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We aimed to compare the effects of periodic resistance training (RT) and continuous RT on muscle strength and size. Fifty-five healthy, untrained participants (age 32 ± 5 years) were randomized to periodic (PRT, n = 20 completed the study, 45% females) or continuous (CRT, n = 22 completed the study, 45% females) groups. PRT completed a 10-week RT, a 10-week detraining, and a second identical 10-week RT. CRT began with a 10-week non-RT, followed by a 20-week RT. RT included twice-weekly supervised whole-body RT sessions. Leg press (LP) and biceps curl (BC) one repetition maximum (1RM), countermovement jump (CMJ) height, muscle cross-sectional area (CSA) of vastus lateralis (VL), and biceps brachii (BB) using ultrasound imaging were measured twice at the beginning and every fifth week during the intervention. Both groups increased (p < 0.001) 1RM in LP and BC, CSA in VL and BB, and CMJ height with no differences between the groups. In PRT, 1RM in LP and BC, CSA in VL and BB, and CMJ height decreased during detraining (p < 0.05). During the first 5 weeks of retraining in PRT, increases in LP 1RM, and VL and BB CSA were greater than in CRT during Weeks 10-15 of their CRT (p < 0.01). PRT and CTR ended up in similar postintervention adaptations, as decreased muscle strength and size during detraining in PRT regained rapidly during retraining. Our results therefore suggest that trainees should not be too concerned about occasional short-term training breaks in their daily lives when it comes to lifelong strength training. Trial Registration: ClinicalTrials.gov identifier: NCT05553769., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Purpose: To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene., Methods: A prospective study with a 1-year follow-up was conducted. A total of 104 patients (160 eyes) with FECD and an equivalent number of age- and sex-matched control subjects without FECD were included. At inclusion, the corneas were graded using the modified Krachmer grade (KG) and patients were genotyped for the number of trinucleotide repeats (TNRs) in the TCF4 gene by the short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, and the Visual Function and Corneal Health Status using a visual disability instrument were measured on 2 visits at 1-year intervals., Results: KGs ranged from 1 to 6, and 46% of eyes had grades 1 to 4. 71% of the patients harbored TNR expansion (>40) versus 13% in control subjects ( P < 0.001). Severity at inclusion was higher in the presence of TNR expansion when considering eyes independently (mean grade ±SD, 4.08 ± 1.42) without TNR expansion and 4.66 ± 1.27 with TNR expansion ( P = 0.024). In 1 year, the ETDRS score significantly decreased by -2.97 (95% confidence interval -4.69 to -1.26, P = 0.001) and the ETDRS score with glare by -4.25 (95% confidence interval -6.22 to -2.27, P < 10 -5 ). There was no relationship between the rate of decline and TNR expansion or KG. Central corneal thickness and Visual Function and Corneal Health Status scores did not significantly vary., Conclusions: It is possible to measure a subtle progression of FECD over a period as short as 1 year. We did not find a relationship between the presence of TNR expansion and the speed of deterioration over 1 year. This work should facilitate the design of future clinical trials on FECD., Competing Interests: Conflicts of interest statement: P. Gain, N. Koizumi, N. Okumura, and G. Thuret were shown using the ICMJE disclosures form. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Loss of regulation of the autonomic nervous system is found in many diseases from the age of 50 to 60 yr and even more so in older patients. The imbalance is usually manifested by an increase in sympathetic tone, long considered to be the most deleterious element in terms of cardiac rhythmic risk, but also by a reduction in the effectiveness of short-term regulation of the baroreflex arc (partial loss of parasympathetic control). Techniques for analysing this autonomic disorder by analysing heart rate regulation are widely available in outpatient clinics and provide interesting indicators of cardiovascular and cerebrovascular risk. Deceleration capacity of cardiac autonomic control has been identified for its prognostic role in high-risk patients and in the general population. Further research is indicated to assess the value of this marker in anaesthetic risk management by targeting procedures with greater risk of intraoperative and postoperative autonomic dysfunction., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Anorexia nervosa (AN) in older adult women is primarily described through reviews or case reports focusing on psychiatric traits, with no comprehensive studies evaluating their complete nutritional and hormonal profiles. This study aimed to describe a group of women with anorexia nervosa aged above 35 years old (AN35), and compare them with young women with anorexia nervosa (ANY) and normal-weight control participants., Method: Anthropometric, metabolic, nutritional, and psychiatric parameters were collected and compared among three groups of women: 50 AN35, 37 ANY, and 38 controls., Results: AN35 exhibited a mean disease duration of 271 ± 19 months, with 94% chronic forms and 58% restrictive types. Despite having similar BMI as ANY, AN35 displayed more altered parameters, including higher liver enzymes (p = 0.007), free T 3 (p = 0.0046) and leptin (p < 0.0001); and lower albumin (p = 0.0029), and white cells (p < 0.0001). AN35 showed significant heterogeneity in hormonal adaptation, such as free T 3. Half of the patients aged above 51 years revealed high gonadotropin levels despite being undernourished. Additionally, AN35 groups presented with 50% of bones fractures, decreased T-scores under -2.5 (p < 0.0001 for femoral), and altered micro architectural HRPQT parameters compared to ANY., Conclusion: Anorexia nervosa in older adult women is predominantly chronic. Nutritional parameters changes with age suggests a significant heterogeneity and possible adaptation of energy balance and bodyweight set point for others. Complications may be severe, altering the quality of life, and sometimes potentially lethal. These findings highlight the potential adaptation of energy balance with age, and should assist clinicians in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To demonstrate the feasibility and efficacy  of a new video-observation training method (intensive visual simulation) to improve upper limb function., Design: Small sample, randomized, evaluator-blind, monocentric study., Patients: Seventeen early subacute ischaemic stroke patients with complete hemiplegia were  randomly assigned to the therapeutic group (n = 8) or control group (CG, n = 9)., Methods: Thirty sessions of intensive visual simulation combined with corrected visual feedback (therapeutic group) or uncorrected visual feedback (control group) were performed over 6 weeks on top of a standard rehabilitation programme., Main Outcome Measure: 400-point hand assessment test (400p-HA)., Secondary Outcome Measures: Box and Blocks (B&B), Purdue Pegboard test, Minnesota., Results: The 400p-HA test improved significantly from T0 to 6 months for both groups, with a significant difference between groups at 3 months (MW-UT p = 0.046) and 4 months (MW-UT p = 0.046) in favour of the therapeutic group. One-phase exponential modelling of 400p-HA showed a greater plateau for the therapeutic group (F test p = 0.0021). There was also faster recovery of the ability to perform the B&B tests for the therapeutic group (log-rank test p = 0.03)., Conclusion: This study demonstrated the feasibility and potential efficacy of an intensive visual simulation training programme to improve upper limb  function in subacute stroke patients. A larger study is needed to confirm these results.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

