Changes in thyroid function and evolution of subclinical thyroid disease in older men.

OBJECTIVE: Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. DESIGN, PARTICIPANTS AND MEASUREMENTS: Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. RESULTS: At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. CONCLUSIONS: In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

A defect in cell wall recycling confers antibiotic resistance and sensitivity in Staphylococcus aureus.

WalKR is a two-component system that is essential for viability in Gram-positive bacteria that regulates the all-important autolysins in cell wall homeostasis. Further investigation of this essential system is important for identifying ways to address antibiotic resistance. Here, we show that a T101M mutation in walR confers a defect in autolysis, a thickened cell wall, and decreased susceptibility to antibiotics that target lipid II cycle, a phenotype that is reminiscent of the clinical resistance form known as vancomycin intermediate-resistant Staphylococcus aureus. Importantly, this is accompanied by dramatic sensitization to tunicamycin. We demonstrate that this phenotype is due to partial collapse of a pathway consisting of autolysins, AtlA and Sle1, a transmembrane sugar permease, MurP, and GlcNAc recycling enzymes, MupG and MurQ. We suggest that this causes a shortage of substrate for the peptidoglycan biosynthesis enzyme MraY, causing it to be hypersensitive to competitive inhibition by tunicamycin. In conclusion, our results constitute a new molecular model for antibiotic sensitivity in S. aureus and a promising new route for antibiotic discovery.

Imaging Findings in Cirrhotic Liver: Pearls and Pitfalls for Diagnosis of Focal Benign and Malignant Lesions.

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,. HCC usually has typical imaging characteristics, such as the major features established by the Liver Imaging Reporting and Data System. However, HCC can also have a spectrum of atypical or uncommon appearances, such as cystic HCC, hypovascular HCC, or macroscopic fat-containing HCC. HCCs with certain genetic mutations such as CTNNB-1-mutated HCC can harbor unique imaging features not seen in other types of HCC. In addition, malignancies that are less common than HCC, such as cholangiocarcinoma and metastases, which can be difficult to differentiate, can still occur in cirrhotic livers. Atypical imaging features of benign and malignant lesions can be challenging to accurately diagnose. Therefore, familiarity with these features and an understanding of the prevalence of disease entities in cirrhotic livers are key in the daily practice of radiologists for evaluation of cirrhotic livers. The authors illustrate the typical and atypical features of benign and malignant lesions in cirrhosis and discuss the technical pitfalls and unique advantages associated with various imaging modalities in assessing cirrhotic livers, including noncontrast and contrast-enhanced US, CT, and MRI. Work of the U.S. Government published under an exclusive license with the RSNA. Quiz questions for this article are available in the supplemental material.

Feeding mode influences dynamic gut microbiota signatures and affects susceptibility to anti-CD3 mAb-induced intestinal injury in neonatal mice.

Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of ß-diversity including expansion of f_Enterobacteriaceae and f_Enterococcaceae in the ileum of FF pups compared with DF pups by postnatal day (P)2. Together with gut dysbiosis, the FF cohort also had greater ileal mucosa physiological inflammatory activity compared with DF pups by P2 but maintained normal histological features. Interestingly, FF but not DF mouse pups developed necrotizing enterocolitis (NEC)-like intestinal injury within 24 h after anti-CD3 mAb treatment, suggesting that FF influences the susceptibility to intestinal injury in neonates. We further found that NEC-like incidence in anti-CD3 mAb-treated FF neonatal pups was attenuated by antibiotic treatment. Collectively, our data suggest that FF predisposes mouse pups to anti-CD3 mAb-induced intestinal injury due to abnormal f_Enterobacteriaceae and f_Enterococcaceae colonization. These findings advance our understanding of FF-associated microbial colonization and intestinal inflammation, which may help inform the development of new therapeutic approaches to GI diseases like NEC in infants.NEW & NOTEWORTHY This report shows that a feeding mode profoundly affects gut colonization in neonatal mice. Furthermore, our results demonstrate that formula feeding predisposes mouse pups to anti-CD3 mAb-induced necrotizing enterocolitis (NEC)-like intestinal injury upon inadequate microbial colonization. The study suggests the role of the combined presence of formula feeding-associated dysbiosis and mucosal inflammation in the pathogenesis of NEC and provides a new mouse model to study this disease.

Pulmonary CTA Reporting: AJR Expert Panel Narrative Review.

Pulmonary CTA is a ubiquitous study interpreted by radiologists with different levels of experience in a variety of practice settings. Pulmonary embolism (PE) can range from an incidental and clinically insignificant finding to a clinically significant thrombus that can be managed on an outpatient basis to a potentially fatal condition requiring immediate medical or invasive management. Accordingly, a clear and concise pulmonary CTA report should effectively communicate the most pertinent findings to help the treating medical team diagnose or exclude PE and provide information to guide appropriate management. In this Expert Panel Narrative Review, we discuss the purpose of the radiology report for pulmonary CTA, the optimal report format, and the relevant findings that need to be addressed and their clinical significance.

Transgastric Abdominal Ultrasonography in Anesthesia and Critical Care: Review and Proposed Approach.

The use of transesophageal echocardiography (TEE) in the operating room and intensive care unit can provide invaluable information on cardiac as well as abdominal organ structures and function. This approach may be particularly useful when the transabdominal ultrasound examination is not possible during intraoperative procedures or for anatomical reasons. This review explores the role of transgastric abdominal ultrasonography (TGAUS) in perioperative medicine. We describe several reported applications using 10 views that can be used in the diagnosis of relevant abdominal conditions associated with organ dysfunction and hemodynamic instability in the operating room and the intensive care unit.

2020 MR Safety for Cardiac Devices: An Update for Radiologists [Formula: see text].

Magnetic resonance imaging (MRI) is a unique and powerful diagnostic tool that provides images without ionizing radiation and, at times, can be the only modality to properly assess and diagnose some pathologies. Although many patients will need an MRI in their lifetime, many of them are still being unjustly denied access to it due to what were once considered absolute contraindications, including MR nonconditional pacemakers and implantable cardioverter-defibrillators. However, there are a number of large studies that have recently demonstrated that MRI can safely be performed in these patients under certain conditions. In addition, there are an increasing number of novel cardiac devices implanted in patients who may require an MRI. Radiologists need to familiarize themselves with these devices, identify which patients with these devices can safely undergo MRI, and under which conditions. In this article, we will review the current literature on MR safety and cardiac devices, elaborate on how to safely image patients with cardiac devices, and share the expertise of our tertiary cardiac institute.

Assessment of left ventricular ejection fraction with cardiofocal collimators: Comparison between IQ-SPECT, planar equilibrium radionuclide angiography, and cardiac magnetic resonance.

BACKGROUND: IQ-SPECT has been shown to significantly reduce acquisition time and administered dose while preserving image quality in myocardial perfusion imaging. Whether IQ-SPECT provides accurate left ventricular ejection fractions (LVEF) with gated blood pool SPECT (GBPS) remains unknown. METHODS: Sixty patients underwent IQ-SPECT GBPS and planar imaging. Among those patients, 11 underwent both cMRI and GBPS. GBPS LVEF, LVEDV, and LVESV were calculated using 2 validated software; QBS (Cedars-Sinai Medical Center, Los Angeles, USA) and MHI (Montreal Heart Institute, Montreal, Canada). LVEF, LVEDV, and LVESV obtained with the different modalities were compared. RESULTS: Average planar LVEF was 48 ± 11% (mean ± SD), average LVEDV was 177 ± 59 mL (range 63 to 342 mL), and average LVESV was 96 ± 46 mL (range 16 to 234 mL). GBPS LVEF and their correlation coefficient with planar LVEF were 40 ± 12% (r = 0.70) and 44 ± 12% (r = 0.83) with QBS and MHI, respectively. Correlation coefficient between cMRI and planar LVEF was 0.65 and were 0.69 and 0.52 between cMRI and GBPS using QBS and MHI, respectively. CONCLUSIONS: LVEF calculated with GBPS using IQ-SPECT correlates with planar measurements. Correlation is best using the MHI method and variation is independent of LVEDV.

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review.

BACKGROUND: Kava is a beverage made from the ground roots of the plant Piper Methysticum and has long-held a significant place within Pacific island communities. Active compounds were extracted from kava, and secondary metabolites include kavalactones, chalcones, cinnamic acid derivatives and flavanones. It is thought that components of kava may exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. METHODS: We conducted a systematic review to summarize available evidence of the anticancer effects of kava components and investigate their potential use for oral squamous cell carcinoma (OSCC) treatment. Eligible studies were identified through a comprehensive search of OVID EMBASE, OVID MEDLINE and Web of Science, as at April 2018. RESULTS: Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins. Further, they were associated with a dose-dependent reduction of angiogenesis. CONCLUSION: There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma.

Comparison of the Efficacy and Safety of Early Rule-Out Pathways for Acute Myocardial Infarction.

BACKGROUND: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients. METHODS: Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease. RESULTS: The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9-98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0-99.9; P<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (P<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease. CONCLUSIONS: Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01852123.

Outcomes following surgical repair using layered closure of unrepaired 4th degree perineal tear in rural western Uganda.

INTRODUCTION: In many rural low-income countries, perineal tears at time of vaginal birth are not repaired at time of delivery. The aims of this study are to describe the surgical technique for management of the unrepaired 4th degree tear, performed without flaps, and short-term follow up on anal incontinence symptoms using a validated questionnaire. METHODS: Women presenting to fistula camps in western Uganda with unrepaired 4th degree tears were interviewed using the Cleveland Clinic Continence Score. Interviews were undertaken pre-operatively, at 4-6 weeks post-operatively and 12 months following surgery. Repair of the 4th degree tear was performed in layers, with an overlapping anal sphincter repair and reconstruction of the perineal body, without flaps. All women were examined prior to discharge. RESULTS: 68 women completed pre-operative Cleveland Clinic Continence Scores. Prior to surgery, 59 % of women complained of daily incontinence to solid stools. Over 70 % of women complained of restriction to lifestyle due to the unrepaired 4th degree tear. About 50 % of the women are rejected by their husbands because of the condition. Only 1 woman had wound breakdown on Day 2. At 4 to 6 weeks follow-up, 61 women were contacted and all reported perfect continence. CONCLUSION: This study highlights the hidden problem of unrepaired 4th degree tears in rural areas of low-income countries where most deliveries are undertaken in the village without professional health care workers. These tears have significant impact on quality of life and anal incontinence. Short-term outcomes following surgical repair using a layered closure are promising.

Antibiotics for preventing recurrent sore throat.

BACKGROUND: Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. OBJECTIVES: To assess the effects of antibiotics in patients with recurrent sore throat. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. MAIN RESULTS: We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

Carpal angles as measured on CT and MRI: can we simply translate radiographic measurements?

OBJECTIVE: To determine the reliability of carpal angles measured on CT and MRI compared to radiography and assess if these measurements are interchangeable. MATERIALS AND METHODS: Our institutional ethic research committee approved this study. For this retrospective study, two independent observers measured the scapholunate (SL), capitolunate (CL), radiolunate (RL), and radioscaphoid (RS) angles on 21 sets of exams, with each set including a radiograph, CT, and MRI of the same wrist. Inter- and intra-observer agreements were evaluated with the intraclass correlation coefficient (ICC). Linear mixed models and two-way contingency tables were used to determine if the angles measured on cross-sectional modalities were significantly different from those obtained on radiography. RESULTS: Inter-observer agreement was strong (ICC >0.8) for all angles, except for the RL angle measured on MRI (ICC 0.68). Intra-observer agreement was also strong for all angles, except for the CL angle measured on CT (ICC 0.66). SL angles measured on CT and MRI were not statistically different from those measured on radiographs (p = 0.37 and 0.36, respectively), unlike CL, RL, and RS angles (p < 0.05). Accuracy between modalities varied between 76 and 86% for the SL angle and ranged between 43 and 76% for the other angles. CONCLUSIONS: CL, RL, and RS angles showed large intermodality variability. Therefore, their measurements on CT or MRI could potentially lead to miscategorization. Conversely, our data showing no significant difference between modalities, SL angle could be measured on CT and MRI to assess wrist instability with a lower risk of error.

A systematic review of the management of eosinophilic dermatosis of hematological malignancy.

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a cutaneous manifestation seen in patients with hematoproliferative and lymphoproliferative disorders, most commonly chronic lymphocytic leukemia. This systematic review aimed to summarize the therapeutic interventions of EDHM. A comprehensive search yielded 71 studies, predominantly case reports and series. The most frequently reported modalities were systemic and topical corticosteroids, as well as treatment of the underlying malignancy. Responses to these treatments varied. Targeted therapies, including dupilumab and omalizumab, showed promise, as did other modalities such as montelukast, dapsone, doxycycline, and phototherapy. Higher-quality studies should be conducted to facilitate higher-quality management recommendations for EDHM.

Cross-Sectional and Longitudinal Associations Between Treatment for Herpes Virus Infection and the Dispensing of Antidementia Medicines: An Analysis of the Australian Pharmaceutical Benefits Scheme Database.

Background: Evidence from previous observational studies suggest that infection by herpes simplex virus (HSV) and varicella zoster virus (VZV) increase the risk of dementia. Objective: To investigate if older adults exposed to HSV treatment have lower risk of dementia than the rest of the population. Methods: We used the 10% Australian Pharmaceutical Benefits Scheme (PBS) database from 2013 to 2022 to ascertain the cross-sectional, time-series and longitudinal association between exposure to HSV treatment and the dispensing of antidementia medicines. Participants were men and women aged 60 years or older. We used Anatomical Therapeutic Chemical (ATC) codes to identify medicines dispensed for the treatment of HSV and dementia. Results: During the year 2022 6,868 (1.2%) of 559,561 of participants aged 60 years or over were dispensed antidementia agent. The odds ratio (OR) of being dispensed an antidementia agent among individuals dispensed treatment for HSV was 0.73 (99% CI = 0.56-0.95). Multilevel logistic regression for the 2013-2022 period for those dispensed HSV treatment was 0.87 (99% CI = 0.75-1.00). Split-time span series from 2013 was associated with hazard ratio of 0.98 (99% CI = 0.89-1.07) for individuals dispensed relative to those not dispensed HSV treatment. All analyses were adjusted for age, sex, and the dispensing of medicines for the treatment of diabetes, hyperlipidemia, hypertension, and ischemic heart disease. Conclusions: The dispensing of antiviral medicines for the treatment of HSV and VZV is consistently, but not conclusively, associated with decreased dispensing of antidementia medicines. This suggests that treatment of HSV and VZV infections may contribute to reduce the risk of dementia.

Scattered Crypt Intestinal Epithelial Cell Apoptosis Induces Necrotizing Enterocolitis Via Intricate Mechanisms.

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear. METHODS: A novel triple-transgenic mouse model, namely, 3xTg-iAPcIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IEC-specific overexpression of Fasl transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The 3-days-old neonatal 3xTg-iAPcIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms. RESULTS: Treatment of 3xTg-iAPcIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated Ifng, Rip3, CD8+ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8+ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAPcIEC mouse pups, underlining their central roles in NEC pathogenesis. CONCLUSIONS: Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8+ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC.

Value of CT and 18F-FDG PET/CT Imaging for Preoperative Screening in Advanced Heart Failure Therapy Candidates.

This study assesses the impact of contrast-enhanced chest and abdominal computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in preoperative screening of heart transplantation or ventricular assist device candidates. Patients who underwent both studies within a 6-month interval at our institution between 2014 and 2021 were reviewed for significant findings, defined as possible contraindications or actionable findings. Among the 79 included patients, significant findings were found in 38 (48.1%) with CT and in 18 (22.8%) with FDG-PET/CT (P = 0.0015). FDG-PET/CT identified 10 additional significant findings, but none of these precluded patient listing for heart transplantation. Use of FDG-PET/CT may lead to unnecessary investigations when performed indiscriminately in all patients.

La présente étude se penche sur l'incidence du recours à une tomodensitométrie (TDM) thoracique et abdominale avec produit de contraste et à une tomographie par émission de positrons au fluorodésoxyglucose marqué au fluor 18 (TEP-18FDG) lors d'évaluation préopératoire de candidats à une transplantation cardiaque ou à l'implantation d'un dispositif d'assistance ventriculaire. Les résultats obtenus de 79 patients qui ont subi ces deux examens dans un intervalle maximal de six mois à notre établissement entre 2014 et 2021 ont été analysés à la recherche de conclusions pertinentes, définies comme des contre-indications possibles à l'intervention ou des résultats ayant un impact direct sur la prise en charge du patient. De telles conclusions ont été constatées chez 38 participants (48,1 %) suite à une TDM et 18 participants (22,8 %) suite à une TEP-18FDG (p = 0,0015). La TEP-18FDG a permis de relever 10 résultats d'importance supplémentaires, mais aucun d'entre eux n'aurait entraîné l'inadmissibilité du patient à une transplantation cardiaque. L'utilisation de la TEP-18FDG pourrait donner lieu à des examens non nécessaires lorsqu'elle est réalisée sans distinction chez tous les patients.

PRKN/parkin-mediated mitophagy is induced by the probiotics Saccharomyces boulardii and Lactococcus lactis.

Mitochondrial impairment is a hallmark feature of neurodegenerative disorders, such as Parkinson disease, and PRKN/parkin-mediated mitophagy serves to remove unhealthy mitochondria from cells. Notably, probiotics are used to alleviate several symptoms of Parkinson disease including impaired locomotion and neurodegeneration in preclinical studies and constipation in clinical trials. There is some evidence to suggest that probiotics can modulate mitochondrial quality control pathways. In this study, we screened 49 probiotic strains and tested distinct stages of mitophagy to determine whether probiotic treatment could upregulate mitophagy in cells undergoing mitochondrial stress. We found two probiotics, Saccharomyces boulardii and Lactococcus lactis, that upregulated mitochondrial PRKN recruitment, phospho-ubiquitination, and MFN degradation in our cellular assays. Administration of these strains to Drosophila that were exposed to paraquat, a mitochondrial toxin, resulted in improved longevity and motor function. Further, we directly observed increased lysosomal degradation of dysfunctional mitochondria in the treated Drosophila brains. These effects were replicated in vitro and in vivo with supra-physiological concentrations of exogenous soluble factors that are released by probiotics in cultures grown under laboratory conditions. We identified methyl-isoquinoline-6-carboxylate as one candidate molecule, which upregulates mitochondrial PRKN recruitment, phospho-ubiquitination, MFN degradation, and lysosomal degradation of damaged mitochondria. Addition of methyl-isoquinoline-6-carboxylate to the fly food restored motor function to paraquat-treated Drosophila. These data suggest a novel mechanism that is facilitated by probiotics to stimulate mitophagy through a PRKN-dependent pathway, which could explain the potential therapeutic benefit of probiotic administration to patients with Parkinson disease.

Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.

Macrophages are dominant innate immune cells. They demonstrate remarkable heterogeneity and plasticity that are essential for homeostasis and host defense. The heterogeneity of tissue macrophages is shaped by the ontogeny, tissue factors, and environmental signals, a pattern in a tissue-associated latitudinal manner. At the same time, macrophages have long been considered as mainly plastic cells. These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation, including coordination of signal transducer, epigenetic elements, and transcription factors, conclusively determine the macrophage phenotypes and functions. With the development of cutting-edge technologies, such as fate-mapping, single-cell transcriptomics, ipsc platform, nanotherapeutic materials, etc., our understanding of macrophage biology and the roles in the pathogenesis of diseases is much advanced. This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases. The latitudinal regulation covers the tissue macrophage origins, tissue factors, and environmental signals, reflecting the macrophage heterogeneity. The longitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases (i.e., inflammatory bowel disease). In addition, how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

CTA of Acute Pulmonary Embolism: Best Practices.

Pulmonary CTA is a commonly performed study and the radiologist's role is not limited to simply producing a report. The process from identifying the appropriate patients who will benefit from the study to improving performance in the radiology department requires the radiologist's involvement, expertise, and leadership. The focus of this narrative review is to highlight the different steps and the ways to improve the quality in the assessment of thromboembolic disease where the radiologists can have an impact. This article provides an update on the commonly used and more recently published clinical decision tools, specific parameter adjustments of pulmonary CTA for more challenging patients and potential improvement for the radiology department.