Microdialysis in the femoral head of the minipig and in a blood cloth of human blood

Introduction Microdialysis can detect ischemia in soft tissue. In a previous study, we have shown the development of ischemia in the femoral head removed from patients undergoing total hip replacement. That study also raised some methodological questions that this study tries to answer: what is happening in the dead space around the catheter in the drill canal, and is there an equilibrium period after the insertion of the catheter? Material and methods In an ex-vivo study using 5 syringes with 5 mL human blood, a microdialysis catheter was inserted and microdialysis was performed over 3 h. In an in-vivo study, a drill hole was made in the proximal part of the femur in 6 mature Göttingen minipigs and microdialysis was performed over 3 h. The pigs were kept normoventilated during the experiment. Results The ex-vivo microdialysis results showed that lactate kept a steady level and glucose and glycerol both fell; pyruvate fell but leveled out. The mean lactate/pyruvate ratio increased from 13 (SD 4) to 32 (SD 6) (p <0.001). In vivo, relative recovery was 57% (SD 11). Lactate increased, pyruvate stayed constant, and glucose and glycerol levels fell. The lactate/pyruvate ratio increased from 30 (8) initially to 37 (8) after 1 h (p = 0.007) but no statistically significant change from 1 to 2 h was observed. Interpretation The ex-vivo study showed a clear washout pattern, and was different from what we see in bone. The in-vivo study indicated that an equilibrium period is necessary or that a reference measurement in healthy bone must be used when performing short measurements in bone

Patient safety in distal femoral resection knee arthroplasty for non-tumor indications:a single-center consecutive cohort study of 45 patients

Background: Distal femoral resection knee arthroplasty may be a viable option for several indications other than bone tumors. Resection knee arthroplasty appears to be becoming more common, but patients requiring this type of surgery are often elderly and with high comorbidity. The aim of this study was to report in-hospital complications, readmissions, reoperations, and mortality after distal femoral resection knee arthroplasty for non-tumor indications. Methods: We retrospectively identified a consecutive cohort of 45 knees (45 patients) treated with distal femoral resection knee arthroplasty in a single institution between 2012 and 2021. Indications for surgery were failure of osteosynthesis (8), primary fracture treatment (2), periprosthetic fracture (22), and revision arthroplasty with severe bone loss (13). A major reoperation was defined as a major component exchange procedure or amputation. Mean follow-up was 3.9 years. Results: The mean age was 71.3 years (SD 12.3), and 64.4% were female; 8.9% were ASA I, 40% ASA II, and 51% ASA III. Median length of stay was 7 days (range 3–19) with no major in-hospital complications, but 55.6% (n = 25) required blood transfusion. The 90-day readmission rate was 17.8% (n = 8), of which 50% was prosthesis-related. Four patients (8.9%) underwent major reoperation due to infection (n = 2), mechanical failure (n = 1), or periprosthetic fracture (n = 1). The mortality rate was 0% ≤ 90 days and 2.2% ≤1 year. Conclusions: Distal femoral resection knee arthroplasty in this fragile patient population appears to be a viable and safe option considering that it is a limp salvage procedure most cases.</p

Preoperative hypoalgesia after cold pressor test and aerobic exercise is associated with pain relief six months after total knee replacement

Objectives: Chronic pain after total knee replacement (TKR) is not uncommon. Preoperative impaired conditioning pain modulation (CPM) has been used to predict chronic postoperative pain. Interestingly, exercises reduce pain sensitivity in patients with knee osteoarthritis (KOA). This pilot study investigated the association between exercise-induced hypoalgesia (EIH) and CPM on post-TKR pain relief. Methods: Before and 6 months post-TKR, 14 patients with chronic KOA performed the cold pressor test on the nonaffected leg and 2 exercise conditions (bicycling and isometric knee extension), randomized and counterbalanced. Before and during the cold pressor test and after exercises test stimuli were applied to extract the pain sensitivity difference: computer-controlled cuff inflation on the affected lower leg until the participants detected the cuff pain threshold (cPPT) and subsequently the cuff pain tolerance (cPTT) and manual pressure pain thresholds (PPTs) at the legs, arm, and shoulder. Clinical pain intensity (numerical rating scale [NRS]) and psychological distress (questionnaires) were assessed. Results: Clinical pain intensity, psychological distress, cPPT, and PPT at the affected leg improved post-TKR compared with pre-TKR (P&lt;0.05). Preoperatively, the CPM and bicycling EIH assessed by the increase in cPTT correlated with reduction in NRS pain scores post-TKR (P&lt;0.05). Improved CPM and EIH responses after TKR were significantly correlated with reduction in NRS pain scores post-TKR (P&lt;0.05). Discussion: In KOA patients, hypoalgesia after cold pressor stimulation and aerobic exercise assessed preoperatively by cuff algometry was associated with pain relief 6 months after TKR. EIH as a novel preoperative screening tool should be further investigated in larger studies.</p

Knee function, quality of life, pain, and living conditions after distal femoral resection knee arthroplasty for non-tumor indications

