UNASSIGNED: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients.
UNASSIGNED: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported.
UNASSIGNED: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.

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BACKGROUND: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.
METHODS: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients. By utilizing an immunogenic skin transplant model and existing transplantation medicine reagents, we facilitated the clinical translation of our findings. Specifically, antigen-specific Tregs were used.
RESULTS: Our study demonstrated that combining the available induction therapies with drug-induced T-cell proliferation due to lymphopenia effectively increased the Treg/T effector ratios. This results in significant Treg accumulation within the graft, leading to long-term tolerance after the transfer of antigen-specific Tregs. Importantly, all the animals achieved operational tolerance, which boosted the presence of adoptively transferred Tregs within the graft.
CONCLUSIONS: This protocol offers a means to establish tolerance by utilizing antigen-specific Tregs. These results have promising implications for future trials involving adoptive Treg therapy in organ transplantation.

BACKGROUND: Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia.
METHODS: Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life.
CONCLUSIONS: This study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy.
BACKGROUND: ClinicalTrials.gov NCT05556720. Registered on 23rd August 2022.

Mitochondrial dynamics are central to the pathophysiology of cellular damage and inflammatory responses. In the context of solid organ transplantation, mitochondria are implicated in immune activation in donor organs that occurs after brain death, as they are critical to the regulation of cellular stress response, cell death, and display energetic adaptations through the adjustment of respiratory capacity depending on the cellular milieu. Mitochondrial damage activates mitochondrial systems of fission, fusion, biogenesis, and mitochondrial autophagy, or mitophagy. The mechanistic pathways as well as therapies targeting mitochondrial physiology have been studied as plausible ways to mitigate the negative effects of brain death on donor organs, though there is no summative evaluation of the multiple efforts across the field. This mini-review aims to discuss the interplay of donor brain death, mitochondrial dynamics, and impact on allograft function as it pertains to heart, lung, liver, and kidney transplants.

Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients\' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called \"bottom-up\" proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, \"Top-down\" proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT.

UNASSIGNED: We sought to understand how safety culture may evolve during disruption, by using the COVID-19 pandemic as an example, to identify vulnerabilities in the system that could impact patient outcomes.
UNASSIGNED: A cross-sectional analysis of transplant personnel at a high-volume transplant center was conducted using the Safety Attitudes Questionnaire (SAQ). Survey responses were scaled and evaluated pre- and post-COVID-19 (2019 and 2021).
UNASSIGNED: Two-hundred and thirty-eight responses were collected (134 pre-pandemic and 104 post-pandemic). Represented organ groups included: kidney (N = 89;38%), heart (N = 18;8%), liver (N = 54;23%), multiple (N = 66;28%), and other (N = 10;4%). Responders primarily included nurses (N = 75;34%), administration (N = 50;23%), and physicians (N = 24;11%). Workers had high safety, job satisfaction, stress recognition, and working conditions satisfaction (score >75) both before and after the pandemic with overlapping responses across both timepoints. Stress recognition, safety, and working conditions improved post-COVID-19, but teamwork, job satisfaction, and perceptions of management were somewhat negatively impacted (all p > 0.05).
UNASSIGNED: Despite the serious health care disruptions induced by the pandemic, high domain ratings were notable and largely maintained in a high-volume transplant center. The SAQ is a valuable tool for healthcare units and can be used in longitudinal assessments of transplant culture of safety as a component of quality assurance and performance improvement initiatives.

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We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.