Risk factors of major complications after flap surgery in the treatment of stage III and IV pressure injury in people with spinal cord injury/disorder: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To identify risk factors associated with major complications after flap surgery in people with spinal cord injury or disorder (SCI/D) and stage III and IV pressure injury (PI). SETTING: Swiss hospital specialized in the treatment of people with SCI/D using the Basel Decubitus Approach. METHODS: We examined 60 risk factors for major postoperative complications in PIs over sacrum/coccyx, ischium or trochanter between 01/2016 and 12/2021. We performed descriptive analysis and computed global p-values using likelihood ratio tests adjusted for clustering of PIs in individuals. RESULTS: We included 220 PI treatment procedure from 149 individuals. The study population consisted of 163 (74%) men, 133 (60%) traumatic SCI, 136 (58%) stage IV PI, 198 (90%) individuals with paraplegia, 93 (42%) with osteomyelitis, and 85 (39%) with recurrent PI. Major complications 42 (19%) occurred more often in individuals with stage IV PI (p < 0.01), individuals without osteomyelitis (p < 0.03), and individuals with pathological blood concentrations of cystatin c (p < 0.028), calcium (p < 0.048), and vitamin B12 (p < 0.0049) as well as normal blood concentrations of HbA1c (p < 0.033). Immobilization (p < 0.0089) and hospital stay (p < 0.0001) of individuals with major complications was longer. CONCLUSION: In the Basel Decubitus Approach, stage IV PI, absence of osteomyelitis, reduced vitamin B12 and calcium, elevated cystatin c, and normal HbA1c should be addressed to reduce major complications.

Molecular characterization of chronic cutaneous wounds reveals subregion- and wound type-specific differential gene expression.

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

Combining reconstructive and ablative surgical treatment of chronic breast cancer-related lymphedema (BCRL): safe and effective.

PURPOSE: We investigated whether a one-stage combination of vascularized lymph node transfer (VLNT) with water jet-assisted liposuction (WAL) can be safely performed and results in improved patient outcomes such as a greater reduction in arm volume when treating chronic breast cancer-related lymphedema (BCRL). METHODS: In this retrospective cohort study, we included all patients from our encrypted lymphedema database treated for chronic BCRL with VLNT or VLNT + WAL who had a minimum follow-up of two years. We analyzed patient-specific variables including arm circumferences as well as patient-reported outcomes before and after surgery as well as surgery time, surgery-related complications and patient satisfaction. RESULTS: Only the mean preoperative differences of the circumferences between the lymphedematous and the unaffected arm in individual patients showed a statistically significant difference between treatment groups (p < 0.05). Indeed, patients treated with VLNT + WAL had consistently larger differences in individual sets of arms and therefore more pronounced chronic BCRL. The mean surgery time was significantly longer in the VLNT + WAL group (p < 0.05). Complications were seldom and similar in both groups. Using a numeric rating scale, the level of patient satisfaction following treatment did not differ significantly between groups (p = 0.323). CONCLUSIONS: Our findings suggest that a one-stage combination of VLNT with WAL does not result in more complications even though it also entails a longer surgery time. This is acceptable as secondary interventions resulting in overall longer surgery times and higher costs can be avoided. A one-stage combination might be especially favourable for patients suffering from more severe chronic BCRL.

Determination of Microplastics' Vertical Concentration Transport (Rouse) Profiles in Flumes.

The transport behavior of microplastics (MPs) in the fluvial environment is scarcely researched. Besides settling velocities and critical shear stress for erosion, only a few investigations aim at MPs' vertical concentration profile and the underlying theory required. Therefore, this paper's experiments investigate vertical concentration profiles of approximately spherical MP particles (d = 1-3 mm) with densities close to water (0.91-1.13 g/cm3) in flow channels, coupling them with fundamental theory for the first time. The experiments were conducted in a tiling flume (slope of 0-2.4%) at 67 and 80 mm water depth, with a turbulent flow, velocities ranging from 0.4 to 1.8 m/s, and turbulence kinetic energy from 0.002 to 0.08 m2/s2. The measured profiles confirm the assumption that the concentration profile shapes of settling plastics are similar to those of sediments and running reversed for buoyant plastics. Furthermore, the hypothesis of the Rouse formula's applicability for floating and sinking plastics could be confirmed for approximately uniform flows. Future studies tying in with this research should increase particle properties and hydraulic parameter variation.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Effect of a computerized decision support system on the treatment approach of stage III or IV pressure injury in patients with spinal cord injury: a feasibility study.

