Micronutrients Deficiency in Patients Receiving Parenteral Nutrition: Effect of Multivitamin Supply Shortage

Background: Total parenteral nutrition (TPN) is a life-saving therapy for patients with chronic intestinal failure. TPN typically consists of macronutrients (amino acids, dextrose, and lipids) as well as micronutrients (multi-vitamins [MVI] and trace elements) to meet fluid, calorie, and micronutrient needs. With the early years of PN administration, multiple deficiencies were noted leading to guidelines regarding need for daily use of essential trace element and MVI preparation for parenteral use. Unfortunately, during the last few years we have seen multiple shortages of PN related supplies including the most recent shortage of parenteral MVI preparation. Major organizations such as ASPEN have developed recommendations regarding management of shortages, however their clinical impact has not been fully evaluated. The current study evaluated the impact of MVI shortage on change in clinical practice and the prevalence of deficiency. Method(s): A retrospective review of electronic medical records for patients who received TPN during time of shortage in IV multivitamins supply due to COVID-19 crisis between January 2021 and June 2021. In our program, the shortage affected one TPN supplier. We included patients who received their TPN from affected supplier and who were tested for micronutrients including Vitamins A, B12, C, and D in the 6 months preceding the shortage in supply (period 1) as well as during the shortage period (period 2). Period 1 was defined as from July 1, 2020, to December 31, 2020, and period 2 was defined as from January 1, 2021, to June 30, 2021. In addition to baseline clinical characteristics, we captured changes in studied micronutrients. Result(s): Current retrospective analysis of a prospectively maintained database noted 21 patients (mean age of 63.3 +/- 13.8, 62% female) were impacted by MVI shortage during study period (Table 1). Most common primary diagnosis was Crohn's disease (33.3%) followed by enterocutaneous fistula (19%), and gastrointestinal dysmotility (14.3%). In 19/21 (90%) patients, MVI was administered 3 days per week in PN. In the remaining two patients who had short bowel,MVI was continued 7 days per week. Additionally, 19/21 (90%) patients also were supplemented orally with Vitamin D (17/21), Vitamin B12 (5/21), MVI (3/21), Vitamin C (1/21). There was a decline in average Vitamin C levels between the two study periods (Table 2) with a trend towards a decline in average 25-hydroxy vitamin D levels, while mean vitamin A and B12 levels did not change significantly. There was a significant increase in Vitamin D and C deficiencies, while no increase in deficiencies in Vitamin E, A, and B12 levels was noted (Figure 1). Conclusion(s): Unfortunately, shortages of key PN related supplies have become commonplace in the last few years. The most recent shortage affected MVI supplies. Our group managed the shortage through a combination of reduction of parenteral MVI administration to 3 days per week along with additional supplementation of specific micronutrients orally. Although with this strategy, there was an increase in Vitamin D and C levels falling below reference range, no significant deficiencies were noted. (Table Presented).

Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

Indirect Calorimetry Critical in Identifying Early Hypometabolism and Late-Stage Hypermetabolism in Post-surgical Patients

