[The year 2023 placed in perspective by hospital internists]. / Année 2023 mise en perspective par les internistes hospitaliers.

This article features a selection of ten topics chosen, reviewed, and commented for you by chief residents at the Department of Internal Medicine at Centre hospitalier universitaire vaudois (CHUV). This selection synthesizes the novelties and essential reminders of 2023 in internal medicine. By analyzing the standout publications of the year, it offers an overview of progress in diagnosis and patient management within the hospital and their transition to outpatient care. From oral anticoagulation to community-acquired pneumonias, encompassing the management of heart and kidney failure, each key aspect is explored. This compilation provides practitioners with an essential resource to remain at the forefront of current developments, thereby stimulating more informed and effective care for patients.

Cet article propose une sélection de dix sujets choisis, revus et commentés pour vous par les cheffes et chefs de clinique du Service de médecine interne du Centre hospitalier universitaire vaudois (CHUV). Cette sélection synthétise les nouveautés et rappels essentiels de 2023 en médecine interne. En analysant les publications phares de l'année, elle offre une vue d'ensemble des progrès dans le diagnostic et la prise en charge des patients intrahospitaliers et leur transition ambulatoire. De l'anticoagulation orale aux pneumonies communautaires en passant par la prise en charge des insuffisances cardiaque et rénale, chaque aspect clé est exploré. Cette compilation fournit aux praticiens une ressource essentielle pour rester à la pointe des développements actuels, stimulant ainsi des soins plus éclairés et efficaces pour les patients.

Efficient Memory-Enhanced Transformer for Long-Document Summarization in Low-Resource Regimes.

Long document summarization poses obstacles to current generative transformer-based models because of the broad context to process and understand. Indeed, detecting long-range dependencies is still challenging for today's state-of-the-art solutions, usually requiring model expansion at the cost of an unsustainable demand for computing and memory capacities. This paper introduces Emma, a novel efficient memory-enhanced transformer-based architecture. By segmenting a lengthy input into multiple text fragments, our model stores and compares the current chunk with previous ones, gaining the capability to read and comprehend the entire context over the whole document with a fixed amount of GPU memory. This method enables the model to deal with theoretically infinitely long documents, using less than 18 and 13 GB of memory for training and inference, respectively. We conducted extensive performance analyses and demonstrate that Emma achieved competitive results on two datasets of different domains while consuming significantly less GPU memory than competitors do, even in low-resource settings.

Increased Arterial Responsiveness to Angiotensin II in Mice Conceived by Assisted Reproductive Technologies.

Since the first report in 1978, the number of individuals conceived by Assisted Reproductive Technologies (ART) has grown incessantly. In parallel, with the recent emergence of possible underlying mechanisms of ART-induced epigenetic changes in the renin-angiotensin system, the cardiovascular repercussions of ART in mice and human offspring (including arterial hypertension, vascular dysfunction, and cardiac remodeling) have become increasingly recognized. Here, we hypothesized that ART may increase arterial responsiveness to angiotensin II (ANG II) by epigenetically modifying the expression of its receptors. To test this hypothesis, we assessed the vasoconstrictor responsiveness to ANG II in isolated aortas from ART and control mice. We also examined ANG II receptor (ATR) type 1 and 2 expression and the promoter methylation of the At1aR, At1bR and At2R genes. We found that the vasoconstrictor response to ANG II was markedly increased in ART mice compared to controls. This exaggerated vasoconstrictor responsiveness in ART mice correlated with a significant increase in the ANG II receptor (ATR) type 1 to ATR type 2 protein expression ratio in the aorta; this was mainly driven by an increase in AT1R expression, and by hypomethylation of two CpG sites located in the At1bR gene promoter leading to increased transcription of the gene. We conclude that in mice, ART increase the vasoconstrictor response to ANG II in the aorta by epigenetically causing an imbalance between the expression of vasoconstrictor (AT1R) and vasodilator (AT2R) ANG II receptors. Unbalanced expression of AT1R and AT2R receptors seems to be a novel mechanism contributing to ART-induced arterial hypertension in mice.

