Subsequent Graft Research Articles

#1436 Donor plasma cystatin C, but not creatinine, is associated with measured GFR at one year after kidney transplantation

Abstract Background and Aims Although widely used during deceased kidney donor selection, donor plasma creatinine has limited capacity to predict future recipient kidney graft function. Cystatin C is a muscle-mass independent kidney function marker that could serve as alternative for this purpose. However, the association between donor cystatin C and subsequent recipient graft function remains unclear. We aim to assess the association of pre-donation cystatin C concentrations with recipient iothalamate-measured GFR (mGFR) one year after kidney transplantation and compare it to the association of donor creatinine concentrations. Method All deceased kidney donors, within the affiliated donation region of the University Medical Center Groningen (UMCG), who donated at least one kidney to a kidney transplant recipient (KTR) affiliated to the same hospital during a period of 15 years (2004-2019) were included. We excluded all subjects with missing data on donor plasma cystatin C or recipient mGFR at 1 year. Donor plasma creatinine concentrations were measured using an enzymatic assay, while donor cystatin C concentrations were measured using a validated particle-enhanced turbidimetric immunoassay (Roche). Associations of donor plasma creatinine and cystatin C concentrations with recipients’ mGFR one year after transplant were assessed using linear regression. Results A total of 53 deceased kidney donors (55% male, age 47 ± 18 years, 47% donation after circulatory death) donated a kidney to 53 kidney transplant recipients (55% male, age 57 ± 12 years). Median pre-donation plasma creatinine and cystatin C concentrations were 64 [55 to 82] μmol/L and 0.64 [0.51 to 0.82] mg/L respectively. Mean recipient mGFR one year after transplantation was 52.7 ± 17.1 ml/min. In univariable linear regression, higher donor cystatin C was significantly associated with lower mGFR (β −0.42, 95% CI: −0.67 to −0.16, p = 0.002), while donor creatinine was not associated (β −0.03 95% CI: −0.32 to 0.25, p = 0.81). The association between donor cystatin C and recipients’ mGFR remained independent of adjustment for potential confounders, including donor sex and age, t (p = 0.008). Conclusion Higher donor cystatin C, but not creatinine, is associated with lower measured GFR one year after kidney transplant. Consequently, donor cystatin C could be valuable for inclusion in the pre-transplant evaluation of deceased kidney donors.

#1492 Metabolic switch in CD8+ T cells may influence immune response in chronic antibody-mediated rejection (CAMR)

