Annals of translational medicine最新文献

Background and objective: Total ankle replacement has become an increasingly popular surgical procedure for treatment of end-stage ankle arthritis. Though ankle arthrodesis has historically been considered the gold standard treatment, advancements in implant design, functional outcomes, and survivorship have made total ankle replacement a compelling alternative. Particularly, in the past 20 years, total ankle replacement has undergone tremendous innovation, and the field of research in this procedure continues to grow. In this review, we aim to summarize the history, evolution, advancements, and future directions of total ankle replacement as described through implant design, indications, surgical procedures, complications, and outcomes.

Methods: Literature searches were conducted in PubMed to identify relevant articles published prior to March 2023 using the following keywords: "total ankle replacement", "total ankle arthroplasty", and "total ankle".

Key content and findings: Total ankle replacement has demonstrated significant improvements in surgical technique, implant design, survivorship, and clinical and functional outcomes in the modern era. The procedure reports high patient satisfaction, low complication rates, and improved functional abilities that challenge the current gold standard treatment for ankle arthritis.

Conclusions: Though there are areas of improvement for total ankle replacement, the procedure demonstrates promising outcomes for patients with end-stage ankle arthritis to improve pain and functional abilities. Research studies continue to explore various the facets of total ankle replacement, including outcomes, risk factors, novel techniques and modalities, and complications, to direct future innovation and to optimize patient results.

Background and objective: Digital replantation for traumatic amputation has become the standard of care with advances in microsurgical techniques and technology. While digital replantation has progressed significantly, there are still gaps in knowledge in many aspects. Some of the controversial topics in digital replantation include the indications and contraindications, anesthesia, number of vessel anastomoses, mechanism of injury, role of vein graft, distal fingertip replantation, and postoperative management. This article is a narrative review that discusses these controversies and current issues pertaining to digital replantation.

Methods: PubMed, Web of Science, and Google scholar were searched using keywords relating to "digit replantation", "amputation", and "digital replant" with the following terms: "indications", "contraindications", "anaesthesia", "survival", "vessels", "mechanism of injury", "vein graft", "outcome", and "thrombophylaxis". Relevant articles pertaining to digital replantation and deemed by the authors as current or controversial were included.

Key content and findings: The reported survival rates of digital replantation are high. With the advancement of microsurgical techniques and technology, the boundaries of digital replantation continue to be pushed. Various methods have been described recently to improve the success rates of difficult replants, such as strategies for venous outflow and vein grafting. However, there are still aspects of digital replantation that remain unanswered, such as the number of veins to anastomose and the thromboprophylaxis regime.

Conclusions: The review delves into controversial aspects of digital replantation, including contraindications, anesthesia, and postoperative management. Indications and contraindications will continue to evolve alongside advancements in microsurgical techniques and anesthesia. It highlights key factors influencing survival rates, such as the number of repaired vessels and the mechanism of injury. Finally, the review consolidates strategies for managing challenging digital replantations.

Background and objective: While significant sensation recovery improvements in neurotized breasts following reconstruction have been reported, sensation testing methods and surgical techniques have been widely variable. This narrative review aims to summarize available literature on current neurotization practices and sensory recovery outcomes in patients undergoing innervated breast reconstruction.

Methods: A comprehensive literature search of PubMed Medline, Web of Science, and Embase was conducted to identify all studies reporting outcomes of neurotization in breast reconstruction surgeries. Data analyzed included operative times, neurotization techniques, sensory outcomes, and methods as well as patient reported outcomes.

Key content and findings: Despite the heterogeneity of various studies reviewed, all forms of neurotization achieved earlier and superior sensory recovery throughout the reconstructed breast skin compared to non-innervated breasts. In absence of randomized controlled trials or high-quality comparative studies, further evidence is required to objectively confirm this technique offers better sensory recovery.

Conclusions: Neurotization at the time of breast reconstruction may lead to improved sensation and patient reported outcomes delineating improved quality of life compared to non-innervated breasts. Future studies need to standardize the way that breast sensation is measured and determine pre-operative variables leading to expected changes in final sensation recovery to help manage surgical outcome expectations of both the surgeon and the patient.

