Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

The psychological examination and evaluation of unrelated kidney donors in Israel: a suggested model.

Altruistic organ donors represent a special population when compared to related living donors, requiring appropriate protection and attention regarding informed consent and psychological aspects related to the donation. Following the introduction of the Israeli Transplant Law of 2008, a retrospective study of altruistic donor files revealed that important psycho-diagnostic aspects were not emphasized in the existing guidelines. Thus, a new tool was formulated which incorporated those elements, including assessment of emotional maturity, ego strength, degree of interest in others, reality testing, degree of pressure to donate, anxiety, dysphoric and depressive factors and the ability to function under stress. The study examined 598 cases reviewed by the Central Evaluation Board over the period May 2008 - June 2016. Overall, 23.4% candidates were disqualified of whom 41% were declined on grounds related to mental health. Most of the donors were rejected based on 3-5 elements. Of these, a deficient assessment of reality in ambiguous situations, lack of emotional maturity, and lacking or partial ability to function effectively under stress, were most commonly cited as reasons for rejection. This model allowed the detection of important conditions previously not incorporated into existing guidelines and may serve as a model for other transplantation programs worldwide.

Phage Therapy in Israel, Past, Present, and Future.

The fascinating scientific history of phage therapy has been documented in numerous publications. In this study, however, we focus on an angle of the story that hitherto has remained relatively neglected, namely, phage therapy treatments, and the protagonists that conducted these in Mandatory-Palestine and subsequently the state of Israel, as part of a global trend. We complete the story by describing efforts in the new era of phage therapy in present-day Israel.

Brain Death Determination in Israel: The First 9 Years of Experience Following Changes Made by the Brain and Respiratory Death Determination Law.

BACKGROUND: Changes accommodating requirements of religious authorities in Israel resulted in the Brain and Respiratory Death Determination Law (BRDDL), which came into effect in 2009. These included considering patient wishes regarding the brain respiratory death determination (BRDD), mandatory performance of apnea and ancillary testing, establishment of an accreditation committee, and accreditation required for physicians performing BRDD. OBJECTIVES: To assess the impact of the legislation from 2010-2019. METHODS: Data collected included the number of formal BRDDs and accredited physicians. Obstacles to declaring brain death and interventions applied were identified. RESULTS: Obstacles included lack of trained physicians to perform BRDD and interpret ancillary test results, inability to perform apnea or ancillary testing, and non-approach to next-of-kin objecting to BRDD. Interventions included physician training courses, additional ancillary test options, and legal interpretation of patient wishes for non-determination of BRD. As a result, the number of non-determinations related to next-of-kin objecting decreased (26 in 2010 to 5 in 2019), inability to perform apnea or ancillary testing decreased (33 in 2010 to 2 in 2019), and number of physicians receiving accreditation increased (210 in 2010 to 456 in 2019). Last, the consent rate for organ donation increased from 49% to 60% in 2019. CONCLUSIONS: The initial decrease in BRDDs has reversed, thus enabling more approaches for organ donation. The increased consent rate may reflect in part the support of the rabbinate and confidence of the general public that BRDD is performed and monitored according to strict criteria.

A Comparison of Recalled Pain Memory Following Living Kidney Donation Between Directed and non-Directed, Altruistic Donors.

Introduction: Pain following donor nephrectomy for living kidney donation is common. In Israel, non-directed, altruistic donations account for 45% of all kidney transplants. Design: This cross-sectional, retrospective survey included 2 groups of donors derived from the data of Israel Transplant, namely directed and non-directed, altruistic donors, who donated between 2015 to 2018. The degree of recalled pain memory post-surgery was assessed using the Visual Analog Scale at 5 time points: immediately post-surgery, after 1 week, 1 month and 3 months post-surgery and in the month preceding completion of the questionnaire. In addition, continued requirement for analgesics for more than one-month post-surgery, the degree of interference with daily activities in the month preceding the questionnaire and the recalled time to return to full-time employment were also noted. Results: In total, 246 (131 directed and 115 non-directed, altruistic) donors were included in the study. Non-directed, altruistic donors reported statistically significantly lower degrees of recalled pain memory at all time points, a lower requirement for prolonged analgesic use and less recalled interference with daily activities due to pain. In addition, these donors recalled returning significantly earlier to full-time employment. Finally, no significant differences in the degree of recalled pain memory were noted for directed donors according to their relation to the recipient, apart from donation to a spouse. Conclusion: These unique findings, if validated in a prospective study, could provide important information to potential non-directed, altruistic donors regarding the expected level of post-surgical pain and their return to full-time employment.

