Effect of co-pigments on anthocyanins of Rhododendron arboreum and insights into interaction mechanism.

The impact of intermolecular copigmentation between five phenolic acids, two flavonoid and three amino acids with R. arboreum anthocyanins (ANS) and its isolated cyanidin-3-O-monoglycosides were investigated through experimental and theoretical approach. On addition of different copigments, phenolic acid induced strong hyperchromic (0.26-0.55 nm) and bathochromic shift (6.6-14.2 nm). The color intensity and stability of ANS with, storage at 4 °C & 25 °C, sunlight, oxidation and heat were evaluated by chromaticity, anthocyanin content, kinetic and structural simulation analysis. The strongest copigmentation reaction was observed with narningin (NA) and also showed high thermostability and highest half-life i.e. 3.39 h-1.24 h at 90-160 °C. The cyanidin-3-O-monoglycosides were analysed for their copigmentation effect and observations revealed that NA displayed best copigmentation effect to cyanidin-3-O-arabinoside (B) followed by cyanidin-3-O-galactoside (A), and cyanidin-3-O-rhamnoside (C). Additionally, structural simulation and steered molecular dynamics insights NA is the most favourable co-pigment involving π-π stacking and H-bonding.

Dual Mobility Total Hip Replacements in Young Patients- A Systematic Review.

Background: There is little consensus on outcomes of dual Mobility total hip replacement (DM-THR) in younger patients. We performed a systematic review to examine this. Methods: A systematic review of all observational studies and randomised controlled trials of patients under 70 with primary DM-THR in MEDLINE, EMBASE, Pubmed, Cochrane was performed according to PRISMA guidelines. Collected data included demographics, revision, dislocation and infection rates and functional scores. Results: Twelve papers studying 738 DM-THR in 664 patients were included. The mean patient age was 46.9 years (13.5-69.0), with 319 (48.0%) being female and 419 (52.0%) being male. After an average follow-up of 90.0 months (1-371 months), the revision rate was 12.7% (84 hips), 0 dislocations were reported but 2.5% (15 hips) underwent intra-prosthetic dislocation. 32.1% hip revisions were due to aseptic loosening. Conclusion: Limited literature surrounding the use of DM-THR suggests favourable stability but higher revision rates than conventional THR.

The flexibility and convenience of using a standard orthopaedic table in peri-articular knee fractures: Allowing ligamentotaxis and improving imaging accessibility.

Tibial plateau and distal femoral fractures are common injuries presenting a significant operative challenge. Complexity of the fracture often needs multi-planar surgical access. A combined two-staged procedure is frequently suggested both in supine and prone position to address this issue. However, this will significantly increase the operative time and eventually impact the outcome, in addition to the complications associated with prone positioning. In this study we used a standard orthopaedic table to position these patients in order to grant access to the postro-medial and a postro-lateral structures while the patient stays in supine setup, at the same time, giving the flexibility to change the alignment from valgus to varus and vice versa. This facilitates fracture reduction while addressing the anatomical structure of the knee. A further advantage is the unobstructed imaging access throughout the surgical fixation. This facilitates the reduction in operative time hence leading to a better outcome in these difficult fractures. We tested this positioning technique in more than 40 patients over a 4-year period at two different centres in the United Kingdome. We found that this approach is safe, reproducible and relatively easy to set up in the two centres.

External snapping hip syndrome is associated with an increased femoral offset.

BACKGROUND: External snapping hip syndrome (ESH) is postulated to be one of the causes of greater trochanteric pain syndrome, which also includes greater trochanteric bursitis and tendinopathy or tears of the hip abductor mechanism. However, it was not yet described what kind of bony morphology can cause the snapping and whether symptomatic and asymptomatic individuals have different imaging features. PURPOSE: It was the purpose of this study to look for predisposing morphological factors for ESH and to differentiate between painful and asymptomatic snapping. METHODS: A consecutive cohort with ESH and available magnetic resonance imaging (MRI) between 2014 and 2019 was identified. The control group consisted of patients that underwent corrective osteotomies around the knee for mechanical axis correction and never complained of hip symptoms nor had undergone previous hip procedures. The following parameters were blindly assessed for determination of risk factors for ESH: CCD (corpus collum diaphysis) angle; femoral and global offset; femoral antetorsion; functional femoral antetorsion; translation of the greater trochanter (GT); posterior tilt of the GT; pelvic width/anterior pelvic length; intertrochanteric width. Hip and pelvic offset indexes were calculated as ratios of femoral/global offset and intertrochanteric/pelvic width, respectively. For the comparison of symptomatic and asymptomatic snapping, the following soft-tissue signs were investigated: presence of trochanteric bursitis or gluteal tendinopathy; presence of surface bony irregularities on trochanter major and ITB (Iliotibial band) thickness. RESULTS: A total of 31 hips with ESH were identified. The control group (n = 29) consisted of patients matched on both age (± 1) and gender. Multiple regression analysis determined an increased hip offset index to be independent predictor of ESH (r = + 0.283, p = 0.025), most likely due to the higher femoral offset in the ESH group (p = 0.031). Pearson correlation analysis could not identify any significant secondary factors. No differences were found between painful and asymptomatic snapping on MRI. CONCLUSIONS: A high hip offset index was found as an independent predictor for external snapping hip in our cohort, mainly due to increased femoral offset. No imaging soft-tissue related differences could be outlined between symptomatic and asymptomatic external snapping. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00590 .

Intermediate-Term Outcome of 3-Dimensional Corrective Osteotomy for Malunited Distal Radius Fractures With a Mean Follow-Up of 6 Years.

PURPOSE: Our study aimed to analyze the functional and radiological intermediate-term outcome of 3-dimensional-guided corrective osteotomies for malunited distal radius fractures and to evaluate the progression of osteoarthritis after this intervention. METHODS: All patients with malunited distal radius fractures who underwent 3-dimensional-guided corrective osteotomies from October 2008 to January 2015 were included. Pre- and postoperative range of motion, grip strength, and postoperative patient-reported outcomes were assessed. Pre- and postoperative osteoarthritis grading was performed using conventional radiographs and the osteoarthritis grading system described by Knirk and Jupiter. Additionally, the evaluation of articular stepoff was performed using pre- and postoperative computed tomography. RESULTS: Fifteen patients, with a mean follow-up of 6 years (range, 4.1-10.4 years), were included. According to rater 1, 8 cases had no postoperative osteoarthritis progression, 6 cases had progression of 1 grade, and 1 case had progression of 2 grades. According to rater 2, there was no progression in 11 cases, and there was progression of 1 grade in 2 cases and progression of 2 grades in 2 cases. Compared with before the surgery, the patients demonstrated a mean improvement of 14.8 kg (±12.6 kg) in grip strength after the surgery. At the last follow-up, the mean Patient-Rated Wrist Evaluation score was 11.8 (±12.0), the mean Disabilities of the Arm, Shoulder and Hand score was 11.1 (±11.4), and the mean residual pain score on the visual analog scale was 0.8 (±1.0). CONCLUSIONS: The intermediate-term outcome of 3-dimensional-guided corrective osteotomies for distal radius intra-articular malunions showed excellent patient-reported outcomes and no clinically relevant progression of osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Adjustable Loop Femoral Cortical Suspension Devices for Anterior Cruciate Ligament Reconstruction: A Systematic Review.

BACKGROUND: Anterior cruciate ligament (ACL) injury is a common sports injury. Symptomatic knee instability after this injury is usually treated operatively through ACL reconstruction. The surgery involves a tendon graft being fixed in bony tunnels drilled through femur and tibia. The fixation of the graft is of critical importance to achieving good results. One of the commonest devices used to fix the graft in the femoral bony tunnel is a fixed loop cortical suspensory device. More recently, adjustable loop cortical suspension devices have been introduced, and have gained popularity for ACL reconstruction. These allow for adjusting the length of the suspension loop after insertion. There is currently much debate concerning whether the adjustable loop devices are superior or inferior to the fixed loop devices. PURPOSE: To critique and review the current biomechanical and clinical evidence on the use of adjustable loop devices in hamstring ACL reconstruction. To our knowledge, there have been no previous reviews of this topic. STUDY DESIGN: Systematic review. METHODS: This systematic review was conducted in accordance with PRISMA. Five databases were searched using multiple search terms and MeSH terms where possible. The following limits were applied: papers published in English and papers published in the last 21 years. RESULTS: Eleven laboratory and six clinical studies were reviewed. The laboratory-based studies have frequently shown elongation of adjustable loop devices to more than 3 mm under loading protocols, whereas the clinical studies have not shown any significant differences between the patients with fixed loop and the ones with adjustable loop devices. CLINICAL SIGNIFICANCE: This review shows a discrepancy between laboratory-based and clinical studies. The review of clinical studies in our paper would give future researchers confidence and act as a prompt to construct randomised clinical trials to investigate these devices further. CONCLUSION: We feel that more robust clinical randomised studies and trials are needed to evaluate these new devices.

Combined Correction of Tibial Torsion and Tibial Tuberosity-Trochlear Groove Distance by Supratuberositary Torsional Osteotomy of the Tibia.

BACKGROUND: Increased external tibial torsion and tibial tuberosity-trochlear groove distance (TTTG) affect patellofemoral instability and can be corrected by tibial rotational osteotomy and tibial tuberosity transfer. Thus far, less attention has been paid to the combined correction of tibial torsion and TTTG by supratuberositary osteotomy. PURPOSE: To quantify the effect of a supratuberositary torsional osteotomy on TTTG. STUDY DESIGN: Descriptive laboratory study. METHODS: Seven patients who underwent supratuberositary osteotomy to treat patellofemoral instability and an additional 13 patients with increased TTTG were included (N = 20). With 3-dimensional (3D) surface models, supratuberositary rotational osteotomies were simulated with predefined degrees of rotation. Concomitant 3D TTTG was measured by a novel and validated measurement method. In addition, all operated patients underwent 2-dimensional (2D) radiographic evaluation with pre- and postoperative computed tomography data. Absolute differences among simulated, predicted, and achieved postoperative corrections were compared. RESULTS: A total of 500 supratuberositary osteotomies were simulated. The linear regression estimate yielded a change of -0.68 mm (95% CI, -0.72 to -0.63; P < .0001) in 3D TTTG per degree of tibial rotation, and 2D and 3D TTTG measurements in the operated patients were comparable in pre- and postoperative measurements (preoperative, 19.8 ± 2.5 mm and 20.0 ± 2.4 mm; postoperative, 13.6 ± 3.8 mm and 14.6 ± 3.4 mm, respectively). Postoperative 2D TTTG deviated in absolute terms from predicted (regression) and simulated TTTG by 1.4 ± 1.0 mm and 1.5 ± 0.6 mm. Inter- and intrarater reliability (intraclass correlation coefficient) for radiological and simulated measurements ranged between 0.883 and 0.996 and were almost perfect. CONCLUSION: In supratuberositary osteotomy, TTTG changes by -0.68 mm per degree of internal tibial rotation. The absolute mean difference between postoperative predicted TTTG and 2D TTTG was only 1.4 mm. Thus, TTTG correction can be successfully predicted by the degree of tibial rotation. CLINICAL RELEVANCE: TTTG correction can be successfully predicted by the degree of tibial rotation. Therefore, in selected cases, tibial torsional deformity and TTTG can be corrected by 1 osteotomy. However, isolated rotations have been performed, and unintended translational movements during tibial rotation may alter the postoperative results.

Biomechanical testing of fixed and adjustable femoral cortical suspension devices for ACL reconstruction under high loads and extended cyclic loading.

PURPOSE: To compare loop elongation after 5000 cycles, loop-elongation at failure, and load at failure of the fixed-loop G-Lok device and three adjustable-loop devices (UltraButton, RigidLoop Adjustable and ProCinch RT), during testing over extended cycles under high loading. METHODS: Five devices of each type were tested on a custom-built rig fixed to an Instron machine. The testing protocol had four stages: preloading, cyclic preconditioning, incremental cyclic loading and pull-to-failure. Outcome measures were loop elongation after 5000 cycles, loop-elongation at failure, and load at failure. RESULTS: The loop elongation after 5000 cycles for G-Lok was 1.46 ± 0.25 mm, which was comparable to that of RigidLoop (1.51 ± 0.16 mm, p = 1.000) and ProCinch (1.60 ± 0.09 mm, p = 1.000). In comparison, the loop elongation for UltraButton was 2.66 ± 0.28 mm, which was significantly larger than all other devices (p = 0.048). The failure load for all devices ranged between 1455 and 2178 N. G-Lok was significantly stronger than all adjustable-loop devices (p = 0.048). The elongation at failure was largest for UltraButton (4.20 ± 0.33 mm), which was significantly greater than G-Lok (3.17 ± 0.33 mm, p = 0.048), RigidLoop (2.88 ± 0.20 mm, p = 0.048) and ProCinch (2.78 ± 0.08 mm, p = 0.048). There was no significant difference in elongation at failure for the rest of the devices. CONCLUSIONS: Our study has shown that the G-Lok fixed-loop device and the three adjustable-loop devices (UltraButton, RigidLoop Adjustable and ProCinch RT) all elongated less than 3 mm during testing over an extended number of cycles at high loads, nonetheless, the fixed loop device performed best in terms of least elongation and highest load at failure.

Anterior talofibular ligament lesion is associated with increased flat foot deformity but does not affect correction by lateral calcaneal lengthening.

BACKGROUND: Several risk factors for adult acquired flatfoot deformity (AAFD) have been identified in literature. To this date, little attention has been paid to the lateral ligament complex and its influence on AAFD, although its anatomic course and anatomic studies suggest a restriction to flatfoot deformity. The aim of this study was to assess the influence of the anterior talofibular ligament (ATFL) on AAFD and on radiologic outcome following common operative correction by lateral calcaneal lengthening. METHODS: We reviewed all patients that underwent lateral calcaneal lengthening for correction of AAFD between January 2008 and July 2018 at our clinic. Patients were grouped according to the preoperative MRI findings into those with an intact ATFL and those with an injured ATFL. Two independent readers assessed common radiographic flatfoot parameters on preoperative and postoperative radiographs. RESULTS: Sixty-four flatfoot corrections in 63 patients were included, whereby the ATFL was intact in 29 cases, and in 35 cases the ligament was injured. An ATFL lesion was overall radiologically associated with increased flatfoot deformity with a statistically significant difference between the two groups for preoperative talometatarsal-angle (p = 0.002), talocalcaneal-angle (p = 0.000) and talonavicular uncoverage-angle (p = 0.005). No difference between the two groups could be observed regarding the success of operative correction or operative consistency after lateral calcaneal lengthening. CONCLUSION: The ATFL seems to influence the extent of AAFD. In patients undergoing lateral calcaneal lengthening, the integrity of the ligament seems not to influence the degree of correction or the consistency of the postoperative result.

A domestic porcine model for studying the effects of radiation on head and neck cancers.

BACKGROUND: Radiation therapy (RT) of the head and neck region is often accompanied by serious side effects. Research in this area is needed to improve treatment outcomes and ameliorate therapy tolerance. Laboratory rodents are barely matching today's clinical standards in RT research. Yet domestic swine (Sus scrofa domestica) have previously proved suitable for various advanced tests in clinical research and training. We therefore investigated whether S. scrofa domestica is also appropriate for irradiation of the mandible. STUDY DESIGN: A common scheme for irradiation treatment of S. scrofa domestica mandibles in a split-mouth design was acquired by applying computed tomography (CT) scanning under sedation. Basing on close anatomic resemblance, a standard treatment plan comprising 2 opposed irradiation fields could be accomplished. RESULTS: RT was carried out in a clinical environment with 2 × 9 Gy. The resulting operating procedure facilitated complication-free sedation, transport, positioning, CT scanning, and effective irradiation. CONCLUSION: Based on common standards applied for RT in humans, domestic pigs can be employed to progress RT clinical research. Due to their human-like anatomy, physiology, size, and weight, the swine model is expedient for advancing experimental RT of the head and neck area.

Acute double flexor tendon ruptures following injection of collagenase clostridium histolyticum (Xiapex) for Dupuytren's contracture.

We report a case of acute (24 h) double flexor tendon rupture of the little finger after a single injection of collagenase clostridium histolyticum into a palmar Dupuytren's contracture cord which caused metacarpophalangeal joint contracture. Tendon surgery was performed 48 h postinjury with primary repair and standard rehabilitation but it resulted in poor active flexion due to adhesions. Previous papers have suggested that a needle inserted into the flexor tendon can be detected prior to the injection of collagenase by asking the patient to actively move the finger, but our test on an awake patient showed that when a 27-gauge needle was inserted into the flexor tendons through a thick palmar cord, the syringe did not move significantly when the patient moved the finger, and therefore this test does not minimise the risk of iatrogenic tendon injury when using collagenase (Xiapex) for Dupuytren's contracture.

Isolation of mesenchymal stem cells from human bone and long-term cultivation under physiologic oxygen conditions.

Bone-derived stroma cells contain a rare subpopulation, which exhibits enhanced stemness characteristics. Therefore, this particular cell type is often attributed the mesenchymal stem cell (MSC). Due to their high proliferation potential, multipotential differentiation capacity, and immunosuppressive properties, MSCs are now widely appreciated for cell therapeutic applications in a multitude of clinical aspects. In line with this, maintenance of MSC stemness during isolation and culture expansion is considered pivot. Here, we provide step-by-step protocols which allow selection for, and in vitro propagation of high quality MSC from human bone.

BMP-2 immobilized on nanocrystalline diamond-coated titanium screws; demonstration of osteoinductive properties in irradiated bone.