BACKGROUND: Stage III and IV pressure injuries (PIs) in patients with spinal cord injury (SCI) require complex interdisciplinary and interprofessional treatment approaches that are difficult to implement. Practical aspects, such as information exchange and coordination, remain challenging. We investigated whether a computerized decision support system (CDSS) could increase treatment adherence and improve clinical outcomes and interprofessional collaboration. METHOD: In this feasibility study, a core team developed the initial treatment process and adapted it based on several discussions with clinical experts and information technologists. The CDSS followed the Basel Decubitus Approach and was used in a clinic specializing in SCI. Thirty patients with SCI admitted for stage III/IV PI between July 2016 and May 2017 were randomly allocated to standard or CDSS-supported care. Between-group differences in treatment adherence, complication rates, length of stay, and costs were analyzed using descriptive statistics. The use of the CDSS and potential barriers and facilitators were evaluated through interprofessional focus groups, transcribed verbatim, and thematically analyzed (30 participants). RESULTS: No differences in SCI characteristics, comorbidities, or PI characteristics (localization: ischium [number (n) = 19 PI, 63%], sacrum [n = 10 PI, 33%], recurrent PI [n = 21, 70%]) were found between the two groups. Furthermore, no statistically significant differences were observed in treatment adherence, frequency of major (20% vs. 13% between CDSS and control group) and minor (33% vs 27%) complications, and length of stay (98 [±28] vs 81 [±23] days). Healthcare professionals found the CDSS to be helpful for visualizing the treatment process. However, the high workload and difficulties in the information technology processes, such as missing reminders, slow computer performance and data processing, and poor accessibility, hindered the effective implementation of the CDSS. CONCLUSION: The implementation of the CDSS to support the treatment of stage III/IV PI in patients with SCI was feasible and included definitions of milestones, interventions, and outcomes. However, to assess the impact of the CDSS, a longer observation period is required. Further, the technical difficulties must be addressed, and solid integration of the CDSS into the clinical information system is necessary. TRIAL REGISTRATION: This quality improvement project received a declaration of no objection from the Ethics Committee of Northwest and Central Switzerland (EKNZ UBE-16/003), and ethical approval was received for the focus groups (EKNZ Req-2017-00860).

Risk constellation of hospital acquired pressure injuries in patients with a spinal cord injury/ disorder - focus on time since spinal cord injury/ disorder and patients' age.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The aim of this study was to evaluate how time since spinal cord injury/disorder (SCI/D) and patients' age influence risk constellation for hospital acquired pressure injuries (HAPI) in patients with a SCI/D. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: We collected patients' characteristics and 85 risk factors for HAPI development in adults with SCI/D with at least one HAPI during their inpatient stay between August 2018 and December 2019. We analyzed patients' characteristics and HAPI risk factors using descriptive statistics according to time since SCI/D ( < 1 year, 1-15 years, > 15 years) and patients' age (18-35 years, 35-65 years, > 65 years). RESULTS: We identified 182 HAPI in 96 patients. Comparing patients with SCI/D < 1 year with the other groups, autonomic dysreflexia (p < 0.001), abnormal body temperature (p = 0.001), hypertensive episode (p = 0.005), and pneumonia (p < 0.001) occurred more frequently; mean hemoglobin (p < 0.001), albumin (p = 0.002) and vitamin D levels (p = 0.013) were significantly lower, and patients with time since SCI/D < 1 year scored fewer points (10-12) on the Braden Scale (p < 0.001). Comparing groups per patients' age, only the SCIPUS score was higher in patients > 65 years compared to the other two groups (p = 0.002). CONCLUSIONS: Different risk factor constellation seem to be underlying HAPI development with more differences in patients time since SCI/D than patients' age. Awareness of these differences in risk factor constellation depending on time since SCI/D in these patients might lead to different HAPI prevention strategies. SPONSORSHIP: The study team didn't receive any additional sponsorship.

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.

