Editorial Commentary: The Statistical Fragility Index of Medical Trials Is Low By Design: Critical Evaluation of Confidence Intervals Is Required.

The Fragility Index (FI) provides the number of patients whose outcome would need to have changed for the results of a clinical trial to no longer be statistically significant. Although it's a well-intended and easily interpreted metric, its calculation is based on reversing a significant finding and therefore its interpretation is only relevant in the domain of statistical significance. Its interpretation is only relevant in the domain of statistical significance. A well-designed clinical trial includes an a priori sample size calculation that aims to find the bare minimum of patients needed to obtain statistical significance. Such trials are fragile by design! Examining the robustness of clinical trials requires an estimation of uncertainty, rather than a misconstrued, dichotomous focus on statistical significance. Confidence intervals (CIs) provide a range of values that are compatible with a study's data and help determine the precision of results and the compatibility of the data with different hypotheses. The width of the CI speaks to the precision of the results, and the extent to which the values contained within have potential to be clinically important. Finally, one should not assume that a large FI indicates robust findings. Poorly executed trials are prone to bias, leading to large effects, and therefore, small P values, and a large FI. Let's move our future focus from the FI toward the CI.

How accurate are positive preoperative aspiration culture results in shoulder periprosthetic joint infection? A concordance study.

BACKGROUND: The concordance between preoperative synovial fluid cultures and intraoperative tissue cultures for identifying pathogenic microorganisms in shoulder periprosthetic joint infection (PJI) remains poorly understood. The purpose of our study was to examine the diagnostic accuracy of positive synovial fluid culture results in early pathogen identification for shoulder PJI. METHODS: A total of 35 patients who met the Musculoskeletal Infection Society criteria for PJI following primary anatomic or reverse arthroplasty and the study inclusion criteria were identified retrospectively from a single institution (multiple surgeons) from January 2011 to June 2021. The inclusion criteria required a positive preoperative intra-articular synovial fluid sample within 90 days analyzed within the same institution and intraoperative tissue cultures at the time of arthrotomy. Concordance was determined when the organism(s) identified from the aspirate correlated with the intraoperative specimens. RESULTS: Overall concordance was identified in 28 of 35 patients (80%), with similar concordance for anatomic (21 of 24, 88%) and reverse (7 of 11, 64%) shoulder arthroplasties (P = .171). Culture discordance occurred in 7 of 35 patients (20%): of these, 5 (14%) had no corresponding intraoperative culture growth whereas 2 (6%) had polymicrobial intraoperative cultures. Monomicrobial Cutibacterium acnes PJI cases were the most common (24 of 35, 69%) and had an overall concordance rate of 79%. Of 5 discordant C acnes patients, 2 had polymicrobial intraoperative cultures and 3 had negative intraoperative culture results; all the patients with negative intraoperative culture results had received antibiotics between the time of aspiration and surgery. Considered separately, concordance in patients who had a positive aspirate finding for C acnes and did not receive antibiotics prior to surgery was 19 of 21 (90%), with a sensitivity of 100% (95% confidence interval, 82%-100%) and a corresponding positive predictive value of 0.91 (95% confidence interval, 58%-93%). CONCLUSION: Preoperative positive aspiration culture results demonstrated favorable sensitivity and specificity when compared with intraoperative tissue cultures in identifying pathogenic microorganisms in shoulder PJI patients. These findings are congruent with literature from hip and knee arthroplasty. Ultimately, confidence in the accuracy of positive preoperative aspiration culture results in shoulder PJI may facilitate the development of early, targeted treatment strategies while directing patient expectations and risk.

Is Metformin Use Associated with Prolonged Overall Survival in Patients with Soft Tissue Sarcoma? A SEER-Medicare Study.

