Comparative Outcomes of Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation with Patellar Realignment for Patellar Instability with Associated Cartilage Defects.

PURPOSE: The purpose of this study was to determine clinical and functional outcomes in patients treated with autologous chondrocyte implantation (ACI) or osteochondral allograft (OCA) transplantation for chondral defects secondary to patellar instability with concomitant medial patellofemoral ligament (MPFL) reconstruction and tibial tubercle osteotomy (TTO) for patellar realignment. METHODS: A retrospective review identified patients who underwent ACI or OCA transplantation with concomitant MPFL reconstruction and TTO . Patients were excluded if they did not have concomitant MPFL reconstruction and TTO, had the presence of other intra-articular pathologies, or failed to complete postoperative subjective outcome evaluations at a minimum of 2 years following surgery. Subjective outcome measures included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and Short Form Health Survey (SF-12) physical scores, collected a minimum of 2 years after surgery. Defect location, size, complications, and rate of subsequent surgery were determined. RESULTS: Eighteen total patients were included in this study. The ACI cohort included 11 patients with 13 total defects that were treated with ACI. The OCA cohort included 7 patients with 10 total defects that were treated with OCA. This was due to a number of patients in either group having multiple cartilage defects. Twenty-three total chondral defects were compared to analyze clinical and functional outcomes following surgical correction (ACI: n=13, OCA: n=10). Five defects were noted on the femoral condyle and 18 on the patellar facets/central ridge. Defects were comparable between groups including, size measured during index-arthroscopy (ACI = 3.34 cm2, 95% CI [2.3 cm2 - 4.4 cm2] vs OCA = 4.03 cm2, 95% CI [3.1 cm2 - 5.0 cm2]; P=.351), Outerbridge classification (ACI = 54.8% grade 4 vs OCA = 60.0% grade 4; P=1.000), and AMADEUS score (ACI = 47.1 vs OCA = 58.6; P=.298). Postoperative outcomes were comparable including revision rate (ACI = 15.4% vs OCA = 10.0%; P=1.000) and 2-year IKDC scores (ACI = 74.2, 95% CI [65.2 - 83.2] vs OCA = 51.2, 95% CI [30.3 - 72.1]; P=.077). ACI did have significantly higher 2-year KOOS JR (85.1, 95% CI [76.9 - 93.3] vs 63.7, 95% CI [49.1 - 78.3]; P=.031) and SF-12 scores (54.1, 95% CI [52.0 - 56.2] vs 42.6, 95% CI [35.8 - 49.4]; P=.007) compared to OCA. CONCLUSION: ACI or OCA transplantation for chondral defects with concomitant MPFL reconstruction and TTO can be safely performed in an outpatient setting with functional and clinical outcomes being comparable. LEVEL OF EVIDENCE: Retrospective Case Series Study (Level 3).

A singular, broadly-applicable model for estimating on- and off-path walking travel rates using airborne lidar data.

Accurate prediction of walking travel rates is central to wide-ranging applications, including modeling historical travel networks, simulating evacuation from hazards, evaluating military ground troop movements, and assessing risk to wildland firefighters. Most of the existing functions for estimating travel rates have focused on slope as the sole landscape impediment, while some have gone a step further in applying a limited set of multiplicative factors to account for broadly defined surface types (e.g., "on-path" vs. "off-path"). In this study, we introduce the Simulating Travel Rates In Diverse Environments (STRIDE) model, which accurately predicts travel rates using a suite of airborne lidar-derived metrics (slope, vegetation density, and surface roughness) that encompass a continuous spectrum of landscape structure. STRIDE enables the accurate prediction of both on- and off-path travel rates using a single function that can be applied across wide-ranging environmental settings. The model explained more than 80% of the variance in the mean travel rates from three separate field experiments, with an average predictive error less than 16%. We demonstrate the use of STRIDE to map least-cost paths, highlighting its propensity for selecting logically consistent routes and producing more accurate yet considerably greater total travel time estimates than a slope-only model.

Adaptation of WHO COVID-19 guidelines by Caribbean countries and territories.

