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Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in Pneumocystis jirovecii pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of Pneumocystis jirovecii pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for Pneumocystis jirovecii pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.

The potential of information technology has influenced the efficiency and quality of healthcare worldwide. Currently, several republics are incorporating electronic health records (EHRs). Due to reluctance of technological adaptation & implementational complexities, electronic health record systems are not in practice. Due to the emphasis on achieving general compatibility, users may perceive systems as being imposed and providing insufficient customizability, which may exacerbate issues in a setting of national implementation. EHS improves patient safety and confidentiality and ensures operative, effective, well-timed, reasonable, and patient-centred care, all of which substantially impact healthcare quality. Blockchain technology has been used by the EHS system, which supports web-based accessibility and availability. The difficulties of exchanging medical data can now be overcome by consumers using an infrastructure based on cloud computing. A variety of cryptographic approaches have been employed to encrypt and safeguard the data. This review paper aims to highlight the role and impact of blockchain in EHR. The proposed research describes cryptography methods, their classifications, and the challenges associated with EHR to identify gaps and countermeasures.

The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.

A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Catheter ablation (CA) has emerged as an effective therapy for AF. We conducted a meta-analysis to update the current clinical evidence on the efficacy of CA for AF in patients with HCM. We searched PubMed, Embase, Cochrane and Clinicaltrials.gov for interventional and observational studies assessing single and multiple procedure success rate of CA in HCM patients. Our meta-analysis included 25 studies involving 1817 patients. Success rate following single procedure was 40.4% (95% CI 33.1 to 48.0%) at latest follow-up. The pooled success rate following multiple procedures was 51.4% (95% CI 42.9% to 60.0%) at latest follow-up. In the subgroup analysis for AF subtype, TCA was more successful for paroxysmal AF compared to non-paroxysmal AF. For the subset of studies reporting drug-free success rate, single and multiple procedures had a success rate of 33.4% (95% CI 19.3 to 49.1%) and 51.8% (95% CI 41.3 to 62.2%) at latest follow-up, respectively. CA is a suitable option for AF in patients with HCM. Success rate is greater in paroxysmal AF, after multiple procedures and with antiarrhythmic drugs.

The cubic perovsike strontium titanate SrTiO$_3$ (STO) is one of the most studied, polarizable transition metal oxides. When excess charge is introduced to this material, e.g., through doping or atomic defects, STO tends to host polarons: Quasi-particles formed by excess charge carriers coupling with the crystal phonon field. Their presence alters the materials properties, and is a key for many applications. Considering that polarons form preferentially on or near surfaces, we study small polaron formation at the TiO$_2$ termination of the STO(001) surface via density functional theory calculations. We model several supercell slabs of Nb-doped and undoped STO(001) surfaces with increasing size, also considering the recently observed as-cleaved TiO$_2$ terminated surface hosting Sr-adatoms. Our findings suggest that small polarons become less stable at low concentrations of Nb-doping, in analogy with polarons localized in the bulk. Further, we inspect the stability of different polaron configurations with respect to Nb- and Sr-impurities, and discuss their spectroscopic properties., Comment: 8 pages, 7 figures, 1 table

Red cell distribution width (RDW) serves as an independent predictor towards the prognosis of coronary artery disease (CAD) in patients undergoing percutaneous coronary intervention (PCI). A systematic search of databases such as PubMed, Embase, Web of Science, and Cochrane library was performed on October 10th, 2019, to elaborate the relationship between RDW and in hospital and long term follow up, all-cause and cardiovascular mortality, major adverse cardiac events (MACE) and development of contrast-induced nephropathy (CIN) in patients with CAD undergoing PCI. Twenty-one studies qualified this strict selection criterion (number of patients = 56,425): one study was prospective, and the rest were retrospective cohorts. Our analysis showed that patients undergoing PCI with high RDW had a significantly higher risk of in-hospital all-cause mortality (OR 2.41), long-term all-cause mortality (OR 2.44), cardiac mortality (OR 2.65), MACE (OR: 2.16), and odds of developing CIN (OR: 1.42) when compared to the patients with low RDW. Therefore, incorporating RDW in the predictive models for the development of CIN, MACE, and mortality can help in triage to improve the outcomes in coronary artery disease patients who undergo PCI.

Introduction: Catheter-associated urinary tract infection (CAUTI) is one of the most common nosocomial infections in hospitals, accounting for 36% of all health care-associated infections. Areas covered: We aimed to address the potential impact of antimicrobial coating of catheter materials for the prevention of CAUTI and to analyze the progress made in this field. We conducted literature searches in the PubMed, Embase, and Cochrane Library databases, and found 578 articles. Data from 60 articles in either the preclinical or clinical stage were analyzed in this expert review. Expert opinion: The literature review revealed many promising methods for preventing CAUTI. Recent studies have suggested the combination of silver-based products and antibiotics, owing to their synergistic effect, to help address the problem of antibiotic resistance. Other coating materials that have been tested include nitric oxide, chlorhexidine, antimicrobial peptides, enzymes, and bacteriophages. Because of heterogeneity among studies, it is difficult to reliably comment on the clinical efficacy of different coating materials. Future research should focus on double-blind randomized clinical trials for evaluating the role of these potential coating agents.

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.

Multiple myeloma (MM) is genetically complex disease. Identification of mutations and aberrant signaling pathways that contribute to the progression of MM and drug resistance has potential to lead to specific targets and personalized treatment. Aberrant signal pathways include: RAS pathway activation due to RAS or BRAF mutations (targeted by vermurafenib alone or combined with cobimetinib), BCL2 overexpression especially in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-kB pathway activation (treated with DANFIN combined with bortezomib), MDM2 overexpression (targeted by DS-3032b) and targeting the PI3K/mTOR pathway (targeted by BEZ235). Cyclin D1 (CCND1), and MYC are also emerging as key potential targets. In addition, histone deacetylase (HDAC) inhibitors are already in use for the treatment of MM in combination therapy and targeted inhibition of FGFR3 (AZD4547) is effective in myeloma cells with t(4;14) translocation. Bromodomain and extra terminal (BET) protein antagonists decrease the expression of MYC and have displayed promising anti-myeloma activity. A better understanding of the alterations in signaling pathways that promote MM progression will further inform the development of precision therapy for patients.

INTRODUCTION: The aim of our study is to evaluate risk factors associated with the development of C. difficile infection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence and report outcomes of CDI in our patient population. METHODS: We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI. RESULTS: The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, gender, cancer type, transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus and no patient underwent colectomy. There was no mortality associated with CDI at our center. CONCLUSION: CDI has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, gender, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of greater than four lines of antibiotics were observed among those with CDI compared to those without CDI.

Supplementary material

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.

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

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.

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Multiple myeloma (MM) is a neoplastic proliferation of plasma cells. It is the second most common hematological malignancy in the US. Although it is associated with poor prognosis, newer therapies have improved outcomes in MM patients. This review aims to describe novel therapies used for the treatment of relapsed/refractory multiple myeloma (RRMM). Methods: A literature search was performed on Embase and clinicaltrials.gov using the keyword "Multiple Myeloma" from 1/1/2016 to 6/25/2020 for identifying ongoing clinical trials in the treatment of RRMM. After detailed scrutiny, we included 23 ongoing clinical trials (N=4362). We excluded case reports, case series, review articles, meta-analysis, and observational studies. Results: We summarized the interim results from ongoing clinical trials evaluating treatment of RRMM under following newer categories of drugs: Immunomodulatory drugs In a phase 1b/IIa trial (NCT02773030, N=51) evaluating the efficacy of a novel immunomodulators, iberdomide CC-220 + dexamethasone (Dex) yielded an overall response rate (ORR) of 31%, clinical benefit (CB) was seen in 51% of the patients, and disease control (DC) in 88% of the patients and it was well tolerated by RRMM patients. There are other ongoing clinical trials evaluating the efficacy of Avadomide (CC-122), CC-92480 in RRMM. Alkylating agents In a phase I/II trial (NCT01897714, N=45), melphalan-flufenamide (melflufan) + Dex yielded an ORR of 31%, it was well tolerated with 49% CB. Phase III OCEAN trial (NCT03151811, N=450) is currently ongoing to compare melflufen + Dex vs. pomalidomide (Pom) + Dex. Apoptotic agents A phase 3 trial BELLINI (NCT02755597, N=291) evaluated the efficacy of veneteclox (Ven, Bcl-2 inhibitor) by randomizing patients to either Ven or Placebo arm. With a median follow up of 28.6 months (m), progression free survival (PFS) was 23.2m in the Ven arm vs. 11.4m in placebo. The interim results from a phase I/II trial (NCT03314181, N=104) of Ven + daratumumab (Dara) + Dex showed ORR of 96% with ≥ very good partial response (VGPR) of 96%. The addition of Bortezomib (Bor) to VenDaraDex had a slightly low ORR of 92%, with ≥VGPR of 79%. Another phase I/II trial (NCT01794520, N=117) is in progress to assess the efficacy and safety of Ven as monotherapy. Monoclonal Antibodies (MoAb) A phase I/II trial (NCT01421186, N=91) evaluated the efficacy of MOR202, which is a novel MoAb. MOR202 was evaluated in three arms; MOR202 + Dex, MOR202 + Lenalidomide (Len) + Dex and MOR202 + Pom + Dex. The interim analysis showed the ORR of 65% with MOR202 + Len + Dex which was better than ORR of 48% with MOR202 + Pom + Dex, while the use of MOR202 + Dex yielded only 28% ORR. Antibody-drug conjugate (ADC) Four ongoing trials are evaluating the efficacy of ADC (belantamab mafodotin), and the interim results are available for two trials. In phase II DREAMM-2 trial (NCT03525678, N=221) evaluating 2 doses of GSK2857916, 2.5mg/kg dose yielded ORR of 31% while 3.4mg/kg showed ORR of 34%. Another phase I trial (NCT02064387, N=79) evaluated belantamab mafodotin in RRMM and other hematologic malignancies expressing B-cell maturation antigen (BCMA). The results were promising with ORR of 60%. Bispecific T-cell engagers (BiTE) Phase I trial of BiTE AMG 420 (NCT02514239, N=43) showed favorable results with ORR 70%, and CR 12%. The interim results from another phase I trial (NCT03486067, N=115) which evaluated the efficacy of BiTE CC-93269 showed 43% ORR and CR 17%. CAR-T Cell therapy CAR-T cell therapy is also being studied in RRMM with JNJ-68284528 directed against BCMA in a phase Ib trial (NCT03548207, N=118). The interim analysis of 29 response evaluable patients out of 118 reported 100% ORR with stringent CR 76%. PK13 Inhibitors In a phase I/II study (NCT00401011, N=84) evaluating perifosine + Bor +/- Dex, ORR of 41% was observed in Bor RR patients, and therapy was well tolerated with PFS of 6.4m and mOS of 25m. Conclusion: This review demonstrates novel and promising therapies which are currently in early phase clinical trials for the treatment of RRMM. Based on interim results, Iberdomide, melflufan, Ven, MoAb MOR202, ADC belantamab mafodotin, BiTE Molecule AMG 420, BCMA CAR-T cell therapy and perifosine have shown promising early activity and safety data in RRMM patients. Additional exploratory clinical trials are needed to confirm the efficacy and safety of these agents. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

We investigate a multi-field model of dark energy in this paper. We develop a model of dark energy with two multiple scalar fields, one we consider, is a multifield tachyon and the other is multi-field phantom tachyon scalars. We make an analysis of the system in phase space by considering inverse square potentials suitable for these models. Through the development of an autonomous dynamical system, the critical points and their stability analysis is performed. It has been observed that these stable critical points are satisfied by power law solutions. Moving on towards the analysis we can predict the fate of the universe. A special feature of this model is that it affects the equation of state parameter w to alter from being it greater than negative one to be less than it during the evolutionary phase of the universe. Thus, its all about the phantom divide which turns out to be decisive in the evolution of the cosmos in these models., Comment: 10 pages, 3 figures, 10 sub figures, 2 tables

Pakistan’s economy experienced many ups and downs during the last four decades. These structural shifts (asymmetries) cannot be detected via linear econometric models. This paper employs the Markov Regime-Switching vector autoregression (MS-VAR) model with time-varying transition probabilities to identify the high and low growth regimes. After establishing structural shifts in the data, next, we estimate the linear VAR model in each regime to test the effects of fiscal shocks on output, and we also test the twin deficit hypothesis as well as the crowding-out investment effect. Different specifications of MS-VAR models with Constant Transition Probability (CTP) and time-varying transition probability (TVTP) were tested, among which the best fit model with four regimes is chosen for analysis. The four regimes identified are the low growth regimes from 1973 to 1979 and from 1989 to 1999 and the high growth regimes from 1980 to 1988 and from 2000 to 2010. The results from the subsample analysis show that the response of output to positive spending shock is increasing in high growth regimes and decreasing in low growth regimes. Similarly, a tax shock has a statistically insignificant impact on output except for the last regime where a tax shock is positively associated with output growth. An expansionary fiscal policy crowds-out private investment in low growth regimes (i.e. in first and third regimes) while a positive effect on private investment is observed during high growth regimes (second and fourth regimes). Lastly, twin deficit is observed in all regimes.

