Fibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer.

Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler skin (velvet) regenerate, whereas back skin forms fibrotic scar. Single-cell multi-omics reveal that uninjured velvet fibroblasts resemble human fetal fibroblasts, whereas back skin fibroblasts express inflammatory mediators mimicking pro-fibrotic adult human and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: back skin fibroblasts amplify myeloid infiltration and maturation during repair, whereas velvet fibroblasts adopt an immunosuppressive phenotype that restricts leukocyte recruitment and hastens immune resolution. Ectopic transplantation of velvet to scar-forming back skin is initially regenerative, but progressively transitions to a fibrotic phenotype akin to the scarless fetal-to-scar-forming transition reported in humans. Skin regeneration is diminished by intensifying, or enhanced by neutralizing, these pathologic fibroblast-immune interactions. Reindeer represent a powerful comparative model for interrogating divergent wound healing outcomes, and our results nominate decoupling of fibroblast-immune interactions as a promising approach to mitigate scar.

Repertoire-scale measures of antigen binding.

Antibodies and T cell receptors (TCRs) are the fundamental building blocks of adaptive immunity. Repertoire-scale functionality derives from their epitope-binding properties, just as macroscopic properties like temperature derive from microscopic molecular properties. However, most approaches to repertoire-scale measurement, including sequence diversity and entropy, are not based on antibody or TCR function in this way. Thus, they potentially overlook key features of immunological function. Here we present a framework that describes repertoires in terms of the epitope-binding properties of their constituent antibodies and TCRs, based on analysis of thousands of antibody-antigen and TCR-peptide-major-histocompatibility-complex binding interactions and over 400 high-throughput repertoires. We show that repertoires consist of loose overlapping classes of antibodies and TCRs with similar binding properties. We demonstrate the potential of this framework to distinguish specific responses vs. bystander activation in influenza vaccinees, stratify cytomegalovirus (CMV)-infected cohorts, and identify potential immunological "super-agers." Classes add a valuable dimension to the assessment of immune function.

Interventions for postburn pruritus.

BACKGROUND: Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are. OBJECTIVES: To assess the effects of interventions for treating postburn pruritus in any care setting. SEARCH METHODS: In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies. AUTHORS' CONCLUSIONS: There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.

Medial Patellofemoral Ligament Reconstruction Using Pedicled Quadriceps Tendon Autograft Yields Similar Clinical and Patient-Reported Outcomes but Less Donor-Site Morbidity Compared With Gracilis Tendon Autograft.

PURPOSE: To compare clinical and patient-reported outcome measures (PROMs) in patients with recurrent patellar dislocation after medial patellofemoral ligament (MPFL) reconstruction using either a gracilis tendon (GT) or quadriceps tendon autograft (QT). METHODS: All MPFL reconstruction performed between 2017 and 2019 were reviewed retrospectively. Only patients with isolated MPFL reconstruction, without any major patellofemoral risk factors and a minimum follow-up of 24 months, were included in the study. Patients were matched with respect to sex, age, and body mass index. All patients were evaluated clinically and using PROMs. RESULTS: A total of 64 patients with an average follow up of 28.7 ± 7.5 months were included in this study. The mean Kujala score (GT: 84.8 ± 12.9, QT: 88.9 ± 10.1), Lysholm score (GT: 89.4 ± 10.2, QT: 88.4 ± 5.0), and visual analog scale score for pain (GT: 1.9 ± 1.8, QT: 1.1 ± 1.3) did not significantly differ between both groups. Tegner activity level was significantly greater (P = .027) in the QT group (5.5 ± 1.9) compared with the GT group (4.6 ± 1.8), but within the minimal clinically important differences. Occasional patellar instability events, but no recurrent dislocation, were reported in 12.5% in the GT group and 6.3% in the QT group (P = .39). Of all patients, 90.6% in the QT and 68.8% in the HT group exceeded the PASS for the Kujala score (P = .06). Significantly more patients (59.4%) treated with GT reported donor-site morbidity in the form of sensitivity deficit at the lower leg compared with those treated with QT (3.1%, P = .001). CONCLUSIONS: GT and QT MPFL reconstruction have comparable PROMs and patellar redislocation rates 2 years' postoperatively. Significantly more patients treated with GT reported lower-leg sensitivity deficit compared with those treated with QT. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Retrospective evaluation of radiological and clinical outcomes after surgical treatment of proximal femoral fractures utilizing PFNA and PFNA augmented.

