Developing a core outcome set for acetabular fractures: a systematic review protocol.

BACKGROUND: Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies. METHODS: Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative. DISCUSSION: It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357644.

Pedicled ALT-flap for soft tissue reconstruction in the trochanteric area.

BACKGROUND: Coverage of soft tissue defects following surgery at the trochanteric area is challenging. Revision surgery in case of compromised wound healing may lead to soft tissue defects requiring reconstruction with pedicled or free flaps. Previous access to the hip joint may jeopardize neurovascular structures relevant to the flap. OBJECTIVE: In this study, we evaluated if the use of a pedicled anterior lateral thigh (ALT) flap is a valuable option for soft tissue reconstruction. METHODS: In this retrospective study, seven patients were included. Defect etiology was tumor resection in one case, screw osteosynthesis in another case and total hip arthroplasty in three cases. All patients underwent reconstruction by proximal pedicled anterior lateral thigh (ALT) flap. RESULTS: Pedicled ALT flap was a safe procedure in all cases. One patient showed delayed wound healing with need for additional surgery. No further complications were observed. CONCLUSIONS: Pedicled ALT flap transfer represents a reliable option for soft tissue coverage in the trochanteric area after primary surgery such as hip arthroplasty, osteosynthesis or tumor resection.

Is nail-plate docking worth the effort? A biomechanical analysis of docking a plate and a nail in peri-implant femur fractures.

Purpose: The ideal treatment of peri-implant femur fractures (PIFFs) remains unclear due to the thin clinical and biomechanical evidence concerning the most suitable form of osteosynthesis. The purpose of the present study was thus to determine the biomechanical stability that results from combining a cephalomedullary nail and a plate for proximal PIFFs, especially when the nail-plate docking technique is applied. Methods: Twenty four PIFFs were simulated in both 12 foam and 12 composite specimens and were stabilized via a combination of a cephalomedullary nail and a plate. The control group (n = 6) had a nail and a plate without a connection, while the intervention group (n = 6) had a screw that connected the plate with the interlocking screw hole of the nail, thereby creating a nail-plate docking system. The specimens were evaluated under axial and torsional loading using a material-testing machine and a 3D metrology system. Results: The data regarding stiffness, failure load, and failure displacement showed significantly higher stability for specimens without nail-plate docking. For docked specimens, a non-significant trend toward a higher resistance to torque was observed. Both techniques displayed no significant difference in fracture gap displacement or total displacement. Conclusion: The present study suggests that nail-plate docking of a cephalomedullary nail, and a plate significantly decreases the stiffness and stability of osteosynthesis under axial loading. However, there seems to be a tendency toward higher resistance to torque. Therefore, surgeons should consider this technique if higher torsional stability is necessary, and they should decide against it, if axial stability is preferred.

Maduramycin, a novel glycosylation modulator for mammalian fed-batch and steady-state perfusion processes.

Controlling high-mannose (HM) content of therapeutic proteins during process intensification, reformulation for subcutaneous delivery, antibody-drug conjugate or biosimilar manufacturing represents an ongoing challenge. Even though a range of glycosylation levers to increase HM content exist, modulators specially increasing M5 glycans are still scarce. Several compounds of the polyether ionophore family were screened for their ability to selectively increase M5 glycans of mAb products and compared to the well-known α-mannosidase I inhibitor kifunensine known to increase mainly M8-M9 glycans. Maduramycin, amongst other promising polyether ionophores, showed the desired effect on different cell lines. For fed-batch processes, a double bolus addition modulator feed strategy was developed maximizing the effect on glycosylation by minimizing impact on culture performance. Further, a continuous feeding strategy for steady-state perfusion processes was successfully developed, enabling consistent product quality at elevated HM glycan levels. With kifunensine and maduramycin showing inverse effects on the relative HM distribution, a combined usage of these modulators was further evaluated to fine-tune a desired HM glycan pattern. The discovered HM modulators expand the current HM modulating toolbox for biotherapeutics. Their application not only for fed-batch processes, but also steady-state perfusion processes, make them a universal tool with regards to fully continuous manufacturing processes.

Raman-controlled pyruvate feeding to control metabolic activity and product quality in continuous biomanufacturing.

BACKGROUND: Despite technological advances ensuring stable cell culture perfusion operation over prolonged time, reaching a cellular steady-state metabolism remains a challenge for certain manufacturing cell lines. This study investigated the stabilization of a steady-state perfusion process producing a bispecific antibody with drifting product quality attributes, caused by shifting metabolic activity in the cell culture. MAIN METHODS: A novel on-demand pyruvate feeding strategy was developed, leveraging lactate as an indicator for tricarboxylic acid (TCA) cycle saturation. Real-time lactate monitoring was achieved through in-line Raman spectroscopy, enabling accurate control at predefined target setpoints. MAJOR RESULTS: The implemented feedback control strategy resulted in a three-fold reduction of ammonium accumulation and stabilized product quality profiles. Stable and flat glycosylation profiles were achieved with standard deviations below 0.2% for high mannose and fucosylation. Whereas galactosylation and sialylation were stabilized in a similar manner, varying lactate setpoints might allow for fine-tuning of these glycan forms. IMPLICATION: The Raman-controlled pyruvate feeding strategy represents a valuable tool for continuous manufacturing, stabilizing metabolic activity, and preventing product quality drifting in perfusion cell cultures. Additionally, this approach effectively reduced high mannose, helping to mitigate increases associated with process intensification, such as extended culture durations or elevated culture densities.

[Analysis of a differentiated resuscitation room activation at a national trauma center]. / Analyse einer differenzierten Schockraumalarmierung an einem überregionalen Traumazentrum.

BACKGROUND: In order to continue to efficiently provide both personnel-intensive and resource-intensive care to severely injured patients, some hospitals have introduced individually differentiated systems for resuscitation room treatment. The aim of this study was to evaluate the concept of the A and B classifications in terms of practicability, indications, and potential complications at a national trauma center in Bavaria. METHODS: In a retrospective study, data from resuscitation room trauma patients in the year 2020 were collected. The assignment to A and B was made by the prehospital emergency physician. Parameters such as the injury severity score (ISS), Glasgow outcome scale (GOS), upgrade rate, and the indication criteria according to the S3 guidelines were recorded. Statistical data comparisons were made using t­tests, χ2-tests, or Mann-Whitney U­tests. RESULTS: A total of 879 resuscitation room treatments (A 473, B 406) met the inclusion criteria. It was found that 94.5% of resuscitation room A cases had physician accompaniment, compared to 48% in resuscitation room B assignments. In addition to significantly lower ISS scores (4.1 vs. 13.9), 29.8% of B patients did not meet the treatment criteria defined in the S3 guidelines. With a low upgrade rate of 4.9%, 98% of B patients had a GOS score of 4 or 5. CONCLUSION: The presented categorization is an effective and safe way to manage the increasing number of resuscitation room alerts in a resource-optimized manner.

Experimental magnesium phosphate cement paste increases torque of trochanteric fixation nail advanced™ blades in human femoral heads.

BACKGROUND: The use of polymethylmethacrylate cement for in-situ implant augmentation has considerable disadvantages: it is potentially cytotoxic, exothermic and non-degradable. Therefore, the primary aim of this study was to develop a magnesium phosphate cement which meets the requirements for in-situ implant augmentation as an alternative. Secondly, this experimental cement was compared to commercial bone cements in a biomechanical test set-up using augmented femoral head blades. METHODS: A total of 40 human femoral heads were obtained from patients who underwent total hip arthroplasty. After bone mineral density was quantified, specimens were assigned to four treatment groups. A blade of the Trochanteric Fixation Nail Advanced™ was inserted into each specimen and augmented with either Traumacem™ V+, Paste-CPC, the experimental magnesium phosphate cement or no cement. A rotational load-to-failure-test (0° to 90°) was performed. FINDINGS: A conventional two-component magnesium phosphate cement failed in-situ implant augmentation consistently due to filter pressing. Only a glycerol-based magnesium phosphate paste was suitable for the augmentation of femoral head blades. While the blades augmented with Traumacem™ V+ yielded the highest maximum torque overall (22.1 Nm), the blades augmented with Paste-CPC and the magnesium phosphate paste also showed higher maximum torque values (15.8 and 12.8 Nm) than the control group (10.8 Nm). INTERPRETATION: This study shows for the first time the development of a degradable magnesium phosphate cement paste which fulfills the requirements for in-situ implant augmentation. Simultaneously, a 48% increase in stability is demonstrated for a scenario where implant anchorage is difficult in osteoporotic bone.

Impact of a Femoral Fracture on Outcome after Traumatic Brain Injury-A Matched-Pair Analysis of the TraumaRegister DGU®.

Traumatic brain injury (TBI) is the leading cause of death and disability in polytrauma and is often accompanied by concomitant injuries. We conducted a retrospective matched-pair analysis of data from a 10-year period from the multicenter database TraumaRegister DGU® to analyze the impact of a concomitant femoral fracture on the outcome of TBI patients. A total of 4508 patients with moderate to critical TBI were included and matched by severity of TBI, American Society of Anesthesiologists (ASA) risk classification, initial Glasgow Coma Scale (GCS), age, and sex. Patients who suffered combined TBI and femoral fracture showed increased mortality and worse outcome at the time of discharge, a higher chance of multi-organ failure, and a rate of neurosurgical intervention. Especially those with moderate TBI showed enhanced in-hospital mortality when presenting with a concomitant femoral fracture (p = 0.037). The choice of fracture treatment (damage control orthopedics vs. early total care) did not impact mortality. In summary, patients with combined TBI and femoral fracture have higher mortality, more in-hospital complications, an increased need for neurosurgical intervention, and inferior outcome compared to patients with TBI solely. More investigations are needed to decipher the pathophysiological consequences of a long-bone fracture on the outcome after TBI.

[The severely injured older cyclist-Evaluation of the TraumaRegister DGU® : Retrospective, multicenter cross-sectional study based on the TraumaRegister DGU®]. / Der schwer verletzte ältere Fahrradfahrer ­ Auswertung des TraumaRegister DGU® : Retrospektive, multizentrische Querschnittstudie anhand des TraumaRegister DGU®.

BACKGROUND: Contrary to the trend of decreasing traffic fatalities, the number of cyclists killed in Germany has been steadily increasing in recent years. With the increasing popularity of cycling in all age groups, the number of accidents with sometimes serious injuries is rising. In the course of this, the question arises what influence age has on the type and severity of injuries, the probability of survival and the length of hospital stay in seriously injured cyclists. METHODS: A retrospective analysis of data from the TraumaRegister DGU® (TR-DGU) from 2010 to 2019 was performed. All severely injured cyclists with a maximum abbreviated injury scale (MAIS) of 3+ (n = 14,651) in the TR-DGU were included in this study and the available parameters were evaluated. A subdivision into three age groups (60-69, 70-79, and ≥ 80 years) and a control group (20-59 years) was carried out. RESULTS: Injuries to the head were by far the most common, accounting for 64.2%. There was a marked increase in severe head injuries in the 60-plus years age group. Furthermore, with increasing age, the probability of prehospital intubation, catecholamine requirement, intensive care and hospital length of stay, and mortality increased. CONCLUSION: Head injuries represent the most common serious injury, especially among older cyclists. As helmet wearing was not recorded in the TraumaRegister DGU® during the evaluation period, no conclusion can be drawn about its effect. Furthermore, a higher age correlates with a longer hospital stay and a higher mortality, but does not represent an independent risk factor for death in severely injured patients.

Gantry-Free High-Resolution Cone-Beam CT: Efficacy for Distal Radius and Scaphoid Fracture Detection and Characterization.

OBJECTIVES: Gantry-free cone-beam CT (CBCT) allows for comfortable patient positioning due to an open scanner architecture. Since CBCT without gantry is not yet established for clinical wrist trauma imaging, this study's aim was to investigate its diagnostic value in the preoperative workup of patients with distal radius and scaphoid fractures. METHODS: Within a 12-month period, 113 patients with severe wrist trauma underwent both radiography and CBCT with the same gantry-free multi-use scanner before surgery. Two radiologists retrospectively analyzed all datasets for the morphology of distal radius (n = 95) and scaphoid fractures (n = 20). In all 115 wrists (two bilateral injuries), surgical reports served as the standard of reference. RESULTS: While accuracy for distal radius fractures was comparable among CBCT and radiographs, the former was superior with regard to scaphoid fractures (Reader 1: 100.0% vs. 75.0%; Reader 2: 100.0% vs. 65.0%). Accuracy for multi-fragmentary radius injuries (100.0% vs. 90.5%; 100.0% vs. 93.7%), and articular affliction (99.0% vs. 84.2%; 100.0% vs. 83.2%) was also higher in CBCT. Regarding scaphoid fractures, CBCT proved superior for diagnosis of proximal pole or waist involvement (100.0% vs. 70.0%; 100.0% vs. 65.0%) and comminuted patterns (100.0% vs. 70.0%; 100.0% vs. 75.0%). Median effective dose of CBCT was as low as 3.65 µSv compared with 0.16 µSv for standard radiography. CONCLUSION: Gantry-free CBCT allows for excellent diagnostic accuracy in the assessment of distal radius and scaphoid fracture morphology. Even in patients with limited mobility, very low radiation dose is sufficient to maintain high image quality.