BACKGROUND: Metformin, an oral drug used to treat patients with diabetes, has been associated with prolonged survival in patients with various visceral carcinomas. Although the exact mechanisms are unknown, preclinical translational studies demonstrate that metformin may impair tumor cellular metabolism, alter matrix turnover, and suppress oncogenic signaling pathways. Currently used chemotherapeutic agents have not been very successful in the adjuvant setting or for treating patients with metastatic sarcomas. We wanted to know whether metformin might be associated with improved survival in patients with a soft tissue sarcoma. QUESTIONS/PURPOSES: In patients treated for a soft tissue sarcoma, we asked: (1) Is there an association between metformin use and longer survival? (2) How does this association differ, if at all, among patients with and without the diagnosis of diabetes? METHODS: The Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database was used to identify patients with a diagnosis of soft tissue sarcoma from 2007 to 2016. Concomitant medication use was identified using National Drug Codes using the Medicare Part D event files. This database was chosen because of the large number of captured sarcoma patients, availability of tumor characteristics, and longitudinal linkage of Medicare data. A total of 14,650 patients were screened for inclusion. Patients with multiple malignancies, diagnosis at autopsy, or discrepant linkage to the Medicare database were excluded. Overall, 4606 patients were eligible for the study: 598 patients taking metformin and 4008 patients not taking metformin. A hazard of mortality (hazard ratio) was analyzed comparing patients taking metformin with those patient groups not taking metformin and expressed in terms of a 95% confidence interval. Cox regression analysis was used to control for patient-specific, disease-specific, and treatment-specific covariates. RESULTS: Having adjusted for disease-, treatment-, and patient-specific characteristics, patients taking metformin experienced prolonged survival compared with all patients not taking metformin (HR 0.76 [95% CI 0.66 to 0.87]). Associated prolonged survival was also seen when patients taking metformin were compared with those patients not on metformin irrespective of a diabetes diagnosis (HR 0.79 [95% CI 0.66 to 0.94] compared with patients with a diagnosis of diabetes and HR 0.77 [95% CI 0.67 to 0.89] compared with patients who did not have a diagnosis of diabetes). CONCLUSION: Without suggesting causation, we found that even after controlling for confounding variables such as Charlson comorbidity index, tumor grade, size, stage, and surgical/radiation treatment modalities, there was an association between metformin use and increased survival in patients with soft tissue sarcoma. When considered separately, this association persisted in patients not on metformin with and without a diabetes diagnosis. Although metformin is not normally prescribed to patients who do not have a diabetes diagnosis, these data support further study, and if these findings are substantiated, it might lead to the performance of multicenter, prospective clinical trials about the use of metformin as an adjuvant therapy for the treatment of soft tissue sarcoma in patients with and without a preexisting diabetes diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Surgical approach to pediatric mediastinal masses based on imaging characteristics.

BACKGROUND: Pediatric mediastinal masses may be resected using an open or video-assisted thoracoscopic surgery (VATS) approach. We sought to define the preoperative imaging findings predicting amenability to VATS. METHODS: This multicenter retrospective study of pediatric patients undergoing either VATS or open surgical mediastinal mass resection between 2008 and 2018 evaluated the preoperative imaging descriptors associated with VATS. Postoperative endpoints included length of stay (LOS), 30-day readmission, 90-day mortality and complication rates. RESULTS: Mediastinal mass resection was performed in 33 patients. Median tumor size was 6 cm, and 51.5% had anterior mediastinal tumors. The 23 (69.7%) patients who underwent VATS were significantly older (144 months vs 32, P = 0.01) and larger (33.6 kg vs 13.8 P = 0.03). Preoperative imaging characteristics in VATS included "well circumscribed", "smooth margins" and "cystic", while the open surgery group were "heterogeneous" and "coarse calcification". The open group had more germ cell tumors (60.0% vs 13.0%, P = 0.16) but no difference in malignancy. VATS patients had shorter LOS (2 days vs 6.5, P = 0.24). Readmission, complication and mortality rates were similar. CONCLUSIONS: Pediatric patients with apparent malignancy frequently underwent open resection compared with the thoracoscopic group, although final malignant pathology was similar. Equivalent outcomes and shorter LOS should favor a minimally invasive approach. LEVEL OF EVIDENCE: Level III.

