Apoptotic Cells for Therapeutic Use in Cytokine Storm Associated With Sepsis– A Phase Ib Clinical Trial

BackgroundSepsis has no proven specific pharmacologic treatment and reported mortality ranges from 30%–45%. The primary aim of this phase IB study was to determine the safety profile of Allocetra™-OTS (early apoptotic cell) infusion in subjects presenting to the emergency room with sepsis. The secondary aims were to measure organ dysfunction, intensive care unit (ICU) and hospital stays, and mortality. Exploratory endpoints included measuring immune modulator agents to elucidate the mechanism of action.MethodsTen patients presenting to the emergency room at the Hadassah Medical Center with sepsis were enrolled in this phase Ib clinical study. Enrolled patients were males and females aged 51–83 years, who had a Sequential Organ Failure Assessment (SOFA) score ≥2 above baseline and were septic due to presumed infection. Allocetra™-OTS was administered as a single dose (day +1) or in two doses of 140×106 cells/kg on (day +1 and +3), following initiation of standard-of-care (SOC) treatment for septic patients. Safety was evaluated by serious adverse events (SAEs) and adverse events (AEs). Organ dysfunction, ICU and hospital stays, and mortality, were compared to historical controls. Immune modulator agents were measured using Luminex® multiplex analysis.ResultsAll 10 patients had mild-to-moderate sepsis with SOFA scores ranging from 2–6 upon entering the study. No SAEs and no related AEs were reported. All 10 study subjects survived, while matched historical controls had a mortality rate of 27%. The study subjects exhibited rapid resolution of organ dysfunction and had significantly shorter ICU stays compared to matched historical controls (p<0.0001). All patients had both elevated pro- and anti-inflammatory cytokines, chemokines, and additional immune modulators that gradually decreased following treatment.ConclusionAdministration of apoptotic cells to patients with mild-to-moderate sepsis was safe and had a significant immuno-modulating effect, leading to early resolution of the cytokine storm.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT03925857. (https://clinicaltrials.gov/ct2/show/study/NCT03925857).

KESHARANJANA YOGA IN BHAISHAJYA RATNAVALI: A REVIEW

Bhaishajya Ratnavali by Kaviraj Govinda Das Sen of 18th century is an authentic book of Ayurveda science includes systematic description of diseases along with treatment aspects. Under Kshudraroga Chikitsa Prakarana, detailed information regarding kesharanjana has been explained with description of kesharanjana yoga. This article mainly focuses on the kesharanjana yoga mentioned in this book for better nourishment and coloring of hair. Review on kesharanjana yoga mentioned in Bhaishajya Ratnavali was analyzed and summarized for better usage and understanding. Initially author explains few preparations to apply as lepa (application) over scalp or hairs and later nasya (inhalation therapy) procedure for hair care. Most of the drugs used are rasayana (immune modulator) in nature and has keshya (hair tonic) property which forms the prime factor in using these drugs. Direct application as lepa and also nasya procedure would help in better nourishment and also proper growth of hair. Owing to the properties of drugs used for the preparations which are useful in many conditions of hair problems. By following these yogas and with proper pathya one can get benefited from khalitya, palitya, and other conditions of hair.

DOP90 Physician global assessment of IBD Activity is associated with COVID-19 severity in patients aged less than 50 years

Background SECURE-IBD is an international database that monitors COVID-19 outcomes in IBD patients. We examined the influence of IBD activity (reflected by Physician Global Assessment (PGA)) on COVID-19 severity, while exploring the modifying effect of age. Methods We analyzed 3,028 cases reported to SECURE-IBD from March 13-November 17, 2020. PGA was categorized as remission/mild (reference) vs moderate vs severe. Outcomes used as surrogates of severe SARS-CoV2 infection were hospitalization and a composite of ICU/ventilation/death. Using generalized estimating equations (GEE) to account for clustering by country, we determined the unadjusted association between disease activity and COVID-19 outcomes, overall and by age decade. We included the following covariates in multivariable GEE models a priori: time of COVID-19 diagnosis, age, sex, comorbidities (0, 1, ≥2), IBD type, systemic corticosteroids (CS), anti-TNF monotherapy, anti-TNF plus immune modulator, immune modulator monotherapy, and mesalamine. We included additional covariates (country GDP, race, BMI, anti-integrins and ustekinumab) if they changed the estimate by ≥10%. We also built models stratified by age; the age cut-off for stratification was determined using Joinpoint regression (selecting the age at which outcome rates significantly changed). Results COVID-19 was more severe in patients with more active IBD: hospitalization rates 19% (remission/mild), 26% (moderate) and 45% (severe); ICU/ventilation/death rates 5% (remission/mild), 6% (moderate) and 12% (severe) (p<0.05, Figure 1). In unadjusted analyses, higher PGA was associated with an increased risk of hospitalization (moderate: OR 1.53, 95% CI 1.24–1.88; severe: OR 3.30, 95% CI 2.44–4.46) and ICU/ventilation/death (moderate: OR 1.44, 95% CI 1.10–1.87; severe: OR 2.58, 95% CI 1.71–3.90). As per Figure 2, the magnitude of association between severe PGA (vs remission/mild) and adverse outcomes was greatest in patients ≤50 years. Joinpoint regression also supported a significant change in the rate of ICU/ventilation/death at 50 years. In multivariable analyses (Figure 3), PGA remained significantly associated with hospitalization, but not ICU/ventilation/death. However, in multivariable analyses stratified by age, PGA was consistently associated with both hospitalization and ICU/ventilation/death in patients ≤50, but not >50 years. Conclusion Our data suggest an association between IBD activity, as assessed by PGA, and severe COVID-19 outcome with an increased risk in younger patients. Adequate IBD treatment despite the pandemic is needed to avert poor outcome to symptomatic SARS-CoV2 infections.