Application of platelet-rich fibrin and freeze-dried bone allograft following apicoectomy: A comparative assessment of radiographic healing.

Background: Apicoectomy conceptualizes surgically maintaining a tooth with an endodontic lesion that cannot be resolved by conventional endodontic (re-) treatment. To achieve this, continuous improvement in surgical techniques, materials and instruments is being done to enhance the outcome of periapical endodontic surgeries. The purpose of this study was to compare, radiographically, the healing kinetics of platelet-rich fibrin (PRF) and mineralized freeze-dried bone allograft (FDBA) in patients undergoing apicoectomy. Materials and Methods: Nineteen patients (aged 18-40 years) were included in the study and randomly assigned to groups A or B, where they received PRF or FDBA, respectively. Following apicoectomy, PRF gel and FDBA graft were prepared and placed in the osseous defect followed by placement of PRF membrane for graft stabilization and flap closure. Radiographic follow-up was done at the 1st, 3rd, 6th and 12th months for evaluation of healing using Molven's criteria. Statistical analysis was done with Pearson's and McNemar's Chi-square tests. Results: A highly significant difference (P = 0.002) in radiographic healing was observed at 6 months. Complete healing was observed in 50% of cases in Group A whereas in Group B, none of the cases presented with complete radiographic healing. However, at the end of 12 months, complete radiographic healing was observed in both groups. Conclusion: Our data suggest that PRF accelerates bone healing as compared to FDBA and is both time and cost-efficient.

Nerve regeneration in rat peripheral nerve allografts: An assessment of the role of endogenous neurotrophic factors in nerve cryopreservation and regeneration.

Peripheral nerve injury is a common clinical problem that often leads to significant functional impairment or even complete paralysis. Allograft has been proposed as a potential repair strategy for peripheral nerve injuries. Furthermore, peripheral nerve cryopreservation may result in nearly unlimited supply of grafts. However, the concentration of neurotrophic factors secreted by Schwann cells (SCs) in the local micro-environment after transplantation may not be sufficient for the survival of neuronal soma and axonal regeneration. Here, we investigated the effect of endogenous neurotrophic factors (ENTFs) on nerve regeneration in rats after the allograft of a cryopreserved sciatic nerve. ENTFs were highly expressed in the sciatic nerves pretreated for 14 days. Although the number of surviving cells in the sciatic nerves and their immunogenicity were low in the 14-day group after 4 weeks of cryopreservation, they continued to express high levels of ENTFs in vitro. At 1 week postoperation, the 14-day Allo group showed low plasma levels of interleukin-2, interferon-γ and tumour necrosis factor-alpha and low cellular immune response. At 20 weeks postoperation, nerve regeneration and functional recovery in the 14-day Allo group was similar to that in the fresh isograft group but better than that in the cryopreserved-fresh allograft and fresh allograft groups. Thus, ENTFs were induced in vitro after pretreatment of the sciatic nerve. Following cryopreservation, the sciatic nerves with high levels of ENTFs continued to express high levels of ENTFs in vitro. The immune response after allograft was weak, which promoted recipient nerve regeneration.

Histomorphometrical Assessment of Sinus Augmentation Using Allograft (Particles or Block) and Simultaneous Implant Placement.

The aim of the present study was to compare the clinical, radiological and histomorphometrical outcome of simultaneous implant placement following augmentation of atrophic maxillary sinuses using allograft (block or particles). Consecutive patients with maxillary residual alveolar ridge height ≤3 mm, scheduled for sinus floor augmentation with simultaneous implant placement, were randomly included. Allograft bone-block or bone-particles served as grafting material. Simultaneously, dental implants were inserted. Biopsies were taken at second stage surgery (after 9 months) for histomorphometric evaluation. Initially 38 sinus augmentations (29 individuals) were allocated for the study. In 4 out of 21(19%) sinuses using particles it was impossible to stabilize the implants and a second stage insertion was preferred, leaving 34 sinuses for histomorphometric evaluation. The difference in the ability to perform simultaneous implant placement was statistically significant (p < 0.05). Ninety implants were inserted simultaneously. All implants osseointegrated. None of the implants was lost up to the end of follow-up time (Range 50-120 months, Mean 74.5 ± 13.5 months). Bone gain radiographically 12.3 ± 1 mm vs. 11.2 ± 1 mm (block vs. particles respectively) and new bone formation histomorphometrically 27.7 ± 15% vs. 32.1 ± 19% (block vs. particles respectively) showed no statistically significant differences between the two groups. Sinus augmentation using allograft (particles or block) and simultaneous implant placement is predictable. All outcome parameters are similar when sinus bone-blocks augmentation is compared to bone-particles augmentation (radiological new bone gain, implant survival, hisomorphometricly new bone formation) despite the ability to stabilize implants, when placed simultaneously with sinus augmentation. Blocks may be advisable when simultaneous implant placement is imperative in cases with residual alveolar bone height ≤3 mm.

