Live-donor kidney transplant outcome prediction (L-TOP) using artificial intelligence.

Outcome prediction for live-donor kidney transplantation improves clinical and patient decisions and donor selection. However, the concurrently used models are of limited discriminative or calibration power and there is a critical need to improve the selection process. We aimed to assess the value of various artificial intelligence (AI) algorithms to improve the risk stratification index. We evaluated pre-transplant variables among 66 914 live-donor kidney transplants (performed between 01/12/2007-01/06/2021) from the United Network of Organ Sharing database, randomized into training (80%) and test (20%) sets. The primary outcome measure was death-censored graft survival. We tested four machine learning models for discrimination (time-dependent concordance index, CTD, and area under the ROC curve) and calibration (integrated Brier score, IBS). We used decision curve analysis to assess the potential clinical utility. Among the models, the deep Cox mixture model showed the best discriminative performance (AUC = 0.70, 0.68, and 0.68 at 5, 10, and 13 years post-transplant, respectively). CTD reached 0.70, 0.67, and 0.66 at 5, 10, and 13 years post-transplant. The IBS score was 0.09, indicating good calibration. In comparison, applying the Living Kidney Donor Profile Index (LKDPI) on the same cohort produced a CTD of 0.56 and an AUC of 0.55-0.58 only. Decision curve analysis showed an additional net benefit compared to the LKDPI, 'Treat all' and 'Treat None' approaches. Our AI-based deep Cox mixture model, termed Live-Donor Kidney Transplant Outcome Prediction outperforms existing prediction models, including the LKDPI, with the potential to improve decisions for optimum live donor selection by ranking potential transplant pairs based on graft survival. This model could be adopted to improve the outcomes of paired exchange programs.

Deceased-Donor Kidney Transplant Outcome Prediction Using Artificial Intelligence to Aid Decision-Making in Kidney Allocation.

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007-2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes.

Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper.

Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries. In India, majority of deceased donations happen following brain death (BD). While existing legislation allows for DCDD, there have been only few reports of kidney transplantation following DCDD from India. This document, prepared by a multidisciplinary group of experts, reviews international best practices in DCDD and outlines the path for DCDD in India. Ethical, medical, legal, economic, procedural, and logistic challenges unique to India have been addressed. The practice of withdrawal of life-sustaining treatment (WLST) in India, laid down by the Supreme Court of India, is time-consuming, possible only in patients in a permanent vegetative state, and too cumbersome for day-to-day practice. In patients where continued medical care is futile, the procedure for WLST is described. In controlled DCDD (category-III), decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Families that are inclined toward organ donation are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. In donation following neurologic determination of death (DNDD), if cardiac arrest occurs during the process of BD declaration, the protocol for DCDD category-IV has been described in detail. In DCDD category-V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the ICU. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and techniques, such as normothermic regional perfusion (nRP) and ex vivo machine perfusion, has been provided. The outcomes of transplantation following DCDD are comparable to those following DBDD or living donor transplantation. Documents and checklists necessary for successful execution of DCDD in India are described. How to cite this article: Seth AK, Mohanka R, Navin S, Gokhale AGK, Sharma A, Kumar A, et al. Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper. Indian J Crit Care Med 2022;26(4):421-438.

Implementation and Experiences of Telehealth: Balancing Policies With Practice in Countries of South Asia, Kuwait, and the European Union.

This viewpoint summarizes the discussion that occurred during the "Translating Policy to Practice in Telehealth-Lessons from Global Implementation Experiences" panel that was held virtually at Telemedicon2020, December 18-20, 2020. This panel brought together policy and implementation experts from some countries of South Asia, Kuwait, and the European Union to share their experiences in the development and implementation of telehealth standards and of the scale up of telehealth interventions within health systems. Several common themes arose from the discussion, including the significant role of people; encouragement by respective government policymakers; addressing concerns, particularly related to privacy, confidentiality, and security; and capacity building of human resources. These are discussed in turn, along with the future directions identified by the panelists, which emphasized the need for active encouragement toward the adoption and diffusion of digital health in general and of telehealth in particular. All stakeholders, ranging from governmental policymakers to common citizens, need to come together to build trusting partnerships to realize the advantages offered by telehealth.

Organ commercialism, trafficking and transplant tourism.

The gap between demand and supply of organs continues to widen worldwide, encouraging transplant commercialism. While solid organ commerce is most prevalent in impoverished countries, commercialisation of body parts such as tissues is prevalent in economically developed countries. A number of international legal instruments and transplant societies define, condemn, and criminalise these practices and have issued statements related to organ commercialism. In contrast, limited attention has been paid to illicit and unethical activities associated with the procurement and clinical use of tissues. In India, The Transplantation of Human Organs (Amendment) Act, 2011, has taken multiple measures to combat organ and tissue commerce and as a result the number of such instances seems to be on the decline. However, the fight against unethical organ procurement through the internet and the social media is challenging and requires the cooperation of global bodies. Keywords: Organ trade, Declaration of Istanbul, tissue commerce, organ transplants, transplant tourism.

NOTTO COVID-19 Vaccine Guidelines for Transplant Recipients.

In December 2019, novel coronavirus (SARS-CoV-2) infection started in Wuhan and resulted in a pandemic within a few weeks' time. Organ transplant recipients being at a risk for more severe COVID-19 if they get SARS CoV-2 viral infection, COVID-19 vaccine has a significant role in these patients. The vaccine is a safer way to help build protection and would either prevent COVID-19 infection or at least diminish the severity of the disease. It would also reduce the risk of the continuing transmission and enhance herd immunity. Immuno-compromised patients should not receive live vaccines as they can cause vaccine-related disease and hence the guidelines suggest that all transplant recipients should receive age-appropriate 'inactivated vaccine' as recommended for general population. Though trials have not been undertaken on transplant recipients, efficacy and safety of COVID-19 vaccine have been scientifically documented for few vaccines among the general population.

Bold policy changes are needed to meet the need for organ transplantation in India.

Twenty-five years after India passed legislation to legalize brain death, deceased donor transplantation remains underdeveloped while the country has established formidable capacity for living donor transplantation. Because of a large number of potential deceased donors, there is hope that deceased donation could help meet India's enormous need for organ transplantation. However, significant policy and practical barriers limit progress. The vast majority of potential deceased donors are poor motor vehicle accident victims who present for care in hospitals without the necessary infrastructure or expertise to support deceased donation. In contrast, transplant infrastructure and expertise are concentrated in private hospitals and are only accessible to those with the ability to pay. Given these realities, the potential of deceased donor transplantation can only be recognized if Indians who are likely to donate organs are also provided access to transplantation. In this viewpoint, we review the current status of organ transplantation in India and propose new policies to establish a national organization to oversee deceased donor services in all states, to fund resources needed to support deceased donation, to leverage the existing living donor infrastructure to advance deceased donor transplantation, and call for establishment of government policy on funding for posttransplant care and immunosuppression.

Benefit to Few Versus Risk to Many: An Ethical Dilemma During Coronavirus Disease 2019 Pandemic for Deceased-Donor Organ Transplant in a Resource-Limited Developing Country.

The tools in our armamentarium to prevent the transmission of coronavirus disease 2019, known as COVID-19, are social distancing; frequent handwashing; use of facial masks; preventing nonessential contacts/travel; nationwide lockdown; and testing, isolation, and contact tracing. However, the World Health Organization's suggestions to isolate, test, treat, and trace contacts are difficult to implement in the resourcelimited developing world. The points to weigh before performing deceased-donor organ transplant in developing countries are as follows: limitations in standard personal protective equipment (as approved by the World Health Organization), testing kits, asymptomatic infections, negative-pressure isolation rooms, intensive care unit beds, ventilator support, telehealth, availability of trained health care workers, hospital beds, the changing dynamic of this pandemic, the unwillingness of recipients, education updates, and additional burdens on the existing health care system. This pandemic has created ethical dilemmas on how to prioritize the use of our facilities, equipment, and supplies in the cash-strapped developing world. We believe that, at the present time, we should aim to resolve the COVID-19 pandemic that is affecting a large sector of the population by diverting efforts from deceased-donor organ transplant. Transplant units should conduct case-bycase evaluations when assessing the convenience of carrying out lifesaving deceased-donor organ transplant, appropriately balanced with the resources needed to address the current pandemic.

