Risk of acute kidney injury in critically-ill patients with COVID-19 compared with seasonal influenza: a retrospective cohort study.

Background: The SARS-CoV-2 virus can bind to angiotensin-converting enzyme 2 receptors on host renal cells and may cause acute kidney injury (AKI). The comparative risks of AKI in patients severely ill with COVID-19 and influenza A have not been examined. Methods: This is a retrospective cohort study including patients with positive PCR results for SARS-CoV-2 or influenza A virus admitted to the intensive care units (ICUs) of 15 public hospitals in Hong Kong between 1st January 2013 and 30th April 2023. Patients who were already on chronic dialysis or had missing values in the confounder model were excluded. Data were retrieved from Hong Kong Hospital Authority's electronic healthcare records. The primary outcome was incident AKI during ICU stay. Secondary outcomes included acute kidney disease (AKD) and hospital mortality. All analyses were examined in multivariable regression adjusting for potential confounders (age, sex, baseline eGFR, PaO2/FiO2 ratio, baseline comorbidities, APACHE IV predicted risk of death, Charlson Comorbidity Index, emergent hospital admission, admission from elderly home, reason for ICU admission, presence of bacterial co-infections, use of medications [including vasopressors, antiviral medications, steroids and nephrotoxic antibiotics], as well as anaemia and leucocytosis). Patients were matched in a 1:1 ratio using a propensity score generated based on the full confounder model. The analyses were repeated using inverse probability weighting and in propensity-score matched cohorts. Findings: A total of 5495 ICU patients were identified. After excluding 1093 (19.9%) patients who met the exclusion criteria and 74 (1.3%) patients who had one or more missing values in the logistic regression model, a total of 4328 patients were included in the final analysis, with 2787 (64.4%) patients who tested positive for SARS-CoV-2 reverse transcription (RT)-PCR and 1541 (35.6%) patients who tested positive for influenza A virus RT-PCR. The comorbidity burden was greater in patients with COVID-19 (Charlson Comorbidity Index 3 [2-4] vs. 3 [1-4]), but the median APACHE IV predicted risk of death was significantly lower (0.19 [0.08-0.38] vs. 0.25 [0.11-0.52]). A total of 1053 (37.8%) patients with COVID-19 and 828 (53.7%) patients with influenza A developed AKI of any stage during ICU stay. In adjusted analysis, the risk of AKI was significantly lower in patients with COVID-19 compared with influenza A (adjusted odds ratio 0.51, 95% confidence interval 0.42-0.61, P < 0.0001]. The risk of stage 3 AKI and AKD were also significantly lower in patients with COVID-19. These results remained robust in multiple pre-planned sensitivity analyses including inverse probability weighting and propensity score matching. Interpretation: Our results suggest that the risk of AKI in patients severely ill with COVID-19 was lower than in patients with influenza A. The burden of concurrent organ failure complicating respiratory viral infections, such as the higher disease-attributable risk of AKI associated with influenza, should be clarified. Funding: An unrestricted philanthropic donation from Mr and Mrs Laurence Tse, The Wai Im Charitable Foundation, Chan Sui Kau Family Benefits and Charitable Foundation, So Ka Wing and Lee Sau Ying Charitable Foundation, Mr & Mrs Tam Wing Fun Edmund Renal Research Fund, the Theme-Based Research Scheme of the Research Grants Council, Hong Kong Special Administrative Region, The Government of the Hong Kong Special Administrative Region; Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government; Emergency COVID-19 Project, Major Projects on Public Security, National Key Research and Development Program; Emergency Collaborative Project of Guangzhou Laboratory; the National Key Research and Development Program of China; Sanming Project of Medicine in Shenzhen China; and the High Level-Hospital Program, Health Commission of Guangdong Province, China.

Value of the surgical pancreatic duct anatomy and associated outcomes in pancreatic cancer.

