Statin-Induced Necrotizing Autoimmune Myopathy: A Case Report

In the landscape of contemporary medicine, statins stand out as a cornerstone in the prevention and management of atherosclerotic cardiovascular diseases. By inhibiting the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme, statins effectively lower cholesterol levels, thus mitigating the risk of heart attacks and strokes.1 Despite their widespread adoption and generally well-tolerated nature, the clinical panorama of statin therapy is occasionally marred by side effects, including muscle-related adverse events. These range from relatively common and benign myalgias to the rare and severe statin-induced necrotizing autoimmune myopathy (SINAM), a condition marked by muscle weakness and profoundly elevated levels of creatine kinase (CK) that persist even after the discontinuation of the offending statin2 (Table 1)

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model

Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study

Purpose: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb–July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. Results: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32–81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7–8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months’ treatment duration; median of 4 mm [IQR − 20, 4]. In a small subset of patients ( n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month’s duration of BrET. Discussion: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer

Background Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. Methods Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. Results Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. Conclusions These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection

Multimodal functional imaging and clinical correlates of pain regions in chronic low-back pain patients treated with spinal cord stimulation: a pilot study.

OBJECTIVE: Spinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions. METHODS: Multi-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis. RESULTS: Arterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients. CONCLUSION: The present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools

The Emerging Role of NaF-PET/CT in Detecting Vascular Microcalcification in the Pathogenesis of Neurological Dysfunction

Cerebrovascular disease (CVD) is a global health concern, and early detection is crucial for effective intervention. This case report presents a 31-year-old male patient with multiple cardiac risk factors who underwent positron emission tomography/computed tomography (PET/CT) with 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) to evaluate for the presence and degree of atherosclerosis in the aorta, carotid arteries, coronary arteries, iliac arteries, and the femoral arteries. Elevated NaF uptake within the bilateral carotid arteries signified substantial ongoing vascular microcalcification. Reduced global brain metabolism and region-specific hypometabolism measured with FDG PET indicated potential cerebrovascular mechanisms that may be influencing neurological function. The findings highlight the potential of emerging PET tracers, such as NaF, to improve the diagnostic accuracy and therapeutic management of CVD. This case emphasizes the importance of a comprehensive diagnostic approach as well as continued investigation into CVD pathophysiology using PET-based techniques, which may guide the development of innovative therapeutic strategies

Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer

<div><h3>Background</h3><p>Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents <em>in vitro</em> and <em>in vivo</em>. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment.</p> <h3>Methods</h3><p>Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively.</p> <h3>Results</h3><p>Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls.</p> <h3>Conclusions</h3><p>These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.</p> </div

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions