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Tobias Winkler Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Sven Geissler Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Tazio Maleitzke Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Trauma Orthopaedic Research Copenhagen Hvidovre (TORCH), Department of Orthopaedic Surgery, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Carsten Perka Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany

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Georg N Duda Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Alexander Hildebrandt Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany

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  • Advanced therapies are expected to play a crucial role in supporting repair after injury, halting the degeneration of musculoskeletal tissue to enable and promote physical activity.

  • Despite advancements, the progress in developing advanced therapies in orthopaedics lags behind specialties like oncology, since innovative regenerative treatment strategies fall short of their expectations in musculoskeletal clinical trials.

  • Researchers should focus on understanding the mechanism of action behind the investigated target before conducting clinical trials.

  • Strategic research networks are needed that not only enhance scientific exchange among like-minded researchers but need to include early on commercial views, companies and venture perspectives, regulatory insights and reimbursement perspectives. Only in such collaborations essential roadblocks towards clinical trials and go-to-patients be overcome.

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Djandan Tadum Arthur Vithran Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

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Anko Elijah Essien Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China

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Masoud Rahmati Research Centre on Health Services and Quality of Life, Aix Marseille University, Marseille, France
Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran
Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran

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Michael Opoku Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China

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Dong Keon Yon Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea
Department of Pediatrics, Kyung Hee University College of Medicine, Seoul, Republic of Korea

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Guillermo F López Sánchez Division of Preventive Medicine and Public Health, Department of Public Health Sciences, School of Medicine, University of Murcia, Murcia, Spain

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Ai Koyanagi Research and Development Unit, Parc Sanitari Sant Joan de Deu, Barcelona, Spain

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Lee Smith Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK

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Jae Il Shin Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea

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Wenfeng Xiao Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

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Shuguang Liu Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China

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Yusheng Li Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

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Objective

  • The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis.

Methods

  • A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1–34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment.

Results

  • Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01–0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00–0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1–34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32–2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45–0.072), with no significant difference observed in mortality rates between treatment and control groups.

Conclusion

  • Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

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Xinhui Wu Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

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Xiaoxin Fang Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China

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Feng Lu Nanjing Medical University, Jiangning, Nanjing, China

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Qiong Chen Jinhua TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

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Junjian Liu Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

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Longpo Zheng Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
Orthopedic Intelligent Minimally Invasive Diagnosis and Treatment Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

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  • Ferroptosis is a novel form of programmed cell death, distinguished from apoptosis, autophagy, and programmed necrosis and has received much attention since it was defined in 2012.

  • Ferroptotic cells physiologically exhibit iron metabolism dysregulation, oxidative stress, and lipid peroxidation. Morphologically, they show plasma membrane disruption, cytoplasmic swelling, and mitochondrial condensation.

  • Osteoporosis is taken more and more seriously as the proportion of the aging population continues to increase globally. Interestingly, ferroptosis has been demonstrated to be involved in the development and progression of osteoporosis in many extant studies.

  • The review summarizes iron metabolism, lipid peroxidation, and the different regulatory signals in ferroptosis. Changes in signaling mechanisms within osteoblasts, osteoclasts, and osteocytes after ferroptosis occur are explained here.

  • Studies showed ferroptosis play an important role in different osteoporosis models (diabetes osteoporosis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis). Inhibitors and EC (Exos) targeting ferroptosis could ameliorate bone loss in osteoporotic mice by protecting cells against lipid peroxidation. Shortly, we hope that more effective and appropriate clinical therapy means will be utilized in the treatment of osteoporosis.

Open access
Mara Meyer Günderoth Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany

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Alexandra Bannach-Brown Berlin Institute of Health at Charité – Universitätsmedizin Berlin, QUEST Center for Responsible Research, Berlin, Germany

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Tobias Winkler Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany

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Johannes Keller Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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Robert Karl Zahn Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany

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Tazio Maleitzke Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Trauma Orthopaedic Research Copenhagen Hvidovre (TORCH), Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Purpose

  • The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced.

Methods

  • A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation’s risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics.

Results

  • Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected.

Conclusion

  • There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

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Peter Richard Almeida University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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Lipalo Mokete University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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Nkhodiseni Sikhauli University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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Ahmad Mota University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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Bayanda Ndindwa University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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Jurek R T Pietrzak University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

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  • Total joint arthroplasty (TJA) is rising globally, with an associated increase in associated complications, necessitating increased efforts in prevention of these complications with pre-operative optimisation.

  • Malnutrition has been highlighted as one of the most important pre-operative modifiable risk factors to be addressed in TJA, with the term malnutrition in orthopaedic surgery having a broad definition that encompasses a wide range of nutritional abnormalities from undernutrition to overnutrition contributing to the outcomes of TJA.

  • Complications associated with malnutrition include periprosthetic joint infection (PJI), periprosthetic fracture, dislocations, aseptic loosening, anaemia, prolonged length of stay (LOS), increased mortality, and raised health care costs.

  • Standardised nutritional scoring tools, anthropometric measurements, and serological markers are all options available in pre-operative nutritional assessment in TJA, but there is no consensus yet regarding the standardisation of what parameters to assess and how to assess them.

  • Abnormal parameters identified using any of the assessment methods results in the diagnosis of malnutrition, and correction of these parameters of overnutrition or undernutrition have shown to improve outcomes in TJA.

  • With the multiple nutritional parameters contributing to the success of total joint arthroplasty, it is imperative that orthopaedic surgeon has a thorough knowledge regarding nutritional peri-operative optimisation in TJA.

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Bowen Lai Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Heng Jiang Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Yuan Gao Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Xuhui Zhou Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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  • Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively.

  • Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022.

  • The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field.

  • Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP.

  • This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

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Yu Ren Department of Pharmacy, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China

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Hui Yu Department of Hematology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
Department of Hematology, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang, China

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Zhangfu Wang Department of Orthopedics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China

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Wenjun Pan Department of Orthopedics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China

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Lin Chen Department of Orthopedics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China

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Hua Luo Department of Orthopedics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China

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Purpose

  • For many decades, patients recovering from wound closure have been instructed not to bathe. Although studies have shown that earlier postoperative bathing does not increase the risk of wound infection, it remains rare in practice for patients to be allowed earlier postoperative bathing. We performed this meta-analysis to determine how earlier bathing affected rates of wound infection, other complications, and patient satisfaction.

Methods

  • This systematic review conforms to PRISMA guidelines. The PubMed, EMBASE, Medline, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception dates to December 31, 2022. We estimated pooled values for the efficacy of trial of earlier bathing versus delayed bathing using the odds ratio and their associated 95% CI, and we used the I 2 statistic to assess heterogeneity between studies contributing to these estimates.

Results

  • Of the 1813 articles identified by our search, 11 randomized controlled trials including 2964 patients were eligible for inclusion. The incidence of wound infection did not differ significantly between the earlier bathing and delayed bathing groups, nor did rates of other wound complications such as redness and swelling, or wound dehiscence. However, the incidence of hematoma in the delayed bathing group was higher than in the earlier bathing group. Reported patient satisfaction was significantly higher in the earlier bathing group.

Conclusion

  • The medical community, health authorities, and government should create and disseminate clinical practice guidelines to guide patients to evidence-based beneficial treatment.

Open access
Xiangji Dang Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, P.R. China
Department of Pharmaceutical, Lanzhou University Second Hospital, Lanzhou, Gansu province, P.R. China

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Mei Liu The First Clinical Medical School, Gansu University of Chinese Medicine, Gansu, P.R. China

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Qiang Yang Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu province, P.R. China

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Jin Jiang Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu province, P.R. China

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Yan Liu Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China

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Hui Sun Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu province, P.R. China

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Jinhui Tian Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, P.R. China

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Purpose

  • This study sought to determine if the use of tranexamic acid (TXA) in preexisting thromboembolic risk patients undergoing total joint arthroplasty (TJA) was linked to an increased risk of death or postoperative complications.

Methods

  • We conducted a comprehensive search for studies up to May 2023 in PubMed, Web of Science, EMBASE, and the Cochrane Library. We included randomized clinical trials, cohort studies, and case–control studies examining the use of TXA during TJA surgeries on high-risk patients. The Cochrane Risk of Bias instrument was used to gauge the excellence of RCTs, while the MINORS index was implemented to evaluate cohort studies. We used mean difference (MD) and relative risk (RR) as effect size indices for continuous and binary data, respectively, along with 95% CIs.