INTRODUCTION: Pancreatic cancer recurrence following surgery is a significant challenge, and personalized surgical care is crucial. Topographical variations in pancreatic duct anatomy are frequent but often underestimated. This study aimed to investigate the potential importance of these variations in outcomes and patient survival after Whipple's procedures. METHODS: Data were collected from 105 patients with confirmed pancreatic head neoplasms who underwent surgery between 2008 and 2020. Radiological measurements of pancreatic duct location were performed, and statistical analysis was carried out using IBM SPSS. RESULTS: Inferior pancreatic duct topography was associated with an increased rate of metastatic spread and tumour recurrence. Additionally, inferior duct topography was associated with reduced overall and recurrence-free survival. Posterior pancreatic duct topography was associated with decreased incidence of perineural sheet infiltration and improved overall survival. DISCUSSION: These findings suggest that topographical diversity of pancreatic duct location can impact outcomes in Whipple's procedures. Intraoperative review of pancreatic duct location could help surgeons define areas of risk or safety and deliver a personalized surgical approach for patients with beneficial or deleterious anatomical profiles. This study provides valuable information to improve surgical management by identifying high-risk patients and delivering a personalized surgical approach with prognosis stratification.

Degron-based bioPROTACs for controlling signaling in CAR T cells.

Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in pre-clinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation. In contrast to small molecule regulation, genetic circuits offer a more precise method to control CAR signaling in an autonomous, cell-by-cell fashion. Here, we describe a programmable protein degradation tool that adopts the framework of bioPROTACs, heterobifunctional proteins that are composed of a target recognition domain fused to a domain that recruits the endogenous ubiquitin proteasome system. We develop novel bioPROTACs that utilize a compact four residue degron and demonstrate degradation of cytosolic and membrane protein targets using either a nanobody or synthetic leucine zipper as a protein binder. Our bioPROTACs exhibit potent degradation of CARs and can inhibit CAR signaling in primary human T cells. We demonstrate the utility of our bioPROTACs by constructing a genetic circuit to degrade the tyrosine kinase ZAP70 in response to recognition of a specific membrane-bound antigen. This circuit is able to disrupt CAR T cell signaling only in the presence of a specific cell population. These results suggest that bioPROTACs are a powerful tool for expanding the cell engineering toolbox for CAR T cells.

VetLLM: Large Language Model for Predicting Diagnosis from Veterinary Notes.

Lack of diagnosis coding is a barrier to leveraging veterinary notes for medical and public health research. Previous work is limited to develop specialized rule-based or customized supervised learning models to predict diagnosis coding, which is tedious and not easily transferable. In this work, we show that open-source large language models (LLMs) pretrained on general corpus can achieve reasonable performance in a zero-shot setting. Alpaca-7B can achieve a zero-shot F1 of 0.538 on CSU test data and 0.389 on PP test data, two standard benchmarks for coding from veterinary notes. Furthermore, with appropriate fine-tuning, the performance of LLMs can be substantially boosted, exceeding those of strong state-of-the-art supervised models. VetLLM, which is fine-tuned on Alpaca-7B using just 5000 veterinary notes, can achieve a F1 of 0.747 on CSU test data and 0.637 on PP test data. It is of note that our fine-tuning is data-efficient: using 200 notes can outperform supervised models trained with more than 100,000 notes. The findings demonstrate the great potential of leveraging LLMs for language processing tasks in medicine, and we advocate this new paradigm for processing clinical text.

Clinical Outcomes of Left Atrial Appendage Occlusion Versus Switch of Direct Oral Antcoagulant in Atrial Fibrillation: A Territory-Wide Retrospective Analysis.

