A study protocol for live and deceased donor uterus transplantation as a treatment for women with uterine factor infertility.

AIM: Uterus transplantation (UTx) is an emerging treatment option for women with uterine factor infertility (UFI) or the absence of a functional uterus. This is the study protocol for the first human UTx clinical trial in Australia. MATERIALS AND METHODS: This protocol outlines the approved training program used to plan, diagnose, screen, and treat patients who may be eligible for UTx using living and deceased donors. This multi-site clinical research study includes three tertiary hospital sites within New South Wales (NSW), Australia - Prince of Wales, Royal Hospital for Women and Westmead Hospitals. Our UTx protocol is based on that used by our collaborative partner, the inaugural UTx team in Gothenburg, Sweden. The Swedish UTx team provides ongoing preceptorship for the Australian UTx team. Ethics approval for six UTx procedures using living or deceased donors (Western Sydney Local Health District Human Research Ethics Committee: 2019/ETH138038) was granted in 2020. RESULTS: Results from surgeries and live births will be published. Data will be prospectively entered into the registry of the International Society of Uterus Transplantation (ISUTx), a sub-section of The Transplantation Society (TTS). TRIAL ID: ACTRN12622000917730. DISCUSSION: A multidisciplinary research team has been formed between three tertiary hospitals in Sydney - The Royal Hospital for Women, Prince of Wales and Westmead Hospitals; and with the Swedish UTx, University of Gothenburg. The Swedish team pioneered animal and human UTx studies since 1998, including publishing the first live birth after UTx. (1) This Australian trial commenced in January 2023. CONCLUSION: Uterus transplantation gives women with UFI the opportunity to be gestational and genetic mothers. It is a complex procedure for both the donor and recipient, with medical and surgical risks. An extensive multidisciplinary approach is required to optimise patient safety and graft outcomes. This protocol outlines our Australian UTx team strategy for screening, recruitment, surgical approach, and clinical management of UTx recipients and donors.

Transmission and Non-transmission of Melanoma From Deceased Solid Organ Donors to Transplant Recipients: Risks and Missed Opportunities.

BACKGROUND: Biovigilance concerns are in tension with the need to increase organ donation. Cancer transmission risk from donor to recipient may be overestimated, as non-transmission events are rarely reported. We sought to estimate melanoma transmission risk in deceased organ donation and identify missed opportunities for donation in an Australian cohort with high melanoma prevalence. METHODS: We used a population-based approach and linked deceased organ donors, transplant recipients, and potential donors forgone, 2010-2018, with the Central Cancer Registry (CCR), 1976-2018. We identified melanomas using ICD-O-3 classification, assessed the probability of transmission, and compared suspected melanoma history in potential donors forgone with melanoma notifications in the CCR. RESULTS: There were 9 of 993 donors with melanoma in CCR; 4 in situ low-risk and 5 invasive high-to-unacceptable risk. Four were unrecognized before donation. Of 16 transplant recipients at risk, we found 0 of 14 transmission events (2 recipients had insufficient follow-up). Of 35 of 3588 potential donors forgone for melanoma risk alone, 17 were otherwise suitable for donation; 6 of 35 had no melanoma in CCR, 2 of 35 had in situ melanomas and 9 of 35 had thin invasive melanomas (localized, ≤0.8 mm thickness). CONCLUSIONS: Our findings contribute to current evidence that suggests donors with melanomas of low metastatic potential may provide an opportunity to safely increase organ donation and so access to transplantation.

Deceased donor availability for uterus transplantation in Australia.