Results

  • Our comprehensive study, incorporating data from 11 diverse studies involving 812 993 patients, conducted a meta-analysis demonstrating significant positive outcomes associated with TXA administration. The findings revealed substantial reductions in critical parameters, including overall blood loss (MD = −237.33; 95% CI (−425.44, −49.23)), transfusion rates (RR = 0.45; 95% CI (0.34, 0.60)), and 90-day unplanned readmission rates (RR = 0.86; 95% CI (0.76, 0.97)). Moreover, TXA administration exhibited a protective effect against adverse events, showing decreased risks of pulmonary embolism (RR = 0.73; 95% CI (0.61, 0.87)), myocardial infarction (RR = 0.47; 95% CI (0.40–0.56)), and stroke (RR = 0.73; 95% CI (0.59–0.90)). Importantly, no increased risk was observed for mortality (RR = 0.53; 95% CI (0.24, 1.13)), deep vein thrombosis (RR = 0.69; 95% CI (0.44, 1.09)), or any of the evaluated complications associated with TXA use.

Conclusion

  • The results of this study indicate that the use of TXA in TJA patients with preexisting thromboembolic risk does not exacerbate complications, including reducing mortality, deep vein thrombosis, and pulmonary embolism. Existing evidence strongly supports the potential benefits of TXA in TJA patients with thromboembolic risk, including lowering blood loss, transfusion, and readmission rates.

Open access
Heiner Fangerau Department for the History, Philosophy and Ethics of Medicine, Medical Faculty, Heinrich-Heine University Duesseldorf Centre Health & Society, Moorenstraße 5, Düsseldorf, Germany

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  • The use of artificial intelligence (AI) in medicine and surgery is currently predicted to be very promising.

  • However, AI has the potential to change the doctor’s role and the doctor–patient relationship. It has the potential to support people’s desires for health, along with the potential to nudge or push people to behave in a certain way.

  • To understand these potentials, we must see AI in the light of social developments that have brought about changes in how medicine’s role, in a given society, is understood.

  • The trends of ‘privatisation of medicine’ and ‘public-healthisation of the private’ are proposed as a contextual backdrop to explain why AI raises ethical concerns different from those previously caused by new medical technologies, and which therefore need to be addressed specifically for AI.

Open access
Tristan Ferry Service de Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
Université Claude Bernard Lyon 1, Villeurbanne, France
Centre de Références des IOA Complexes de Lyon, CRIOAc Lyon, Lyon, France
StaPath team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France
Education and Clinical Officer of the ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA)

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Jolien Onsea Department of Trauma Surgery, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Department of Development and Regeneration, KU Leuven, Oude Markt 13, Leuven, Belgium

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Tiphaine Roussel-Gaillard Institut des Agents Infectieux, Centre de Biologie et de Pathologie du Nord, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

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Cécile Batailler Service de Chirurgie Orthopédique et de Médecine du Sport, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

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Thomas Fintan Moriarty AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, Switzerland

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Willem-Jan Metsemakers Department of Trauma Surgery, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Department of Development and Regeneration, KU Leuven, Oude Markt 13, Leuven, Belgium

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  • The treatment of musculoskeletal infections (MSIs), including periprosthetic joint infection (PJI) and fracture-related infection (FRI), is often complicated by biofilm-related challenges necessitating multiple revision surgeries and incurring substantial costs.

  • The emergence of antimicrobial resistance (AMR) adds to the complexity of the problem, leading to increased morbidity and healthcare expenses.

  • There is an urgent need for novel antibacterial strategies, with the World Health Organization endorsing non-traditional approaches like bacteriophage (phage) therapy.

  • Phage therapy, involving the targeted application of lytic potent phages, shows promise in the treatment of MSIs.

  • Although historical clinical trials and recent case studies present significant milestones in the evolution of phage therapy over the past century, challenges persist, including variability in study designs, administration protocols and phage selection. Efforts to enhance treatment efficacy consist of personalized phage therapy and combination with antibiotics.

  • Future perspectives entail addressing regulatory barriers, standardizing treatment protocols, and conducting high-quality clinical trials to establish phage therapy’s efficacy for the treatment of MSIs.

  • Initiatives like the PHAGEFORCE study and the PHAGEinLYON Clinic programme aim to streamline phage therapy, facilitating personalized treatment approaches and systematic data collection to advance its clinical utility in these challenging infections.

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