Background: Indirect calorimetry (IC) is the gold-standard procedure for measuring resting energy expenditure (REE) in hospitalized patients. Predictive energy equations commonly use static variables and rarely account for changes in REE throughout hospitalization. We hypothesize that predictive equations are typically inaccurate in surgical intensive care unit (ICU) patients. More specifically, we hypothesize that predictive equations often overpredict measured resting energy expenditure (mREE) in early-stage critical illness and underpredict needs later in surgical ICU stay, leading to over-/under-feeding and associated complications. Method(s): This prospective observational trial enrolled surgical ICU patients who underwent emergent or urgent operations for abdominal trauma, perforated viscus, or ischemic bowel within 72 hours of their surgical procedure. Metabolic assessments were performed using the COSMED Q-NRG + Metabolic Monitor ventilator, mask, and canopy at regular intervals during and post ICU admission until hospital discharge. Measurements were categorized by post-surgical intervention ICU admission days 0-3, 4-7, 8-14, 15-21, and 22-28. Patients with multiple measurements taken during the same time interval were averaged. mREE reported in calories (kcal) per kilogram (kg) of admission body weight per day were compared in obese (BMI > 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. Compared to IC, the Mifflin St Jeor (MSJ) equation determined predicted REE using ICU admission anthropometrics. Data are reported as mean+/-standard error of the mean (SEM) and median (interquartile range), and a two-sided p-value of <0.05 was determined significant. Result(s): In total, 18 surgical ICU patients who contributed 47 IC measurements were included in the analysis (Table 1). Most measures were obtained within the first 7 days of post-surgical ICU admission (72%). mREE peaked between days 8-14 in obese and non-obese subgroups (20.6 vs 28.5 kcal/kg;p = 0.02) and was lowest during 0-3 days of post-surgical ICU admission in both groups. Across all 5-time intervals, average kcal/ kg ranged from 14.7-20.6 among obese patients and from 20.1-28.5 in non-obese counterparts (Table 2). Non-obese patients had higher mREE per kg of body weight than obese patients at all time points (Figure 1). MSJ over-predicted mREE during the first 7 days post ICU admission in non-obese patients and within the first 3 days in obese patients and underpredicted mREE in both groups thereafter. Conclusion(s): Equations such as MSJ over- and under-predict mREE in post-operative surgical ICU patients depending on the days elapsed since post-surgical ICU admission. ASPEN's current guideline recommendation of 12-25 kcal/kg may also underfeed post-surgical populations while 25 kcal/kg may not support hypermetabolism among non-obese patients seen in week 2 following post-surgical ICU admission. Alternatively, MSJ multiplied by a 1.2 activity factor may account for hypermetabolism during this time. Notably, non-obese patients experienced greater hypermetabolism than obese patients during week 2 which is consistent with our previously published data in mechanically ventilated COVID- 19 patients. Additionally, the striking dichotomy between the mREE of obese and non-obese patients at all post-surgical time points should be considered in the clinical care of patients. Ultimately, IC remains the gold-standard means of measuring REE and is a critical tool to capture the dynamic nature of energy requirements in post-surgical populations as weight-based and predictive equations continually fall short. (Table Presented).

A cross sectional study to assess the prevalance of psychiatric morbidity in recovered patients of COVID 19 infection attending a tertiary care centre in hubballi

Background -The Coronavirus Disease 2019 (COVID-19) is a severe multiorgan pathology which, apart from cardio-respiratory manifestations, affects the function of the central nervous system (CNS). Most reviewed studies have reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects Aim -This study aims to document the prevalence of psychiatric disorders among participants who had recovered from covid 19 attending the out patient department of a tertiary care hospital. Methods -A Cross sectional study was done to assess the prevalence of psychiatric disorders among 136 recovered patients of COIVD 19 infection with the help of MINI International Neuropsychiatric Schedule 7.0.2 Results -Prevalence of psychiatric morbidity was 17.64% with majority of the patient(9.55%) having found to be suffering from Depressive disorders. Conclusion -The psychiatric morbidity among recovered recovered patients of COVID 19 infection was found to be higher than the general populus, Given the growing incidence of these cases in our community, we consider that further studies based on psychiatric symptoms description, sociodemographic factors, physical symptoms and COVID-19related severity should be conducted.

The Effects of Nitrogen Fertilisation on the Anatomical Properties of the Populus alba L. Clone 'Villafranca' Juvenile Wood.

This study investigates the effect of nitrogen fertilisation on the anatomical properties of the juvenile wood of the Populus alba L. clone 'Villafranca' from an experimental trial near the Drava River in Croatia. Nitrogen was applied for two consecutive years, and the immediate and potential post-treatment effects were investigated. The correlation between annual ring width (ARW) and individual wood anatomical properties was also examined. The fertilisation effect was confirmed after the first year of nitrogen application for all wood anatomical properties except the vessel lumen area (VLA). Fibre length (FL) was reduced, and double cell wall thickness (DCWT), ray area (RA), and cell wall area (CWA) increased. In contrast, the vessel lumen diameter (VLD) and vessel lumen area changed inconsistently between treatments. The second year of nitrogen application was determined to be effective for FL only. Due to the insignificant results in the second year of the application of nitrogen, the post-fertilisation effect of nitrogen fertilisation was not confirmed.

The challenge of meeting protein requirements in critically ill patients in the COVID era

Critically ill patients often face progressive and rapid losses of body and muscle mass due to hypermetabolism and increased protein catabolism. Certain population groups (such as obese patients or those requiring Continuous Renal Replacement Therapy (CRRT) require a higher protein provision as advised by both ASPEN1 and ESPEN2. Furthermore, critically ill patients often receive significant energy provision from non-nutritional sources such as propofol. As a consequence, calorie provision via enteral feed is commonly restricted to avoid overfeeding, and protein provision to the patient is further compromised. Retrospective data was collected for 58 patients who were either confirmed or suspected of COVID-19 and admitted to the Intensive Care Unit (ICU) during April 2020. 31% (n=18) of patients were unable to meet their protein requirements from the feed formula alone, based on initial dietetic assessment. Recommended protein requirements were not achieved in any patients who were obese (n=10;defined as BMI ≥30 kg/m2) or receiving CRRT (n=6). The maximum protein provision for obese patients was 1.5g/kg IBW and 1.6g/kg for patients receiving CRRT. The situation was exacerbated for patients receiving high dose propofol (defined as >10 ml/hr), where protein provision decreased to 0.8 – 1.2g/kg and 1.1 – 1.3g/kg respectively. [Formula presented] In the non-obese, non-CRRT ICU population, the available enteral feeding regimes were appropriate to meet the majority of patients’ protein requirements (as shown in Figure 1). However the review almost certainly overestimates protein provision, as percentage feed delivery was not assessed and the results assume 100% feed delivery. We know from previous audits on our unit that feed delivery is often <80% of target, and although this review was based on COVID-19 patients, the ‘typical’ patients in ICU often have specific nutrition requirements, which includes high protein. The challenges faced during COVID-19 has raised awareness of the importance of protein delivery in ICU and our review highlights the need to continually monitor and augment protein delivery in critically ill patients. The findings support the need for a high protein supplement in specific population groups;particularly those who may be obese, require CRRT or are receiving high dose propofol in an ICU setting. 1 McClave S A, Taylor B E, Martindale R G et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) J Parenter Enteral Nutr 2016;40(2): 159-211. 2 Singer P, Blaser A R, Berger M M et al. ESPEN Guideline on clinical nutrition in the intensive care unit Clin Nut 2019;38: 48-79

The Association Between Screening Tools Used to Assess Nutrition Status in an Acute Care Setting

Background: Screening tools to assess both the risk of malnutrition (such as the Malnutrition Screening Tool, MST) and wound development (Braden scale) are frequently utilized in the hospital setting. Hospital-acquired pressure injuries (HAPIs) result in considerable patient harm, including expensive treatments, increased length of stays, and increased mortality. Malnutrition is a significant risk factor in the development and progression of HAPIs. Therefore, identifying malnutrition risk and prevalence is an important step in preventing HAPIs. However, processes which involve multiple screening steps consume resources such as staff and time which have become scarce during the COVID-19 pandemic. While the Braden scale contains a nutrition component as a sub-score, little is known about the validity of this sub-scale to capture malnutrition risk. We aimed to explore the association between a validated malnutrition screening tool (MST) and the Braden nutrition scale to determine their use in generating nutrition consults. Methods: We conducted a retrospective chart review of adult patients who developed a HAPI during hospital admission. Baseline MST scores (0-6) and Braden nutrition sub-scale score (1-4) were collected. Higher MST scores represent increased risk of malnutrition, while lower Braden nutrition sub-scores represent poor nutrition status. Documentation of a malnutrition diagnosis using the ASPEN guidelines (yes/no) was also collected for each patient. Pearson correlation coefficients and linear regression were used to assess the association between the MST and Braden nutrition sub-score in the entire cohort. A sub-analysis was conducted in the patients with a diagnosis of malnutrition. Logistic regression was performed to evaluate the association between the Braden nutrition sub-scores and a malnutrition diagnosis. Results: The cohort included 133 patients with a mean age of 69.3 years, with 69.9% being male. 77 patients had malnutrition status recorded, with 64.9% diagnosed with malnutrition. There was a significant correlation between Braden nutrition sub-score and MST (R = -0.28;p < 0.001) in the overall cohort and in subjects with malnutrition (R = -0.35;p = 0.01). Linear regression confirmed that low Braden scale nutrition subscores (poor nutrition status) were predicted by high MST scores (risk for malnutrition) (p = < 0.001). Logistic regression modeling showed a higher Braden nutrition sub-score (better nutrition status) was associated with a diagnosis of malnutrition (OR: 0.45;p=0.057). Conclusion: The results of this study demonstrate that the MST and the Braden nutrition sub-scores are correlated in a cohort of hospitalized patients who developed a HAPI. Use of both screening tools may not be necessary for identifying those that warrant further assessment and interventions for malnutrition.