Background Left atrial appendage occlusion (LAAO) has emerged as an alternative to oral anticoagulation therapy for stroke prevention in atrial fibrillation, but data comparing LAAO with direct oral anticoagulant (DOAC) are sparse. Methods and Results This cohort study compared LAAO (with or without prior anticoagulation) with a switch of one DOAC to another DOAC by 1:2 propensity score matching. The primary outcome was a composite of all-cause mortality, ischemic stroke, and major bleeding. A total of 2350 patients (874 in the LAAO group and 1476 in the DOAC switch group) were included. After a mean follow-up of 1052±694 days, the primary outcome developed in 215 (24.6%) patients in the LAAO group and in 335 (22.7%) patients in the DOAC switch group (hazard ratio [HR], 0.94 [95% CI, 0.80-1.12]; P=0.516). The LAAO group had a lower all-cause mortality (HR, 0.49 [95% CI, 0.39-0.60]; P<0.001) and cardiovascular mortality (HR, 0.49 [95% CI, 0.32-0.73]; P<0.001) but similar risk of ischemic stroke (HR, 0.83 [95% CI, 0.63-1.10]; P=0.194). The major bleeding risk was similar overall (HR, 1.18 [95% CI, 0.94-1.48], P=0.150) but was lower in the LAAO group after 6 months (HR, 0.71 [95% CI, 0.51-0.97]; P=0.032). Conclusions LAAO conferred a similar risk of composite outcome of all-cause mortality, ischemic stroke, and major bleeding, as compared with DOAC switch. The risks of all-cause mortality and cardiovascular mortality were lower with LAAO.

SPECT/CT Scan: A New Diagnostic Tool in Pain Medicine.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the role of SPECT/CT in identifying facet joint arthropathy and the outcomes of interventions with SPECT/CT as an adjunct. RECENT FINDINGS: A positive finding of facet arthropathy on SPECT/CT is associated with a higher likelihood of a unilateral procedure and a significantly more effective intervention compared with those performed on patients with facet arthropathy diagnosed only by clinical and/or radiologic examination. Surgical treatment of SPECT/CT-positive findings appears to have a good effect; however, due to limitations in the available studies, no strong conclusion can be drawn. SPECT/CT has a good correlation identifying pain generators in chronic neck and back pain. SPECT/CT-targeted facet interventions demonstrate a higher success rate, but SPECT/CT is not recommended as a first-line diagnostic tool prior to diagnostic facet interventions. More robust studies are needed to confirm the higher success of surgical treatment for SPECT/CT-positive facet arthropathy.

Evaluating progress in automatic chest X-ray radiology report generation.

Artificial intelligence (AI) models for automatic generation of narrative radiology reports from images have the potential to enhance efficiency and reduce the workload of radiologists. However, evaluating the correctness of these reports requires metrics that can capture clinically pertinent differences. In this study, we investigate the alignment between automated metrics and radiologists' scoring of errors in report generation. We address the limitations of existing metrics by proposing new metrics, RadGraph F1 and RadCliQ, which demonstrate stronger correlation with radiologists' evaluations. In addition, we analyze the failure modes of the metrics to understand their limitations and provide guidance for metric selection and interpretation. This study establishes RadGraph F1 and RadCliQ as meaningful metrics for guiding future research in radiology report generation.

Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study.

OBJECTIVES: The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined. DESIGN: Retrospective observational study. SETTING: Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System). PATIENTS: All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69-0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38-0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively). CONCLUSIONS: In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.

Australasian Sleep Association position statement on consensus and evidence based treatment for primary snoring.

Primary snoring impacts a significant portion of the adult population and has the potential to significantly impair quality of life. The purpose of these guidelines is to provide evidence-based recommendations to assist Australasian practitioners in the management of adult patients who present with primary snoring without significant obstructive sleep apnoea. The Timetable, Methodology and Standards by which this Position Statement has been established is outlined in the Appendix S1. The main recommendations are: Weight loss, and reduced alcohol consumption should be recommended, where appropriate If clinical judgement dictates, benzodiazepine and opioid reduction or avoidance may be advised Positional therapy should be considered in supine dominant snorers In dentate patients, Mandibular advancement devices (MAD) should be recommended as a first line treatment following assessment by both an appropriate Dentist and Sleep physician Continuous positive airway pressure (CPAP) devices may be recommended in patients with primary snoring in those already committed to their use or willing to try Surgical treatment of primary snoring by an appropriately credentialled surgeon may be advised and includes nasal (adjunctive), palatal and other interventions This position statement has been designed based on the best available current evidence and our combined expert clinical experience to facilitate the management of patients who present with primary snoring. It provides clinicians with a series of both non-surgical and surgical options with the aim of achieving optimal symptom control and patient outcomes. This is the first such set of recommendations to be established within Australasia and has also been reviewed and endorsed by the Australasian Sleep Association.

