BMWi funded the MACSS (Medical Allround-Care Service Solutions) as part of the funding project &#34;Smart Service World&#34;. In addition, the H2020 EU project &#34;BigMedilytics&#34; as well as the health insurance companies AOK Nordost and Techniker Krankenkasse are supporting the project.

The protocol follows the current guidelines of the ethics and data protection committees at Charit&#233; - Universit&#228;tsmedizin Berlin and is in compliance with current EU GDPR.
1. Perspective of the telemedicine team
<ol>
	<li>Screening for patients 
	NOTE: Key data of the project are provided in Table 1.
	<ol>
		<li>Ask the nurse to screen incoming outpatients or patients on the ward for eligibility. Ask the telemedicine team (nurse and physician) to talk to patients in the outpatient clinic or on the ward about the content, data protection, and aim of the project.</li>
		<li>After agreeing, ensure that the patients provide written consent. Ensure that the nurse documents refusals and reasons for not participating and checks again with patients who need time for consideration.</li>
	</ol>
	</li>
	<li>Role of the nurse in the patient onboarding process
	<ol>
		<li>Ask the patient to show his/her smartphone and support the patient in downloading the app from Apple Store or Play Store. 
		&#8203;NOTE: If the patient does not own an adequate smartphone, the telemedicine team provides a smartphone for the time of participation.</li>
		<li>Search for the patient in the transplant database (TBase).
		<ol>
			<li>Click on the Onboarding into MACCS project button. Ensure that the patient registers on the registration web page with the initial login data automatically created by the transplant database.</li>
			<li>Ask the patient to create new login data and digitally confirm consent when redirected to the consent page. Ensure that the patient logs out of the registration page after the platform establishes a safe connection between the patient app and transplant EHR (TBase).</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Patient training by the nurse
	<ol>
		<li>Show where to find laboratory values and how these are presented; how to find the text messaging function and how to send a message; how to start a video consultation; how to find a medication plan and how to confirm medication intake; and check the current medication plan for correctness. 
		&#8203;NOTE: The current medication plan is transferred to the app automatically once the connection is established.</li>
		<li>Demonstrate how to submit vital signs, blood sugar, well-being status, and confirm or decline medication intake. Train the patient how to take the immunosuppressive drugs correctly, and how to measure the heart rate and blood pressure correctly.</li>
		<li>Set the patient&#39;s current body weight in the telemedicine dashboard by clicking on the Therapeutic Plan button, fill in Weight in kg, and click on Confirm Data.</li>
		<li>Define the therapeutic plan for home measurements with the patient and fill out the Frequency table in TBase. 
		NOTE: The individual adherence plan is one part of adherence calculation and is documented in the dashboard.</li>
		<li>Discuss with the patients when to contact them in to remind them to forward data; encourage the patients to always call in case of medical or technical problems. Explain the working hours of the telemedicine team, morning hotline for urgent issues, and what to do in case of medical problems or emergencies during and after the regular working hours of the telemedicine team.</li>
		<li>Check whether data have been received the next day, and call patients to explain that the data have arrived and ask about any technical issues they may have faced.</li>
	</ol>
	</li>
	<li>Daily routine of the telemedicine team 
	NOTE: Monday to Friday from 8 a.m. to 4 p.m. (Table 2). Outside regular working hours, the nephrologist-on-call has full access to the transplant database and the telemedicine dashboard. The telemedicine team consists of at least one experienced nurse for every 300 patients, and at least one experienced medical doctor for every 600 patients. One medical doctor is always on duty (Table 1). Currently, the telemedicine team consists of two nurses, three junior physicians, and four senior nephrologists.
	<ol>
		<li>Daily routine of the nurses
		<ol>
			<li>Start the day with a structured process in reviewing incoming vital signs in the telemedicine dashboard (Table 3). Filter patients according to their critical values as defined in Table 4 and, if necessary, call the patient or discuss the case with a physician from the telemedicine team.</li>
			<li>Review well-being data. Call patients if the well-being score is low or if it decreases by more than 2 points. Consult a physician of the telemedicine team if the reason for the decrease in well-being is critical. Review less critical, but suspicious values and, if necessary, discuss these cases with a physician from the telemedicine team.</li>
			<li>Control incoming medical messages and take action, if necessary. Document all calls and activities in the telemedicine dashboard chart.</li>
			<li>Identify patients who did not document data in the app as previously agreed. Call the patients and ask about potential technical problems as the reason for the missing data. If technical data transmission is working, remind the patient to regularly forward data as agreed.</li>
			<li>Answer incoming calls (on medical and technical questions) from patients and local nephrologists. Ask patients at regular intervals about satisfaction with the telemedicine service and usability of the app, and document this information, which is forwarded to the development team for evaluation and continuous improvement.</li>
		</ol>
		</li>
		<li>Routine of the physicians on duty in the telemedicine center
		<ol>
			<li>Review reports from the nurses on critical values, e.g., high blood pressure (acute onset or over longer periods). Contact the senior nephrologist of the transplant team, or the physician who saw the patient during the last inpatient stay in severe cases.</li>
			<li>Call the patient, take medical history, and give advice, e.g., how to measure the blood pressure correctly or advise on other medical problems. Follow the patient closely over the next days if a change of medication or an unclear situation has occurred.</li>
			<li>In severe cases, advise the patient to contact the local nephrologist for a visit, to go to the next emergency room, or to come to the kidney transplant center for follow-up.</li>
			<li>Contact the local nephrologist or emergency room upfront, if needed. Update the senior nephrologist at regular intervals and have a daily brief consultation with the team in the kidney transplant center on problematic cases. Document all contacts and activities in the telemedicine dashboard. 
			&#8203;NOTE: All physicians and nurses in the regular transplant service have full access to the transplant database, including all data in the telemedicine dashboard.</li>
			<li>Review reports from the nurse on non-adherent patients, analyze the type of non-adherence, and determine a procedure to improve adherence, together with the regular transplant team or local nephrologist. Aim to strengthen adherence through advice and telephone calls or video consultations.</li>
			<li>Contact a psychologist for behavior therapy to strengthen adherence, if necessary. Follow patients with documented non-adherence more closely. Provide regular feedback to the senior nephrologist and development team.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
2. Perspective of local nephrologists
<ol>
	<li>Training of local nephrologists by the telemedicine team
	<ol>
		<li>Inform the local nephrologists about the project through letters, events, and congresses and offer central training courses and video courses.</li>
		<li>Make an appointment with local nephrologists for a training and onboarding visit. During the visit, explain the project in detail to the physicians and nurses, discuss data protection, and answer questions.</li>