Abstract Background and Aims CAMR is the main cause of chronic graft injury and subsequent graft loss, but its pathogenesis is still largely unclear. Our group demonstrated an increase in CD8+ T cells infiltrating biopsies from CAMR patients (PMID: 20595199), but their role remains to be defined. Recently, immunometabolism has emerged as a field connecting cell energy metabolism with the immune cell differentiation and functions. Particularly, the permanent aerobic glycolysis of CD8+ lymphocytes induces their transition from naïve to activated state and effector T cells (PMID: 37315709). Thus, the aim of the study was to investigate the molecular mechanisms underlying the development of CAMR by the analysis of gene expression profiles of CD8+ T lymphocytes in conjunction with their metabolic state. Method We enrolled 14 patients with biopsy-proven CAMR and 12 stable transplant recipients with normal graft histology and function (control group). CD8+ T cells were purified by CD8 MicroBeads (Miltenyi Biotec) then counted (TC20™ Automated Cell Counter). Gene expression profiles of CD8+ T lymphocytes isolated from both groups were assessed using Agilent microarrays. Data obtained were statistically and functionally evaluated (IPA software) and validated by qPCR. Oxygen consumption rate (OCR) in CD8+ and CD8- cells was measured by a Resipher oxygen sensing lid (Lucid Scientific Inc., USA). The contribution of mitochondrial respiration to OCR was investigated in isolated CD8+ T cells from CAMR and controls treated with rotenone/antimycin A (Rot/AA), oligomycin (Olygo) or carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) to evaluate spare respiratory capacity (SRC), ATP-linked respiration, proton leak and maximal respiration. Results Gene expression profiles of CD8+ T cells showed a characteristic alteration of lipid metabolism in CAMR patients with the triglyceride biosynthesis pathway (p = 2.69E-3) as the most altered pathway and several genes de-regulated all potentially involved in the altered metabolic state of CD8+ T cells. Among others, we validated the increased expression of Nicotinamide Phosphoribosyltransferase (NAMPT) (FC = +2.39), the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD+) salvage pathway involved in the glycolysis progression, mostly activated in effector T cells. We then decided to evaluate the OCR and the metabolic state of CD8+T cells. Basal OCR was higher in CD8+ rather than CD8- cells, but with different trends among cells isolated from control and CAMR patients. Indeed, CD8+ cells from CAMR patients showed higher OCR compared to control, while OCR was lower in CD8- from CAMR rather than control patients. CD8+ OCR from both CAMR and control patients was mostly dependent on mitochondrial respiration, since it was deeply reduced by Rot/AA treatment. Interestingly, inhibitory response to Oligo treatment by CD8+ cells from CAMR patients was modest, while OCR was noticeably stimulated by FCCP in these cells, suggesting that mitochondrial oxygen uptake was not ATP linked but rather associated with increased uncoupling. These data suggest that CD8+ T cells from CAMR patients are activated effector T cells primarily utilizing aerobic glycolysis. To confirm this hypothesis, we evaluated the gene expression levels of: i) HIF1a, which involves permanent dependence on glycolysis even in the presence of oxygen (Warburg effect); ii) fatty acid transporter CD36, whose levels mimic an energy dependence on the beta oxidation of fatty acids, a process activated in memory T cells. We confirmed an increased expression of HIF1a and a reduced expression of CD36 in CD8+T cells from CAMR patients compared to controls (p<0.05), that confirm the T effector phenotype. Conclusion Our data suggest that CD8+ T cell from CAMR patients showed permanent dependency on glycolysis leading to altered immune phenotype and response, thus indicating novel opportunities to modulate the immune system for therapeutic purposes in kidney transplanted patients and reduce graft rejection.

#1450 Polygenic risk score of native IgA nephropathy predicts risk of post-transplant disease recurrence

