British medical bulletin最新文献

Introduction: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient's ones. Ex vivo HSC gene therapy (HSC-GT) is a form of HSCT in which HSCs, usually from an autologous source, are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow (BM) niche, which is required for the engraftment of infused cells. Here, we review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.

Sources of data: Literature was reviewed from PubMed-listed peer-reviewed articles. No new data are presented in this article.

Areas of agreement: Chemotherapy exerts short and long-term toxicity to haematopoietic and non-haematopoietic organs. Whenever chemotherapy is solely used to allow engraftment of donor HSCs, rather than eliminating malignant cells, as in the case of HSC-GT for inborn genetic diseases, non-genotoxic approaches sparing off-target tissues are highly desirable.

Areas of controversy: In principle, HSCs can be temporarily moved from the BM niches using mobilizing drugs or selectively cleared with targeted antibodies or immunotoxins to make space for the infused cells. However, translation of these principles into clinically relevant settings is only at the beginning, and whether therapeutically meaningful levels of chimerism can be safely established with these approaches remains to be determined.

Growing points: In pre-clinical models, mobilization of HSCs from the niche can be tailored to accommodate the exchange and engraftment of infused cells. Infused cells can be further endowed with a transient engraftment advantage.

Areas timely for developing research: Inter-individual efficiency and kinetics of HSC mobilization need to be carefully assessed. Investigations in large animal models of emerging non-genotoxic approaches will further strengthen the rationale and encourage application to the treatment of selected diseases.

Background: Coronavirus disease 2019 (COVID-19) and human immunodeficiency virus (HIV) are intersecting pandemics, with implications for care at an individual and global scale.

Sources of data: PubMed search with relevant articles and their references reviewed.

Areas of agreement: COVID-19 has changed the delivery of care to people living with HIV (PLWH). Vaccines are efficacious and safe for PLWH; patient care for symptomatic COVID-19 is similar to that of people without HIV.

Areas of controversy: It remains unclear whether PLWH experience increased COVID-19-specific mortality. Treatments to reduce severity in early COVID-19 infection lack evidence in PLWH.

Growing points: The effects of the COVID-19 pandemic on HIV-related morbidity and mortality are yet to be seen. COVID-19 epidemiology among PLWH is complicated by changes to the severe acute respiratory syndrome coronavirus 2, population behaviours and vaccine availability.

Areas timely for developing research: Global trends in HIV-related morbidity and mortality should be monitored to appreciate the effects of the COVID-19 pandemic. The benefits of early antiviral and/or neutralizing monoclonal antibody (nMAb) treatment for PLWH and nMAb prophylaxis require investigation.

Introduction: It is unclear whether hydrodilatation is beneficial in the management of frozen shoulder compared with other common conservative management modalities. This systematic review evaluates the efficacy of hydrodilatation for the management of frozen shoulder.

Sources of data: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An extensive search of PubMed, Embase, Scopus, Cochrane Central, Web of Science and CINAHL databases using multiple keyword combinations of 'shoulder', 'rotator', 'adhesive capsulitis', 'hydrodilatat*', 'distension' since inception of the databases to June 2023 was implemented.

Areas of agreement: Hydrodilatation leads to at least transient more marked improvements in shoulder disability and passive external rotation compared with intra-articular corticosteroid injections.

Areas of controversy: Hydrodilatation improves passive external rotation in the longer term. Moreover, hydrodilatation may be a preferable option over manipulation under anaesthesia, given its lower cost and better patient convenience.

Growing points: Intensive mobilization after hydrodilatation is a promising adjuvant treatment option for patients suffering from a frozen shoulder.

Areas timely for developing research: Although current evidence suggests that hydrodilatation provides a transient improvement in disability in patients with frozen shoulder, its clinical relevance remains unclear. Further research is necessary to establish its role in the management of the condition.

Introduction: Transient bone osteoporosis (TBO) is characterized by persistent pain, loss of function, no history of trauma and magnetic resonance image (MRI) findings of bone marrow edema.

Source of data: PubMed, Google scholar, EMABSE and Web of Science were accessed in February 2023. No time constrains were used for the search.