INTRODUCTION: The primary aim of this study was to evaluate the clinical and radiological outcomes after surgical treatment of proximal femoral fractures utilizing the Proximal Femoral Nail Antirotation (PFNA), with the main focus on complications and reoperations. The secondary aim was to compare the outcomes of patients with and without cement augmentation of the cephalomedullary nails. MATERIALS AND METHODS: All patients with an acute proximal femoral fracture consequently treated with a PFNA between January 2011 and Dezember  2018 were evaluated. Clinical and radiological data were assessed for intra- and postoperative complications, including treatment failure. In addition, intra- and postoperative radiographs were used to determine the position of the implant, and any migration, via Tip-Apex-Distance (TAD) and the caput-collum-diaphyseal angle (CCD). The accuracy of the fracture reduction was rated according to Baumgaertners criteria. RESULTS: Two hundred sixty-four consecutive patients (mean age 78.8 ± 12.0; 73.1% female) were included. The predominant OTA/AO fracture classification was 31A1 (153 cases, 58.0%). The average duration of surgery was 63.1 ± 28.0 min and showed no significant differences between PFNA and PFNA with augmentation. The implant positioning was rated as good in 222 cases (84.1%). Two hundred sixty-three patients (99.6%) showed evidence of healing within the time frame of three months postoperatively, one case of delayed union healed after secondary dynamization. During the observational period, 18 patients (6.8%) required a total of 23 additional surgeries. Overall, a lower reoperation rate was observed following the use of the augmentation option (2/86 patients (2.3%) vs. 16/178 patients (9.0%), p = 0.04). In particular, there were no cases of cut-out or cut-through among patients who underwent augmentation as part of osteosynthesis. CONCLUSIONS: Overall reoperation rate after surgical treatment of proximal femoral fractures utilizing the Proximal Femoral Nail Antirotation (PFNA) was 6.8%, with 23 additional surgeries performed in 18 patients. The usage of the PFNA with augmentation showed equally good implant positioning, excellent healing rates and fewer postoperative complications compared to the PFNA implant alone with a similar overall duration of surgery.

Tripterygium wilfordii derivative celastrol, a YAP inhibitor, has antifibrotic effects in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is characterised by extensive tissue fibrosis maintained by mechanotranductive/proadhesive signalling. Drugs targeting this pathway are therefore of likely therapeutic benefit. The mechanosensitive transcriptional co-activator, yes activated protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid celastrol is a YAP1 inhibitor; however, if celastrol can alleviate SSc fibrosis is unknown. Moreover, the cell niches required for skin fibrosis are unknown. METHODS: Human dermal fibroblasts from healthy individuals and patients with diffuse cutaneous SSc were treated with or without transforming growth factor ß1 (TGFß1), with or without celastrol. Mice were subjected to the bleomycin-induced model of skin SSc, in the presence or absence of celastrol. Fibrosis was assessed using RNA Sequencing, real-time PCR, spatial transcriptomic analyses, Western blot, ELISA and histological analyses. RESULTS: In dermal fibroblasts, celastrol impaired the ability of TGFß1 to induce an SSc-like pattern of gene expression, including that of cellular communication network factor 2, collagen I and TGFß1. Celastrol alleviated the persistent fibrotic phenotype of dermal fibroblasts cultured from lesions of SSc patients. In the bleomycin-induced model of skin SSc, increased expression of genes associated with reticular fibroblast and hippo/YAP clusters was observed; conversely, celastrol inhibited these bleomycin-induced changes and blocked nuclear localisation of YAP. CONCLUSIONS: Our data clarify niches within the skin activated in fibrosis and suggest that compounds, such as celastrol, that antagonise the YAP pathway may be potential treatments for SSc skin fibrosis.