Probabilistic Prediction of Laboratory Test Information Yield.

Low-yield repetitive laboratory diagnostics burden patients and inflate cost of care. In this study, we assess whether stability in repeated laboratory diagnostic measurements is predictable with uncertainty estimates using electronic health record data available before the diagnostic is ordered. We use probabilistic regression to predict a distribution of plausible values, allowing use-time customization for various definitions of "stability" given dynamic ranges and clinical scenarios. After converting distributions into "stability" scores, the models achieve a sensitivity of 29% for white blood cells, 60% for hemoglobin, 100% for platelets, 54% for potassium, 99% for albumin and 35% for creatinine for predicting stability at 90% precision, suggesting those fractions of repetitive tests could be reduced with low risk of missing important changes. The findings demonstrate the feasibility of using electronic health record data to identify low-yield repetitive tests and offer personalized guidance for better usage of testing while ensuring high quality care.

Use of High-Resolution Ultrasound to Guide Alcohol Neurolysis for Chronic Pain.

BACKGROUND: The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our percutaneous treatments, we established a clinical pathway that utilized ultrasound (US) guidance for steroid injection and alcohol ablation for patients with painful neuropathy. OBJECTIVES: To describe a collaborative neuropathy treatment pathway developed by a neurosurgeon, pain physicians, and a sonologist, describing early clinical experiences and patient-reported outcomes. STUDY DESIGN: A retrospective case series was performed. METHODS: Patients that received percutaneous alcohol ablation with US guidance for neuropathy were identified through a retrospective review of a single provider's case log. Demographics and treatment information were collected from the electronic medical record. Patients were surveyed about their symptoms and treatment efficacy. Descriptive statistics were expressed as medians and the interquartile range ([IQR]; 25th and 75th data percentiles). Differences in the median follow-up pain scores were assessed using a Wilcoxon signed-rank test. RESULTS: Thirty-five patients underwent US-guided alcohol ablation, with the average patient receiving one treatment (range: 1 to 2), having a median duration of 4.8 months until reinjection (IQR: 2.9 to 13.1). The median number of steroid injections that individuals received before US-guided alcohol ablation was 2 (IQR: 1 to 3), and the median interval between steroid injections was 3.7 months (IQR: 2.0 to 9.6). Most (20/35 [57%]) patients responded to the survey, and the median pain scores decreased by 3 units (median: -3, IQR: -6 to 0; P < 0.001) one week following the alcohol ablation. This pain reduction remained significant at one month (P < 0.001) and one year (P = 0.002) following ablation. Most (12/20 [60%]) patients reported that alcohol ablation was more effective in improving their pain than oral pain medications. LIMITATIONS: Given the small sample size, treatment efficacy for alcohol neurolysis cannot be generalized to the broader population. CONCLUSIONS: US-guided percutaneous treatments for neuropathic pain present a growing opportunity for interprofessional collaboration between neurosurgery, clinicians who treat chronic pain, and sonologists. US can provide valuable diagnostic information and guide accurate percutaneous treatments in skilled hands. Further studies are warranted to determine whether a US-guided treatment pathway can prevent unnecessary open surgical management.

Incidence, Prediction, and Outcomes of Major Bleeding After Percutaneous Coronary Intervention in Chinese Patients.

