Investigation of Inkjet-Printed Masks for Fast and Easy Photolithographic NIL Masters Manufacturing.

Modern optical systems often require small, optically effective structures that have to be manufactured both precisely and cost-effectively. One option to do this is using nanoimprint lithography (NIL), in which the optical structures are replicated as masters using a stamping process. It would also be advantageous to manufacture the master structures quickly and easily. A master manufacturing process based on a photolithographic image of an inkjet-printed mask is presented and investigated in this paper. An essential element is that a deliberate blurring of the printed structure edge of the mask is used in the photolithographic process. Combined with the use of a non-linear photoresist, this allows for improved edge geometries of the master structure. We discuss the inkjet-printed photomask, the custom photolithography system to prevent imaging of the printing dot roughness and the manufacturing processes of NIL polymer masks as well as their subsequent stamp imprinting. Finally, it was shown that stamp geometries with a width of 1.7 µm could be realised using inkjet-printed photomasks in the master manufacturing process. This methodology opens up the potential of fast and simple master manufacturing for the development and manufacturing of optical elements.

Coagulopathy management of multiple injured patients - a comprehensive literature review of the European guideline 2019.

The European guideline on the management of trauma-induced major bleeding and coagulopathy summarises the most relevant recommendations for trauma coagulopathy management. The management of trauma-induced major bleeding should interdisciplinary follow algorithms which distinguish between life-threatening and non-life-threatening bleeding. Point-of-care viscoelastic methods (VEM) assist target-controlled haemostatic treatment. Neither conventional coagulation assays nor VEM should delay treatment in life-threatening trauma-induced bleeding. Adjustments may be rational due to local circumstances, including the availability of blood products, pharmaceuticals, and employees.

HIPGEN: a randomized, multicentre phase III study using intramuscular PLacenta-eXpanded stromal cells therapy for recovery following hip fracture arthroplasty : a study design.

AIMS: The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. METHODS: HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%. CONCLUSION: The HIPGEN study assesses the efficacy, safety, and tolerability of intramuscular PLX-PAD administration for the treatment of muscle injury following arthroplasty for hip fracture. It is the first phase III study to investigate the effect of an allogeneic cell therapy on improved mobilization after hip fracture, an aspect which is in sore need of addressing for the improvement in standard of care treatment for patients with FNF. Cite this article: Bone Jt Open 2022;3(4):340-347.

Therapeutic anticoagulation complications in the elderly: a case report.

BACKGROUND: The demographic transition leads to a continuously growing number of elderly patients who receive therapeutic anticoagulation by reason of several comorbidities. Though therapeutic anticoagulation may reduce the number of embolic complications in these patients, major complications such as bleeding complications need to be kept in mind when considering such therapy. However, evidence regarding the choice of anticoagulation agents in chronic kidney disease patients of higher age is limited. In this report, a guideline-based anticoagulation treatment which led to a fulminant atraumatic bleeding complication is discussed. CASE PRESENTATION: We present the case of an 85-year-old female stage V chronic kidney disease patient who suffered from a diffuse arterial, subcutaneous bleeding in her lower left leg due a therapeutic anticoagulation using low molecular weight heparin (LMWH). Anticoagulation was started in accordance with general recommendations for patients with atrial fibrillation, and the dosage was adapted for the patient's renal function. Nevertheless, the above-mentioned complication occurred, and the bleeding led to a hemorrhagic shock and an acute kidney injury on top of a chronic kidney disease. The hematoma required surgical evacuation and local coagulation in the operating room. In the further course, the patient underwent additional four surgical interventions due to a superinfected skin necrosis, including skin grafting. Furthermore, the patient needed continuous renal replacement therapy, as well as intensive care unit treatment, for a total of 47 days followed by 36 days of geriatric rehabilitation. Afterwards, she was discharged from the hospital to her previous nursing home. DISCUSSION AND CONCLUSIONS: Although therapeutic anticoagulation may sufficiently protect patients at cardiovascular risk, major complications such as bleeding complications may occur at any time. Therefore, physicians need to regularly re-evaluate any prior indication for therapeutic anticoagulation. With this case report, we hope to draw attention to the cohort of geriatric patients and the need for more and well differentiated study settings to preferably prevent any potentially avoidable complications.

The inter-individual anatomical variation of the trochlear notch as a predisposition for simple elbow dislocation.

