Neurological monitoring and management for adult extracorporeal membrane oxygenation patients: Extracorporeal Life Support Organization consensus guidelines.

BACKGROUND: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence­based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Ketamine analgo-sedation for mechanically ventilated critically ill adults: A rapid practice guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

Melatonin Alleviates Intestinal Barrier Damaging Effects Induced by Polyethylene Microplastics in Albino Rats.

There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0-6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1ß and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1ß concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP's toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.

Downregulation of aquaporin 3 in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease. Aquaporin 3 (AQP3) is a glycerol/water channel involved in several physiological functions. Evaluation of the tissue expression and localization of AQP3 in the skin of PV patients. Twenty-seven PV patients and 30 controls were included. The patients were subjected to history taking, clinical evaluation, Autoimmune Bullous Skin Disorder Intensity Score and 4-mm punch biopsy. The biopsies were stained using anti-human AQP3 antibody and the immunofluorescence pattern and intensity were evaluated using a scoring system and ImageJ software analysis. AQP3 was expressed in the basal epidermis in 27 (100%) and in the suprabasal epidermis in 19 PV patients (70.4%). It was expressed in all controls in basal and suprabasal layers. Intensity of AQP3 immunofluorescence was strong in 2 (7.4%), moderate in 19 (70.4%) and weak in 6 patients (22.2%) while it was strong in 18 (60%) and moderate in 12 controls (40%). AQP3 expression was significantly lower in patients than controls in the suprabasal epidermis (p = 0.001). Patients with extensive disease had significantly weaker AQP3 intensity than those with marked disease (p = 0.005) Downregulation of AQP3 in patients with PV, especially in the suprabasal layers and in extensive clinical disease, suggests a potential role of AQP3 in the pathogenesis of PV.

Rheumatologists' knowledge and perception of COVID-19 and related vaccines: the vaXurvey2 online survey.

The study aimed to explore the experience of coronavirus disease-2019 (COVID-19) infection and vaccine adverse events (AEs) among rheumatologists. A validated questionnaire was distributed as a Google form to rheumatologists across the country via social networking sites from late December 2021 till early January 2022. The questionnaire included questions regarding participants' socio-demographic details, COVID-19 infection and vaccination details with special emphasis on AEs. Out of 246 responses, 228 were valid. 200 (81.3%) responders had received the vaccine. The mean age of the 228 participants was 37.9 ± 8.5 years, 196 were females and 32 males (F:M 6.1:1) from 18 governorates across the country. Comorbidities were present in 54 subjects (27%). There was a history of highly suspicious or confirmed COVID-19 infection in 66.7% that were all managed at home. The COVID-19 vaccine was received by 200 and a booster dose of 18.5%. Obesity and musculoskeletal involvement co-morbidities were present only in those with AEs (9.1% and 5.5% respectively). AEs were present in 82%; 66.7% had injection-site tenderness, 50% fatigue, 35.5% fever, 15% chills, 42.5% myalgia, 14.5% arthralgia, 8% low back pain, headache 31%, dizziness 10%, sleepliness 16% and 15% developed post-vaccine. There were no differences according to the geolocation regarding the occurrence of COVID-19 infection (p = 0.19) or AEs post-vaccine (p = 0.58). The adverse events were mostly mild to moderate and tolerable which makes this work in agreement with other studies that support the broad safety of the vaccine in favor of the global benefit from mass vaccination.

Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.

OBJECTIVES: This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries. METHODS: The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed. RESULTS: The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents (p = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents (p = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries. CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.

Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt.

OBJECTIVES: The aim of the present work was to explore the perspectives of Egyptian Rheumatology staff members as regards the coronavirus disease-19 (COVID-19) vaccine. METHODS: The survey is composed of 25 questions. Some questions were adapted from the global rheumatology alliance COVID-19 survey for patients. RESULTS: 187 rheumatology staff members across Egypt from 18 universities and authorizations actively participated with a valid response. The mean time needed to complete the survey was 17.7 ± 13 min. Participants were 159 (85%) females (F:M 5.7:1). One-third agreed that they will be vaccinated once available, 24.6% have already received at least one dose, 29.4% are unsure while 16% will not take it. Furthermore, 70.1% agreed that they will recommend it to the rheumatic diseases (RD) patients once available, 24.1% are not sure while 5.9% will not recommend it. RD priority to be vaccinated against COVID-19 in descending order include SLE (82.9%), RA (55.1%), vasculitis (51.3%), systemic sclerosis (39.6%), MCTD (31.6%), Behcet's disease (28.3%). The most common drugs to be avoided before vaccination included biologics (71.7%), DMARDs (44.4%), biosimilars (26.7%), IVIg (17.1%) and NSAIDs (9.1%). CONCLUSIONS: The results of the study and specifically the low rate of acceptability are alarming to Egyptian health authorities and should stir further interventions to reduce the levels of vaccine hesitancy. As rheumatic disease patients in Egypt were not systematically provided with the vaccine till present, making the vaccine available could as well enhance vaccine acceptance. Further studies to investigate any possible side effects, on a large scale of RD patients are warranted.