The normative role of the World Health Organization (WHO) involves creating evidence-based, principled guidelines to guide its Member States in making well-informed public health decisions. While these guidelines often need to be adapted to ensure contextual relevance, foster better implementation and adherence, adapting existing guidelines is more efficient than creating new ones. Here we describe the adaptation of the WHO coronavirus disease 2019 (COVID-19) living guideline on pharmacological interventions for the Caribbean using the grading of recommendations, assessment, development and evaluation (GRADE)-ADOLOPMENT method. The Caribbean Public Health Agency and the Pan American Health Organization led the effort, assembling a diverse panel of 16 experts from seven Caribbean countries and territories. The adaptation process, involving 15 steps, was guided by an experienced methodologist and included selecting relevant clinical questions and prioritizing them based on regional needs. The panel evaluated the latest WHO guidelines and integrated additional local data. They adjusted the direction and strength of several recommendations to better fit the Caribbean context, considering local values and preferences, resources, accessibility, feasibility and impact on health equity. Ultimately, we changed the direction of two recommendations and the strength of five, tailoring them to regional realities. This effort highlights the importance of adapting global guidelines to local settings, improving their applicability and effectiveness. The adaptation process also serves as a valuable opportunity for skill transfer and capacity-building in guideline development. Continued research is needed to assess the impact of these adaptations on health-care outcomes in the Caribbean.

Le rôle normatif de l'Organisation mondiale de la santé (OMS) consiste à élaborer des lignes directrices fondées sur des données scientifiques et sur des principes afin d'aider ses États membres à prendre des décisions éclairées en matière de santé publique. Bien qu'elles nécessitent souvent des adaptations pour garantir leur pertinence par rapport à des contextes précis et pour favoriser une meilleure mise en œuvre et adhésion, il est plus efficace d'adapter les lignes directrices existantes que d'en créer de nouvelles. La présente publication décrit l'adaptation de la ligne directrice évolutive de l'OMS sur les interventions pharmacologiques dans le cadre de la maladie à coronavirus (COVID-19) pour les Caraïbes en appliquant la méthodologie GRADE (classement des recommandations, de l'appréciation, du développement et de l'évaluation)-ADOLOPMENT. L'Agence de santé publique des Caraïbes et l'Organisation panaméricaine de la Santé ont dirigé les travaux en réunissant un groupe diversifié de 16 experts issus de sept pays et territoires des Caraïbes. Le processus d'adaptation, comptant 15 étapes et encadré par un méthodologiste expérimenté, a consisté à sélectionner des questions cliniques pertinentes et à les classer par ordre de priorité selon les besoins régionaux. Ce groupe a évalué les dernières lignes directrices de l'OMS et a intégré des données locales supplémentaires. Il a ensuite ajusté l'orientation et le poids de plusieurs recommandations afin de mieux les adapter au contexte des Caraïbes, en tenant compte des valeurs et des préférences locales, des ressources, de l'accessibilité, de la faisabilité et de l'impact sur l'équité en matière de santé. En fin de compte, l'orientation de deux recommandations et le poids de cinq autres ont été modifiés, en les adaptant aux réalités régionales. Cet effort souligne l'importance d'adapter des lignes directrices mondiales aux contextes locaux, afin d'en améliorer l'applicabilité et l'efficacité. Le processus d'adaptation représente également une occasion précieuse de transfert de compétences et de renforcement des capacités en matière d'élaboration de lignes directrices. Des recherches continues s'imposent pour évaluer l'impact de ces adaptations sur les résultats des soins de santé dans les Caraïbes.

La función normativa de la Organización Mundial de la Salud (OMS) consiste en elaborar directrices basadas en pruebas y principios para orientar a sus Estados Miembros en la toma de decisiones de salud pública bien fundamentadas. Aunque con frecuencia es necesario adaptar estas directrices para garantizar su pertinencia contextual y fomentar una mejor implementación y observancia, la adaptación de directrices existentes es más eficiente que la creación de otras nuevas. Aquí describimos la adaptación de la directriz vigente de la OMS sobre la enfermedad por coronavirus (COVID-19) relativa a las intervenciones farmacológicas para el Caribe utilizando el método de clasificación de valoración, elaboración y evaluación de las recomendaciones (GRADE)-ADOLOPMENT. La Agencia de Salud Pública del Caribe y la Organización Panamericana de la Salud lideraron la iniciativa, que reunió a un variado grupo de 16 expertos de siete países y territorios caribeños. El proceso de adaptación, que comprendió 15 pasos y fue guiado por un metodólogo experimentado, incluyó la selección de preguntas clínicas pertinentes y su priorización en función de las necesidades regionales. El grupo evaluó las últimas directrices de la OMS e integró datos locales adicionales. Ajustaron la orientación y la fuerza de varias recomendaciones para adaptarlas mejor al contexto caribeño, teniendo en cuenta los valores y preferencias locales, los recursos, la accesibilidad, la viabilidad y el impacto en la equidad sanitaria. Finalmente, cambiamos la orientación de dos recomendaciones y la fuerza de cinco para adaptarlas a las realidades regionales. Esta iniciativa destaca la importancia de adaptar las directrices mundiales a los contextos locales, lo que mejora su aplicabilidad y eficacia. El proceso de adaptación también constituye una valiosa oportunidad para la transferencia de conocimientos y el desarrollo de capacidades en la elaboración de directrices. Es necesario seguir investigando para evaluar el impacto de estas adaptaciones en los resultados de la atención sanitaria en el Caribe.

Society for Cardiovascular Magnetic Resonance 2023 Cases of SCMR Case Series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases are presented in this manuscript.

Magnetic resonance imaging insights from active surveillance of women with ductal carcinoma in situ.

New approaches are needed to determine which ductal carcinoma in situ (DCIS) is at high risk for progression to invasive ductal carcinoma (IDC). We retrospectively studied DCIS patients who declined surgery (2002-2019), and received endocrine therapy (ET) and breast MRI. Baseline MRI and changes at 3 months and 6 months were analyzed by recursive partitioning to stratify IDC risk. Sixty-two patients (63 DCIS; 1 bilateral) with a mean follow-up of 8.5 years were included. Fifty-one percent remained on active surveillance (AS) without evidence of IDC, with a mean duration of 7.6 years. A decision tree based on MRI features of lesion distinctness and background parenchymal enhancement (BPE) at baseline and change after 3 months of ET stratified patients into low, intermediate, and high risk for progression to IDC. MRI imaging features in patients treated with ET and undergoing AS, may help determine which DCIS lesions are at low versus high risk for IDC.

Target regimen profiles for tuberculosis treatment.

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles. We used a similar process as for the 2016 profiles, including a baseline treatment landscape analysis, an initial stakeholder survey, modelling studies estimating the impact and cost-effectiveness of novel tuberculosis treatment regimens, and an extensive stakeholder consultation. We developed target regimen profiles for the treatment of rifampicin-susceptible and rifampicin-resistant tuberculosis, as well as a pan-tuberculosis regimen that would be appropriate for patients with any type of tuberculosis. We describe the revised target regimen profile characteristics, with specific minimal and optimal targets to be met, rationale and justification, and aspects relevant to all target regimen profiles (drug susceptibility testing, adherence and forgiveness, treatment strategies, post-tuberculosis lung disease, and cost and access considerations). We discuss the trade-offs of proposed characteristics for decision-making at developmental or operational levels. We expect that, following these target regimen profile revisions, tuberculosis treatment developers will produce regimens that are quality-assured, affordable and widely available, and that meet the needs of affected populations.