BACKGROUND: Uterus transplantation is an emerging treatment option for uterine factor infertility. Most uterus transplantation research programs use living donors, although this comes with considerable surgical and psychological risks and not all women desiring uterus transplantation will have an available living donor. A deceased donor program eliminates donor risks; however, the availability of deceased uterus donors is currently unknown in Australia. AIMS: To establish the feasibility of a deceased donor uterus transplantation program in Australia and consider expanded inclusion criteria for this model. MATERIALS AND METHODS: A retrospective review of the New South Wales (NSW) Organ and Tissue Donation Service database was undertaken to identify potential deceased uterus donors, with comparison to the broad deceased donor inclusion criteria from three international uterus transplantation trials including female, brain-dead, multi-organ donation, no major abdominal surgery, and <60 years of age. RESULTS: Between January 1, 2018, and December 31, 2022, 648 deceased donors were available in NSW. Of these, 43% (279/648) were female and 67% of the women (187/279) were also multi-organ donors. When the brain-dead donor-only and age criteria (<60 years) were applied, a total of 107 deceased donors met the available criteria for uterus transplantation, with an average of 21 deceased donors per year in NSW. CONCLUSIONS: There appears to be adequate deceased donor organ availability to establish a deceased uterus transplantation program in NSW, Australia. Should interest in uterus transplantation increase, including criteria such as older and nulliparous donors could increase organ availability for a uterus transplantation program.

Organ donation by children in Australia, 2000-2019: impact of the 2009 National Reform Program. A population-based registry data study.

OBJECTIVES: To assess the impact of the 2009 National Reform Program for organ donation in Australia on the number and characteristics of organ donors under 16 years of age. DESIGN, SETTING, PARTICIPANTS: Retrospective observational time series study; analysis of Australia and New Zealand Organ Donation (ANZOD) registry data for all consented potential deceased organ donors under 16 years of age during 2000-2019, and of numbers of donors aged 16 years or more reported in ANZOD annual reports. MAIN OUTCOME MEASURES: Difference between 2000-2008 (pre-reform) and 2009-2019 (reform period) in annual organ donor rates (donors per million population), by age group (under 16 years, 16 years or more), reported as incidence rate ratio (IRR). SECONDARY OUTCOMES: Differences in child donor characteristics during 2000-2008 and 2009-2019. RESULTS: During 2000-2019, 400 children under 16 years of age were consented potential deceased organ donors, of whom 374 were actual deceased donors (94%): 146 during 2000-2008, 228 during 2009-2019. The median annual rate was 3.3 (interquartile range [IQR], 3.0-4.3) actual donors per million population during 2000-2008 and 4.2 (IQR, 3.6-5.2) donors per million population during 2009-2019 (IRR, 1.15; 95% confidence interval [CI], 0.93-1.42). In contrast, the difference between the two periods was statistically significant for donors aged 16 years or more, rising from 11.7 (IQR, 11.2-11.8) to 19.9 (IQR, 18.3-24.4) actual donors per million population (IRR, 1.75; 95% CI, 1.66-1.85). The median age of actual organ donors under 16 was similar during 2000-2008 (11 years; IQR, 7-14 years) and 2009-2019 (10 years; IQR, 4-14 years), as was the proportion of donors in this age group under 10 kg (2000-2008: four of 146, 3%; 2009-2019: 14 of 228, 6%). CONCLUSIONS: Despite its overall effect on organ donation rates, the National Reform Program was not effective in increasing the numbers of donors under 16 years of age. Relying on broad initiatives for adult donors may not be appropriate for achieving this aim.

A 12-Year Audit of Neurological Outcomes Associated with Core Body Temperature >37.5°C in Children with Severe Traumatic Brain Injury.

Hyperthermia exposure is associated with poor neurological outcomes in patients with severe traumatic brain injury (TBI). Our aim was to describe fever in children with severe TBI admitted to a pediatric intensive care unit (PICU) for at least 72 hours and to evaluate associations between fever using a novel approach to describe thermal exposure and neurobehavioral outcomes. The cohort included children from birth to 17 years of age admitted to the PICU between 2000 and 2012 for at least 72 hours who had severe TBI with intracranial pressure monitoring. Patients with non-accidental TBI or pre-existing developmental delays were excluded. Hyperthermia was defined as a core temperature >37.5°C. Hourly temperature measurements were used to calculate the area under the curve (AUC) using the linear trapezoidal rule. Each participant was followed up at the Brain Injury Clinic 6 and 18 months postinjury. Neurobehavioral outcome scores were analyzed against AUC using standard statistical methods. Ninety-eight patients admitted with severe TBI met the study inclusion criteria. Hyperthermia/fever was common (89.7%), and patients remained hyperthermic for a median of 9.4 hours. However, no statistically significant association was found between AUC and abnormal neurological outcomes. The follow-up rates were good at 6 (86.7%) and 18 months (83.7%). The neurological deficit improved with time, with "favorable outcomes" increasing from 72% to 94% at the respective follow-up months. Our study used a novel method to describe patients' fever, providing a different indicator of thermal exposure than that previously reported. In addition, the AUC was well correlated with the maximum temperature recorded and the proportion of time >37.5°C, indicating that it is a good surrogate for thermal exposure. Interestingly, the neurological disabilities of the patients improved over time.

