RNA-seq unravels distinct expression profiles of keloids and Dupuytren's disease.

Keloid scars and Dupuytren's disease are two common, chronic, and incurable fibroproliferative disorders that, among other shared clinical features, may induce joint contractures. We employed bulk RNA sequencing to discern potential shared gene expression patterns and underlying pathological pathways between these two conditions. Our aim was to uncover potential molecular targets that could pave the way for novel therapeutic strategies. Differentially expressed genes (DEGs) were functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein-interaction (PPI) networks were constructed by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Molecular Complex Detection (MCODE) plugin was used for downstream analysis of the PPI networks. A total of 1922 DEGs were identified within Dupuytren's and keloid samples, yet no overlapping gene expression profiles were detected. Significantly enriched GO terms were related to skin development and tendon formation in keloid scars and Dupuytren's disease, respectively. The PPI network analysis revealed 10 genes and the module analysis provided six protein networks, which might play an integral part in disease development. These genes, including CDH1, ERBB2, CASP3 and RPS27A, may serve as new targets for future research to develop biomarkers and/or therapeutic agents.

Clinical Acuity in the Emergency Department and Injury Severity Determine Hospital Admission of Older Patients with Low Energy Falls: Outcomes from a Prospective Feasibility Study.

BACKGROUND: Low energy falls (LEF) in older adults constitute a relevant cause for emergency department (ED) visits, hospital admission and in-hospital mortality. Patient-reported outcome measures containing information about patients' medical, mental and social health problems might support disposition and therapy decisions. We investigated the value of a tablet-based (self-)assessment in predicting hospital admission and in-hospital mortality. METHODS: Patients 65 years or older, consecutively presenting with LEF to our level I trauma center ED (from November 2020 to March 2021), were eligible for inclusion in this prospective observational study. The primary endpoint was hospital admission; secondary endpoints were in-hospital mortality and the use of the tablet for self-reported assessment. Multivariate logistic regression models were calculated to measure the association between clinical findings and endpoints. RESULTS: Of 618 eligible patients, 201 patients were included. The median age was 82 years (62.7% women). The hospital admission rate was 45.3% (110/201), with an in-hospital mortality rate of 3.6% (4/110). Polypharmacy (odds ratio (OR): 8.48; 95% confidence interval (95%CI) 1.21-59.37, p = 0.03), lower emergency severity index (ESI) scores (OR: 0.33; 95%CI 0.17-0.64, p = 0.001) and increasing injury severity score (ISS) (OR: 1.54; 95%CI 1.32-1.79, p < 0.001) were associated with hospital admission. The Charlson comorbidity index (CCI) was significantly associated with in-hospital mortality (OR: 2.60; 95%CI: 1.17-5.81, p = 0.03). Increasing age (OR: 0.94; 95%CI: 0.89-0.99, p = 0.03) and frailty (OR: 0.71; 95%CI: 0.51-0.99, p = 0.04) were associated with the incapability of tablet use. CONCLUSIONS: The severity of fall-related injuries and the clinical acuity are easily accessible, relevant predictors for hospital admission. Tablet-based (self-)assessment may be feasible and acceptable during ED visits and might help facilitate comprehensive geriatric assessments during ED stay.

Rehabilitation following operative treatment of acute Achilles tendon ruptures: a systematic review and meta-analysis.

Purpose: The aim of this systematic review and meta-analysis was to compare re-rupture rates, complication rates, functional outcomes, as well as return to work (RTW)/sport (RTS) among different rehabilitation protocols following operative treatment of acute Achilles tendon ruptures. Methods: Systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five databases were searched for randomized controlled trials (RCTs) comparing at least two rehabilitation protocols following surgical repair of acute Achilles tendon ruptures. Rehabilitation protocols were classified as a variation of either non-weightbearing (NWB) or weightbearing (WB) and immobilization (IM) or mobilization (M). The data collection consisted of re-ruptures, complications, and RTW/RTS. Results: Out of 2760 studies screened, 20 RCTs with 1007 patients were eligible. Fourteen studies included a group consisting of WB + M (Group 1), 11 of WB + IM (Group 2), 3 of NWB + M (Group 3), and 13 of NWB + IM (Group 4). Outcome parameters available for a meta-analysis were re-ruptures, complications, RTW, and RTS. Re-ruptures overall occurred in 2.7%, with prevalences ranging between 0.04 and 0.08. Major complications occurred in 2.6%, with prevalences ranging between 0.02 and 0.03. Minor complications occurred in 11.8% with prevalances ranging between 0.04 to 0.17. Comparing the odds-ratios between the four different groups revealed no significant differences with overall favourable results for group 1 (WB+M). Conclusion: Early functional rehabilitation protocols with early ankle M and WB following surgical repair of acute Achilles tendon ruptures are safe and they apparently allow for a quicker RTW and RTS and seem to lead to favourable results.

Trends of incidence and treatment strategies for operatively treated distal fibula fractures from 2005 to 2019: a nationwide register analysis.

INTRODUCTION: Valid epidemiological data about distal fibular fractures and their treatment strategies are missing. Innovative osteosynthesis techniques were introduced and improved during the past 15 years. The aim of this study was to investigate the epidemiologic development and the implementation of new treatment strategies in a nationwide register in Germany over a period of 15 years. MATERIALS AND METHODS: Data of the German Federal Statistical Office from 2005 until 2019 were screened. Adults with a fracture of the distal fibula were included. Data were separated for gender, age and treatment strategy. RESULTS: During the past 15 years, there was a steady annual incidence of distal fibula fractures of 74 ± 32 per 100,000 people without any significant changes (p = 0.436). 60.1% ± 0.6% of all fractures occurred in females. The annual incidence for male was nearly constant over the different age groups, whereas for female, there was a clear increase in incidence above the age of 40. Whereas 66% of fractures in between 20 and 30 years of age occurred in male, approximately 70% of fractures above the age of 60 occurred in females. The relative quantity of locking plates increased from 2% in 2005 to 34% in 2019. In 2019, only 1.02% of the patients were operated with an intramedullary nail. CONCLUSIONS: Operatively treated distal fibular fractures revealed an age dependent increase in incidence in postmenopausal women compared to younger females. Regarding the treatment strategy, there was an increase in application of locking plates. The data implicate a typical fragility fracture related age and gender distribution for distal fibula fractures.

The T-pod is as stable as supraacetabular fixation using 1 or 2 Schanz screws in partially unstable pelvic fractures: a biomechanical study.

INTRODUCTION: Unstable fractures of the pelvis remain the predominant cause of severe hemorrhage, shock and early death in severely injured patients. The use of pelvic binders has become increasingly popular, particularly in the preclinical setting. There is currently insufficient evidence available about the stability of the pelvic binder versus supraacetabular fixation using 1 or 2 Schanz screws. We aimed to analyze the stability of the pelvic binder and supraacetabular fixateurs using either 1 or 2 Schanz screws in a cadaver model of an induced pelvic B-type fracture. MATERIALS AND METHODS: The study was undertaken in 7 human fresh-frozen cadaveric pelvises with induced AO-type B fractures. Three stabilization techniques were compared: T-POD (pelvic bandage), supraacetabular external fixator with 1 pin on each side and external fixator with 2 pins on each side. Stability and stiffness were analyzed in a biomechanical testing machine using a 5-step protocol with static and dynamic loading, dislocation data were retrieved by ultrasound sensors at the fracture sites. RESULTS: No significant differences in fracture fragment displacement were detected when using either the T-POD, a 1-pin external fixator or a 2-pin external fixator (P > 0.05). The average difference in displacement between the three methods was < 1 mm. CONCLUSIONS: Pelvic binders are suitable for reduction of pelvic B-type fractures. They provide stability comparable to that of supraacetabular fixators, independently of whether 1 or 2 Schanz screws per side are used. Pelvic binders provide sufficient biomechanical stability for transferring patients without the need to first replace them with surgically applied external fixators. However, soft tissue irritation has to be taken into consideration and prolonged wear should be avoided. LEVEL OF EVIDENCE: Level III.

Tape suture for stabilization of incomplete posterior pelvic ring fractures-biomechanical analysis of a new minimally invasive treatment for incomplete lateral compression pelvic ring fractures.

BACKGROUND: Incomplete lateral compression fractures (including AO Type B2.1) are among the most common pelvic ring injuries. Although the treatment of choice remains controversial, sacroiliac (SI) screws are commonly used for the operative treatment of incomplete lateral compression fractures of the pelvic ring. However, the disadvantages of SI screws include the risk of nerve root or blood vessel injury. Recently, tape sutures have been found useful as stabilizing material for the treatment of injuries of the syndesmosis, the rotator cuff and knee ligaments. In this current study, we aimed to test the biomechanical feasibility of tape sutures to stabilize the pelvis in the setting of AO Type B2.1 injury. METHODS: Six human cadaveric pelvises underwent cyclic loading to compare the biomechanical stability of different osteosynthesis methods in a B2.1 fracture model. The methods tested in this experiment were a FiberTape® suture and the currently established SI screw. A 3D ultrasound tracking system was used to measure fracture fragment motion. Linear regression was used to model displacement and stiffness at the posterior and anterior pelvic ring. RESULTS: At the posterior fracture site, the FiberTape® demonstrated similar displacement (2.2 ± 0.8 mm) and stiffness (52.2 ± 18.0 N/mm) compared to the sacroiliac screw (displacement 2.1 ± 0.6 mm, P >  0.999; stiffness 50.8 ± 13.0 N/mm, P > 0.999). Considering the anterior fracture site, the FiberTape® again demonstrated similar displacement (3.8 ± 1.3 mm) and stiffness (29.5 ± 9.0 N/mm) compared to the sacroiliac screw (displacement 2.9 ± 0.8 mm, P = 0.2196; stiffness 37.5 ± 11.5 N/mm, P = 0.0711). CONCLUSION: The newly presented osteosynthesis, the FiberTape®, shows promising results for the stabilization of the posterior pelvic ring in AO Type B2.1 lateral compression fractures compared to a sacroiliac screw osteosynthesis based on its minimal-invasiveness and the statistically similar biomechanical properties.