Enhancing Bone Infection Diagnosis with Raman Handheld Spectroscopy: Pathogen Discrimination and Diagnostic Potential.

Osteomyelitis is a bone disease caused by bacteria that can damage bone. Raman handheld spectroscopy has emerged as a promising diagnostic tool for detecting bone infection and can be used intraoperatively during surgical procedures. This study involved 120 bone samples from 40 patients, with 80 samples infected with either Staphylococcus aureus or Staphylococcus epidermidis. Raman handheld spectroscopy demonstrated successful differentiation between healthy and infected bone samples and between the two types of bacterial pathogens. Raman handheld spectroscopy appears to be a promising diagnostic tool in bone infection and holds the potential to overcome many of the shortcomings of traditional diagnostic procedures. Further research, however, is required to confirm its diagnostic capabilities and consider other factors, such as the limit of pathogen detection and optimal calibration standards.

Retrospective evaluation of radiological and clinical outcomes after surgical treatment of proximal femur fractures utilizing TFNA.

INTRODUCTION: The aim of this study was to evaluate the clinical and radiological outcomes of patients treated with the TFN-Advanced™ Proximal Femoral Nailing system (TFNA¸ DePuy Synthes, West Chester, PA) including intra- and postoperative complications. MATERIALS AND METHODS: All patients with an acute proximal femur fracture consequently treated with a TFNA between September 2014 and December 2018 were evaluated. Clinical and radiological data were assessed for intra- and postoperative complications, including treatment failure. In addition, intra- and postoperative X-rays were used to determine the position of the implant, and any migration, via tip-apex-distance (TAD) and the caput-collum-diaphyseal angle (CCD). The accuracy of the fracture reduction was rated by both observers according to Baumgartners criteria. RESULTS: 275 consecutive patients (mean age 77.5 ± 14.1; 70.2% female) were included. The predominant OTA/AO fracture classification was 31A2 (140 cases, 50.7%). The average surgical time was 69 min (± 39.8). The reduction quality was good in 253 cases (92.0%) and acceptable in 22 cases (8.0%). In 18 cases, a pre-defined primary outcome parameter (6.5%) was recorded after a mean of 8.2 ± 8.0 months. During the observational period, 19 patients (6.9%) required a total of 23 additional surgeries. Implant removal was not considered a failure in the absence of pain. Significant group differences were observed with younger age (p = 0.001), lower Charlson Comorbidity Index (CCI)-score (p = 0.041) and lower rate of osteoporosis (p = 0.015) in the failure group. There were no cases of cut-out or cut-through among the patients who underwent augmentation as part of osteosynthesis. CONCLUSIONS: Proximal femur fractures treated with the TFNA show low complication rates and high levels of radiological healing. Implant-related complications might be more common in patients with younger age, a lower CCI-score and lower frequency of osteoporosis. Usage of cement augmentation could potentially be beneficial to reduce postoperative cut-through and cut-out.

Radiographic and clinical outcome of tibial plateau fractures treated with bone allograft.

BACKGROUND: To determine the clinical outcome of patients who had been treated with bone allografts during open reduction and internal fixation (ORIF) of tibial head fractures. METHODS: Patients who suffered a medial, lateral, or bicondylar fracture of the tibial plateau and underwent surgical treatment by open reduction and internal fixation (ORIF) using human femoral head bone allografts were included. Patients were invited to provide information for the following: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Five Dimension score (EQ-5D), Lower Extremity Functional Scale (LEFS) and Parker Mobility Score. Bone mineral density (BMD) of the allograft area and the healthy human bone tissue were measured by quantitative computed tomography. RESULTS: A total of 22 patients with a mean follow-up time of 2.88 ± 2.46 years were included in our study. The most common fractures observed in this study were classified as Schatzker II (11 patients, 50.0%) or AO/OTA 41.B3 (12 patients, 54.5%) fractures. Postoperative WOMAC total was 13.0 (IQR = 16.3, range 0-33). Median quality of life (EQ-5D) score was 0.887 ± 0.121 (range 0.361-1.000). Median Lower Extremity Functional Scale (LEFS) score was 57.5 ± 19.0 (range 33-79). Mean Parker Mobility Score was 9 (range 6-9). Median bone mineral density (BMD) for the whole group was 300.04 ± 226.02 mg/cm3 (range - 88.68 to 555.06 mg/cm3) for region of interest (ROI 5) (central), 214.80 ± 167.45 mg/cm3 (range - 7.16 to 597.21 mg/cm3) for ROI 1-4 (marginal zones: medial, lateral, ventral, dorsal) and 168.14 ± 65.54 mg/cm3 (range 17.47-208.97 mg/cm3) for healthy bone tissue (femur and tibia). CONCLUSION: Based on WOMAC scores, LEFS, ambulatory status, and quality of life findings, it can be concluded that following tibial head ORIF with allograft bone patients has promising results.

Clinical performance of the Femoral Neck System within 1 year in 125 patients with acute femoral neck fractures, a prospective observational case series.

INTRODUCTION: Osteosynthesis of femoral neck fractures (FNFs) is an important treatment option, especially for younger patients. We aimed to assess the rate of early implant-related complications in FNF osteosynthesis using the Femoral Neck System (FNS). PATIENTS AND METHODS: Consecutive patients diagnosed with displaced or nondisplaced FNFs were treated with FNS in this prospective, observational, multicenter investigation. Patients were followed up for minimally 3 months and up to 12 months if radiologic bone union and no pain was not achieved beforehand. Predefined treatment-related adverse events (AEs, defined as implant failure, loss of reduction, iatrogenic fractures, deep infection, and surgical revision), radiologic bone union, and patient-reported Harris hip score (HHS) and EQ-5D-5L index score were assessed. RESULTS: One hundred and twenty-five patients were included in the study. Thirty-eight (30.4%) fractures were displaced (Garden III and IV), and 37 (29.6%) were vertical fractures (Pauwels type III). Predefined treatment-related AE rate at 3 months was 8 patients, 6.4% (95% CI, 2.8-12.2), and at 12 months, 11 patients, 8.8% (95% CI, 4.5-15.2). Cumulative incidences of bone union were 68% at 3 months, 90% at 6 months, and 98% at 12 months. The mean changes of HHS and EQ-5D-5L index score between preinjury and at 12 months were -7.5 (95% CI, [ - 21.1] to [6.2]) and - 0.03 (95% CI, [ - 0.21] to [0.15]), respectively; neither were statistically significant. CONCLUSION: The current study on osteosynthesis of FNFs with the FNS resulted in treatment-related complication rates of 6.4% (95% CI, 2.8-12.2) at 3 months and 8.8% (95% CI, 4.5-15.2) at 12 months. On average, patients returned to preinjury function and quality of life. The current study may also indicate that the conventional wisdom of treating stable FNF in patients aged between 60 and 80 years with osteosynthesis may need to be reconsidered. REGISTRATION: The study is registered with ClinicalTrials.gov (registration number: NCT02422355).

Comparison of human skin- and nerve-derived Schwann cells reveals many similarities and subtle genomic and functional differences.

Skin is an easily accessible tissue and a rich source of Schwann cells (SCs). Toward potential clinical application of autologous SC therapies, we aim to improve the reliability and specificity of our protocol to obtain SCs from small skin samples. As well, to explore potential functional distinctions between skin-derived SCs (Sk-SCs) and nerve-derived SCs (N-SCs), we used single-cell RNA-sequencing and a series of in vitro and in vivo assays. Our results showed that Sk-SCs expressed typical SC markers. Single-cell sequencing of Sk- and N-SCs revealed an overwhelming overlap in gene expression with the exception of HLA genes which were preferentially up-regulated in Sk-SCs. In vitro, both cell types exhibited similar levels of proliferation, migration, uptake of myelin debris and readily associated with neurites when co-cultured with human iPSC-induced motor neurons. Both exhibited ensheathment of multiple neurites and early phase of myelination, especially in N-SCs. Interestingly, dorsal root ganglion (DRG) neurite outgrowth assay showed substantially more complexed neurite outgrowth in DRGs exposed to Sk-SC conditioned media compared to those from N-SCs. Multiplex ELISA array revealed shared growth factor profiles, but Sk-SCs expressed a higher level of VEGF. Transplantation of Sk- and N-SCs into injured peripheral nerve in nude rats and NOD-SCID mice showed close association of both SCs to regenerating axons. Myelination of rodent axons was observed infrequently by N-SCs, but absent in Sk-SC xenografts. Overall, our results showed that Sk-SCs share near-identical properties to N-SCs but with subtle differences that could potentially enhance their therapeutic utility.

Standardized fracture creation in the distal humerus and the olecranon for surgical training and biomechanical testing.

INTRODUCTION: Surgical training and biomechanical testing require models that realistically represent the in vivo injury condition. The aim of this work was to develop and test a method for the generation of distal humerus fractures and olecranon fractures in human specimens, while preserving the soft tissue envelope. METHODS: Twenty-one cadaveric upper extremity specimens (7 female, 14 male) were used. Two different experimental setups were developed, one to generate distal humerus fractures and one to generate olecranon fractures. Specimens were placed in a material testing machine and fractured with a predefined displacement. The force required for fracturing and the corresponding displacement were recorded and the induced energy was derived of the force-displacement graphs. After fracturing, CT imaging was performed and fractures were classified according to the AO classification. RESULTS: Eleven distal humerus fractures and 10 olecranon fractures with intact soft tissue envelope could be created. Distal humerus fractures were classified as AO type C (n = 9) and as type B (n = 2), all olecranon fractures were classified as AO type B (n = 10). Distal humerus fractures required significantly more load than olecranon fractures (6077 N ± 1583 vs 4136 N ± 2368, p = 0.038) and absorbed more energy until fracture than olecranon fractures (17.8 J ± 9.1 vs 11.7 J ± 7.6, p = 0.11), while the displacement at fracture was similar (5.8 mm ± 1.6 vs 5.9 mm ± 3.1, p = 0.89). CONCLUSION: The experimental setups are suitable for generating olecranon fractures and distal humerus fractures with intact soft tissue mantle for surgical training and biomechanical testing.

Lessons learned with the Cobra prosthesis in elderly patients with complex distal radius fractures-a retrospective follow-up study.

INTRODUCTION: Recently, the Cobra prostheses were introduced in the treatment of distal radius fractures (DRF) of elderly patients. Fracture prostheses provide an alternative treatment option for complex fractures where conservative therapy seems not acceptable and osteosynthesis seems not possible. Data reporting the feasibility of the Cobra prosthesis are sparse. Therefore, this retrospective follow-up study investigated the clinical and radiological mid-term outcome of the Cobra implant in complex DRFs of elderly patients. MATERIALS AND METHODS: Thirteen patients (mean age 73.5 years, range 65-87 years) were retrospectively evaluated with at least a 1-year follow-up after surgery. Objective and subjective clinical parameters as well as the radiological outcome and complications were analyzed. RESULTS: The mean follow-up period was 31.2 months. Seven cases required a cemented prosthesis. The mean relative range-of-motion compared to the healthy side was 72.3% and 51.8% for extension and flexion, respectively, and 87.9% and 85.7% for pronation and supination, respectively. The mean grip strength was 78.3% compared to the non-operated side. Eight patients were very satisfied, five patients were partly satisfied with the result. The DASH, PRWE, MHQ and Lyon-Scores averaged 39.1, 36.2, 64.9 and 63.3 points, respectively. The mean VAS-Score for pain was 1.1 at rest and 3.2 during activities. Perioperative complications included one dissection of the extensor pollicis longus tendon, one heterotopic ossification, one radiocarpal dislocation and two cases of an ulnar impaction syndrome due to implant subsidence. CONCLUSION: The prosthetic treatment of complex DRFs in elderly patients with the Cobra implant led to clinically and radiologically satisfactory mid-term results. The Cobra prosthesis still does not represent a gold standard but can be regarded as a feasible salvage option for complex DRFs when osteosyntheses may not be possible and non-operative treatment will lead to further functional restrictions and wrist pain during performing activities of daily life in high functional demand patients.

Retrospective comparison of conservative treatment and surgery for widely displaced olecranon fractures in low-demanding geriatric patients.

INTRODUCTION: The aim of this study was to evaluate the difference of the clinical outcome of elderly patients who were treated surgically or conservatively for a displaced olecranon fracture (Mayo type IIA or IIB). PATIENTS AND METHODS: Patients above the age of 70 years who were treated surgically (n = 11) for a displaced Mayo type IIA and IIB olecranon fracture between July 2015 and February 2019 were retrospectively compared with patients who were treated conservatively (n = 6). The range of motion, elbow strength, grip strength, VAS, DASH, OES, MEPI and Broberg and Morrey scores were evaluated. RESULTS: The conservative group showed a non-union with a persistent fracture gap of 17 mm (SD 12 mm) at the articular rim and 31 mm (15 mm) at the dorsal rim while there was no case of non-union in the surgical group. The arch of motion was 120° in the conservative group and 136° in the surgical group. There was no obvious difference in elbow extension strength in comparison to the healthy contralateral side (p = 0.20; 88% group I/87% group II). There was no difference in the OES (p = 0.30; 42 (SD 7) vs. 45 (SD 5)) and MEPI score (p = 0.46; (SD 8) vs. 96 (SD 19)). The conservative group presented a slightly worse DASH [p = 0.10; 26 (SD 25) vs 7 (SD 14)] and a significantly worse Broberg and Morrey score (p = 0.02; 84(SD 9) vs. 95 (SD 7)). The conservative group presented one complication (ulnar nerve palsy), while the surgical group presented two cases (prolonged lymphedema; blocked forearm rotation due to screw length with consecutive revision surgery). CONCLUSION: Widely displaced olecranon fractures can successfully be treated conservatively in low-demanding geriatric patients with a satisfactory outcome. Patient selection is essential as patients that are more active might benefit from surgical treatment. Yet, treatment risks and benefits need to be balanced carefully in regard to the patient`s demands and requests.

Arthroscopic debridement of the dorsal capsule in intraarticular distal radius fractures: does it provide superior outcomes?

INTRODUCTION: Distal radius fractures (DRFs) are very common. One of the most significant complications after intraarticular DRF is arthrofibrosis with loss of wrist motion and pain. Wrist arthroscopy has become increasingly popular in the treatment of DRF with the advantage of good visualization of the joint surface and soft tissue injuries. In intraarticular DRFs injuries of the dorsal capsule are a characteristic finding which potentially cause loss of wrist motion. In this study, we investigated if arthroscopic debridement of dorsal capsule injuries at time of surgical fixation provides superior outcomes compared to the same treatment without debridement. MATERIALS AND METHODS: Between 2013 and 2017, we included 42 patients who underwent arthroscopy-assisted palmar plating for intraarticular DRFs in a prospective randomized controlled study. In group A (intervention group), the dorsal capsule tears were debrided during primary surgery, while in group B these were left in place. Active range of motion (AROM), grip strength, subjective outcomes and radiographic results were assessed 3, 6 and 12 months after primary surgery. A subgroup analysis was performed for patient age, fracture severity and duration of immobilization. RESULTS: Arthroscopic debridement of the dorsal capsule improved AROM in patients over 60 years of age, more severe fractures (AO 23 C2/C3) and prolonged postoperative immobilization for more than two weeks, while it was not relevant for younger patients with simple fractures and short immobilization. CONCLUSIONS: Debridement of the injured dorsal capsule in arthroscopic-assisted surgical treatment of intraarticular DRFs can improve surgical performance and optimize patient outcomes in a specific subgroup of patients.

Surgical treatment of the bony mallet thumb: a case series and literature review.