Background: Distal femoral resection knee arthroplasty is a limb salvage procedure. The impact of distal femoral resection arthroplasty on patient function and health status is unknown. The aim of this study was to report knee function, quality of life, knee pain, and living conditions after distal femoral resection knee arthroplasty for non-tumor indications. Methods: Of 52 patients (52 knees) undergoing distal femoral resection knee arthroplasty in a single institution between 2012 and 2021, 22 were excluded as 3 patients had ≤90 days follow-up, 6 had died, and 13 declined or were unable to participate for unrelated reasons. Thus, 30 patients were included and interviewed by telephone in March 2021 (mean follow-up 3.5 years after surgery). Patient completed the Oxford Knee Score (0–48, 48 best), EQ-5D-5L, and the Copenhagen Knee ROM, and information on pain and living conditions was obtained. Results: The mean age was 67.9 years (SD 13.6), and 21 (70%) were female. Mean total Oxford Knee Score was 29.9 (SD 10.5), mean Copenhagen Knee ROM flexion was 116° (SD 21.6), and mean extension was − 2° (SD10.1). Mobility aids were used by 18 (60%) patients, i.e. a cane (30%), walker (26.7%) or wheelchair (3.3%). Mean EQ-5Dindex score was 0.70 (SD 0.22) and mean EQ-5D VAS score was 55.4 (SD 23.9). Nine (30%) patients used paracetamol or NSAID and 2 (6.7%) used opioids for knee pain. Mean VAS knee pain score was 1.30 (SD 2.2) at rest and 2.8 (SD 3.1) when walking. Most (90%) patients lived in their own home, with only 3 patients in nursing homes. Two-thirds (66.7%) required no home care, 5 (16.6%) received home care 1–2 times over 2 weeks, and 5 (16.6%) every day. Conclusion: Distal femoral resection knee arthroplasty appears to be a viable treatment option for non-tumor indications. Acceptable patient outcomes were achieved in terms of functional status and quality of life, especially considering treatment alternatives such as femoral amputation.</p

One-stage versus two-stage revision of the infected knee arthroplasty - a randomized multicenter clinical trial study protocol

Background: A two-stage prosthesis exchange procedure has been the gold standard in surgical treatment of the chronically infected knee arthroplasty so far. This includes 2 surgeries/hospitalizations and an interim period of 2–3 months between surgeries with impaired health, functional status and quality of life of the patients. A one-stage exchange procedure holds many obvious advantages compared to the two-stage approach, but outcomes of a one-stage versus two-stage procedures have never been investigated in a randomized clinical trial. The purpose of this study is primarily to investigate time-adjusted differences in functional status of patients after one-stage versus two-stage revision. Secondary, to report time-adjusted differences in quality of life, complications (including re-revisions due to infection) and mortality. Methods: This study is a pragmatic, multi-center, randomized, non-inferiority trial comparing one-stage versus two-stage revision of the infected knee arthroplasty. Seven Danish hospitals are currently participating in the study, but additional hospitals can enter the study if adhering to protocol. Ninety-six patients will be included prospectively. Follow-up will be with PROM-questionnaires and clinical controls up to 10 years. The patients who are not able to participate in the randomized trial are followed in a parallel cohort study. PROM’s: Oxford Knee Score and EQ5D + EQ5D VAS questionnaires are completed preoperatively and sent out to the study participants at 6 weeks, 3, 6, 9, 12, 18 and 24 months as well as 5 and 10 years postoperatively. In addition a tailor made cost questionnaire on the non-treating hospital resource use, community health and social service use, travel costs, time off work and informal care are sent out. Discussion: If one of the two treatment alternatives is found superior in both domains of quality of life (both knee-specific and generic) and health economics, that treatment should be promoted. Other outcomes will open informed discussions about treatment strategies for periprosthetic knee infections. Trial registration: The randomized trial is registered on ClinicalTrials.gov with ID NCT03435679, initial release date January 31, 2018 and the cohort study is registered with ID NCT04427943, submitted January 8, 2020 and posted June 11, 2020.</p

MP-AzeFlu improves the quality-of-life of patients with allergic rhinitis

PURPOSE: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities. PATIENTS AND METHODS: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥ 50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 μg azelastine HCL and 50 μg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from “not at all troubled” (0 mm) to “extremely troubled” (100 mm). RESULTS: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ∼ 14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex. CONCLUSION: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease. REGISTRATION: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019

Effect of Specific Immunoglobulin E Response and Comorbidities on Effectiveness of MP-AzeFlu in a Real-Life Study

Acknowledgements: We would like to thank the subjects who participated in the trial. Funding Sources: This study was supported by MEDA Pharma GmbH & Co. KG (a Mylan Company), Bad Homburg, Germany. Technical, editorial, and medical writing assistance were provided under the direction of the authors by Strategix, an affiliate of The Lynx Group, LLC. This assistance was supported by MEDA Pharma GmbH & Co. KG (a Mylan Company).Peer reviewedPublisher PD

MP-AzeFlu Improves the Quality-of-Life of Patients with Allergic Rhinitis

Acknowledgments: We would like to thank the subjects who participated in the trial. The abstract of this paper was presented at the EAACI Congress 2020 as an oral presentation. The presentation’s abstract was published in Allergy: Van Weissenbruch R, Klimek L, Galffy G, et al. MP-Azeflu improves quality of life of patients with allergic rhinitis: a real-world study Funding: Technical, editorial, and medical writing assistance were provided under the direction of the authors by Erin Burns, PhD, and Strategix, an affiliate of The Lynx Group, LLC. Funding for this support was provided by Mylan Inc.Peer reviewedPublisher PD

Allergic Rhinitis and Asthma Symptoms in a Real-Life Study of MP-AzeFlu to Treat Multimorbid Allergic Rhinitis and Asthma

Acknowledgements We would like to thank the subjects who participated in the trial. Funding This study was supported by MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany. Technical, editorial, and medical writing assistance was provided under the direction of the authors by Strategix, an affiliate of The Lynx Group, LLC. Funding for this support was provided by Mylan Inc.Peer reviewedPublisher PD

Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach

Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT) derived from heterologous species (immunized animal or mouse hybridoma) together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R) domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa) is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH) that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80%) to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP), the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme