British medical bulletin最新文献

Introduction: Chondral defects of the knee are common and their treatment is challenging.

Source of data: PubMed, Google scholar, Embase and Scopus databases.

Areas of agreement: Both autologous matrix-induced chondrogenesis (AMIC) and membrane-induced autologous chondrocyte implantation (mACI) have been used to manage chondral defects of the knee.

Areas of controversy: It is debated whether AMIC and mACI provide equivalent outcomes for the management of chondral defects in the knee at midterm follow-up. Despite the large number of clinical studies, the optimal treatment is still controversial.

Growing points: To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up.

Areas timely for developing research: AMIC may provide better outcomes than mACI for chondral defects of the knee. Further studies are required to verify these results in a clinical setting.

Introduction: This paper explores how the built environment impacts upon health and well-being and suggests that there are opportunities for more integrated working between professionals and citizens to create healthier, happier places.

Sources of data: Policy and practice guidance is presented from the urban planning and design fields. Evidence and data are presented from a range of disciplines on housing, green infrastructure and mental well-being.

Areas of agreement: There is an overwhelming agreement around the principles and rationale of incorporating health in planning and design processes.

Areas of controversy: These principles are not always implemented in practice. Challenges also exist around how different disciplines create and use evidence.

Growing points: More innovative ways of working which incorporates health, public health, planners, designers and citizens, which responds to the needs of communities, should be tested.

Areas timely for developing research: Health and public health professionals can contribute to the evidence base using objective measures to assess the impact of the built environment on mental health and well-being.

Introduction or background: Mosaic overgrowth syndromes (OS) are a proteiform ensemble of rare diseases displaying asymmetric overgrowth involving any tissue type, with degrees of severity ranging from isolated malformation to life-threatening conditions such as pulmonary embolism. Despite discordant clinical presentations, all those syndromes share common genetic anomalies: somatic mutations of genes involved in cell growth and proliferation. The PI3K-AKT-mTOR signaling pathway is one of the most prominent regulators of cell homeostasis, and somatic oncogenic mutations affecting this pathway are responsible for mosaic OS. This review aims to describe the clinical and molecular characteristics of the main OS involving the PI3K-AKT-mTOR pathway, along with the treatments available or under development.

Sources of data: This review summarizes available data regarding OS in scientific articles published in peer-reviewed journals.

Areas of agreement: OS care requires a multidisciplinary approach relying on clinical and radiological follow-up along with symptomatic treatment. However, no specific treatment has yet shown efficacy in randomized control trials.

Areas of controversy: Clinical classifications of OS led to frequent misdiagnosis. Moreover, targeted therapies directed at causal mutated proteins are developing in OSs through cancer drugs repositioning, but the evidence of efficacy and tolerance is still lacking for most of them.

Growing points: The genetic landscape of OS is constantly widening and molecular classifications tend to increase the accuracy of diagnosis, opening opportunities for targeted therapies.

Areas timely for developing research: OS are a dynamic, expanding field of research. Studies focusing on the identification of genetic anomalies and their pharmacological inhibition are needed.

Background: Winged scapula (WS) is a critical complication of axillary surgery in patients treated for breast cancer, and is associated with pain, impairment of the upper extremity's function and poor performance in daily activities.

Sources of data: A systematic review and meta-analysis were performed following the PRISMA guidelines. Two independent reviewers searched PubMed, Embase and Virtual Health Library databases from January 1, 2000 to December 1, 2020. Clinical studies evaluating the diagnosis and epidemiology of WS among breast cancer surgery (BCS) patients were included.

Areas of agreement: The diagnosis of WS relies almost entirely on physical assessment. Studies have suggested a high variability in the report of the incidence of WS given the subjectivity of its diagnosis, and the different criteria used during clinical assessment.

Areas of controversy: The diagnosis of WS in BCS patients remains a challenge given the lack of standardized diagnostic protocols. Physical examination cannot rely on one manoeuvre only, as it may overlook patients with subtle injuries or overweight and contributing to the underreporting of its incidence.