Transplant Outcomes From Deceased Donors Dying With Burns Injury, a Systematic Review.

AIM: The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation. METHODS: Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively. RESULTS: Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes. CONCLUSION: A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.

Paediatric acute respiratory distress syndrome: consider the role of lymphatics.

We present a case of a 7-day-old male infant with severe respiratory disease requiring venoarterial extracorporeal membrane oxygenation therapy with evidence of lymphangiectasia on lung biopsy. Differentiating primary versus secondary lymphangiectasis in this patient remains a riddle despite extensive investigations including an infective screen, lung biopsy and whole-genome sequencing. In addition to the standard therapies used in paediatric acute respiratory distress syndrome, such as lung-protective ventilation, permissive hypoxaemia and hypercarbia, nursing in the prone position, early use of muscle relaxants, rescue intravenous corticosteroids and broad-spectrum antibiotics, the patient was also given octreotide despite the absence of a chylothorax based on the theoretical benefit of altering the lymphatic flow. His case raises an interesting discussion around the role of lymphatics in the pathophysiology of paediatric and adult respiratory distress syndrome and prompts the exploration of novel agents which may affect lymphatic vessels used as an adjunctive therapy.

Characteristics and Donation Outcomes of Potential Organ Donors Perceived to Be at Increased Risk for Blood-borne Virus Transmission: An Australian Cohort Study 2010-2018.

BACKGROUND: Safely increasing organ donation to meet need is a priority. Potential donors may be declined because of perceived blood-borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS: We conducted a cohort study of all potential organ donors referred in NSW, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B, and/or behavioral risk factors. RESULTS: There were 624 of 5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298 of 5749 (5.2%) with HCV (including HBV coinfections) and 239 of 5749 (4.2%) with increased risk behaviors (no known BBV). Potential donors with HCV and those with increased risk behaviors were younger and had fewer comorbidities than baseline risk potential donors (P < 0.001). Many potential donors (82 with HCV, 38 with risk behaviors) were declined for donation purely because of perceived BBV transmission risk. Most were excluded before BBV testing. When potential donors with HCV did donate, they donated fewer organs than baseline risk donors (median 1 versus 3, P < 0.01), especially kidneys (odds ratio 0.08, P < 0.001) and lungs (odds ratio 0.11, P = 0.006). CONCLUSIONS: Many potential donors were not accepted because of perceived increased BBV transmission risk, without viral testing, and despite otherwise favorable characteristics. Transplantation could be increased from potential donors with HCV and/or increased risk behaviors.

Paediatric kidney transplants from donors aged 1 year and under: an analysis of the Australian and New Zealand Dialysis and Transplant Registry from 1963 to 2018.

Kidneys from very small donors have the potential to significantly expand the donor pool. We describe the collective experience of transplantation using kidneys from donors aged ≤1 year in Australian and New Zealand. The ANZDATA registry was analysed on all deceased donor kidney transplants from donors aged ≤1 year. We compared recipient characteristics and outcomes between 1963-1999 and 2000-2018. From 1963 to 1999, 16 transplants were performed [9 (56%) adults, 7 (44%) children]. Death-censored graft survival was 50% and 43% at 1 and 5 years, respectively. Patient survival was 90% and 87% at 1 and 5 years, respectively. From 2000 to 2018, 26 transplants were performed [25 (96%) adults, 1 (4%) children]. Mean creatinine was 73 µmol/l ±49.1 at 5 years. Death-censored graft survival was 85% at 1 and 5 years. Patient survival was 100% at 1 and 5 years. Thrombosis was the cause of graft loss in 12% of recipients in the first era from 1963 to 1999, and 8% of recipients in the second era from 2000 to 2018. We advocate the judicious use of these small paediatric grafts from donors ≤1 year old. Optimal selection of donor and recipients may lead to greater acceptance and success of transplantation from very young donors.

New blood-borne virus infections among organ transplant recipients: An Australian data-linked cohort study examining donor transmissions and other HIV, hepatitis C and hepatitis B notifications, 2000-2015.

BACKGROUND: Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. METHODS: We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. RESULTS: Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. CONCLUSION: This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.

Conflicts of interest in the context of end of life care for potential organ donors in Australia.

End-of-life (EOL) care has become an integral part of intensive care medicine and includes the exploration of possibilities for deceased organ and tissue donation. Donation physicians are specialist doctors with expertise in EOL processes encompassing organ and tissue donation, who contribute significantly to improvements in organ and tissue donation services in many countries around the world. Donation physicians are usually also intensive care physicians, and thus they may be faced with the dual obligation of caring for dying patients and their families in the intensive care unit (ICU), whilst at the same time ensuring organ and tissue donation is considered according to best practice. This dual obligation poses specific ethical challenges that need to be carefully understood by clinicians, institutions and health care networks. These obligations are complementary and provide a unique skillset to care for dying patients and their families in the ICU. In this paper we review current controversies around EOL care in the ICU, including the use of palliative analgesia and sedation specifically with regards to withdrawal of cardiorespiratory support, the usefulness of the so-called doctrine of double effect to guide ethical decision-making, and the management of potential or perceived conflicts of interest in the context of dual professional roles.

Effect of language and country of birth on the consent process and medical suitability of potential organ donors; a linked-data cohort study 2010-2015.

PURPOSE: Australia has unmet need for transplantation. We sought to assess the impact of cultural and linguistic diversity (CALD) on family consent and medical suitability for organ donation. METHOD: Cohort study of New South Wales donor referrals, 2010-2015. Logistic regression estimated effects of primary language other than English and birthplace outside Australia (odds ratios OR, with 95% confidence intervals, 95%CI). Outcomes were whether families were asked for consent to donation, provided consent for donation, and whether the referral was medically suitable for donation. RESULTS: Of 2977 organ donor referrals, a similar proportion of families had consent for donation was sought between non-English speakers and English speakers (p = .07), and between overseas-born compared to Australian-born referrals (p = .3). However, consent was less likely to be given for both non-English speakers than English speakers (OR 0.44, 95%CI:0.29-0.67), and those overseas-born than Australian-born (OR 0.54, 95%CI:0.41-0.72). For referrals both overseas-born and non-English speaking, families were both less likely to be asked for consent (OR 0.67; 95%CI:0.49-0.91) or give consent (OR 0.24; 95%CI0.16-0.37). There was no difference in medical suitability between English speakers and non-English speakers (p = .6), or between Australian-born and overseas-born referrals (p = .6). CONCLUSION: Intervention to improve consent rates from CALD families may increase donation.

Weekend effect: analysing temporal trends in solid organ donation.

BACKGROUND: Research suggests patients treated over weekends experience poorer outcomes. Only one US-based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia. METHODS: We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals. RESULTS: Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted. CONCLUSIONS: In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA.

Communication with Families Regarding Organ and Tissue Donation after Death in Intensive Care (COMFORT): a multicentre before-and-after study.