Spacecraft Observations and Theoretical Understanding of Slow Electron Holes.

We present Magnetospheric Multiscale observations showing large numbers of slow electron holes with speeds clustered near the local minimum of double-humped velocity distribution functions of background ions. Theoretical computations show that slow electron holes can avoid the acceleration that otherwise prevents their remaining slow only under these same circumstances. Although the origin of the slow electron holes is still elusive, the agreement between observation and theory about the conditions for their existence is remarkable.

Effect of Vancomycin Soaking on Anterior Cruciate Ligament Graft Biomechanics.

PURPOSE: To evaluate the effect of soaking of anterior cruciate ligament (ACL) grafts in vancomycin solution on graft biomechanical properties at the time of implantation. METHODS: The central third of patellar tendons was harvested from mature bovine knees and prepared as a tendon-only graft or a bone-tendon-bone (BTB) graft. Tendons were wrapped in gauze soaked in vancomycin solution (VS) (5 mg/mL) or normal saline (NS) and left to stand for 30 minutes at room temperature, simulating graft exposure times in the operating room during ACL reconstruction. Tensile testing was carried out on a materials testing system with (1) low-magnitude loading (60 N at 3 mm/s) with repeated testing of tendon-only grafts; and (2) high-magnitude loading (600 N at 10 mm/min) of BTB grafts. For tendon-only grafts, specimens were first wrapped in NS-soaked gauze and underwent testing, with repeated testing performed after wrapping in gauze soaked in VS or buffered VS (pH 7.0). For BTB grafts, specimens were randomly assigned to treatment with VS or NS. RESULTS: For tendon-only grafts, there was no difference in Young's modulus (YM) after soaking with VS soaking (baseline, 12.69 MPa; treatment, 16.07 ± 4.44 MPa; P = .99) or buffered VS (baseline, 12.45 ± 4.55 MPa; treatment, 15.56 ± 2.83 MPa; P = .99). For BTB grafts, there were no differences in elongation strain (VS, 46.8% ± 7.0%; NS, 31.5% ± 13.5%, P = .19) or YM (VS, 158.4 ± 15.8 MPa; NS, 158.5 ± 23.3 MPa, P = .99). CONCLUSIONS: According to controlled biomechanical tests, vancomycin soaking of patellar tendon grafts does not adversely affect time-zero material properties. CLINICAL RELEVANCE: This study suggests that vancomycin wrapping has no immediate adverse effects on the biomechanical properties of ACL grafts. Randomized controlled trials are warranted to validate the widespread use of vancomycin soaking of tendon grafts for infection prophylaxis during ACL reconstruction.

Growth Factor Delivery to a Cartilage-Cartilage Interface Using Platelet-Rich Concentrates on a Hyaluronic Acid Scaffold.

PURPOSE: To determine whether (1) human leukocyte-platelet-rich plasma (L-PRP) or (2) leukocyte-platelet-rich fibrin (L-PRF) delivered on a hyaluronic acid (HA) scaffold at a bovine chondral defect, a simulated cartilage tear interface, in vitro would improve tissue formation based on biomechanical, histologic, and biochemical measures. METHODS: L-PRF and L-PRP were prepared from 3 healthy volunteer donors and delivered in conjunction with HA scaffolds to defects created in full-thickness bovine cartilage plugs harvested from bovine femoral condyle and trochlea. Specimens were cultured in vitro for up to 42 days. Treatment groups included an HA scaffold alone and scaffolds containing L-PRF or L-PRP. Cartilage repair was assessed using biomechanical testing, histology, DNA quantification, and measurement of sulfated glycosaminoglycan and collagen content at 28 and 42 days. RESULTS: L-PRF elicited the greatest degree of defect filling and improvement in other histologic measures. L-PRF-treated specimens also had the greatest cellularity when compared with L-PRP and control at day 28 (560.4 µg vs 191.4 µg vs 124.2 µg, P = .15); at day 48, there remained a difference, although not significant, between L-PRF versus L-PRP (761.1 µg vs 589.3 µg, P = .219) . L-PRF had greater collagen deposition when compared with L-PRP at day 42 (40.1 µg vs 16.3 µg, P < .0001). L-PRF had significantly greater maximum interfacial strength compared with the control at day 42 (10.92 N vs 0.66 N, P = .015) but had no significant difference compared with L-PRP (10.92 N vs 6.58 N, P = .536). L-PRP facilitated a greater amount of sulfated glycosaminoglycan production at day 42 when compared with L-PRF (15.9 µg vs 4.3 µg, P = .009). CONCLUSIONS: Delivery of leukocyte-rich platelet concentrates in conjunction with a HA scaffold may allow for improvements in cartilage healing through different pathways. L-PRF was not superior to L-PRP in its biomechanical strength, suggesting that both treatments may be effective in improving biomechanical strength of healing cartilage through different pathways. CLINICAL RELEVANCE: The delivery of platelet-rich concentrates in conjunction HA scaffolds may augment healing cartilaginous injuries.

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute.

Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage. In the current study, we use a decellularization and oxidation protocol to produce a porcine bone scaffold and examine whether it possesses osteoinductive potential and can be used to create a tissue-engineered bone microenvironment. The decellularization protocol was patented by our lab and consists of chemical decellularization and oxidation steps using combinations of deionized water, trypsin, antimicrobials, peracetic acid, and triton-X100. To test if the bone scaffold was a viable host, preosteoblasts were seeded and analyzed for markers of osteogenic differentiation. The osteoinductive potential was observed in vitro with similar osteogenic markers being expressed in preosteoblasts seeded on the scaffolds and demineralized bone matrix. To assess these properties in vivo, scaffolds with and without preosteoblasts preseeded were subcutaneously implanted in mice for 4 weeks. MicroCT scanning revealed 1.6-fold increased bone volume to total volume ratio and 1.4-fold increase in trabecular thickness in scaffolds after implantation. The histological analysis demonstrates new bone formation and blood vessel formation with pentachrome staining demonstrating osteogenesis and angiogenesis, respectively, within the scaffold. Furthermore, CD31+ staining confirmed the endothelial lining of the blood vessels. These results demonstrate that porcine bone maintains its osteoinductive properties after the application of a patented decellularization and oxidation protocol developed in our laboratory. Future work must be performed to definitively prove osteogenesis of human mesenchymal stem cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant clinical model in vivo. The ability to create a functional bone microenvironment using decellularized xenografts will impact regenerative medicine, orthopedic reconstruction, and could be used in the research of multiple diseases.

How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model.