Background: The patterns of late major bleeding (MB) after percutaneous coronary intervention (PCI) remain unknown in Chinese patients. Objectives: This study sought to determine the incidence, prediction, and long-term outcomes of late MB in Chinese patients. Methods: This was a retrospective cohort study from 14 hospitals in Hong Kong. Participants were patients undergoing first-time PCI without MB within 30 days or death within 1 year. Patients were stratified by the presence of late MB, defined as MB between 30 and 365 days. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiac events (MACE). Results: A total of 32,057 patients were analyzed. After adjustment for baseline characteristics, periprocedural characteristics, and medications on discharge, the risks of all-cause mortality at 5 years were significantly higher with late MB (HR: 2.15; 95% CI: 1.92-2.41; P < 0.001). Late MB was also associated with a higher risk of MACE (HR: 1.57; 95% CI: 1.03-1.50; P < 0.001), myocardial infarction (HR: 1.25; 95% CI: 1.04-1.52; P = 0.02), and stroke (HR: 1.38; 95% CI: 1.09-1.73; P = 0.006). The CARDIAC (anti-Coagulation therapy, Age, Renal insufficiency, Drop In hemoglobin, baseline Anemia in Chinese patients) score had a good discriminating power for prediction of MB within 365 days (area under the receiver-operating characteristic curve: 0.76). Conclusions: Late MB was independently associated with a higher risk of mortality, MACE, myocardial infarction, and stroke in patients undergoing PCI. The CARDIAC score is a simple model that can predict MB after PCI. Prevention of MB represents an important strategy to optimize cardiovascular outcomes for patients undergoing PCI.

Expert-level detection of pathologies from unannotated chest X-ray images via self-supervised learning.

In tasks involving the interpretation of medical images, suitably trained machine-learning models often exceed the performance of medical experts. Yet such a high-level of performance typically requires that the models be trained with relevant datasets that have been painstakingly annotated by experts. Here we show that a self-supervised model trained on chest X-ray images that lack explicit annotations performs pathology-classification tasks with accuracies comparable to those of radiologists. On an external validation dataset of chest X-rays, the self-supervised model outperformed a fully supervised model in the detection of three pathologies (out of eight), and the performance generalized to pathologies that were not explicitly annotated for model training, to multiple image-interpretation tasks and to datasets from multiple institutions.

Potent GCN2 Inhibitor Capable of Reversing MDSC-Driven T Cell Suppression Demonstrates In Vivo Efficacy as a Single Agent and in Combination with Anti-Angiogenesis Therapy.

General control nonderepressible 2 (GCN2) protein kinase is a cellular stress sensor within the tumor microenvironment (TME), whose signaling cascade has been proposed to contribute to immune escape in tumors. Herein, we report the discovery of cell-potent GCN2 inhibitors with excellent selectivity against its closely related Integrated Stress Response (ISR) family members heme-regulated inhibitor kinase (HRI), protein kinase R (PKR), and (PKR)-like endoplasmic reticulum kinase (PERK), as well as good kinome-wide selectivity and favorable PK. In mice, compound 39 engages GCN2 at levels ≥80% with an oral dose of 15 mg/kg BID. We also demonstrate the ability of compound 39 to alleviate MDSC-related T cell suppression and restore T cell proliferation, similar to the effect seen in MDSCs from GCN2 knockout mice. In the LL2 syngeneic mouse model, compound 39 demonstrates significant tumor growth inhibition (TGI) as a single agent. Furthermore, TGI mediated by anti-VEGFR was enhanced by treatment with compound 39 demonstrating the complementarity of these two mechanisms.

Transfer learning enables prediction of myocardial injury from continuous single-lead electrocardiography.