Atorvastatin: In-Vivo Synergy with Metronidazole as Anti-Blastocystis Therapy.

Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA was apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with high reduction in Blastocystis shedding (93.4-97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%) were recorded in groups of combination treatments AVA 20-40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.

Hsa-miR-195 targets PCMT1 in hepatocellular carcinoma that increases tumor life span.

MicroRNAs are small 19-25 nucleotides which have been shown to play important roles in the regulation of gene expression in many organisms. Downregulation or accumulation of miRNAs implies either tumor suppression or oncogenic activation. In this study, differentially expressed hsa-miR-195 in hepatocellular carcinoma (HCC) was identified and analyzed. The prediction was done using a consensus approach of tools. The validation steps were done at two different levels in silico and in vitro. FGF7, GHR, PCMT1, CITED2, PEX5, PEX13, NOVA1, AXIN2, and TSPYL2 were detected with high significant (P < 0.005). These genes are involved in important pathways in cancer like MAPK signaling pathway, Jak-STAT signaling pathways, regulation of actin cytoskeleton, angiogenesis, Wnt signaling pathway, and TGF-beta signaling pathway. In vitro target validation was done for protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1). The co-transfection of pmirGLO-PCMT1 and pEGP-miR-195 showed highly significant results. Firefly luciferase was detected using Lumiscensor and t test analysis was done. Firefly luciferase expression was significantly decreased (P < 0.001) in comparison to the control. The low expression of firefly luciferase validates the method of target prediction that we used in this work by working on PCMT1 as a target for miR-195. Furthermore, the rest of the predicted genes are suspected to be real targets for hsa-miR-195. These target genes control almost all the hallmarks of liver cancer which can be used as therapeutic targets in cancer treatment.

Psoriasis knowledge gaps and misconceptions in the Middle East and North Africa (MENA) regions: patients' survey-based study.

BACKGROUND: Misconceptions among psoriatic patients often lead to a negative impact on disease outcomes. OBJECTIVES: Our main target was knowledge assessment among a sample of psoriatic patients in the Middle East and North Africa (MENA) region where data are scarce. METHODS: The present study is a cross-sectional descriptive survey. It consists of an online questionnaire comprising 19 questions designed to assess psoriasis knowledge and five demographic questions. The questionnaire link was posted on the official Facebook page of the Kasr Al Ainy Psoriasis Unit (KAPU). RESULTS: The questionnaire was taken by 527 participants, but only 396 responses were complete and adequate for analysis. The mean psoriasis knowledge score was higher in females (P = 0.005) and participants with advanced education degrees (P < 0.001). Patients reporting regular follow-ups with dermatologists were more likely to acknowledge joint involvement (P = 0.044) but also incorrectly assume biologics are a final cure (P = 0.038). In addition, they were more likely to assume psoriasis affects pregnancy (P = 0.013). Patients with a family history of psoriasis showed a better mean knowledge score than those without (P = 0.01). Only 54.55% of participants reported knowledge of possible disease exacerbation by drugs. A minority (26.77%) of our patients responded that a diet change could not permanently cure psoriasis. CONCLUSION: This study reports knowledge gaps in a cohort of Arabic-speaking psoriasis patients, especially regarding areas of extracutaneous involvement, the hereditary nature of the disease, and the effect of psoriasis on pregnancy and fertility. Most participants were unaware that biological therapy and a change in diet do not offer a permanent cure. Dermatologists in our region must reach out to their patients and correct the various misconceptions reported in this study.

GRADE guidance 39: using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

BACKGROUND AND OBJECTIVE: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Focused extracorporeal shockwave therapy for youth sports-related apophyseal injuries: case series.

BACKGROUND: Apophyseal overuse injuries are self-limited with skeletal maturity; however, they may be a source of significant pain and time lost from training. There is a lack of consensus for its management with the current available treatment, which might lag behind the ongoing development of regenerative medicine. The current retrospective case study aimed to assess the potential effectiveness and short-term safety of extracorporeal shockwave therapy (ESWT) in apophyseal injuries. METHODS: Data from 22 growing athletes [15 patients with Osgood-Schlatter disease and seven patients with Sever's disease] who received ESWT at a sports medicine unit in a university hospital were reviewed. All patients received low energy (= 0.1 mJ/mm2) level-focused ESWT using electrohydraulic generation technology. The clinical focusing technique was used upon applying ESWT. RESULTS: The number of sessions received to achieve full recovery ranged from 1 to 3 sessions. The time from treatment initiation to previous activity level was 2 weeks in 14 patients (63.3%), 4 weeks in seven patients (31.8%) and 11 weeks in one patient (4.5%). No adverse events were reported. No recurrence occurred up to 3 months after the last session. CONCLUSION: ESWT is a potentially safe and effective treatment for apophyseal injuries. It may facilitate an early return to sport activities.

Ultrasound surveillance for deep venous thrombosis and subsequent venous thromboembolism in adults with trauma: A systematic review and meta-analysis.