Des traitements de la tuberculose plus simples, plus courts, plus sûrs et plus efficaces, facilement accessibles à toutes les personnes atteintes de tuberculose, font cruellement défaut. En 2016, l'Organisation mondiale de la santé (OMS) a élaboré des profils de schéma thérapeutique cible pour le traitement de la tuberculose, afin de sensibiliser les concepteurs de médicaments aux caractéristiques importantes des schémas thérapeutiques et aux besoins des patients et des programmes au niveau national. Compte tenu des avancées récentes dans le traitement de la tuberculose, l'OMS a révisé et mis à jour ces profils de schéma thérapeutique. Nous avons appliqué un processus similaire à celui des profils de 2016, y compris une analyse de base des différentes possibilités thérapeutiques, une enquête initiale auprès des parties prenantes, des études de modélisation estimant l'impact et le rapport coût-efficacité des nouveaux schémas thérapeutiques pour la tuberculose, ainsi qu'une vaste consultation des parties prenantes. Nous avons élaboré des profils de schéma thérapeutique cible pour le traitement de la tuberculose sensible à la rifampicine ou résistant à la rifampicine, ainsi qu'un schéma multiforme qui conviendrait aux patients atteints de n'importe quel type de tuberculose. Nous décrivons les caractéristiques du profil révisé de schéma thérapeutique cible, avec les objectifs minimaux et optimaux spécifiques à atteindre, le raisonnement et les aspects pertinents pour tous les profils de schéma thérapeutique cible (tests de sensibilité aux médicaments, observance thérapeutique et manque d'observance («forgiveness¼), stratégies de traitement, maladie pulmonaire post-tuberculeuse et considérations de coût et d'accès). Nous discutons des compromis des caractéristiques proposées pour la prise de décisions au niveau du développement ou au niveau opérationnel. Nous espérons qu'à la suite de ces révisions du profil de schéma thérapeutique cible, les concepteurs de traitements antituberculeux produiront des schémas dont la qualité est assurée, qui sont abordables et largement disponibles et qui répondent aux besoins des populations touchées.

Se necesitan con urgencia tratamientos más sencillos, breves, seguros y eficaces contra la tuberculosis que sean fácilmente accesibles para todas las personas con tuberculosis. En 2016, la Organización Mundial de la Salud (OMS) elaboró perfiles objetivo de esquemas terapéuticos para el tratamiento de la tuberculosis con el fin de que los fabricantes de medicamentos conocieran tanto las características importantes de estos esquemas como las necesidades programáticas y de los pacientes en cada país. Teniendo en cuenta los recientes avances pioneros en el tratamiento de la tuberculosis, la OMS ha revisado y actualizado estos perfiles de esquemas terapéuticos. Se ha seguido un proceso similar al de los perfiles de 2016, que incluye un análisis de referencia del panorama terapéutico, una encuesta inicial a las partes interesadas, estudios de modelización para estimar el impacto y la rentabilidad de los nuevos esquemas terapéuticos para el tratamiento de la tuberculosis, y una amplia consulta a las partes interesadas. Se desarrollaron perfiles objetivo de esquemas terapéuticos para el tratamiento de la tuberculosis sensibles a la rifampicina y resistente a la rifampicina, así como un esquema farmacológico capaz de tratar todas las formas de tuberculosis que sería apropiado para pacientes con cualquier tipo de tuberculosis. Se describieron las características revisadas de los perfiles objetivo de los esquemas terapéuticos, con los objetivos mínimos y óptimos específicos que deben alcanzarse, los fundamentos y la justificación, y los aspectos relevantes para todos los perfiles objetivo de los esquemas terapéuticos (pruebas de sensibilidad a los fármacos, adherencia y olvido, estrategias de tratamiento, enfermedad pulmonar postuberculosa, y consideraciones de coste y acceso). Se discutieron las ventajas y desventajas de las características propuestas para la toma de decisiones a nivel de desarrollo u operativo. Se espera que, tras estas revisiones de los perfiles objetivo de los esquemas terapéuticos, las personas encargadas del desarrollo de tratamientos para la tuberculosis elaboren esquemas terapéuticos de calidad garantizada, asequibles y ampliamente disponibles, y que respondan a las necesidades de las poblaciones afectadas.

Association Between Preoperative Patient Resilience and Patient-Reported Outcomes After Rotator Cuff Repair.

