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Current and future role of double-lung transplantation for bilateral lung cancer

Technological advances have progressively enhanced the survival rate of lung transplant recipients and expanded its indications for various diseases, including the recent coronavirus disease 2019 (COVID-19). However, according to the International Society for Heart and Lung Transplantation, lung cancer constituted a mere 0.1% of the indications for lung transplantation over the past two decades. This statistic has remained stagnant, and numerous lung cancer patients continue to be excluded from lung transplantation candidacy. Contrary to the general exclusion of lung cancer patients from transplantation, the post-transplant survival rate for these patients is not inferior to that of patients with non-cancerous diseases. Furthermore, lung transplantation may offer curative treatment for patients with bilateral lung cancer whose respiratory insufficiency has advanced independently of cancer progression. This review aims to elucidate and examine the role of double lung transplantation (DLT) in bilateral lung cancer. We summarize the established indications for lung transplantation, appropriate histologic or molecular subtypes of lung cancer for transplantation, technical advances to minimize recurrence, post-DLT survival outcomes for lung cancer patients, and related translational research. We suggest that although DLT for bilateral lung cancer presents challenges, it may be considered a potential treatment option in select circumstances.

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Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review

Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n=2417 patients) and two studies on heart transplant recipients (n=122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11years post kidney transplant; five to 5.7years post heart transplant) and follow-up (ranging from 0.4 to 5.25years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.

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Best practices during COVID-19 pandemic in solid organ transplant programs in Spain

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n=9), peritransplant period (n=7), postransplant period (n=8) and training and communication (n=6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

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Outcomes of live renal donors with a history of nephrolithiasis; A systematic review

The clinical outcomes of kidney donors with a prior history of nephrolithiasis are poorly defined. We conducted a systematic review assessing the post-donation clinical outcomes of kidney donors with a history of nephrolithiasis. Electronic databases (Ovid and Embase) were searched between 1960 and 2021 using key terms and Medical Subject Headings (MeSH) - nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Primary outcome was donor stone-related event. Secondary outcomes were renal function upon follow-up or post-operative nephrectomy complications. In summary, 340 articles were identified through database search. We identified 14 studies (16 cohorts) comprising 432 live donors followed up for a median of 26months post live kidney donation. Six donors donated the stone-free kidney whilst 23 live donors had bilateral stones. Mean stone size was 4.2±1.4mm (1-16) with average follow up duration of 21.1months (1-149). Twelve studies provided primary outcome (n=138 patients) and eight (n=348) for secondary outcomes. One donor had a stone-related event upon follow up. A total of 195 patients had eGFR <60 upon follow up. However, they were not significantly different when compared to renal function of live donors that didn't have pre-donation nephrolithiasis. Many of the studies couldn't provide long term follow up, coupled with limited data regarding the nature of the pre-donation stone disease. In conclusion, this systematic review shows that we have very limited information upon which to base recommendation regarding pre-donation risk of post-donation complications. Longer term follow up is required and lifelong follow up with live donor registries will aid further understanding.

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Outcomes from organ donation following medical assistance in dying: A scoping review

To collate and summarize the current international literature on the transplant recipient outcomes of organs from Medical Assistance in Dying (MAiD) donors, as well as the actual and potential impact of organ donation following MAiD on the donation and transplantation system. The provision of organ donation following MAiD can impact the donation and transplantation system, as well as potential recipients of organs from the MAiD donor, therefore a comprehensive understanding of the potential and actual impact of organ donation after MAiD on the donation and transplantation systems is needed. Scoping review using the JBI framework. We searched for published (MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Academic Search Complete), and unpublished literature (organ donation organization websites worldwide). Included references discussed the actual and potential impact of organ donation following MAiD on the donation and transplantation system. All references were screened, extracted and analysed by two independent reviewers. We included 78 references in this review and our finding were summarized across three categories: (1) Impact in the donor pool: (2) statistics on organ donation following MAiD; and (3) potential and actual impact of MAiD on the donation and transplant system. The potential impact of the MAiD donor on the transplant waiting list is relatively small as this process is still rare, however, due to the current organ shortage worldwide the contribution of this procedure should not be disregarded. Additionally, despite being limited, the existing research provided scanty evidence that organs retrieved from MAiD donors are associated with satisfactory graft function and survival rates and that outcomes from transplant recipients are comparable to those of organs from donation following brain death and may be better than those of organs from other types of donation after circulatory determined death. Still, further studies are required for comprehensive and reliable evidence.

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The short- and long-term outcomes in living-donor liver transplantation using small-for-size graft: A systematic review and meta-analysis

A standard graft-to-recipient weight ratio (GRWR) ≥0.8% is widely accepted in living-donor liver transplantation (LDLT); however, the potential donor pool is expanded to patients adopting small-for-size graft (SFSGs) with GRWR <0.8%. This study aimed to investigate the effect of SFSG on short- and long-term outcomes following LDLT. Electronic databases were searched from January 1995 to January 2022 for studies comparing short- or long-term outcomes between patients with SFSG (GRWR <0.8%, SFSG group) and sufficient volume graft (GRWR ≥0.8%, non-SFSG group). The primary outcomes were one-, three-, and five-year overall survival (OS) and graft survival (GS), while the secondary outcome was postoperative complications. Twenty-four studies comprising 7996 patients were included. In terms of OS, SFSG group had poor three-year OS (HR: 1.48, 95% CI [1.01, 2.15], p=0.04), but there were no significant differences between two groups in one-year OS (HR: 1.50, 95% CI [0.98, 2.29], p=0.06) and five-year OS (HR: 1.40, 95% CI [0.95, 2.08], p=0.02). In GS, there were no significant differences in one-year (HR 1.31, 95% CI [1.00, 1.72], p=0.05), three-year (HR 1.33, 95% CI [0.97, 1.82], p=0.07), and five-year GS (HR 1.17, 95% CI [0.95, 1.44], p=0.13). The SFSG group had comparable postoperative complications, except for a high incidence of vascular complications and small-for-size syndromes. Expanding the potential donor pool in LDLT to SFSG with GRWR <0.8% can be acceptable in terms of comparable long-term OS and GS, despite the risk for vascular complications and small-for-size syndrome.

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Technical challenges in LDLT – Overcoming small for size syndrome and venous outflow reconstruction

Living Donor Liver Transplantation (LDLT) emerged as an alternative treatment option for patients with end-stage liver disease waiting for an organ from a deceased donor. In addition to allowing for a faster access to transplantation, LDLT provides improved recipient outcomes when compared to deceased donor LT. However, it represents a more complex and demanding procedure for the transplant surgeon. In addition to a comprehensive preoperative donor assessment and stringent technical considerations during the donor hepatectomy to ensure upmost donor safety, the recipient procedure also comes with intrinsic challenges during LDLT. A proper approach during both procedures will result in favorable donor and recipient's outcomes. Hence, it is critical for the transplant surgeon to know how to overcome such technical challenges and avoid deleterious complications. One of the most feared complications following LDLT is small-for-size syndrome (SFSS). Although, surgical advances and deeper understanding of the pathophysiology behind SFSS has allowed for a safer implementation of LDLT, there is currently no consensus on the best strategy to prevent or manage this complication. Therefore, we aim to review current practices in technically challenging situations during LDLT, with a particular focus on management of small grafts and venous outflow reconstructions, as they possess one of the biggest technical challenges faced during LDLT.

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