Striving for more just allocation of liver allografts between patients with and without hepatocellular carcinoma: successes and challenges.

PURPOSE OF REVIEW: Recently the United Network for Organ Sharing (UNOS) adopted new rules for the allocation of liver allografts for recipients with hepatocellular carcinoma (HCC) in hopes of removing regional variation in HCC practice and regional differences in patient survival. Understanding how previous changes to HCC allocation have both succeeded and failed to match the pretransplant mortality of HCC and non-HCC patients on the waitlist will help us to better evaluate these changes and predict where we may again fail. RECENT FINDINGS: Previous revisions of the HCC allocation rules were successful in more accurately matching the waitlist mortality of HCC and non-HCC patients. Efforts to select for less aggressive tumor biology have resulted in better disease free and patient survival. Several articles have also supported the practice of using locoregional therapies to downstage the patients to within Milan criteria. New rules seek to reduce the amount of geographic disparity in the allocation system. SUMMARY: Over time UNOS has steady improved the liver allocation polices to attempt to match pretransplant mortality for patients with HCC and without HCC. The latest changes to the organ allocation rules succeed in implementing some of these best practices. However, one can also predict several ongoing challenges to fair allocation that may not have been addressed by recent changes.

Sinus floor elevation using a new bovine bone grafting material: case report and bone grafting materials update / Actualización en materiales de relleno óseo: reporte de un caso clínico de elevamiento del piso del seno maxilar usando un nuevo material de relleno óseo bovino

Bone grafting is important to preserve the alveolar bone ridge height and volume for dental implant placement. Even though implant-supported overdentures present highly successful outcomes, it seems that a great number of edentulous individuals have not pursued implant-based rehabilitation. The cost of the treatment is one of the reasons of discrepancy between highly successful therapy and its acceptance. Therefore, the development of biomaterials for bone grafting with comparable characteristics and biological effects than those renowned internationally, is necessary. In addition, domestic manufacture would reduce the high costs in public health arising from the application of these biomaterials in the dental feld. The purpose of this clinical case report is to provide preliminary clinical evidence of the efficacy of a new bovine bone graft in the bone healing process when used for sinus floor elevation. (AU)

El uso de injertos óseos es importante para preservar la altura y el volumen de la cresta alveolar para la colocación de implantes dentales. Si bien las sobredentaduras implanto-soportadas presentan resultados altamente exitosos, la mayoría de las personas desdentadas no han sido rehabilitadas mediante implantes dentales. Uno de los principales motivos por los cuales los pacientes no aceptan este tipo de tratamiento, altamente exitoso, es el elevado costo del mismo. Por ello, es necesario el desarrollo de biomateriales de injerto óseo con características y efectos biológicos comparables a los reconocidos internacionalmente. Asimismo, la fabricación nacional reduciría los altos costos en Salud Pública derivados de la aplicación de estos biomateriales en el campo dental. El objetivo de esta comunicación es presentar un caso clínico a fin de proporcionar evidencia preliminar acerca de la eficacia de un nuevo injerto de hueso bovino en el proceso de cicatrización ósea en el levantamiento del piso del seno maxilar. (AU)

Association Between Declined Offers of Deceased Donor Kidney Allograft and Outcomes in Kidney Transplant Candidates.

Importance: In the United States, substantial disparities in access to kidney transplant exist for wait-listed candidates with end-stage renal disease. The implications of transplant centers' willingness to accept kidney offers for access to transplant and mortality outcomes are unknown. Objective: To determine the outcomes for wait-listed kidney transplant candidates after the transplant center's refusal of a deceased donor kidney offer. Design, Setting, and Participants: This cohort study obtained data from the United Network for Organ Sharing Potential Transplant Recipient data set on all deceased donor kidney offers in the United States made between January 1, 2008, and December 31, 2015. The final study cohort included adult patients who were wait-listed for kidney transplant and received at least 1 allograft offer during the study period (N = 280 041). Data analysis was conducted from June 1, 2018, to March 30, 2019. Exposure: Candidate state of residence. Main Outcomes and Measures: Waiting list outcome event groups included received deceased donor allograft, received living donor allograft, died while on the waiting list, removed from the waiting list without a transplant, or still on the waiting list at the end of follow-up. Results: Among the 280 041 kidney transplant candidates included in the study, the mean (SD) age at wait-listing was 51.1 (13.1) years, and male patients were predominant (171 517 [61.2%]). In this cohort, 81 750 candidates (29.2%) received a deceased donor kidney allograft, 30 870 (11.0%) received a living donor allograft, 25 967 (9.3%) died while on the waiting list, and 59 359 (21.2%) were removed from the waiting list. Overall, 10 candidates with at least 1 previous allograft offer died each day during the study period. Time to first offer was similar for candidates who received deceased donor kidney allograft compared with those who died while waiting (median [interquartile range {IQR}] time, 79 [16-426] days vs 78 [17-401] days, respectively). Deceased donor allograft recipients had a median of 17 offers (IQR, 6-44) over 422 days (IQR, 106-909 days), whereas candidates who died while waiting received a median of 16 offers (IQR, 6-41) over 651 days (IQR, 304-1117 days). Most kidneys (84%) were declined on behalf of at least 1 candidate before being accepted for transplant. As reported by centers, organ or donor quality concerns accounted for 8 416 474 (92.6%) of all declined offers, whereas offers were infrequently refused because of patient-related factors (232 193 [2.6%]), logistical limitations (49 492 [0.5%]), or other concerns. The odds of death after an offer and the median number of offers received prior to death varied considerably by state. Conclusions and Relevance: This study found that transplant candidates appeared to receive a large number of viable deceased donor kidney offers that were refused on their behalf by transplant centers, potentially exacerbating the detrimental consequences of the organ shortage; increased transparency in organ allocation process and decisions may improve patient-centered care and access to kidney transplant.

Assessment of Trends in Transplantation of Liver Grafts From Older Donors and Outcomes in Recipients of Liver Grafts From Older Donors, 2003-2016.

Importance: In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years. Objective: To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort. Design, Setting, and Participants: Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used. Exposures: Year of liver transplant and age of liver donor. Main Outcomes and Measures: Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality. Results: In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization-level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors. Conclusions and Relevance: These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

A quality improvement pilot assessment of the safety and associated outcomes of a viable cryopreserved umbilical tissue allograft as an adjunct surgical wrap in peroneus brevis tendon repair.

Surgical tendon repairs of the lower extremity are frequently associated with post-operative (post-op) risks that result in poor patient outcomes. Initially, increased pain levels may contribute to extended post-op rehabilitation while the development of tissue adhesions and fibrosis limit long-term functionality through reduced range of motion. Several surgical methods describing incorporation of various augmentative graft materials in tendon repair exist. However, reports demonstrating technique and both short- and long-term patient outcomes are lacking. Recently, advances in tissue preservation technology have led to the commercialization of human placental allografts. Of these available allogeneic biomaterials, the components found in human placental membranes may provide anti-inflammatory, antimicrobial, anti-adhesive, and antifibrotic properties to benefit surgical outcomes.Here, the authors introduce and technically describe the use of a viable cryopreserved umbilical tissue (vCUT) (Stravix, Osiris Therapeutics, Inc., Columbia, MD) as a complementary surgical wrap in primary tendon repair, with particular focus on the peroneus brevis. A pilot study was undertaken to assess the safety and potential for secondary rehabilitative outcomes associated with the use of vCUT in 5 tendon repair cases. The use of vCUT as a surgical tendon wrap was evaluated via the following primary endpoints at post-op day 7:Secondary investigative endpoints included clinical and rehabilitative outcome measures for comparative pain reduction and transition times to both controlled ankle movement (CAM) boot and normal shoe ambulation.All patients were followed for an average of 24.15 months (range 16.75-26.5 months) after surgery. For primary safety measures, erythema, tenderness, drainage, heat, and swelling was absent in all 5 surgical sites. None of the patients required post-op use of narcotics past day 7. The potential for long-term rehabilitative improvement with adjunct use of vCUT was also demonstrated through reduced pain and reduced transition times to functional and non-assisted ambulation in normal shoewear as compared to historical controls managed without vCUT.This surgical technique is simple and safe for patients and preliminary findings have demonstrated favorable clinical and rehabilitative outcomes over historically observed controls.

Cessation of extracorporeal photopheresis in chronic lung allograft dysfunction: effects on clinical outcome in adults.

BACKGROUND: Extracorporeal photopheresis (ECP) has been reported to be safe and the ultimate treatment option in lung transplant recipients with chronic lung allograft dysfunction (CLAD), the main overall cause of mortality in lung transplant recipients. However, ECP is not reimbursed in selected health jurisdictions, and reimbursement by health insurance providers is a major issue. In Switzerland, ECP is not recognised by the health authorities as a therapy option for CLAD; thus by the end of 2014, ECP had to be stopped in the majority of adult lung transplant recipients cared for at the University Hospital Zurich because of lack of continuous funding. OBJECTIVE: To describe the outcome of lung transplant recipients after forced cessation of ECP treatment. METHOD: We retrospectively analysed outcome of 12 lung transplant recipients undergoing ECP for different phenotypes of CLAD (bronchiolitis obliterans syndrome, restrictive allograft syndrome) at our centre followed-up for 12 months after forced cessation of ECP. RESULTS: Within the 12 months after treatment cessation, seven patients (58%) died with a median survival of 207 days (range 6-365 days). Lung function (FEV1, forced expiratory volume in 1 second) declined significantly 6 months after ECP cessation (p = 0.003). CONCLUSION: Our data support the role of ECP as valuable treatment option in lung transplant recipients with CLAD.

Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts.

AIM OF THE STUDY: Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. MATERIALS AND METHODS: Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 µL phosphate buffered saline and the ALLO/SVF group received 100 µL SVF (2.25 ± 0.45 × 10(7) cells) locally where the grafting was performed. RESULTS: Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). CONCLUSIONS: Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection.

Temporal in vivo assessment of fresh osteochondral allograft transplants to the distal aspect of the femur by dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) and zonal T2 mapping MRI.

BACKGROUND: Zonal T2 mapping and dGEMRIC (delayed gadolinium-enhanced magnetic resonance imaging of cartilage) are diagnostic quantitative techniques to evaluate the biochemical health of articular cartilage. We adapted these techniques to investigate the results of osteochondral allograft transplantation and correlated the findings with patient-reported outcomes. METHODS: Nine patients with contained ICRS (International Cartilage Repair Society) grade-4 defects of the articular portion of a femoral condyle were treated with fresh osteochondral allografts and were evaluated prospectively with dGEMRIC and T2 mapping before and after gadolinium administration. The KOOS (Knee Injury Osteoarthritis Outcome Score) and IKDC (International Knee Documentation Committee) subjective scores were obtained at baseline and at one and two years postoperatively. For quantitative T2 mapping, regions of interest were drawn in the deep and superficial layers of allograft and control cartilage. For dGEMRIC analyses, the relaxation rate, post-gadolinium change in relaxation rate, and ratio between changes in the allograft and control regions of interest were calculated from T1 values. RESULTS: The mean ratio between the post-gadolinium changes in the allograft and control cartilage was 1.13 at one year and 1.55 at two years, and the ratio increased in eight of nine patients from one to two years. There was no difference between the mean T2 values in the deep zone of the allograft and control cartilage at one or two years (p > 0.05), but mean T2 values were higher in the superficial zone of the allograft cartilage at one (p < 0.0001) and two (p < 0.028) years. The mean improvement from baseline was significant at one and two years for the IKDC and all five KOOS subdomains (p < 0.05). All or nearly all patients showed improvements in all clinical outcomes scores at one year. CONCLUSIONS: Functional MRI techniques can be applied to noninvasively assess the biochemical health of cartilage after osteochondral allograft transplantation. The MRI findings correlated with certain patient-reported outcomes in the early postoperative period. Relative glycosaminoglycan content and the collagen structure of allograft cartilage may undergo time-dependent degeneration. A patient's perception of clinical outcome and quality of life is likely multifactorial and is impacted by more than the health of the allograft cartilage.

Assessment of the regenerative potential of allogeneic periodontal ligament stem cells in a rodent periodontal defect model.

BACKGROUND AND OBJECTIVE: The complex microenvironment of the periodontal wound creates many challenges associated with multitissue regeneration of periodontal lesions. Recent characterization of mesenchymal stem cell-like populations residing in periodontal ligament tissues has shown that these cells exhibit features of postnatal stem cells. Despite these advances, a lack of consistency in design of preclinical studies and a limited study of allogeneic transplantation applications has restricted our understanding of their clinical utility in the treatment of periodontal disease. The aim of this study was to assess the regenerative potential of allogeneic periodontal ligament stem cells (PDLSCs) in a rat periodontal fenestration defect mode and to identify an optimal end time-point suitable for quantitative assessment of tissue regeneration. MATERIAL AND METHODS: Periodontal fenestration defects, created in Sprague Dawley rats, were treated with allogeneic PDLSCs seeded onto Gelfoam(®) (Absorbable gelatin sponge; Pharmacia Corporation, Kalamazoo, MI, USA) or with Gelfoam(®) alone, or remained untreated. Experimental rats were killed at 7, 14, 21 or 28 d after surgery and the tissues were processed for immunohistochemical and histomorphometric examination. RESULTS: Defects treated with PDLSCs showed significantly greater percentage bone fill and length of new bone bridge compared with the untreated group or the group treated with Gelfoam(®) alone on days 14 and 21. Similarly, a statistically significant difference was achieved within specimens retrieved on day 21 for analysis of regeneration of cementum/periodontal ligament (PDL)-like structures. CONCLUSION: The present investigation shows that allogeneic PDLSCs have a marked ability to repair periodontal defects by forming bone, PDL and cementum-like tissue in vivo. The results suggest that treatment periods of 14 and 21 d are optimal end time-points for quantitative assessment of periodontal regeneration within the rodent fenestration-defect model utilized in the present study.