Background: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts., Objectives: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates., Methods: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates., Results: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF., Conclusions: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications., Competing Interests: Funding Support and Author Disclosures Dr Haissaguerre has received grant support from Biosense Webster. Dr Marijon has received grant support and consulting fees from Medtronic, Boston Scientific, Abbott, Microport, Biotronik, and Zoll. Pr Gandjbakhch has received lecture fees from Biotronik; and consulting fees from Medtronic, Microport, and Abbott. Dr Tilz is a consultant for Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; has received speaker honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and Lifetech; and has received research grants from Abbott, Biosense Webster, and Lifetech. Dr Roten has received research grants from Medtronic, the Swiss National Foundation, the Swiss Heart Foundation, the Immanuel and Ilse Straub Foundation, and the Sitem Insel Support Fund, all for work outside the submitted study; and has received speaker/consulting honoraria from Abbott and Medtronic. Dr Reichlin has receivedresearch grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Sitem Insel support funds, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study; and has received speaker/consulting honoraria or travel support from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study. Support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic for work outside the submitted study. Dr Sacher has receivedspeaking honorarium from Abbott, Boston Scientific, and Biosense Webster; and equity from InHeart. Dr Nogami has received lecture fees from Abbott; and endowments from Medtronic. Dr Massoullié has received lecture fees from Boston Scientific, Biosense Webster, and Abbot. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest No conflict.

Pediatric bone injuries are traditionally diagnosed using radiography. However, ultrasonography is emerging as an alternative due to its speed and minimal invasiveness. This study assessed the diagnostic capabilities of ultrasound before radiography in a group of 186 children with suspected long bone fractures at Saint Etienne University Hospital (Saint-Priest-en-Jarez, France). Patients with open trauma and severe deformity were excluded. Ultrasonography demonstrated 88.2% sensitivity and 86.4% specificity, with better results for forearm injuries. Of the 186 cases, 162 were consistent with radiography and 24 varied. Factors influencing an accurate diagnosis included the presence of indirect signs, operator experience, and examination duration, while indirect signs often led to misinterpretation. Although ultrasound cannot completely replace radiography due to its limitations in identifying deeper fractures, this study revealed its substantial efficacy and ease, supporting its potential utility in pediatric trauma emergencies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Since the late 2000s, Europe has granted approval for various thrombotic risk-related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident., Objectives: The study aims to take stock of current reversal strategies for DOACs, with a particular emphasis on the latest compounds that have been developed or are currently under development., Methods: For obtaining information regarding the ongoing reversal strategies and the compounds under development, we referred to ClinicalTrials website, PubMed, and Google Scholar., Results: In 2024, two specific antidotes to DOACs have already received approval when reversal of anticoagulation is needed owing to life-threatening or uncontrolled bleeding: idarucizumab that reverses the effects of dabigatran, and andexanet alfa, designed to counteract activated factor X inhibitors such as apixaban and rivaroxaban. Furthermore, ciraparantag, a potential universal reversal agent, is currently in advanced stages of clinical development. Concerns remain regarding the safety of specific reversal agents, especially concerning the risk of thrombosis. Additionally, the cost of these antidotes remains high. Consequently, nonspecific strategies to counteract anticoagulant medications, including activated charcoal, hemodialysis, and concentrates of coagulation factors, still have utility., Conclusion: With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Background: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition., Methods: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery., Results: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86])., Conclusions: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916)., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aim: To investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD)., Methods: Descemet's membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and pseudophakic bullous keratopathy (PBK). They were compared with healthy samples obtained from body donation to science. Samples were fixed in 0.5% paraformaldehyde and flat mounted. Surface roughness of DMs was quantified using CCM and the AltiMap software that provided the maximum peak (S p ) and valley (S v ) heights, the mean square roughness (R q ) and the asymmetry coefficient (S sk )., Results: The physiological roughness of healthy samples was characterised by an R q of 0.12±0.05 µm, which was two times rougher than in PBK (R q =0.06±0.03 µm), but both were still flat with a symmetrical distribution between peaks and valleys (S sk close to 0, n peaks =n valleys ), smaller than 1 µm. In FECD, the maximum peak height was 5.10±2.40 µm, up to 5.8 and 8.3 times higher than the control and PBK, respectively. The maximum valley depth was half than the peak (2.28±0.89 µm). The surface with guttae was very rough (R q =0.45±0.14 µm) and the S sk =1.84± 0.43 µm, greater than 0, confirms an asymmetric surface with high peaks and low valleys (n peaks >n valleys ). Moreover, the CCM provided quantitative parameters allowing to distinguish different types of guttae from different patients., Conclusions: CCM is an innovative approach to describe and quantify different morphologies of guttae. It could be useful to analyse the different stages of FECD and define subgroups of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Introduction: Sexual health is essential to the overall health. People suffering from severe mental illness (SMI) experience a deterioration in their sexual health. These patients and their caregivers seem unwilling to engage in a dialogue concerning sexual health within the context of mental health care., Aim: The study investigated nurses' and care assistants' beliefs and attitudes regarding the sexual health of people with SMI on the psychiatric care pathway., Methods: Twenty semi-structured interviews were conducted with nurses and care assistants. Data were subject to a thematic analysis., Results: Three main themes emerged: (1) The formalization of the care approach towards people with a SMI in hospitals; (2) the place given to sexual health in psychiatry units; (3) nurses and care assistants are not equipped to deal with patients' sexual health., Discussion: Caregivers consider that sexual health is a fundamental right and an indicator of good health. They nevertheless believe that the psychiatric hospital remains a place of acute care where sexual health is not considered., Implication for Practice: This research justifies that it is necessary to question the representations of nurses and care assistants before implementing a tailored intervention that integrates the consideration of sexual health into the holistic care of the patient on the psychiatric care pathway., (© 2023 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

Introduction: Africa is experiencing a gradual demographic shift due to rising life expectancy and increasing urbanisation. In sub-Saharan Africa, elderly individuals typically reside with their children. The rise in life expectancy by almost a decade and the prevalence of precarious living conditions raise concerns about the sustainability of the healthcare system, which has traditionally relied on intergenerational solidarity., Methods: The research aims to analyse the evolving role of older adults in Cameroonian society and to examine the potential impact of this change on intergenerational relationships and the health of older adults. A qualitative methodology was employed, using intergenerational focus groups in Cameroon., Results: Traditionally, older adults held a central role in knowledge transmission through discourse. However, the modernisation of society is challenging this position.The emergence of new technologies, particularly communication tools, is leading to a questioning of older adults' experiential knowledge. Societal changes are contributing to a decline in respect for older adults in discourse. Older adults deplore these societal changes and fear for their place in society while young people are questioning the central role of older people in society., Discussion: These changes could reduce the sense of usefulness of older people, with negative consequences for their health. Several studies have highlighted the impacts of ageism on the health of older adults in industrialised countries. However, there are little data on the impact of the marginalisation of older adults on their health in industrialising societies. Further research is needed to study the impact on the health of older adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Speculum examination is an intrusive practice in the clinical care of women. It requires privacy and patients may experience discomfort or anxiety related to the procedure, which can result in delays or avoidance of necessary healthcare. Speculum self-insertion originated in the United States in the 1970s as part of the self-help movement. However, this clinical practice is largely unknown among healthcare providers and has rarely been assessed., Aim: This study investigates the women's views and healthcare providers' experiences of the self-insertion method., Method: A qualitative study was conducted between December 2021 and October 2022, including fieldwork combining semi-structured interviews (10 women) and focus groups associated with individual interviews of 13 healthcare providers. The data collected were independently coded by 2 authors and analysed using an inductive approach and grounded theory method., Results: Speculum self-insertion was described as a way to decrease discomfort and facilitate speculum insertion. Self-insertion was proposed as a means of allowing women to participate in the examination, reducing their vulnerability against power imbalances in the doctor-patient relationship. Both patients and healthcare providers have reported that speculum self-insertion is a method that can contribute to improving trust and communication during the examination., Conclusion: The practice of speculum self-insertion during the consultation is an alternative to traditional practitioner insertion and may be offered to all women by any practitioner who wishes to use this technique., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with Anorexia Nervosa (AN) and athletes share intense physical activity and pituitary hormonal disturbances related to absolute (AN) or relative (athletes) undernutrition. Pituitary gland (PG) structure evaluations in those conditions are scarce, and did not differentiate anterior from posterior lobe. We evaluated the structure-function relationship of anterior and posterior PG in AN and athletes, and potential reversibility of this alteration in a group of weight-recovered patients (AN&#95;Rec). Manual delineation of anterior (AP) and posterior (PP) PG was performed on T1-weighted MR images in 17 women with AN, 15 women with AN&#95;Rec, 18 athletes women and 25 female controls. Anthropometric, hormonal, and psychometric parameters were explored and correlated with PG volumes. AP volume (APV) was lower in AN (448 ± 82 mm 3 ), AN&#95;Rec (505 ± 59 mm 3 ), and athletes (540 ± 101 mm 3 ) vs. Controls (615 ± 61 mm 3 , p < 0.00001, p < 0.00001 and p = 0.02, respectively); and smaller in AN vs. AN&#95;Rec (p = 0.007). PP volume did not show any differences between the groups. APV was positively correlated with weight (R = 0.36, p = 0.011) in AN, and luteinizing hormone (R = 0.35, p = 0.014) in total group. In AN, mean growth hormone (GH) was negatively correlated with global pituitary volume (R = 0.31, p = 0.031) and APV (R = 0.29, p = 0.037). Absolute and relative undernutrition led to a decreased anterior pituitary gland volume, which was reversible with weight gain, correlated with low bodyweight, and blockade of gonadal hypothalamic-pituitary axis. Intriguing inverse correlation between anterior pituitary gland volume and GH plasma level could suggests a low storage capacity of anterior pituitary gland and increased reactivity to low insulin-like growth factor type 1., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This systematic review aims to summarize the impact of vaccination against influenza, shingles, and pneumococcus on the incidence on the risk of cardiovascular events in the elderly. This protocol was developed in accordance with PRISMA guidelines. We conducted a literature search and identified all relevant articles published regarding the matter up to September 2022. We retrieved 38 studies (influenza vaccine = 33, pneumococcal vaccine = 5, and zoster vaccine = 2). A total of 28 and 2 studies have shown that influenza and pneumococcal vaccines significantly lower the risk of cardiovascular disease in the elderly. Also, repeated influenza vaccination shows a consistent and dose-dependent protective effect against acute coronary syndromes and stroke. Moreover, dual influenza and pneumococcal vaccination was associated with lower risks of some cardiovascular events (stroke, congestive heart failure, ischemic heart disease, and myocardial infarction). However, the impact of PCV13 on cardiovascular events has not been studied, nor has the currently recommended vaccination schedule (PCV13 + PPV23). As for herpes zoster vaccination, only the protective effect against stroke has been studied with the live attenuated herpes zoster vaccine, but no studies have been conducted with the recombinant subunit herpes zoster vaccine. This review outlines the benefits of the vaccines mentioned above beyond their preventive action on infectious diseases. It is intended for health professionals who wish to inform and advise their elderly patients., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

Within-host spread of pathogens is an important process for the study of plant-pathogen interactions. However, the development of plant-pathogen lesions remains practically difficult to characterize beyond the common traits such as lesion area. Here, we address this question by combining image-based phenotyping with mathematical modelling. We consider the spread of Peyronellaea pinodes on pea stipules that were monitored daily with visible imaging. We assume that pathogen propagation on host-tissues can be described by the Fisher-KPP model where lesion spread depends on both a logistic growth and an homogeneous diffusion. Model parameters are estimated using a variational data assimilation approach on sets of registered images. This modelling framework is used to compare the spread of an aggressive isolate on two pea cultivars with contrasted levels of partial resistance. We show that the expected slower spread on the most resistant cultivar is actually due to a significantly lower diffusion coefficient. This study shows that combining imaging with spatial mechanistic models can offer a mean to disentangle some processes involved in host-pathogen interactions and further development may allow a better identification of quantitative traits thereafter used in genetics and ecological studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Leclerc et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: The authors have no funding or conflicts of interest to declare

Background: In recent years, knowledge about cancer associated thrombosis has evolved considerably., Methods: Practical guidelines were drafted on the initiative of the INNOVTE FCRIN Network, led by the French Speaking Society of Respiratory Diseases (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of different scientific societies practicing in various settings. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS)., Results: After a literature review, guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease and management from the data of available clinical trials and observational studies : epidemiology, initial treatment, treatment duration, extended treatment, recurrent thrombosis, central venous catheter thrombosis, incidental thrombosis, treatment in case of thrombocytopenia., Conclusion: These evidence-based guidelines are intended to guide the practical management of patients with cancer associated thrombosis., Competing Interests: Declaration of Competing Interest I. Mahé: Grants: BMS, Pfizer; Consulting fees : BMS/Pfizer, Leo-Pharma, Sanofi, Aventis, Astra-Zeneca; Support for attending meeting: BMS/Pfizer, Leo-Pharma. P. Girard: Payment or Honoria for lectures: Leo-Pharma, MBS/Pfizer, Bayer; Support for attending meeting: Leo-Pharma; L. Bertoletti: Grants: MSD, Bayer; Payment or Honoria for lectures: Leo-Pharma, MBS/Pfizer, MSD, Viatris; Support for attending meeting: Leo-Pharma, MBS/Pfizer, MSD, Viatris. S. Laporte: Consulting fees: Ferring; Payment or Honoria for lectures: Pfizer, Lilly. F Couturaud : Grants: Bayer, BMS, Pfizer, GSK, Astra, Leo-Pharma, MSD, Roche; Payment or Honoria for lectures: Bayer, BMS, GSK, Astra, Leo-Pharma, Sanofi, MSD; Support for attending meeting: Astra, MSD. P. Mismetti : None O. Sanchez : Consulting fees: Bayer, BMS/Pfizer, Leo-Pharma, Sanofi/Aventis, Boehringer, Inari, Boston Scientifics, MSD; Payment or Honoria for lectures: Bayer, BMS/Pfizer, Leo-Pharma, Sanofi Aventis, Boehringer, Inari, Boston Scientifics, MSD, Viatris; Support for attending meetings and/or travel: Oxyvie, BMS/Pfizer, (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Fatigue is the most common and disabling symptom in multiple sclerosis (MS), being reported by 55% to 78% of patients with MS (PwMS). Etiology of MS-related fatigue remains poorly understood, but an increased neuromuscular fatigability (i.e., greater loss of torque during exercise) could contribute to this phenomenon. This study aimed to characterize the correlates of MS-related fatigue in PwMS using a comprehensive group of physiological and psychosocial measures, with a particular focus on fatigability., Methods: Forty-two relapsing-remitting PwMS and 20 healthy subjects were recruited. PwMS were assigned in two groups (high (HF) and low (LF) fatigue) based on two fatigue questionnaires (Fatigue Severity Scale and Modified Fatigue Impact Scale). The main outcomes of this study are derived from incremental cycling completed to task failure (i.e., inability to pedal around 60 rpm). Maximal voluntary contraction (MVC), rating of perceived exertion, and central and peripheral parameters measured using transcranial magnetic and peripheral nerve stimulation were assessed in the knee extensor muscles before, during, and after the fatiguing task. Other potential correlates of fatigue were also tested., Results: MVC torque decreased to a greater extent for the HF group than LF group after the third common stage of the incremental fatiguing exercise (-15.7% ± 6.6% vs -5.9% ± 13.0%, P < 0.05), and this occurred concurrently with a higher rating of perceived exertion for HF (11.8 ± 2.5 vs 9.3 ± 2.6, P < 0.05). Subjective parameters (depression, quality of life) were worse for HF compared with LF and healthy subjects ( P < 0.001). Moreover, MVC torque loss at the final common stage and maximal heart rate explained 29% of the variance of the Modified Fatigue Impact Scale., Conclusions: These results provide novel insight into the relationship between MS-related fatigue and fatigability among PwMS. The HF group exhibited greater performance fatigability, likely contributing to a higher perceived exertion than the LF group when measured during a dynamic task., (Copyright © 2023 by the American College of Sports Medicine.)

Small extracellular vesicles (EVs) are characterized by the membrane expression of CD63, CD81 and CD9 tetraspanins. Their size is inferior to 200 nm. They share the same characteristics as the native cells and are found in human fluids. Specific membrane protein biomarkers expressed on small EV are useful for the diagnosis of tumoural pathologies. Clear cell renal cell carcinoma (CCRCC) is diagnosed by imaging examinations and/or tissue biopsy. Carbonic anhydrase IX (CAIX) is a powerful biomarker of CCRCC. The detection of CAIX on small EV from the urine of patients could constitute a liquid biopsy for CCRCC. We have set up a specific protocol for the preparation, the immunostaining characterization and the transmission electron microscopy observation of small EVs isolated from the urine of CCRCC patients. The background labelling was significantly reduced. We successfully detected biomarkers on urinary small EVs from CCRCC patients. This technique could be extended with antibodies directed against other EV biomarkers for the detection and the monitoring of cancer diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Data on recurrence after the end of anticoagulation for a first event of cancer-associated venous thromboembolism (VTE) are scarce., Objectives: Our aim was to assess predictors of VTE recurrence during a 1-year follow-up period., Methods: This study is an analysis of RIETE, an international, multicenter, prospective cohort study of patients diagnosed with VTE. Patients had to have active cancer at the time of VTE and to have withdrawn from anticoagulation after 3 months of full treatment. Analyses were performed using Fine and Gray models, with death as a competing risk, and multiple imputation of missing data was performed by chained equations., Results: Among 14 318 patients with cancer-associated VTE, 3414 had undergone time-limited anticoagulation for at least 3 months. The cumulative incidence function for recurrent VTE was 10.2% (95% CI, 9.1-11.5) at 1 year. Chronic kidney disease (a subhazard ratio [sHR] of 1.08 for 10-mL/min decrease in glomerular filtration rate; 95% CI, 1.02-1.14); cancer of the lung, brain, stomach, esophagus, liver, or ovary (sHR, 3.56; 95% CI, 1.07-11.80; compared with cancer of the oropharynx, larynx, or melanoma); cancer of the pancreas, the biliary tract, or of unknown origin (sHR, 6.86; 95% CI, 1.89-24.85); inferior vena cava filter (sHR, 3.16; 95% CI, 1.75-5.71); postthrombotic syndrome (sHR, 2.09; 95% CI, 1.06-4.15); and residual pulmonary thrombotic obstruction (sHR, 2.58; 95% CI, 1.38-4.82) were predictive of recurrence. Surgery during the 2 months before VTE was predictive of absence of recurrence (sHR, 0.60; 95% CI, 0.40-0.92)., Conclusion: One year after anticoagulant cessation for cancer-associated VTE, approximately 10% of patients experienced recurrence. Discontinuing anticoagulant therapy seems safe, mainly in surgery-associated VTE., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess tocilizumab (TCZ) as an emergent treatment for corticosteroid-resistant active Graves' orbitopathy (GO)., Methods: We conducted a single-centre prospective study. We assessed TCZ in patients with active corticosteroid-resistant GO. Each patient received intravenous TCZ every four weeks until symptom stabilization. Our primary outcome was GO activity evaluated by the clinical activity score (CAS). The secondary outcomes included variation in thyroid-stimulating immunoglobulin (TSI)., Results: We included ten patients. Three patients had compressive neuropathy with visual field impairment and vision loss. CAS improved significantly in 100% of the patients included in the analysis, with a decrease in the mean CAS of 4.5 ± 1.2 points ( p  = .003). There was a significant decrease in the TSI after therapy, from 21.7 ± 22.9 at baseline to 4.0 ± 3.3 ( p  = .006). A mean of three infusions was necessary to drastically decrease the TSI amount. The baseline mean before TCZ was 4.7 ± 1.2 and the final mean after TCZ IV infusion was 0.2 ± 0.4., Conclusions: Our study showed the efficiency of TCZ in patients with GO resistant to corticosteroid therapy, as shown in previous studies. Our present work adds two important pieces of information: TCZ might be particularly useful for GO with compressive neuropathy and it is efficient regardless of initial TSI level. Considering the numerous advantages over steroids (high response rate and lower rate of adverse events), further randomized controlled trials should be conducted to assess the possible place of TCZ as a first-line treatment.

Objective: To systematically review randomised controlled trials (RCTs) using a wearable physical activity monitoring device as an intervention to increase daily walking activity and improve physical capacities in patients with cardiovascular disease (CVD)., Design: Systematic review and meta-analysis of RCTs., Data Sources: PubMed, Embase and Web of Science from inception to June 2022., Eligibility Criteria: Randomised controlled studies including patients with CVD over 18 years of age at the end of a cardiac rehabilitation programme comparing an intervention group using a wearable physical activity monitoring device with feedback with usual care or with a control group receiving no feedback on their physical activity and reporting a change in the daily number of steps and/or a change in the distance covered in the 6-minute walk test (6-MWT) or a change in peak oxygen uptake (V̇O2 peak ) as endpoints., Results: Sixteen RCTs were included. The intervention of wearing a physical activity monitoring device with feedback significantly improved daily number of steps compared with controls (standardised mean difference (SMD) 0.85; 95% CI (0.42; 1.27); p<0.01). The effect was greater when the duration of the intervention was less than 3 months (SMD 1.0; 95% CI (0.18; 1.82); p<0.01) than when the duration of the intervention was 3 months or longer (SMD 0.71; 95% CI (0.27; 1.16); p<0.01), but no significant interaction was found between subgroups (p=0.55). 