Renal Transplant Guidelines with Reference to COVID-19 Infection.

Development of COVID-19 pandemic has affected organ transplant activity significantly. To start with, government of India had adviced stoppage of "elective" surgeries so as to cope with resources and manpower for COVID-19 patients. As majority of hospitals are having both COVID and Non-COVID patients, there is obvious fear of cross-infection. Also, transplant patients being immunocompromised, there is higher risk of acquiring COVID-19 infection along with atypical presentation and unpredicted course of the disease. Result was that across India, elective living related kidney transplant came to a halt. Cadaver renal transplant, being emergency in nature still done, though very few. With passing time, once it became clear that pandemic is not going to be controlled sooner, need has been felt to restart renal transplant activity. Keeping various issues in mind in relation to elective living related renal transplant and emergency deceased donor renal transplant, these guidelines have been framed to help transplant professionals for restarting renal transplant program again in the country, while keeping both health care workers and patient safe.

Heart transplantation in India-looking back as we celebrate 25 years of the transplant law.

India's heart transplantation programme is the number one programme in South Asia with an average heart transplantation rate of 0.2 per million population (pmp) versus the global average of 1.06 pmp (2016-2018). The deceased donation rate was 0.67 pmp in India in 2018. The law which made it possible has completed 25 years. In the first 5 years, after the law was passed, less than 50 hearts had been transplanted. The foundation for the deceased donation programme was laid through the creation of an 'Organ Sharing Network' in the year 2000 by Multi Organ Harvesting Aid Network (MOHAN) Foundation, a non-governmental organisation in Chennai. The role of the Health Department of Tamil Nadu in streamlining the deceased donation process in 2008-2009 changed the course of the programme. The heart transplantation programme evolved due to a handful of committed hospitals from the private sector. The challenge was in the identification and certification of brain death, and this continues to be the main reason for the low donation rate. The referral government hospitals, which usually receive traumatic head injuries that result in brain death, seldom possess the infrastructure or financial autonomy to start a transplant programme. Hence, expensive transplants like heart and liver have catered to the needs of the economically affordable class mostly. To improve the donation rate will require innovative thinking by taking steps such as strengthening the national programme and creating cross-subsidy formulas in organ sharing so that the less affordable too have access to such surgeries. To showcase the success of the programme, it is also imperative to start a heart transplant outcome registry to study the short- and long-term outcomes.

Deceased-Donor Organ Transplantation in India: Current Status, Challenges, and Solutions.

Tamil Nadu, Gujarat, Telangana, Maharashtra, Kerala, Chandigarh, Karnataka, National Capital Territory of Delhi, and Rajasthan are states and union territories having active deceased-donor organ transplant programs in India. Transplant data (2013-2018) have been collected by the National Organ and Tissue Transplant Organization from all states and union territories of India and submitted to the Global Observatory on Donation and Transplantation. From 2013 to 2018, 49155 transplants were reported in India, including 39000 living-donor organ recipients and 10 155 deceased-donor organ recipients. These transplants were for kidney (living donor = 32584, deceased donor = 5748), liver (living donor = 6416, deceased donor = 2967), heart (deceased donor = 895), lung (deceased donor = 459), pancreas (deceased donor = 78), and small bowel (deceased donor = 8). According to 2018 data, India was the second largest transplanting country in the world in terms of the absolute number of transplants. Here, we discuss the status, progress, challenges, and solutions for deceaseddonor organ transplantation. The plan to increase rates of organ donation in India include the following points: teamwork and focus by intensive care unit doctors; public education on organ donation using social media; professional education and family donation conversation programs for brain death declaration and donor management; organ procurement organizations; international collaboration and regular meetings and updates for organizations working in the field of organ transplantation; grief counseling and reporting of potential donation for families of recently deceased people; nonfinancial incentivization to families of potential organ donors; expert committees and standard operating protocols for use of marginal donor organs, donation after circulatory death programs, and machine perfusion; maintenance of transparency and ethics in organ donation, allocation, and transplantation as directed by governmental, nongovernmental, and intergovernmental entities; and regular audit of progress and registry data.