Abstract Background and Aims IgA nephropathy (IgAN) is a polygenic immune-mediated progressive glomerular disease. Recent GWAS reported that high genome-wide polygenic risk score (IgAN GPS), including 1 249 077 variants mapping to systemic immune pathways, was associated with risk of end stage kidney disease (ESKD). Post transplant (KTx) IgAN recurrence occurs in 30% of cases and it is a major cause of graft loss. Pathogenesis and predictors of IgAN recurrence are still not well defined. Herein, we studied the role of native IgAN GPS and clinical factors in predicting post-KTx IgAN recurrence and graft failure in a large cohort of KTx recipients. Method Four thousand one hundred eighty six KTx recipients from 6 sites were genome wide genotyped and imputed against multi-ancestry reference panels, retrieving >10 million variants. In each recipient, native IgAN GPS was computed and standard-normalized (i.e. expressed in units of standard deviations from the mean distribution in matched controls). Native kidney disease diagnosis, clinical parameters, and post-KTx outcome data were retrieved retrospectively from clinical charts. The IgAN GPS was tested as predictor of native IgAN in the entire KTx cohort in a logistic regression model adjusted for sex, age, recruitment site, and first 5 PCs. IgAN GPS was tested as predictor of age at transplantation (proxy for age at ESKD) among KTx recipients with native IgAN in a linear regression model adjusted for sex, recruitment site, and first 5 PCs. In recipients with native IgAN, recipient and donor parameters were individually tested as predictors for time to IgAN recurrence and time to graft failure in Cox proportional hazards models adjusted for recruitment site and first 5 PCs. Predictors with P-value < .1 were included in the multivariable models. Recipient IgAN GPS was added to the clinical models and tested for prediction of time-to IgAN recurrence, and, among KTx recipients with IgAN recurrence, of time-to subsequent graft failure. Results Three hundred sixty nine KTx recipients were affected by native IgAN, 271 were of male sex, median age at transplantation was 45 years, and 149 received a living donor KTx. Over a median follow-up time of 46 months, 96 IgAN recurrence events occurred, and, among KTx recipients with recurrent IgAN, 27 subsequent graft failure events occurred after 100 months post KTx. IgAN GPS significantly predicted native IgAN cases among all KTx recipients (OR [95% CI]: 1.95 [1.76,2.16], p = 5.60E-07, AUROC 0.73), and lower age at transplantation among recipients with native IgAN (beta [s.e.]: −1.11[0.55], p = 0.04). Clinical model for IgAN recurrence included age, sex, year of transplant, HLA mismatch, recruitment site, and first 5 PCs; clinical model for graft failure included age, sex, year of transplant, HLA mismatch, type of donation, donor age, sex, rejection events, recruitment site, and first 5 PCs. At the multivariable analysis, IgAN GPS, lower age at transplantation, lower HLA mismatch, and higher year of transplant were independently associated with time to IgAN recurrence (Fig. 1a). Among KTx recipients with recurrent IgAN, higher IgAN GPS predicted time-to graft failure independently from clinical factors (Fig. 1b), but not in non-recurrent cases. Conclusion In the KTx setting, IgAN GPS was an independent predictor of IgAN recurrence, suggesting shared genetic susceptibility between native and recurrent IgAN. In addition, associations of IgAN GPS with lower age at transplantation, and with graft failure among recurrent IgAN cases, suggest that IgAN GPS may be predictive of a more aggressive native as well as recurrent disease. Associations with lower HLA mismatch advocate donor-recipient genetic similarities as potential additional predictors of IgAN recurrence. These data, which need external validation, may provide potential new insights into the pathobiology and prediction of recurrent IgAN.

#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief

Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.

Safety and infectious outcomes in pediatric kidney transplant recipients after COVID-19 vaccination: A pediatric nephrology research consortium study.

Adult kidney transplant recipients (KTRs) fully vaccinated against COVID-19 have substantial morbidity and mortality related to SARS-CoV-2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID-19 vaccination series in pediatric KTRs. A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID-19 were enrolled and data were collected pertaining to SARS-CoV-2 infection incidence and severity, graft outcomes and post-vaccination safety profile, as well as overall patient survival. A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5-15). SARS-CoV-2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post-transplant, within the defined follow-up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor-specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA-tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed. Observationally, infectious outcomes of SARS-CoV-2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort.

Strategic Use of Biodegradable Temporizing Matrix (BTM) in Wound Healing: A Case Series in Asian Patients.

Skin and soft tissue reconstruction has long been based on the reconstructive ladder. However, a skin substitute has become popular due to its predictable outcomes, without donor-site morbidity. The biodegradable temporizing matrix (BTM; NovoSorb, PolyNovo Ltd., Port Melbourne, Australia) is a synthetic skin substitute that has recently gained its clinical application. Compared with those of other dermal templates, the clinical efficacy and performance of the BTM are not well established, especially among the Asian population. This study aims to share our experience and strategy of using BTM in various wound conditions. The data of patients who underwent skin and soft tissue reconstruction with BTM at a single institution between January 2022 and December 2023 were reviewed. The patient demographics, wound characteristics, surgical details, secondary procedures, and complications were recorded and analyzed. Postoperative 6-month photographs were collected and independently evaluated by two plastic surgeons and two wound care center nurses using the Manchester Scar Scale (MSS). This study included 37 patients, consisting of 22 males and 15 females with a mean age of 51.8 years (range, 18-86 years old). The wound etiologies included trauma (67.6%), necrotizing soft tissue infection (16.2%), burns (10.8%), toe gangrene (2.7%), and scar excision (2.7%). The average wound area covered by BTM was 50.6 ± 47.6 cm2. Among the patients, eight received concomitant flap surgery and BTM implantation, 20 (54.1%) underwent subsequent split-thickness skin grafts (STSG), and 17 had small wounds (mean: 21.6 cm2) healed by secondary intention. Infection was the most common complication, affecting six patients (n = 6 [16.2%]), five of whom were treated conservatively, and only one required debridement. Thirty-three patients (89.2%) had good BTM take, and only four had BTM failure, requiring further reconstruction. At the last follow-up, 35 out of the 37 patients (94.6%) achieved successful wound closure, and the total MSS score was 10.44 ± 2.94, indicating a satisfactory scar condition. The patients who underwent BTM grafting without STSG had better scar scores than those who received STSG (8.71 ± 2.60 vs. 11.18 ± 2.84, p = 0.039). In conclusion, the BTM is effective and feasible in treating various wounds, with relatively low complication rates, and it can thus be considered as an alternative for skin and soft tissue reconstruction. When combined with adipofasical flap reconstruction, it achieves a more comprehensive anatomical restoration.