6-MWT distance and V̇O2 peak showed only small effects (SMD 0.34; 95% CI (-0.11; 0.80); p=0.02 and SMD 0.54; 95% CI (0.03; 1.03); p=0.07, respectively)., Conclusion: The use of wearable physical activity monitoring devices appears to help patients with CVD to increase their daily walking activity and thus their physical activity, particularly in the short term., Prospero Registration Number: CRD42022300423., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Open kinetic chain (OKC) exercise is an effective method to improve muscle function during rehabilitation after anterior cruciate ligament reconstruction (ACLR); however, there is controversy about its use in the early phase of rehabilitation., Purpose: To determine (1) whether the use of OKC and closed kinetic chain (CKC) exercises improves quadriceps and hamstring strength in the early phase of rehabilitation after ACLR and (2) whether the early use of OKC exercise affects graft laxity at 3 and 6 months postoperatively in patients with a hamstring tendon graft., Study Design: Cohort study; Level of evidence, 3., Methods: This study included an intervention group that underwent OKC + CKC exercises (n = 51) and a control group that underwent CKC exercise only (n = 52). In the intervention group, OKC exercise for the quadriceps and hamstring was started at 4 weeks after ACLR. At 3 and 6 months postoperatively, isokinetic testing was performed to calculate the limb symmetry index (LSI) and the peak torque to body weight ratio (PT/BW) for the quadriceps and hamstring. Anterior knee laxity was measured by an arthrometer., Results: At 3 and 6 months postoperatively, quadriceps strength was higher in the intervention group than in the control group for the LSI (3 months: 76.14% ± 0.22% vs 46.91% ± 0.21%, respectively; 6 months: 91.05% ± 0.18% vs 61.80% ± 0.26%, respectively; P < .001 for both) and PT/BW (3 months: 1.81 ± 0.75 vs 0.85 ± 0.50 N·m/kg, respectively; 6 months: 2.40 ± 0.73 vs 1.39 ± 0.70 N·m/kg, respectively; P < .001 for both). There were similar findings regarding hamstring strength for the LSI (3 months: 86.13% ± 0.22% vs 64.26% ± 0.26%, respectively; 6 months: 91.90% ± 0.17% vs 82.42% ± 0.24%, respectively; P < .001 at three months, P = .024 at 6 months) and PT/BW (3 months: 1.09 ± 0.36 vs 0.67 ± 0.39 N·m/kg, respectively; 6 months: 1.42 ± 0.41 vs 1.07 ± 0.39 N·m/kg, respectively; P < .001 for both). No significant difference in laxity was observed between the intervention and control groups at 3 or 6 months., Conclusion: Early use of OKC exercise for both the quadriceps and the hamstring, in addition to conventional CKC exercise, resulted in better correction of quadriceps and hamstring strength deficits without increasing graft laxity., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Background: It is well documented that moderate-to-vigorous intensity physical activity (MVPA) is effective in the prevention of major chronic diseases. Even though the current international physical activity (PA) guidelines still mainly focus on MVPA, the topic of the most recent epidemiological studies has shifted from MVPA to light intensity physical activity (LPA), owing to the necessity of promoting all activities vs. sedentary behavior (SB). However, the evidence remains currently limited. Thus, the clarification of the effects of LPA and the close relationship with SB is crucial to promote public health., Method: PA and SB were assessed by a validated self-administered questionnaire (POPAQ) investigating 5 different types of PA during the 7 previous days. PA was measured in metabolic equivalent of task (MET)-h, which refers to the amount of energy (calories) expended per hour of PA. SB was measured in hour/day. Medical histories and examinations were taken during each clinical visit to determine clinical events. All-cause mortality was established using the same procedure and by checking local death registries. The relationships between the intensity of PA (light, moderate to vigorous) and mortality and between the periods of SB and mortality or CV events were analyzed by splines and COX models, adjusted for sex and year of birth., Results: From the 1011 65-year-old subjects initially included in 2001 (60% women), the last 18-year follow-up has been currently completed since 2019. A total of 197 deaths (19.2%, including 77 CV deaths) and 195 CV events (19.3%) were reported. Averages (standard deviation) of MVPA, LPA and SB were, respectively, 1.2 h/d (0.3), 5.8 h/d (1.1), and 6.6 h/d (2.3). For all-cause deaths, as well as CV deaths, the splines were significant for LPA ( p  = 0.04 and p  = 0.01), and MVPA ( p  < 0.001 and p  < 0.001), but not for SB ( p  = 0.24 and p  = 0.90). There was a significant reduction in CV events when SB was decreasing from 10.9 to 3.3 h/d., Conclusion: The PROOF cohort study shows a clear dose-response between the dose of LPA, MVPA, SB and risk of mortality. These findings provide additional evidence to support the inclusion of LPA in future PA guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dupré, Brégère, Berger, Pichot, Celle, Garet, Fundenberger, Barth, Guyot, Bongue, Barthélémy, Roche and Hupin.)

Aims: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management and outcome are sparse., Methods and Results: This international multicenter registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553,729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed at 214 centers in 35 countries. In 78 centers 138 patients (0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (p<0.0001)) were diagnosed with an oesophageal fistula. Periprocedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8%, and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) (odds ratio 7.463 (2.414, 23.072) p<0.001)., Conclusions: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD., (© 2023. The Author(s).)

Background: To report the long-term outcomes of round autologous anterior lens capsules (ALCs) cut by a femtosecond laser (FSL) and transplanted onto refractory macular holes (MHs) in a prospective interventional study., Methods: Three eyes of three patients were included for persistent MH after reattached rhegmatogenous retinal detachment (RRD) (n = 2) or RRD recurrence by persistent MH (n = 1), in a university hospital. A 6 mm diameter ALC disc was carefully extracted during FSL-assisted lens extraction, stained with 0.06% trypan blue, decellularised, transplanted using a catheter and unfolded over the MH. Gas or silicone-oil tamponade was used. At 1 year, the main criterion was anatomic success, defined as complete MH closure. Secondary criteria were changes in best corrected visual acuity (BCVA), ellipsoid zone (EZ) and external limiting membrane (ELM) defects, complications., Results: Baseline data were: minimum and maximum diameters, respectively 887, 1079 and 1180 μm; 1260, 1213 and 1350 μm; central posterior staphyloma in two highly myopic eyes; number of prior surgeries 2 ± 1. At 1 year, the three MHs were closed with stable transplanted ALCs. Distant BCVA improved respectively from 3.0, 0.8, 3.0 to 1.0, 0.2, 0.7 logMAR, i.e. all eyes achieved ≥0.3 logMAR improvement. All patients had decreased EZ and ELM defects, without reaching normal profile. No adverse event occurred., Conclusions: FSL-cut ALC helps standardise this challenging surgery: it prevents from tears and facilitates manipulation, so that the ALC disc is perfectly transparent and biocompatible, with a large MH overlap. One-year follow-up highlighted that this technique helps safely close refractory MHs with satisfactory visual recovery., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Fatigue is a major symptom in many diseases, often among the most common and severe ones and may last for an extremely long period. Chronic fatigue impacts quality of life, reduces the capacity to perform activities of daily living, and has socioeconomical consequences such as impairing return to work. Despite the high prevalence and deleterious consequences of fatigue, little is known about its etiology. Numerous causes have been proposed to explain chronic fatigue. They encompass psychosocial and behavioral aspects (e.g., sleep disorders) and biological (e.g., inflammation), hematological (e.g., anemia) as well as physiological origins. Among the potential causes of chronic fatigue is the role of altered acute fatigue resistance, i.e. an increased fatigability for a given exercise, that is related to physical deconditioning. For instance, we and others have recently evidenced that relationships between chronic fatigue and increased objective fatigability, defined as an abnormal deterioration of functional capacity (maximal force or power), provided objective fatigability is appropriately measured. Indeed, in most studies in the field of chronic diseases, objective fatigability is measured during single-joint, isometric exercises. While those studies are valuable from a fundamental science point of view, they do not allow to test the patients in ecological situations when the purpose is to search for a link with chronic fatigue. As a complementary measure to the evaluation of neuromuscular function (i.e., fatigability), studying the dysfunction of the autonomic nervous system (ANS) is also of great interest in the context of fatigue. The challenge of evaluating objective fatigability and ANS dysfunction appropriately (i.e.,. how?) will be discussed in the first part of the present article. New tools recently developed to measure objective fatigability and muscle function will be presented. In the second part of the paper, we will discuss the interest of measuring objective fatigability and ANS (i.e. why?). Despite the beneficial effects of physical activity in attenuating chronic fatigue have been demonstrated, a better evaluation of fatigue etiology will allow to personalize the training intervention. We believe this is key in order to account for the complex, multifactorial nature of chronic fatigue., Competing Interests: GM is a member of the Myocene Scientific Advisory Board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Millet, Bertrand, Lapole, Féasson, Rozand and Hupin.)

Elderly represents a growing population and cardiovascular diseases (CVD) is one of the leading causes of mortality in this population. Sex differences are involved in CVD with middle-aged males being at higher risk than females. After menopause, females are no longer protected by hormones and the role of sex on cardiovascular parameters involved in CVD, such as endothelial function and blood viscosity, is still unclear. The purpose of this study was to investigate the effect of sex on endothelial function, blood viscosity and CVD in elderly. Clinical investigation and blood analyses were performed on 182 (93 females and 89 males) elderly participants (mean age: 75.83 ± 1.22). Health status of participants were classified. Sex differences in endothelial function, blood viscosity, high density lipoprotein (HDL), hematocrit, and red blood cell (RBC) aggregation were assessed. CVD prevalence was higher in males (27.0%) than in females (5.4%) ( p < 0.001). Females had higher vasoreactivity ( p = 0.014) and HDL ( p < 0.001) level than males. Blood viscosity was higher in males than in females at any shear rate ( p < 0.001). Hematocrit was greater in males than in females ( p < 0.001) while RBC aggregation did not differ between the two populations. To conclude, females have less CVD than age-matched males that might be due to their greater vascular function and lower blood viscosity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Raberin, Martin, Celle, Hupin, Roche, Barthelemy and Connes.)

Background/aim: Rejection is the main cause of graft failure after penetrating keratoplasty (PK). Its prevention by repeated instillation of steroid eye-drops has not evolved in decades. Poor adherence and discontinuous nature of eye-drop treatment may explain some PK failures. In a rabbit model, we previously demonstrated that a subconjunctival dexamethasone implant was well tolerated and prevented rejection efficiently in the first 5-6 weeks. This clinical trial investigates its tolerance and safety after PK., Methods: Single-centre, phase II non-randomised tolerance and safety pilot study (NCT02834260). Designed to analyse the risk of elevated intraocular pressure (IOP), discomfort and resorption time. Fourteen patients with a low rejection risk indication of PK were enrolled between January 2017 and August 2018. The implant was injected in the 12 o'clock position, 5 mm from the limbus, at the end of PK. A steroid eye-drop treatment was planned when implant resorption was complete. Patients were monitored regularly for 12 months: IOP (main outcome measure at 1 month), discomfort and redness scores, implant status, rejection episode and central corneal thickness by optical coherence tomography. An independent data safety monitoring committee verified safety aspects., Results: No increase in IOP or other adverse event related to the implant was observed. Average resorption time was 6 weeks. The switch to steroid eye-drops was uneventful. One patient, included despite preoperative corneal neovascularisation (unintended protocol deviation) experienced a rejection., Conclusions: This is the first proof of concept that dropless immunosuppression is possible after low rejection risk PK., Trial Registration Number: NCT02834260., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The pathophysiology underlying olfactory dysfunction is still poorly understood, and more efficient biomolecular tools are necessary to explore this aspect. Immunohistochemistry (IHC) on cross sections is one of the major tools to study the olfactory epithelium (OE), but does not allow reliable counting of olfactory sensory neurons (OSNs) or cartography of the OE. In this study, we want to present an easy immunostaining technique to compensate for these defects of IHC. Using the rat model, we first validated and pre-screened the key OSN markers by IHC on cross sections of the OE. Tuj-1, OMP, DCX, PGP9.5, and N-cadherin were selected for immunostaining on flat-mounted OE because of their staining of OSN dendrites. A simple technique for immunostaining on flat-mounted septal OE was developed: fixation of the isolated septum mucosa in 0.5% paraformaldehyde (PFA) preceded by pretreatment of the rat head in 1% PFA for 1 hour. This technique allowed us to correctly reveal the olfactory areas using all the 5 selected markers on septum mucosa. By combining the mature OSN marker (OMP) and an immature OSN marker (Tuj-1), we quantified the mature (OMP+, Tuj-1-), immature (OMP-, Tuj-1+), transitory (OMP+, Tuj-1+) and total OSN density on septal OE. They were respectively 42080 ± 11820, 49384 ± 7134, 14448 ± 5865 and 105912 ± 13899 cells per mm2 (mean ± SD). Finally, the same immunostaining technique described above was performed with Tuj-1 for OE cartography on ethmoid turbinates without flat-mount., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gavid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Carbon plates have been used to increase running shoes' longitudinal bending stiffness (LBS), leading to reductions in the energy cost of level running (Cr). However, whether or not this is true during uphill (UH) running remains unknown. The aim of our study was to identify the effect of LBS on Cr during UH running., Methods: Twenty well-trained male runners participated in this study. Cr was determined using gas exchange during nine 4-minute bouts performed using 3 different LBS shoe conditions at 2.22 and 4.44 m/s on level and 2.22 m/s UH (gradient: + 15%) running. All variables were compared using 2-way analyses of variance (LBS × speed/grade effects)., Results: There was no significant effect of LBS (F = 2.04; P = .14, ηp2=.11) and no significant LBS × grade interaction (F = 0.31; P = .87, ηp2=.02). Results were characterized by a very large interindividual variability in response to LBS changes., Conclusions: The current study contributes to a growing body of literature reporting no effect of LBS on Cr during level and UH running. Yet, the very large interindividual differences in response to changes in LBS suggest that increasing shoe LBS may be beneficial for some runners.

Purpose: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis., Source: A systematic review and a meta-analysis were conducted to identify and assess randomised control trials and observational studies with prospective enrolment that included trauma patients and compared adjustment of LMWH thromboprophylaxis versus no adjustment. The primary and secondary endpoints were VTE and bleeding, respectively. The Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated using the Mantel-Haenszel method., Principal Findings: Nine studies were included in the meta-analysis. No significant reduction in the risk of VTE was observed with adjusted doses of LMWH compared with fixed doses when considering only randomised control trials (OR 1.02 [95% CI, 0.09 to 11.6]) or all trials (OR 0.70 [95% CI, 0.34 to 1.42]). Similarly, there was no significant difference in bleeding risk (OR 1.36, 95% CI 0.59 to 3.10)., Conclusion: This meta-analysis shows that, to date, there is no evidence to justify adjusting LMWH doses, in agreement with the recommendations of the American College of Chest Physicians., (Copyright © 2022 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: In severe chronic obstructive pulmonary disease (COPD) patients, the application of an inspiratory pressure support (IPS) during exercise increases exercise tolerance and the benefit of exercise training during pulmonary rehabilitation (PR). Moreover, it improves quadriceps endurance after a session of cycling exercise suggesting a reduced muscle fatigue. We looked for the persistence of this effect after PR and sought an association between the improved quadriceps endurance with IPS and the training load during PR. Patients and methods: We studied 20 patients with severe COPD (6 in stage 3and 14 in stage 4 of GOLD) before and after PR. As part of a PR program, patients completed 16 cycling sessions over 6 weeks with the addition of IPS during exercise. As a surrogate of muscular fatigue, quadriceps endurance was measured at 70% of maximal strength in a control condition, after a constant work rate exercise test (CWR) with IPS (TlimQ IPS) or with a sham ventilation (TlimQsham), in a random order. These tests were repeated similarly at the end of PR. Results: PR was associated with a significant increase in maximal power output, cycling endurance, quadriceps strength and endurance. Session training load (power output x duration of the session) increased by 142% during the course of the program. Before PR, CWR duration increases with IPS compared to sham ventilation (Δtime = +244s, p = 0.001). Compared to control condition, post-exercise TlimQ reduction was lower with IPS at isotime than at the end of CWR or than with sham ventilation (-9 ± 21%, -18 ± 16% and -23 ± 18%, respectively, p = 0.09, p < 0.0001 and p < 0.0001). After PR, the post-exercise decrease of TlimQ was reduced after IPS compared to sham (-9 ± 18% vs. -21 ± 17%, respectively, p = 0.004). No relationship was found between the prevention of quadriceps fatigue and the training load. Conclusion: In severe COPD patients, the beneficial effect of a ventilator support on quadriceps endurance persisted after PR with IPS. However, it was not related to the increase in training load, and could not predict the training response to non-invasive ventilation during exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Labeix, Court Fortune, Muti, Berger, Chomette-Ballereau, Barthelemy, Féasson and Costes.)

Background: Musculoskeletal Disorders (MSDs) are very common conditions in the workplace. Among professional drivers, there would be an increased risk of developing these disorders. Identifying the associated factors would allow us to better devise effective prevention strategies. Our objective was to determine the prevalence of MSDs among taxi drivers in the city of Yaoundé and to search for associated factors, mainly the level of physical activity., Methods: We conducted an analytical cross-sectional study of 151 adult male professional taxi drivers. We used a non-probabilistic consecutive and non-exhaustive sampling method. Sociodemographic, anthropometric and occupational data were collected. MSDs over the past 12 months were assessed using the Nordic Questionnaire and physical activity level was determined by the World Health Organization (WHO) Global Physical Activity Questionnaire (GPAQ). Univariate logistic regression models, followed by a multivariate logistic regression, were used to determine factors associated with the presence of MSDs., Results: The overall prevalence of MSDs was 86.8% (95% CI 80.8 - 91.4); the most affected areas were mainly the lower back (72.8%) the neck (42.4%), and the knees (29.1%). Job dissatisfaction was associated with MSDs (OR = 2.1 95%CI = 1.1-3.9). Most taxi drivers (62.9%) had a low physical activity level and no association was found between the physical activity level and MSDs., Conclusions: MSDs are common ailments among taxi drivers in Yaoundé (Cameroon). There is a need to think about how to address job dissatisfaction and better identify other associated factors in order to define good prevention strategies., (© 2022. The Author(s).)