BACKGROUND: While successful subtalar joint arthrodesis provides pain relief, resultant alterations in ankle biomechanics need to be considered, as this procedure may predispose the remaining hindfoot and tibiotalar joint to accelerated degenerative changes. However, the biomechanical consequences of isolated subtalar joint arthrodesis and additive fusions of the Chopart's joints on tibiotalar joint biomechanics remain poorly understood. QUESTIONS/PURPOSES: We asked: What is the effect of isolated subtalar fusion and sequential Chopart's joint fusions of the talonavicular and calcaneocuboid joints on tibiotalar joint (1) mechanics and (2) kinematics during loading for neutral, inverted, and everted orientations of the foot? METHODS: We evaluated the total force, contact area, and the magnitude and distribution of the contact stress on the articular surface of the talar dome, while simultaneously tracking the position of the talus relative to the tibia during loading in seven fresh-frozen cadaver feet. Each foot was loaded in the unfused, intact control condition followed by three randomized simulated hindfoot arthrodesis modalities: subtalar, double (subtalar and talonavicular), and triple (subtalar, talonavicular, and calcaneocuboid) arthrodesis. The intact and arthrodesis conditions were tested in three alignments using a metallic wedge insert: neutral (flat), 10° inverted, and 10° everted. RESULTS: Tibiotalar mechanics (total force and contact area) and kinematics (external rotation) differed owing to hindfoot arthrodeses. After subtalar arthrodesis, there were decreases in total force (445 ± 142 N, 95% CI, 340-550 N, versus 588 ± 118 N, 95% CI, 500-676 N; p < 0.001) and contact area (282 mm(2), 95% CI, 222-342 mm(2), versus 336 ± 96 mm(2), 95% CI, 265-407 mm(2); p < 0.026) detected during loading in the neutral position; these changes also were seen in the everted foot position. Hindfoot arthrodesis also was associated with increased external rotation of the tibiotalar joint during loading: subtalar arthrodesis in the neutral loading position (3.3° ± 1.6°; 95% CI, 2°-4.6°; p = 0.004) and everted loading position (4.8° ± 2.6°; 95% CI, 2.7°-6.8°; p = 0.043); double arthrodesis in neutral (4.4° ± 2°; 95% CI, 2.8°-6°; p = 0.003) and inverted positions (5.8° ± 2.6°; 95% CI, 3.7°-7.9°; p = 0.002), and triple arthrodesis in all loaded orientations including neutral (4.5° ± 1.8°; 95% CI, 3.1°-5.9°; p = 0.002), inverted (6.4° ± 3.5°; 95% CI, 3.6°-9.2°; p = 0.009), and everted (3.6° ± 2°; 95% CI, 2°-5.2°; p = 0.053) positions. Finally, after subtalar arthrodesis, additive fusions at Chopart's joints did not appear to result in additional observed differences in tibiotalar contact mechanics or kinematics with the number of specimens available. CONCLUSIONS: Using a cadaveric biomechanical model, we identified some predictable trends in ankle biomechanics during loading after hindfoot fusion. In our tested specimens, fusion of the subtalar joint appeared to exert a dominant influence over ankle loading. CLINICAL RELEVANCE: A loss or deficit in function of the subtalar joint may be sufficient to alter ankle loading. These findings warrant consideration in the treatment of the arthritic hindfoot and also toward defining biomechanical goals for ankle arthroplasty in the setting of concomitant hindfoot degeneration or arthrodesis.

Towards a Graphene-Based Low Intensity Photon Counting Photodetector.

Graphene is a highly promising material in the development of new photodetector technologies, in particular due its tunable optoelectronic properties, high mobilities and fast relaxation times coupled to its atomic thinness and other unique electrical, thermal and mechanical properties. Optoelectronic applications and graphene-based photodetector technology are still in their infancy, but with a range of device integration and manufacturing approaches emerging this field is progressing quickly. In this review we explore the potential of graphene in the context of existing single photon counting technologies by comparing their performance to simulations of graphene-based single photon counting and low photon intensity photodetection technologies operating in the visible, terahertz and X-ray energy regimes. We highlight the theoretical predictions and current graphene manufacturing processes for these detectors. We show initial experimental implementations and discuss the key challenges and next steps in the development of these technologies.

Reduced taste function and taste papillae density in children with chronic kidney disease.