Background: Mental and emotional health can affect outcomes after orthopaedic surgery, and patient resilience has been found to be significantly related to postoperative functional outcomes. Purpose: To evaluate the relationship between preoperative patient resilience and 2-year postoperative patient-reported outcomes after rotator cuff repair (RCR). It was hypothesized that patients with low preoperative resilience will have worse patient-reported outcomes at 2 years after RCR versus those with high resilience. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary arthroscopic RCR in 2020 at a single institution and completed the Brief Resilience Scale (BRS) preoperatively were identified. Other inclusion criteria were American Shoulder and Elbow Surgeons (ASES) and Single Assessment Numeric Evaluation (SANE) scores at the 2-year follow-up. Outcomes were compared in patients as divided into low resilience (BRS score >1 SD below the mean), normal resilience (BRS score ≤1 SD of the mean), and high resilience (BRS score >1 SD above the mean) groups. Results: Overall, 100 patients (52 male, 48 female; mean age, 60 ± 9 years) were included in this study. Mean BRS scores did not change significantly from preoperative to 2-year follow-up (3.8 ± 0.7 vs 3.9 ± 0.8, P = .404). All patients had preoperative ASES scores. Low-resilience patients (n = 17) had significantly lower preoperative ASES scores compared with normal (n = 64) and high resilience (n = 19) patients (35 vs 42 vs 54, respectively; P = .022). There were no significant group differences in postoperative outcomes (revision rate, ASES score, ASES score improvement from preoperative to 2-year follow-up, or SANE score). Multivariate analysis indicated that preoperative resilience was not significantly associated with ASES score improvement (ß estimate = -5.64, P = .150), while resilience at 2-year follow-up was significantly related to ASES score improvement (ß estimate = 6.41, P = .031). Conclusion: Patient-reported outcomes at 2-year follow-up did not differ based on preoperative patient resilience for arthroscopic RCR patients. Multivariate analysis also showed that preoperative resilience was not associated with improvement in ASES scores; however, resilience at 2-year follow-up was associated with ASES score improvement.

Comparing the Performance of ChatGPT-4 and Medical Students on MCQs at Varied Levels of Bloom's Taxonomy.

Introduction: This research investigated the capabilities of ChatGPT-4 compared to medical students in answering MCQs using the revised Bloom's Taxonomy as a benchmark. Methods: A cross-sectional study was conducted at The University of the West Indies, Barbados. ChatGPT-4 and medical students were assessed on MCQs from various medical courses using computer-based testing. Results: The study included 304 MCQs. Students demonstrated good knowledge, with 78% correctly answering at least 90% of the questions. However, ChatGPT-4 achieved a higher overall score (73.7%) compared to students (66.7%). Course type significantly affected ChatGPT-4's performance, but revised Bloom's Taxonomy levels did not. A detailed association check between program levels and Bloom's taxonomy levels for correct answers by ChatGPT-4 showed a highly significant correlation (p<0.001), reflecting a concentration of "remember-level" questions in preclinical and "evaluate-level" questions in clinical courses. Discussion: The study highlights ChatGPT-4's proficiency in standardized tests but indicates limitations in clinical reasoning and practical skills. This performance discrepancy suggests that the effectiveness of artificial intelligence (AI) varies based on course content. Conclusion: While ChatGPT-4 shows promise as an educational tool, its role should be supplementary, with strategic integration into medical education to leverage its strengths and address limitations. Further research is needed to explore AI's impact on medical education and student performance across educational levels and courses.

Tumor microenvironmental determinants of high-risk DCIS progression.

Ductal carcinoma in situ (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes PIK3CA and TP53 were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with PIK3CA mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.

Pharmaceutical and biotech industry perspectives on optimizing patient experience and treatment adherence through subcutaneous drug delivery design.

Subcutaneous (SC) drug delivery can be a safe, effective alternative to the traditional intravenous route of administration, potentially offering notable advantages for both patients and healthcare providers. The SC Drug Development & Delivery Consortium convened in 2018 to raise awareness of industry challenges to advance the development of patient-centric SC drug delivery strategies. The SC Consortium identified better understanding of patient preferences and perspectives as necessary to optimize SC product design attributes and help guide design decisions during SC product development. This manuscript provides a comprehensive overview of patient-centric factors for consideration in the SC drug delivery design and development process with the aim of establishing a foundation of existing knowledge for patient experiences related to SC drug delivery. This overview is informed by the outcomes of a multi-step survey of Consortium members and key pharmaceutical stakeholders. Framed in the context of the patient's treatment journey, the survey findings offer future perspectives to fill data gaps to advance patient-centric SC drug delivery.

Performance evaluation of the FastIC readout ASIC with emphasis on Cherenkov emission in TOF-PET.

Objective.The efficient usage of prompt photons like Cherenkov emission is of great interest for the design of the next generation, cost-effective, and ultra-high-sensitivity time-of-flight positron emission tomography (TOF-PET) scanners. With custom, high power consuming, readout electronics and fast digitization the prospect of sub-300 ps FWHM with PET-sized BGO crystals have been shown. However, these results are not scalable to a full system consisting of thousands of detector elements.Approach.To pave the way toward a full TOF-PET scanner, we examine the performance of the FastIC ASIC with Cherenkov-emitting scintillators (BGO), together with one of the most recent SiPM detector developments based on metal trenching from FBK. The FastIC is a highly configurable ASIC with 8 input channels, a power consumption of 12 mW ch-1and excellent linearity on the energy measurement. To put the timing performance of the FastIC into perspective, comparison measurements with high-power consuming readout electronics are performed.Main results.We achieve a best CTR FWHM of 330 ps for 2 × 2 × 3 mm3and 490 ps for 2 × 2 × 20 mm3BGO crystals with the FastIC. In addition, using 20 mm long LSO:Ce:Ca crystals, CTR values of 129 ps FWHM have been measured with the FastIC, only slightly worse to the state-of-the-art of 95 ps obtained with discrete HF electronics.Significance.For the first time, the timing capability of BGO with a scalable ASIC has been evaluated. The findings underscore the potential of the FastIC ASIC in the development of cost-effective TOF-PET scanners with excellent timing characteristics.

Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.

Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12 f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.

Physiological and Molecular Mechanisms Associated with Potato Tuber Dormancy.

Tuber dormancy is an important physiological trait that impacts postharvest storage and end use qualities of potatoes. Overall, dormancy regulation of potato tuber is a complex process driven by genetic as well as environmental factors. Elucidation of the molecular and physiological mechanisms that influence different dormancy stages of tuber has wider potato breeding and industry relevant implications. Therefore, the primary objective of this review is to present the current knowledge on the diversity in tuber dormancy traits among wild relatives of potatoes and discuss how genetic and epigenetic factors contribute to the tuber dormancy. Advancements in understanding of key physiological mechanisms involved in tuber dormancy regulations, such as apical dominance, phytohormone metabolism, and oxidative stress responses were also discussed. This review highlights the impacts of common sprout suppressors on the molecular and physiological mechanisms associated with tuber dormancy and other storage qualities. Collectively, the literature suggests that significant changes in expressions of genes associated with cell cycle, phytohormone metabolism, and oxidative stress response influence initiation, maintenance, and termination of dormancy in potato tubers. Commercial sprout suppressors mainly alter the expressions of genes associated with cell cycle and stress responses and suppress sprout growth rather than prolonging the tuber dormancy.

Evaluation of Failed ACL Reconstruction: An Updated Review.

Failure rates among primary Anterior Cruciate Ligament Reconstruction (ACLR) range from 3.2% to 11.1%. Recently, there has been increased focus on surgical and anatomic considerations which predispose patients to failure, including excessive posterior tibial slope (PTS), unaddressed high-grade pivot shift, and improper tunnel placement. The purpose of this review was to provide a current summary and analysis of the literature regarding patient-related and technical factors surrounding revision ACLR, rehabilitation considerations, overall outcomes and return to sport (RTS) for patients who undergo revision ACLR. There is a convincingly higher re-tear and revision rate in patients who undergo ACLR with allograft than autograft, especially amongst the young, athletic population. Unrecognized Posterior Cruciate Ligament (PLC) injury is a common cause of ACLR failure and current literature suggests concurrent operative management of high-grade PLC injuries. Given the high rates of revision surgery in young active patients who return to pivoting sports, the authors recommend strong consideration of a combined ACLR + Anterolateral Ligament (ALL) or Lateral extra-articular tenodesis (LET) procedure in this population. Excessive PTS has been identified as an independent risk factor for ACL graft failure. Careful consideration of patient-specific factors such as age and activity level may influence the success of ACL reconstruction. Additional technical considerations including graft choice and fixation method, tunnel position, evaluation of concomitant posterolateral corner and high-grade pivot shift injuries, and the role of excessive posterior tibial slope may play a significant role in preventing failure.

Self-reported side effects of COVID-19 vaccines among health professions students in India.

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Knowledge, Attitudes, and Practices of Hand Hygiene, Mask Use, and Social Distancing among Public Hospital and Polyclinic Nurses in Barbados during the Coronavirus 2019 Pandemic.

BACKGROUND: Nurses are essential members of the healthcare workforce and were among the first-line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of infection, resulting in several reported deaths among nursing staff. Several preventive measures were adopted to contain the spread of the COVID-19 virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. METHOD: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) in Barbados from March 2021 to December 2021 was conducted. A nonsystematic convenience sampling method was employed to recruit nurses who were readily available and willing to participate. A questionnaire captured the sociodemographic information and knowledge and practices related to hand hygiene, the use of face masks, and social distancing. Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). RESULTS: Of the 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). The findings revealed that 45.8% had poor knowledge of hand hygiene, and that the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% confidence interval 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask wearing, 53.6% of nurses had average knowledge, and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% confidence interval 1.5, 7.4) of having good knowledge compared to nursing assistants. A total of 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by the WHO. CONCLUSIONS: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

A scoping review of endoscopic and robotic techniques for lateral neck dissection in thyroid cancer.

Introduction: Lateral neck dissection (LND) in thyroid cancer has traditionally been performed by a transcervical technique with a large collar incision. With the rise of endoscopic, video-assisted, and robotic techniques for thyroidectomy, minimally invasive LND is now being performed more frequently, with better cosmetic outcomes. Methods: The purpose of this paper is to review the different minimally invasive and remote access techniques for LND in thyroid cancer. A comprehensive literature review was performed using PubMed and Google Scholar search terms "thyroid cancer" and "lateral neck dissection" and "endoscopy OR robot OR endoscopic OR video-assisted". Results: There are multiple surgical options now available within each subset of endoscopic, video-assisted, and robotic LND. The approach dictates the extent of the LND but almost all techniques access levels II-IV, with variability on levels I and V. This review provides an overview of the indications, contraindications, surgical and oncologic outcomes for each technique. Discussion: Though data remains limited, endoscopic and robotic techniques for LND are safe, with improved cosmetic results and comparable oncologic and surgical outcomes. Similar to patient selection in minimally invasive thyroidectomy, it is important to consider the extent of the LND and select appropriate surgical candidates.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Incidence, Presentation, and Natural History of Adrenal Hemorrhage: An Institutional Analysis.

INTRODUCTION: Adrenal hemorrhage (AH) can occur due to multiple etiologies with variable radiographic appearance, often indistinguishable from underlying adrenal neoplasms. There is a lack of AH literature and evidence-based guidelines. Our study aimed to understand the prevalence and etiology of AH, follow-up, and incidence of underlying neoplasm. METHODS: An institutional database was queried from January 2006 to October 2021 for patients with AH on imaging, excluding patients with known malignancies, adrenal masses, or prior adrenal surgery. Demographics, medical history, hematoma size, laterality, biochemical evaluation, intervention, and additional imaging were reviewed. RESULTS: Of 490,301 imaging reports queried, 530 (0.11%) with AH met inclusion criteria. Most imaging (n = 485, 91.5%) was performed during trauma evaluation. Two patients underwent dedicated intervention at presentation. Interval imaging was performed in 114 (21.5%) patients at a median of 2.6 (interquartile range 0.99-13.4) mo, with resolution (n = 84, 73.7%) or decreased size of AH (n = 21, 18.4%) in most patients. Only 10 patients (1.9%) saw an outpatient provider in our system to address AH or evaluate for underlying mass, and 9 (1.7%) underwent biochemical screening. Thirteen patients (11% of 118 patients with any follow-up) had evidence of an adrenal mass, confirmed on serial imaging (n = 10) or adrenalectomy (n = 3). Scans performed for nontrauma indications were significantly more likely to have an underlying mass (n = 6/26 [23.1%]) than those performed for trauma evaluation (n = 7/92 [7.6%], P = 0.04). CONCLUSIONS: AH is a rare finding associated with an increased rate of underlying adrenal mass, particularly when unrelated to trauma. Most AH resolves spontaneously without intervention. Follow-up imaging at 6 mo can help distinguish mass-associated AH from simple hemorrhage.