Growing points: BCS patients undergoing axillary lymph node dissection experience a significantly higher incidence of WS than those undergoing sentinel lymph node dissection. The global incidence of WS after BCS is 16.79%. Additionally, the anterior flexion test and the push-up test are the most commonly performed diagnostic manoeuvers.

Areas timely for developing research: Further studies should aim for objective diagnostic tests, especially when the condition is not evident.

Introduction: Male factor infertility concerns 7-10% of men and among these 40-60% remain unexplained.

Sources of data: This review is based on recent published literature regarding the genetic causes of male infertility.

Areas of agreement: Screening for karyotype abnormalities, biallelic pathogenic variants in the CFTR gene and Y-chromosomal microdeletions have been routine in andrology practice for >20 years, explaining ~10% of infertility cases. Rare specific conditions, such as congenital hypogonadotropic hypogonadism, disorders of sex development and defects of sperm morphology and motility, are caused by pathogenic variants in recurrently affected genes, which facilitate high diagnostic yield (40-60%) of targeted gene panel-based testing.

Areas of controversy: Progress in mapping monogenic causes of quantitative spermatogenic failure, the major form of male infertility, has been slower. No 'recurrently' mutated key gene has been identified and worldwide, a few hundred patients in total have been assigned a possible monogenic cause.

Growing points: Given the high genetic heterogeneity, an optimal approach to screen for heterogenous genetic causes of spermatogenic failure is sequencing exomes or in perspective, genomes. Clinical guidelines developed by multidisciplinary experts are needed for smooth integration of expanded molecular diagnostics in the routine management of infertile men.

Areas timely for developing research: Di-/oligogenic causes, structural and common variants implicated in multifactorial inheritance may explain the 'hidden' genetic factors. It is also critical to understand how the recently identified diverse genetic factors of infertility link to general male health concerns across lifespan and how the clinical assessment could benefit from this knowledge.

Introduction: Chondral defects of the knee are common and their management is challenging.

Source of data: Current scientific literature published in PubMed, Google scholar, Embase and Scopus.

Areas of agreement: Membrane-induced autologous chondrocyte implantation (mACI) has been used to manage chondral defects of the knee.

Areas of controversy: Hyaluronic acid membrane provides better outcomes than a collagenic membrane for mACI in the knee at midterm follow-up is controversial.

Growing points: To investigate whether hyaluronic acid membrane may provide comparable clinical outcomes than collagenic membranes for mACI in focal defects of the knee.

Areas timely for developing research: Hyaluronic acid membrane yields a lower rate of failures and revision surgeries for mACI in the management of focal articular cartilage defects of the knee compared with collagenic scaffolds at midterm follow-up. No difference was found in patient reported outcome measures (PROMs). Further comparative studies are required to validate these results in a clinical setting.

Introduction: Despite advances in technology including the development of more sophisticated methods of monitoring blood glucose and delivering insulin, many individuals with type 1 diabetes continue to experience significant challenges in optimizing glycaemic control. Alternative treatment approaches to insulin are required. Increasing efforts have focused on developing treatments aimed at targeting the underlying disease process to modulate the immune system, maximize beta cell function and enhance endogenous insulin production and action.

Sources of data: Literature searches with keywords 'Type 1 diabetes and immunotherapy', publications relating to clinical trials of immunotherapy in type 1 diabetes.

Areas of agreement: Insulin therapy is insufficient to achieve optimal glycaemic control in many individuals with type 1 diabetes, and new treatment approaches are required. Studies have showed promising results for the use of immunotherapy as a means of delaying disease onset and progression.

Areas of controversy: The optimal way of identifying individuals most likely to benefit from immunotherapies.

Growing points: A better understanding of the natural history of type 1 diabetes has made it possible to identify individuals who have developed autoimmunity but have not yet progressed to clinical diabetes, offering opportunities not only to develop treatments that delay disease progression, but prevent its development in the first place. A consensus on how to identify individuals who may benefit from immunotherapy to prevent disease onset is needed.

Areas timely for developing research: The development of optimal strategies for preventing and delaying progression of type 1 diabetes, and monitoring the response to immunointervention.