New perspectives of biological therapy for severe asthma in adults and adolescents.

Severe asthma is associated with increased morbidity, mortality, healthcare costs and impaired quality of life. Asthma is no longer considered as a single entity but as a heterogeneous disease with different clinical presentations (phenotypes) and variable underlying mechanistic biological pathways (endotypes). Two different endotypes are based on the inflammatory Type 2 T-helper response: T2-high and T2-low. The understanding of these endotypes has revolutionised the management of severe asthma. Recent guidelines from the 2019 European Respiratory Society/American Thoracic Society (ERS/ATS) and Global Initiative for Asthma (GINA) 2021 specifically address the diagnosis and the management of severe asthma in adults, but less evidence exists for the paediatric population. Presently, five biologics for the treatment of severe asthma are approved, i.e., omalizumab (anti-IgE antibody), mepolizumab and reslizumab (anti-IL-5 antibody), benralizumab (anti-IL-5 receptor antibody) and dupilumab (anti-IL-4 receptor alpha antibody). This article reviews the pathological mechanisms of severe asthma, clinical biomarkers related to the T2-high endotype, and their use for the prediction of the severity of the disease and response to biological therapy. Furthermore, future developments of biologics for severe asthma are presented.

Altitude-Induced Sleep Apnea Is Highly Dependent on Ethnic Background (Sherpa Vs. Tamang).

Heiniger, Grégory, Simon Walbaum, Claudio Sartori, Alban Lovis, Marco Sazzini, Andrew Wellman, and Raphael Heinzer. Altitude-Induced Sleep Apnea Is Highly Dependent on Ethnic Background (Sherpa Vs. Tamang). High Alt Med Biol. 23:165-172, 2022. Rationale: High altitude-induced hypocapnic alkalosis generates central sleep apnea (CSA). In Nepal, two ethnic groups live at medium-to-high altitude: Tamangs originate from low-altitude Tibeto-Burman populations, whereas Sherpas descend from high-altitude Tibetans. Objective: To compare apnea severity at low and high altitude between Sherpas and Tamangs. Methods: Polygraphy recordings, including airflow and oxygen saturation, were performed in Nepal at "low" (2,030 m) and "high" (4,380 m) altitudes. Resting ventilation (V̇E) and mixed-exhaled CO2 (FECO2) were also measured at the same altitudes. Differences in apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and % of nocturnal periodic breathing (NPB) at the two altitudes were compared between ethnicities. Measurements and Main Results: Twenty Sherpas and 20 Tamangs were included (males, median [interquartile range] age: 24.5 [21.5-27.8] years vs. 26.0 [21.5-39.8] years, body mass index: 23.9 [22.1-26.1] kg/m2 vs. 25.21 [20.6-27.6] kg/m2). Compared with Tamangs, Sherpas showed a lower increase in AHI (+7.5 [2.6-17.2]/h vs. +31.5 [18.2-57.3]/h, p < 0.001), ODI (+13.8 [5.5-28.2]/h vs. +42.0 [22.6-77.6]/h, p < 0.001), and NPB proportion (+0.9 [0-3.5]% vs. +12.8 [3.1-27.4]%, p < 0.001) from low to high altitude. Resting V̇E was higher in Sherpas versus Tamangs at both low (8.45 [6.89-10.70] l/min vs. 6.3 [4.9-8.3] l/min, p = 0.005) and high (9.7 [8.5-11] l/min vs. 8.74 [7.39-9.73] l/min, p = 0.020) altitudes, whereas the mean ± standard deviation FECO2 decrease between low and high altitude was greater in Tamangs versus Sherpas (-0.50% ± 0.44% vs. -0.80% ± 0.33%, p < 0.023). Conclusion: Overall, altitude-adapted Sherpas showed a 3.2-times smaller increase in sleep-disordered breathing between low and high altitude compared with Tamangs, and higher ventilation and a smaller drop in FECO2 at high altitude. These data suggest that genetic differences in breathing control can be protective against CSA.

