The evolution of poller screws.

Compared to other techniques, poller screws with intramedullary nailing are technically simple, practical, and reproducible for the fixation of metaphyseal fractures. In addition, poller screws do not require special instruments or hardware and are minimally invasive. This review takes a historical perspective to evaluate poller screws holistically. A non-systematic search on PubMed was performed using 'Poller screw' or 'Blocking screw' to find early use of poller blocking screws. Relevant references from these primary studies were then followed up. In 1999, Krettek et al. first coined the term poller screws after the small metal bollards that block and direct traffic. Poller screws were introduced as an adjunct to aid the union of metaphyseal long bone fractures during intramedullary nailing. However, as more evidence was published, the true effectiveness of poller screws was not appreciated, leading to split opinions. Through our research, we have built upon our understanding of poller screws, and we present a novel classification of poller screws over the years while exploring our novel technique and what we believe to be the fourth generation of poller screws. Currently, there is a paucity of research focussing on poller screws. However, studying the original evidence regarding poller screws through the most recent articles has demonstrated a confusion of research in this field. Therefore, we suggest a more organised approach to classify the use of poller screws.

Preleukemic single-cell landscapes reveal mutation-specific mechanisms and gene programs predictive of AML patient outcomes.

Acute myeloid leukemia (AML) and myeloid neoplasms develop through acquisition of somatic mutations that confer mutation-specific fitness advantages to hematopoietic stem and progenitor cells. However, our understanding of mutational effects remains limited to the resolution attainable within immunophenotypically and clinically accessible bulk cell populations. To decipher heterogeneous cellular fitness to preleukemic mutational perturbations, we performed single-cell RNA sequencing of eight different mouse models with driver mutations of myeloid malignancies, generating 269,048 single-cell profiles. Our analysis infers mutation-driven perturbations in cell abundance, cellular lineage fate, cellular metabolism, and gene expression at the continuous resolution, pinpointing cell populations with transcriptional alterations associated with differentiation bias. We further develop an 11-gene scoring system (Stem11) on the basis of preleukemic transcriptional signatures that predicts AML patient outcomes. Our results demonstrate that a single-cell-resolution deep characterization of preleukemic biology has the potential to enhance our understanding of AML heterogeneity and inform more effective risk stratification strategies.

Using Pre-Clinical Studies to Explore the Potential Clinical Uses of Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem cells.

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.

Management of a Hot Swollen Joint in the Acute Setting.

BACKGROUND: The presentation of a hot swollen joint is common in the emergency department, general practice, rheumatology and orthopedic clinics. There is a wide set of differential diagnoses for a hot swollen joint, thus making it difficult to diagnose and manage, especially for junior doctors. Initially, it is pertinent to exclude/diagnose medical and surgical emergencies. OBJECTIVE: This paper aims to summarize the key indications within the history, examination and investigations in order to quickly and effectively diagnose a hot swollen joint based on the original 2006 management guidelines and the papers discussing other possible indications and management strategies published since then. RESULTS: Currently, the management of crystal and non-infectious arthropathies is well recognized with little disparity. However, the treatment of infectious arthritis is not concrete, and there are discrepancies in management between doctors. CONCLUSION: We have summarized the key indications and provided a diagnostic flow chart to aid with the management of a hot swollen joint.

Supramaximal calcium signaling triggers procoagulant platelet formation.

Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some platelets to become procoagulant, using the high-affinity Ca2+ indicator Fluo-4, which may become saturated during platelet stimulation, or low-affinity Fluo-5N, which reports only very high cytosolic Ca2+ concentrations. All activated platelets had high Fluo-4 fluorescence. However, in Fluo-5N-loaded platelets, only the procoagulant platelets had high fluorescence, indicating very high cytosolic Ca2+. This finding indicates a novel, "supramaximal" Ca2+ signal in procoagulant platelets (ie, much higher than normally considered maximal). Supramaximal Ca2+ signaling and the percentage of procoagulant platelets were inhibited by cyclosporin A, a mitochondrial permeability transition pore blocker, and Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, with no effect on Fluo-4 fluorescence. In contrast, Synta-66, an Orai1 blocker, reduced Fluo-4 fluorescence but did not directly inhibit generation of the supramaximal Ca2+ signal. Our findings show a distinct pattern of Ca2+ signaling in procoagulant platelets and provide a new framework to interpret the role of platelet signaling pathways in procoagulant platelets. This requires reassessment of the role of different Ca2+ channels and may provide new targets to prevent formation of procoagulant platelets and limit thrombosis.