INTRODUCTION: The aim of this study was to provide a more precise statement on the outcome after surgical treatment of a bony mallet thumb and possibly give a treatment recommendation regarding the surgical fixation method. PATIENTS AND METHODS: All patients (n = 16) who underwent a surgical treatment for an acute bony mallet thumb fracture between January 2006 and July 2019 were enrolled. The surgical method, complications, the range of motion, tip pinch, lateral key pinch, overall grip strength, visual analog score, Disability of the Arm, Shoulder and Hand Score, Mayo Wrist Score, Patient-Rated Wrist Evaluation Score, Buck-Gramcko Score and radiologic parameters were evaluated. Further, a comprehensive literature search on PubMed was conducted covering a period from 1956 to 2021 to include all possible matching articles on the treatment of the bony mallet thumb (n = 21 articles). RESULTS: Surgical treatment was very inhomogenous including indirect and direct K-wire fixation, screw fixation, plate fixation and anchor fixation methods. The IP joint range of motion and thumb strength ranged from 66 to 94% in comparison to the contralateral side. An open reduction led to worse functional scores compared to a closed reduction. Treatment methods in the literature were also very inhomogenous with a very low patient count, often even pooling data of bony mallet thumb fractures with bony mallet finger fractures. The risk for infection was higher in K-wire fixation methods than in open reduction and internal fixation methods. CONCLUSION: The evidence for the best treatment of a bony mallet thumb fracture is low. On one hand the functional outcome can be inferior using an open reduction approach, but on the other hand, K-wire fixation methods with a closed reduction approach showed a higher risk for infection. Future multi-center research must be conducted to find the best treatment procedure for the best outcome of the patient.

The Limit of Detection Matters: The Case for Benchmarking Severe Acute Respiratory Syndrome Coronavirus 2 Testing.

BACKGROUND: Resolving the coronavirus disease 2019 (COVID-19) pandemic requires diagnostic testing to determine which individuals are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard is to perform reverse-transcription polymerase chain reaction (PCR) on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of approximately 100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss infected patients. However, the relative clinical sensitivity of these assays remains unknown. METHODS: Here we model the clinical sensitivities of assays based on their LoD. Cycle threshold (Ct) values were obtained from 4700 first-time positive patients using the Abbott RealTime SARS-CoV-2 Emergency Use Authorization test. We derived viral loads from Ct based on PCR principles and empiric analysis. A sliding scale relationship for predicting clinical sensitivity was developed from analysis of viral load distribution relative to assay LoD. RESULTS: Ct values were reliably repeatable over short time testing windows, providing support for use as a tool to estimate viral load. Viral load was found to be relatively evenly distributed across log10 bins of incremental viral load. Based on these data, each 10-fold increase in LoD is expected to lower assay sensitivity by approximately 13%. CONCLUSIONS: The assay LoD meaningfully impacts clinical performance of SARS-CoV-2 tests. The highest LoDs on the market will miss a majority of infected patients. Assays should therefore be benchmarked against a universal standard to allow cross-comparison of SARS-CoV-2 detection methods.

Enhanced external counterpulsation: A unique treatment for the "No-Option" refractory angina patient.

WHAT IS KNOWN AND OBJECTIVES: Coronary artery disease (CAD) is the leading cause of death in the United States. For patients on whom guideline-driven measures have been tried, enhanced external counterpulsation (EECP) is the only truly noninvasive and safe intervention for which a reduction of angina symptoms and nitrate use, increased exercise tolerance, and improvement in myocardial ischaemia have been shown. The objective of this study was to demonstrate, by way of literature review, the efficacy of EECP as a treatment modality for the relief of refractory angina and improvement in quality of life in CAD patients. METHODS: This article reviewed the safety and efficacy of EECP in patients with refractory angina, by conducting a sweeping search and analysis of existing published literature. RESULTS AND DISCUSSION: Critical review of a multitude of studies revealed that EECP consistently reduces angina pectoris, extends time to exercise-induced ischaemia, decreases dependency on nitroglycerine for frequent chest pain, increases maximum workload, and improves the quality of life in patients with symptomatic stable angina. The literature reviewed also indicated that EECP is well-tolerated by the vast majority of patients, with relatively few adverse events reported. CONCLUSION: The present study suggests that EECP is a safe and likely best available method of treatment for patients presenting with symptomatic CAD not amenable to further revascularization.