Development and preclinical evaluation of a cable-clamp fixation device for a disrupted pubic symphysis.

BACKGROUND: Traumatic separation of the pubic symphysis can destabilize the pelvis and require surgical fixation to reduce symphyseal gapping. The traditional approach involves open reduction and the implantation of a steel symphyseal plate (SP) on the pubic bone to hold the reposition. Despite its widespread use, SP-fixation is often associated with implant failure caused by screw loosening or breakage. METHODS: To address the need for a more reliable surgical intervention, we developed and tested two titanium cable-clamp implants. The cable served as tensioning device while the clamp secured the cable to the bone. The first implant design included a steel cable anterior to the pubic symphysis to simplify its placement outside the pelvis, and the second design included a cable encircling the pubic symphysis to stabilize the anterior pelvic ring. Using highly reproducible synthetic bone models and a limited number of cadaver specimens, we performed a comprehensive biomechanical study of implant stability and evaluated surgical feasibility. RESULTS: We were able to demonstrate that the cable-clamp implants provide stability equivalent to that of a traditional SP-fixation but without the same risks of implant failure. We also provide detailed ex vivo evaluations of the safety and feasibility of a trans-obturator surgical approach required for those kind of fixation. CONCLUSION: We propose that the developed cable-clamp fixation devices may be of clinical value in treating pubic symphysis separation.

Life-threatening pelvic injuries are often associated with disruption of a joint within the hip bones, called the pubic symphysis. Disruption can lead to a gap and subsequent instability of the pelvis. The current treatment is to stabilize the joint with a steel plate and screws, however this often becomes unstable soon after the operation. In this study, we analyzed two alternatives for stabilization that use cables and clamps instead of the plate. Further, we tested a surgical approach for implantation. The cables and clamps were as stable as a steel plate so offer an alternative approach to stabilize the pubic symphysis.

Simultaneous treatment of trauma patients in a dual room trauma suite with integrated movable sliding gantry CT system: an observational study.

The trauma center of the University Hospital Wuerzburg has developed an advanced trauma pathway based on a dual-room trauma suite with an integrated movable sliding gantry CT-system. This enables simultaneous CT-diagnostics and treatment of two trauma patients. The focus of this study was to investigate the quality of the concept based on defined outcome criteria in this specific setting (time from arrival to initiation of CT scan: tCT; time from arrival to initiation of emergency surgery: tES). We analyzed all trauma patients admitted to the hospital's trauma suite from 1st May 2019 through 29th April 2020. Two subgroups were defined: trauma patients, who were treated without a second trauma patient present (group 1) and patients, who were treated simultaneously with another trauma patient (group 2). Simultaneous treatment was defined as parallel arrival within a period of 20 min. Of 423 included trauma patients, 46 patients (10.9%) were treated simultaneously. Car accidents were the predominant trauma mechanism in this group (19.6% vs. 47.8%, p < 0.05). Prehospital life-saving procedures were performed with comparable frequency in both groups (intubation 43.5% vs. 39%, p = 0.572); pleural drainage 3.2% vs. 2.2%, p = 0.708; cardiopulmonary resuscitation 5% vs. 2.2%, p = 0.387). At hospital admission, patients in group 2 suffered significantly more pain (E-problem according to Advanced Trauma Life Support principles©; 29.2% vs. 45.7%, p < 0.05). There were no significant differences in the clinical treatment (emergency procedures, vasopressor and coagulant therapy, and transfusion of red blood cells). tCT was 6 (4-10) minutes (median and IQR) in group 1 and 8 (5-15.5) minutes in group 2 (p = 0.280). tES was 90 (78-106) minutes in group 1 and 99 (97-108) minutes in group 2 (p = 0.081). The simultaneous treatment of two trauma patients in a dual-room trauma suite with an integrated movable sliding gantry CT-system requires a medical, organizational, and technical concept adapted to this special setting. Despite the oftentimes serious and life-threatening injuries, optimal diagnostic and therapeutic procedures can be guaranteed for two simultaneous trauma patients at an individual medical level in consistent quality.