OBJECTIVE: To implement a best-practice intervention offering deceased organ donation, testing whether it increased family consent rates. DESIGN: A multicentre before-and-after study of a prospective cohort compared with pre-intervention controls. SETTING: Nine Australian intensive care units. PARTICIPANTS: Families and health care professionals caring for donor-eligible patients without registered donation preferences or aged ≤ 16 years. INTERVENTION: A multicomponent intervention including offers of deceased organ donation from specially trained designated requesters using a structured conversation separate to end-of-life discussions. MAIN OUTCOME MEASURE: Proportion of families consenting to organ donation. RESULTS: Consent was obtained in 87/164 cases (53%) during the intervention period compared with 14/25 cases (56%) pre-intervention (P = 0.83). The odds ratio (OR) of obtaining consent during the intervention period relative to preintervention was 1.13 (95% CI, 0.48-2.63; P = 0.78). During the intervention period, designated requesters obtained consent in 55/98 cases (56%), compared with 32/66 cases (48%) in which the medical team managing patient care raised donation (P = 0.34). Factors independently associated with increased consent were: family-raised organ donation (OR, 4.34; 95% CI, 1.79-10.52; P = 0.001), presence of an independent designated requester (OR, 3.84; 95% CI, 1.35- 10.98; P = 0.012), and multiple donation conversations per case (OR, 3.35; 95% CI, 1.93-5.81; P < 0.001). Consent decreased when patients were of non-Christian religion (OR, 0.18; 95% CI, 0.04-0.91; P = 0.038) and end-of-life and donation meetings were separate (OR, 0.38; 95% CI, 0.16-0.89; P = 0.026). CONCLUSION: Implementation of a multicomponent intervention did not increase consent rates for organ donation, although some components of the intervention exerted significant effect. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000815763. ClinicalTrials.gov: NCT01922310.

Patterns of organ donation in children in Australia and New Zealand.

OBJECTIVES: Paediatric organ donation (OD) represents a small proportion of total OD in Australia and New Zealand. Our aim was to describe the patterns of paediatric OD, specifically, the demographic characteristics and donation outcomes over two time periods. DESIGN: We performed a retrospective study using national OD and intensive care registry data from intensive care units in Australia and New Zealand from 1 January 2000 to 31 December 2015. Data were analysed between two time periods. Paediatric data were compared with adult data. PARTICIPANTS: Organ donors aged under 16 years in paediatric and mixed adult and paediatric ICUs. RESULTS: There were 267 paediatric organ donors, representing 5.4% of all donors. The rate of OD as a percentage of ICU deaths was comparable to adults (6.0% v 4.6%; P < 0.001). Over the entire period, donations after brain death totalled 244 (91.4%), and donations after circulatory death (DCDs) totalled 23 (8.6%). DCDs increased from 0.7% to 17% between the time periods (P < 0.001). Children aged under 2 years had a lower rate of donation than the general paediatric cohort (1.2% v 6.0%; P < 0.001). CONCLUSIONS: Paediatric OD rates have not changed over time but are comparable to adults when expressed as a percentage of ICU deaths. Paediatric DCD has increased significantly over time.

COMmunication with Families regarding ORgan and Tissue donation after death in intensive care (COMFORT): protocol for an intervention study.

BACKGROUND: Discussing deceased organ donation can be difficult not only for families but for health professionals who initiate and manage the conversations. It is well recognised that the methods of communication and communication skills of health professionals are key influences on decisions made by families regarding organ donation. METHODS: This multicentre study is being performed in nine intensive care units with follow-up conducted by the Organ and Tissue Donation Service in New South Wales (NSW) Australia. The control condition is pre-intervention usual practice for at least six months before each site implements the intervention. The COMFORT intervention consists of six elements: family conversations regarding offers for organ donation to be led by a "designated requester"; family offers for donation are deferred to the designated requester; the offer of donation is separated from the end-of-life discussion that death is inevitable; it takes place within a structured family donation conversation using a "balanced" approach. Designated requesters may be intensivists, critical care nurses or social workers prepared by attending the three-day national "Family Donation Conversation" workshops, and the half-day NSW Simulation Program. The design is pre-post intervention to compare rates of family consent for organ donation six months before and under the intervention. Each ICU crosses from using the control to intervention condition after the site initiation visit. The primary endpoint is the consent rate for deceased organ donation calculated from 140 eligible next of kin families. Secondary endpoints are health professionals' adherence rates to core elements of the intervention; identification of predictors of family donation decision; and the proportion of families who regret their final donation decision at 90 days. DISCUSSION: The pragmatic design of this study may identify 'what works' in usual clinical settings when requesting organ donation in critical care areas, both in terms of changes in practice healthcare professionals are willing and able to adopt, and the effect this may have on desired outcomes. The findings of this study will be indicative of the potential benefits of the intervention and be relevant and transferrable to clinical settings in other states and countries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000815763 (24 July 2013). ClinicalTrials.gov: NCT01922310 (14 August 2013) (retrospectively registered).