Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2 days at high altitude (3375 m), 16 young preterm-born (gestational age, 29 ± 1 weeks) and 15 age-matched term-born (40 ± 0 weeks) adults were exposed to two consecutive 4 min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P = 0.036), but not in preterm-born (-4 ± 27%, P = 0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P = 0.026) but not in preterm-born adults (-21 ± 107%, P = 0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P < 0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P = 0.012) and lower hypercapnic (P = 0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine.

Take home figureAdapted from Bärtsch and Gibbs2 Physiological response to hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000 m), is ensured by an increase in pulmonary ventilation, an increase in cardiac output by increasing heart rate, changes in vascular tone, as well as an increase in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial pressure of arterial carbon dioxide.

[Work on a building site at high altitude: physiopathological features and entailments for the occupational medicine]. / Il lavoro in un cantiere in alta quota: generalità fisiopatologiche e analisi di una casistica occupazionale.

SUMMARY: Introduction. From a physiological perspective the high altitude is defined by altitudes higher than 3000 meters above sea level: at this altitude the atmospheric pressure is reduced to 525 mmHg and the partial pressure of Oxygen drops to 110 mmHg in the ambient air follows and 60 mmHg in the alveolar air. To stay at altitudes above 3000 m s.l.m. therefore places the human organism in front of a notable reduction of the functional respiratory reserve already in conditions of rest, leading to inevitable repercussions on the ability to sustain physical effort. Materials and methods. A population of 39 workers employed in the construction sector at a high altitude construction site (2200-3480 m) was examined. Data relating to sex, age, body mass index, smoking, residence altitude, mountaineering history (maximum altitude reached over a lifetime, frequency of ascents, time spent at high altitude, both for pleasure and for work) and sport practice were collected. Among them, for 25 workers the data of the ergometric tests in normobaric hypoxia (pO2, desaturation and peak values of heart rate, respiratory frequency, ventilation) conducted with simplified mode were collected. Purpose. The study aims to analyze the health of a group of workers exposed to the risk related to staying at high altitude in light of the indications of the scientific literature on health surveillance. Results. The data relating to the group of workers studied with regard to anamnestic data and to the results of ergospirometric examinations in hypoxic conditions are described. Conclusions. In working conditions at high altitude it is necessary to consider both the effect of high altitude in itself, similar to a sort of substantially unchangeable "background risk", and the ways in which high altitude interacts with other risk factors characteristic of the work site activity (which are the same as for any construction site activity that takes place at sea level), considering also the pathophysiological or frankly pathological conditions of which the worker is a carrier. This evaluation can be articulated on two levels: a first level concerning the suitability of the individual for access and the simple prolonged stay in altitude where the work activity will be performed; a second level regarding the suitability of the worker to carry out the work tasks required by the specific task in the particular environmental conditions.

Chronic and acute effects of endurance training on telomere length.

Telomere shortening is considered a cellular marker of health status and biological ageing. Exercise may influence the health and lifespan of an individual by affecting telomere length (TL). However, it is unclear whether different endurance exercise levels may have beneficial or detrimental effects on biological aging. The aims of the study were to assess both chronic and acute effects of endurance training on TL after an exceptional and extreme trail race. TL was assessed in 20 endurance athletes (17 males; age = 45.4 ± 9.2 years) and 42 age- and gender-matched sedentary controls (32 males; age = 45.9 ± 9.5 years) with quantitative real-time PCR at baseline conditions. Of the 20 runners enrolled in the 'Tor des Géants ®' ultra-distance trail race, 15 athletes (12 males; age = 47.2 ± 8.5 years) were re-evaluated at the intermediate point and 14 athletes (11 males; age = 47.1 ± 8.8 years) completed the competition and were analysed at the final point. Comparison between the two groups (endurance athletes vs. sedentary controls) revealed a significant difference in TL (1.28 ± 0.4 vs. 1.02 ± 0.3, P = 0.005). TL was better preserved in elder endurance runners compared with the same age control group (1.3 ± 0.27 vs. 0.91 ± 0.21, P = 0.003). TL was significantly reduced at the intermediate (0.88 ± 0.36 vs. 1.11 ± 0.34, P = 0.002) and final point compared with baseline measurements (0.86 ± 0.4 vs. 1.11 ± 0.34, P = 0.0006) for athletes engaged in the ultra-marathon race. Our data suggest that chronic endurance training may provide protective effects on TL attenuating biological aging. Conversely, acute exposure to an ultra-distance endurance trail race implies telomere shortening probably caused by oxidative DNA damage.

Prevalence of Drug Use in Ultraendurance Athletes.

PURPOSE: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires. METHODS: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start of ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use. RESULTS: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared. CONCLUSIONS: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes.

Epidemiology of stroke in northern Italy: the Cerebrovascular Aosta Registry, 2004-2008.

Our aim was to prospectively ascertain the incidence of first-ever stroke and ischaemic stroke subtypes, mortality, functional outcome and recurrence in northern Italy. We identified all possible cases of stroke (1st January 2004 and 31st December 2008). Multiple overlapping sources were used. Standard definitions for incident cases, pathological types and infarction subtypes were used. Patient characteristics were identified and analysed, case-fatality was ascertained from administrative databases, and outcome was assessed in all surviving patients by modified Rankin Scale. We identified 1,326 incident strokes. The pathological diagnosis was confirmed in 94% of cases. The incidence of first-ever stroke was 80.2 per 100,000 (95% CI 73-87) when adjusted to world population. The incidence of embolic stroke was significantly greater in women than in men (p < 0.001) whereas the incidence of atherothrombotic stroke was significantly greater in men than in women (p < 0.001). The case-fatality of incident strokes was 9.5% at 7 day, 16.1% at 28 day, and 29.9% at 1 year. Case-fatality of ischaemic stroke was lower than that of other pathological types (p < 0.0001). Hypertension was the most important risk factor, and atrial fibrillation was the most common in embolic stroke. Increasing age, female gender and embolic stroke subtypes were associated with an adverse outcome. Data on stroke incidence and case-fatality were similar to those of other high-income countries. However, differences were found in the distribution of risk factors and prognosis across the stroke types and ischaemic stroke subtypes. Gender differences in long-term functional outcomes were significant.

Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults.

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. -15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. -13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm.

Effects of Electrical Stimulation on Delayed Onset Muscle Soreness (DOMS): Evidences from Laboratory and In-Field Studies.

Intense, long exercise can increase oxidative stress, leading to higher levels of inflammatory mediators and muscle damage. At the same time, fatigue has been suggested as one of the factors giving rise to delayed-onset muscle soreness (DOMS). The aim of this study was to investigate the efficacy of a specific electrical stimulation (ES) treatment (without elicited muscular contraction) on two different scenarios: in the laboratory on eleven healthy volunteers (56.45 ± 4.87 years) after upper limbs eccentric exercise (Study 1) and in the field on fourteen ultra-endurance athletes (age 47.4 ± 10.2 year) after an ultra-running race (134 km, altitude difference of 10,970 m+) by lower exercising limbs (Study 2). Subjects were randomly assigned to two experimental tasks in cross-over: Active or Sham ES treatments. The ES efficacy was assessed by monitoring the oxy-inflammation status: Reactive Oxygen Species production, total antioxidant capacity, IL-6 cytokine levels, and lactate with micro-invasive measurements (capillary blood, urine) and scales for fatigue and recovery assessments. No significant differences (p > 0.05) were found in the time course of recovery and/or pre-post-race between Sham and Active groups in both study conditions. A subjective positive role of sham stimulation (VAS scores for muscle pain assessment) was reported. In conclusion, the effectiveness of ES in treating DOMS and its effects on muscle recovery remain still unclear.

Comparative Effectiveness of an Artificial Air Pocket Device to Delay Asphyxiation in Supine Individuals Critically Buried in Avalanche Debris.

Importance: Approximately 70% of individuals critically buried in avalanche debris die within 35 minutes as a result of asphyxial cardiac arrest. An artificial air-pocket device (AAPD) that separates inhaled air from exhaled air may delay the onset of severe hypoxemia and eventual asphyxia during snow burial. Objective: To investigate the efficacy of a new AAPD during snow burial in a supine position. Design, Setting, and Participants: This comparative effectiveness trial was performed in winter 2016 with data analysis in November 2016 and November 2022. Each trial used a simulated critical avalanche burial scenario, in which a trough was dug in a snow pile and an additional air pocket of 0.5 L volume was punched into the lateral wall for each control trial. All participants were buried in a supine position. Trials could be voluntarily terminated at any time, with a maximum length of 60 minutes; trials were automatically terminated if the participant's peripheral oxygen saturation (Spo2) dropped to less than 84%. Exposures: Each participant conducted 2 trials, one in which they breathed into the AAPD (intervention trial) and the other in which they breathed into the prepared air pocket (control trial). Main Outcomes and Measures: Measurements included Spo2, cerebral oxygenation, ventilatory parameters, respiratory gas concentrations, and visual-analogue scales. Kaplan-Meier survival curves and rank test for matched survival data were used to analyze the total burial time in each trial. Results: A total of 13 volunteers (9 men; mean [SD] age, 33 [8] years) were exposed to the intervention and control trials. Intervention trials were terminated less often (2 of 13 trials) as a result of hypoxemia than control trials (11 of 12 trials). Similarly, survival curves showed a longer duration of burial in the intervention compared with the control trials for the time to reach an Spo2 less than 84% (rank test for matched survival data: P = .003). The intervention trials, compared with the control trials, also had slower rates of decrease in fraction of inspired oxygen (mean [SD] rate, -0.8 [0.4] %/min vs -2.2 [1.2] %/min) and of increase in fraction of inspired carbon dioxide (mean [SD] rate, 0.5 [0.3] %/min vs 1.4 [0.6] %/min) and expired ventilation per minute (mean [SD] rate, 0.5 [1.0] L/min2 vs 3.9 [2.6] L/min2). Conclusions and Relevance: This comparative effectiveness trial found that the new AAPD was associated with delaying the development of hypoxemia and hypercapnia in supine participants in a critical burial scenario. Use of the AAPD may allow a longer burial time before asphyxial cardiac arrest, which might allow longer times for successful rescue by companions or by prehospital emergency medical services.

[Work at high altitude: concepts of physiopathology, risk factors, health surveillance and criteria for the development of work capacity evaluation criteria]. / Il lavoro in alta quota: nozioni di fisiopatologia, fattori di rischio, sorveglianza sanitaria e criteri per l'elaborazione del giudizio di idoneità.

Work at high altitude (elevation equal to or greater than 3000 m above sea level) results in a physiological adaptation of the human organism to changing environmental conditions. The main problem related to the altitude is represented by the reduction of partial pressure of oxygen (hypoxia) that occurs in proportion to the reduction of barometric pressure. Our study, starting with an analysis of the human body's physiological response to acute hypoxic conditions and acclimatization for reaching protracted stays, takes into consideration all risk factors related to the performance of work at high altitude. We identified risk factors related to physical environment of high altitude and represented by temperature, humidity, latitude, speed wind, atmospheric pressure and hypoxia, risk factors related to the worker and represented by age, sex, state of health and individual susceptibility, degree of training. With reference to the state of health we analyzed the major pathophysiological conditions that can create situations of susceptibility to high altitude. We then analyzed risk factors related to the characteristics of the job that are represented by the degree of physical effort and energy expenditure required, by the personal protective equipment (PPE) used and by the concomitant exposure to other occupational risk factors of physical and chemical nature. It was finally addressed the decision making process related to the formulation of the judgment of suitability for performance of work activities at high altitude. The health protocol proposed requires an accurate anamnestic investigation aimed at gathering information on pre-existing pathophysiological conditions that need, once identified, clinical and instrumental tests specific and targeted. These clinical protocols are analyzed and proposed for the main pathophysiologic conditions that pose a risk to health at high altitude. For workers, in which clinical investigation and medical history has not shown significant pathophysiological conditions, we propose a basic health protocol, including clinical and instrumental examinations, modulated in relation to age of workers. Among the specific instrumental tests necessary to process a judgment of suitability to work in complex cases, the ergospirometric test performed under conditions of hypoxia was considered. This test is important for the study of the main predictive parameters in assessing the ability to work at high altitude. The test involves measurement of three key parameters (heart rate, oxygen saturation, ventilation) that are then integrated in the construction of variables useful for the interpretation of the test: cardiac response and ventilatory response to hypoxia, desaturation at rest and during exercise, respiratory rate.

High-altitude mountain telemedicine.

INTRODUCTION: An innovative teleconsultation platform has been designed, developed and validated between summer 2017 and winter 2018, in five mountain huts and in three remote outpatient clinical centres of the Italian region Valle d'Aosta of the Mont Blanc massif area. METHODS: An ad-hoc videoconference system was developed within the framework of the e-Rés@MONT (Interreg ALCOTRA) European project, to tackle general health problems and high-altitude diseases (such as acute mountain sickness, high-altitude pulmonary and cerebral oedema). The system allows for contacting physicians at the main hospital in Aosta to perform a specific diagnosis and to give specific advice and therapy to the patients in an extreme environment out-hospital setting. At an altitude between 1500-3500 m, five trained nurses performed clinical evaluations (anamnesis, blood pressure, heart rate, oxygen saturation), electrocardiographic and echography monitoring on both tourists and residents as necessary; all of the collected data were sent to the physicians in Aosta. RESULTS: A total of 702 teleconsultation cases were performed: 333 dismissed (47%), 356 observed (51%) and 13 immediate interventions (2%). In 30 cases the physicians decided there was no need for helicopter and ambulance rescue intervention and hospital admissions. The main physiological measures, the classified pathologies, the severe cases and the cost savings are described in this article. DISCUSSION: The e-Rés@MONT teleconsultation platform has been discussed in terms of treated cases, feasibility, proactivity in reducing complexities, direct and indirect advantages, and diagnostics help; moreover, general and specific pros and cons have been debated, and future steps have been exposed.

Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Kinetics of Cardiac Remodeling and Fibrosis Biomarkers During an Extreme Mountain Ultramarathon.

Objectives: The effects of ultra-distance on cardiac remodeling and fibrosis are unclear. Moreover, there are no data reporting the kinetics of cardiac alterations throughout the event and during recovery. Our aim was to investigate the kinetics of biological markers including new cardiac fibrosis biomarkers suppression of tumorigenicity 2 (ST2) and galectin-3 (Gal-3) during and after an extreme mountain ultramarathon. Methods: Fifty experienced runners participating in one of the most challenging mountain ultramarathons (330 km, D+ 25,000 m) were enrolled in our study. Blood samples were collected at four time points: before (Pre-), at 148 km (Mid-), at the finish line (Post-), and 3 days after the recovery period (Recov-). Results: The cardiac fibrosis biomarkers (ST2 and Gal-3) increased from Pre- to Mid-. During the second half, ST2 remained higher than pre-values as opposed to Gal-3. Necrosis, ischemia, and myocyte injury biomarkers increased until Mid- then decreased but remained higher at Recov- than Pre-values. Oxidative stress appeared at Mid-. Lipid peroxides remained higher at Recov- compared to Pre-. The maximal value in most of these biomarkers was observed at Mid- and not at Post-. Conclusions: The present study supports biphasic kinetics of cardiac fibrosis biomarkers, with a relative recovery during the second half of the event that seems specific to this extreme event. Overall, performing at such an extreme ultramarathon seems less deleterious for the heart than shorter events.

Blood C-reactive protein concentration with ABCD² is a better prognostic tool than ABCD² alone.

BACKGROUND: Increased C-reactive protein (CRP) is a known predictor of vascular events in asymptomatic individuals and stroke patients. Only a few studies included transient ischaemic attack (TIA) patients. We assessed CRP levels in addition to traditional risk factors in a cohort of patients with TIA to examine the relationship of these parameters to the occurrence of ischaemic stroke. METHODS: This is a prospective, longitudinal clinical evaluation of the efficacy of CRP as a prognostic indicator. CRP levels were measured in 194 TIA patients and in 1,024 asymptomatic individuals (recruited from a project on stroke prevention, the PrATO, which was ongoing at the same time in the Aosta Valley). A clinical risk score was determined using the ABCD² score in TIA patients. The area under the receiver operating characteristic curve (AUC) was used to evaluate the significance of the markers as predictors. Two models were evaluated: model 1 used the ABCD² score and model 2 used serum CRP levels in addition to the ABCD²) score. The primary outcome was an ischaemic stroke. RESULTS: Within 2 years ischaemic strokes occurred in 33/194 patients. The Cox proportional hazards models, after adjustments for conventional risk factors, identified CRP levels ≥3 mg/l and ABCD² scores ≥4 as independent predictors of stroke. The corresponding AUCs were 0.565 and 0.636, based on model 1 and model 2, respectively; this represented a statistically significant difference (p = 0.043). The absolute integrated discrimination improvement was 0.0249 (p = 0.007) and the relative integrated discrimination improvement was 2.3710. The net benefit became significant from a predicted probability ≥10% and was 0.077 when based on model 1 and 0.087 when based on model 2. CONCLUSIONS: Routine CRP measurements in the acute phase might be a useful tool for identifying TIA patients who are at a higher risk of ischaemic stroke. The additional use of CRP levels for the risk assessment in TIA patients improves risk definition in terms of the ABCD² score alone.

Recommendations for traveling to altitude with neurological disorders.

BACKGROUND: Several neurological conditions might worsen with the exposure to high altitude (HA). The aim of this review was to summarize the available knowledge on the neurological HA illnesses and the risk for people with neurological disorders to attend HA locations. METHODS: A search of literature was conducted for several neurological disorders in PubMed and other databases since 1970. The neurological conditions searched were migraine, different cerebrovascular disease, intracranial space occupying mass, multiple sclerosis, peripheral neuropathies, neuromuscular disorders, epileptic seizures, delirium, dementia, and Parkinson's disease (PD). RESULTS: Attempts were made to classify the risk posed by each condition and to provide recommendations regarding medical evaluation and advice for or against traveling to altitude. Individual cases should be advised after careful examination and risk evaluation performed either in an outpatient mountain medicine service or by a physician with knowledge of HA risks. Preliminary diagnostic methods and anticipation of neurological complications are needed. CONCLUSIONS: Our recommendations suggest absolute contraindications to HA exposure for the following neurological conditions: (1) Unstable conditions-such as recent strokes, (2) Diabetic neuropathy, (3) Transient ischemic attack in the last month, (4) Brain tumors, and 5. Neuromuscular disorders with a decrease of forced vital capacity >60%. We consider the following relative contraindications where decision has to be made case by case: (1) Epilepsy based on recurrence of seizure and stabilization with the therapy, (2) PD (± obstructive sleep apnea syndrome-OSAS), (3) Mild Cognitive Impairment (± OSAS), and (4) Patent foramen ovale and migraine have to be considered risk factors for acute mountain sickness.

Validation of a Score for the Detection of Subjects with High Risk for Severe High-Altitude Illness.

PURPOSE: A decision tree based on a clinicophysiological score (severe high-altitude illness (SHAI) score) has been developed to detect subjects susceptible to SHAI. We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ), and to specify the rule for a progressive acclimatization. METHODS: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of the SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of the SHAI score, ACZ prescription, and use and fulfillment of the acclimatization rule. RESULTS: The occurrence of SHAI was 22.6%, similar to what was observed 18 yr before (23.7%), whereas life-threatening forms of SHAI (high-altitude pulmonary and cerebral edema) were less frequent (2.6%-0.8%, P = 0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400-m daily altitude gain were respected (P < 0.001). CONCLUSIONS: This multicenter study confirmed the interest of the SHAI score in predicting the individual risk for SHAI. The conditions for an optimized acclimatization (400-m rule) were also specified, and we proposed a rational decision tree for the prescription of ACZ, adapted to each individual tolerance to hypoxia.

[High altitude pulmonary edema: the importance of early diagnosis]. / Edema polmonare da alta quota: l'importanza di una diagnosi precoce.

In high altitude setting is present a syndrome linked to hypoxia, exercise and low temperatures, causing multiple organ damage, which may also lead to death. The main clinical pictures are represented by acute mountain sickness, high altitude pulmonary edema (HAPE), high altitude cerebral edema. A clinical case with the main determinants of HAPE, during a trek in the Himalayas valley is described.

Tendon morphological changes after a prolonged ski race can be detected by ultrasound echo intensity.

BACKGROUND: Ultrasound imaging techniques have been used to assess the characteristics of skeletal muscles and tendons. Such techniques (gray scale analysis) allow qualitative evaluation and have been used recently to assess the internal structure of muscles and tendons by computer-aided gray scale analysis. We hypothesized that changes in the internal structure of the Achilles and patellar tendons after a ski mountaineering race competition could be detected with ultrasound. METHODS: Twenty athletes were recruited during the 19th Millet Tour du Rutor extreme, a three-day ski mountaineering competition. Ultrasound measurements of the Achilles and patellar tendons were carried out before the first race and immediately after each of the three competition days. Tendon thickness, cross-sectional area (CSA), and ultrasound gray scale analysis were calculated. RESULTS: Significant differences (p < 0.05) were observed between the pre- and post-race measurements for the Achilles tendon thickness and CSA, while no significant differences were noted for the patellar tendon thickness and CSA. However, gray scale analysis of both the Achilles and patellar tendons showed significantly higher post-race values, than the pre-race values (p < 0.05). CONCLUSIONS: Achilles and patellar tendons of healthy athletes are highly responsive to an acute increase in mechanical load. Those changes can be detected from classical (thickness and CSA) and innovative (gray scale) ultrasound-based parameters. TRIAL REGISTRATION: This study was approved by the Azienda USL Valle d'Aosta Ethics Committee (protocol no. 23/03/2018.0026243.I).

Acute Effects of Triathlon Race on Oxidative Stress Biomarkers.

The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9 ± 7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%; p < 0.0001), TBARS (HIR +57%; IR +101%), PC (HIR +101%; IR +130%) and urinary neopterin (HIR +19%, IR +27%) significantly (range p < 0.05-0.0001) increased. Moreover, HIR showed an increase in total Cys +28%, while IR showed total aminothiols, Cys, Hcy, CysGly, and GSH increase by +48, +30, +58, and +158%, respectively (range p < 0.05-0.0001). ROS production was significantly correlated with TBARS and PC (R 2 = 0.38 and R 2 = 0.40; p < 0.0001) and aminothiols levels (range R 2 = 0.17-0.47; range p < 0.01-0.0001). In particular, ROS was directly correlated with the athletes' age (R 2 = 0.19; p < 0.05), with ultraendurance years of training (R 2 = 0.18; p < 0.05) and the days/week training activity (R 2 = 0.16; p < 0.05). Finally, the days/week training activity (hours/in the last 2 weeks) was found inversely correlated with the IL-6 postrace (R 2 = -0.21; p < 0.01). A strenuous performance, the Ironman® distance triathlon competition, alters the oxidant/antioxidant balance through a great OxS response that is directly correlated to the inflammatory parameters; furthermore, the obtained data suggest that an appropriate training time has to be selected in order to achieve the lowest ROS production and IL-6 concentration at the same time.

Community-based study of stroke incidence in the Valley of Aosta, Italy. CARe-cerebrovascular Aosta Registry: years 2004-2005.

The purpose of our study was to determine the incidence of stroke, case-fatality rate and disability at 1 year in the Valley of Aosta (Italy) in the years 2004 and 2005. All suspected strokes occurring between January 1, 2004, and December 31, 2005, in the resident population of the Valley of Aosta were identified according to the WHO criteria for stroke and included in a stroke registry (Cerebrovascular Aosta Registry, CARe) after revision by a clinical panel. Multiple overlapping sources were used to ascertain the cases. In the study period, 553 incident strokes were registered. A CT scan was performed in 94.2% of cases. The crude annual incidence rate was 223 (95% CI 197-249) per 100,000 inhabitants. After age and sex adjustment to the 'European' population, the stroke incidence rate was 126 (95% CI 106-146). In the 1-year follow-up, only a small number of patients with a first-ever stroke in their life time suffered a new event. Compared with the previous study performed in our region (Valley of Aosta) in 1989, a marked decline in the incidence rate was seen after adjustment to the 'European' population, and the 28-day case-fatality rate declined dramatically between 1989 and 2004-2005.