BACKGROUND: Irradiation results in impaired bone healing. Thus, osteosynthesis procedures are afflicted with increased failure rates. To improve osseointegration bone morphogenetic protein-2 (BMP-2) immobilized on nanocrystalline diamond (NCD)-coated implant surfaces might be 1 solution. METHODS: By 4 weeks after irradiation of pig's mandible with a dose of 60 Gy a fracture was accomplished. Osteosynthesis was performed either with titanium osteosynthesis screws or NCD-coated screws with immobilized BMP-2. Nonirradiated animals served as control. After 1, 2, 4, and 8 weeks screws were evaluated histologically. Bone biopsies were gained to extract mesenchymal stem or precursor cells (MSCs). RESULTS: MSCs after irradiation demonstrated a behavior comparable to that of unirradiated cells. Consequently, immobilized BMP-2 resulted in an initial increased bone contact ratio (p = .014) but demonstrated no sustainable effect compared with osseointegration in nonirradiated bone (p = .08). CONCLUSION: Immobilized BMP-2 demonstrates an osteoinductive effect in irradiated bone. MSCs as effector cells possess protective mechanisms to overcome the destructive effect of irradiation.

Mesenchymal stem cells show radioresistance in vivo.

Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.

Age-specific changes of mesenchymal stem cells are paralleled by upregulation of CD106 expression as a response to an inflammatory environment.

Regeneration, tissue remodeling, and organ repair after injury, which rely on the regulated activity of tissue-borne stem cells, become increasingly compromised with advancing age. Mesenchymal stroma cells were isolated from bone of differently aged healthy donors. The rare population of mesenchymal stem cells (MSCs) contained in the primary cell isolates barely declined in number, yet the stem cells displayed diminished long-term proliferation potential relative to the donor age and the expression of vascular cell adhesion molecule-1 (VCAM-1; CD106) was elevated on primary MSCs. In CD106(bright) MSCs, the abundance of a panel of stemness transcription factors remained unchanged. Because the CD106 level could be further enhanced by proinflammatory cytokines, we considered the rate of VCAM-1 expression to be a good reflection of an endogenous inflammatory milieu to which the MSCs are exposed. Treatment of MSCs with increasing doses of interferon-γ exerted no immediate influence on their self-renewal capacity. However, it impacted on the differentiation potential toward the adipogenic or osteogenic lineage. Moderately elevated levels of inflammatory stimuli supported osteoblastogenesis whereas the same treatment reduced adipogenic differentiation in MSCs from young and intermediately aged donors. In MSCs from elderly donors, however, osteoblastogenesis was greatly diminished in an inflammatory environment whereas adipogenic differentiation remained unchanged. Conclusively, moderate levels of inflammatory stimuli are being interpreted by MSCs at a young age as instructive signals for osteoblastogenesis, whereas at old age, an inflammatory milieu may effectively suppress bone remodeling and repair by tissue-borne MSCs while uninterrupted adipogenic differentiation may lead to adipose upgrowth.

Cast and padding indices used for clinical decision making in forearm fractures in children.

PURPOSE: We assessed the reliability and practicality of two radiographic measurements--cast index and padding index--of the quality of plaster cast in clinical decision making in forearm fractures in children. METHODS: 40 orthopedic surgeons (20 consultants and 20 registrars) were asked to predict the risk of re-displacement in 5 randomly selected cases. Subsequently, these surgeons were taught these indices and they were then requested to use them to predict re-displacement. RESULTS: Every one of the 40 surgeons showed an increase in the number of correct responses. For consultants, the accuracy improved from 33% to 72% and for the registrars it improved from 28% to 81%. This improvement was statistically significant. INTERPRETATION: We suggest that cast and padding indices are simple, reliable, and reproducible radio-graphic tools that can be used in clinics and wards to predict re-displacement of forearm fractures in children following initial reduction.

Infusion of routinely stored blood may limit reperfusion injury to acutely ischemic myocardial cells.

Emergency thrombolysis and restoration of blood supply to acutely ischemic myocardium kills many reversibly injured muscle cells by free radicals generation and calcium influx. Such reversibly injured cells form the major bulk during the initial 10-20 min of ischaemia and in an era where emergency recanalization of arteries is possible, reperfusion injury becomes significant. Therefore, researchers have been trying to find out ways to limit the reperfusion injury by using antioxidants, complement inhibitors or by reperfusion of leucodepleted autologous blood. Red cell concentrates routinely available in blood banks are already depleted of plasma and hence calcium (chelated to the anticoagulant), leukocytes and most viable plasma proteins including complement. They have reduced oxygen content by virtue of storage; hence there might be less free radical generation. So infusion of such a blood through an intracoronary catheter might limit reperfusion injury. Addition of antioxidants or controlling the oxygen content while infusing this blood might give additional benefits. This hypothesis might be tested in animals by inducing controlled ischaemia with reperfusion of homologous cross-matched and group tested blood followed by cardiac radioactive scans. If the experimental results permit, clinical trials might be carried out eventually.