PURPOSE: Besides the multi-layered capsule-ligamentous complex of the elbow joint the high bony congruence in the ulnohumeral joint contributes to elbow stability. Therefore, we assume that specific anatomical configurations of the trochlear notch predispose to dislocation. In case of ligamentous elbow dislocation both conservative and surgical treatment is possible without a clear treatment algorithm. Findings of constitutional bony configurations could help deciding for the best treatment option. METHODS: In this retrospective matched-pair analysis we compared MRI imaging from patients sustaining a primary traumatic elbow dislocation (instability group) with patients suffering from chronic lateral epicondylitis (control group), treated between 2009 and 2019. Two independent observers measured different anatomical landmarks of the trochlear notch in a multiplanar reconstructed standardized sagittal trochlear plane (SSTP). Primarily, opening angle and relative depth of the trochlear notch were determined. After adjustment to the proximal ulnar rim in the SSTP, coronoid and olecranon angle, the articular angle as well as the ratio of the tip heights of the trochlear notch were measured. RESULTS: We compared 34 patients in the instability group (age 48 ± 14 years, f/m 19/15) with 34 patients in the control group (age 47 ± 16 years, f/m 19/15). Instability group showed a significantly larger opening angle (94.1° ± 6.9° vs. 88.5° ± 6.9°, p = 0.0002), olecranon angle (60.9° ± 5.3° vs. 56.1° ± 5.1°, p < 0.0001) and articular angle (24.7° ± 6.4° vs. 22.3° ± 5.8°, p = 0.02) compared to the control group. Measuring the height from the coronoid (ch) and olecranon (oh) tip also revealed a significantly larger tip ratio (tr = ch/oh) in the instability group (2.7 ± 0.8 vs. 2.2 ± 0.5, p < 0.0001). The relative depth (61.0% ± 8.3% vs. 62.7% ± 6.0%, p = 0.21) of the trochlear notch as well as the coronoid angle (32.8° ± 4.5° vs. 31.7° ± 5.2°, p = 0.30) showed no significant difference in the instability group compared to the control group. The interrater reliability of all measurements was between 0.83 and 0.94. CONCLUSION: MRI of patients with elbow dislocation show that there seems to be a bony anatomical predisposition. According to the results, it seems reasonable to include predisposing bony factors in the decision-making process when surgical stabilization and conservative treatment is possible. Further biomechanical studies should prove these assumptions to generate critical bony values helping surgeons with decision making. LEVEL OF EVIDENCE: III.

Mesenchymal Stromal Cell-Based Therapy-An Alternative to Arthroplasty for the Treatment of Osteoarthritis? A State of the Art Review of Clinical Trials.

Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and to date no regenerative treatment has been established in clinical practice. This review evaluates the current literature on the clinical translation of mesenchymal stromal cell (MSC)-based therapy in OA management with a focus on safety, outcomes and procedural specifics. PubMed, Cochrane Library and clinicaltrials.gov were searched for clinical studies using MSCs for OA treatment. 290 articles were initially identified and 42 articles of interest, including a total of 1325 patients, remained for further examination. Most of the included studies used adipose tissue-derived MSCs or bone-marrow-derived MSCs to treat patients suffering from knee OA. MSC-based therapy for knee OA appears to be safe and presumably effective in selected parameters. Yet, a direct comparison between studies was difficult due to a pronounced variance regarding methodology, assessed outcomes and evidence levels. Intensive scientific engagement is needed to identify the most effective source and dosage of MSCs for OA treatment in the future. Consent on outcome measures has to be reached and eventually patient sub-populations need to be identified that will profit most from MSC-based treatment for OA.

Mesenchymal stromal cell and bone marrow concentrate therapies for musculoskeletal indications: a concise review of current literature.

The interest on applying mesenchymal stromal cells (MSCs) in orthopedic disorders has risen tremendously in the last years due to scientific successes in preclinical in vitro and animal model studies. In a wide range of diseases and injuries of the musculoskeletal system, MSCs are currently under evaluation, but so far have found access to clinical use only in few cases. The current assignment is to translate the acquired knowledge into clinical practice. Therefore, this review aims at presenting a synopsis of the up-to-date status of the use of MSCs and MSC related cell products in musculoskeletal indications. Clinical studies were included, whereas preclinical and animal study data not have been considered. Most studies published so far investigate the final outcome applying bone marrow derived MSCs. In fewer trials the use of adipose tissue derived MSCs and allogenic MSCs was investigated in different applications. Although the reported results are equivocal in the current literature, the vast majority of the studies shows a benefit of MSC based therapies depending on the cell sources and the indication in clinical use. In summary, the clinical use of MSCs in patients in orthopedic indications has been found to be safe. Standardized protocols and clear definitions of the mechanisms of action and the mode and timing of application as well as further coordinated research efforts will be necessary for finally adding MSC based therapies in standard operating procedures and guidelines for the clinicians treating orthopedic disorders.