Osteomyelitis and antibiotic treatment in patients with grade IV pressure injury and spinal cord lesion-a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze characteristics and treatment of osteomyelitis (OM) in the treatment of grade IV pressure injury (PI) in patients with spinal cord injury/disorder (SCI/D) following the Basel Decubitus Concept. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients with SCI/D were admitted for grade IV PI treatment between 1st January 2010 and 28th February 2015. Patients, SCI/D, and PI characteristics were collected from chart reviews. Descriptive statistics and differences between groups with and without OM were evaluated. RESULTS: In total, 117 patients (87 male, 30 female) with 130 PI grade IV were included. In 95 patients (81%), OM was diagnosed histologically. In 87 cases, more than one bacterial species was involved. Out of 49 different bacterial species, Enterococcus faecalis and Staphylococus aureus were most frequently observed. Amoxicillin/clavulanic acid and ciprofloxacin were the most frequently used out of 24 different antibiotics. Length of antibiotic treatment varied between <8 days and >91 days with 31 patients receiving antibiotics for about 8 weeks. Complications occurred in all groups of antibiotic duration. Having a paraplegia, no OM and sacral PI was associated with increased complication rates, but the number of patients did not allow comprehensive risk factor analysis. CONCLUSION: Because the variety of patients concerning SCI/D, PI, and OM characteristics did not show a conclusive relation between length of antibiotic treatment and complication rates, the development of a subgroup specific treatment concept for PI in patients with SCI/D would be favorable to further optimize antibiotic treatment.

Risk factors for hospital acquired pressure injury in patients with spinal cord injury during first rehabilitation: prospective cohort study.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVES: First, describe pressure injury (PI) and associated risk factors in individuals with spinal cord injury/disorder (SCI/D) during first rehabilitation. Second, evaluate a prediction model for hospital acquired PI (HAPI) development. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients ≥18 years of age with SCI/D were included during first rehabilitation between 08/2018 and 12/2019. We performed a systematic literature search to identify risk factors for PI development. Patients were classified according to HAPI developed. Between group differences of patients' characteristics and risk factors were analyzed using descriptive statistics. Logistic predictive models were performed to estimate HAPI development and receiver operator characteristic (ROC) curve was used to test the model. RESULTS: In total, 94 patients were included, 48 (51.1%) developed at least one HAPI and in total 93 were observed, mainly stage I and stage II HAPI according to the European Pressure Ulcer Advisory Panel. We found nine significantly associated risk factors: completeness of SCI/D, pneumonia, sedative medications, autonomic dysreflexia, Braden ≤12 points, SCIPUS ≥9 points, lower admission SCIM and lower admission FIM-cognition, longer length of stay (LOS) (p ≤ 0.0005). In a predictive model, none of the risk factors was associated with HAPI development (AUC = 0.5). CONCLUSION: HAPIs in patients with SCI/D during first rehabilitation are a frequent and complex condition and associated with several risk factors. No predictive model exists but with the identified risk factors of this study, larger studies can create a tailored and flexible HAPI risk prediction model.

An Updated Definition of Plastic Surgery.

ABSTRACT: Modern medicine tends to provide comprehensive medical services based on disease or pathological features. As a result, the overlap between plastic surgery and other surgical departments greatly deepened. What was exclusively done by plastic surgeons are nowadays frequently practiced by other surgeons as well. Thus, generating confusion as to whether plastic surgery is an independent subject or a tool. Therefore, in this new era of modern medicine, it is necessary to reconsider the definition of plastic surgery.

High Mortality of Non-Fournier Necrotizing Fasciitis With Enterobacteriales: Time to Rethink Classification?

This cohort study describes mortality predictors of necrotizing fasciitis (NF). Higher age, chronic kidney disease, and higher Charlson score increased the mortality rate. Mortality was >3 times higher in monomicrobial gram-negative NF than in type I or type II NF. Highest mortality was found with Enterobacteriales in non-Fournier NF.

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid-Supplemented Tumescent Solution.