EPR spectroscopic evidence of iron-catalysed free radical formation in chronic mountain sickness: Dietary causes and vascular consequences.

Chronic mountain sickness (CMS) is a high-altitude (HA) maladaptation syndrome characterised by elevated systemic oxidative-nitrosative stress (OXNOS) due to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability. To better define underlying mechanisms and vascular consequences, this study compared healthy male lowlanders (80 m, n = 10) against age/sex-matched highlanders born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 10) and without (CMS-, n = 10) CMS. Cephalic venous blood was assayed using electron paramagnetic resonance spectroscopy and reductive ozone-based chemiluminescence. Nutritional intake was assessed via dietary recall. Systemic vascular function and structure were assessed via flow-mediated dilatation, aortic pulse wave velocity and carotid intima-media thickness using duplex ultrasound and applanation tonometry. Basal systemic OXNOS was permanently elevated in highlanders (P = <0.001 vs. lowlanders) and further exaggerated in CMS+, reflected by increased hydroxyl radical spin adduct formation (P = <0.001 vs. CMS-) subsequent to liberation of free 'catalytic' iron consistent with a Fenton and/or nucleophilic addition mechanism(s). This was accompanied by elevated global protein carbonylation (P = 0.046 vs. CMS-) and corresponding reduction in plasma nitrite (P = <0.001 vs. lowlanders). Dietary intake of vitamins C and E, carotene, magnesium and retinol were lower in highlanders and especially deficient in CMS + due to reduced consumption of fruit and vegetables (P = <0.001 to 0.028 vs. lowlanders/CMS-). Systemic vascular function and structure were also impaired in highlanders (P = <0.001 to 0.040 vs. lowlanders) with more marked dysfunction observed in CMS+ (P = 0.035 to 0.043 vs. CMS-) in direct proportion to systemic OXNOS (r = -0.692 to 0.595, P = <0.001 to 0.045). Collectively, these findings suggest that lifelong exposure to iron-catalysed systemic OXNOS, compounded by a dietary deficiency of antioxidant micronutrients, likely contributes to the systemic vascular complications and increased morbidity/mortality in CMS+. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT01182792; URL: www.clinicaltrials.gov.

[The Internal medicine articles that struck us the most in 2021]. / Année 2021 mise en perspective par les internistes hospitaliers.

The year 2021 has seen many breakthroughs in general internal medicine, despite the ongoing COVID-19 pandemic, with multiple implications in our daily clinical practice. From shorter antibiotic treatment duration in community-acquired pneumonia, to new indications for colchicine treatment, without forgetting better targets of hemoglobin for transfusion, questioning of the interest of high dose vitamin D substitution when preventing falls in older patients and finally disappointing hopes for new indications of albumin substitution in cirrhosis, the literature is full of new evidence. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles, chosen, summarized, and commented for you.

L'année 2021, malgré la pandémie de Covid-19, a vu de nombreux progrès en médecine interne générale, avec de multiples implications pour notre pratique quotidienne. D'une durée diminuée d'antibiothérapie pour le traitement de la pneumonie communautaire à de nouvelles indications au traitement de colchicine, en passant par des précisions sur les cibles de transfusion érythrocytaire, ainsi qu'une remise en question de l'intérêt de la vitamine D à haute dose dans la prévention des chutes chez la personne âgée, et pour finir des espoirs déçus de nouvelle indication à la substitution d'albumine dans la cirrhose, les nouveautés abondent dans la littérature. Chaque année, les cheffes et chefs de clinique du Service de médecine interne du CHUV se réunissent pour partager leurs lectures : voici une sélection de dix articles choisis, revus et commentés pour vous.

Post-exercise accumulation of interstitial lung water is greater in hypobaric than normobaric hypoxia in adults born prematurely.

