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Introduction Le traitement du cancer a ete profondement modifie ces dernieres annees avec l’introduction des inhibiteurs du checkpoint immunologiques (ICI). Le pronostic de certains cancers, tels le melanome ou le cancer pulmonaire non a petites cellules s’en est trouve largement ameliore [1] , [2] . Ces traitements sont cependant a l’origine d’effets secondaires appeles effets indesirables lies a l’immunotherapie (EILI), dont les atteintes les plus frequentes (digestives, cutanees, endocriniennes) sont maintenant bien decrites, et relativement simples a diagnostiquer et traiter [3] . A contrario, certaines atteintes plus rares comme la myocardite sont peu decrites, alors que le taux de mortalite est eleve (jusqu’a 40 %) et de prise en charge plus delicate. Patients et methodes Nous avons conduit une etude transversale retrospective multicentrique sur une periode allant de juillet 2019 a novembre 2020. Les criteres d’inclusion etaient : traitement par un inhibiteur du checkpoint immunologique, survenue d’une suspicion de myocardite en s’appuyant sur les criteres de la societe europeenne de cardiologie, donnees de suivi disponibles pour chaque patient. Les myocardites etaient classees en possible/probable/definies selon des criteres internationaux, la severite a ete cotee en utilisant la classification CTCAE v5.0. Resultats Vingt-neuf patients ont ete inclus, de 6 centres differents, avec un âge median de 69 (32-83) ans. Les cancers traites etaient majoritairement pulmonaires (10 patients), des melanomes (8 patients), ou urotheliaux (4 patients). La myocardite survenait dans un delai median de 39 (2-181) jours, principalement avec des anti-PD1 (16 patients, 55 %). La plupart des patients (83 %) etaient symptomatiques, la dyspnee etant le symptome le plus frequent (17 patients, 59 %). Tous avaient une troponine HS elevee, avec une mediane de 5,35 fois la normale superieure, l’ECG montrait des anomalies chez 19 patients (68 %), alors que l’ETT etait disponible chez 27 patients et montrait une FEVG alteree chez 10 d’entre eux (37 %). Une IRM cardiaque a ete realisee chez 24 patients, montrant une prise de contraste tardive chez 9 d’entre eux (37 %). Quatorze patients (48 %) ont subi une coronarographie, et 6 ont beneficie d’une biopsie endomyocardique. Ces dernieres montraient chez 5 patients une infiltration lymphocytaire, majoritairement CD8+. Parmi les toxicites associees, la myosite etait la plus frequente (13 patients, 45 %), suivie du syndrome sec (11 patients, 38 %). Les patients les plus severes (CTCAE grade 4 et 5, n = 11) avaient un taux plus important de maladies auto-immunes systemiques preexistantes (5 patients contre 1, p = 0,018), une frequence cardiaque plus elevee a l’admission (113 contre 79,5, p = 0,001), une troponinemie d’entree plus elevee (42 fois la norme superieure contre 3,55, p = 0,001), et presentaient plus souvent des anticorps anti-recepteur de l’acetylcholine (5 contre 0, p = 0,001). L’analyse en courbe ROC nous a permis de selectionner une valeur seuil de troponinemie a 4,89 fois la norme superieur (sensibilite = 90,9 %, specificite 66,7 %) pour predire l’evolution vers une forme grave. Concernant le traitement, la plupart des patients (28) ont recu des corticoides, le plus souvent apres des bolus initiaux (19 patients, 68 %). Les autres modalites de traitement concernaient les plasmaphereses (10 patients), les immunoglobulines polyvalentes (8 patients), et d’autres immunosuppresseurs (5 patients). 7 patients (24 %) sont morts lors de la prise en charge initiale. Nous disposions d’une evaluation de la reponse carcinologique chez 21 patients, dont seulement 1 presentait une progression de la maladie. Au cours du suivi (d’une mediane de 4 mois), 7 patients supplementaires sont decedes. 6 patients ont recu a nouveau un traitement par ICI, seulement 1 ayant presente une rechute de myocardite. Conclusion Certains facteurs de mauvais pronostic ont ete mis en evidence, comme un taux eleve de troponine a l’admission, ce qui pourrait aider a la decision therapeutique. La mortalite est moindre dans notre serie, possiblement par le depistage de formes subintrantes en dosant la troponine de facon systematique. Cependant, la contre-indication definitive de l’immunotherapie sera peut etre a rediscuter selon la balance benefice/risque.

We aimed to assess lung fluid balance before and after gradual ascent to 5150m. Lung diffusion capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO) and ultrasound lung comets (ULCs) were assessed in 12 healthy lowlanders at sea-level, and on Day 1, Day 5 and Day 9 after arrival at Mount Everest Base Camp (EBC). EBC was reached following an 8-day hike at progressively increasing altitudes starting at 2860m. DLCO was unchanged from sea-level to Day 1 at EBC, but increased on Day 5 (11±10%) and Day 9 (10±9%) vs. sea-level (P≤0.047). DmCO increased from sea-level to Day 1 (9±6%), Day 5 (12±8%), and Day 9 (17±11%) (all P≤0.001) at EBC. There was no change in ULCs from sea-level to Day 1, Day 5 and Day 9 at EBC. These data provide evidence that interstitial lung fluid remains stable or may even decrease relative to at sea-level following 8days of gradual exposure to high-altitude in healthy humans.

High-altitude ascent induces left (LV) and right (RV) ventricular adaptations secondary to hypoxia-related hemodynamic and myocardial alterations. Since cardiopulmonary decrements observed with aging (e.g., decreased LV compliance and increased pulmonary vascular resistance) may limit cardiac plasticity, this study examined myocardial adaptability throughout an 11 day sojourn to 5893 m in young and older-aged trekkers.Echocardiography was performed on 14 young (8 men; 32 ± 5 years) and 13 older-aged (8 men; 59 ± 5 years) subjects on non-trekking days (Day 0: 880 m; Day 3: 3100 m; Day 8: 4800 m; Day 12/post-climb: 880 m). RV systolic pressure (mmHg) was systematically higher in older-aged subjects (p 0.01) with similar progressive increases observed during ascent for young and older subjects, respectively (Day 0: 18 ± 1 vs 20 ± 2; Day 3: 25 ± 2 vs 29 ± 3; Day 8: 30 ± 2 vs 35 ± 2). Estimates of LV filling pressure (E/E') were systematically higher in older subjects (p 0.01) with similar progressive decreases observed during ascent for young and older-aged subjects, respectively (Day 0: 5.6 ± 0.3 vs 6.7 ± 0.5; Day 3: 5.1 ± 0.2 vs 6.1 ± 0.3; Day 8: 4.7 ± 0.3 vs 5.4 ± 0.3). Overall, RV end-diastolic and end-systolic area increased at altitude (p 0.01), while LV end-diastolic and end-systolic volume decreased (p 0.01). However, all RV and LV morphological measures were similar on Day 3 and Day 8 (p 0.05), and returned to baseline post-climb (p 0.05). Excluding mild LV dilatation in some older-aged trekkers on Day 8/Day 12 (p 0.01), altitude-induced morphological and functional adaptations were similar for all trekkers (p 0.05).Altitude-induced myocardial adaptations are chamber specific, secondary to RV and LV hemodynamic alterations. Despite progressive hemodynamic alterations during ascent, morphological and functional cardiac perturbations plateaued, suggesting rapid myocardial adaptation which was mostly comparable in young and older-aged individuals.

Purpose We determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude. Methods At sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (Vc) were measured at rest before maximal oxygen consumption (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{\text{O}}_{2\hbox{max} }$$\end{document}V˙O2max) was determined in seven adults. Then, DLCO, DmCO and Vc were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization. Results Immediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10 %, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or Vc (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20 % increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and Vc (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{\text{O}}_{2\hbox{max} }$$\end{document}V˙O2max from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude. Conclusion These data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.

STUDY OBJECTIVES To determine the impact of averaging window-length on the "desaturation" indexes (DIs) obtained via overnight pulse oximetry (SpO2) at high altitude. DESIGN Overnight SpO2 data were collected during a 10-day sojourn at high altitude. SpO2 was obtained using a commercial wrist-worn finger oximeter whose firmware was modified to store unaveraged beat-to-beat data. Simple moving averages of window lengths spanning 2 to 20 cardiac beats were retrospectively applied to beat-to-beat SpO2 datasets. After SpO2 artifacts were removed, the following DIs were then calculated for each of the averaged datasets: oxygen desaturation index (ODI); total sleep time with SpO2 < 80% (TST < 80), and the lowest SpO2 observed during sleep (SpO2 low). SETTING South Base Camp, Mt. Everest (5,364 m elevation). PARTICIPANTS Five healthy, adult males (35 ± 5 y; 180 ± 1 cm; 85 ± 4 kg). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS 49 datasets were obtained from the 5 participants, totalling 239 hours of data. For all window lengths ≥ 2 beats, ODI and TST < 80 were lower, and SpO2 low was higher than those values obtained from the beat-to-beat SpO2 time series data (P < 0.05). CONCLUSIONS Our findings indicate that increasing oximeter averaging window length progressively underestimates the frequency and magnitude of sleep disordered breathing events at high altitude, as indirectly assessed via the desaturation indexes.

Osteoarthritis is the most common form of arthritis and is a leading cause of disability in the elderly. Given the anticipated increase in osteoarthritis prevalence, the need to identify risk factors for incident osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical function decline, and disability is an especially high priority. Findings have implicated several factors, including genetic factors, aging, joint deformity and injury, obesity, and hormonal deficiencies in the pathogenesis of osteoarthritis. Recent studies have identified risk factors associated with progression of the disease including varus-valgus alignment, bone marrow edema lesions, varus thrust, a reduced hip abduction moment, and obesity. Predictors of function decline in osteoarthritis include lower self-efficacy, knee laxity, less aerobic exercise, worse joint proprioception, and greater knee pain.