Transplant nephropathology: Wherefrom, wherein, and whereto.

Renal pathology is a relatively recent entry in nephrology. While diseases of the kidney are old, their study began in the 19th century with the report of Richard Bright of the lesions of end-stage kidney disease. Its easy diagnosis from albuminuria soon elevated Bright's nephritis into a leading cause of death. The transformative events in the care of these cases were renal replacement therapy that converted a fatal into a chronic disease, and kidney biopsy that allowed study of the course and pathogenesis of kidney disease. Apart from its fundamental contributions to clinical nephrology, biopsy of renal allografts became an integral component of the evaluation and care of kidney transplant recipients. The Banff transplant pathology conferences launched in 1991 led to developing the classification of allograft pathology into an essential element in the evaluation, treatment, and care of allograft recipients with spirit of discovery. That success came at the cost of increasing complexity leading to the recent realization that it may need the refinement of its consensus-based system into a more evidence-based system with graded statements that are easily accessible to the other disciplines involved in the care of transplanted patients. Collaboration with other medical disciplines, allowing public comment on meeting reports, and incorporation of generative artificial intelligence (AI) are important elements of a successful future. The increased pace of innovation brought about by AI will likely allow us to solve the organ shortage soon and require new classifications for xenotransplantation pathology, tissue engineering pathology, and bioartificial organ pathology.

Tumor promoting effect of spheroids in an orthotopic prostate cancer mouse model.

In this study, we aimed to establish a technique for intraprostatic implantation of prostate cancer (PCa) spheroids and to identify the impact of three-dimensional organization of PCa cells on tumor progression and metastasis in a representative in vivo model. 40,000 LNCaP cells were implanted into the prostate of immunodeficient SCID mice either as single cells (n = 8) or as preformed 3D spheroids (n = 8). For a follow up of 20 weeks, tumor growth was monitored by serum PSA and high-resolution 3D ultrasonography. Eventually, animals were sacrificed and autopsied. The organ dissects were analyzed for the presence of metastases by histology (H&E) and immunohistochemistry (AMACR, AR, Ki-67, CK5, CK8, E-Cadherin, Vimentin). Solid intraprostatic tumors developed in 50% of mice after spheroid implantation and in 50% of mice after implantation of a single cells. Primary tumors of LNCaP spheroids evolved earlier, exhibiting a shorter tumor doubling time whilst developing larger tumor volumes, which was reflected by a higher immunohistochemical expression of Ki-67 and AR, too. Spheroid tumors established lung and lymph node metastases in 75% of mice, in contrast to 50% of mice after single cell implantation. Our technique enables a variety of studies regarding the influence of the tumor microenvironment on PCa progression.

From intestinal failure to transplantation: Review on the current need for transplant indications under multidisciplinary transplant programs worldwide.

INTRODUCTION: Intestinal failure, defined as the loss of gastrointestinal function to the point where nutrition cannot be maintained by enteral intake alone, presents numerous challenges in children, not least the timing of consideration of intestine transplantation. OBJECTIVES: To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care. METHODS: The review is based on the authors' experience supported by an in-depth review of the published literature. RESULTS: The history of parenteral nutrition, including out-patient (home) administration, and intestine transplantation are reviewed along with the complications of intestinal failure that may become indications for consideration of intestine transplantation. Current management strategies for children with intestinal failure are discussed along with changes in need for intestine transplantation, recognizing the difficulty in generalizing recommendations due to the high level of heterogeneity of intestinal pathology and residual bowel anatomy and function. DISCUSSION: Advances in the medical and surgical care of children with intestinal failure have resulted in improved transplant-free survival and a significant fall in demand for transplantation. Despite these improvements a number of children continue to fail rehabilitative care and require intestine transplantation as life-saving therapy or when the burden on ongoing parenteral nutrition becomes too great to bear.

Factors Associated with Chronic Rejection in Liver Transplant Recipients: A Retrospective Cohort Study From Shiraz Organ Transplant Center.

OBJECTIVES: Identification of chronic rejection risk factors in liver transplant recipients is critical for early detection and prevention of further graft loss. We investigated characteristics of liver transplant recipients who had experienced chronic rejection and the associated risk factors versus patients without chronic rejection. MATERIALS AND METHODS: Data from 3022 adult liver transplant recipients between 2011 and 2018 were analyzed; of these, 80 patients had experienced chronic rejection. The control group included 98 randomly selected liver transplant recipients who did not have chronic rejection. RESULTS: The age of the recipients and the donors was significantly lower in the group with chronic rejection versus the group without chronic rejection.The results indicated that chronic rejection was significantly associated with the sex of the recipients (hazard ratio 3.2, 95% CI 1.77-6.08; P < .001) and with the sex concordance between the recipients and donors (hazard ratio 2.93, 95% CI 1.67-5.13; P < .001, respectively). Also, in the group without chronic rejection, there were no male donors; however, the group with chronic rejection had mostly male donors (P <.001). Cold ischemia time was longer in patients with chronic rejection versus that shown in the control group (P = .031), and there was a significant difference between the 2 groups in acute rejection frequency (P < .001). CONCLUSIONS: Recipient sex and sex concordance were independent risk factors for chronic rejection. Most transplantrecipients with chronic rejection responded to medicaltreatment, and the rate of graftloss was low among our recipients.

Total Face Reconstruction with Flap Prefabrication and Soft-Tissue Expansion Techniques.

SUMMARY: Total facial deformities always lead to psychological and functional consequences, making plastic and reconstructive surgery a great challenge. The skin of the anterior chest area is matched in thickness, texture, and color to the head and face. The purpose of this article was to discuss and evaluate reconstructive surgeons' experiences with obtaining a monoblock flap from the anterior thoracic area for entire face reconstruction using flap prefabrication, soft-tissue expansion, and facial plastic surgery following skin flap transplantation. Two patients underwent prefabricated expanded anterior thoracic flap reconstructions for total facial deformities; data collection included face defect size, flap type, the shape of the expander, expansion time, and complications. All the face flaps that were transplanted survived without major complications. It is concluded that using a prefabricated expanded flap to reconstruct an entire facial soft-tissue defect can provide a high degree of matching, a wide enough covering area, and a thin enough skin thickness to cover the face. Autologous flap grafting is easy to implement and has a high application value.

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Impact of OPTN policy 3.7D providing waiting time modification for candidates affected by race-inclusive eGFR calculations: Early results from a single center.

INTRODUCTION: OPTN Policy 3.7D, implemented January 5, 2023, mandates that all kidney transplant programs modify waiting time for candidates affected by race-inclusive eGFR calculations. We report the early impact of this policy change. METHODS: Our transplant program reviewed all listed transplant candidates and identified patients potentially eligible for waiting time modification. Eligible candidates received waiting time modification after submission of supporting evidence to the OPTN. We reviewed the impact on waiting time and transplant activity through October 1, 2023. RESULTS: Forty-six adult patients on our center's active waiting list self-identified as Black/African American. 25 (54.3%) candidates qualified for waiting time modification. A median 451 (321, 1543.5) additional days of waiting time was added for qualifying patients. Of the 25 patients who qualified for waiting time modification, 11 patients received a deceased donor kidney in the early period following waiting time modification, including 5 patients transplanted within 1 month after modification. CONCLUSIONS: Policy 3.7D is one of few national mandates to address specifically structural racism within transplantation. Implementation has yielded near immediate effects with greater than 40% of time-adjusted patients at our center receiving a deceased donor kidney transplant in the initial months after policy enactment. Early assessment demonstrates great potential impact for this policy.

Rinoplastia secundaria: infección nasal en el postoperatorio / Secondary rhinoplasty: postoperative nasal infection

La rinoplastia es una de las intervenciones más comunes en cirugía plástica. Se opera aquí una rinoplastia secundaria por vía abierta injertando los alares y la punta con cartílagos auriculares, mientras el tabique cartilaginoso fue usado para los spreader grafts. Se describe aquí una infección posoperatoria de su punta nasal. Al 9no día de su posoperatorio comienza con la punta nasal congestiva y levemente inflamada. Se medica con una crema con antibióticos, pero el día 14 aparece con la punta nasal muy inflamada y con colección. Cuando en el consultorio el cirujano la ve, como cualquier absceso, decide realizarle drenaje con un trocar 18G, 3 miniincisiones en la piel debajo de la punta nasal, de la que drena un líquido amarronado. Luego con el mismo trocar se realiza un lavado dentro de la cavidad con rifampicina solución. Se medica con trimetoprima-sulfametoxazol (Bactrimforte®) 2 comp/día. Al otro día se observa una notable mejoría. Se continuó con lavado diario durante 4 días con el mismo antibiótico evolucionando rápidamente bien. El Bactrim se lo continúa por 20 días. Al mes la punta nasal está muy bien, deshinchada con cicatrices apenas visibles. A los cuatro meses, la punta está muy blanda, las alas nasales y las narinas normales, la punta con buena proyección igual que el dorso con los spreader graft.

Rhinoplasty is one of the most common interventions in plastic surgery. A secondary open rhinoplasty was carried out grafting the allae and the tip of the nose with conchae cartilage, while the septum was used for spreader grafts. We are here describing this post operatory with a tip of the nose infection.In the control, at the 9th postoperative day, the nasal tip began to be congested and at the 14th post op day the patient showed a clear inflammatory collection. In the office, the surgeon decided to evacuate it with three punctureslike little incisions at the inferior part of the skin tip with a trocar 18G. Through them, drained brownish purulent secretion. With the same trocar, rifampicin solution was injected through these little incisions, like washing the subdermal area. It was medicated with trimethoprim-sulfamethoxazole (Bactrim forte®) 2 tablets/day. The following day, there was a clear improvement in the congestion and erythema of the nose. This procedure of washing was repeated for four days. There was a quick evolution of the inflammatory process and 20 more days, there was no sign of the infection. Four months later, the tip of the nose was soft and the result was considered optimal by the patient and doctors.

Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

Applications of motivational interviewing in adolescent solid organ transplant.

BACKGROUND: Adolescence is a developmental period that is known for the highest risk of difficulties with adoption and maintenance of health behaviors for successful transplant. Motivational interviewing (MI) has been demonstrated to be an effective strategy in the management of modifiable factors impacting adherence in both adult transplant and analogous pediatric chronic illness populations. AIMS: This paper describes MI and its applicability to adolescent transplant, providing examples of its potential use at each stage of the transplant journey. MATERIALS AND METHODS: Literature on the principles and utilization of MI are reviewed, as well as the use of MI in adult transplant and similar pediatric populations. RESULTS: Evidence suggests high applicability of concepts of MI to pediatric transplant. DISCUSSION: Systems-level factors influencing health behavior change are discussed, along with the importance of recognizing and managing provider bias in MI-based interactions. MI does not require a licensed behavioral health provider to use it effectively; rather, it can be used by various multidisciplinary team members throughout the course of clinical care. CONCLUSION: MI shows great promise as a useful intervention through all stages in the transplant journey. Though particularly well-suited to adolescents, its principles are effective across the lifespan, including with caregivers. It represents an interactional style for use by multidisciplinary team members in many patient-and caregiver-facing scenarios. As the goal is to support the patient's autonomy in decision-making, it is important for providers to recognize their own biases. Further resources for training are provided.

The nuts and bolts of transplant infectious disease training.

The number of transplant infectious disease (TID) fellowship programs has expanded rapidly in the past 5 years, with the creation of many new programs and the expansion of training tracks and dedicated years as the demand for TID physicians grows drastically. This editorial focuses on major factors and complexities that programs should consider in TID fellowship creation, as well as highlighting examples of formative experiences, programmatic structure, and fellow resources that trainees can use to identify their desired career path in TID.

The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions.

Rationale: Stem cell-based therapies have emerged as promising tools for tissue engineering and regenerative medicine, but their therapeutic efficacy is largely limited by the oxidative stress-induced loss of transplanted cells at injured tissue sites. To address this issue, we aimed to explore the underlying mechanism and protective strategy of ROS-induced MSC loss. Methods: Changes in TFAM (mitochondrial transcription factor A) signaling, mitochondrial function, DNA damage, apoptosis and senescence in MSCs under oxidative stress conditions were assessed using real-time PCR, western blotting and RNA sequencing, etc. The impact of TFAM or lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) knockdown or overexpression on mitochondrial function, DNA damage repair, apoptosis and senescence in MSCs was also analyzed. The effect of mitochondrion-targeted antioxidant (Mito-TEMPO) on the survival of transplanted MSCs was evaluated in a mouse model of renal ischemia/reperfusion (I/R) injury. Results: Mitochondrial ROS (mtROS) bursts caused defects in TFAM signaling and overall mitochondrial function, which further impaired NEAT1 expression and its mediated paraspeckle formation and DNA repair pathways in MSCs, thereby jointly promoting MSC senescence and death under oxidative stress. In contrast, targeted inhibition of the mtROS bursts is a sufficient strategy for attenuating early transplanted MSC loss at injured tissue sites, and coadministration of Mito-TEMPO improved the local retention of transplanted MSCs and reduced oxidative injury in ischemic kidneys. Conclusions: This study identified the critical role of the mitochondria‒paraspeckle axis in regulating cell survival and may provide insights into developing advanced stem cell therapies for tissue engineering and regenerative medicine.

The increasing need for ABO blood group genotyping and quality assurance implications for laboratory implementation.

ABO blood group antigens are critical determinants of immunologic self and non-self and are ubiquitously expressed on all cellular tissues. Antibodies against non-self ABO antigens are naturally present and can mediate pathologic reactions against incompatible transfused blood cells and transplanted tissues. Laboratory testing for ABO antigens and isoagglutinins is essential for safe and effective transfusion and transplantation. Testing for ABO antigens has traditionally depended on serologic testing. However, there is increasing need for evaluation of genetic analysis of ABO antigens, to enable evaluation of ABO blood group in cases where serologic testing may be ambiguous or impossible to accurately perform. The clinical need for ABO genotyping is being addressed by the development of multiple molecular diagnostic approaches. Recent data have clearly demonstrated the potential utility of ABO genotyping in solid organ transplantation, yet widespread implementation has been slow. We propose that this lag is related to practical considerations in laboratory testing, including limited regulatory guidance on the performance and reporting of these assays and the absence of widely available external proficiency testing programs for quality assurance. Here we describe approaches to ABO genotyping, current initiatives in developing ABO genotyping proficiency testing programs, and laboratory quality assurance considerations for ABO genotyping.

The Importance of Multiorgan Procurement in the Improvement of Residents' Open Surgical Skills.

INTRODUCTION: The multiorgan procurement (MOP) represents a chance for the general surgery resident to learn the fundamental steps of open abdominal surgery. The objective of this study was to evaluate the impact of MOP on the residents' open surgical skills. METHODS: Residents' surgical skills were assessed during a 6-month transplant rotation (October 2020-March 2021) using a modified Objective Structured Assessment of Technical Skills with the global rating scale. The surgeries were self-assessed by residents and tutors based on 9 specific steps (SS) and 4 general skills (GS). Each item was rated from 1 (poor) to 5 (excellent) with a maximum score of 45 points for SS and 20 for GS. A crossed-effects linear regression analysis was performed both to evaluate any associations between GS/SS scores and some prespecified covariates, and to study differences in the assessments performed by residents and tutors. RESULTS: Residents actively participated in a total of 59 procurements. In general, there were no significant differences in SS/GS mean scorings between residents (n = 15) and tutors (n = 5). There was a significantly positive association between mean GS/SS scorings and the number of donor surgeries performed (at least 5). Comparing the evaluations of the tutors with the residents, this significance was retained only when scorings were assigned by the tutors. CONCLUSIONS: MOP was shown to improve basic open surgical skills among residents. Awareness of the utility of a clinical rotation in transplant surgery should be raised also on an institutional level.

Protocol for transplanting pancreatic islets into the parametrial fat pad of female mice.

Although the male epididymal fat pad is an effective site for islet transplantation, females lack this tissue. Here, we present a protocol to assess the parametrial fat pad (PFP) adjacent to the uterine horn in females as an alternative site for islet transplantation. We describe steps for islet isolation from the pancreas, counting, transplantation into PFP, and monitoring for engraftment. Transplantation into PFP is minimally invasive, time efficient, and supports long-term engraftment of syngeneic islets and rejection of allogeneic islets. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.

"You don't know what you don't know": A qualitative study of informational needs of patients, family members, and living donors to inform transplant system metrics.

INTRODUCTION: Informational needs and potential use of transplant metrics, especially among patients, remain understudied and a critical component of the transplant community's commitment to patient-centered care. We sought to understand the perspectives and needs of patients, family members/caregivers, living donors, and deceased donor family members. METHODS: We examined decision-making experiences and perspectives on the needs of these stakeholder groups for data about the national transplant system among 58 participants of 14 focus groups and 6 interviews. RESULTS: Three major themes emerged: 1) informational priorities and unmet needs (transplantation system processes, long-term outcomes data, prelisting data, patient-centered outcomes, and ability to compare centers and regions); 2) challenges obtaining relevant and trustworthy information (patient burden and effort, challenges with medical jargon, and difficulty finding trustworthy information); and 3) burden of facing the unknown (stress and anxiety leading to difficulty processing information, challenges facing the transplant journey when you "don't know what you don't know"). CONCLUSION: Patient, family member, and living donor participation in shared decision-making has been limited by inadequate access to patient-centered information. New metrics and patient-facing data presentations should address these content gaps using best practices to improve understanding and support shared decision-making.