Use of Fish Skin Grafts for Wound Management: Report of 5 Pediatric Cases

Abstract Background Managing wounds and scars in children presents a significant challenge for surgical and rehabilitation teams. Studies have already explored the potential of fish skin grafts with Omega-3 in hard-to-heal lower extremity chronic ulcers and deep-burn management. Aims The purpose of this study is to assess the safety and outcome of intact fish skin grafts with Omega-3 when used as skin replacement therapy in the pediatric population. Methods This article was conducted in adherence to our hospital's ethical guidelines. Patients enrolled in this study were identified retrospectively. Their medical records were reviewed, and data was collected concerning patient demographics, initial mode of injury, indication for fish skin placement, operative data, postoperative care, complications and outcomes. The acellular dermal matrix was obtained from North Atlantic codfish skin (Gadus morhua) farmed in Isafjordur, Iceland. Results All patients underwent meticulous wound debridement and patch application under general anesthesia and were discharged the same day. Wound surface ranged between 10 and 110 cm2 (mean: 53 cm2). Standard analgesic medications were taken for a maximum period of 48 hours in all patients. Upon follow-up at our outpatient clinic, shrinkage in the wound surface was observed in all patients after a few days, followed by early wound granulation. Two patients underwent subsequent split-thickness grafting to achieve healing. The mean time required to achieve complete epithelialization was 48.6 days (range: 29 – 62 days). No hypersensitivity or allergic reaction was reported. The definitive outcome was satisfactory in all wounds, meaning complete wound coverage. Conclusion The findings from this case series reveal that fish skin grafts with Omega-3 can be an effective and a safe scaffold in the process of repairing damaged tissues in the pediatric population. We have been able to accomplish a quality skin replacement therapy, with no donor site morbidity.

Synthesis of cyclodextrin-based demulsifier for treatment of oily wastewater through hydrophobic modification strategy

The discharge of oily wastewater not only has an impact on the environment, but also poses a threat to human health. Therefore, the treatment of oily wastewater is crucial. In current work, a novel demulsifier (CD-LA) was prepared using β-cyclodextrin (β-CD) as raw material by the acylation of –OH and subsequent grafting of dodecylamine. The demulsifier was intended for the treatment of oily wastewater. Detailed examinations were conducted on the surface morphology, chemical composition, interfacial activity, and the capacity of CD-LA to engage competitively at the interface. This substance demonstrated a pronounced ability to lower interfacial tension, indicating its utility in supplanting asphaltenes at the oil–water boundary. This action facilitates the weakening or disruption of the interfacial film, which is critical for the successful separation of oily wastewater. The findings revealed that CD-LA excelled in clarifying oily wastewater, proving effective under near-neutral conditions and in environments with elevated salinity. Separated water phase could obtain light transmittance (WT) of 89.75 % and oil removal rate (WR) of 99.83 % after the oily wastewater was demulsified with a concentration of 50 mg/L at room temperature.

Grafting of voltage stabilizer onto EPDM surface and its inhibition effect on the breakdown of EPDM/XLPE interface

Surface discharge on the EPDM/XLPE interface is threatening the safe operation of power cable system and limiting the further improvement of its voltage level. To improve the electrical strength of EPDM/XLPE interface, the surface of EPDM was modified by grafting of voltage stabilizer 4-allyloxy-2-hydroxybenzophenone (AOHBP) based on liquid-phase impregnation and subsequent free radical grafting reaction thermally initiated by DCP. EPDM samples were modified by mixed reagents of DCP and AOHBP with different mass ratios of 1:2, 1:3 and 1:4, respectively. The SEM observation and XRD analysis results indicate that the crystals of AOHBP with a uniform distribution are covered on the surface of EPDM during the sample preparation process and then dissolved after extraction by acetone. The FTIR and ATR results show that the AOHBP molecules are successfully grafted onto the surface of EPDM samples, but there remain a lot of ungrafted reagent molecules on the surface of EPDM before solvent extraction. The grafting rate of AOHBP increases with the proportion of DCP in the mixed reagents. As for the unextracted modified EPDM samples, both the AC and DC breakdown voltage of the EPDM/XLPE interface are increased compared with pure EPDM, and further increased after the ungrafted molecules are extracted because the effect of voltage stabilizer on scavenging high-energy electrons is more efficiently utilized at a smoother interface. The interface breakdown voltage of the sample modified with 1:2 mass ratio of DCP/AOHBP mixed solution is the highest because of its highest grafting rate of voltage stabilizer. This work has proposed a new technical path to improve the electrical aging resistance of polymer insulating surface.

Successful renal transplantation using polytetrafluoroethylene (PTFE) in a patient with complete iliocaval thrombosis: A case report

Heterotopic renal transplant is a well-established technique providing reachable access to the iliac vessels and urinary bladder. Rarely though, surgeons may encounter patients with focal or diffuse vascular thrombosis which would require additional technical maneuvers to overcome such obstruction and prevent catastrophic complications. We present a case of a 43-year-old female with complete iliocaval thrombosis prior to transplant precluding a retroperitoneal approach wherein we used a long segment of synthetic graft as a bridge between the graft renal vein and infrahepatic vena cava. The graft had immediate function and follow-up ultrasound demonstrated patent vasculature. This case highlights the value of preoperative imaging and being surgically prepared for nontraditional sites of vascular anastomosis. Selection of venous drainage in such cases should provide adequate venous outflow minimizing the risk of thrombosis and subsequent graft failure.

Descemet Membrane Endothelial Keratoplasty for Penetrating Keratoplasty

ABSTRACT Background: Descemet membrane endothelial keratoplasty (DMEK) has been utilized more frequently during recent years to treat penetrating keratoplasty (PKP) graft failures. The perioperative evaluation technique of anterior segment optical coherence tomography (AS-OCT) is increasingly significant. Our goal is to discuss DMEK surgical and clinical for subsequent PKP graft failure, along with significant surgical modifications and adjustments in accordance with preoperative assessment utilizing AS-OCT. Materials and Methods: Patients’ records who performed DMEK for PKP failure were retrospectively reviewed. Demographic information, PKP graft size determined by postoperative problems, corneal donor endothelial cell density (ECD), AS-OCT, central pachymetry, visual acuity (VA) evaluated in Snellen units, intraoperative surgical procedure modifications, and postoperative ECD were all included in the data collection. Results: The observation was conducted with 16 patients with 16 eyes, nine males and seven females. The observation period is 18 months. DMEK was performed at an average age of 63. Preoperative AS-OCT was performed on all patients, and based on cases, surgical plans were created. Before processing DMEK, the mean VA is 0.04, and central pachymetry is 685 m. They improved considerably to 0.3 (P value = 0.001) and 542 m (P value = 0.008) at the most recent follow-up. About 93.75% of the grafts were adhered to after the procedure. Late decompensation caused a 6.25% graft failure rate. Graft detachment rates and cases requiring rebubble rates were respectively 18.75%. Conclusion: In DMEK for failed PKP, a good case-specific preoperative assessment by AS-OCT is essential. As a result, it relies on developing a surgical strategy that can improve surgical outcomes, lower the risk of complications, and quicken visual recovery.

Incidence, Risk Factors, and Outcomes of Posttransplant Erythrocytosis Among Simultaneous Pancreas-Kidney Transplant Recipients.

Posttransplant erythrocytosis (PTE) is a well-known complication of kidney transplantation. However, the risk and outcomes of PTE among simultaneous pancreas-kidney transplant (SPKT) recipients are poorly described. We analyzed all SPKT recipients at our center between 1998 and 2021. PTE was defined as at least 2 consecutive hematocrit levels of >51% within the first 2 y of transplant. Controls were selected at a ratio of 3:1 at the time of PTE occurrence using event density sampling. Risk factors for PTE and post-PTE graft survival were identified. Of 887 SPKT recipients, 108 (12%) developed PTE at a median of 273 d (interquartile range, 160-393) after transplantation. The incidence rate of PTE was 7.5 per 100 person-years. Multivariate analysis found pretransplant dialysis (hazard ratio [HR]: 3.15; 95% confidence interval [CI], 1.67-5.92; P < 0.001), non-White donor (HR: 2.14; 95% CI, 1.25-3.66; P = 0.01), female donor (HR: 1.50; 95% CI, 1.0-2.26; P = 0.05), and male recipient (HR: 2.33; 95% CI, 1.43-3.70; P = 0.001) to be associated with increased risk. The 108 cases of PTE were compared with 324 controls. PTE was not associated with subsequent pancreas graft failure (HR: 1.36; 95% CI, 0.51-3.68; P = 0.53) or kidney graft failure (HR: 1.16; 95% CI, 0.40-3.42; P = 0.78). PTE is a common complication among SPKT recipients, even in the modern era of immunosuppression. PTE among SPKT recipients was not associated with adverse graft outcomes, likely due to appropriate management.

UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial

BackgroundGood vision highly depends on the transparency of the cornea, which is the “windscreen” of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient’s cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide.MethodsThis parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints).DiscussionBased on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness.Trial registrationClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

NovoSorb® Biodegradable Temporising Matrix (BTM): What we learned from the first 300 consecutive cases

IntroductionExtensive full-thickness soft-tissue defects remain a challenge in reconstructive surgery. NovoSorb® Biodegradable Temporising Matrix (BTM) represents a novel dermal substitute and was evaluated in wounds deriving from different aetiologies and to highlight risk factors for poor take rates. MethodsAll patients treated with BTM at our department between March 2020 and October 2022 were included. Differences in univariate and linear regression models identified predictors and risk factors for take rates of BTM and split-thickness skin grafts (STSG). ResultsThree hundred patients (mean age 54.2±20.1 years, 66.3% male, 59.7% burns, 19.7% trauma, 20.6% others) were evaluated. Mean take rates of BTM and STSG after BTM delamination were 82.7±25.2% and 86.0±22.6%. Multiple regression analyses showed that higher body mass index (BMI,OR-0.43,95%CI-0.86,-0.01,p=0.44), prior allograft transplantation (OR-15.12,95%CI-26.98,-3.31,p=0.041), longer trauma-to-BTM-application intervals (OR-0.01,95%CI-0.001,-0.001,p=0.038), positive wound swabs before BTM (OR-7.15,95%CI-13.50,-0.80,p=0.028), and peripheral artery disease (OR-10.80,95%CI-18.63,-2.96,p=0.007) were associated with poorer BTM take. Higher BMI (OR-0.40,95%CI-0.76,-0.08,p=0.026), increasing BTM graft surface areas (OR-0.58,95%CI -1.00,-0.17,p=0.005), prior allograft (OR-12.20,95%CI -21.99, -2.41, p=0.015) or autograft transplantations (OR-22.42,95%CI-38.69,-6.14,p=0.001), tumour as the aetiology of the wound (OR-37.42,95%CI-57.41,-17.83,p=0.001) diabetes (OR-6.64,95%CI-12.80,-0.48,p=0.035), and impaired kidney function (OR-5.90,95%CI-10.94,-0.86,p=0.021) were associated with poorer STSG take after delamination of BTM, whereas higher BTM take rates were associated with better STSG take (OR0.40,95%CI0.31,0.50,p<0.001). ConclusionExtensive complex wounds of different aetiologies unsuitable for immediate STSG can be successfully reconstructed by means of two-staged BTM-application und subsequent skin grafting. Importantly, presence of wound contamination or infection and prior allograft coverage appear to jeopardize good BTM and STSG take.