BACKGROUND: Taste loss may contribute to the loss of appetite in children with chronic kidney disease (CKD) and other serious medical conditions that result in malnutrition. Traditional methods for measurement of taste loss commonly use aqueous tastant solutions that can induce nausea, vomiting, or even pain in the mouth. An alternative is to measure fungiform papillae density on the anterior tongue since this correlates with taste sensitivity. Here we aimed to develop a non-invasive method for assessing papillae density on the anterior tongue and to use the method to determine if CKD patients [estimated glomerular filtrate (eGFR < 60 ml/min/1.73 m(2))] have a lower density than clinical controls (CC)(eGFR > 89 ml/min/1.73 m(2)). METHODS: Thirty-five healthy adults participated in the development of a method, which was assessed by 24 children, 12 of whom were CKD patients and 12 were clinical controls. RESULTS: Similar papillae densities were found using invasive and non-invasive methods (F(1,34) = 0.647, p = 0.427). The CKD group had a significantly lower papillae density (X(2) = 7.17, p = 0.007) and poorer taste sensitivity than the CC group (p = 0.0272), and the density correlated significantly with eGFR (r = 0.56, p < 0.01). CONCLUSIONS: Loss of taste in children with CKD is due to the reduced number of papillae and their taste-sensing receptor cells.

Using a statistically calibrated biphasic finite element model of the human knee joint to identify robust designs for a meniscal substitute.

This paper describes a methodology for selecting a set of biomechanical engineering design variables to optimize the performance of an engineered meniscal substitute when implanted in a population of subjects whose characteristics can be specified stochastically. For the meniscal design problem where engineering variables include aspects of meniscal geometry and meniscal material properties, this method shows that meniscal designs having simultaneously large radial modulus and large circumferential modulus provide both low mean peak contact stress and small variability in peak contact stress when used in the specified subject population. The method also shows that the mean peak contact stress is relatively insensitive to meniscal permeability, so the permeability used in the manufacture of a meniscal substitute can be selected on the basis of manufacturing ease or cost. This is a multiple objective problem with the mean peak contact stress over the population of subjects and its variability both desired to be small. The problem is solved by using a predictor of the mean peak contact stress across the tibial plateau that was developed from experimentally measured peak contact stresses from two modalities. The first experimental modality provided computed peak contact stresses using a finite element computational simulator of the dynamic tibial contact stress during axial dynamic loading. A small number of meniscal designs with specified subject environmental inputs were selected to make computational runs and to provide training data for the predictor developed below. The second experimental modality consisted of measured peak contact stress from a set of cadaver knees. The cadaver measurements were used to bias-correct and calibrate the simulator output. Because the finite element simulator is expensive to evaluate, a rapidly computable (calibrated) Kriging predictor was used to explore extensively the contact stresses for a wide range of meniscal engineering inputs and subject variables. The predicted values were used to determine the Pareto optimal set of engineering inputs to minimize peak contact stresses in the targeted population of subjects.

Comparison of transposition techniques to reduce gap associated with high ulnar nerve lesions.

PURPOSE: To determine in a cadaveric model which of 3 anterior transposition techniques allows for maximum gap reduction for high ulnar nerve lesions. METHODS: Six fresh-frozen human adult upper extremity cadaveric transhumeral specimens were used. We anchored the ulnar nerve to bone 10 cm proximal and distal to the medial epicondyle along its exact course while keeping the elbow in 30° flexion as the baseline measurement. We then used a thick suture to mimic and measure the exact course of the nerve between the pins in varying elbow positions. The nerve was then transposed first subcutaneously, then intramuscularly, and then submuscularly while taking exact measurements of the distance the nerve had to travel in varying degrees of elbow flexion for each transposition method. We performed comparative analysis to analyze gap reduction with respect to transposition method and elbow position. RESULTS: Transposing the ulnar nerve reduced the repair gap required to cross the elbow regardless of transposition technique. When comparing individual techniques, however, the greatest gap reduction was achieved by intramuscular, followed by submuscular and finally subcutaneous transposition. A maximum gap reduction of 25 mm (average, 23 mm) was achieved using intramuscular transposition with the elbow in 90° flexion. Subcutaneous transposition actually increased the repair gap when the elbow was in an extended position. CONCLUSIONS: An intramuscular transposition with the elbow in 90° flexion provided the best gap reduction. However, post-neurorrhaphy mobilization may compromise repair site integrity and vascularity if elbow flexion is required to achieve a primary repair, and these factors should be considered carefully when planning treatment. CLINICAL RELEVANCE: This study provides guidance on techniques to reduce nerve gap for primary repair of the ulnar nerve at the elbow using transposition and elbow flexion.

Cleaning practices of transport vehicles by commercial and non-commercial livestock markets users in Scotland.

BACKGROUND: Livestock markets are critical intermediaries in the movement of cattle and sheep between herds and to abattoirs. Disease prevention strategies promoting Cleansing & Disinfection (C&D) of vehicles moving animals from markets are in place in Scotland to reduce the risk of widespread transmission of pathogens within the livestock industry. However, little is known about how market users implement C&D on their vehicles and how these may differ between sectors of the industry. METHODS: An online questionnaire was completed by 72 Scottish market users to investigate C&D practices on livestock transport vehicles. Respondents were grouped based on their farming activities and biosecurity practices were compared between commercial and non-commercial users. RESULTS: The results showed a lower-than-expected use of brush or disinfectant and a shorter-than-expected time spent on C&D. Particularly, 43.6 % of respondents spent less than 30 min to C&D their vehicle, with no significant differences between respondents from commercial and non-commercial sectors (P = 0.75). Overall, we found little differences in C&D practices and level of training between sectors, highlighting the industrywide deficit in biosecurity knowledge. CONCLUSIONS: These results highlight a need to improve the messaging and awareness on good C&D practices on transport vehicles. Regular training on C&D practices is recommended, particularly for commercial livestock transport.

Advances with Platelet-Rich Plasma for Bone Healing.

Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic. The aim of this narrative review is to describe and relate pre-clinical in-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery. In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.

Current Concepts in Management of Acromioclavicular Joint Injury.

Background: The management of acromioclavicular joint injuries requires a thorough understanding of the anatomy and biomechanics of the joint, as well as knowledge of the pertinent physical exam findings and classification to determine an appropriate treatment approach, whether operative or nonoperative. In this article, we present a narrative review of the current state of understanding surrounding these issues. Although there are a large number of options for operative intervention, we additionally present our experience with anatomic coracoclavicular ligament reconstruction (ACCR) with imbrication of the deltoid fascia. Methods: A retrospective review of prospectively collected data on a total of 45 patients who had undergone ACCR between 2003 and 2016 were collected. Results: We found that improvements were seen in American Shoulder and Elbow Surgeons Score (ASES) (53 ± 19 to 81 ± 23), Simple Shoulder Test (SST) (6 ± 3 to 12 ± 13), Constant-Murley (CM) (60 ± 18 to 92 ± 8), and Rowe (67 ± 14 to 89 ± 11) and the mean post-operative SANE score was 86 ± 17. Conclusions: ACCR has the advantage of addressing both horizontal and vertical stability with good outcomes.

Changes in fungiform papillae density during development in humans.

The anterior region of the human tongue ceases to grow by 8-10 years of age and the posterior region at 15-16 years. This study was conducted with 30 adults and 85 children (7-12 year olds) to determine whether the cessation of growth in the anterior tongue coincides with the stabilization of the number and distribution of fungiform papillae (FP) on this region of the tongue. This is important for understanding when the human sense of taste becomes adult in function. This study also aimed to determine whether a small subpopulation of papillae could be used to predict the total number of papillae. FP were photographed and analyzed using a digital camera. The results indicated that the number of papillae stabilized at 9-10 years of age, whereas the distribution and growth of papillae stabilized at 11-12 years of age. One subpopulation of papillae predicted the density of papillae on the whole anterior tongue of 7-10 year olds, whereas another was the best predictor for the older children and adults. Overall, the population, size, and distribution of FP stabilized by 11-12 years of age, which is very close to the age that cessation of growth of the anterior tongue occurs.

Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients.

Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.

Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients.

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.