INTRODUCTION: In reconstructive surgery, fat volume augmentation is often necessary for esthetic or functional reasons. As an alternative to synthetic and xenogeneic materials, autologous fat grafting (AFG) based on liposuction is gaining popularity, yet successful transplantation and long-term volume maintenance are difficult. Standard tumescent solution formulations neglect adipocyte and stromal vascular fraction (SVF) cell survival during extraction, as well as SVF differentiation into adipocytes thereafter, all of which are crucial for the success of AFG. Here we hypothesized that addition of ascorbic acid (AA) to the tumescent solution could prevent liposuction-induced cell damage. MATERIALS AND METHODS: The effect of 0.1 mmol/L AA in tumescent solution was investigated in a previously described ex vivo model of AFG. Briefly, excision fat was infiltrated with tumescent solution, with or without AA, and incubated for 20 minutes at 37°C. Hand-assisted liposuction was then performed with a blunt cannula. Total cell viability, clonogenicity, and differentiation capacity of the SVF cells were assessed. RESULTS: With AA, 10.3% more cells and in particular 14.9% more adipocytes survived liposuction. Clonogenicity, adipocyte and osteoblast differentiation by SVF cells remained unchanged. CONCLUSIONS: Addition of AA successfully improved survival of adipocytes during liposuction without affecting SVF growth and differentiation. This study therefore identified a useful supplement to the tumescent solution which may lead to improving AFG success.

Vascularized Bone Autograft for the Treatment of Chondroblastoma of the Talus at Imminent Risk of Joint Breakdown: Three Case Reports.

Surgical treatment options in a chondroblastoma of the talus breaching the subchondral layer with imminent risk of talar collapse in the weightbearing area are limited. A joint-preserving surgery should be advocated. Because current treatment options such as curettage, cryosurgery, or radiofrequency ablation may not be able to prevent a talar dome breakdown in large defects, nonvascularized bone grafting has been advocated to fill the void. To overcome the lack of vitality, a vascularized bone autograft might be an attractive alternative. We present 3 cases where a large talar defect owing to a chondroblastoma was treated with a vascularized bone autograft. In 1 of the cases, a free microvascular iliac crest bone graft was used, whereas in the other 2 cases, a vascularized graft was harvested from the medial femoral condyle. Computed tomographic scans demonstrated a stable incorporation of the graft in all cases. All patients were highly satisfied with the obtained results and showed a clinical functional outcome similar to the contralateral foot after 36, 60, and 72 months. At the latest radiographic follow-up, no evidence of recurrence was observed. In conclusion, a free vascularized bone autograft can be used to treat a large talar defect owing to chondroblastoma in young patients.

Regeneration of nerve crush injury using adipose-derived stem cells: A multimodal comparison.

INTRODUCTION: To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose-derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. METHODS: In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. RESULTS: CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. DISCUSSION: Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.

Nutritional blood parameters and nutritional risk screening in patients with spinal cord injury and deep pressure ulcer-a retrospective chart analysis.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To describe (i) the nutritional blood parameters (NBP) and the nutritional risk screening (NRS) in patients with spinal cord injury (SCI) and pressure ulcers (PU) III and IV according to the EPUAP classification, and (ii) the relationship between both NBP and NRS. SETTING: SCI acute care and rehabilitation clinic in Switzerland. METHODS: The NBPs were measured upon the admission of patients treated for PU III and IV between 11/2011 and 12/2014. Descriptive analyses and group comparisons were done. RESULTS: A total of 170 patients, including 42 (25%) women, 19 (12%) people with paraplegia and 104 (61%) people with traumatic SCI, were admitted and analyzed. Pathologic blood values and NBP were found for c-reactive protein (83%), vitamin D (73%), protein (41%), erythrocyte sedimentation rate (ESR) (41%), albumin (34%), hemoglobin (34%), zinc (29%), folic acid (22%), transferrin (15.3%), and copper (1.2%). Overall, the NRS was >3 in 39% of the patients, wherefrom 28% in patients with PU III and 44% with PU IV (p=0.07). No statistical significant differences were found between patients with PU III and IV in terms of NBP and NRS. CONCLUSIONS: We found abnormal values in NBP and in NRS in a significant number of patients with SCI and PU of both III and IV. Both laboratory examinations and nutritional assessments at admission can help to detect and correct the nutritional deficits in patients at risk. Neither the grade of the PUs, nor the NBP or the NRS can replace one another.

Extending the limits of the anterior tibial artery as the recipient vessel for around the knee and proximal lower extremity defect reconstruction using the free anterolateral thigh and gracilis flap.

