Search

We aimed to compare the outcomes of COVID-19 Renal Transplant Recipients (RTRs) managed on an ambulatory basis to that of inpatient management.We performed a retrospective study in Lucknow, India, comparing the ambulatory management with the historical cohort managed in the hospital.R RTRs with mild COVID-19 were managed by supervised home-based self-monitoring (HBSM), a strategy to manage this high-risk group on an outpatient basis during the second wave of the pandemic. The primary outcome was the clinical deterioration to a higher severity category among RTRs with mild COVID-19 managed by HBSM compared to hospitalized patients within two weeks of disease onset.Of the 149 RTRs with mild COVID-19, 94 (63%) and 55 (37%) were managed by HBSM and in the hospital, respectively. The proportion of RTRs who clinically deteriorated to a higher severity category (moderate or severe category) was similar among both groups (28.7% versus 27.2%, P=0.849). Among RTRs with clinical deterioration, COVID-19-related death was reported in two patients of the HBSM group and in none of the patients of the hospitalized group. Graft dysfunction was higher in the hospitalized group (7.4% versus 27.2%, P=0.002). Median time to complete clinical recovery (7 days in both groups), secondary bacterial infections (25% versus 33.3%, P=0.41), and the mean decline in EQ-5D score from baseline at six weeks (-6.6 versus-4.3, P=0.105) were found to be similar in both groups.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016&ndash, 2017) of adult (&ge, 18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p &lt, 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07&ndash, 1.09), IHD (aOR 1.24, 95% CI 1.21&ndash, 1.28), acute MI (aOR 1.23, 95% CI 1.19&ndash, 1.28), AFib (aOR 1.21, 95% CI 1.16&ndash, 1.27), and TIA (aOR 1.19, 95% CI 1.11&ndash, 1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06&ndash, 1.14), ICeH (aOR 1.22, 95% CI 1.08&ndash, 1.38), TIA (aOR 1.36, 95% CI 1.25&ndash, 1.47), IHD (aOR 1.37, 95% CI 1.33&ndash, 1.41), acute MI (aOR 1.44, 95% CI 1.38&ndash, 1.49), AFib (aOR 1.10, 95% CI 1.06&ndash, 1.15), and CHF (aOR 1.03, 95% CI 1.02&ndash, 1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

An attempt was made to develop nutrient rich extruded snacks from lesser utilized protein rich shrimp (Solenocera crassicornis) flour using twin screw extruder. The extruded were in order to fried and packed in to High Density Polyethelene (HDPE). The extruded were analyzed for physical, texture profile, proximate composition and sensory characteristics at the interval of 10 days for 50 days of storage (DOS). The experiment shows the physical property like expansion ratio (mm) and texture profile characteristics such as hardness (gmF) and crispiness (gm) were not affected at the end of storage period. Among the different studies, the product made from rice/shrimp T1 based extruded scored as higher as 5 (out of 5) by sensory evaluation for all attributes. Consequently, all the extruded were maintained the physical properties, nutritional quality and overall acceptability. This research demonstrated that shrimp flour at 15% can be successfully incorporated for development of extruded were: expansion ratio 3.32, 2.75 and 3.06 (mm), crispiness 291, 252 and 210 (gm), protein 12.69, 18.74 and 15.09 (%), enegy value 540, 489 and 524 (Kcal), TPC 0.36, 0.34 and 0.34 (log cfu/gm) in rice T1, wheat T2 and corn T3 based extruded respectively. Overall, the quality assessment of extruded were not changed significantly (P>0.05) throughout study.

