Why surveys are 'very hard': exploring challenges and insights for collection of authentic patient experience information with speakers of Australian First Nations languages.

INTRODUCTION: Health services collect patient experience data to monitor, evaluate and improve services and subsequently health outcomes. Obtaining authentic patient experience information to inform improvements relies on the quality of data collection processes and the responsiveness of these processes to the cultural and linguistic needs of diverse populations. This study explores the challenges and considerations in collecting authentic patient experience information through survey methods with Australians who primarily speak First Nations languages. METHODS: First Nations language experts, interpreters, health staff and researchers with expertise in intercultural communication engaged in an iterative process of critical review of two survey tools using qualitative methods. These included a collaborative process of repeated translation and back translation of survey items and collaborative analysis of video-recorded trial administration of surveys with languages experts (who were also receiving dialysis treatment) and survey administrators. All research activities were audio- or video-recorded, and data from all sources were translated, transcribed and inductively analysed to identify key elements influencing acceptability and relevance of both survey process and items as well as translatability. RESULTS: Serious challenges in achieving equivalence of meaning between English and translated versions of survey items were pervasive. Translatability of original survey items was extensively compromised by the use of metaphors specific to the cultural context within which surveys were developed, English words that are familiar but used with different meaning, English terms with no equivalent in First Nations languages and grammatical discordance between languages. Discordance between survey methods and First Nations cultural protocols and preferences for seeking and sharing information was also important: the lack of opportunity to share the 'full story', discomfort with direct questions and communication protocols that preclude negative or critical responses constrained the authenticity of the information obtained through survey methods. These limitations have serious implications for the quality of information collected and result in frustration and distress for those engaging with the survey. CONCLUSION: Profound implications for the acceptability of a survey tool as well as data quality arise from differences between First Nations cultural and communication contexts and the cultural context within which survey methods have evolved. When data collection processes are not linguistically and culturally congruent there is a risk that patient experience data are inaccurate, miss what is important to First Nations patients and have limited utility for informing relevant healthcare improvement. Engagement of First Nations cultural and language experts is essential in all stages of development, implementation and evaluation of culturally safe and effective approaches to support speakers of First Nations languages to share their experiences of health care and influence change.

Mid-Term Follow Up of the Nexel Total Elbow Arthroplasty.

INTRODUCTION: Aseptic loosening is one of the most common complications of total elbow arthroplasty (TEA). Modern implants, such as the Nexel, have been designed in an attempt to decrease loosening. The present study aims to report implant survivorship, radiographic assessment of loosening and lucency, and patient-reported outcome measures (PROMs) in patients treated with the Nexel TEA at mid-term follow-up. METHODS: Consecutive series of adult patients underwent TEA using the Nexel by a single surgeon via standardized technique. Patients with minimum 3 year follow-up with radiographic and PROM data were included. Survivorship was defined by the absence of revision. Loosening was assessed via Wrightington method by three independent fellowship-trained shoulder and elbow surgeons. Lucency was analyzed across individual radiographic zones on orthogonal radiographs. PROMs included the Quick Dash (QDASH), Patient Rated Elbow Evaluation (PREE), and EuroQoL (EQ5D). RESULTS: 38 consecutive patients (22 female, 16 male) with mean age of 67 underwent TEA via triceps-sparing isolated medial window approach. Mean follow-up was 5.5 years (range 3-9). Primary diagnoses were: 19 osteoarthritis (OA), 9 rheumatoid arthritis (RA), 9 post-traumatic arthritis (PA), 1 conversion of elbow arthrodesis. Overall survivorship was 97.4%, with one patient undergoing revision for infection. Loosening was found in 5.3% of elbows, averaged across three observers. Lucency was most pronounced at the level of the humeral condyles. PROMs demonstrated significant and clinically meaningful improvements in 76%, 92%, and 73% of patients for QDASH, PREE, and EQ5D, respectively. No significant correlations were found between patient age, gender, loosening, lucency, and PROMs. CONCLUSION: At mid-term follow-up, the Nexel TEA demonstrated excellent overall survivorship and low rate of implant loosening. The single failure requiring revision for infection was conversion of a prior elbow arthrodesis. PROMs overall exhibited marked and consistent improvement from preop to final postop follow-up. Although promising, these results should be interpreted with some caution as long term data regarding this prosthesis are still lacking.

Effectiveness of an Artificial Intelligence-Enabled Intervention for Detecting Clinical Deterioration.

Importance: Inpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness. Objective: To evaluate the effectiveness of an artificial intelligence deterioration model-enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference. Design, Setting, and Participants: This cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022. Exposure: An artificial intelligence deterioration model-enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians. Main Outcomes and Measures: The primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization. Results: During the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a -10.4-percentage point (95% CI, -20.1 to -0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold. Conclusions and Relevance: Using a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model-enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.

Artificial Intelligence-Generated Draft Replies to Patient Inbox Messages.

Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.

Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease.

This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae.

Comparative evaluation of transcutaneous oxygen tension vs ankle-brachial index as predictors of reoperation following below-knee amputation.

OBJECTIVE: Decision-making regarding level of lower extremity amputation is sometimes challenging. Selecting an appropriate anatomic level for major amputation requires consideration of tradeoffs between postoperative function and risk of wound complications that may require additional operations, including debridement and/or conversion to above-knee amputation (AKA). We evaluated the utility of common, non-invasive diagnostic tests used in clinical practice to predict the need for reoperations among patients undergoing primary, elective below knee-amputations (BKAs) by vascular surgeons. METHODS: Patients undergoing elective BKA over a 5-year period were identified using Current Procedural Terminology codes. Medical records were reviewed to characterize demographics, pre-amputation testing transcutaneous oxygen tension (TcPO2), and ankle-brachial index (ABI). The need for ipsilateral post-BKA reoperation (including BKA revision and/or conversion to AKA) regardless of indication was the primary outcome. Associations were evaluated using univariable and multivariable logistic regression models. Cutpoints for TcPO2 values associated with amputation reoperation were evaluated using receiver operating characteristic curves. RESULTS: We identified 175 BKAs, of which 46 (26.3%) required ipsilateral reoperation (18.9% BKA revisions and 14.3% conversions to AKA). The mean age was 63.3 ± 14.8 years. Most patients were male (65.1%) and White (72.0%). Mean pre-amputation calf TcPO2 was 40.0 ± 20.5 mmHg, and mean ABI was 0.64 ± 0.45. In univariable models, post-BKA reoperation was associated with calf TcPO2 (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = .013) but not ABI (OR, 0.53; 95% CI, 0.19-1.46; P = .217). Univariable associations with reoperation were also identified for age (OR, 0.97; 95% CI, 0.94-0.990; P = .003) and diabetes (OR, 0.43; 95% CI, 0.21-0.87; P = .019). No associations with amputation revision were identified for gender, race, end-stage renal disease, or preoperative antibiotics. Calf TcPO2 remained associated with post-BKA reoperation in a multivariable model (OR, 0.97; 95% CI, 0.94-0.99; P = .022) adjusted for age (OR, 0.98; 95% CI, 0.94-1.01; P = .222) and diabetes (OR, 0.98; 95% CI, 0.94-1.01; P = .559). Receiver operating characteristic analysis suggested a TcPO2 ≥38 mmHg as an appropriate cut-point for assessing risk for BKA revision (area under the curve = 0.682; negative predictive value, 0.91). CONCLUSIONS: Reoperation after BKA is common, and reoperation risk was associated with pre-amputation TcPO2. For patients undergoing elective BKA, higher risk of reoperation should be discussed with patients with an ipsilateral TcPO2 <38 mmHg.

Mediational pathways exploring the link between adverse childhood experiences and physical health in a transgender population.

BACKGROUND: Adverse childhood experiences (ACEs) consist of instances of abuse, neglect, or household dysfunction occurring before adulthood. Prevalence rates of ACEs are higher among specific populations, including gender minorities. In addition to ACEs, transgender individuals (TG) face many personal, social, and structural factors that have the potential to negatively impact their physical health. OBJECTIVE: This study examines exploratory mediational pathways between ACEs and two health outcomes (i.e., general health and days physically ill) in TG. Mediators include everyday discrimination, social support, gender non-affirmation, and mental distress. METHODS: Cross-sectional data from the U.S. Transgender Population Health Survey (TransPop) was used to conduct a serial/parallel mediation analysis. The TransPop survey included a total of 274 TG. RESULTS: For both outcome variables, the same three indirect pathways were significant. First, ACEs were associated with increased mental distress, which was associated with a decrease in general health and an increase in days physically ill. Second, ACEs were associated with increased discrimination, which was associated with increased mental distress, and this was associated with a decrease in general health and an increase in days physically ill. Finally, ACEs were associated with discrimination, which was associated with increased gender non-affirmation which was associated with increased mental distress, and this was associated with a decrease in general health and an increase in days physically ill. CONCLUSION: Interventions focused on reducing discrimination, gender non-affirmation, and poor mental health may be vital to improving the health of TG and to mitigating the indirect role of ACEs on TG health.

Accidental Gunshot Wound Fatalities Related to Dropped Firearms.

ABSTRACT: A death resulting from the accidental discharge of a firearm represents a rare but oftentimes preventable tragedy. Such deaths may occur in a variety of settings. One such setting involves the discharge of a loaded firearm, which occurs when it is accidentally dropped, thrown, or falls to the ground. We report on 3 cases in which a loaded firearm discharged when it was dropped, resulting in the deaths of 3 individuals. In 2 cases, the person carrying the dropped firearm was killed, whereas in the third case, a child standing near the person who dropped the weapon was killed. We discuss the risk factors involved in these tragic incidents and present preventive strategies.

A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models.

Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A-APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was aimed to provide preclinical evidence that 3K3A-APC is efficacious and safe as a wound healing agent. 3K3A-APC, like wild-type APC, demonstrated positive effects on proliferation of human skin cells (keratinocytes, endothelial cells and fibroblasts). Similarly it also increased matrix metollaproteinase-2 activation in keratinocytes and fibroblasts. Topical 3K3A-APC treatment at 10 or 30 µg both accelerated mouse wound healing when culled on Day 11. And at 10 µg, it was superior to APC and had half the dermal wound gape compared to control. Further testing was conducted in excisional porcine wounds due to their congruence to human skin. Here, 3K3A-APC advanced macroscopic healing in a dose-dependent manner (100, 250 and 500 µg) when culled on Day 21. This was histologically corroborated by greater collagen maturity, suggesting more advanced remodelling. A non-interference arm of this study found no evidence that topical 3K3A-APC caused either any significant systemic side-effects or any significant leakage into the circulation. However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.

Treatment of Oral Disease in Eight Pet Pot-Bellied Pigs (Sus scrofa domesticus): A Case Series.

Evidence of porcine oral pathology in client-owned domestic pigs has been reported in recent literature. The most common abnormalities are missing teeth and periodontal disease. This case series reviews the diagnosis and treatment of dental disease in 8 pet Vietnamese Pot-Bellied Pigs (Sus scrofa domesticus) over a 6-year period (2015-2021). Inclusion criteria included pigs over 1 year of age that had at least 2 sequential visits involving photographs, full-mouth intraoral radiographs, and dental charting. Eight pigs were identified for study inclusion. The study population included 4 castrated males, 3 spayed females, and 1 intact female. The 8 subjects had a total of 28 visits. Fifty-five intraoral dental extractions were performed and complete healing of 44 extraction sites was observed (11 sites were lost to follow up). Canine tooth reduction was performed on 52 tusks in 7 pigs with exposure of 1 pulp that was treated by partial pulpectomy and direct pulp capping. Restoration of carious lesions was performed on 4 teeth. The most commonly extracted teeth were the right and left maxillary first molars (10 of 47 teeth). Reasons for tooth extraction included: periodontal disease, complicated crown fracture, nonvital +/- periapical pathology, and persistent deciduous teeth. Additional treatments ranged from type 1 crown lengthening with restoration of carious lesions, tusk trimming, closed and open root planing, dental extractions, ultrasonic scaling, and polishing. This article stresses the importance of routine dental healthcare and early intervention for periodontal disease in pigs.

Personalized dietary management of advanced prostate cancer using nutrigenomics: a case report.

While there are emerging reports in the scientific literature on potential associations between cholesterol/lipids and prostate cancer, information on the dietary management of these cancer patients is currently lacking. We report on a 57-year-old white Australian male diagnosed with advanced prostate cancer who had personalized dietary management in preparation for and following his medical treatment: radiation and radical prostatectomy. Dietary recommendations were based on his blood results and nutrigenomic tests which showed a history of and genetic predisposition to dyslipidemia. Nutritional analysis also confirmed the need for dietary modification of his fat intake. Eighteen months post medical and dietary intervention his PSA level was reported at 0.1 ug/L and all blood lipid levels were within reference ranges. At two years there was no detectable disease recurrence and androgen deprivation therapy (ADT) was not required. Personalized dietary recommendations could be a clinically beneficial addition to the multidisciplinary management of prostate cancer patients.

Use of comprehensive genomic profiling for biomarker discovery for the management of non-small cell lung cancer brain metastases.

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests. Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score. Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes. Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future. Statement of translation relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.

Single laboratory evaluation of umbilical cord blood units processing methodologies for banking.

OBJECTIVE: To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. METHODS: Historical data were compiled and the analytical results obtained for the 3 different methods were compared. RESULTS: The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. CONCLUSION: These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality.

Simulating Cardiac Fluid Dynamics in the Human Heart.

Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin, flexible valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions. However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the cardiac valves are limited in their abilities to predict valve performance, resolve fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac fluid dynamics in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first fluid-structure interaction model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and predicts fine-scale flow features. None of these outputs are prescribed; instead, they emerge from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical devices or clinical interventions. They also can serve as platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients.

Isolation and molecular characterization of an FSK2-type dehydrin from Atriplex halimus.