Introduction: Multiple myeloma (MM) is an incurable malignancy, and clinical trials with newer agents have shown improved patient outcomes. Ixazomib (Ixa) is a proteasome inhibitor and induces apoptosis in cancer cells. It is commonly used with immunomodulators for the treatment of MM. We conducted a systematic review and meta-analysis to assess the efficacy of Ixazomib alone and in combination with other drugs for the treatment of newly diagnosed multiple myeloma (NDMM). Methods: A literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used the following MeSH and Emtree terms; "ixazomib" AND "Multiple Myeloma" from inception till 06/05/2020. We screened 1,558 articles and included 3 randomized clinical trials (RCTs) (N=901) and 12 non-randomized clinical trials (NRCT) (N=632). We excluded case reports, case series, preclinical trials, review articles, observational studies, meta-analysis, and ongoing clinical trials that did not report interim efficacy outcomes. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 15 clinical trials (N=1533), Ixa based regimens were used in patients with age range of 39-92 years. (Table 1) In 3 clinical trials (N=170), Ixa with Lenalidomide (Len) and dexamethasone (Dex) yielded a pooled overall response rate (ORR) of 90% (95% CI=0.82-0.94, I2=32%), a pooled complete response (CR) of 23% (95% CI=0.16-0.32, I2=24%) and a pooled ≥very good partial response and better (≥VGPR) of 39% (95% CI=0.24-0.57, I2 =76%) when used as induction therapy for NDMM patients. As consolidation therapy (N=88), pooled ORR was 91% (95% CI=0.79-0.97, I2=0), pooled CR was 36% (95% CI=0.27-0.47, I2=0) and pooled ≥VGPR was 70% (95% CI=0.53-0.84, I2=60%). (Fig 1-3) In 5 clinical trials (N=233), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR, CR, and ≥VGPR of 76% (95% CI=0.70-0.81, I2 =0), 12% (95% CI=0.07-0.20, I2=44%), and 25% (95% CI=0.14-0.39, I2=78%), respectively. (Fig 1-3) The lower dose of Cyc 300mg/m2 had similar efficacy as 400mg/m2 with better safety profile in elderly patients. In a RCT (N=175) of Ixa with multiple combinations, Ixa + Dex yielded ORR 55% (95% CI=0.40-0.69), CR 14% (95% CI=0.07-0.28) and ≥VGPR 24% (95% CI=0.13-0.39). Ixa+ thalidomide (Thal) + Dex fostered ORR 82% (95% CI=0.70-0.90), CR 15% (95% CI=0.08-0.26), and VGPR 43% (95% CI=0.31-0.55). Ixa + bendamustine + Dex yielded ORR of 73% (95% CI=0.41-0.91), CR 9% (95% CI=0.01-0.44), and ≥VGPR 27% (95% CI=0.09-0.59). In one clinical trial (N=53), Ixa + melphalan (Mel) + prednisone (Pred) combination yielded pooled ORR, CR, and ≥VGPR of 66% (95% CI=0.52-0.77), 13% (95% CI=0.06-0.25), and 30% (95% CI=0.19-0.44), respectively. In a phase II trial (N=40), Ixa + daratumumab (Dara) + Len + Dex yielded an ORR, CR and ≥VGPR of 97% (95% CI=0.84-1), 15% (95% CI=0.07-0.28), and 35% (95% CI=0.22-0.51) respectively. (Fig 1-3) In a phase III RCT by Dimopholous et al. (N=656), Ixa maintenance therapy after stem cell transplant (SCT) yielded an ORR, CR, and ≥VGPR of 76%, 15%, and 54%, respectively. They observed 28% reduction in the risk of progression or death with Ixa vs. placebo, median progression free survival (mPFS) was 26.5 months (95% CI 23·7-33·8) vs 21·3 months [18·0-24·7]; hazard ratio 0·72, 95% CI 0·58-0·89; p=0·0023). Second malignancies were 3% in both ixazomib and placebo group. 27% of the patients in ixazomib group and 20% patients in placebo group experienced serious adverse events. In a clinical trial on unfit and frail patients (N=46) treated with Ixa + daratumumab (Dara) + Dex, pooled ORR and ≥VGPR were 83% (95% CI=0.69-0.91, I2=0), and 33% (95% CI=0.21-0.47, I2=0), respectively. (Fig 1-3) In the phase II trial, ORR, CR, and VGPR with ixazomib and lenalidomide were 64%, 26%, and 53%, respectively. Conclusion: Ixa in combination with Len, Dex, Cyc, Dara, Mel, Pred is effective in the treatment of NDMM patients. In early phase trials, Ixa with Dara, Len, and Dexa showed the highest overall response as induction therapy. Ixazomib maintainance therapy prolongs PFS after SCT as compared to placebo and represents an additional option for post SCT maintainace therapy in NDMM patiens. The safety profile of Ixa was acceptable with most commonly encountered adverse events were hematological including neutropenia and thrombocytopenia. Additional multicenter, double-blind, randomized clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

The present study aims at evaluating a batch scale biosorption potential of Moringa oleifera leaves (MOL) for the removal of Pb(II) from aqueous solutions. The MOL biomass was characterized by FTIR, SEM, EDX, and BET. The impact of initial concentrations of Pb (II), adsorbent dosage, pH, contact time, coexisting inorganic ions (Ca2+, Na+, K+, Mg2+, CO32−, HCO3−, Cl−), electrical conductivity (EC) and total dissolved salts (TDS) in water was investigated. The results revealed that maximum biosorption (45.83 mg/g) was achieved with adsorbent dosage 0.15 g/100 mL while highest removal (98.6%) was obtained at adsorbent biomass 1.0 g/100 mL and pH 6. The presence of coexisting inorganic ions in water showed a decline in Pb(II) removal (8.5% and 5%) depending on the concentrations of ions. The removal of Pb(II) by MOL decreased from 97% to 89% after five biosorption/desorption cycles with 0.3 M HCl solution. Freundlich model yielded a better fit for equilibrium data and the pseudo-second-order well described the kinetics of Pb(II) biosorption. FTIR spectra showed that –OH, C–H, –C–O, –C = O, and –O–C functional groups were involved in the biosorption of Pb(II). The change in Gibbs free energy (ΔG = −28.10 kJ/mol) revealed that the biosorption process was favorable and thermodynamically driven. The results suggest MOL as a low cost, environment-friendly alternative biosorbent for the remediation of Pb(II) contaminated water.