Four-corner arthrodesis of the wrist using Variable Angle Locking Compression Intercarpal Fusion Plate (VA LCP ICF Plate; Synthes®): pre- and postoperative radiological analysis and clinical outcome in long-term evaluation.

Long persisting scaphoid non-unions or scapholunate ligament ruptures can lead to carpal collapse. The resulting clinical symptoms are restrictions in the range of motion, pain, and loss of grip strength. The symptomatic treatment so far offers different options. In our study, the Variable Angle Locking Compression Intercarpal Fusion Plate (VA LCP ICF Plate) by Synthes® was used in 11 cases of advanced carpal collapse for a four-corner fusion of the wrist. The intra- and postoperative as well as follow-up results have been assessed and compared with those of current literature. The results of the Manchester-Modified Disability of the Shoulder, Arm and Hand Score (M²-Dash) showed an average of 41.5 points (MD=44/SD=16.62/MIN=21/MAX=65). One of the re-evaluated patients complained about pain at rest. One patient stated pain after mild strain; 4 patients complained pain after heavy burden (e.g. boxing, weight lifting). Measuring the range of motion, the operated hand showed a maximum in dorsal extension of 78.31% and in flexion of 57.89% compared to the contralateral, non-operated hand. In performance testing the fist clenching sign as well as pinch grip were complete and void of pain in 100%, whereas opposition (dig. man. I to V) was complete in five patients (83.33%), with moderate pain in one patient (16.67%) and a persisting gap of 0.2 cm in n=1 (16.67%). In comparison with the current literature regarding healing rates, complications, and follow-up results, we recommend the Synthes® VA LCP ICF Plate as a good surgical option in patients suffering from advanced carpal collapse.

Hamate's coronal fracture: diagnostic and therapeutic approaches based on a long-term follow-up.

Hamate fractures are commonly divided into hook fractures and body fractures. The coronal fractures as a special form of hamate's body fracture are very rare injuries. Because of unspecific clinical findings and the mostly inconclusive x-ray imaging, these fractures are frequently overseen or misdiagnosed. This leads to further complications like secondary arthritis, persisting pain, and functional deficits in patient's wrist mobility. In our study, a collocation of coronal hamate fractures is analyzed and evaluated with respect to functional outcome after operative treatment and compared to the literature. Furthermore, we compare the strategies for diagnosis and treatment in our clinical center with those presented in the literature. Our standard in the initial diagnostic process is to obtain radiographs in an anterior-posterior, lateral, and 30° oblique view of the wrist. For further diagnosis and preoperative planning, a CT scan of the wrist is obligatory. Due to the high occurrence of comorbidities (especially CMC dislocations) all patients in our cohort obtained operative treatment. In long-term post-operative evaluation, we present the following results: The Manchester-Modified Disability of the Shoulder, Arm and Hand Score (M2 DASH) imposed with an average of 26.22 points (MD=22/ SD=11.31/MIN=18/MAX=52). None of the re-evaluated patients sorrowed for severe pain in rest. Four patients stated pain (ranging from 3 to 5 on numeric analogue scale) after heavy burden (e.g. boxing, weight lifting). In exploring the range of motion of the operated hand the following results are obtained: dorsal extension: average 83.33° (MD=85°/SD=3.54°/MIN=75°/MAX=85°), flexion: average 77.78° (MD=80°/SD=4.41°/MIN=70°/MAX=80°). Additionally, a performance testing was conducted: fist clenching sign: complete without pain in 100%, pinch grip: complete in 77.78%, opposition digitus manus I-V complete in 66.67%. The conservative treatment is not recommended (especially shown in the here presented "add" case with a misdiagnosed fracture). The open approach has its advantages compared to a closed operative procedure and should always be intraoperatively considered as an operative expansion.

A new variant of scaphoid reconstruction: Treatment of scaphoid non-union with avascular bone interponate and high compression screw (Synthes(®)).

Scaphoid fractures as frequently overseen injuries often result in scaphoid non-unions, that need to be treated to prevent carpal collapse and secondary cartilage damage. Vital bone tissue and compression of fracture and bone graft ends seem to be crucial in for ossification and final bone healing. In the present study we compare our results using a high compression screw (HCS Synthes(®)) to results in the literature using different kinds of internal fixation including compression screws of various types. We present 22 patients with scaphoid non-unions treated with a bone graft and a HCS Synthes(®). We evaluated our post-operative results. The Manchester-Modified Disability of the Shoulder, Arm and Hand-Score (M-Dash) imposed with an average of 29.8 points (MD=29 / SD=9.46 / MIN=18 / MAX=48). None of the re-evaluated patients sorrowed for pain in rest. Five patients stated pain (ranging from 4 to 8 on numeric analogue scale) after heavy burden (e.g. boxing, weight lifting).In exploring the range of motion of the operated hand we deliver the following results: dorsal extension: average 72.73° (MD=80° / SD=17.23° / MIN=30° / MAX=85°), flexion: average 73.64° (MD=80° / SD=8.97° / MIN=60° / MAX=80°), ulnar deviation: average 39.09°, (MD=40° / SD=2.02° / MIN=35° / MAX=40°), radial deviation: average 29.09°, (MD=30° / SD=3.01° / MIN=20° / MAX=30°). Additionally a performance testing was conducted: fist clenching sign: complete without pain in 100%, pinch grip: complete in 100%, moderate pain in n=1 (8.33%), opposition digitus manus I-V complete in 100%, moderate pain n=2 (16.67%). Three patients with persisting fracture gap had a scaphoid bone fractured in the proximal third; one patient even with a very small proximal fragment. One persisting non-union was localized in the middle third (period between injury and operation = 5 years). In conclusion, our patients showed better healing rates compared to results presented in the literature. Non-unions localized in the proximal third of the scaphoid did not seem to benefit using this technique.

The impact of arterial vessel injuries associated with pediatric supracondylar humeral fractures.

BACKGROUND: Pediatric supracondylar humeral fractures are regularly complicated by vascular compromise. However, the treatment regimen for pulseless hands with good capillary refill time is discussed controversially. The aim of the present study was to present our treatment strategy in a series of children sustaining supracondylar humeral fractures associated with impaired peripheral blood flow. METHODS: Medical charts of all children sustaining supracondylar humeral fractures treated between 1995 and 2009 were reviewed. Treatment and the course of patients with impaired peripheral blood flow were evaluated. Patients were invited for a follow-up examination. RESULTS: Forty of 499 patients sustaining a supracondylar humeral fracture presented with peripheral pulselessness. Two children underwent immediate vascular surgery. In the remaining 38 patients, the fracture was reduced, followed by a re-evaluation of the peripheral circulation. Twenty-four of those patients had normal peripheral pulse and capillary refill time, and no further therapy was necessary. Fourteen patients had a persisting absent peripheral pulse after fracture reduction. While in 4 of those patients-including 3 patients with prolonged peripheral capillary refill time-vascular surgery was performed, 10 patients were successfully treated with "watchful waiting." At follow-up of 3.5 years (range, 2-6 years), the performed diagnostic workup including capillary refill time and blood pressure was without pathologic findings in all patients. CONCLUSION: Our data suggest that blood flow often recovers following reduction of supracondylar fractures with impaired peripheral vascularization. In cases of a "pink pulseless hand" (absent peripheral pulse and good peripheral capillary refill time), "watchful waiting" instead of immediate surgical exploration might be a treatment option. However, further studies with more patients have to be conducted to formulate a recommendation for the treatment of these severe injuries. LEVEL OF EVIDENCE: Therapeutic study, level V.

Iatrogenic ulnar nerve injury after pin fixation and after antegrade nailing of supracondylar humeral fractures in children.

BACKGROUND AND PURPOSE: Ulnar nerve injury may occur after pinning of supracondylar fractures in children. We describe the outcome and compare the rates of iatrogenic injuries to the ulnar nerve in a consecutive series of displaced supracondylar humeral fractures in children treated with either crossed pinning or antegrade nailing. METHODS: Medical charts of all children sustaining this fracture treated at our department between 1994 and 2009 were retrospectively reviewed regarding the mode of treatment, demographic data including age and sex, the time until implant removal, the outcome, and the rate of ulnar nerve injuries. RESULTS: 503 children (55% boys) with an average age of 6.5 years sustained a type-II, type-III, or type-IV supracondylar fracture. Of those, 440 children were included in the study. Antegrade nailing was performed in 264 (60%) of the children, and the others were treated with crossed pins. Iatrogenic ulnar nerve injury occurred in 0.4% of the children treated with antegrade nailing and in 15% of the children treated with crossed pinning. After median 3 (1.6-12) years of follow-up, the clinical outcome was good and similar between the 2 groups. INTERPRETATION: Intramedullary antegrade nailing of displaced supracondylar humeral fractures can be considered an adequate and safe alternative to the widely performed crossed K-wire fixation. The risk of iatrogenic nerve injury after antegrade nailing is small compared to that after crossed pinning.

Energy recovery from sewage sludge by means of fluidised bed gasification.

Because of its potential harmful impact on the environment, disposal of sewage sludge is becoming a major problem all over the world. Today the available disposal measures are at the crossroads. One alternative would be to continue its usage as fertiliser or to abandon it. Due to the discussions about soil contamination caused by sewage sludge, some countries have already prohibited its application in agriculture. In these countries, thermal treatment is now presenting the most common alternative. This report describes two suitable methods to directly convert sewage sludge into useful energy on-site at the wastewater treatment plant. Both processes consist mainly of four devices: dewatering and drying of the sewage sludge, gasification by means of fluidised bed technology (followed by a gas cleaning step) and production of useful energy via CHP units as the final step. The process described first (ETVS-Process) is using a high pressure technique for the initial dewatering and a fluidised bed technology utilising waste heat from the overall process for drying. In the second process (NTVS-Process) in addition to the waste heat, solar radiation is utilised. The subsequent measures--gasification, gas cleaning and electric and thermal power generation--are identical in both processes. The ETVS-Process and the NTVS-Process are self-sustaining in terms of energy use; actually a surplus of heat and electricity is generated in both processes.

Cloning, functional identification and sequence analysis of flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase cDNAs reveals independent evolution of flavonoid 3',5'-hydroxylase in the Asteraceae family.

Flavonoids are ubiquitous secondary plant metabolites which function as protectants against UV light and pathogens and are involved in the attraction of pollinators as well as seed and fruit dispersers. The hydroxylation pattern of the B-ring of flavonoids is determined by the activity of two members of the vast and versatile cytochrome P450 protein (P450) family, the flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H). Phylogenetic analysis of known sequences of F3'H and F3'5'H indicated that F3'5'H was recruited from F3'H before the divergence of angiosperms and gymnosperms. Seven cDNAs were isolated from species of the Asteraceae family, all of which were predicted to code for F3'Hs based on their sequences. The recombinant proteins of four of the heterologously in yeast expressed cDNAs exhibited the expected F3'H activity but surprisingly, three recombinant proteins showed F3'5'H activity. Phylogenetic analyses indicated the independent evolution of an Asteraceae-specific F3'5'H. Furthermore, sequence analysis of these unusual F3'5'H cDNAs revealed an elevated rate of nonsynonymous substitutions as typically found for duplicated genes acquiring new functions. Since F3'5'H is necessary for the synthesis of 3',4',5'-hydroxylated delphinidin-derivatives, which normally provide the basis for purple to blue flower colours, the evolution of an Asteraceae-specific F3'5'H probably reflects the adaptive value of efficient attraction of insect pollinators.

Causes and consequences of pedestrian injuries in children.

UNLABELLED: Pedestrian-car collisions are in motorised countries one of the leading causes of unintentional-injury-related death and morbidity among children. The objective of this study was to assess correlations between the mode and the severity or post-traumatic sequels of the injury. A 12-year (1989-2001) retrospective study of children aged 0-16 years injured in pedestrian-motor-vehicle collisions was undertaken. An anonymous survey with questionnaires completed by families was conducted. In this time period, 501 children (average age: 7.9 years) were injured. The lack of visibility of the vehicle (45%) and/or the pedestrian (39%) was the leading cause of injury. The mean injury severity score was 6.0 (1-75) and the mortality rate was 0.8% ( n=4, injury severity scores 47, 75, 75, 75). In this study, 217 questionnaires were analysed. When the children were injured, 37% of them were alone, 32.3% were in the presence of accompanying adults, and 24.0% were in the presence of other children. The latter group suffered the highest injury severity score ( P=0.016). Positive correlations were noted between injury severity score and impact speed ( r=0.31, P<0.001) and the distances that the children were thrown off or transported on the vehicle front ( r=0.29, P<0.001). Physical sequels were reported by 27% of the families, and 23% noted psychological disturbances. A positive correlation was noted between impact speed and the occurrence of physical sequels ( P<0.001). The number of deformed parts per vehicle was correlated to the occurrence of behavioural disturbances ( P<0.004). CONCLUSION: The incidence of post-traumatic sequels seems to be associated with higher speed at impact, lack of braking attempts, and higher numbers of vehicle parts deformed.