Background ALRN-6924 is a stabilized, cell-permeating alpha-helical peptide that mimics the p53 tumor suppressor protein to disrupt p53’s interactions with its endogenous inhibitors, MDM2 and MDMX. ALRN-6924 has been evaluated in > 175 cancer patients and demonstrated single-agent activity and a well-tolerated single-agent safety profile. MDM2 amplification is an oncogenic event found in up to 4% of all cancers. Co-amplification of MDM2 and cyclin-dependent kinase 4 (CDK4), which are co-located on chromosome 12q13, provides the rationale for combined use of the MDM2-inhibitor ALRN-6924 and the CDK4/6 inhibitor palbociclib in this population, and is further supported by enhanced combination activity in preclinical models. Methods This trial is designed to enroll 25 patients with solid tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplifications. Patients have exhausted or are not eligible for other treatment options. ALRN-6924 is given at a dose of 3.1 mg/kg as IV infusion on Days 1, 8 and 15, and palbociclib is given as an oral dose of 100 mg/day on Days 1-21 of every 28-day treatment cycle. The first nine patients enrolled were evaluated for safety and tolerability after completion of one treatment cycle (safety lead-in). Anti-tumor activity is evaluated with imaging every 8 weeks. Results Patient enrollment started in December 2018. As of April 30, 12 patients were enrolled; tumor types include liposarcoma (N = 10), osteosarcoma and glioblastoma (1 of each); 11/12 patients had tumors that were MDM2 and CDK4 co-amplified. The combination was generally well tolerated with transient, self-resolving Grade 3 and 4 neutropenia (N = 7) emerging as the principal but not dose limiting toxicity. Other Grade 3 and 4 adverse events include thrombocytopenia, leukopenia, increased ALT, pulmonary embolism, and fall. An interim analysis of activity and safety (N = 15 patients with ≥2 post baseline CT scans) is scheduled for early September 2019 and the results will be presented. Conclusions The combination of ALRN-6924 and palbociclib at pharmacologically relevant doses is feasible and generally well tolerated. Clinical trial identification NCT02909972. Legal entity responsible for the study Aileron Therapeutics, Inc. Funding Aileron Therapeutics, Inc. Disclosure F. Meric-Bernstam: Honoraria (self): Sumitomo Dainippon Pharma; Dialectica; Advisory / Consultancy: Genentech; Advisory / Consultancy: Inflection Biosciences; Advisory / Consultancy: Pieris; Advisory / Consultancy: Darwin Health; Advisory / Consultancy: Samsung bioepis; Advisory / Consultancy: Aduro; Advisory / Consultancy: Spectrum; Advisory / Consultancy: OrigiMed; Advisory / Consultancy: Debio; Advisory / Consultancy: Xencor; Advisory / Consultancy: Jackson Laboratory; Advisory / Consultancy: Mersana; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Zymeworks; Advisory / Consultancy: Kolon Life Sciences; Advisory / Consultancy: Parexel International; Research grant / Funding (institution): Novartis; AstraZeneca; Taiho; Genentech; Calithera; Debio; Bayer; PUMA; CytoMx; Research grant / Funding (institution): Aileron; Zymeworks; Curis; Pfizer; eFFECTOR; Abbvie; Guardant Health; Daiichi Sankyo; GSK; Travel / Accommodation / Expenses: Taiho; Genentech; Debio; Pfizer. S.G. DuBois: Advisory / Consultancy: Loxo Oncology; Travel / Accommodation / Expenses: Loxo Oncology; Travel / Accommodation / Expenses: Genentech. G.I. Shapiro: Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Merck KGaA/EMD Serono; Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Sierra Oncology; Advisory / Consultancy, Research grant / Funding (institution), Advisory Board: Pfizer; Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy, Advisory Board: G1 Therapeutics; Advisory / Consultancy, Advisory Board: Roche; Advisory / Consultancy, Advisory Board: Bicycle Therapeutics; Advisory / Consultancy, Advisory Board: Fusion Pharmaceuticals; Advisory / Consultancy, Advisory Board: Astex; Advisory / Consultancy, Advisory Board: Almac; Advisory / Consultancy, Advisory Board: Ipsen; Advisory / Consultancy, Advisory Board: Bayer; Advisory / Consultancy, Advisory Board: Angiex; Advisory / Consultancy, Advisory Board: Daiichi Sankyo; Licensing / Royalties, Compositions and Methods for Predicting Response and Resistance to CDK4/6 Inhibition: Patent pending (work) on palbociclib. M.R. Patel: Research grant / Funding (institution): Aileron Therapeutics, Inc. T. Bauer: Advisory / Consultancy: Ignyta; Guardant Health; Loxo; Pfizer; Moderna Therapeutics; Pfizer; Speaker Bureau / Expert testimony, Speaker’s bureau: Bayer; Research grant / Funding (institution): Daiichi Sankyo; Medpacto; Incyte; Mirati; MedImmune; Abbvie; AstraZeneca; Leap Therapeutics; Research grant / Funding (institution): MabVax; Stemline Therapeutics; Merck; Lilly; GSK; Novartis; Pfizer; Research grant / Funding (institution): Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; Ignyta; Calithera; Kolltan; Research grant / Funding (institution): Principa; Peleton, Immunocore; Roche; Aileron; BMS; Amgen; Moderna; Research grant / Funding (institution): Sanofi; Boehrnger Ingelheim; Astellas; Five Prime; Jacobio; top Alliance; Loxo; Janssen; Clovis; Research grant / Funding (institution): Takeda; Karyopharm; Onyx; Phosplatin; Foundation Medicine; ARMO; Travel / Accommodation / Expenses: Astellas; AstraZeneca; Celgene; Clovis; EMD Serono; Genentech; Lilly; Travel / Accommodation / Expenses: Merck; Novartis; Pharmacyclics; Sysmex. D. Pinchasik: Full / Part-time employment, former Aileron employee: Aileron Therapeutics, Inc. A. Annis: Shareholder / Stockholder / Stock options: Aileron Therapeutics, Inc.; Full / Part-time employment: Aileron Therapeutics, Inc. M. Aivado: Shareholder / Stockholder / Stock options: Aileron Therapeutics, Inc.; Full / Part-time employment: Aileron Therapeutics, Inc. V. Vukovic: Full / Part-time employment: Aileron Therapeutics, Inc. All other authors have declared no conflicts of interest.