Dehydrins form the group II LEA protein family and are known to play multiple roles in plant stress tolerance and enzyme protection. They harbor a variable number of conserved lysine rich motifs (K-segments) and may also contain three additional conserved motifs (Y-, F- and S-segments). In this work, we report the isolation and characterization of an FSK2-type dehydrin from the halophytic species Atriplex halimus, which we designate as AhDHN1. In silico analysis of the protein sequence revealed that AhDHN1 contains large number of hydrophilic residues, and is predicted to be intrinsically disordered. In addition, it has an FSK2 architecture with one F-segment, one S-segment, and two K-segments. The expression analysis showed that the AhDHN1 transcript is induced by salt and water stress treatments in the leaves of Atriplex seedlings. Moreover, circular dichroism spectrum performed on recombinant AhDHN1 showed that the dehydrin lacks any secondary structure, confirming its intrinsic disorder nature. However, there is a gain of α-helicity in the presence of membrane-like SDS micelles. In vitro assays revealed that AhDHN1 is able to effectively protect enzymatic activity of the lactate dehydrogenase against cold, heat and dehydration stresses. Our findings strongly suggest that AhDHN1 can be involved in the adaptation mechanisms of halophytes to adverse environments.

Anemia: Evaluation of Suspected Anemia.

Anemia is a common condition encountered in inpatient and outpatient primary care settings. When anemia is detected, it is essential to investigate the cause to provide appropriate treatment. Patients may present with symptomatic anemia (eg, fatigue, weakness, shortness of breath), or anemia may be an incidental finding on laboratory evaluation. Initial evaluation consists of a thorough history and physical examination and a complete blood cell count (CBC). Careful examination of the CBC and the mean corpuscular volume provides important clues to the classification and cause of anemia. Supplemental tests may include a peripheral blood smear; reticulocyte count; iron panel (ie, ferritin and iron levels, total iron-binding capacity, transferrin saturation); and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin.

Clonal Complexes Distribution of Staphylococcus aureus Isolates from Clinical Samples from the Caribbean Islands.

The aim of this study was to comprehensively characterise S. aureus from the Caribbean Islands of Trinidad and Tobago, and Jamaica. A total of 101 S. aureus/argenteus isolates were collected in 2020, mainly from patients with skin and soft tissue infections. They were characterised by DNA microarray allowing the detection of ca. 170 target genes and assignment to clonal complexes (CC)s and strains. In addition, the in vitro production of Panton-Valentine leukocidin (PVL) was examined by an experimental lateral flow assay. Two isolates were identified as S. argenteus, CC2596. The remaining S. aureus isolates were assigned to 21 CCs. The PVL rate among methicillin-susceptible S. aureus (MSSA) isolates was high (38/101), and 37 of the 38 genotypically positive isolates also yielded positive lateral flow results. The isolate that did not produce PVL was genome-sequenced, and it was shown to have a frameshift mutation in agrC. The high rate of PVL genes can be attributed to the presence of a known local CC8-MSSA clone in Trinidad and Tobago (n = 12) and to CC152-MSSA (n = 15). In contrast to earlier surveys, the USA300 clone was not found, although one MSSA isolate carried the ACME element, probably being a mecA-deficient derivative of this strain. Ten isolates, all from Trinidad and Tobago, were identified as MRSA. The pandemic ST239-MRSA-III strain was still common (n = 7), but five isolates showed a composite SCCmec element not observed elsewhere. Three isolates were sequenced. That showed a group of genes (among others, speG, crzC, and ccrA/B-4) to be linked to its SCC element, as previously found in some CC5- and CC8-MRSA, as well as in S. epidermidis. The other three MRSA belonged to CC22, CC72, and CC88, indicating epidemiological connections to Africa and the Middle East.

c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities.

The brain is one of the most common metastatic sites among breast cancer patients, especially in those who have Her2-positive or triple-negative tumors. The brain microenvironment has been considered immune privileged, and the exact mechanisms of how immune cells in the brain microenvironment contribute to brain metastasis remain elusive. In this study, we found that neutrophils are recruited and influenced by c-Met high brain metastatic cells in the metastatic sites, and depletion of neutrophils significantly suppressed brain metastasis in animal models. Overexpression of c-Met in tumor cells enhances the secretion of a group of cytokines, including CXCL1/2, G-CSF, and GM-CSF, which play critical roles in neutrophil attraction, granulopoiesis, and homeostasis. Meanwhile, our transcriptomic analysis demonstrated that conditioned media from c-Met high cells significantly induced the secretion of lipocalin 2 (LCN2) from neutrophils, which in turn promotes the self-renewal of cancer stem cells. Our study unveiled the molecular and pathogenic mechanisms of how crosstalk between innate immune cells and tumor cells facilitates tumor progression in the brain, which provides novel therapeutic targets for treating brain metastasis.

Physician wellness: Managing stress and preventing burnout.

Physician burnout is increasing, but navigating its prevention involves a complex intersection of physical, psychological, social, and organizational strategies.