For large scale production of clonal plants, somatic embryogenesis (SE) has many advantages over other clonal propagation methods such as the rooting of cuttings. In particular, the SE process is more suited to scale up and automation, thereby reducing labor costs and increasing the reliability of the production process. Furthermore, the plants resulting from SE closely resemble those from seeds, as somatic embryos, like zygotic (seed) embryos, develop with good connection between root and shoot, and without the plagiotropism often associated with propagation by cuttings. For practical purposes in breeding programs and for deployment of elite clones, it is valuable that a virtually unlimited number of SE plants can be generated from one original seed embryo; and SE cultures (clones) can be cryostored for at least 20 years, allowing long-term testing of clones. To date, there has however been limited use of SE for large-scale plant production mainly because without automation it is labor-intensive. Development of automation is particularly attractive in countries with high labor costs, where conifer forestry is often of great economic importance. Various approaches for automating SE processes are under investigation and the progress is reviewed here, with emphasis on conifers. These approaches include simplification of culture routines with preference for liquid rather than solid cultures, use of robotics and automation for the harvest of selected individual mature embryos, followed by automated handling of germination and subsequent planting. Different approaches to handle the processes of somatic embryogenesis in conifers are outlined below, followed by an update on efforts to automate the different steps, which are nearing an operational stage.

We investigate one-dimensional position microscopy of a three-level atom moving through a stationary wave region under the condition of electromagnetically induced transparency. The precise position information of an atom is observed on the resonance absorption and dispersion distribution spectrum of a weak probe field. Single and multiple localization peaks are observed in specific directions of the corresponding wave numbers and phase of the standing wave fields. The strength of space-independent Rabi frequency reduces the position uncertainty in the localized peaks without disturbing the probability of the atom. In a hot atomic medium the localized probability of an atom is reduced which depends upon the temperature of that medium. Our results provide useful applications in the development of laser cooling, atom nanolithography and Bose–Einstein condensation.

This study aims to investigate the perspectives of non-native English as a Foreign Language (EFL) teachers across mother tongue and gender, and their male and female adult students, regarding the use of Arabic in the EFL classrooms at the university level in Saudi Arabia. The study specifically seeks to investigate the perspectives of non-native Arab and non-Arab EFL teachers as they, working in the native Arab setting, often resort to Arabic (Al-Nofaie, 2010; Machaal, 2012). However, there are glaring research gaps about non-native EFL teachers’ and adult learners’ beliefs on the use of first language (L1) in the classroom. For this purpose, the study used quantitative research design, and administered two questionnaires, one for the teachers and the other for the students. Students’ questionnaire complemented that of the teachers. Forty teachers and sixty students were selected based on stratified random sampling. The findings of the study revealed that all camps of teachers, Arab, non-Arab, male, female, and students were in favour of judicious bilingual approach. The study finds statistically significant difference between the beliefs of Arab and non-Arab EFL teachers about the use of L1. The findings suggest that Arab EFL teachers’ use of Arabic is extensive, while non-Arab EFL teachers’ use of Arabic is well-timed. The study suggested practical implications for the improvement of English Language Teaching (ELT) in Saudi Arabia by recommending planned, occasional and judicious use of L1 while teaching EFL adult learners.

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.

Introduction Amyloidosis is a rare disease and there are currently no FDA approved therapies for AL amyloidosis. Most of the therapeutic and disease data come from expert guidelines, consensus and retrospective review papers. There is a paucity of data specifically for relapsed/refractory AL amyloidosis (RRAL). We conducted this systematic review of clinical trials, retrospective and prospective cohort studies to evaluate patterns of relapse and therapeutic options for RRAL. Methods PubMed and Clinicaltrials.gov were searched for clinical trials, retrospective and prospective cohort studies on RRAL. Studies were selected according to PRISMA guidelines. Cross-trial comparison of included studies and meta-analysis could not be performed for a number of reasons but mainly due to a limited number of studies on one particular treatment regimen. Results From a total of 511 studies, 11 studies (n= 698 patients) met our inclusion criteria. Five were phase I/II clinical trials, five retrospective cohort studies, and one prospective cohort study. Most studies had less than 50 patients. The largest study, a retrospective cohort by Tandon et al. included 366 patients. Mean age was 61.2. Three studies reported 2 median prior lines of therapy (n= 22, 28, and 84 patients); two reported 3 median prior lines of therapy (n= 25 and 24) and 6 studies didn't specify this data. Prior treatment options included proteasome inhibitors (PI), most commonly bortezomib (n= 259), followed by melphalan (n=211), high dose melphalan and stem cell transplant (HDM/SCT [n= 207]) and IMiDs most commonly lenalidomide (n=154). Time to progression (TTP) from first-line treatment was reported in only 4 studies as 1 month, 5 months, 5 months and 34 months respectively. The study reporting a TTP of 34-months had 11 patients who received HDM/SCT as first line treatment. Three studies reported information about their criteria for initiation of subsequent treatment. Subsequent treatment was mostly a combination regimen with dexamethasone or an alkylating agent. The only agent evaluated as single agent was bortezomib in a phase I/II clinical trial by Reece et al. Therapeutic options for RRAL are PI (non-specific) based therapy (n= 145), lenalidomide (n= 105), bortezomib (n= 99), IMiD (non-specific) based therapy (n=83), melphalan based therapy (n= 33), carfilzomib (n=28), pomalidomide (n=27), ASCT (n= 25), daratumumab (n=25) and bendamustine (n=22). Efficacy: Hematologic responses were reported to be following: bortezomib + dexamethasone/melphalan (85%, n=17/20), daratumumab + dexamethasone (76%, n= 19/25), HDM/ASCT (73%, n= 8/11), single agent bortezomib (67%, n=23/34), carfilzomib ± dexamethasone (63%, n= 15/24), lenalidomide + dexamethasone (61%, n=51/84), bendamustine + dexamethasone (55%, 11/22) and pomalidomide + dexamethasone (50%, 12/24). Five of eleven studies reported organ responses which ranged from 18% to 23%. The studies which reported organ responses had evaluated the following agents: single agent bortezomib, carfilzomib ± dexamethasone, lenalidomide + dexamethasone, and bendamustine + dexamethasone. Best survival outcomes were seen with bortezomib with median overall survival (OS) 62 months. With bendamustine and dexamethasone (retrospective cohort study n=22) median OS was 31 months. With lenalidomide + dexamethasone (prospective cohort study n=24 ) median OS was 14 months. For the remaining studies, the median OS was either not reported or not reached at the time of presentation of data. Conclusion AL amyloidosis patients progressing after front line therapy show good responses with bortezomib (median overall survival of 62 months). Novel combinations using lenalidomide, pomalidomide, carfilzomib, daratumumab, and bendamustine show promising efficacy. Ongoing trials of daratumumab (AMYDARA trial) and ixazomib (TOURAMALINE-AL1) will bring further insight into therapeutic armamentarium for RRAL patients. After relapse, a salvage HDM/ASCT can be considered. Comparisons of regimen efficacy between studies are not practical because of multiple factors which include but are not limited to heterogenous nature of AL patients, small sample sizes, variable prior treatments, exposure to novel agents, observational study versus clinical trial and variable endpoints. Table Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

