Consequences of Pausing Heated Humidification during Invasive Ventilation.

BACKGROUND: During invasive mechanical ventilation, where medical gases are very dry and the upper airway is bypassed, appropriate gas conditioning and humidification are mandatory at all times. Results of in vitro studies suggest that dry gases may improve lung deposition during nebulization, but this has not been confirmed through in vivo studies. The objective of this study was to measure gas humidity under multiple conditions to better describe gas hygrometry when heated humidifiers are turned off. METHODS: We measured, on a bench, the hygrometry of different gases at steady state: medical gases, at the Y-piece without humidifier, with the humidifier switched off, and with humidifier switched on. We measured gas humidity every 10-60 s during dynamic conditions after switching off the heated humidifier and after switching on the heated humidifier. Hygrometry was measured by using the psychrometric method with at least 3 measurements for each tested condition. RESULTS: We performed 287 psychrometric measurements in different situations. The mean ± SD gas absolute humidity at steady state during different conditions were the following: 1.6 ± 0.2 mg H2O/L for the medical gases, 4.5 ± 0.9 mg H2O/L at the Y-piece without humidifier, 9.1 ± 0.3 mg H2O/L at the Y-piece with heated humidifier turned off, and 34.2 ± 2.2 mg H2O/L at the Y-piece with the heated humidifier turned on. During the dynamic evaluation, after turning off the humidifier, humidity was < 30 mg H2O/L after a few minutes, attained 15 mg H2O/L after 15 min, and was below 10 mg H2O/L after 1 h but never reached the level of dry medical gases. After turning on the heated humidifier, the gas hygrometry reached 30 mg H2O/L after 5 min. CONCLUSIONS: When heated humidifiers are turned off, gas humidity levels are very low but not as low as medical gases. The clinical impact of repeated shutdowns is unknown. As recommended, heated humidifiers should never be turned off during nebulization.

Computer-Aided Intra-Operatory Positioning of an MRgHIFU Applicator Dedicated to Abdominal Thermal Therapy Using Particle Swarm Optimization.

PURPOSE: Transducer positioning for liver ablation by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is challenging due to the presence of air-filled organs or bones on the beam path. This paper presents a software tool developed to optimize the positioning of a HIFU transducer dedicated to abdominal thermal therapy, to maximize the treatment's efficiency while minimizing the near-field risk. METHODS: A software tool was developed to determine the theoretical optimal position (TOP) of the transducer based on the minimization of a cost function using the particle swarm optimization (PSO). After an initialization phase and a manual segmentation of the abdomen of 5 pigs, the program randomly generates particles with 2 degrees of freedom and iteratively minimizes the cost function of the particles considering 3 parameters weighted according to their criticality. New particles are generated around the best position obtained at the previous step and the process is repeated until the optimal position of the transducer is reached. MR imaging data from in vivo HIFU ablation in pig livers was used for ground truth comparison between the TOP and the experimental position (EP). RESULTS: As compared to the manual EP, the rotation difference with the TOP was on average -3.1 ± 7.1° and the distance difference was on average -7.1 ± 5.4 mm. The computational time to suggest the TOP was 20s. The software tool is modulable and demonstrated consistency and robustness when repeating the calculation and changing the initial position of the transducer.

Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma.

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8+PD-1+ T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome immune resistance of ovarian cancers.

Dual-Energy CT in Acute Stroke: Could Non-Contrast CT Be Replaced by Virtual Non-Contrast CT? A Feasibility Study.

Purpose: We aimed to evaluate whether virtual non-contrast cerebral computed tomography (VNCCT) reconstructed from intravenous contrast-enhanced dual-energy CT (iv-DECT) could replace non-contrast CT (NCCT) in patients with suspected acute cerebral ischemia. Method: This retrospective study included all consecutive patients in whom NCCT followed by iv-DECT were performed for suspected acute ischemia in our emergency department over a 1-month period. The Alberta Stroke Program Early CT Score (ASPECTS) was used to determine signs of acute ischemia in the anterior and posterior circulation, the presence of hemorrhage, and alternative findings, which were randomly evaluated via the consensus reading of NCCT and VNCCT by two readers blinded to the final diagnosis. An intraclass correlation between VNCCT and NCCT was calculated for the ASPECTS values. Both techniques were evaluated for their ability to detect ischemic lesions (ASPECTS <10) when compared with the final discharge diagnosis (reference standard). Results: Overall, 148 patients (80 men, mean age 64 years) were included, of whom 46 (30%) presented with acute ischemia, 6 (4%) presented with intracerebral hemorrhage, 11 (7%) had an alternative diagnosis, and 85 (59%) had no pathological findings. The intraclass correlation coefficients of the two modalities were 0.97 (0.96-0.98) for the anterior circulation and 0.77 (0.69-0.83) for the posterior circulation. The VNCCT's sensitivity for detecting acute ischemia was higher (41%, 19/46) than that of NCCT (33%, 15/46). Specificity was similar between the two techniques, at 94% (97/103) and 98% (101/103), respectively. Conclusions: Our results show that VNCCT achieved a similar diagnostic performance as NCCT and could, thus, replace NCCT in assessing patients with suspected acute cerebral ischemia.

Plasma and platelet lipidome changes in Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by the progressive accumulation of globotriaosylceramide (Gb3) leading to systemic manifestations such as chronic kidney disease, cardiomyopathy, and stroke. There is still a need for novel markers for improved FD screening and prognosis. Moreover, the pathological mechanisms in FD, which also include systemic inflammation and fibrosis, are not yet fully understood. METHODS: Plasma and platelets were obtained from 11 ERT (enzyme-replacement therapy)-treated symptomatic, 4 asymptomatic FD patients, and 13 healthy participants. A comprehensive targeted lipidomics analysis was conducted quantitating more than 550 lipid species. RESULTS: Sphingadiene (18:2;O2)-containing sphingolipid species, including Gb3 and galabiosylceramide (Ga2), were significantly increased in FD patients. Plasma levels of lyso-dihexosylceramides, sphingoid base 1-phosphates (S1P), and GM3 ganglioside were also altered in FD patients, as well as specific plasma ceramide ratios used in cardiovascular disease risk prediction. Gb3 did not increase in patients' platelets but displayed a high inter-individual variability in patients and healthy participants. Platelets accumulated, however, lyso-Gb3, acylcarnitines, C16:0-sphingolipids, and S1P. CONCLUSIONS: This study identified lipidome changes in plasma and platelets from FD patients, a possible involvement of platelets in FD, and potential new markers for screening and monitoring of this disease.

MiR-155-5p Differentially Regulates IL-13Rα1 and IL-13Rα2 Expression and Signalling, Driving Abnormal Lung Epithelial Cell Phenotype in Severe Asthma.

MiR-155-5p is known to increase in innate and adaptive immune cells in response to IL-13 and is associated with asthma severity. However, little is known about its role in airway structural cells. BECs isolated from healthy donors and severe asthma patients were stimulated with IL-13. MiR-155-5p expression and release were measured by RT-PCR in BECs and in their derived exosomes. Modulation of miR-155-5p in BECs was performed using transfection of miR-155-5p inhibitor and mimic. IL-13Rα1, IL-13Rα2, MUC5AC, IL-8 and Eotaxin-1 expression were measured by RT-PCR and western blot. BECs repair process was assessed by wound healing assay. IL-13Rα1 and IL-13Rα2 expression and downstream pathways were evaluated by western blot. Dual Luciferase assay was used to determine miR-155-5p target genes associated to IL-13 receptors signaling. BECs from severe asthma showed an increased expression and exosomal release of miR-155-5p at baseline that was amplified by IL-13 stimulation. BECs from asthmatics expressed more IL-13Rα1 and less IL-13Rα2 than healthy donors and IL-13Rα1 but not IL-13Rα2 induced miR-155-5p expression under IL-13 stimulation. MiR-155-5p overexpression favored MUC5AC, IL-8 and Eotaxin-1 through IL-13Rα1/SOCS1/STAT6 pathway to the detriment of a delayed repair process with a downregulated IL-13Rα2/MAPK14/c-Jun/c-Fos signaling. Dual Luciferase assay confirmed that miR-155-5p modulates both IL-13 receptors pathways by directly targeting SOCS1, c-Fos and MAPK14. MiR-155-5p is overexpressed in severe asthma BECs and regulates IL-13Rα1 and IL-13Rα2 expression and signaling, favoring expression of mucin and eosinophils related genes to detriment of airway repair. These results show that miR-155-5p may contribute to airway epithelial cell dysfunction in severe asthma.

Dorsal wrist ganglion: clinical and imaging correlation in symptomatic population based on high-field MRI.

OBJECTIVES: To determine prevalence in the symptomatic population of dorsal mucoid cysts centered on dorsal capsuloscapholunate septum (DCSS) using high-field magnetic resonance imaging (MRI) for anatomoclinical and epidemiological correlations. MATERIALS AND METHODS: This single-center retrospective study analyzed all 3-Tesla MRIs consecutively performed for painful wrists in 295 patients. Two blinded readers performed measurements. The protocol included T1 spin echo and 3D proton density sequences with fat saturation. Inter-observer reliability was assessed using kappa and intra-class correlation coefficients for cyst detection and volumetry, respectively. Disagreements concerning cyst detection were resolved by a consensus reading. Cyst size, relationship to extrinsic and scapholunate ligaments (SL), continuity of SL, minimum distance to the posterior interosseous nerve (PIN), cyst communication with joint, and anatomical classifications of cysts were analyzed. Correlation tests were performed to assess associations. RESULTS: Two-hundred ninety-five patients (mean age 39.6 +/- 15.6 (standard deviation), 161 males) were evaluated for detection of dorsal wrist cysts identified in 150/295. In this subgroup, the mean age was 38.7 years (15-75), the sex ratio of 0.6 (59% women), and the median volume cyst of 8.7 mm3 (0.52-2555). Cyst detection, volume, and major axis measurements showed very high agreement between observers, respectively, 0.89, 0.96, and 0.91. 42 patients had dorsal SL pain. A weak negative correlation was found between distance to PIN and dorsal SL pain (r = -0.2415; p < 0.05) and a weak positive correlation between Guérini's classification and dorsal SL pain (r = 0.2466; p < 0.05). CONCLUSION: High-field MRI is the modality of choice for the detection, anatomical, and volumetric assessment of dorsal cysts. Preoperative assessment will be aided by the proposed revised anatomical classification. CLINICAL RELEVANCE STATEMENT: High-field MRI is the modality of choice for the anatomical study of dorsal ganglion cysts. It allows the radiologist to accurately describe the anatomical relationships, size, and visibility of the pedicle, essential information for the surgeon's preoperative assessment. KEY POINTS: Dorsal mucoid wrist ganglion is a condition for which prevalence remains to be determined. High-field MRI is a reproducible imaging modality for the detection and assessment of dorsal wrist cysts. High-field MRI has a key role in the preoperative management of dorsal mucoid cysts.

Trapeziometacarpal joint imaging: Normal high-resolution MRI, US and CT compared with cadaveric specimens and pathological imaging findings.

INTRODUCTION: The trapeziometacarpal (TMC) joint is a complex joint, whose anatomy and function are different from the metacarpophalangeal joints of the long fingers. The stability of this joint is ensured at three levels by multiple structures: osteochondral, capsulo-ligamentous, and musculo-tendinous. The anatomical and biomechanical structures ensuring the stability of the TMC joint are perfectly evaluated on magnetic resonance imaging (MRI), with a high degree of confidence. All described ligaments are anatomically visible and perfectly assessed on MRI and ultrasound (US): the dorsoradial ligament, the posterior oblique ligament, the intermetacarpal ligament, the ulnar collateral ligament, the two bundles of the anterior oblique ligament (break ligament), as well as the superficial anterior oblique and deep anterior oblique ligaments. METHODOLOGY: This educational review assesses the TMC joint anatomy using high-field MRI and US compared with cadaveric specimens as well the biomechanics of this joint. In addition, it highlights pathological patterns of traumatic (sprain, dislocation, and fractures) and degenerative diseases. RESULTS AND CONCLUSION: Knowledge of TMC joint anatomy is crucial to the radiologists' understanding and assessment of various traumatic and degenerative pathologies, and thus helps clinicians and surgeons choose the appropriate treatment.

High-Resolution Magnetic Resonance Neurography at 7T: A Pilot Study of Hand Innervation.

The emergence of 7T clinical MRI technology has sparked our interest in its ability to discern the complex structures of the hand. Our primary objective was to assess the sensory and motor nerve structures of the hand, specifically nerves and Pacinian corpuscles, with the dual purpose of aiding diagnostic endeavors and supporting reconstructive surgical procedures. Ethical approval was obtained to carry out 7T MRI scans on a cohort of volunteers. Four volunteers assumed a prone position, with their hands (N = 8) positioned in a "superman" posture. To immobilize and maintain the hand in a strictly horizontal position, it was affixed to a plastic plate. Passive B0 shimming was implemented. Once high-resolution 3D images had been acquired using a multi-transmit head coil, advanced post-processing techniques were used to meticulously delineate the nerve fiber networks and mechanoreceptors. Across all participants, digital nerves were consistently located on the phalanges area, on average, between 2.5 and 3.5 mm beneath the skin, except within flexion folds where the nerve was approximately 1.8 mm from the surface. On the phalanges area, the mean distance from digital nerves to joints was approximately 1.5 mm. The nerves of the fingers were closer to the bone than to the surface of the skin. Furthermore, Pacinian corpuscles exhibited a notable clustering primarily within the metacarpal zone, situated on the palmar aspect. Our study yielded promising results, successfully reconstructing and meticulously describing the anatomy of nerve fibers spanning from the carpus to the digital nerve division, alongside the identification of Pacinian corpuscles, in four healthy volunteers (eight hands).

Drivers of coastal benthic communities in a complex environmental setting.

Analyzing the environmental factors affecting benthic communities in coastal areas is crucial for uncovering key factors that require conservation action. Here, we collected benthic and environmental (physical-chemical-historical and land-based) data for 433 transects in Taiwan. Using a k-means approach, five communities dominated by crustose coralline algae, turfs, stony corals, digitate, or bushy octocorals were first delineated. Conditional random forest models then identified physical, chemical, and land-based factors (e.g., light intensity, nitrite, and population density) relevant to community delineation and occurrence. Historical factors, including typhoons and temperature anomalies, had only little effect. The prevalent turf community correlated positively with chemical and land-based drivers, which suggests that anthropogenic impacts are causing a benthic homogenization. This mechanism may mask the effects of climate disturbances and regional differentiation of benthic assemblages. Consequently, management of nutrient enrichment and terrestrial runoff is urgently needed to improve community resilience in Taiwan amidst increasing challenges of climate change.

Evaluation of new predictive scores for sudden cardiac death in childhood hypertrophic cardiomyopathy in a French cohort.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is rare in children, and sudden cardiac death (SCD) is difficult to predict. Two prognostic scores - HCM Risk-Kids and Precision Medicine for Cardiomyopathy (PRIMaCY) - were developed to assess the risk of SCD in the next 5 years in children with HCM. AIMS: To test the ability of these scores to predict SCD in children with HCM. Also, to identify factors associated with a severe cardiac rhythmic event (SCRE) (ventricular fibrillation, sustained ventricular tachycardia, heart transplant for rhythmic reasons or SCD). METHODS: Retrospective, multicentre, observational study at 10 medical centres in the Nord-Pas-de-Calais region, France. RESULTS: This study included 72 paediatric patients with HCM during 2009-2019 who were followed for a median (interquartile range [IQR]) of 8.5 (5.0-16.2) years. Eleven patients (15.3%) presented with SCRE. HCM Risk-Kids was high, with a median (IQR) score of 6.2% (2.1-12.8%; significant threshold≥6.0%) and the PRIMaCY median (IQR) score was 7.1% (2.6-15.0%; significant threshold≥8.3%). The positive predictive value was only 27.1% (95% confidence interval [CI] 21.5-32.5%) for HCM Risk-Kids (with a threshold of≥6.0%) and 33.2% (95% CI 27.1-38.9%) for the PRIMaCY score (with a threshold of≥8.3%). The negative predictive values were 95.4% (95% CI 92.3-97.7%) and 93.0% (95% CI 89.8-96.2%), respectively. Three of 28 patients with an implantable cardioverter defibrillator (ICD) experienced complications (including inappropriate shocks). CONCLUSION: HCM Risk-Kids and the PRIMaCY score have low positive predictive values to predict SCD in paediatric patients. If used alone, they could increase the rate of ICD implantation and thus ICD complications. Therefore, the scores should be used in combination with other data (genetic and magnetic resonance imaging results).

Soft extracellular matrix drives endoplasmic reticulum stress-dependent S quiescence underlying molecular traits of pulmonary basal cells.

Cell culture on soft matrix, either in 2D and 3D, preserves the characteristics of progenitors. However, the mechanism by which the mechanical microenvironment determines progenitor phenotype, and its relevance to human biology, remains poorly described. Here we designed multi-well hydrogel plates with a high degree of physico-chemical uniformity to reliably address the molecular mechanism underlying cell state modification driven by physiological stiffness. Cell cycle, differentiation and metabolic activity could be studied in parallel assays, showing that the soft environment promotes an atypical S-phase quiescence and prevents cell drift, while preserving the differentiation capacities of human bronchoepithelial cells. These softness-sensitive responses are associated with calcium leakage from the endoplasmic reticulum (ER) and defects in proteostasis and enhanced basal ER stress. The analysis of available single cell data of the human lung also showed that this non-conventional state coming from the soft extracellular environment is indeed consistent with molecular feature of pulmonary basal cells. Overall, this study demonstrates that mechanical mimicry in 2D culture supports allows to maintain progenitor cells in a state of high physiological relevance for characterizing the molecular events that govern progenitor biology in human tissues. STATEMENT OF SIGNIFICANCE: This study focuses on the molecular mechanism behind the progenitor state induced by a soft environment. Using innovative hydrogel supports mimicking normal human lung stiffness, the data presented demonstrate that lung mechanics prevent drift while preserving the differentiation capabilities of lung epithelial cells. Furthermore, we show that the cells are positioned in a quiescent state in the atypical S phase. Mechanistically, we demonstrate that this quiescence: i) is driven by calcium leakage from the endoplasmic reticulum (ER) and basal activation of the PERK branch of ER stress signalling, and ii) protects cells from lethal ER stress caused by metabolic stress. Finally, we validate using human single-cell data that these molecular features identified on the soft matrix are found in basal lung cells. Our results reveal original and relevant molecular mechanisms orchestrating cell fate in a soft environment and resistance to exogenous stresses, thus providing new fundamental and clinical insights into basal cell biology.

Azithromycin resistance in Escherichia coli and Salmonella from food-producing animals and meat in Europe.

OBJECTIVES: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS: mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS: Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales.

Pain reflects the informational value of nociceptive inputs.

ABSTRACT: Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signaled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants' pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is, when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.

Temporal Bone Fractures and Related Complications in Pediatric and Adult Cranio-Facial Trauma: A Comparison of MDCT Findings in the Acute Emergency Setting.

PURPOSE: The purpose of this study was to analyze the prevalence of and complications resulting from temporal bone fractures in adult and pediatric patients evaluated for cranio-facial trauma in an emergency setting. METHODS: A retrospective blinded analysis of CT scans of a series of 294 consecutive adult and pediatric patients with cranio-facial trauma investigated in the emergency setting was conducted. Findings were compared between the two populations. Preliminary reports made by on-call residents were compared with the retrospective analysis, which was performed in consensus by two experienced readers and served as reference standard. RESULTS: CT revealed 126 fractures in 116/294 (39.5%) patients, although fractures were clinically suspected only in 70/294 (23.8%); p < 0.05. Fractures were longitudinal, transverse and mixed in 69.5%, 10.3% and 19.8% of cases, respectively. Most fractures were otic-sparing fractures (95.2%). Involvement of the external auditory canal, ossicular chain and the osseous structures surrounding the facial nerve was present in 72.2%, 8.7% and 6.3% of cases, respectively. Temporal bone fractures extended into the venous sinuses/jugular foramen and carotid canal in 18.3% and 17.5% of cases, respectively. Vascular injuries (carotid dissection and venous thrombosis) were more common in children than in adults (13.6% versus 5.3%); however, the observed difference did not reach statistical significance. 79.5% of patients with temporal bone fractures had both brain injuries and fractures of the facial bones and cranial vault. Brain injuries were more common in adults (90.4%) than in children (63.6%), p = 0.001. Although on-call residents reliably detected temporal bone fractures (sensitivity = 92.8%), they often missed trauma-associated ossicular dislocation (sensitivity = 27.3%). CONCLUSIONS: Temporal bone fractures and related complications are common in patients with cranio-facial trauma and need to be thoroughly looked for; the pattern of associated injuries is slightly different in children and in adults.

MRI classification of uterosacral ligament involvement in endometriosis: the Hôtel-Dieu classification.

OBJECTIVE: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep infiltrating endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis. METHODS: Twenty-two women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analysed retrospectively, blinded to histopathology, and a classification of the preoperative aspect of USLs linked to PPVs was designed. RESULTS: According to their aspects, 6 radiological types of USL were identified. The "L-category" corresponded to linear types with regular or irregular margins, including types 1, 2, 3A, and 3B. The "N-category" corresponded to haemorrhagic or nodular types, including types 4, 5A, 5B, and 6. For the L-category, PPVs ranged from 75% to 88%, depending on the USL radiological type. For the N-category, PPVs were 100% for each type. In women with endometriosis symptoms, MRI underestimated USL involvement, especially for type 1. Among the 6 uteri with lateral deviation, only one false-positive result concerning the stretched USL was induced. CONCLUSIONS: In women with endometriosis symptoms, our MRI classification identified 2 USL categories, corresponding to 2 kinds of PPV; in these symptomatic patients, a normal MRI does not rule out a DIE diagnosis. ADVANCES IN KNOWLEDGE: Our MRI classification of USL involvement in endometriosis may be used as a non-invasive staging of the disease, making it much clearer for clinicians and patients. Hence, we are able to propose a suitable diagnostic and therapeutic procedure for each radiological type.

Mental health and burnout during medical school: Longitudinal evolution and covariates.

BACKGROUND: Medical students' rate of depression, suicidal ideation, anxiety, and burnout have been shown to be higher than those of the same-age general population. However, longitudinal studies spanning the whole course of medical school are scarce and present contradictory findings. This study aims to analyze the longitudinal evolution of mental health and burnout from the first to the last year of medical school using a wide range of indicators. Moreover, biopsychosocial covariates that can influence this evolution are explored. METHOD: In an open cohort study design, 3066 annual questionnaires were filled in by 1595 different students from the first to the sixth year of the Lausanne Medical School (Switzerland). Depression symptoms, suicidal ideation, anxiety symptoms, stress, and burnout were measured along with biopsychosocial covariates. The longitudinal evolution of mental health and burnout and the impact of covariates were modelled with linear mixed models. RESULTS: Comparison to a same-aged general population sample shows that medical students reported significantly more depression symptoms and anxiety symptoms. Medical students' mental health improved during the course of the studies in terms of depression symptoms, suicidal ideation, and stress, although suicidal ideation increased again in the last year and anxiety symptoms remained stable. Conversely, the results regarding burnout globally showed a significant worsening from beginning to end of medical school. The covariates most strongly related to better mental health and less burnout were less emotion-focused coping, more social support, and more satisfaction with health. CONCLUSION: Both improvement of mental health and worsening of burnout were observed during the course of medical school. This underlines that the beginning and the end of medical school bring specific challenges with the first years' stressors negatively impacting mental health and the last year's difficulties negatively impacting burnout.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

BACKGROUND: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. METHODS: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. RESULTS: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002). CONCLUSION: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Current iron therapy in the light of regulation, intestinal microbiome, and toxicity: are we prescribing too much iron?

Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron deficiency, while in industrialized nations, reduced food intake and dietary preferences affect iron status. Other causes that can lead to iron deficiency are conditions and diseases that result in reduced intestinal iron absorption and blood loss. In addition, iron absorption and its bioavailability are influenced by the composition of the diet. Individuals with increased iron needs, including infants, adolescents, and athletes, are particularly vulnerable to deficiency. Severe iron deficiency can lead to anemia with performance intolerance or shortness of breath. In addition, even without anemia, iron deficiency leads to mental and physical fatigue, which points to the fundamental biological importance of iron, especially in mitochondrial function and the respiratory chain. Standard oral iron supplementation often results in gastrointestinal side effects and poor compliance. Low-dose iron therapy seems to be a valid and reasonable therapeutic option due to reduced hepatic hepcidin formation, facilitating efficient iron resorption, replenishment of iron storage, and causing significantly fewer side effects. Elevated iron levels influence gut microbiota composition, favoring pathogenic bacteria and potentially disrupting metabolic and immune functions. Protective bacteria, such as bifidobacteria and lactobacilli, are particularly susceptible to increased iron levels. Dysbiosis resulting from iron supplementation may contribute to gastrointestinal disorders, inflammatory bowel disease, and metabolic disturbances. Furthermore, gut microbiota alterations have been linked to mental health issues. Future iron therapy should consider low-dose supplementation to mitigate adverse effects and the impact on the gut microbiome. A comprehensive understanding of the interplay between iron intake, gut microbiota, and human health is crucial for optimizing therapeutic approaches and minimizing potential risks associated with iron supplementation.