Plasma-Activated Polydimethylsiloxane Microstructured Pattern with Collagen for Improved Myoblast Cell Guidance.

We focused on polydimethylsiloxane (PDMS) as a substrate for replication, micropatterning, and construction of biologically active surfaces. The novelty of this study is based on the combination of the argon plasma exposure of a micropatterned PDMS scaffold, where the plasma served as a strong tool for subsequent grafting of collagen coatings and their application as cell growth scaffolds, where the standard was significantly exceeded. As part of the scaffold design, templates with a patterned microstructure of different dimensions (50 × 50, 50 × 20, and 30 × 30 μm2) were created by photolithography followed by pattern replication on a PDMS polymer substrate. Subsequently, the prepared microstructured PDMS replicas were coated with a type I collagen layer. The sample preparation was followed by the characterization of material surface properties using various analytical techniques, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). To evaluate the biocompatibility of the produced samples, we conducted studies on the interactions between selected polymer replicas and micro- and nanostructures and mammalian cells. Specifically, we utilized mouse myoblasts (C2C12), and our results demonstrate that we achieved excellent cell alignment in conjunction with the development of a cytocompatible surface. Consequently, the outcomes of this research contribute to an enhanced comprehension of surface properties and interactions between structured polymers and mammalian cells. The use of periodic microstructures has the potential to advance the creation of novel materials and scaffolds in tissue engineering. These materials exhibit exceptional biocompatibility and possess the capacity to promote cell adhesion and growth.

Kidney Retransplantation in Children.

Pediatric kidney transplant recipients will likely require a retransplant in their lifetime. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant effect to improve short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that most pediatric renal allograft recipients will require 1 or more retransplants during their lifetime. In the West, an increasing number of patients on the deceased donor wait list are awaiting a retransplant; in the US, 15% of current annual transplants are retransplants. Unfortunately, the use of a second or subsequent grafts in pediatric recipients has inferior long-term graft survival rates compared with initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplant, with the most significant being the cause of the prior transplant failure. Nonadherenceassociated graft loss poses unresolved ethical issues that may affect a patient's access to retransplant. Graft nephrectomy prior to retransplant may benefit selected patients, but the effect of an in situ failed graft on the development of panel reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this presentation be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Fasciotomy in the upper limb after compartment syndrome due to snakebite with subsequent grafting and z-plasty: case report

Fasciotomy in the upper limb after compartment syndrome due to snakebite with subsequent grafting and z-plasty: case report

