Arterial Grafts for Coronary Bypass: A Critical Review After the Publication of ART and RADIAL.

Observational and randomized evidence shows that arterial grafts have better patency rates than saphenous vein grafts (SVGs) in coronary artery bypass grafting. Observational studies suggest that the use of multiple arterial grafts is associated with longer postoperative survival, but this must be interpreted in the context of treatment allocation bias and hidden confounders intrinsic to the study designs. Recently, a pooled analysis of 6 randomized trials comparing the radial artery with the SVG as the second conduit and the largest randomized trial comparing the use of single and bilateral internal thoracic arteries have provided apparently divergent results about a clinical benefit with the use of >1 arterial conduit. However, both analyses have methodological limitations that may have influenced their results. At present, it is unclear whether the well-documented increased patency rate of arterial grafts translates into clinical benefits in the majority of patients undergoing coronary artery bypass grafting. A large randomized trial testing the arterial grafts hypothesis (ROMA [Randomized Comparison of the Clinical Outcome of Single Versus Multiple Arterial Grafts]) is underway and will report the results in a few years.

Advances in the repair of segmental nerve injuries and trends in reconstruction.

Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of nonneuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, noncritical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be used, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system.

Myelomeningocele Repair Combining a Double Cryopreserved Amniotic Membrane Homograft and the Keystone Flap in a 3-Year-Old Child: A Case Report.

INTRODUCTION: Early repair in patients affected by myelomeningocele (MMC) is of paramount importance in order to prevent infection, minimize neural tissue damage, and reduce mortality. Treatment must include duraplasty and possibly an adequate soft tissue coverage. Delayed surgery in MMC patients can be more tedious due to the less clear borders between the placode and the skin. Moreover, the risks of wound infection and breakdown increase significantly. CASE PRESENTATION: We present the unusual case of a large MMC in a 3-year-old patient treated by combining the recently described cryopreserved amniotic membrane (AM) as homograft for dural reconstruction and a bilateral Keystone flap for soft tissue reconstruction. DISCUSSION: Thanks to its anti-inflammatory and elastic proprieties, the AM can play an important role in preventing adhesion between the reconstructed layers, thus reducing the risk of spinal cord tethering. The Keystone flap, at the same time, allows the wound tension to be distributed widely over the flap margins and not only along the midline, which overlies the duraplasty, enhancing the scar quality and lowering the risk of cerebrospinal fluid recurrence and wound dehiscence, with no donor site morbidity.

How Thick Is the Oral Mucosa around Implants after Augmentation with Different Materials: A Systematic Review of the Effectiveness of Substitute Matrices in Comparison to Connective Tissue Grafts.

This systematic review aimed to assess the effectiveness of xenogeneic collagen matrices (XCMs) and acellular dermal matrices (ADMs) in comparison to connective tissue grafts (CTGs) for the augmentation of oral mucosa around dental implants. MEDLINE and the Web of Science were searched for clinical studies that compared substitute materials for the augmentation of oral mucosa to the subepithelial connective tissue graft around dental implants during or after implantation. The review was conducted according to the recommendations of the PRISMA statement. From an initial search result set of 1050 references, seven articles were included in the review. The study designs were heterogeneous, so no meta-analysis could be performed. Both the CTG and either type of substitute material resulted in increased mucosal thickness. Four studies showed no significant difference, while three demonstrated a significant difference, favoring the CTGs over alternative materials. Soft tissue augmentation around dental implants is a safe procedure and leads to thicker mucosal tissue. The subepithelial connective tissue graft can still be regarded as the gold standard, but substitute materials may be an acceptable alternative in some situations, such as for pain-sensitive patients, among inexperienced surgeons, and for sites with an already thick biotype.

Differences in Cellular Composition of Peripheral Blood Stem Cell Grafts from Healthy Stem Cell Donors Mobilized with Either Granulocyte Colony-Stimulating Factor (G-CSF) Alone or G-CSF and Plerixafor.