The Deglycosylated Form of 1E12, a Monoclonal Anti-PF4 IgG, Strongly Inhibits Antibody-Triggered Cellular Activation in Vaccine-Induced Thrombotic Thrombocytopenia, and Is a Potential New Treatment for Vιττ

[Formula presented] Introduction Vaccine-induced thrombotic thrombocytopenia (VITT) is a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, likely due to anti-platelet factor 4 (PF4) IgG antibodies. The specificity and platelet-activating activity of VITT antibodies strikingly resemble that of antibodies detected in “autoimmune” heparin-induced thrombocytopenia (HIT), but their features remain poorly characterized. In particular, a better knowledge of these antibodies should help to understand the mechanisms leading to hypercoagulability and the particular thrombotic events observed in VITT, but rarely in typical HIT. We have recently developed a chimeric IgG1 anti-PF4 antibody, 1E12, which strongly mimics “autoimmune” HIT antibodies in terms of specificity and cellular effects. Therefore, we assessed whether 1E12 could mimic VITT antibodies. We then evaluated the capability of DG-1E12, a deglycosylated form of 1E12 unable to bind FcγR, to inhibit cellular activation induced by VITT antibodies. Methods and Results Using a PF4-sensitized serotonin release assay (PF4-SRA) (Vayne C, New Engl J Med, 2021), we demonstrated that 1E12 (5 and 10 μg/mL) strongly activated platelets, with a pattern similar to that obtained with human VITT samples (n=7), i.e. in a PF4-dependent manner and without heparin. This platelet activation was inhibited by low heparin concentration (0.5 IU/mL), an effect also observed with VITT samples. Serotonin release induced by 1E12 was also fully inhibited by IV-3, a monoclonal antibody blocking FcγRIIa, or by IdeS, a bacterial protease that cleaves IgG and strongly inhibits the binding of IgG antibodies to FcγRIIa. This inhibitory effect of IV-3 and IdeS strongly supports that interactions between pathogenic anti-PF4 IgG and FcγRIIa play a central role in VITT. Incubation of 1E12 or VITT samples with isolated neutrophils (PMN) and platelets with PF4 (10 µg/mL) strongly induced DNA release and NETosis, supporting that PMN are involved in the processes leading to thrombosis in VITT. Furthermore, when whole blood from healthy donors incubated with 1E12 or VITT plasma was perfused in capillaries coated with von Willebrand Factor, numerous large platelet/leukocyte aggregates containing fibrin(ogen) were formed. To investigate whether 1E12 and VITT antibodies recognize overlapping epitopes on PF4, we then performed competitive assays with a deglycosylated form of 1E12 (DG-1E12), still able to bind PF4 but not to interact with Fcγ receptors. In PF4-SRA, pre-incubation of DG-1E12 (50 µg/mL) dramatically reduced platelet activation induced by VITT antibodies, which was fully abrogated for 9 of the 14 VITT samples tested. Additional experiments using a whole blood PF4-enhanced flow cytometry assay recently designed for VITT diagnosis (Handtke et al, Blood 2021), confirmed that DG-1E12 fully prevented platelet activation induced by VITT antibodies. Moreover, when platelets and neutrophils were pre-incubated with DG-1E12 (100 µg/mL), NETosis and thus DNA release, nuclear rounding, and DNA decondensation induced by VITT antibodies were completely inhibited. Finally, DG-1E12 (100 µg/mL) also fully abolished VITT antibody-mediated thrombus formation in whole blood in vitro under vein flow conditions. Comparatively, DG-1E12 did not inhibit ALB6, a murine monoclonal anti-CD9 antibody, which also strongly activates platelets in a FcγRIIa-dependent manner. Conclusions Our results show that 1E12 exhibits features similar to those of human VITT antibodies in terms of specificity, affinity and cellular effects, and could therefore be used as a model antibody to study the pathophysiology of VITT. Our data also demonstrate that DG-1E12 prevents blood cell activation and thrombus formation induced by VITT antibodies, likely due to the competitive effect of its Fab fragment on antibody binding to PF4. DG-1E12 may allow the development of a new drug neutralizing the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT. Disclosures: T iele: Bristol Myers Squibb: Honoraria, Other;Pfizer: Honoraria, Other;Bayer: Honoraria;Chugai Pharma: Honoraria, Other;Novo Nordisk: Other;Novartis: Honoraria;Daichii Sankyo: Other. Pouplard: Stago: Research Funding. Greinacher: Macopharma: Honoraria;Biomarin/Prosensa: Other, Research Funding;Sagent: Other, Research Funding;Rovi: Other, Research Funding;Gore inc.: Other, Research Funding;Bayer Healthcare: Other, Research Funding;Paringenix: Other, Research Funding;BMS: Honoraria, Other, Research Funding;MSD: Honoraria, Other, Research Funding;Boehringer Ingelheim: Honoraria, Other, Research Funding;Aspen: Honoraria, Other, Research Funding;Portola: Other;Ergomed: Other;Instrument Laboratory: Honoraria;Chromatec: Honoraria. Gruel: Stago: Other: symposium fees, Research Funding. Rollin: Stago: Research Funding.

Rivaroxaban for Improvement in Thromboembolism Outcomes in Patients with Multiple Myeloma on Lenalidomide-Based Therapy: The Rithmm Feasibility Pilot Trial

Introduction:The association between thrombosis (TE) and cancer has been well established. The risk for thrombosis in Multiple Myeloma (MM) is further compounded by therapy-related factors, which increase the risk for both arterial and venous TE. Lenalidomide + dexamethasone (Ld) is the most widely used backbone therapy for MM and may increase the risk of TE. The current standard TE prophylaxis for patients on Ld is low dose aspirin (ASA) for low risk patients or low molecular weight heparin for high risk patients. Direct oral anticoagulants have been used empirically and have been evaluated in small prospective cohort studies with promising results. Methods: RithMM is an ongoing open label Canadian multicenter pilot feasibility RCT to assess the efficacy and safety of daily oral rivaroxaban 10 mg (Riva) versus ASA 81 mg in patients with MM on Ld-based therapy. Our primary objective is to assess the feasibility of accrual of patients with MM starting on Ld-based therapy. Patients not on therapeutic anticoagulation or antiplatelet agents for another indication (e.g. atrial fibrillation) are eligible for RithMM. Primary clinical endpoints are major cardiovascular (CV) events or major bleeding as per the ISTH criteria. The study will be considered feasible if 86 patients in 4 Canadian sites (London, Ottawa, Halifax, Niagara) can be enrolled in 12 months after each site activation. Sites are expected to accrue an average of 1.8 patients per month. Patients are randomly assigned to receive ASA (control) or Riva (intervention) using a simple randomization sequence run by the Redcap system, utilizing an automated assignment procedure. Patients enter the study at the time of anticoagulant initiation and are followed for 6 months, or until they withdraw from the study;die or develop a primary clinical outcome;whichever comes first. Herein we present the interim analysis of RithMM after study completion in 2 of 4 sites. Feasibility assessment: 17 patients were randomized to ASA and 17 to Riva (1 patient did not take the study drug). Feasibility assessment was severely impacted by the temporary but prolonged research activity closures secondary to the COVID-19 pandemic that limited direct patient accrual and led to significant delays in REB approval of the participating sites. The first patient was enrolled in January 2019 in London. Ottawa opened in October 2019, Halifax in December 2020 and Niagara in May 2021. A total of 34 patients have been enrolled: 22 London, 11 Ottawa and 2 Halifax. London was the only site actively accruing for 12 consecutive months. Ottawa opened for 3 months, held accrual for 9 months, then reopened for 7 months. Halifax was open for only 1 month. Niagara opened in May 2021, the time of study data lock for this . In addition, 7 potentially eligible patients were not screened given that they were enrolled in a MM treatment trial that did not permit enrolment in another trial. The accrual rate was excellent for London (105%) and Ottawa (52% in 10 months). The drop-out rate was 6% (2 patients) and drug compliance 100%. Clinical Outcomes: Baseline characteristics are depicted in the table. One patient in the ASA arm developed a proximal deep vein thrombosis 2 months after starting treatment, and another developed a clinically relevant nonmajor bleeding 6 weeks after starting ASA. Discussion: This is the interim analysis of the RithMM pilot trial that aims to evaluate the feasibility of accrual of MM patients on Ld -base therapy to assess the efficacy and safety of Riva versus ASA in preventing TE complications. The study was initiated during the COVID-19 pandemic turmoil, which severely impacted in the proper activation of 3 of the 4 participating sites. Despite this significant limitation, 2 sites were able to maintain the accrual of patients. Only 1 site remained opened according to the pre-specified consecutive 12- month study period. Despite this barrier, we could still attain an excellent accrual rate of 39.5% in 2 sites (London and Ottawa). The incidence of TE or bleeding was low, with o difference between ASA and Riva. However, the study was not powered to assess these outcomes. Lastly, Ld is the most widely used backbone therapy in MM, both in upfront and relapsed settings. Our group does not anticipate any barriers to achieving successful completion of accrual provided the hospital's activities remain safe and research activities open. [Formula presented] Disclosures: Louzada: Celgene: Honoraria;Janssen: Honoraria;Pfizer: Honoraria;Amgen: Honoraria. McCurdy: Sanofi: Honoraria;GSK: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Celgene: Consultancy, Honoraria. Phua: Pfizer: Honoraria;Amgen: Honoraria;AstraZeneca: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Le Gal: Aspen: Honoraria;Bayer: Honoraria;Pfizer: Honoraria;LEO Pharma: Honoraria;BMS: Honoraria;Sanofi: Honoraria. Lam: Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees;Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Rivaroxaban 10 mg oral daily for thrombosis prophylaxis in myeloma patients on lenalidomide-based therapy. Health Canada approved the off label use for study purposes