Versatility in the Use of Cadaveric Skin Grafts for Wound Management

Background. Cadaveric skin grafts were initially used for the management of acute burn wounds. The biological coverage of the wound improves the quality of the wound bed, which prepares it to receive an autologous skin graft. The benefits of cadaveric skin graft in burn wounds have led to its use in the management of acute and chronic wounds of diverse etiologies. Objective. To evaluate the use of cadaveric skin graft and subsequent autologous split-thickness skin graft (STSG) in the management of wounds of diverse etiologies at a single institution. Materials and Methods. A retrospective analysis was performed of patients with wounds of different etiologies managed with cadaveric skin grafts followed by a second procedure in which autologous STSG was performed from May 2017 through May 2022 in the Plastic and Reconstructive Surgery Department of German Hospital, Buenos Aires, Argentina. Results. A total of 25 patients with wounds of different etiologies were included. The mean affected body surface area (BSA) was 1.87%. The mean engraftment percentage of the cadaveric skin graft was 96.6%. The mean engraftment percentage of the STSG was 90.6%. All patients demonstrated improvement in local edema and inflammation, reduced secretions, and reduced pain after treatment. Two patients (8%) had complications, with 1 case of delayed healing of the donor site and 1 case of hypertrophic scarring. Conclusions. Cadaveric skin graft with subsequent STSG is a simple, safe, and effective alternative for the management of complex wounds of diverse etiologies. This technique is particularly useful in patients with multiple comorbidities who are at risk of recurrence and of developing multiple wounds during their lifetime.

A Comparison of Efficacy of Autologous Platelet-rich Plasma and Conventional Sutures in Anchoring Split Skin Graft on Wounds

Abstract Context: Split thickness skin grafting (STSG) restores cutaneous cover over wounds thus protecting the underlying surface from contamination, fluid loss and stimulates healing. Autologous platelet rich plasma (PRP) provides a large number of platelets and high concentration of growth factors which promote overall uptake of STSG. Aims: The aim of this study was to assess the immediate, subsequent adhesion and final take of STSG with application of PRP over recipient site. Methods and Material: 1 year Randomised Control Trial where 80 wounds of various aetiologies were randomised into intervention group (n=40) which received PRP before placing STSG on recipient site and control group (n=40) in which the graft was fixed in place with sutures alone. Immediate graft adhesion and subsequent graft uptake were compared between the two groups and statistical analysis was done with: SPSS Version 20. Results: Irrespective of aetiology, and size, among a total of 80 wounds 87.5% grafts had adhered by 1st minute of application in the intervention group compared to nil in control group (p&lt; 0.0001). Graft uptake was assessed on first three consecutive dressings. There was significantly better graft uptake in intervention group compared to control group [third dressing uptake (98.29%, 93%, p&lt; 0.0001) respectively].Difference in seroma and haematoma formation were also compared between the two groups and found to be not significant. (p&gt;0.05) Conclusions: Application of topical PRP facilitates STSG uptake. It decreases operative time by decreasing mobility of graft over the wound bed. Thus, use of PRP improves outcome of split thickness skin graft in wounds of various aetiologies and we recommend use of the same at recipient site of STSG. CTRI/2021/06/034401

A Tubular Vena Cava Conduit Used to Lengthen a Kidney Transplant Renal Artery Injured During Organ Procurement

Organ transplantation is limited by the supply of transplantable organs, and the supply of organs cannot meet the needs of patients on the waiting list. Ensuring transplantation of any procured organ is therefore mandatory. Organ injury, mostly to the organ's vasculature, can occur during multi-organ procurement, preventing subsequent transplantation. In such a context, vascular reconstructions of arterial or venous organ injuries can be useful. This report describes the case of an obese 64 year old female with a history of diabetic nephropathy who underwent a cadaveric kidney transplant (right kidney with one main renal artery, one inferior polar artery, one vein, and one ureter). The ex situ preparation of the graft revealed that the main renal artery was injured and cut close to the renal hilum (0.8 cm length, 6 mm diameter), not allowing graft implantation. In order to increase the length of the main renal artery, the donor inferior vena cava was used to create a tubular conduit, allowing subsequent graft implantation. Cold and warm ischaemic times were respectively 12 hours and 36 minutes, with immediate graft function. The patient was discharged on day 8 (serum creatinine level was 95 μmol/L). Twelve month follow up was uneventful (serum creatinine level was 108 μmol/L and duplex ultrasonography showed homogeneous blood flow throughout the graft). This case report highlights the possibility of overcoming an injured kidney graft artery by creating a tubular vena cava conduit in order to allow subsequent transplantation. Vascular reconstructions of organs injured during procurement should be considered.