OBJECTIVE: Chest pain is common, and current risk-stratification methods, requiring 12-lead electrocardiograms (ECGs) and serial biomarker assays, are static and restricted to highly resourced settings. Our objective was to predict myocardial injury using continuous single-lead ECG waveforms similar to those obtained from wearable devices and to evaluate the potential of transfer learning from labeled 12-lead ECGs to improve these predictions. METHODS: We studied 10 874 Emergency Department (ED) patients who received continuous ECG monitoring and troponin testing from 2020 to 2021. We defined myocardial injury as newly elevated troponin in patients with chest pain or shortness of breath. We developed deep learning models of myocardial injury using continuous lead II ECG from bedside monitors as well as conventional 12-lead ECGs from triage. We pretrained single-lead models on a pre-existing corpus of labeled 12-lead ECGs. We compared model predictions to those of ED physicians. RESULTS: A transfer learning strategy, whereby models for continuous single-lead ECGs were first pretrained on 12-lead ECGs from a separate cohort, predicted myocardial injury as accurately as models using patients' own 12-lead ECGs: area under the receiver operating characteristic curve 0.760 (95% confidence interval [CI], 0.721-0.799) and area under the precision-recall curve 0.321 (95% CI, 0.251-0.397). Models demonstrated a high negative predictive value for myocardial injury among patients with chest pain or shortness of breath, exceeding the predictive performance of ED physicians, while attending to known stigmata of myocardial injury. CONCLUSIONS: Deep learning models pretrained on labeled 12-lead ECGs can predict myocardial injury from noisy, continuous monitor data early in a patient's presentation. The utility of continuous single-lead ECG in the risk stratification of chest pain has implications for wearable devices and preclinical settings, where external validation of the approach is needed.

Sensitivity of ventricular systolic function to afterload during veno-arterial extracorporeal membrane oxygenation.

AIMS: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction. METHODS AND RESULTS: A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V-A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V-A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P < 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P < 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P = 0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. CONCLUSIONS: We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.

IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation.

Excess bone loss due to increased osteoclastogenesis is a significant clinical problem. Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation. The role of IFT80, an IFT complex B protein, in osteoclasts (OCs) is completely unknown. Here, we demonstrate that deletion of IFT80 in the myeloid lineage led to increased OC formation and activity accompanied by severe bone loss in mice. IFT80 regulated OC formation by associating with Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) to promote protein stabilization and proteasomal degradation of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). IFT80 knockdown resulted in increased ubiquitination of Cbl-b and higher TRAF6 levels, thereby hyperactivating the receptor activator of nuclear factor-κß (NF-κß) ligand (RANKL) signaling axis and increased OC formation. Ectopic overexpression of IFT80 rescued osteolysis in a calvarial model of bone loss. We have thus identified a negative function of IFT80 in OCs.

Survivals of Angiography-Guided Percutaneous Coronary Intervention and Proportion of Intracoronary Imaging at Population Level: The Imaging Paradox.

Background: There is a significant disparity between randomized controlled trials and observational studies with respect to any mortality benefit with intracoronary imaging during the percutaneous coronary intervention (PCI). This raises a suspicion that the imaging paradox, in which some operators may become over reliant on imaging and less proficient with angiography-guided PCI, might exist. Method: This was a retrospective cohort study from 14 hospitals under the Hospital Authority of Hong Kong between January 1, 2010 and December 31, 2017. Participants were patients who underwent first-ever PCI. The association between mortality risks of patients undergoing angiography-guided PCI and three tertiles (low, medium, and high) of the proportion of PCI done under intracoronary imaging guidance at a population level (background imaging rate), were evaluated after confounder adjustment by multivariable logistic regression. Results: In an adjusted analysis of 11,816 patients undergoing angiography-guided PCI, the risks of all-cause mortality for those were higher in the high-tertile group compared with the low-tertile group (OR, 1.45, 95% CI, 1.10-1.92, P = 0.008), the risks of cardiovascular mortality were higher in the high-tertile group compared with the low-tertile group (OR, 1.51, 95% CI, 1.08-2.13, P = 0.017). The results were consistent with multiple sensitivity analyses. Threshold analysis suggested that the mortality risks of angiography-guided PCI were increased when the proportion of imaging-guided PCI exceeded approximately 50%. Conclusions: The risks of the all-cause mortality and cardiovascular mortality were higher for patients undergoing angiography-guided PCI in practices with a higher background imaging rate.