBR1 and CBR3), aldo-keto reductases (AKR, type 1A1, 1C3, 7A2) and topoisomerase2β (Top2β). β blockers and ACE inhibitors have not only been shown to slow down the progression of cardiac dysfunction but also produce symptomatic improvement. Our case report describes a patient with acute myeloblastic leukaemia who developed severe cardiomyopathy acutely after starting the anthracycline-based regimen. Nevertheless, with timely intervention her symptoms improved and subsequently she successfully received allogeneic stem cell transplantation.

Candida albicans is a common human pathogen. Occasionally, it can cause peritonitis in immunocompromised and postsurgical patients. We report a case of a male patient who presented with abdominal pain and distention. He had a history of end-stage liver disease secondary to alcoholism. His peritoneal fluid culture revealed C albicans, and (1–3)-β-d glucan (BDG) level was elevated. His hospital course was complicated by sepsis and renal failure. He was treated with antifungals for spontaneous fungal peritonitis. Fungal peritonitis should be suspected in patients with chronic liver disease particularly with elevated BDG levels.