Development of the Asian Transplant Registry Under the Asian Society of Transplantation.

INTRODUCTION: In the Asian region, no international organ transplantation registry exists. Individual centers maintain their own database, or some countries developed a national registration system. To promote collaboration among Asian transplantation societies, the Asian Society of Transplantation (AST) has developed an international transplantation registry for the Asian countries that has been named as the Asian Society Transplant Registry (ASTREG). METHODS: In 2017, the AST council formed a registry committee to develop 2 kinds of databases: ASTREG-N (nationwide level), which collects yearly aggregated data of participating countries, and ASTREG-H (hospital level), which collects the data of transplant recipients and donors from individual centers. RESULTS: ASTREG-N collects each country's aggregate data of solid-organ transplantation, such as the total number of transplantations and deceased donors. ASTREG-H collects 5 transplant domains, namely recipient baseline characteristics, immunosuppression, post-transplant event, annual post-transplant evaluation, and donor traits. For the ASTREG-H project, South Korea, Philippines, Mongolia, and Myanmar are the current participants. A web-based secure data entry platform with real-time data visualization and automated data verification systems is currently available. Any participating centers can run this platform as their own data collection system. CONCLUSION: The ASTREG is a collaborative project that will be the representative solid-organ transplantation database in the Asian region. It can aid in the harmonization of transplantation data in the Asian region.

Management of Ameloblastoma with Free Tissue Flap in Comparison with Other Reconstructive Options Available.

AIM: To review the management and reconstruction of ameloblastoma of mandible in different age groups over a period of 11 years. METHODOLOGY: This retrospective study includes 51 cases operated in the Maxillofacial Unit, Bhagwan Mahaveer Jain Hospital, Bangalore, from the year 2007 to 2017. The data of these patients were collected to record demographic data such as age, gender with site of tumour and type of reconstruction after resection, follow-up period and incidence of complications. This study evaluated the outcome in terms of aesthetics, function and choice of reconstruction in different age groups. RESULTS: Most patients were of 21-40 age group. 37 (72.5%) were found to be unicystic ameloblastoma. 41 (80.3%) patients underwent reconstruction following the resection. There was a change in trend seen over a period of time with free grafts and reconstruction plate being historical, except in special situations like old age and unfit patients. According to one-way ANOVA and Tukey's post hoc analysis, free flaps were known to take a longer duration (mean = 503 min) compared to other modes of reconstruction. However, free grafts and free flaps were demonstrated to have a good facial contour and speech with most cases dentally rehabilitated with implants. Among the complications, 1 (16%) case with reconstruction plate showed screw loosening, 2 (28%) cases with free grafts showed graft exposure, and 1 (3.5%) case with free flap had venous congestion, making free flaps the most reliable option. CONCLUSION: Free fibula is the gold standard of mandible reconstruction, but depending on age, medical condition, economic status and size of the defect other modes of reconstruction can be chosen with the acceptance of suboptimal results.

Redefining Death: Urgent Need to Evolve toward a Homogeneous Definition of Death in India.

The interdependent circulatory-respiratory criteria and brainstem criteria are used to define death. Continuing life-support in brainstem dead patients is a legal conundrum for the health-care professionals and an ethical worry for the society at large. There is an urgent need to revisit this subject to evolve a more uniform definition of death irrespective of the circumstances. A compelling take-home message from this discussion is to spread awareness about brainstem death amongst healthcare professionals. HOW TO CITE THIS ARTICLE: Vadi S, Shroff S. Redefining Death: Urgent Need to Evolve Toward a Homogeneous Definition of Death in India. Indian J Crit Care Med 2019;23(8):368-370.