Areas of agreement: TBO is rare and misunderstood, typically affecting women during the third trimester of pregnancy or middle-aged men, leading to functional disability for 4-8 weeks followed by self-resolution of the symptoms.

Areas of controversy: Given the limited evidence in the current literature, consensus on optimal management is lacking.

Growing points: This systematic review investigates current management of TBO.

Areas timely for developing research: A conservative approach leads to the resolution of symptoms and MRI findings at midterm follow-up. Administration of bisphosphonates might alleviate pain and accelerate both clinical and imaging recovery.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.

Sources of data: Recent published literature.

Areas of agreement: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.

Areas of controversy: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.

Growing points: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.

Areas timely for developing research: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

Background: Joint hypermobility (JHM) is a common physical trait. It may occur alone or in combination with musculoskeletal (MSK) pain, outside or within more complex phenotypes. Hypermobility spectrum disorders (HSD) are diagnosed in individuals with JHM and related MSK pain, when an alternative diagnosis cannot be identified. Conversely, the Ehlers-Danlos syndrome (EDS) encompasses a group of rare hereditary connective tissue disorders featuring JHM along with other pleiotropic manifestations. The 2017 EDS Classification identifies 13 different subtypes. Hypermobile EDS (HEDS) is the only EDS variant still lacking a confirmatory test.

Sources of data: Literature was reviewed searching for the most relevant papers related to key arguments. Particular attention was focused on papers published after the 2017 Classification.

Areas of agreement: Definition, epidemiology, assessment tools and patterns of JHM are presented. The morbid nature of the 2017 EDS Classification and of the 'spectrum' is also illustrated.

Areas of controversy: We discuss current limitations and disagreements concerning the 'spectrum', HSD and HEDS.

Growing points: In the clinical context, elucidation of the pathophysiology of pain related to JHM should develop in parallel with the analysis of pleiotropic manifestations of syndromes with JHM.

Areas timely for developing research: Future challenges concerning classification, nosology, diagnosis and management of JHM, EDS and related disorders are discussed.

Introduction: Long COVID is a chronic condition that follows after acute COVID-19 and is characterized by a wide range of persistent, cyclic symptoms.

Sources of data: PubMed search for publications featuring 'Long COVID' or 'post-acute sequelae of COVID-19'.

Areas of agreement: Long COVID occurs frequently post-acute COVID-19, with a majority of people experiencing at least one symptom (such as cough, fatigue, myalgia, anosmia and dyspnoea) 4 weeks after infection.

Areas of controversy: The specific symptoms and the minimum duration of symptoms required to be defined as Long COVID.

Growing points: There is a consistent reduction in Long COVID incidence amongst vaccinated individuals, although the extent of this effect remains unclear.

Areas timely for developing research: There is an urgent need to understand the causes of Long COVID, especially extreme fatigue more than 6 months after infection. We must understand who is at risk and whether reinfections similarly risk Long COVID.

Introduction: Complex regional pain syndrome (CRPS) is a neurological pain disorder that is challenging to diagnose and manage, resulting in increased morbidity and costs. It most commonly occurs following traumatic injury, such as a fracture, crush injury or surgery. Recent research has evaluated the efficacy of treatments which have contradicted previous hypotheses. This systematic review summarizes these findings to improve clinician's decision-making.

Sources of data: A comprehensive search of PubMed, MEDLINE and Embase databases from inception through January 2021 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened relevant articles discussing the management of CRPS in adult trauma patients. All prospective and retrospective studies, non-randomized comparison studies and case series were considered for inclusion. Data extraction was performed by populating a predefined data abstraction sheet.

Areas of agreement: There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates, sympathectomy and brachial plexus blocks in the management of CRPS.

Areas of controversy: The latest evidence suggests that vitamin C has no significant role to play in the treatment or prevention of CRPS.

Growing points: A multidisciplinary team approach and early diagnosis are imperative for successful treatment of CRPS. The Budapest criteria and the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines should be used when diagnosing CRPS. There is currently no clear evidence of superiority in any treatment.

Areas timely for developing research: There are few high-quality studies that inform the best treatment modalities for CRPS. Though emerging treatments show promise, further research is needed.