		<li>Explain the contract to local nephrologists, who sign the contract with the transplant center with specified terms and conditions. Explain the technical onboarding process in detail, and provide assistance and documents on how to include patients in the project.</li>
	</ol>
	</li>
	<li>Onboarding process of patients by local nephrologists using the software system (Table of Materials) 
	&#8203;NOTE: Through a general update, all software users have the option to participate, and the current software version has a built-in functionality for a secure connection to the FHIR server.
	<ol>
		<li>Select the patient participant in the software. Click on the MACCS button; after the local software opens an overlay window, click on Connect. 
		NOTE: The local nephrologist can only include patients who are already participating and have gone through the onboarding process at the transplant center.</li>
		<li>After the local software generates login data (code and QR code), ask the patients to scan the QR code with their smartphones (or enter the code manually) and complete the onboarding process by clicking on the Data Sharing button to indicate agreement. 
		NOTE: The platform now enables an automatic data exchange of pseudonymized data with the transplant center and the patient app.</li>
		<li>Review the data transferred from the transplant center in the local software system.</li>
	</ol>
	</li>
	<li>Interaction of the local nephrologists with the telemedicine team
	<ol>
		<li>Call the telemedicine team if medical or technical problems occur. Ask the transplant center (including the transplant pathologist and senior transplant nephrologist) for telemedicine consultation to discuss the best therapy for the patient, if necessary.</li>
		<li>Attend a (virtual) training session, workshop, or onsite presentation.</li>
	</ol>
	</li>
</ol>
3. Perspective of patients
<ol>
	<li>Onboarding process 
	&#8203;NOTE: Onboarding of patients will take place with the help of the telemedicine team after explanation of the additional services of the project, data protection, and right to withdraw at any time.
	<ol>
		<li>Listen to the telemedicine team and ask questions. Give signed consent and download the app with the help of the nurse.</li>
		<li>After receiving the initial login data from the nurse, change the login data, and confirm participation digitally. Enter the new login data into the app and push Sign in. After the app opens, enter the well-being status, and click on the Send button. Observe the buzzing sound and the confirmation sign (green banner showing Feedback sent).</li>
		<li>Measure the blood pressure, enter the data into the app, and push the Send button. Observe the buzzing sound and the green banner pop-up showing Vital Data Sent. Look at the Show History list and observe the table with all the values and transmission information.</li>
		<li>Open the Communication page and send a text message to the nurse. Start a video session by clicking on the Video button. Open the Lab Results page and look at recent laboratory data. Open the Medication page, scroll through the medication plan, and confirm medication intake. Set the alert function for timely medication intake.</li>
		<li>After the nurse explains how the medication plan can be forwarded and printed out, log out of the app.</li>
	</ol>
	</li>
	<li>Use of the app by patients at home
	<ol>
		<li>Open the app and enter the vital signs. Look at laboratory values, medication plan, and confirm medication intake.</li>
		<li>Send a text message and perform a video consultation. Enter login data in the registration page and look at the consent page, where consent was given for data transfer to the local nephrologist, and where consent can be easily withdrawn.</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Kramer, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+European+Renal+Association+-+European+Dialysis+and+Transplant+Association+(ERA-EDTA)+Registry+Annual+Report+2015:+a+summary.">The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary.</a> Clinical Kidney Journal. 11 (1), 108-122 (2018).</li><li>Haller, M., Gutjahr, G., Kramar, R., Harnoncourt, F., Oberbauer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cost-effectiveness+analysis+of+renal+replacement+therapy+in+Austria.">Cost-effectiveness analysis of renal replacement therapy in Austria.</a> Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association - European Renal Association. 26 (9), 2988-2995 (2011).</li><li>Quality of life (healthcare). Wikipedia, The Free Encyclopedia Available from: <a target="_blank" href="https://en.wikipedia.org/wiki/Quality_of_life_(healthcare)">https://en.wikipedia.org/wiki/Quality_of_life_(healthcare)</a> (2020)</li><li>Sautenet, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developing+consensus-based+priority+outcome+domains+for+trials+in+kidney+transplantation:+a+multinational+delphi+survey+with+patients,+caregivers,+and+health+professionals.">Developing consensus-based priority outcome domains for trials in kidney transplantation: a multinational delphi survey with patients, caregivers, and health professionals.</a> Transplantation. 101 (8), 1875-1886 (2017).</li><li>Tong, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+establishing+core+outcome+domains+for+trials+in+kidney+transplantation:+report+of+the+standardized+outcomes+in+nephrology-kidney+transplantation+consensus+workshops.">Toward establishing core outcome domains for trials in kidney transplantation: report of the standardized outcomes in nephrology-kidney transplantation consensus workshops.</a> Transplantation. 101 (8), 1887-1896 (2017).</li><li>De Geest, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence,+determinants,+and+consequences+of+subclinical+noncompliance+with+immunosuppressive+therapy+in+renal+transplant+recipients.">Incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in renal transplant recipients.</a> Transplantation. 59 (3), 340-347 (1995).</li><li>Posadas Salas, M. A., Srinivas, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Update+on+the+clinical+utility+of+once-daily+tacrolimus+in+the+management+of+transplantation.">Update on the clinical utility of once-daily tacrolimus in the management of transplantation.</a> Drug Design, Development and Therapy. 8, 1183-1194 (2014).</li><li>Haynes, R. B., McDonald, H., Garg, A. X., Montague, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventions+for+helping+patients+to+follow+prescriptions+for+medications.">Interventions for helping patients to follow prescriptions for medications.</a> The Cochrane Database of Systematic Reviews. (2), (2002).</li><li>Fine, R. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonadherence+consensus+conference+summary+report.">Nonadherence consensus conference summary report.</a> American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 9 (1), 35-41 (2009).</li><li>Neuberger, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Practical+recommendations+for+long-term+management+of+modifiable+risks+in+kidney+and+liver+transplant+recipients:+a+guidance+report+and+clinical+checklist+by+the+Consensus+on+Managing+Modifiable+Risk+in+Transplantation+(COMMIT)+group.">Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) group.</a> Transplantation. 101 (4), 1-56 (2017).</li><li>Gordon, E. J., Gallant, M., Sehgal, A. R., Conti, D., Siminoff, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medication-taking+among+adult+renal+transplant+recipients:+barriers+and+strategies.">Medication-taking among adult renal transplant recipients: barriers and strategies.</a> Transplant International: Official Journal of the European Society for Organ Transplantation. 22 (5), 534-545 (2009).</li><li>Zanetti-Yabur, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploring+the+usage+of+a+mobile+phone+application+in+transplanted+patients+to+encourage+medication+compliance+and+education.">Exploring the usage of a mobile phone application in transplanted patients to encourage medication compliance and education.