Glioblastoma (GBM) is the most common brain cancer. Resistance to front-line systemic therapy with temozolomide (TMZ) is correlated with O6-methylguanine-DNA-methyltransferase (MGMT) expression. Second-line treatment with bevacizumab has not improved overall survival. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that has MGMT-independent cell-kill activity against GBM cell-lines and cancer stem cells in vitro. VAL-083 crosses the blood-brain barrier and showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine appropriate VAL-083 dosing for advancement to Phase III trials as a new treatment for recurrent GBM. METHODS: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm, dose-escalation study. Patients received VAL-083 on days 1,2,3 of a 21-day cycle, until reaching MTD. Phase II: Additional patients enrolled at MTD to further assess safety and outcomes. RESULTS: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5-50 mg/m2/d). 40mg/m2/d was confirmed as MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses up to 40mg/m2/d. Dose limiting G4 thrombocytopenia was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related survival improvement was observed. Pharmacokinetic analyses show 1-2h plasma terminal half-life; average Cmax 781ng/mL at 40mg/m2/d. Phase II: 14 patients were enrolled at 40mg/m2/d. To date, safety observations in Phase II are consistent with Phase I. CONCLUSIONS: VAL-083 at 40mg/m2/d exhibits a favorable safety profile and dose-related trend toward clinically meaningful improved survival in refractory GBM patient

Aung Naing1, Jeffrey R. Infante2, Kyriakos P. Papadopoulos3, Karen A. Autio4, Patrick A. Ott5, Deborah J. Wong6, Gerald S. Falchook7, Manish R. Patel2,8 , Shubham Pant9 and Martin Oft10 1 MD Anderson Cancer Center, Houston, TX; 2 Sarah Cannon Research Institute / Tennessee Oncology, PLLC; 3 START Center for Cancer Care, San Antonio, TX; 4 Memorial Sloan-Kettering Cancer Center, New York, NY; 5 Dana-Farber Cancer Institute, Boston, MA; 6 University of California Los Angeles (UCLA), Los Angeles, CA; 7 Sarah Cannon Research Institute at HealthONE, Denver, CO; 8 Florida Cancer Specialists, Sarasota, FL; 9 Oklahoma University, Oklahoma City, OK; 10 ARMO BioSciences, Redwood City CA