Organ donation in the time of COVID-19: the Israeli experience one year into the pandemic-ethical and policy implications.

PURPOSE: To present the response of the Israel National Transplantation Center (NTC) to the evolving challenge of COVID-19, the impact on deceased organ donation and living organ kidney donation during 2020, and resultant policy and ethical implications. METHODS: Data collected included (i) for deceased donors, the total number of potential organ donors, if hospitalized in ICU or general ward, cause of death, number of family authorizations and refusals, number of actual donors, number of organs transplanted/donor and total number of transplants performed; (ii) for living-kidney-donors (related or altruistic), the number of procedures performed; and (iii) the number of patients registered on the national organ waiting-list. RESULTS: Following the first case (February 2020), deceased organ donation continued uninterrupted. The total number of potential donors was similar to 2019 (181 vs. 189). However, the number of families approached for donation decreased significantly (P = 0.02). This may be attributed to COVID-19-imposed limitations including fewer brain death determinations due to limited possibilities for face-to-face donor coordinator-donor family interactions providing emotional support and visual explanations of the medical situation. Fewer donors were admitted to ICU (P = 0.1) and the number of organs retrieved/donor decreased (3.8/donor to 3.4/donor). The overall result was a decrease of 24.2% in the number of transplant procedures (306 vs. 232). Living kidney donation, initially halted, resumed in May and the total number of procedures increased compared to 2019 due to a significant increase in altruistic donations (P < 0.0001), while the number of related-living donations decreased. CONCLUSION: This study of organ donation during a crisis has informed the introduction of policy changes in the NTC including the necessity to mobilize rapidly a "war room", the use of innovative virtual tools for contact-less communication, and the importance of cooperation with hospital authorities in allocating scarce health-care resources. Finally, the pandemic highlighted and intensified ethical considerations, such as under what circumstances living kidney donation be continued in the face of uncertainty, and what information to provide to altruistic donors regarding a prospective recipient, in particular whether all options for related living donation have been exhausted. These should be addressed now.

Derivation and Implementation of a Protocol in Israel for Organ Donation after Cardio-Circulatory Death.

BACKGROUND: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs). OBJECTIVES: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. METHODS: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded. RESULTS: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6-12 months follow-up. CONCLUSIONS: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

Age limitation for organ transplantation: the Israeli example.

In 2013 the Israeli Ministry of Health appointed a public committee to examine the policy of placing an age limitation on candidates listed for organ transplantation. The committee rejected the use of an age limit criterion for listing candidates for transplantation and recommended to abolish it. However, opinions differed regarding the use of recipients' age in shaping a fair organ allocation policy. The committee's recommendations were adopted and put into force as of April 2014. This article unfolds the committee deliberations on accommodating values of formal equality for optimising the use of organ transplantation.

The midwives ordinance of Palestine, 1929: historical perspectives and current lessons.

Until 1929, midwifery in Palestine was relatively open to anyone and only partially regulated by the 1918 Public Health Ordinance, legislated shortly after the beginning of British rule. This article describes the factors that guided the shaping of midwifery and suggests possible sources of inspiration for the British legislator in crafting the Midwives Ordinance in 1929, including American, local (Jews and Arabs), and British ones. The Midwives Ordinance reflects the adjustment of midwifery to changes in the society that evolved under the British Mandate. The ordinance shows how the modern midwife's role contracted relative to the traditional one, in the context of social processes in other countries, east and west. This historical research project is based on interviews, archive documents and research literature. It analyzes the British interests in regulating midwifery, including the rationale of preserving public health and reducing infant mortality, against a background of political power struggles as well as cultural, social and professional diversity in Palestine (the tensions between the powers of doctors, nurses, and pharmacists).

"That was the beginning": The professionalization and Americanization of dentistry in pre-state Israel.

The history of dental practice in Israel dates back to 1953, with the establishment of the Faculty of Dentistry at the Hebrew University. This article will discuss the early roots of American involvement in Israeli dentistry: beginning with the late Ottoman period in Palestine, through the British Mandate, the establishment of the State of Israel in 1948, and the institution of the Faculty of Dentistry at the Hebrew University of Jerusalem. It will introduce the central characters who promoted the professionalization process of dentistry in Israel--a process made possible by the 'Americanization' of the field: importing American knowledge and practice. Moreover, this article will demonstrate that although the majority of dentists and dental practitioners arrived in Palestine from Russia and from Germany, the main professional influence was American.