</a> American Journal of Surgery. 214 (4), 743-747 (2017).</li><li>Shellmer, D. A., Dew, M. A., Mazariegos, G., DeVito Dabbs, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+field+testing+of+Teen+Pocket+PATH((R)),+a+mobile+health+application+to+improve+medication+adherence+in+adolescent+solid+organ+recipients.">Development and field testing of Teen Pocket PATH((R)), a mobile health application to improve medication adherence in adolescent solid organ recipients.</a> Pediatric Transplantation. 20 (1), 130-140 (2016).</li><li>Trnka, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+retrospective+review+of+telehealth+services+for+children+referred+to+a+paediatric+nephrologist.">A retrospective review of telehealth services for children referred to a paediatric nephrologist.</a> BMC Nephrology. 16, 125 (2015).</li><li>Andrew, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Telehealth+model+of+care+for+routine+follow+up+of+renal+transplant+recipients+in+a+tertiary+centre:+A+case+study.">Telehealth model of care for routine follow up of renal transplant recipients in a tertiary centre: A case study.</a> Journal of Telemedicine and Telecare. 26 (4), 232-238 (2020).</li><li>Duettmann, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digital+management+after+kidney+transplantation:+What+is+MACCS.">Digital management after kidney transplantation: What is MACCS.</a> Kidney and Hypertension Diseases. 49 (2020), 7 (2020).</li><li>Duettmann, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=eHealth+in+transplantation.">eHealth in transplantation.</a> Transplant International: Official Journal of the European Society for Organ Transplantation. , (2020).</li><li>Koehler, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+of+telemedical+interventional+management+in+patients+with+heart+failure+(TIM-HF2):+a+randomised,+controlled,+parallel-group,+unmasked+trial.">Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.</a> Lancet. 392 (10152), 1047-1057 (2018).</li><li>Lee, T. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Telemedicine+based+remote+home+monitoring+after+liver+transplantation:+results+of+a+randomized+prospective+trial.">Telemedicine based remote home monitoring after liver transplantation: results of a randomized prospective trial.</a> Annals of Surgery. 270 (3), 564-572 (2019).</li><li>Kaier, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Results+of+a+randomized+controlled+trial+analyzing+telemedically+supported+case+management+in+the+first+year+after+living+donor+kidney+transplantation+-+a+budget+impact+analysis+from+the+healthcare+perspective.">Results of a randomized controlled trial analyzing telemedically supported case management in the first year after living donor kidney transplantation - a budget impact analysis from the healthcare perspective.</a> Health Economics Review. 7 (1), 1 (2017).</li><li>Schmid, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Telemedically+supported+case+management+of+living-donor+renal+transplant+recipients+to+optimize+routine+evidence-based+aftercare:+a+single-center+randomized+controlled+trial.">Telemedically supported case management of living-donor renal transplant recipients to optimize routine evidence-based aftercare: a single-center randomized controlled trial.</a> American journal of transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 17 (6), 1594-1605 (2017).</li><li>Duettmann, W. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+main+diagnoses+of+kidney+transplant+recipients+and+DRG-costs+in+German+health+care+system.">Evaluation of main diagnoses of kidney transplant recipients and DRG-costs in German health care system.</a> Nephrology Dialysis Transplantation. 34, (2019).</li><li>DeVito Dabbs, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomized+controlled+trial+of+a+mobile+health+intervention+to+promote+self-management+after+lung+transplantation.">A randomized controlled trial of a mobile health intervention to promote self-management after lung transplantation.</a> American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 16 (7), 2172-2180 (2016).</li><li>Han, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mobile+medication+manager+application+to+improve+adherence+with+immunosuppressive+therapy+in+renal+transplant+recipients:+A+randomized+controlled+trial.">Mobile medication manager application to improve adherence with immunosuppressive therapy in renal transplant recipients: A randomized controlled trial.</a> PloS One. 14 (11), 0224595 (2019).</li><li>Schmidt, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TBase+-+an+Integrated+Electronic+Health+Record+and+Research+Database+for+Kidney+Transplant+Recipients.">TBase - an Integrated Electronic Health Record and Research Database for Kidney Transplant Recipients.</a> J. Vis. Exp. , e61971 (2021).</li><li>Jiang, Y., Sereika, S. M., DeVito Dabbs, A., Handler, S. M., Schlenk, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+mobile+health+technology+to+deliver+decision+support+for+self-monitoring+after+lung+transplantation.">Using mobile health technology to deliver decision support for self-monitoring after lung transplantation.</a> International Journal of Medical Informatics. 94, 164-171 (2016).</li><li>Rosenberger, E. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+follow-up+of+a+randomized+controlled+trial+evaluating+a+mobile+health+intervention+for+self-management+in+lung+transplant+recipients.">Long-term follow-up of a randomized controlled trial evaluating a mobile health intervention for self-management in lung transplant recipients.</a> American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 17 (5), 1286-1293 (2017).</li><li>Mathes, T., Grosspietsch, K., Neugebauer, E. A. M., Pieper, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventions+to+increase+adherence+in+patients+taking+immunosuppressive+drugs+after+kidney+transplantation:+a+systematic+review+of+controlled+trials.">Interventions to increase adherence in patients taking immunosuppressive drugs after kidney transplantation: a systematic review of controlled trials.</a> Systematic Reviews. 6 (1), 236 (2017).</li><li>Pruette, C. S., Amaral, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Empowering+patients+to+adhere+to+their+treatment+regimens:+A+multifaceted+approach.">Empowering patients to adhere to their treatment regimens: A multifaceted approach.</a> Pediatric Transplantation. , 13849 (2020).</li><li>Lee, H., Shin, B. C., Seo, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effectiveness+of+eHealth+interventions+for+improving+medication+adherence+of+organ+transplant+patients:+A+systematic+review+and+meta-analysis.">Effectiveness of eHealth interventions for improving medication adherence of organ transplant patients: A systematic review and meta-analysis.</a> PloS One. 15 (11), 0241857 (2020).</li><li>Jandovitz, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Telemedicine+pharmacy+services+implementation+in+organ+transplantation+at+a+metropolitan+academic+medical+center.">Telemedicine pharmacy services implementation in organ transplantation at a metropolitan academic medical center.</a> Digital Health. 4, (2018).</li><li>Triplett, K. N., El-Behadli, A. F., Masood, S. S., Sullivan, S., Desai, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digital+medicine+program+with+pediatric+solid+organ+transplant+patients:+Perceived+benefits+and+challenges.">Digital medicine program with pediatric solid organ transplant patients: Perceived benefits and challenges.</a> Pediatric Transplantation. 23 (7), 13555 (2019).</li><li>Eisenberger, U., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medication+adherence+assessment:+high+accuracy+of+the+new+Ingestible+Sensor+System+in+kidney+transplants.">Medication adherence assessment: high accuracy of the new Ingestible Sensor System in kidney transplants.</a> Transplantation. 96 (3), 245-250 (2013).</li></ol>

The authors have nothing to declare.

A comprehensive telemedicine platform was created to improve the care of KTR. The platform was readily accepted by patients with excellent participation in sending vital signs from home. To develop the platform and to provide these services to patients, extensive software engineering was necessary. Critical steps included (a) constant software development with the involvement of all stakeholders from the beginning, and (b) a comprehensive data protection concept, which was achieved with the help of a specialized law firm...

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) as it prolongs life, improves quality of life (QoL), and saves money and resources compared to maintenance dialysis1,2. QoL is defined as the general well-being of individuals, and health-related QoL (HRQoL) is an assessment of how the individual&#39;s well-being may be affected over time by a disease, disability, or disorder3. Recently, QoL, HRQoL, and specific patient-reported outcomes were considered core outcome domains for kidney transplantation, which have become critically important to patients, health professionals, and regulatory agencies4,5. Kidney transplant recipients (KTR) must change their lifestyle after transplantation, adhere to a complex medication schedule, and perform regular self-assessments6. The regular intake of immunosuppressive therapy is of utmost importance to ensure adequate drug blood levels7. Extremely low blood concentrations may result in under-immunosuppression, increasing the risk for rejection or the development of donor-specific antibodies (DSA). Acute rejections and DSA are major causes for graft loss. Extremely high blood concentrations of immunosuppressants may result in over-immunosuppression increasing the risk for drug-related side effects, infections, and malignancies. Therefore, strict adherence and regular control of laboratory values is necessary to adjust immunosuppressive therapy within a narrow therapeutic range.
Other frequent complications of immunosuppressive drugs include diabetes and hypertension, which can lead to costly hospitalizations and reduced QoL. To achieve better transplant survival, close monitoring and adherence are essential. Studies in the general population suggest that only ~50% of patients in the Western world are fully adherent to their medication schedule8. It has been suggested that approximately 20%-30% of graft losses in KTR are linked to non-adherence9,10. There are many reasons for non-adherence including insufficient communication, misunderstanding, and forgetfulness11. Key pillars for better adherence are good and clear communication and an unambiguous written medication plan10. Other important factors for adherence are an individually adapted explanation of the therapeutic concept and the understanding of medication and disease. Patient empowerment, which enables patients to better take care of their health, is the basis for better adherence and behavioral changes12. Being adherent to medication and to a self-assessment plan is crucial for long-term success after kidney transplantation13.
The kidney transplant center at Charit&#233; cares for KTR from the metropolitan area of Berlin and Brandenburg. Many patients travel several hours for a consultation. Long travel times are an important problem in the care of KTR14, especially for elderly and frail patients, and also for those who have to manage a family and are working. Other hurdles are travel costs, inconvenience, and loss of working hours15. Therefore, the Berlin kidney transplant center and local nephrologists (physicians in private practice) share the care after kidney transplantation, which raises the problem of missing or incomplete information during a consultation. To minimize information loss, automatic and safe exchange of key data is needed16. However, to date, data have been stored in different data silos with no interoperability. Today, data exchange relies on telephone, letters, fax, or e-mails with limited data protection and is highly dependent on individuals. Thus, loss of information and incomplete data are common problems, and automatic, secure data exchange according to European (EU) General Data Protection Regulation (GDPR) remains a rare exception.
Several eHealth solutions have been suggested to support patients after transplantation to better utilize the potential of digitalization for the healthcare of this vulnerable patient group17. Early detection of complications allows early intervention by a telemedicine team, resulting in less severe complications, less hospitalizations, or a shorter length of hospital stay, as shown in other telemedicine projects18,19,20,21. A high hospitalization rate is observed in the transplant population22. Approximately one-third of KTR are hospitalized annually with average costs of ~6,600 Euro per hospitalization. As a consequence, telemedicine-driven early interventions offer the opportunity to reduce hospitalizations and, by this means, reduce costs and improve QoL. One interesting target is to improve adherence, e.g., with the help of apps or telemedicine concepts. Due to the permanent availability of apps for smartphones, such apps can be included in interventions that aim to increase adherence. DeVito et al. demonstrated in a randomized controlled trial (RCT) that a user-centered app for lung transplant recipients with regular self-assessments, reminder function, remote vital sign monitoring, and an automatic decision support tool could improve adherence to therapy. But they did not observe significant differences regarding the 12-month hospitalization rate and mortality23.
Schmid et al. conducted an RCT with a comprehensive telemedicine concept after kidney transplantation. They found a significantly higher adherence rate and a dramatic reduction in hospitalizations and costs20,21. These results were confirmed by Lee et al. who reported significantly lower readmission rates within the first 90 days after liver transplantation than the standard of care with the use of additional telemedicine support through smart tablets19. Their telemedicine features consisted of using Bluetooth devices to remotely monitor vital signs, drug reminders, regular self-assessments, as well as access to educational sessions, text messaging and video conferencing tools. Better QoL, general health, and physical function were observed in patients in the telemedicine group. Adherence was excellent (86%) with respect to remote vital signs, but was only 45% for messaging or videoconferencing. However, not all studies could demonstrate positive effects of apps or eHealth solutions17,19. Han et al. investigated an app with a medication reminder, intake documentation, and shared laboratory values, which also provided information about immunosuppressive therapy. They did not observe any significant difference in adherence between intervention and control groups in KTR, most likely due to high drop-out rates. In this RCT, only 47% used the app after 1 month24.
The secure and interoperable MACCS platform for KTR was developed to address the limitations of current post-transplant care, namely the need for close monitoring, regular self-assessments, decreasing adherence, and loss of information between physicians. The platform enables patients to share vital signs, daily medication intake protocols, blood glucose, messages, and well-being with the transplant center via an app (see the Table of Materials). Well-being is captured by a simple question (&#34;how are you feeling today?&#34;) and a 5-point Likert scale with different emojis (smileys) reflecting the current mood of the patient. In the transplant center, all data are stored directly in the electronic health record (EHR) called TBase25. The EHR is tailored for the needs of transplanted patients, is used for regular post-transplant care, and automatically integrates all relevant data from the hospital, outpatient visits, and transplant-specific data such as donor data, ischemia times, and human leukocyte antigen mismatches. A telemedicine dashboard was implemented in the EHR for an easy review of incoming data by the telemedicine team.
The EHR is connected via a secure HL7 FHIR interface with an FHIR server (platform) outside the firewall of the transplant center, which transfers pseudonymized data from the transplant EHR (TBase) to the patient app. This allows the transplant center to send secure messages, laboratory data, and medication plans directly to the patient&#180;s smartphone.&#160;Another important partner in the telemedicine project provides specialized software for local nephrologists and has a market share of ~65% in Germany (see the Table of Materials). The software connects to the HL7 FHIR server and allows direct communication between the transplant center and local nephrologists. The shared data include laboratory values, medical letters, test results, vital signs, and medication plans. With the use of an automatic data exchange, the platform aims to eliminate loss of information, as well as manual, incomplete, insecure, or late data transmission. By this means, workload is reduced, and time-consuming tasks and errors are eliminated to create significant efficiency gains. The platform also facilitates communication between physicians through an easy exchange of notes to prevent information gaps. Another advantage is the fact that data are transmitted directly into the software of the physicians to be used for daily routine. Thus, physicians only work with familiar software and do not need to use different software tools (Figure 1).
The concept of the project is GDPR-compliant, and all of the data are protected according to the highest European standards. Individual data are visible for approved medical personnel only. All information is encrypted and transferred according to HL7 FHIR standards. The patient can give and deny access rights to other physicians through the app and can cancel participation at any time. Data are transmitted only after written informed consent and after a complex onboarding process (digital inclusion process). It is important to mention that all services of the platform are offered as an additional service to patients, free of charge. Thus, patients can choose between regular care or regular care plus telemedicine services. The project started to enroll patients in February 2020, and the additional telemedicine services are supported by two large health insurance companies.
In summary, a comprehensive telemedicine platform for KTR was established. Initially, the German Federal Ministry of Economy and Energy (BMWi) funded the project as part of the open call &#34;Smart Service World&#34; to stimulate the growing number of smart services in healthcare. The basic concept is similar to other comprehensive telemedicine systems18,19,23,26,27. Compared to most telemedicine concepts, the advantages of the platform include its interoperability through standardized HL7 FHIR interfaces and GDPR compliance. The platform has no specific hardware requirements. The apps are free of charge and allow straightforward and easy use. The possibility for an easy multi-channel communication with the telemedicine team might also increase the use of the app for home monitoring. Patients use their regular scale and blood pressure device at home, and no costly and complicated Bluetooth devices are needed. Another innovative feature of the platform is the direct involvement of local nephrologists. Patients are usually treated by a combination of tertiary kidney transplant centers and local nephrologists, who already know the patient from dialysis or predialysis times.
As patients frequently visit their local nephrologists, a comprehensive platform for KTR should also automatically incorporate the local nephrologists to prevent information gaps. Importantly, the platform also implements automatic safe data exchange and communication with local nephrologists, who can use their regular software and have a direct added benefit due to automatic data exchange with the transplant center. In contrast to similar eHealth solutions, the platform is fully integrated into the workflow of the transplant center and the local nephrologist. The platform also fully integrates the local nephrologist in the data exchange of key variables and provides extensive, safe, and easy communication tools for physicians and patients. The direct benefits for users should increase acceptance and reinforce regular use. Further improvements of the platform are under development, and after establishment of an advanced stable platform, a prospective RCT on KTR is planned to provide solid evidence for better outcomes and cost effectiveness.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>comjoodoc EASY app</td>
			<td>comjoo business solutions GmbH</td>
			<td></td>
			<td>Patient app for patients to share information with the transplant center</td>
		</tr>
		<tr>
			<td>HL7 FHIR standard</td>
			<td>Medworxs.io</td>
			<td></td>
			<td>Provider of MACCS API</td>
		</tr>
		<tr>
			<td>FHIR server</td>
			<td>Medworxs.io</td>
			<td></td>
			<td>Host of MACCS patform</td>
		</tr>
		<tr>
			<td>NEPHRO7</td>
			<td>MedVision AG</td>
			<td></td>
			<td>Electronic health record of home nephrologists</td>
		</tr>
		<tr>
			<td>myTherapy</td>
			<td>smartpatient GmbH</td>
			<td></td>
			<td>Patient app for medication intake and alternative transmission of vital signs and well being</td>
		</tr>
		<tr>
			<td>TBase</td>
			<td>Charit&#233; - Universit&#228;tsmedizin Berlin</td>
			<td></td>
			<td>Electronic health record of outpatient care center at Charit&#233;</td>
		</tr>
	</tbody>
</table>

digital home-monitoring of patients after kidney transplantation: the maccs platform

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney transplantation and physicians. Patients provide information such as vital signs, well-being, and medication intake via smartphone apps. The information is transferred directly into a database and electronic health record at the kidney transplant center, which is used for routine patient care and research. Physicians can send an updated medication plan and laboratory data directly to the patient app via this secure platform. Other features of the app are medical messages and video consultations. Consequently, the patient is better-informed, and self-management is facilitated. In addition, the transplant center and the patient's local nephrologist automatically exchange notes, medical reports, laboratory values, and medication data via the platform. A telemedicine team reviews all incoming data on a dashboard and takes action, if necessary. Tools to identify patients at risk for complications are under development. The platform exchanges data via a standardized secure interface (Health Level 7 (HL7), Fast Healthcare Interoperability Resources (FHIR)). The standardized data exchange based on HL7 FHIR guarantees interoperability with other eHealth solutions and allows rapid scalability to other chronic diseases. The underlying data protection concept is in concordance with the latest European General Data Protection Regulation. Enrollment started in February 2020, and 131 kidney transplant recipients are actively participating as of July 2020. Two large German health insurance companies are currently funding the telemedicine services of the project. The deployment for other chronic kidney diseases and solid organ transplant recipients is planned. In conclusion, the platform is designed to enable home monitoring and automatic data exchange, empower patients, reduce hospitalizations, and improve adherence, and outcomes after kidney transplantation.

In the first 5 months between February and July 2020, 172 KTR matched the inclusion criteria and were asked to participate (Table 1). Out of 172 participants, seven needed to borrow a smartphone (four did not own one, three needed a new one); all other patients owned a smartphone. The app does not need wireless access (Wi-Fi) as data can be transferred by mobile phone via regular telecommunication services, and 2/172 patients were equipped with a subscriber identity module (SIM) card for mobile data tran...

Watch this Scientific Journal Video about Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform at JoVE.com

Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform

The MACCS platform&#160;is a comprehensive telemedicine concept aiming at better outcomes after kidney transplantation by sharing key medical information between patients and physicians. A telemedicine team reviews incoming data to detect potential complications and to improve adherence in kidney transplant recipients to achieve better long-term outcomes.

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney ...

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4.1K Views.  Charité Universitätsmedizin Berlin. The MACCS platform is a comprehensive telemedicine concept aiming at better outcomes after kidney transplantation by sharing key medical information between patients and physicians. A telemedicine team reviews incoming data to detect potential complications and to improve adherence in kidney transplant recipients to achieve better long-term outcomes.

Video: Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform

A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation

Since the early pioneering work of Ballinger and Reckard demonstrating that transplantation of islets of Langerhans into diabetic rodents could normalize their blood glucose levels, islet transplantation has been proposed to be a potential treatment for type 1 diabetes 1,2. More recently, advances in human islet transplantation have further strengthened this view 1,3. However, two major limitations prevent islet transplantation from being a widespread clinical reality: (a) the requirement for large numbers of islets per patient, which severely reduces the number of potential recipients, and (b) the need for heavy immunosuppression, which significantly affects the pediatric population of patients due to their vulnerability to long-term immunosuppression. Strategies that can overcome these limitations have the potential to enhance the therapeutic utility of islet transplantation.
Islet transplantation under the mouse kidney capsule is a widely accepted model to investigate various strategies to improve islet transplantation. This experiment requires the isolation of high quality islets and implantation of islets to the diabetic recipients. Both procedures require surgical steps that can be better demonstrated by video than by text. Here, we document the detailed steps for these procedures by both video and written protocol. We also briefly discuss different transplantation models: syngeneic, allogeneic, syngeneic autoimmune, and allogeneic autoimmune.

Transplantation of isolated islets has been proposed to be a potential treatment for type 1 diabetes. Here we describe a method to isolate islets from mouse pancreata and transplant them to the subcapsular space of the kidney.

Since the early pioneering work of Ballinger and Reckard demonstrating that transplantation of islets of Langerhans into diabetic rodents could normalize ...

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.

The degree of vascular dysfunction and contributing physiological mechanisms can be assessed in patients with chronic kidney disease by measuring brachial artery flow-mediated dilation, aortic pulse-wave velocity, and vascular endothelial cell protein expression.

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

Mouse Kidney Transplantation: Models of Allograft Rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

Here, we present a protocol to study the immunology of rejection. The surgical model presented reports a short operating time and a concise technique. Depending on the donor-recipient strain combination, the transplanted kidney may develop acute cellular rejection or chronic allograft damage, defined by interstitial fibrosis and tubular atrophy.

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

Murine Kidney Transplant Technique

The first mouse kidney transplant technique was published in 19731 by the Russell laboratory. Although it took some years for other labs to become proficient in and utilize this technique, it is now widely used by many laboratories around the world. A significant refinement to the original technique using the donor aorta to form the arterial anastomosis instead of the renal artery was developed and reported in 1993 by Kalina and Mottram 2 with a further advancement coming from the same laboratory in 1999 3. While one can become proficient in this model, a search of the literature reveals that many labs still experience a high proportion of graft loss due to arterial thrombosis. We describe here a technique that was devised in our laboratory that vastly reduces the arterial thrombus reported by others 4,5. This is achieved by forming a heel-and-toe cuff of the donor infra-renal aorta that facilitates a larger anastomosis and straighter blood flow into the kidney.

The goal of this manuscript is to describe the steps required to perform a kidney transplant in a mouse, paying particular attention to the details of the arterial anastomosis.

The first mouse kidney transplant technique was published in 19731 by the Russell laboratory. Although it took some years for other labs to become ...

Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods.
Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes.
In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated.

Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

The severe organ shortage has resulted in increased use of marginal kidney grafts for transplantation. This has triggered interest in alternative storage methods, since marginal grafts especially tolerate cold storage poorly. The technique of normothermic ex vivo kidney perfusion (NEVKP) represents a novel preservation method for kidney grafts prior to &#160;transplantation.

Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a ...

Intrasplenic Transplantation of Hepatocytes After Partial Hepatectomy in NOD.SCID Mice

Partial hepatectomy is a versatile and reproducible method to study liver regeneration and the effect of cell based therapeutics in various pathological conditions. Partial hepatectomy also facilitates the increased engraftment and proliferation of transplanted cells by accelerating neovascularization and cell migration towards the liver. Here, we describe a simple protocol for performing 30% hepatectomy and transplantation of cells in the spleen of a non-obese diabetic/severe combined immunodeficient NOD.SCID (NOD.CB17-Prkdcscid/J) mouse. 
In this procedure, two small incisions are made. The first incision is to expose and resect the left lobe of the liver, and another small incision is made to expose the spleen for the intrasplenic transplantation of cells. This procedure does not require any specialized surgical skills, and it can be completed in 5-7 minutes with less stress and pain, faster recovery, and better survival. We have demonstrated the transplantation of hepatocytes isolated from a green fluorescent protein (GFP) expressing mouse (Transgenic C57BL/6-Tg (UBC-GFP) 30Scha/J), as well as hepatocyte like cells of human origin (NeoHep) in partially hepatectomized NOD.SCID mice.

We have described a protocol for performing partial hepatectomy (PHx) and cell transplantation via spleen in NOD.SCID (NOD.CB17-Prkdcscid/J) mice. In this protocol, an incision is made to expose and resect the left lobe of the liver followed by another incision for the intrasplenic transplantation of cells.

Partial hepatectomy is a versatile and reproducible method to study liver regeneration and the effect of cell based therapeutics in various pathological ...

Optical Clearing and Imaging of Immunolabeled Kidney Tissue

Optical clearing techniques render tissue transparent by equilibrating the refractive index throughout a sample for subsequent three-dimensional (3-D) imaging. They have received great attention in all research areas for the potential to analyze microscopic multicellular structures that extend over macroscopic distances. Given that kidney tubules, vasculature, nerves, and glomeruli extend in many directions, which have been only partially captured by traditional two-dimensional techniques so far, tissue clearing also opened up many new areas of kidney research. The list of optical clearing methods is rapidly growing, but it remains difficult for beginners in this field to choose the best method for a given research question. Provided here is a simple method that combines antibody labeling of thick mouse kidney slices; optical clearing with cheap, non-toxic and ready-to-use chemical ethyl cinnamate; and confocal imaging. This protocol describes how to perfuse kidneys and use an antigen-retrieval step to increase antibody- binding without requiring specialized equipment. Its application is presented in imaging different multicellular structures within the kidney, and how to troubleshoot poor antibody penetration into tissue is addressed. We also discuss the potential difficulties of imaging endogenous fluorophores and acquiring very large samples and how to overcome them. This simple protocol provides an easy-to-setup and comprehensive tool to study tissue in three dimensions.

The combination of antibody labeling, optical clearing, and advanced light microscopy allows three-dimensional analysis of complete structures or organs. Described here is a simple method to combine immunolabeling of thick kidney slices, optical clearing with ethyl cinnamate, and confocal imaging that enables visualization and quantification of three-dimensional kidney structures.

Optical clearing techniques render tissue transparent by equilibrating the refractive index throughout a sample for subsequent three-dimensional (3-D) ...

Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.

Stem cell-based therapy has emerged as an efficient strategy to repair injured cardiac tissues after myocardial infarction. We provide an optimal in vivo application for stem cell transplantation using gelatin hydrogels that are able to be enzymatically cross-linked.

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of ...

Robot-Assisted Kidney Transplantation

This paper describes robot-assisted kidney transplantation (RAKT) from a living donor. The robot is docked between the parted legs of the patient, placed in the supine Trendelenburg position. Kidney allografts are provided by a living donor. Before vascular anastomosis, the kidney allograft is prepared by inserting a double-J stent in the ureter, and the temperature for the anastomosis is lowered by wrapping it in an ice-packed gauze. A 12 mm or 8 mm port for the robotic camera and three 8 mm ports for robotic arms are placed. A peritoneal pouch is created for the kidney allograft by raising the peritoneal flaps on both sides over the psoas muscle before dissecting the iliac vessels and bladder. A 6 cm Pfannenstiel incision is made to insert the kidney into the peritoneal pouch, lateral to the right iliac vessels. 
After clamping the external iliac vein with Bulldogs clamps, a venotomy is performed, and the graft renal vein is anastomosed to the external iliac vein in an end-to-side continuous manner with a 6/0 polytetrafluoroethylene suture. After clamping the graft renal vein, the iliac vein is declamped. This is followed by clamping of the external iliac artery, arteriotomy, arterial anastomosis with a 6/0 polytetrafluoroethylene suture, clamping of the graft renal artery, and declamping of the external iliac artery. Reperfusion is then carried out, and ureteroneocystostomy is performed using the Lich-Gregoir technique. The peritoneum is closed at a few locations with polymer locking clips, and a closed-suction drain is placed through one of the working ports. After deflating the pneumoperitoneum, all incisions are closed.

This paper provides technical details for robot-assisted kidney transplantation from a living donor.

This paper describes robot-assisted kidney transplantation (RAKT) from a living donor. The robot is docked between the parted legs of the patient, placed ...