Multiple sclerosis (MS) stands as a chronic inflammatory disease characterized by its neurodegenerative impacts on the central nervous system. The complexity of MS and the significant challenges it poses to patients have made the exploration of effective treatments a crucial area of research. Among the various mechanisms under investigation, the role of inflammation in MS progression is of particular interest. Inflammatory responses within the body are regulated by various cellular mechanisms, one of which involves the nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domains (PYD)-containing protein 3 (NLRP3). NLRP3 acts as a sensor within cells, playing a pivotal role in controlling the inflammatory response. Its activation is a critical step leading to the assembly of the NLRP3 inflammasome complex, a process that has profound implications for inflammatory diseases like MS. The NLRP3 inflammasome's activation is intricately linked to the subsequent activation of caspase 1 and gasdermin D (GsdmD), signaling pathways that are central to the inflammatory process. GsdmD, a prominent member of the Gasdermin protein family, is particularly noteworthy for its role in pyroptotic cell death, a form of programmed cell death that is distinct from apoptosis and is characterized by its inflammatory nature. This pathway's activation contributes significantly to the pathology of MS by exacerbating inflammatory responses within the nervous system. Given the detrimental effects of unregulated inflammation in MS, therapeutics targeting these inflammatory processes offer a promising avenue for alleviating the symptoms experienced by patients. This review delves into the intricacies of the pyroptotic pathways, highlighting how the formation of the NLRP3 inflammasome induces such pathways and the potential intervention points for therapeutic agents. By inhibiting key steps within these pathways, it is possible to mitigate the inflammatory response, thereby offering relief to those suffering from MS. Understanding these mechanisms not only sheds light on the pathophysiology of MS but also paves the way for the development of novel therapeutic strategies aimed at controlling the disease's progression through the modulation of the body's inflammatory response.

Cardiovascular diseases (CVDs), particularly stroke and myocardial infarction (MI) contributed to the leading cause of death annually among the chronic diseases globally. Despite the advancement of technology, the current available treatments mainly served as palliative care but not treating the diseases. However, the discovery of mesenchymal stem cells (MSCs) had gained a consideration to serve as promising strategy in treating CVDs. Recent evidence also showed that MSCs are the strong candidate to be used as stem cell therapy involving cardiovascular regeneration due to its cardiomyogenesis, anti-inflammatory and immunomodulatory properties, antifibrotic effects and neovascularization capacity. Besides, MSCs could be used for cellular cardiomyoplasty with its transdifferentiation of MSCs into cardiomyocytes, paracrine effects, microvesicles and exosomes as well as mitochondrial transfer. The safety and efficacy of utilizing MSCs have been described in well-established preclinical and clinical studies in which the accomplishment of MSCs transplantation resulted in further improvement of the cardiac function. Tissue engineering could enhance the desired properties and therapeutic effects of MSCs in cardiovascular regeneration by genome-editing, facilitating the cell delivery and retention, biomaterials-based scaffold, and three-dimensional (3D)-bioprinting. However, there are still obstacles in the use of MSCs due to the complexity and versatility of MSCs, low retention rate, route of administration and the ethical and safety issues of the use of MSCs. The aim of this review is to highlight the details of therapeutic properties of MSCs in treating CVDs, strategies to facilitate the therapeutic effects of MSCs through tissue engineering and the challenges faced using MSCs. A comprehensive review has been done through PubMed and National Center for Biotechnology Information (NCBI) from the year of 2010 to 2021 based on some specific key terms such as 'mesenchymal stem cells in cardiovascular disease', 'mesenchymal stem cells in cardiac regeneration', 'mesenchymal stem cells facilitate cardiac repairs', 'tissue engineering of MSCs' to include relevant literature in this review.

Hematopoiesis requires a complex interplay between the hematopoietic stem and progenitor cells and the cells of the bone marrow microenvironment (BMM). The BMM is heterogeneous, with different regions having distinct cellular, molecular, and metabolic composition and function. Studies have shown that this niche is disrupted in patients with acute myeloid leukemia (AML), which plays a crucial role in disease progression. This review provides a comprehensive overview of the components of vascular and endosteal niches and the molecular mechanisms by which they regulate normal hematopoiesis. We also discuss how these niches are modified in the context of AML, into a disease-promoting niche and how the modified niches in turn regulate AML blast survival and proliferation. We focus on mechanisms of modifications in structural and cellular components of the bone marrow (BM) niche by the AML cells and its impact on leukemic progression and patient outcome. Finally, we also discuss mechanisms by which the altered BM niche protects AML blasts from treatment agents, thereby causing therapy resistance in AML patients. We also summarize ongoing clinical trials that target various BM niche components in the treatment of AML patients. Hence, the BM niche represents a promising target to treat AML and promote normal hematopoiesis.

Background: Neoadjuvant chemotherapy (NACT) is increasingly being used in the management of locally advanced biliary tract cancer (BTC). The evidence suggests a contributing role of tumor infiltrating immune cells in the prognosis and response. We set out to characterize immune modulation of tumor immune microenvironment in BTC following NACT.

Case description: Patients with BTC who underwent diagnostic biopsy, then NACT then resection between 2014-2018 were identified. Multiplexed immunohistochemical consecutive staining on single slide (MICSSS) analysis was performed with a series of immune markers to characterize T-cells, immune checkpoints etc. on pre- & post-NACT tumor tissue. Density was calculated for each marker. The final analysis included five patients. Median age was 48 (range, 41-56) years, with 4 female, 4 intrahepatic cholangiocarcinoma and 1 gallbladder. All patients received gemcitabine/cisplatin as NACT (median of 5 cycles). Median time from diagnosis to surgery was 4.3 (range, 1.4-7.8) months. All patients were mismatch repair proficient (pMMR). NACT on average produced a depletion of all immune markers. Given small sample size, each patient was considered their own control and changes in mean cell densities post-NACT were calculated. Patient #2 with a 40-fold increase in PD-L1 expression & 5-fold decrease in CD8:FOXP3 ratio after NACT notably had the shortest disease-free interval (DFI). Patient #3 with the longest DFI had the largest increase in CD8:FOXP3 by about 8-fold with a decrease in PD-L1.

Conclusions: Preliminary results suggest NACT may differentially modulate various compartments of the immune tumor contexture despite overall cell depletion. Future studies should focus on strategies to expand immune modulation of tumor microenvironment, including immune-oncology agents to augment the effects of chemotherapy.

The first alpha emitting radiopharmaceutical, ²²³RaCl₂, radium dichloride, was approved 10 years ago into the clinical armament of treating bone metastases in metastatic castration-resistant prostate cancer (mCRPC). In addition to this, the first beta-emitting radionuclide Lu-177 chelated with a prostate-specific membrane antigen (PSMA) compound, got last year its marketing approval for the third line treatment of mCRPC. Therefore, there is great excitement about combining alpha-emitters and prostate cancer targeting PSMA compounds. This review describes the clinical history of alpha-emitting PSMA in treating mCRPC. Here, we present the potential, current status, and opportunities for ²²⁵Ac-PSMA therapy. The work reviews the basic concepts, current treatment outcome, and toxicity, and areas requiring further investigations such as dosimetric aspects in clinical studies covering more than 400 patients. In general, approximately two-thirds of the patients benefit from this third-line therapy. There is also successful evidence of using ²²⁵Ac-PSMA in the second-line of prostate cancer management. The future potential of ²²⁵Ac-PSMA therapy and targeted alpha therapy (TAT) of cancer in general is enormous. According to our overview the clinical experience with ²²⁵Ac-PSMA therapy to date has shown great benefit and physicians dedicated to theragnostics are anxiously waiting for new applications. Hopefully, this review helps in deeper understanding of the strengths and limitations of TAT and may help in creating effective therapy protocols.

[This corrects the article DOI: 10.21037/atm-21-4669.].

Background: The increasing incidence and prevalence of breast malignancies have led to increasing numbers of surgical interventions performed on the axilla and breast, including axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB), and mastectomy. The risk of postoperative complications, like breast cancer-related lymphoedema (BCRL), can have significant deleterious cosmetic and quality of life effects. National guidelines and cancer councils publish recommendations to avoid skin puncturing procedures, such as venepuncture and intravenous (IV) cannulation, on arms ipsilateral to the surgical site to prevent BCRL occurrence. The initial trials that established a link between BCRL and skin puncture were conducted in the 1950s and 1960s; the evolution of surgical management of breast cancer has likely led to large decreases in complication rates.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four databases were systematically searched for relevant articles. Eleven relevant articles were identified for inclusion in the final analysis. Updated Australian and New Zealand College of Anaesthetists & Faculty of Pain Medicine (ANZCA) guidelines were included in the analysis following their publication after the initial search had been completed.

Results: The overall quality and quantity of evidence in this field is sufficient to conclude that skin puncturing procedures on ipsilateral arms should not be avoided in patients with previous breast or axillary surgery. The highest-quality and most recent available evidence does not support an association between BCRL and skin puncturing procedures. Policies and practices that advocate avoiding skin puncture procedures to prevent BCRL may lead to delays in clinical care. The 2023 ANZCA guidelines recommend against avoiding affected arms for peripheral access and suggest the removal of institutional policies preventing this practice.

Conclusions: In patients that have undergone breast surgery or axillary procedures, venous access procedures can be safely performed on the ipsilateral arm. The evidence does not support overarching restrictions on using the ipsilateral arm without pre-existing lymphoedema.