We aimed to gauge the interstitial lung water accumulation following moderate-intensity exercise under normobaric and hypobaric hypoxic conditions in a group of preterm born but otherwise healthy young adults. Sixteen pre-term-born individuals (age = 21±2yrs.; gestational age = 29±3wk.; birth weight = 1160±273 g) underwent two 8 -h hypoxic/altitude exposures in a cross-over manner: 1) Normobaric hypoxic exposure (NH; FIO2 = 0.142±0.001; PIO2 = 90.6±0.9 mmHg) 2) Hypobaric hypoxic exposure (HH; terrestrial high-altitude 3840 m; PIO2 = 90.2±0.5 mmHg). Interstitial lung water was assessed via quantification of B-Lines (using lung ultrasound) before (normoxia) and after 4-h and 8-h of respective exposures. At each time point, B-Lines were quantified before (Pre) and immediately after (Post) a 6-min moderate-intensity exercise. The baseline B-lines count were comparable between both conditions (P = 0.191). A higher B-lines count was noted at Pre-H4 in HH versus NH (P = 0.0420). At Post-H8 B-lines score was significantly higher in HH (4.6 ± 1.6) than in NH (3.1 ± 1.4; P = 0.0073). Furthermore, at this time point, a significantly higher number of individuals with B-line scores ≥5 was observed in HH (n = 7) than in NH (n = 3; P = 0.0420). These findings suggest that short moderate-intensity exercise provokes a significant increase in the interstitial lung water accumulation after 8 h of exposure to terrestrial but not simulated altitude (≈3840 m) in prematurely born adults. Further work is needed to elucidate the exact mechanisms of (moderate-intensity) exercise-induced interstitial lung water accumulation in this population and directly compare the obtained data to full-term born adults.

[Epidemiology and risk factors of nosocomial COVID infections in the Service of internal medicine at CHUV]. / Épidémiologie et facteurs de risque des infections Covid nosocomiales dans le Service de médecine interne du CHUV.

Nosocomial COVID-19 infections are a challenge for hospitals. In order to assess possible demographic, personal, environmental or medical care related risk factors, data of nosocomial cases occurring in the Service of internal medicine at CHUV between February and March 2021 were retrospectively analyzed. Neither personal nor medical care related factors were identified as risk factor for a nosocomial infection. However, a significant number of patients with hospital-acquired COVID infection stayed in a 5-bed ward (versus 1-2 beds) and shared toilets in these rooms. Patient distancing measures and weekly screening led to a subsequent significant reduction of nosocomial SARS-CoV-2 infections.

Les infections Covid-19 nosocomiales sont un défi pour les hôpitaux. Afin d'identifier d'éventuels facteurs de risque démographiques, personnels, environnementaux ou de prise charge, nous avons analysé rétrospectivement les cas nosocomiaux survenus dans le Service de médecine interne du CHUV en février-mars 2021. Aucun facteur personnel ou de prise en charge n'a été mis en évidence. Par contre, un plus grand nombre de patients avec infection nosocomiale avait séjourné dans une chambre à 5 lits (versus 1-2 lits) et utilisé les toilettes communes de ces chambres. La limitation de l'occupation des chambres multiples et des dépistages hebdomadaires ont permis de contrôler la transmission nosocomiale du SARS-CoV-2.

[Focus on tizanidine in primary care medecine]. / Le point sur la tizanidine en médecine de premier recours.

Tizanidine is an alpha2 agonist with central action whose myorelaxant effects are often used off-label against primary backpain in clinical practice. It is mainly metabolized by the liver. The concomitant use of CYP1A2 inhibitor drugs increases the plasmatic concentration and thus can cause serious adverse effects. Severe hypotension is the most memorable example. Its narrow therapeutic range and the interindividual different sensitivity to the molecule justify using it wisely. A clinical case is reported as illustration.

La tizanidine est un agoniste alpha-2-adrénergique d'action centrale dont l'effet myorelaxant est utilisé « hors indication ¼ en pratique médicale pour les lombalgies primaires. Elle est principalement métabolisée au niveau hépatique. Lorsqu'elle est administrée de manière concomitante à un inhibiteur du CYP1A2, sa concentration plasmatique augmente, entraînant potentiellement plusieurs effets indésirables. L'hypotension sévère en est l'exemple le plus probant. Sa marge thérapeutique étroite et la sensibilité variable des sujets à la molécule justifient son utilisation judicieuse. Un cas clinique illustratif est rapporté.

[Organizational Impacts and Clinical Challenges of the COVID-19 Pandemic on a Swiss Tertiary Internal Medicine Department]. / Impacts organisationnels et défis cliniques de la pandémie COVID-19 pour un service hospitalier de médecine interne universitaire.

The rapid progression of COVID-19 is an organizational challenge for all hospitals. To secure the patient overflow, the Department internal medicine of the University Hospital of Lausanne increased nurse and medical workforces as well as bed capacity by 65 %, with extraordinary help from other departments. The implemented crisis management stood upon three pillars : a crisis management team, steering documents and internal communication. In this new form, the Department had already taken care of 442 COVID-19 admissions by April 16, 2020. Alongside organizational challenges, clinical issues such as rapid respiratory distress, clinical suspicions with negative PCR and treatment uncertainties in the absence of sufficient evidence were overcome. Despite the peak of the pandemic appearing to have passed, the next phase could be just as complicated.

La progression rapide du COVID-19 constitue un défi organisationnel pour tous les hôpitaux. Pour anticiper un afflux important de patients, le service de médecine interne du CHUV a ainsi augmenté ses forces de travail médico-soignantes et son nombre de lits de 65 % avec un soutien extraordinaire de toute l'institution. Pour opérer ces changements majeurs, l'organisation de crise mise en place s'est appuyée sur trois piliers : une cellule de conduite, des documents de pilotage et une communication interne. Sous cette nouvelle forme, le service a pris en charge 442 hospitalisations COVID-19 jusqu'au 16 avril 2020. Si les enjeux organisationnels ont été majeurs, la gestion des situations complexes, comme les manifestations respiratoires et les multiples incertitudes cliniques diagnostiques et thérapeutiques, ont été également une gageure. Le pic de la pandémie semble passé, mais la prochaine phase pourrait constituer un nouveau défi organisationnel.

[The management of hypertriglyceridemia and the risk of pancreatitis]. / Prise en charge des hypertriglycéridémies et du risque de pancréatite.

In the face of hypertriglyceridemia, the potential causes must be assessed to choose the best medical therapeutic option. In cases of secondary hypertriglyceridemia, physicians should use treatments targeting the pathophysiological mechanisms underlying the lipid disorder. Lifestyle interventions are the cornerstone of an effective treatment, to achieve controlled glycemia, blood pressure and weight loss. Only in cases where these measures are insufficient, fibrates can be trialed although their clinical benefit is controversial, with special caution when combined with statins (risk of rhabdomyolysis). Plasmapheresis or intravenous insulin therapy are only used in severe situations after a multidisciplinary decision process in the hospital setting. The clinical case presented here reminds us to assess hypertriglyceridemia in the face of any acute pancreatitis.

Les causes d'une hypertriglycéridémie doivent être explorées pour choisir la meilleure approche thérapeutique. En cas d'hypertriglycéridémie secondaire, il est préférable de cibler le mécanisme physiopathologique du désordre lipidique. Les mesures hygiéno-diététiques restent la clé de voûte du traitement, pour atteindre un bon contrôle glycémique, tensionnel et pondéral. Uniquement en cas d'échec, les fibrates peuvent être évoqués bien que leur bénéfice clinique soit controversé, avec une attention particulière en cas de bithérapie par statine et fibrate (risque de rhabdomyolyse). La plasmaphérèse ou l'insulinothérapie intraveineuse sont réservées aux situations sévères et décidées avec les différents spécialistes en milieu hospitalier. Le cas clinique présenté ici est un rappel que l'hypertriglycéridémie devrait être recherchée devant toute pancréatite aiguë.

[The internal medicine articles that struck us the most in 2019]. / L'année 2019 mise en perspective par les internistes hospitaliers.

2019 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From new indications for SGLT2 inhibitors and rivaroxaban, to antibiotic duration for Gram negative bacteriemia, passing by the delay for cardioversion of recent-onset atrial fibrillation or for beginning sacubitril/valsartan after stabilization of a cardiac failure, internal medicine journals are full of novelties. Every year, the chief residents of the CHUV internal medicine ward meet up to share their readings: here is their selection of eleven articles, chosen, summarized and commented for you.

L'année 2019 a vu d'importants progrès dans tous les domaines de la médecine interne, avec un impact important sur notre pratique quotidienne hospitalière. Des nouvelles indications pour les inhibiteurs du SLGT2 et le rivaroxaban, à la durée du traitement des bactériémies à Gram négatif en passant par le délai pour la cardioversion d'une fibrillation auriculaire inaugurale ou celui pour introduire du sacubitril/valsartan après stabilisation d'une insuffisance cardiaque, les nouveautés abondent dans la littérature. Chaque année, les chefs de clinique du Service de médecine interne du Centre Hospitalier Universitaire Vaudois (CHUV) se réunissent pour partager leurs lectures: voici une sélection de onze articles choisis, revus et commentés pour vous.

Swiss Mountain Guides: Medical Education, Knowledge, and Practice.

Background: Mountain guides work daily in remote areas and high-altitude locations where specific hypoxia-related and common medical problems may occur. Arrival of rescue teams can be delayed, so mountain guides often have to rely on their own capabilities to provide first aid. Therefore, IFMGA-recognized Swiss mountain guides receive a specific medical education and are equipped with a dedicated medical kit. This specific education has never been evaluated. Methods: A questionnaire was sent to all Swiss mountain guides through their national association. This questionnaire evaluates guides' activity, type, and frequency of medical events encountered, medical education, and use of the medical kit. Furthermore, clinical vignettes were used to evaluate their subjective and objective knowledge about prevention and treatment of specific altitude-related diseases. Results: A total of 467 guides completed the questionnaire, 54 (11.6%) of them were identified as high-altitude guides (HA-guides), because they spent ≥10 nights above 4000 meters each year. Mountain guides are more exposed to altitude-specific pathologies, such as Acute Mountain Sickness (AMS), High-Altitude Pulmonary Edema (HAPE), and High-Altitude Cerebral Edema (HACE) than to general medical conditions. A majority of participants (in particular HA-guides) considered altitude-related medical knowledge essential but judged their own education as insufficient. A majority of mountain guides were aware of nonpharmacological preventive measures and able to recognize altitude-related diseases. Mountain guides declared themselves as very confident in treating altitude-related diseases. Objective assessment of their knowledge showed some gaps, in particular related to the use of specific medications like nifedipine and dexamethasone. Conclusions: Swiss mountain guides' education in altitude medicine may be improved, in particular concerning the recognition and treatment of severe conditions such as HAPE and HACE. Better knowledge may be especially important for HA-guides. These data have induced experts in the field to adapt the guides teaching curriculum and medical kit.

Low- and High-Altitude Cortisol Awakening Responses Differ Between AMS-Prone and AMS-Resistant Mountaineers.

