Wait Times, Resource Use and Patient-Reported Outcomes for Patients Referred for Total Knee Replacement Surgery

This prospective cohort study evaluated the usual care pathway for patients referred to total knee arthroplasty (TKA). We measured healthcare resource use, costs and health-related quality of life (HRQoL) over the continuum of care. We also determined the proportion of inappropriate referrals and estimated wait times for initial surgical consultation and TKA. We found that two in five patients referred to specialty care were deemed inappropriate surgical candidates. Prior to referral, few conservative treatment options were tried, and many imaging tests ordered by referring providers were unjustified. Overall, the greatest proportion of costs were borne by the patient or private insurer, with the minority incurred by the public payer. Surgery was associated with improved HRQoL. The results of this study can provide valuable guidance on the design and implementation of a new electronic referral pathway (NRP) to promote appropriate and timely referral and manage excessive wait times for TKA

A revised northern European Turonian (Upper Cretaceous) dinoflagellate cyst biostratigraphy: Integrating palynology and carbon isotope events

Organic walled dinoflagellate cyst (dinocyst) assemblage data are presented for a new Turonian regional reference core (Bch-1) drilled at Běchary in the Bohemian Cretaceous Basin, east-central Czech Republic. The detailed stratigraphic framework for the section is summarised based on calcareous nannofossil and macrofossil biostratigraphy, regional e-log correlation, sequence stratigraphy and carbon isotope chemostratigraphy. Dinocyst results obtained for 196 samples from the 405 m long core offer the highest resolution (~ 22 kyr) stratigraphically well-constrained data set available to date for the Turonian Stage, 93.9–89.8 Ma. A dinocyst biostratigraphic framework is presented based on the evolutionary first and last occurrence, first common occurrence, and acmes of key species. Published dinocyst data from English Turonian Chalk successions in East Sussex, Berkshire, Kent and Norfolk are reviewed within a stratigraphic framework provided by macrofossil records and carbon isotope event (CIE) chemostratigraphy. Critical analysis of existing published Turonian dinocyst zonation schemes shows them to be untenable. Correlation of the English Chalk data to Bch-1 provides a basis for defining a regional dinocyst event stratigraphy with 22 datum levels, and a revised dinocyst zonation scheme constrained within a chemostratigraphic framework of 10 major CIEs. The new zones consist of a Cenomanian Litosphaeridium siphoniphorum Zone, followed by the Cauveridinium membraniphorum Zone spanning the uppermost Cenomanian to Lower Coniacian. This is subdivided into: Senoniasphaera turonica (Lower–mid-Middle Turonian); and Raetiaedinium truncigerum (mid-Middle Turonian–mid-Lower Coniacian) subzones. The Oligosphaeridium pulcherrimum Zone (Senonisphaera rotundata Subzone) characterises the Lower Coniacian. The new stratigraphy offers a basis for improved correlation and dating of Upper Cretaceous successions

SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway

Stop-frame filming and discovery of reactions at the single-molecule level by transmission electron microscopy

We report an approach – named chemTEM – to follow chemical transformations at the single-molecule level with the electron beam of a transmission electron microscope (TEM) applied as both a tuneable source of energy and a sub-Angstrom imaging probe. Deposited on graphene, disk-shaped perchlorocoronene molecules are precluded from intermolecular interactions. This allows monomolecular transformations to be studied at the single-molecule level in real time and reveals chlorine elimination and reactive aryne formation as a key initial stage of multi-step reactions initiated by the 80 keV e-beam. Under the same conditions, perchlorocoronene confined within a nanotube cavity, where the molecules are situated in very close proximity to each other, enables imaging of intermolecular reactions, starting with the Diels-Alder cycloaddition of a generated aryne, followed by rearrangement of the angular adduct to a planar polyaromatic structure and the formation of a perchlorinated zigzag nanoribbon of graphene as the final product. ChemTEM enables the entire process of polycondensation, including the formation of metastable intermediates, to be captured in a one-shot ‘movie’. A molecule with a similar size and shape but with a different chemical composition, octathio[8]circulene, under the same conditions undergoes another type of polycondensation via thiyl biradical generation and subsequent reaction leading to polythiophene nanoribbons with irregular edges incorporating bridging sulphur atoms. Graphene or carbon nanotubes supporting the individual molecules during chemTEM studies ensure that the elastic interactions of the molecules with the e-beam are the dominant forces that initiate and drive the reactions we image. Our ab initio DFT calculations explicitly incorporating the e-beam in the theoretical model correlate with the chemTEM observations and give a mechanism for direct control not only of the type of the reaction but also of the reaction rate. Selection of the appropriate e-beam energy and control of the dose rate in chemTEM enabled imaging of reactions on a timeframe commensurate with TEM image capture rates, revealing atomistic mechanisms of previously unknown processes

International Delphi Study on Wound Closure and Incision Management in Joint Arthroplasty Part 2: Total Hip Arthroplasty

This modified Delphi study aimed to develop a consensus on optimal wound closure and incision management strategies for total hip arthroplasty (THA). Given the critical nature of wound care and incision management in influencing patient outcomes, this study sought to synthesize evidence-based best practices for wound care in THA procedures. An international panel of 20 orthopaedic surgeons from Europe, Canada, and the United States evaluated a targeted literature review of 18 statements (14 specific to THA and 4 related to both THA and total knee arthroplasty). There were three rounds of anonymous voting per topic using a modified five-point Likert scale with a predetermined consensus threshold of ≥75% agreement necessary for a statement to be accepted. After three rounds of voting, consensus was achieved for all 18 statements. Notable recommendations for THA wound management included: 1) the use of barbed sutures over non-barbed sutures (shorter closing times and overall cost savings); 2) the use of subcuticular sutures over skin staples (lower risk of superficial infections and higher patient preferences, but longer closing times); 3) the use of mesh-adhesives over silver-impregnated dressings (lower rate of wound complications); 4) for at-risk patients, the use of negative pressure wound therapy over other dressings (lower wound complications and reoperations, as well as fewer dressing changes); and 5) the use of triclosan-coated sutures (lower risk of surgical site infection) over standard sutures. Through a structured modified Delphi approach, a panel of 20 orthopaedic surgeons reached consensus on all 18 statements pertaining to wound closure and incision management in THA. This study provides a foundational framework for establishing evidence-based best practices, aiming to reduce variability in patient outcomes and to enhance the overall quality of care in THA procedures

Identifying Critical Evidence Gaps in Wound Closure and Incision Management After Total Knee Arthroplasty: Delphi Panel Insights

In orthopaedic surgery, particularly total knee arthroplasty (TKA), the management of surgical wounds is critical for optimal wound healing and successful patient outcomes. Despite advances in surgical techniques, challenges persist in effectively managing surgical wounds to prevent complications and infections. This study aimed to identify and address the critical evidence gaps in wound management in TKA, including preoperative optimization, intraoperative options, and for the avoidance of postoperative complications. These are important issues surrounding wound management, which is essential for improving patient recovery and the overall success of the surgery. Utilizing the Delphi method, this study brought together 20 experienced orthopaedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 specific statements about wound management in TKA based on a comprehensive literature review. During these three stages and after further panel review, an alternative goal of the Delphi panel was to also identify critical evidence gaps in the current understanding of wound management practices for TKA. While the panel reached consensus on various wound management practices, they highlighted several major evidence gaps. Also, there was general consensus on issues such as wound closure methods including the use of mesh-adhesive dressings, skin glue, staples, sutures (including barbed sutures),and negative-pressure wound therapy (NPWT). However, it was deemed necessary that further evidence needs to be generated to address the cost-effectiveness of each and develop best practices for promoting patient outcomes. The identification of these gaps points to areas requiring more in-depth research and improvements to enhance wound care in TKA. The identification of these major evidence gaps underscores the need for targeted research in wound management surrounding TKA. Addressing these evidence gaps is crucial for the future development of more effective, efficient, and patient-friendly wound care strategies. Future research should prioritize these areas, focusing on comparative effectiveness studies and further developing clear guidelines for the use of emerging technologies. Bridging these gaps has the potential to improve patient outcomes, reduce complications, and elevate the overall success rate of TKA surgeries

International Delphi Study on Wound Closure and Dressing Management in Joint Arthroplasty: Part 1: Total Knee Arthroplasty

The purpose of this modified Delphi study was to obtain consensus on wound closure and dressing management in total knee arthroplasty (TKA). The Delphi panel included 20 orthopaedic surgeons from Europe and North America. There were 26 statements identified using a targeted literature review. Consensus was developed for the statements with up to three rounds of anonymous voting per topic. Panelists ranked their agreement with each statement on a five-point Likert scale. An a priori threshold of ≥75% was required for consensus. All 26 statements achieved consensus after three rounds of anonymous voting. Wound closure-related interventions that were recommended for use in TKA included: 1) closing in semi-flexion vs extension (superior range of motion); 2) using aspirin for venous thromboembolism prophylaxis over other agents (reduces wound complications); 3) barbed sutures over non-barbed sutures (lower wound complications, better cosmetic appearances, shorter closing times, and overall cost savings); 4) mesh-adhesives over other skin closure methods (lower wound complications, higher patient satisfaction scores, lower rates of readmission); 5) silver-impregnated dressings over standard dressings (lower wound complications, decreased infections, fewer dressing changes); 6) in high-risk patients, negative pressure wound therapy over other dressings (lower wound complications, decreased reoperations, fewer dressing changes); and 7) using triclosan-coated over non-antimicrobial-coated sutures (lower risks of surgical site infection). Using a modified Delphi approach, the panel achieved consensus on 26 statements pertaining to wound closure and dressing management in TKA. This study forms the basis for identifying critical evidence supported by clinical practice for wound management to help reduce variability, advance standardization, and ultimately improve in outcomes during TKA. The results presented here can serve as the foundation for knowledge, education, and improved clinical outcomes for surgeons performing TKAs