This study was conducted to characterize and compare peripheral blood stem cell grafts from healthy donors who underwent granulocyte colony-stimulating factor (G-CSF) mobilization and subsequently received 1 dose of plerixafor after insufficient stem cell yields were achieved at the first apheresis. Aliquots from 35 donors were collected from the first apheresis after mobilization with G-CSF alone and from the second apheresis after additional plerixafor administration. Samples were freshly analyzed for cellular subsets by 8-color flow cytometry. Leukapheresis samples mobilized with additional plerixafor showed a significant increase of total nucleated cells, including B cells, CD4+ and CD8+ T cells, and CD34+ hematopoietic stem and progenitor cells. Absolute numbers of plasmacytoid dendritic cells were also significantly increased, whereas no changes were detected for myeloid dendritic cells. Furthermore, absolute numbers of regulatory T cells increased, with naive CD45RA+ regulatory T cells showing the highest rise. Finally, strikingly higher numbers of myeloid-derived suppressor cells were detected in the plerixafor and G-CSF-mobilized graft. The mobilization of peripheral stem cells in healthy donors with G-CSF and plerixafor led to a significant difference in cellular graft composition compared with G-CSF alone. The clinical impact of the different cell composition for the graft recipient warrants further clinical investigation.

Mechanical Evaluation of Tracheal Grafts on Different Scales.

Tissue engineered (or bioengineered) tracheas are alternative options under investigation when the resection with end-to-end anastomosis cannot be performed. One approach to develop bioengineered tracheas is a complex process that involves the use of decellularized tissue scaffolds, followed by recellularization in custom-made tracheal bioreactors. Tracheas withstand pressure variations and their biomechanics are of great importance so that they do not collapse during respiration, although there has been no preferred method of mechanical assay of tracheas among several laboratories over the years. These methods have been performed in segments or whole tracheas and in different species of mammals. This article aims to present some methods used by different research laboratories to evaluate the mechanics of tracheal grafts and presents the importance of the tracheal biomechanics in both macro and micro scales. If bioengineered tracheas become a reality in hospitals in the next few years, the standardization of biomechanical parameters will be necessary for greater consistency of results before transplantations.

Successful reuse of a transplanted kidney 9 years after initial transplantation: 4-year follow-up.

BACKGROUND: Kidney transplantation is the preferred renal replacement therapy for patients with end-stage renal disease, but the waiting list for kidneys continues to grow because of a shortage of donor organs. The reuse of transplanted kidneys would seem to be a good approach to expand the pool of available organs. Here, we describe the reuse of a kidney 9 years after the initial transplantation. At 4-year follow-up, the second recipient is showing good renal function. CASE PRESENTATION: In 2005, a kidney was transplanted from a 40-year-old man, who suffered brain death due to an intracranial hemorrhage, into a 45-year-old man. Nine years later, the recipient suffered a ruptured cerebral aneurysm, resulting in brain death. The kidney was re-transplanted into a 40-year-old man with diabetic nephropathy who had received hemodialysis for 5 years. During 4 years of follow-up, the graft has functioned well. CONCLUSIONS: This case demonstrates the successful regrafting of a transplanted kidney. We believe this is the longest period for reuse of kidney after initial transplantation. The outcome suggests that a well-functioning transplanted kidney can be reused years after transplantation.

Satisfactory knee function after single-stage posterolateral corner reconstruction in the multi-ligament injured/dislocated knee using the anatomic single-graft technique.

PURPOSE: Increasing importance has been placed on the posterolateral corner (PLC) in maintaining varus and rotational stability of the knee. The goal of this study was to evaluate knee function and clinical stability following a single-graft PLC reconstruction technique and identify factors associated with poor knee function. METHODS: This study identified patients with a multi-ligament knee injury between 2006 and 2013. Patients who received a single-graft fibular collateral ligament and PLC reconstruction with a single-stage surgery during the study period and had a minimum follow-up of 2 years after surgery were included. Functional outcomes were assessed using Lysholm and IKDC scores. Varus and rotational knee laxity and range of motion were assessed using physical examination. RESULTS: The final study cohort included 61 patients who underwent PLC reconstruction using a single-graft technique. The mean IKDC score was 74.1 (± 22.3) and the mean Lysholm score was 80.3 (± 21.8) at mean follow-up of 3.8 years (range 2-9 years). Mean range of motion at final follow-up measured from 0° to 126° [range flexion: 95-145, range extension: 0-5]. Fifty-eight patients (95%) had grade 0 varus laxity in full knee extension, and 54 patients (88.5%) had grade 0 varus laxity at 30° of knee flexion. Female gender was associated with a lower postoperative IKDC score (p = 0.04). CONCLUSION: Surgical treatment of the PLC using a single-graft technique can result in satisfactory knee function and stable physical examination findings at minimum 2 years after surgery. Female gender was predictive of poor knee function after PLC reconstruction. Surgical treatment of PLC injuries should be individualized based on the timing of surgery, specific injured knee structures, and physical examination findings. This study helps validate the use of a single-graft technique for PLC reconstruction and can be used to help counsel patients about expected knee function after surgical treatment of PLC injuries. Level of evidence IV.