Background: Mechanisms underlying acute mountain sickness (AMS) remain unclear. Corticosteroids are effective for prevention and treatment suggesting a role for deficient endogenous cortisol. The cortisol awakening response (CAR), the increase in cortisol secretion over the first 30-45 minutes after morning awakening, better reflects the hypothalamic-pituitary-adrenal (HPA) axis than single cortisol measurements. We hypothesized that CAR may be altered in AMS-prone persons. Methods: Upon arrival at 4554 m (high altitude [HA]), 81 mountaineers agreed to participate. The following morning, they gave three saliva samples after awakening (S1: 0 minute, S2: 30 minutes, S3: 45 minutes). AMS was scored with the 1993 Lake Louise Score (LLS, cut-off ≥5). Minimally 4 weeks after descent, saliva was recollected by 58 of 81 participants at low altitude (LA); 382 ± 309 m, mean ± standard deviation). Cortisol was quantified by immunoassay. Three cortisol indices were analyzed: first sample on awakening (S1), CAR (area under curve with respect to S1) and total post awaking cortisol (area under the curve from ground [AUC-G]). Results: AMS prevalence was 30%. At HA compared to LA, S1 (450 ± 190 vs. 288 ± 159 ng/dL, p < 0.001) and AUC-G (387 ± 137 vs. 276 ± 114 ng/dL·min, p < 0.001) were greater, but CAR was not (50 ± 100 vs. 60 ± 81 ng/dL·min, p = 0.550). AMS+ compared to AMS- participants had higher S1 both at HA (495 ± 209 vs. 384 ± 176 ng/dL, p = 0.016) and LA (354 ± 160 vs. 253 ± 142 ng/dL, p = 0.015) and lower CAR at LA (24 ± 87 vs. 79 ± 72 ng/dL·min, p = 0.013). AUC-G was similar in both groups at HA and LA. Conclusions: Some indices of salivary cortisol response upon awakening differ between AMS+ and AMS-, both at HA and LA, suggesting a link between HPA-axis homeostasis and AMS.

[Hypoxic tests and prediction of high altitude illnesses]. / Tests hypoxiques et prédictiondes pathologies liées à l'altitude.

More and more travelers are exposed to high altitude, for example, 176'000 trekkers/climbers were registered in Nepal in 2017. Individual predispositions, a history of altitude illness, the existence of risk factors and/or comorbidities increase the risk of developing specific altitude-related diseases that are potentially life threatening. Nevertheless, the prediction of these diseases remains difficult, especially in subjects without prior exposure to high altitude. In this context different altitude simulation tests have been developed. Their indication, practice and validity are summarized in this article.

De plus en plus de voyageurs s'exposent à la haute altitude, par exemple 176 000 trekkers/alpinistes ont été enregistrés au Népal en 2017. Des prédispositions individuelles, des antécédents de maladies d'altitude, l'existence de facteurs de risque et/ou comorbidités augmentent le risque de développer des maladies spécifiques liées à l'altitude qui sont potentiellement mortelles. Néanmoins, la prédiction de ces maladies reste difficile, notamment chez des sujets sans exposition préalable à la haute altitude. Dans ce contexte, différents tests de simulation à l'altitude ont été développés. Leurs indication, pratique et validité sont résumées dans cet article.

Exaggerated systemic oxidative-inflammatory-nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression.

KEY POINTS: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative-inflammatory-nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS-) and low-altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. ABSTRACT: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross-sectional study examined to what extent exaggerated systemic oxidative-inflammatory-nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age- and gender-matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS-, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone-based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS-). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

[How to properly use beta-blockers ?] / Comment utiliser correctement les ß-bloquants ?

Known since the 1950s, competitive ß-adrenergic receptor antagonists, namely ß-blockers (BB), constitute today a large and heterogeneous class of drugs with multiple clinical indications. Despite their daily use, can we choose the most appropriate BB for each of these indications? A better knowledge of the individual properties of BB (bioavailability, cardioselectivity, vasodilator and metabolic effects) could help to optimize their clinical benefits especially in polymorbid patients, frequently suffering from metabolic syndrome, peripheral arteriopathy or asthma/chronic obstructive pulmonary disease (COPD) supposed to be potential contraindications to their use.

Connus depuis les années 50, les antagonistes compétitifs des récepteurs ß-adrénergiques, ou ß-bloquants (BB), constituent aujourd'hui une classe ample et hétérogène de médicaments avec de multiples indications cliniques. Malgré leur utilisation quotidienne, savons-nous choisir le BB le plus approprié pour chacune de ces indications ? Une meilleure connaissance des propriétés individuelles des BB (biodisponibilité, cardiosélectivité, effets vasodilatateur et métabolique) devrait permettre d'optimaliser leurs bénéfices surtout chez des patients polymorbides, fréquemment atteints d'un syndrome métabolique, d'une artériopathie périphérique ou d'un asthme/bronchopneumopathie chronique obstructive (BPCO) supposés être des contre-indications potentielles à leur emploi.