BACKGROUND: Studies have shown routine ultrasound surveillance (RUSS) will facilitate deep vein thrombosis (DVT) detection in patients with trauma and reduce the subsequent incidence of pulmonary embolism (PE); however, the findings were inconsistent. In adults with trauma at a high risk of venous thromboembolism, this systematic review and meta-analysis compared RUSS outcomes with those of "no RUSS." METHODS: Three databases were screened for relevant articles from inception to October 18, 2021. Randomized controlled trials (RCTs) and observational studies comparing RUSS with no RUSS were included. We used relative risks (RRs), odds ratios (ORs), and mean differences to pool effect estimates for dichotomous and continuous outcomes. The cochrane risk of bias or the risk of bias in non-randomized studies of interventions were used to assess bias risk. The grading of recommendations, assessment, development, and evaluation framework assessed the certainty of the evidence. FINDINGS: Out of 1685 articles, 5 met the inclusion criteria (RCT: 1; observational studies: 4). Observational studies suggested RUSS is associated with higher odds of DVT detection (OR, 4.87; 95% confidence interval [CI], 3.13-7.57; very low certainty). Whereas higher risks of DVT were associated with RUSS in the RCT (distal DVT: RR, 15.48; 95% CI, 7.62-31.48; low certainty, and proximal DVT: RR, 2.37; 95% CI, 1.04-5.39; very low certainty). Reduced odds of PE risk were observed with the RUSS (OR, 0.47; 95% CI, 0.24-0.91; very low certainty). Observational studies indicated that RUSS had an uncertain effect on mortality (OR, 0.46; 95% CI, 0.06-3.49). In the RCT, times to proximal and distal DVT diagnoses were shorter with RUSS (proximal DVT, mean difference 2.25 days shorter [95% CI, 5.74-1.24]; distal DVT, mean differences 1.56 days shorter [95% CI, 4.22-1.12]; very low certainty for both). Increasing bleeding risk was not linked to the RUSS group (RR, 1.24; 95% CI, 0.31-4.92). INTERPRETATION: The RUSS efficacy in adults with trauma at high risk for venous thromboembolism showed that it increases DVT detection, decreases PE incidence, and shortens the time to DVT diagnosis, with an uncertain impact on mortality. The evidence is low or very low in certainty because of bias, inconsistency, imprecision, and indirectness.

A coiled-coil-based design strategy for the thermostabilization of G-protein-coupled receptors.

Structure elucidation of inactive-state GPCRs still mostly relies on X-ray crystallography. The major goal of our work was to create a new GPCR tool that would provide receptor stability and additional soluble surface for crystallization. Towards this aim, we selected the two-stranded antiparallel coiled coil as a domain fold that satisfies both criteria. A selection of antiparallel coiled coils was used for structure-guided substitution of intracellular loop 3 of the ß3 adrenergic receptor. Unexpectedly, only the two GPCR variants containing thermostable coiled coils were expressed. We showed that one GPCR chimera is stable upon purification in detergent, retains ligand-binding properties, and can be crystallized. However, the quality of the crystals was not suitable for structure determination. By using two other examples, 5HTR2C and α2BAR, we demonstrate that our approach is generally suitable for the stabilization of GPCRs. To provide additional surface for promoting crystal contacts, we replaced in a structure-based approach the loop connecting the antiparallel coiled coil by T4L. We found that the engineered GPCR is even more stable than the coiled-coil variant. Negative-staining TEM revealed a homogeneous distribution of particles, indicating that coiled-coil-T4L receptor variants might also be promising candidate proteins for structure elucidation by cryo-EM. Our approach should be of interest for applications that benefit from stable GPCRs.

Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma.

OBJECTIVE: Osteosarcoma is considered the most common primary malignant tumor that develops from the primary osteoblasts. MiRNAs are small non-coding RNAs that play a key role in tumorigenesis. The aim of this study was to detect the possible relationship between expression levels of miRNA-34a and levels of Signal transducer and activator of transcription 3 (STAT3) and interleukin-6 receptor (IL-6R) in osteosarcoma and the possible role of this relationship in development of metastases in these patients. METHODS: A total of thirty-six (36) bone samples were included in the study. They were divided into 3 groups: Group (I): Twelve normal bone samples as control group. Group (II): Twelve patients with non-metastatic osteosarcoma. Group (III): Twelve patients with metastatic osteosarcoma. MiRNA-34a expression levels were estimated using qRT-PCR. STAT3 and IL-6R levels were measured by ELISA. RESULTS: Expression level of miRNA-34a was downregulated in osteosarcoma groups compared to control group. STAT3 and IL-6R levels were upregulated in osteosarcoma groups compared to control group. This difference in expression levels was found to be more significant in the metastatic group than the non-metastatic one (P<0.001 each). There was a significant positive correlation between STAT3 and IL-6R (r=0.868, P<0.001), and a significant inverse correlation between IL6 and miRNA-34a (r=-0.993, P<0.001). CONCLUSION: miRNA-34a, STAT3 and IL-6R feedback loop could be a potential target for treatment of osteosarcoma and can be used as prognostic indicator for this disease.