Plate osteosynthesis combined with bone cement provides the highest stability for tibial head depression fractures under high loading conditions.

Older patients sustaining tibial head depression fractures often cannot follow the post-operative rehabilitation protocols with partial weight-bearing of the affected limb, leading to osteosynthesis failure, cartilage step-off and arthritis development. Therefore, the aim of this study was to analyse the biomechanical performance of different types of osteosyntheses alone and in combination with bone cement simulating cyclically high loading conditions of tibial head depression fractures. Lateral tibial head depression fractures (AO: 41-B2.2; Schatzker type III) were created in synthetic bones and stabilized using three different osteosyntheses alone and in combination with a commonly used bone cement (chronOS™): 2 screws, 4 screws in the jail technique and a lateral angle-stable buttress plate. After fixation, the lateral tibial plateau was axially loaded in two, from each other independent testing series: In the first test protocol, 5000 cycles with 500 N and in the end load-to-failure tests were performed. In the second test protocol, the cyclic loading was increased to 1000 N. Parameters of interest were the displacement of the articular fracture fragment, the stiffness and the maximum load. The osteosyntheses revealed a higher stiffness in combination with bone cement compared to the same type of osteosynthesis alone (e.g., 500 N level: 2 screws 383 ± 43 N/mm vs. 2 screws + chronOs 520 ± 108 N/mm, increase by 36%, p < 0.01; 4 screws 368 ± 97 N/mm vs. 4 screws + chronOS 516 ± 109 N/mm, increase by 40%, p < 0.01; plate: 509 ± 73 N/mm vs. plate + chronOs 792 ± 150 N/mm, increase by 56%, p < 0.01). Bone cement reduced the displacement of the plate significantly (500 N level: plate: 8.9 ± 2.8 mm vs. plate + chronOs: 3.1 ± 1.4 mm, reduction by 65%, p < 0.01; 1000 N level: 16.9 ± 3.6 mm vs 5.6 ± 1.3 mm, reduction by 67%, p < 0.01). Thus, the highest stiffness and lowest displacement values were found when using the plate with bone cement in both loading conditions (500 N level: 2 screws + chronOs 3.7 ± 1.3 mm, 4 screws + chronOs 6.2 ± 2.4 mm; 1000 N level: 2 screws + chronOs 6.5 ± 1.2 mm, 4 screws + chronOs 5.7 ± 0.8 mm). From a biomechanical perspective, plate osteosynthesis of tibial head depression fractures should always be combined with bone cement, provides higher stability than 2-screw and 4-screw fixation and is a valid treatment option in cases where extraordinary stability is required.

Surgical Fixation of Calcaneal Beak Fractures-Biomechanical Analysis of Different Osteosynthesis Techniques.

The calcaneal beak fracture is a rare avulsion fracture of the tuber calcanei characterized by a solid bony fragment at the Achilles tendon insertion. Treatment usually requires osteosynthesis. However, lack of biomechanical understanding of the ideal fixation technique persists. A beak fracture was simulated in synthetic bones and assigned to five different groups of fixation: A) 6.5-mm partial threaded cannulated screws, B) 4.0-mm partial threaded cannulated screws, C) 5.0-mm headless cannulated compression screws, D) 2.3-mm locking plate, and E) 2.8-mm locking plate. Different traction force levels were applied through an Achilles tendon surrogate in a material-testing machine on all stabilized synthetic bones. Outcome measures were peak-to-peak displacement, total displacement, plastic deformation, stiffness, visual-fracture-line displacement, and mode of implant failure. The 2.3- and 2.8-mm plating groups showed a high drop-out rate at 100 N tension force and failed under higher tension levels of 200 N. The fracture fixation using 4.0-mm partial threaded screws showed a significantly higher repair strength and was able to withhold cyclic loading up to 300 N. The lowest peak-to-peak displacement and the highest load-to-failure and stiffness were provided by fracture fixation using 6.5-mm partial threaded cannulated screws or 5.0-mm headless cannulated compression screws. As anticipated, large 6.5-mm screw diameters provide the best biomechanical fixation. Surprisingly, the 5.0-mm headless cannulated compression screws yield reliable stability despite the absent screw head and washer. When such large screws cannot be applied, 4.0-mm screws also allow reasonable fixation strength. Plate fixation should be implemented with precaution and in combination with a restrictive postoperative motion protocol. Finally, clinical cases about the surgical application and recovery are included.

Interobserver reliability of scapula fracture classifications in intra- and extra-articular injury patterns.

BACKGROUND: Morphology and glenoid involvement determine the necessity of surgical management in scapula fractures. While being present in only a small share of patients with shoulder trauma, numerous classification systems have been in use over the years for categorization of scapula fractures. The purpose of this study was to evaluate the established AO/OTA classification in comparison to the classification system of Euler and Rüedi (ER) with regard to interobserver reliability and confidence in clinical practice. METHODS: Based on CT imaging, 149 patients with scapula fractures were retrospectively categorized by two trauma surgeons and two radiologists using the classification systems of ER and AO/OTA. To measure the interrater reliability, Fleiss kappa (κ) was calculated independently for both fracture classifications. Rater confidence was stated subjectively on a five-point scale and compared with Wilcoxon signed rank tests. Additionally, we computed the intraclass correlation coefficient (ICC) based on absolute agreement in a two-way random effects model to assess the diagnostic confidence agreement between observers. RESULTS: In scapula fractures involving the glenoid fossa, interrater reliability was substantial (κ = 0.722; 95% confidence interval [CI] 0.676-0.769) for the AO/OTA classification in contrast to moderate agreement (κ = 0.579; 95% CI 0.525-0.634) for the ER classification system. Diagnostic confidence for intra-articular fracture patterns was superior using the AO/OTA classification compared to ER (p < 0.001) with higher confidence agreement (ICC: 0.882 versus 0.831). For extra-articular fractures, ER (κ = 0.817; 95% CI 0.771-0.863) provided better interrater reliability compared to AO/OTA (κ = 0.734; 95% CI 0.692-0.776) with higher diagnostic confidence (p < 0.001) and superior agreement between confidence ratings (ICC: 0.881 versus 0.912). CONCLUSIONS: The AO/OTA classification is most suitable to categorize intra-articular scapula fractures with glenoid involvement, whereas the classification system of Euler and Rüedi appears to be superior in extra-articular injury patterns with fractures involving only the scapula body, spine, acromion and coracoid process.

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.

Augmentation of suture anchors with magnesium phosphate cement - Simple technique with striking effect.

BACKGROUND: Suture anchors have a large field of application in orthopedic trauma surgery like the refixation of patellar, quadriceps and Achilles tendon or the treatment of rotator cuff tears. The fixation of suture anchors in osteoporotic bone is difficult, a problem that becomes increasingly relevant in the elderly. METHODS: Two types of suture anchors: 1.) Titanium CorkScrew Fast Track II with a knotted eyelet and 2.) polyether ether ketone (PEEK) SwiveLock C with a knotless eyelet were chosen for evaluation in open cell bone blocks with densities of 5-20 pcf supplied by Sawbones AB. A pilot hole of 7 mm diameter and 20 mm depth was drilled in the bone blocks and filled with an experimental drillable magnesium phosphate cement (powder: 92.5 wt% Mg3(PO4)2, 7.5 wt% MgO, liquid: 25 wt% phytic acid (C6H18O24P6)). Anchors were then inserted into the cement and allowed to cure for 24 h (37 °C, 100% humidity) before pullout testing was conducted with a material testing machine. Suture anchors inserted in the blocks after predrilling and tapping served as control. RESULTS: Through augmentation with magnesium phosphate cement pullout strength and stiffness of the suture anchors could be significantly increased in all bone blocks up to 22-fold. CorkScrew anchors failed by rupture of the eyelet with higher pullout strengths, whereas no failure of SwiveLock C anchors could be observed when reinforced with additional FibreWire at the tip. CONCLUSIONS: We present a simple technique, whereby pullout strength of suture anchors can be significantly increased in bone with compromised density. The experimental resorbable and drillable magnesium phosphate cement proved to be effective in resisting tensile load, dispersing in the adjacent bone, and thus increasing the bone-anchor contact surface. Therefore, the experimental magnesium phosphate cement is a promising candidate for clinical application in the numerous scenarios mentioned.

Effects of pyruvate on primary metabolism and product quality for a high-density perfusion process.

High volumetric productivities can be achieved when perfusion processes are operated at high cell densities. Yet it is fairly challenging to keep high cell density cultures in a steady state over an extended period. Aiming for robust processes, cultures were operated at a constant biomass specific perfusion rate (BSPR) in this study. The cell density was monitored with a capacitance probe and a continuous bleed maintained the targeted viable cell volume. Despite our tightly controlled BSPR, a gradual accumulation of ammonium and changes in cell diameter were observed during the production phase for three different monoclonal antibodies. Although a lot of efforts in media optimization have been made to reduce ammonium in fed-batch process, less examples are known about how media components impact the cellular metabolism and thus the quality of monoclonal antibodies in continuous processes. In this study, we show that a continuous Na-pyruvate feed (2 g/L/day) strongly reduced ammonium production and stabilized fucosylation, sialylation and high mannose content for three different mAbs.

Anterior deltoid muscle tension quantified with shear wave ultrasound elastography correlates with pain level after reverse shoulder arthroplasty.

INTRODUCTION: Reverse shoulder arthroplasty (RSA) leads to medialization and distalization of the centre of rotation of the shoulder joint resulting in lengthening of the deltoid muscle. Shear wave ultrasound elastography (SWE) is a reliable method for quantifying tissue stiffness. The purpose of this study was to analyse if deltoid muscle tension after RSA correlates with the patients' pain level. We hypothesized that higher deltoid muscle tension would be associated with increased pain. MATERIAL AND METHODS: Eighteen patients treated with RSA were included. Constant score (CS) and pain level on the visual analogue scale (VAS) were analysed and SWE was performed on both shoulders. All three regions of the deltoid muscle were examined in resting position and under standardized isometric loading. RESULTS: Average patient age was 76 (range 64-84) years and average follow-up was 15 months (range 4-48). The average CS was 66 points (range 35-89) and the average pain level on the VAS was 1.8 (range 0.5-4.7). SWE revealed statistically significant higher muscle tension in the anterior and middle deltoid muscle region in patients after RSA compared to the contralateral non-operated side. There was a statistically significant correlation between pain level and anterior deltoid muscle tension. CONCLUSION: SWE revealed increased tension in the anterior and middle portion of the deltoid muscle after RSA in a clinical setting. Increased tension of the anterior deltoid muscle portion significantly correlated with an increased pain level. SWE is a powerful, cost-effective, quick, dynamic, non-invasive, and radiation-free imaging technique to evaluate tissue elasticity in the shoulder with a wide range of applications. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Comparing porous tantalum fusion implants and iliac crest bone grafts for spondylodesis of thoracolumbar burst fractures: Prospectice Cohort study.

The aim of this study was to compare two different techniques of performing one-level spondylodesis for thoracolumbar burst fractures using either an autologous iliac crest bone graft (ICBG) or a porous tantalum fusion implant (PTFI). In a prospective nonrandomized study, 44 patients (20 women, 24 men; average age 43.1 ± 13.2 years) suffering from severe thoracolumbar burst fractures were treated with combined anterior-posterior stabilization. An ICBG was used in 21 cases, and a PTFI was used in the other 23 cases. A two-year clinical and radiographic follow-up was carried out. There were no statistically significant differences in age, sex, localization/classification of the fracture, or visual analog scale (VAS) before injury between the two groups. All 44 patients were followed up for an average period of 533 days (range 173-1567). The sagittal spinal profile was restored by an average of 11.1° (ICBG) vs. 14.3° (PTFI) (monosegmental Cobb angle). Loss of correction until the last follow-up tended to be higher in the patients treated with ICBG than in those treated with PTFI (mean: 2.8° vs. 1.6°). Furthermore, significantly better restoration of the sagittal profile was obtained with the PTFI than with the iliac bone graft at the long-term follow-up (mean: ICBG 7.8°, PTFI 12.3°; p < 0.005). Short-segment posterior instrumentation combined with anterior one-level spondylodesis using either an ICBG or a PTFI resulted in sufficient correction of posttraumatic segmental kyphosis. PTFI might be a good alternative for autologous bone grafting and prevent donor site morbidities.