PURPOSE: The aim is to describe a technique with orthograde dissection of the anterior tibial artery (ATA) used as the recipient vessel for the end-to-end (ETE) anastomosis in defect reconstruction around the knee and for proximal/middle third leg defects with free anterolateral thigh (ALT) and gracilis flaps. PATIENTS AND METHODS: Between March 2009 and May 2014, 22 patients undergoing lower extremity reconstruction were evaluated. Of those, 4 patients were included. The locations of injury were 3 defects around the knee and 1 defect at the proximal and middle third of the lower leg (mean defect size 18 x 8.5 cm and a range of 17-20 x 5-10 cm). There were 2 cases after trauma and 2 cases with infection. Two free gracilis and 2 free ALT flaps were performed of equal size to the defects. The mean flap pedicle length was 11 cm (range of 7-16 cm) and the mean length of the mobilized recipient vessels was 10.5 cm (range of 6-14 cm). RESULTS: One flap loss (ALT) occurred, requiring a salvage procedure with a latissimus dorsi flap, whereas wound dehiscence at the donor site and a hematoma below the ALT flap was observed in 2 cases, requiring small revision. After a mean follow-up of 52 months (range of 38-87 months), there was stable soft tissue coverage in all patients. CONCLUSION: By orthograde dissection of the ATA, an adequate vessel length and size may be achieved, improving arc of rotation to successfully cover more distant defects.

From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the Breast by Comparing Take Rate, Quality, and Longevity.

BACKGROUND: Autologous fat grafting (AFG) to the breast is a frequent procedure in aesthetic and reconstructive surgery. Despite pure volume gain, questions remain regarding the engraftment rate, quality, and longevity. Little is known about the role of recipient tissue or innervation of the grafted area. OBJECTIVES: The goal of this study was to determine the optimal recipient layer and muscular pretreatment of AFG. METHODS: Fat was grafted to the breast, pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment included excision of a nerve segment, botulinum toxin (BTX) injection, or no treatment. Magnetic resonance imaging (MRI) and histological workup were carried out after 2 and 6 weeks. RESULTS: Six weeks after AFG, the proportion of viable fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]). The signs of inflammation decreased over time. Intramuscular grafting with intact nerves had a decreasing effect on the viability of the grafted cells compared with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]). CONCLUSIONS: If utilized on an intact nerve, intramuscular injection may lead to inferior results. If the nerve was cut or treated with BTX; however, intramuscular injection tends to be superior. These findings may prove interesting for future studies and eventual clinical application.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

BACKGROUND: Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. METHODS: In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. FINDINGS: For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. INTERPRETATION: Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. FUNDING: Deutsche Arthrose-Hilfe.

Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study.

Stromal Vascular Fraction (SVF) cells freshly isolated from adipose tissue include osteogenic- and vascular-progenitors, yet their relevance in bone fracture healing is currently unknown. Here, we investigated whether human SVF cells directly contribute to the repair of experimental fractures in nude rats, and explored the feasibility/safety of their clinical use for augmentation of upper arm fractures in elderly individuals. Human SVF cells were loaded onto ceramic granules within fibrin gel and implanted in critical nude rat femoral fractures after locking-plate osteosynthesis, with cell-free grafts as control. After 8 weeks, only SVF-treated fractures did not fail mechanically and displayed formation of ossicles at the repair site, with vascular and bone structures formed by human cells. The same materials combined with autologous SVF cells were then used to treat low-energy proximal humeral fractures in 8 patients (64-84 years old) along with standard open reduction and internal fixation. Graft manufacturing and implantation were compatible with intraoperative settings and led to no adverse reactions, thereby verifying feasibility/safety. Biopsies of the repair tissue after up to 12 months, upon plate revision or removal, demonstrated formation of bone ossicles, structurally disconnected and morphologically distinct from osteoconducted bone, suggesting the osteogenic nature of implanted SVF cells. We demonstrate that SVF cells, without expansion or exogenous priming, can spontaneously form bone tissue and vessel structures within a fracture-microenvironment. The gained clinical insights into the biological functionality of the grafts, combined with their facile, intra-operative manufacturing modality, warrant further tests of effectiveness in larger, controlled trials. Stem Cells 2016;34:2956-2966.