Introduction: For more than a decade, bortezomib (V) has become an integral part of initial treatment of AL amyloidosis It is cytotoxic to plasma cells. We report published literature on efficacy and safety of bortezomib based regimens in patients (pts) with newly diagnosed amyloidosis (ND-AL). Methods: Following PRISMA guidelines, we performed a comprehensive literature search for articles published after 2007 using Pubmed, Embase, Clinical Trials.gov, Cochrane Library and Web of Science. Initially, 649 articles were identified and after a thorough screening, we finalized 9 studies involving 213 ND-AL patients. Prospective (n=91) and retrospective (n=122) studies were included. MeSH terms and keywords were bortezomib and newly diagnosed AL amyloidosis. Results: Chemotherapy followed by HDCT versus frontline HDCT / ASCT: In a retrospective study involving 31 pts by Scott et al., with induction chemotherapy with V-based regimens (n=12), with non-V-based regimens (n=6) and frontline (n=13) high dose melphalan (HDM) therapy followed by autologous stem cell transplant (ASCT). Overall hematological response (OHR) and organ response (OR) rates in the entire cohort after ASCT were 77% and 58% respectively. OHR and OR were 92% & 75% in V-pretreated group and 69% & 54% in pts who received no treatment. The trend was similar for other responses (Table 1). In a clinical trial by Huang, X., et al., induction therapy with Vd (V in combination with dexamethasone) prior to HDM/SCT was compared with frontline HDM/SCT in 58 patients. The OHR, and complete response (CR) between Vd+HDM/SCT (20 evaluable pts) and frontline HDM/SCT (23 evaluable pts) groups were 85.7% versus 53.5% and 67.9% versus 35.7% respectively. All organs showed better response in Vd+HDM/SCT group (Table 1). Vd/CyBorD (Cyclophosphamide, bortezomib, dexamethasone) prior to ASCT: In a prospective clinical trial by Sanchorawala et al., 35 pts were given induction with Vd before HDM and ASCT. Among 27 evaluable pts, OHR was 100% with CR in 76.9% and very good partial response (VGPR) in 23% pts. In a study by Hong et al., 20 patients received induction with Vd or CyBorD prior to ASCT. OHR was 89% with CR in 55%, partial response (PR) in 10% and VGPR in 33%. 5-year overall survival (OS) was 80% and 5-year progression free survival (PFS) was 69%. Vd/CyBorD without ASCT: In a retrospective study by Zhao et al., 23 pts received Vd. OHR was 100% with CR in 44% and PR in 38.9% pts. Median overall survival (mOS) was 38 months and 3-year OS was 41-72%. OR was 25% with kidney being the organ showing response in maximum pts (84%). Kikukawa et al., reported 8 pts who received CyBorD, OHR was 100% with CR in 50%, PR in 25% and VGPR in 25% pts. 63% pts showed OR in heart and/or kidney. In a study by Huang, B., et al., Vd was given to 12 renal ND-AL pts and among 10 evaluable pts, OHR was 80% with CR in 50% and PR in 10%. mOS was 8.2 months and OR was 50%. Other Regimens: In a study by Lee et al., involving 19 pts, VMP (bortezomib, melphalan, prednisone) was given as induction therapy. OHR was 84% with CR in 37%, PR in 26% and VGPR in 21% pts. OS was 39% at 2 years and PFS was 8 months. OR was 53% with heart (50%) and kidney (40%). In a retrospective review by Chari et al., 9 pts were treated with a triplet regimen (V, cyclophosphamide or lenalidomide/thalidomide and d). OHR was 88% with CR in 22% and PR in 66% pts. OR was 77% with heart and kidney both at 44%. Conclusion: In ND-AL pts, V-based combination regimens are very effective and well tolerated as induction therapy, or when used as therapy prior to HDM/ASCT and this approach resulted in better outcomes when compared to frontline HDM/ASCT. Three drug combination therapy with V is effective. Kidney and heart were the major organs to show improvement with therapy. Novel combinations need to be studied in randomized prospective clinical trials. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

e19530 Background: Renal impairment (RI) in Multiple Myeloma (MM) adversely affects the prognosis. Removing circulating free light chains via hemodialysis (HD) or plasma exchange (PLEX) along with chemotherapy can improve renal outcomes in MM. Methods: Per PRISMA guidelines a systematic search yielded 7311 articles since 2009 on 4 databases. After screening, 16 studies were included. Results: Main modalities were high cut off (HCO) HD, high flux (HF) HD, conventional HD and PLEX. N = 541 patients underwent HD/PLEX. 375/541 (69.3%) patients received HCO HD. In 2 RCTs, there was no significant difference in renal recovery (55.8% vs 51.6%; 41% vs 33%). The overall survival (OS) between the 2 groups was lower in the HCO group vs conventional HD (55.8% vs 76.6%) at 2 years while there was no significant difference in second study. Conclusions: HCO has failed to show promising efficacy with 2 RCTs failing to show statistical OS difference. There is paucity of data and further trials are needed. [Table: see text]

e19533 Background: Immunotherapy for multiple myeloma (MM) has been of focus in recent years due to its myeloma-specific immune responses. We reviewed literature on non-FDA approved monoclonal antibodies (MoAbs) to highlight future perspectives. Methods: We searched PubMed, EMBASE, Web of Science, Cochrane and Clinicaltrilas.gov to include phase I/II clinical trials. Results: 40 studies (1917 patients) were included. Isatuximab (anti-CD38) and F50067 (anti-CXCR4) were the only MoAbs which produced encouraging results as monotherapy with ORR of 66.7% and 32% respectively. Isatuximab use in combination with Len-Dex produced CBR of 83%, and in combination with pomalidomide and dexamethasone CBR of 73%. Indatuximab Ravtansine, an antibody-drug conjugate, produced ORR 78% and 79% in combination with Len-Dex and pomalidomide + dexamethasone respectively. Conclusions: CD38 remains an important target for further clinical trials in combination therapy. Trials using indatuximab, pembrolizumab, lorvotuzumab, siltuximab, and dacetuzumab in combination therapy produced better outcomes as compared to monotherapies. [Table: see text]

e19043 Background: Mantle Cell Lymphoma (MCL) is generally treated with rituximab (R) in combination with other drugs. However, treatment for relapsed or refractory (RR) MCL is challenging. For Ibrutinib (Ibr), we aim to determine the efficacy in combination therapy for newly diagnosed (ND) and RR MCL. Methods: Per PRISMA guidelines, a systematic review was performed using four databases. Results: Eleven studies with 363 patients were identified, most commonly studied regimens were ibrutinib in combination with R in 2 phase II studies and 2 studies on Ibr in combination with venetoclax. Ibr was also studied as part of the three-drug regimens in combination with bendamustine & R, lenalidomide & R, and obinutuzumab & venetoclax. Ibr was studied in combination with other drugs such as palbociclib, ublituximab, and bortezomib as part of the two-drug regimens. Results summarized in Table. Adverse events included cytopenia, atrial fibrillation, septic shock, tumor lysis syndrome, and GI toxicities. Conclusions: Ibr in combination with R demonstrated the highest overall ORR and CR in treatment of ND MCL, whereas combination with venetoclax and obinutuzumab demonstrated highest overall ORR and CR in treatment of RR MCL. Additional studies are needed to further assess and confirm its role in treatment. [Table: see text]

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.

Yellow rust populations of Pakistan were characterised for their virulence pathotypes/races and pathogenetic variation using seedling evaluation of differential genotypes under glasshouse conditions in Murree (6000 feet above sea level). Differential genotypes comprised a world set, an European set, near isogenic lines and the universally susceptible bread wheat cultivar “Morocco”. Over the two-year study a total of 18 race groups were identified. Out of these 18 race groups, several (68E0, 64E0, 66E0, 70E0, 6E0, 71E0, 6E0, 2E0, 67E0, and 68E16) were found previously. The new race group 70E32 found probably evolved because of mutation from the previously existing 70E16. Virulence frequencies of yellow rust (Yr) resistance genes were also determined on near isogenic lines. The highest virulence frequencies (%) were found for Yr7 (88%), Yr9 (57%), Yr18 (70%), and Yr24 (69%). Virulence frequencies were low for Yr 1 (4%), Yr5 (7%), Yr10 (10%) and Yr15 (4%). Our studies indicated that virulence existed for alm...

e20048Background: Primary plasma cell leukemia (pPCL) is rare but aggressive disease with median overall survival (mOS) of less than one year. Our aim is to review its unique biology, efficacy of a...

Background Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors. Methods We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used. Findings Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%. Interpretation Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).

A 67-year-old asymptomatic man was found to have a total plasma protein level of 10.2 mg/dL on routine work-up. Serum protein electrophoresis (SPEP) revealed an M spike of 4 g/L and an elevated IgG level of 4759, and free kappa chain of 170.72 (H), free lambda chain of 3.15 (L) and kappa:lambda ratio of 54.20. Bone marrow biopsy showed a kappa light chain restricted plasma cell neoplasm involving 20%–30% of marrow cellularity. Fluorescence in situ hybridisation (FISH) test demonstrated polysomy of chromosome 9 in 70%, trisomy 11 in 57% and trisomy 7 in 50.5% of cells. Skeletal survey showed generalised mild osteopaenia …

SUMMARYAll four seed diffusates used for treatment of sunflower seeds, Azadirachtaindica, Capsicum annuum, Coriandrum sativum and Eugenia jambulana, reduced the populations of seed-borne fungi: Alternaria alternata, Drechslera tetramera, Emericellopsis terricola, Fusarium moniliforme, F.semitectum, Macrophomina phaseolina and Phoma oleracea. Of four seed diffusates, those from A.indica and C.sativum controlled the fungal populations almost 100%. Seed germination was increased in seed samples of both sunflower cultivars under study, HO-1 and NK-212. The obtained results indicate that seed diffusates could substitute costly chemicals for safe control of seed-borne diseases, protecting at the same time the environment from chemical pollution.

Education and health sectors are known to have massive impact on the quality of human life. In this context, the health sector is discussed in this study to analyse the impact of fiscal decentralisation on basic health infrastructure in Pakistan. Provincial datasets (1980-2001) from three provinces were used for the analysis of provincial health indicators. It was learnt that the health sector remained neglected both at the national and provincial level. The provincial analysis suggests that federal transfers improved hospital beds availability in the economically active provinces, which were presumably more efficient. Provincial autonomy, on the other hand, failed to play a role in the improvement of the health sector. The analysis highlights the social implications of federal transfers. Differences in results for economically distinct provinces hint towards the efficiency aspect of resource utilisation.

In this paper we study the behavior of the multi-field in phantom inflation, when massive scalar fields work collectively, in which the scale factor is a power law. We evaluate its parameter values by applying certain constraints on our model parameters, and we investigate that before the Big Rip singularity occurs the universe is in phantom inflationary phase. Furthermore, we calculate these values for this period then compare with current observations of CMB, BAO and observational Hubble data. We find that results may be consistent with observations. This implies that in the dark-energy equation of state (EOS) parameter $\omega_{DE}$ at the Big Rip remains finite, with the divergence of pressure and dark energy density., Comment: 9 pages, 1 figure. arXiv admin note: substantial text overlap with arXiv:1208.0021, and text overlap with arXiv:1203.4901 by other authors