Development of an accelerated functional rehabilitation protocol following minimal invasive Achilles tendon repair.

PURPOSE: Surgical repair after acute Achilles tendon rupture leads to lower re-rupture rates than non-surgical treatment. After open repair, early functional rehabilitation improves outcome, but there are risks of infection and poor wound healing. Minimal invasive surgery reduces these risks; however, there are concerns about its stability. Consequently, physicians may have reservations about adopting functional rehabilitation. There is still no consensus about the post-operative treatment after minimal invasive repair. The aim of this study was to define the most effective and safe post-operative rehabilitation protocol following minimal invasive repair. METHODS: A systematic literature search in Embase, MEDLINE and Cochrane Library for prospective trials reporting on early functional rehabilitation after minimal invasive repair was performed. Seven studies were included. RESULTS: One randomized controlled trail, one prospective comparative and five prospective non-comparative studies were identified. Four studies performed full weight bearing, all demonstrating good functional results, an early return to work/sports and high satisfaction. One study allowed early mobilization leading to excellent subjective and objective results. The only randomized controlled trial performed the most accelerated protocol demonstrating a superior functional outcome and fewer complications after immediate full weight bearing combined with free ankle mobilization. The non-comparative study reported high satisfaction, good functional results and an early return to work/sports following combined treatment. CONCLUSION: Immediate weight bearing in a functional brace, together with early mobilization, is safe and has superior outcome following minimally invasive repair of Achilles tendon rupture. Our recommended treatment protocol provides quality assurance for the patient and reliability for the attending physician. LEVEL OF EVIDENCE: II.

Performance characteristics of a novel blood bag in-line closure device and subsequent product quality assessment.

BACKGROUND: In high-volume processing environments, manual breakage of in-line closures can result in repetitive strain injury (RSI). Furthermore, these closures may be incorrectly opened causing shear-induced hemolysis. To overcome the variability of in-line closure use and minimize RSI, Fresenius Kabi developed a new in-line closure, the CompoFlow, with mechanical openers. STUDY DESIGN AND METHODS: The consistency of the performance of the CompoFlow closure device was assessed, as was its effect on component quality. A total of 188 RBC units using CompoFlow blood bag systems and 43 using the standard bag systems were produced using the buffy coat manufacturing method. Twenty-six CompoFlow platelet (PLT) concentrates and 10 control concentrates were prepared from pools of four buffy coats. RBCs were assessed on Days 1, 21, and 42 for cellular variables and hemolysis. PLTs were assessed on Days 1, 3, and 7 for morphology, CD62P expression, glucose, lactate, and pH. A total of 308 closures were excised after processing and the apertures were measured using digital image analysis. RESULTS: The use of the CompoFlow device significantly improved the mean extraction time with 0.46±0.11sec/mL for the CompoFlow units and 0.52±0.13sec/mL for the control units. The CompoFlow closures showed a highly reproducible aperture after opening (coefficient of variation, 15%) and the device always remained opened. PLT and RBC products showed acceptable storage variables with no differences between CompoFlow and control. CONCLUSIONS: The CompoFlow closure devices improved the level of process control and processing time of blood component production with no negative effects on product quality.

Current Aspects of Fragility Fracture Repair.

Due to the demographic developments worldwide, fragility fractures represent an increasing problem for the public health system. The risk of developing osteoporosis increases with age and is relatively higher in women and in the Caucasian population. The stability of bone is reduced because of accentuation of the normal loss of bone mass in ageing, leading to an increased susceptibility to fracture with an increased rate of complications after surgical stabilization. Due to this, the orthopedic surgeon has to assess the quality of the bone during preoperative planning and select the implants and postoperative care accordingly to achieve the best. Over the last 10 years fixed locking implants have been introduced into clinical practice. These represent a new type of angle stable fixation devices that address the mechanical instability between bone and implant. The novel problems associated with this device are due to higher cut-out rates when the bone structure is altered and mass is reduced. The developments in joint replacement have also resulted in longer standing times and lower complication rates with immediate fullweight-bearing after implantation. However, to date, little is known about the mechanisms of fracture healing in osteoporosis or fragility fractures. One future approach may be in supporting biological fracture healing by regenerative therapies using growth hormones and/or (stem) cells. The most frequent initial clinical symptom of osteoporosis is a fracture without a relevant trauma. At this stage, the trauma surgeon should initiate diagnostic procedures, treatment of osteoporosis and tertiary prevention according to the European guidelines. Ultimately, all female patients older than 50 years and all male patients older than 60 years with fractures should be assessed and treated for bone quality. Orthogeriatric specialists or interdisciplinary orthogeriatric teams should initiate a specific surgical treatment followed by early rehabilitation in order to allow the elderly patient to return to daily living as soon as possible.

Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: implications for herceptin-induced cardiomyopathy.

OBJECTIVES: We investigated the effects of erbB2 inhibition by anti-erbB2 antibody on cardiomyocyte survival and mitochondrial function. BACKGROUND: ErbB2 is an important signal integrator for the epidermal growth factor family of receptor tyrosine kinases. Herceptin, an inhibitory antibody to the erbB2 receptor, is a potent chemotherapeutic but causes cardiac toxicity. METHODS: Primary cultures of neonatal rat ventricular myocytes were exposed to anti-erbB2 antibody (Ab) (7.5 mug/ml) for up to 24 h. Cell viability, mitochondrial function, and apoptosis were measured using multiple complementary techniques. RESULTS: ErbB2 inhibition was associated with a dramatic increase in expression of the pro-apoptotic Bcl-2 family protein Bcl-xS and decreased levels of anti-apoptotic Bcl-xL. There was a time-dependent increase in mitochondrial translocation and oligomerization of bcl-associated protein (BAX), as indicated by 1,6-bismaleimidohexane crosslinking. The BAX oligomerization was associated with cytochrome c release and caspase activation. These alterations induced mitochondrial dysfunction, a loss of mitochondrial membrane potential (psi) (76.9 +/- 2.4 vs. 51.7 +/- 0.1; p < 0.05; n = 4), a 35% decline in adenosine triphosphate levels (p < 0.05), and a loss of redox capacity (0.72 +/- 0.04 vs. 0.64 +/- 0.02; p< 0.01). Restoration of Bcl-xL levels through transactivating regulatory protein-mediated protein transduction prevented the decline in psi mitochondrial reductase activity and cytosolic adenosine triphosphate. CONCLUSIONS: Anti-erbB2 activates the mitochondrial apoptosis pathway through a previously undescribed modulation of Bcl-xL and -xS, causing impairment of mitochondrial function and integrity and disruption of cellular energetics.

Cardiac-specific gene expression facilitated by an enhanced myosin light chain promoter.

BACKGROUND: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. METHODS: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v) gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc) reporter gene (Ad.4 x MLC250.Luc). Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 x MLC.Luc or control vectors. For in vivo testing, Ad.4 x MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. RESULTS: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells) was 20.4 versus 0.9 (Ad.4 x MLC250.Luc vs. Ad.CMV). In vivo: Ad.4 x MLC250.Luc significantly reduced luc activity in liver (38.4-fold), lung (16.1-fold), and kidney (21.8-fold) versus Ad.CMV (p =.01); whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 x MLC.Luc) versus 1:1.4 (Ad.CMV.Luc). DISCUSSION: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart.

Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure.

Aortic banding in the rat has become a popular method to induce left ventricular (LV) hypertrophy and heart failure. However, because of often extensive intrathoracic adhesions and inflammatory cell infiltrates resulting from the traditional surgical approach, an uncomplicated second thoracic incision for genetic manipulation is impeded. In this study, we describe a novel surgical technique of aortic banding which avoids opening the sternum and thereby avoids adhesions and surgery-related inflammation. Placing a clip on the ascending aorta using a suprasternal approach in Sprague-Dawley rats created proximal aortic constriction. The present study was initiated to determine whether a replication-deficient adenovirus would enable efficient gene transfer to adult cardiac myocytes undergoing hypertrophy and transitioning to heart failure. Echocardiography performed at week 24 revealed significant concentric hypertrophy and increased fractional shortening followed by LV dilatation with decreased fractional shortening after 27 wk of banding. An adenoviral solution encoding for the reporter green fluorescent protein gene (GFP) was delivered to the heart. Fluorescent microscopy revealed global gene expression throughout hypertrophied and failing hearts. Our studies demonstrate that a novel suprasternal approach can be applied to create an LV hypertrophy model followed by heart failure which also allows investigators to perform genetic manipulations in vivo through gene transfer without the complication of adhesions and surgical trauma-induced inflammation. Furthermore, our approach to delivery of transgenes results in homogenous gene expression in both hypertrophied and failing hearts.