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives.

Tissue engineering and regenerative medicine involve many different artificial and biologic materials, frequently integrated in composite scaffolds, which can be repopulated with various cell types. One of the most promising scaffolds is decellularized allogeneic extracellular matrix (ECM) then recellularized by autologous or stem cells, in order to develop fully personalized clinical approaches. Decellularization protocols have to efficiently remove immunogenic cellular materials, maintaining the nonimmunogenic ECM, which is endowed with specific inductive/differentiating actions due to its architecture and bioactive factors. In the present paper, we review the available literature about the development of grafts from decellularized human tissues/organs. Human tissues may be obtained not only from surgery but also from cadavers, suggesting possible development of Human Tissue BioBanks from body donation programs. Many human tissues/organs have been decellularized for tissue engineering purposes, such as cartilage, bone, skeletal muscle, tendons, adipose tissue, heart, vessels, lung, dental pulp, intestine, liver, pancreas, kidney, gonads, uterus, childbirth products, cornea, and peripheral nerves. In vitro recellularizations have been reported with various cell types and procedures (seeding, injection, and perfusion). Conversely, studies about in vivo behaviour are poorly represented. Actually, the future challenge will be the development of human grafts to be implanted fully restored in all their structural/functional aspects.

[Application of vacuum wound therapy with split thickness skin grafts in the head and neck area]. / Anwendung von Vakuum-Wundtherapie bei Spalthaut-Transplantaten im Kopf-Hals-Bereich.

OBJECTIVE: In vacuum wound therapy (VAC) a negative pressure can continuously clean effusions and enhance the formation of granulation tissue significantly. In visceral, trauma and burns surgery this technique is used frequently in critical wounds. In the head and neck area there is limited experience and publications. Especially in the combined use of split-thickness-skin grafts (STSG) and VAC there is no published evidence. MATERIAL AND METHODS: A retrospective database analysis was done and resulted in 36 single VAC therapies in 13 patients. They were treated between 2012 and 2017 in the Department of Otorhinolaryngology of the University Medical Center Ulm, Germany. A data analysis was performed relating to indications, diagnoses, comorbidities as well as the clinical course and outcome with special focus on STSG. RESULTS: Besides classical indications as pharyngo-cutaneous fistulas and troublesome would healing after flap surgery, 7 cases of VAC use with split-thickness skin grafts were identified. The median treatment duration was 11 days, the VAC dressing was changed twice in average, the median negative pressure was 70 mmHg. Wound closure was successful in 13/13 cases, in 7/13 cases wound closure was achieved by split-thickness skin graft with synchronous VAC therapy, 4/13 cases showed healing by secondary intention, in 2/13 cases a local or distant flap was used. CONCLUSIONS: We first describe the successful use of VAC therapy in combination with STSG in the head and neck area. This was effective in radiated patients and in critically ill patients with sepsis and necrotizing fasciitis.

Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts.

Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.

Ventral-onlay buccal mucosa graft substitution urethroplasty for urethral stricture in women.

OBJECTIVE: To present our outcomes of ventral-onlay buccal mucosa graft (BMG) substitution urethroplasty in treating female urethral stricture (FUS). PATIENTS AND METHODS: We conducted a review of a prospectively collected database of 22 consecutive women (median [range] age 50 [34-72] years) with urethral stricture who underwent ventral onlay BMG substitution urethroplasty after June 2012 and who had a minimum follow-up of 6 months (median 21.5, range 6-51 months). Data were analysed for stricture recurrence, change in median maximum urinary flow rate (Qmax ) and median post-void residual urine volume (PVR). Statistical analysis was performed using the Wilcoxon signed rank test, Student's t-test and the Mann-Whitney U-test. RESULTS: Freedom from stricture recurrence was achieved in 21/22 (95.5%) women. The median (range) Qmax significantly improved, increasing from 7 (3.5-11) to 18 (5-37) mL/s (P <0.05). The median (range) PVR was significantly reduced from 100 (0-300) to 15 (0-150) mL (P < 0.05). Short- and longer-term complication rates were low. One woman developed mild de novo stress urinary incontinence, which settled with conservative management by 6 months. CONCLUSIONS: Early and medium-term results indicate that ventral onlay BMG substitution urethroplasty is an excellent treatment for FUS that can avoid the need for the repeat procedures regularly required after traditional endoscopic management.

Comparison of Efficacy and Complications Among Various Spacer Grafts in the Treatment of Lower Eyelid Retraction: A Systematic Review.

BACKGROUND: Lower eyelid retraction is a difficult problem to treat, but it is a prevalent condition and a common complication of blepharoplasty. The use of spacer grafts to increase eyelid height and improve symptoms has been described for a long time, but the optimal choice of spacer graft material is unknown. OBJECTIVES: The authors reviewed the currently available evidence to determine the best available spacer graft material in terms of efficacy and complications. METHODS: A systematic review of all available literature published between 1985 and the present was performed using the Pubmed, Ovid MEDLINE, and Cochrane library databases. Inclusion criteria were that the studies contain original content assessing the treatment of lower eyelid retraction in humans using a spacer graft and provide quantitative outcomes data. RESULTS: One hundred and twelve articles were reviewed following an initial screen using titles, and 19 articles were chosen for inclusion in this systematic review. Analysis of these articles revealed no spacer graft material that is clearly superior to others. CONCLUSIONS: Due to a lack of high quality evidence, this review did not reveal one spacer graft material that is clearly superior to others. However, a narrative summary of the available evidence reveals unique sets of advantages and disadvantages associated with the various materials currently available. Further research in the form of well-designed studies will be necessary to further clarify advantages of certain spacer graft materials over others. LEVEL OF EVIDENCE: 5.

Role of temperature in reconditioning and evaluation of cold preserved kidney and liver grafts.

PURPOSE OF REVIEW: Organ shortage in transplantation medicine forces surgical research toward the development of more efficient approaches in organ preservation to enable the application of 'less than optimal' grafts. This review summarizes current techniques aiming to recondition cold-stored organ grafts prior to transplantation to reduce reperfusion-induced tissue injury and improve postimplantation graft function. RECENT FINDINGS: End-ischemic reconditioning has classically been attempted by cold oxygenated perfusion. By contrast, evaluation of graft performance prior to transplantation might be facilitated by perfusion at higher temperatures, ideally at normothermia. A drastic temperature shift from cold preservation to warm perfusion, however, has been incriminated to trigger a so-called rewarming injury associated with mitochondrial alterations. A controlled gradual warming up during machine perfusion could enhance the restitution of cellular homeostasis and improve functional outcome upon warm reperfusion. SUMMARY: Machine perfusion after conventional cold storage is beneficial for ulterior function after transplantation. Cold grafts should be initially perfused at low temperatures allowing for restitution of cellular homeostasis under protective hypothermic limitation of metabolic turnover. Delayed slow rewarming of the organ might further mitigate rewarming injury upon reperfusion and also increases the predictive power of evaluative measures, taken during pretransplant perfusion.

A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane.

Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a challenge. They are more susceptible to complications such as infection and amputation and require treatments that promote rapid development of granulation tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable cryopreserved human placental membrane (vCHPM) for DFUs has been established in a level 1 trial. However, complex wounds with exposed deeper structures are typically excluded from randomised controlled clinical trials despite being common in clinical practice. We report the results of a prospective, multicentre, open-label, single-arm clinical trial to establish clinical outcomes when vCHPM is applied weekly to complex DFUs with exposed deep structures. Patients with type 1 or type 2 diabetes and a complex DFU extending through the dermis with evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The mean wound area was 14·6 cm2 , and mean duration was 7·5 months. For patients completing the protocol, the primary endpoint, 100% wound granulation by week 16, was met by 96·3% of patients in a mean of 6·8 weeks. Complete wound closure occurred in 59·3% (mean 9·1 weeks). The 4-week percent area reduction was 54·3%. There were no product-related adverse events. Four patients (13%) withdrew, two (6·5%) for non-compliance and two (6·5%) for surgical intervention.

[Clinical and morphological signs of viral damage to a kidney transplant]. / Kliniko-morfologicheskie priznaki virusnogo porazheniia pochechnogo transplantata.

AIM: Тo compare morphological changes and results of immunohistochemical (IHC) identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in the biopsy specimens with their clinical manifestations in recipients of renal transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted using 71 needle renal transplant biopsy specimens from patients in the study group and 10 renal biopsy specimens from those in the control group. A number of clinical indicators were estimated. RESULTS: IHC examination revealed the expression of adenoviral antigens more commonly in patients with posttransplant nephritis than in recipients without nephritis or in control individuals (p<0.05). The association of patient age and time after kidney transplantation with the severity of viral damage was confirmed: graft loss in children occurred within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in patients with the morphological patterns of polyomavirus nephropathy. Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant associations with morphological changes. CONCLUSION: By taking into account a variety of factors that influence the development of viral nephritis, morphological and IHC examinations should be combined with evaluation of clinical findings.

Evaluation of the semitendinosus tendon graft shift in the bone tunnel: an experimental study.

PURPOSE: The purpose of this study was to measure the semitendinosus tendon graft shift at the tunnel aperture with graft bending using a simulated femoral bone tunnel. METHODS: Eight semitendinosus tendon grafts were used in this study. The median age of the specimen was 53 years (range 46-63). After stripping excess soft tissue, the semitendinosus tendon was doubled over the loop of the EndoButton CL (Smith and Nephew Inc.). The diameter of the graft was measured using a graft-sizing tube (Smith and Nephew Inc.) and verified to be 7.0 mm. A custom-made aluminium fixture, the size was 40.0 mm(3), with 7.0-mm-diameter hole was used as a simulated femoral bone tunnel. The graft was inserted to the tunnel, and EndoButton was positioned to the outside of the tunnel on the fixture. The distal end of the graft was tensioned with 30 N at an angle of 15°, 30°, 45°, 60°, 75° that reproduced the graft bending angle during knee range of motion. The photograph of the tunnel aperture was taken at each graft bending angle using a digital camera, and the graft shift amount in the simulated tunnel was analysed using the computer software (ImageJ). RESULTS: The amount of the graft shift significantly increased when the graft bending angle was increased (P < 0.05). The biggest shift was observed when the graft bending angle was 75° in all specimens, and the value was 1.10 mm ± 0.12. CONCLUSION: The present study suggests that even if the femoral tunnel was created in the centre of the ACL insertion site, the graft shifted within the tunnel in the direction of the tension applied to the graft during knee range of motion. Surgeons may have to consider the graft shift within the bone tunnel as well as the tunnel position in the restoration of the native ACL anatomy.

The versatile subepithelial connective tissue graft: a literature update.

Harmony between hard and soft tissue morphologies is essential for form, function, and a good esthetic outlook. Replacement grafts for correction of soft tissue defects around the teeth have become important to periodontal plastic and implant surgical procedures. Among a multitude of surgical techniques and graft materials reported in literature, the subepithelial connective tissue graft (SCTG) has gained wide popularity and acceptance. The purpose of this article is to acquaint clinicians with the current understanding of the versatile SCTG. Key factors associated with graft harvesting as well as applications, limitations, and complications of SCTGs are discussed. This connective tissue has shown excellent short- and long-term stability, is easily available, and is economical to use. The SCTG should be considered as an alternative in all periodontal reconstruction surgeries.