Constitutive, Basal, and ß-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling.

G protein-coupled receptors (GPCRs) have emerged as key players in regulating (patho)physiological processes, including inflammation. Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed by sensory neurons and known to modulate itch and pain. Several members of MRGPRs are also expressed in mast cells, macrophages, and in cardiovascular tissue, linking them to pseudo-allergic drug reactions and suggesting a pivotal role in the cardiovascular system. However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation of the inflammatory mediator interleukin 6 (IL-6) has not been demonstrated to date. By stimulating human MRGPRD-expressing HeLa cells with the agonist ß-alanine, we observed a release of IL-6. ß-alanine-induced signaling through MRGPRD was investigated further by probing downstream signaling effectors along the Gαq/Phospholipase C (PLC) pathway, which results in an IkB kinases (IKK)-mediated canonical activation of nuclear factor kappa-B (NF-κB) and stimulation of IL-6 release. This IL-6 release could be blocked by a Gαq inhibitor (YM-254890), an IKK complex inhibitor (IKK-16), and partly by a PLC inhibitor (U-73122). Additionally, we investigated the constitutive (ligand-independent) and basal activity of MRGPRD and concluded that the observed basal activity of MRGPRD is dependent on the presence of fetal bovine serum (FBS) in the culture medium. Consequently, the dynamic range for IL-6 detection as an assay for ß-alanine-mediated activation of MRGPRD is substantially increased by culturing the cells in FBS free medium before treatment. Overall, the observation that MRGPRD mediates the release of IL-6 in an in vitro system, hints at a role as an inflammatory mediator and supports the notion that IL-6 can be used as a marker for MRGPRD activation in an in vitro drug screening assay.

Clinical results of the BoneWelding®Fiji® anchor for the treatment of Stener lesions of the thumb.

INTRODUCTION: A new technology (Sportwelding®) was recently presented, which uses ultrasonic energy to meld a resorbable suture anchor at the interface with the host bone. A standardized clinical use was not investigated yet. This study prospectively evaluated the surgical and clinical outcomes of the Fiji Anchor® (Sportwelding®, Schlieren, Switzerland) in the repair of an ulnar collateral ligament lesion of the metacarpophalangeal joint of the thumb. MATERIAL AND METHODS: The range of motion, grip and pinch strength, disability of arm, shoulder and the hand (DASH) and patient rated evaluation (PRWE) score, pain, satisfaction, complications and adverse events were assessed in 24 patients after surgical treatment for an acute displaced rupture or avulsion of the ulnar collateral metacarpophalangeal ligament of the thumb using the Fiji Anchor® after 6, 12 and 52 weeks. RESULTS: At final follow up, the range of motion of the metacarpophalangeal joint reached almost the contralateral side (49.3° SD 11.7°). Thumb opposition showed a Kapandji score of 9.7 (SD 0.5; range 9-10). Grip strength, the lateral, tip and the three jaw pinch showed nearly similar values compared to the contralateral side (83-101%). Pain was low (0.2 SD 0.7 at rest and 0.6 SD 1.0 during load). The DASH score was 5.0 (SD 7.3) and the PRWE score was 4.1 (SD 9.0). 81% of patients were very satisfied at final follow-up. Two patients were rated unstable during the follow-up period due to a second traumatic event. Three cases experienced difficulties during anchor insertion, whereby incorrect anchor insertion resulted in damage to the suture material; however, this was resolved after additional training. CONCLUSION: One advantage of this anchor appears to be its stable fixation in cancellous bone. The surgical treatment of an ulnar collateral ligament lesion of the thumb using the Fiji Anchor® can lead to an excellent clinical outcome with a minor complication rate; however, long-term dangers and the cost effectiveness of the procedure are not known yet.