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT);and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67;D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Formula presented] Disclosures: Carrier: Sanofi: Honoraria;Pfizer: Honoraria, Research Funding;Servier: Honoraria;Bayer: Honoraria;Leo Pharma: Honoraria, Research Funding;BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria;Aspen: Honoraria;Bayer: Honoraria;LEO Pharma: Honoraria;Pfizer: Honoraria;Sanofi: Honoraria. Castellucci: BMS: Honoraria;Pfizer: Honoraria;Amag Pharmaceuticals: Honoraria;The Academy: Honoraria.

A k-mer based approach for classifying viruses without taxonomy identifies viral associations in human autism and plant microbiomes.

Viruses are an underrepresented taxa in the study and identification of microbiome constituents; however, they play an essential role in health, microbiome regulation, and transfer of genetic material. Only a few thousand viruses have been isolated, sequenced, and assigned a taxonomy, which limits the ability to identify and quantify viruses in the microbiome. Additionally, the vast diversity of viruses represents a challenge for classification, not only in constructing a viral taxonomy, but also in identifying similarities between a virus' genotype and its phenotype. However, the diversity of viral sequences can be leveraged to classify their sequences in metagenomic and metatranscriptomic samples, even if they do not have a taxonomy. To identify and quantify viruses in transcriptomic and genomic samples, we developed a dynamic programming algorithm for creating a classification tree out of 715,672 metagenome viruses. To create the classification tree, we clustered proportional similarity scores generated from the k-mer profiles of each of the metagenome viruses to create a database of metagenomic viruses. The resulting Kraken2 database of the metagenomic viruses can be found here: https://www.osti.gov/biblio/1615774 and is compatible with Kraken2. We then integrated the viral classification database with databases created with genomes from NCBI for use with ParaKraken (a parallelized version of Kraken provided in Supplemental Zip 1), a metagenomic/transcriptomic classifier. To illustrate the breadth of our utility for classifying metagenome viruses, we analyzed data from a plant metagenome study identifying genotypic and compartment specific differences between two Populus genotypes in three different compartments. We also identified a significant increase in abundance of eight viral sequences in post mortem brains in a human metatranscriptome study comparing Autism Spectrum Disorder patients and controls. We also show the potential accuracy for classifying viruses by utilizing both the JGI and NCBI viral databases to identify the uniqueness of viral sequences. Finally, we validate the accuracy of viral classification with NCBI databases containing viruses with taxonomy to identify pathogenic viruses in known COVID-19 and cassava brown streak virus infection samples. Our method represents the compulsory first step in better understanding the role of viruses in the microbiome by allowing for a more complete identification of sequences without taxonomy. Better classification of viruses will improve identifying associations between viruses and their hosts as well as viruses and other microbiome members. Despite the lack of taxonomy, this database of metagenomic viruses can be used with any tool that utilizes a taxonomy, such as Kraken, for accurate classification of viruses.