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

Background: Sepsis 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. Methods: Ten 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. Results: All 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. Conclusion: Administration 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 Registration: ClinicalTrials.gov Identifier: NCT03925857. (https://clinicaltrials.gov/ct2/show/study/NCT03925857).

[Truth telling to patients--A discussion of Jewish sources (corrected)].

Defining truth and truth-telling to patients are central topics in philosophy, law, and psychology, with many implications in medicine. In the last hundred years, with the transition from paternalistic medicine to a system in which the patient's autonomy is emphasized, the decision on the quantity and quality of medical information to be disclosed to the patient has become more complicated and requires careful consideration and special sensitivity on the part of the doctor. The Israeli Patients' Rights Act (1996] established guidelines for medical staff about telltting the truth to patients with occasional special authority delegated to the doctor to decide for the benefit of the patient at his discretion and with the approval of the institutional ethics committee, but in practice there are difficulties in implementing the Law. This article reviews a selection of sources from Jewish tradition throughout the ages that deal with truthtelling or concealing the truth in medical contexts and other contexts. Sources are drawn from the Bible, Mishna-Talmud, and halachic Literature, from which.conclusions can be drawn regarding this issue. In our opinion, these sources yield messages and values that are also relevant to the modern medical world. This is especially true in a multi-cultural environment such as Israel that requires the physician to consider the patient's background and to communicate information in accordance with his/her will, in an efficient and sensitive manner.

[Medicine, physicians and medical ethics in Jewish tradition through the ages].

Medicine has always had a place of honor in the Jewish heritage. Since Biblical times, the sources of Judaism have valued the physician's activities and seen them as a partnership with God's deeds. Later, in the times of the Mishna and the Talmud, a model of scholars evolved who were not only learned sages but also had extensive medical and scientific knowledge. Their dealings with various issues in medical ethics were the basis for deliberation on questions that appeared throughout history on the advancement of medical science. The various sources from this period show the sages' sensitivity regarding the subject of human life, saving lives and the importance of the availability of medicine for all segments of the population. During the years following the completion of the Talmud, the medical profession was common among the Jews and they excelled in this field. Jewish doctors left behind a Legacy of values in medicine. Hebrew was considered a significant Language in the medical field and was cited in various medical texts such as in the book written by Vesalius, the "father" of modern anatomy. The rapid progress of medicine poses new challenges in bioethics. There is a need for physicians with extensive medical knowledge along with an understanding of ethical issues in order to offer solutions to new situations. Knowledge of the Jewish literature throughout the ages on a variety of subjects and the essential values which are their foundation can contribute to the modern discussion on biomedical questions. This is even more important in Israeli society where many of the laws are formed based on Jewish values. Engagement with Jewish medical ethics can help in educating physicians to have the ability to contribute to public debate and legislation in a way that would balance between the values and needs which an ethical issue raises.

[Self endangerment to save life--competing Jewish legal and moral obligations].

The obligation to help others often involves personal risk. Consequently, the scope and boundaries of this obligation can present a complex dilemma, which has practical and moral implications, even in the world of medicine. In Jewish medical ethics, the dilemma stems from a confrontation between the duty to help others according to the biblical commandment: "Do not stand idly by your fellow's blood" on the one hand, and between the right and duty of man to defend himself, which is anchored in Jewish law. This article surveys the sources of this quandary in Jewish texts throughout the ages such as the Bible, Mishnah, Talmud, and responsa literature in various contexts. The discussion highlights the essential difference between the formal demands of the law, which protects human rights of self-preservation, and the moral requirement to help others even if it may include personal risk. The sources suggest distinguishing between various levels of risk ranging from high-risk to reasonable or low risk. In this way, the classic sources, provide the foundation and the tools for grappling with modern contemporary Halachic questions such as organ transplantation, and generate a Torah value-based framework to deal with new situations that may arise in the future. It is critical to assess the level of risk and the chances for success, along with other subjective considerations, in order to ensure the optimal ethical course of action.