Evidence and unresolved questions in pulmonary hypertension: Insights from the 5th French Pulmonary Hypertension Network Meeting.

Pulmonary hypertension (PH) continues to present significant challenges to the medical community, both in terms of diagnosis and treatment. The advent of the updated 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines has introduced pivotal changes that reflect the rapidly advancing understanding of this complex disease. These changes include a revised definition of PH, updates to the classification system, and treatment algorithm. While these guidelines offer a critical framework for the management of PH, they have also sparked new discussions and questions. The 5th French Pulmonary Hypertension Network Meeting (Le Kremlin-Bicêtre, France, 2023), addressed these emergent questions and fostering a deeper understanding of the disease's multifaceted nature. These discussions were not limited to theoretical advancements but extended into the practical realms of patient management, highlighting the challenges and opportunities in applying the latest guidelines to clinical practice.

Impact of hospital internships on success in university summative objective structured clinical examinations: Large-scale experience in a French medical school.

BACKGROUND: Objective structured clinical examinations (OSCEs) are extensively used in many medical schools worldwide with the stated objective to assess students' clinical skills acquired during internships. The objective of the present study was to assess the factors associated with success in university summative OSCEs, especially the impact of previous hospital internships in corresponding disciplines and supervision during internships. METHODS: This was a cross-sectional study assessing the results in the summative OSCEs of 4th year medical students during the 2021-2022 academic year in a French medical school. The summative OSCEs included five stations for each student. Each student answered a survey at the end of summative OSCEs about previous internships, the supervision they had and perceived difficulty levels for each station. The scores in each station were assessed according to previous hospital internships in the corresponding discipline. Analysis of predictive factors of success in OSCEs, defined by a score ≥ 10/20 at each station, were performed using univariate and multivariate logistic regression. RESULTS: Out of the 220 students participating in the summative OSCEs, 182 (83%) answered the survey. One hundred and forty-four (79%) of these students had carried out hospital internships in at least one of the disciplines evaluated during the OSCEs. Students having completed an internship in the corresponding discipline had significantly higher OSCEs scores for interrogation, communication, therapeutic education and procedure stations compared to those who had not. Previous internship in corresponding disciplines was independently associated with success in OSCEs in interrogation (OR 9.45 [1.34-66.8] p = 0.02), clinical examination (OR 6.93 [1.88-25.57] p = 0.004, and therapeutic education (OR 3.09 [1.22-7.82] p = 0.02) stations. CONCLUSION: Previous hospital internships in the discipline evaluated by the OSCEs are associated with success in summative OSCEs. This reinforces the importance of student involvement during their hospital internships.

[An expanding spleen]. / Une rate qui s'dilate.

A 24 years-old woman was admitted to hospital for an epistaxis that had not resolved. Biological results show bi-cytopenias (anemia and thrombopenia). Clinically she presents a fourth grade splenomegaly. To explore these cytopenias, a myelogram is performed.

Trust and COVID-19 vaccine hesitancy in the Dominican Republic: a national cross-sectional household survey, June-October 2021.

OBJECTIVE: This study investigates the role of trust in shaping COVID-19 vaccine acceptance in the Dominican Republic (DR) during the COVID-19 pandemic. DESIGN: Cross-sectional household survey. SETTING: Randomly selected households across 134 clusters in the DR, from 30 June 2021 to 12 October 2021. PARTICIPANTS: 5999 participants ≥16 years of age were enrolled. OUTCOME MEASURES: COVID-19 vaccine hesitancy (CVH) data were collected from participants ≥16 years of age and analysed as both an ordinal and binary variable. RESULTS: Overall, CVH was low (5.2% (95% CI 4.6% to 5.8%)), but more common among younger individuals, women and individuals of Mestizo ethnicity. Higher trust in local government, national government, scientists and local doctors (considered official sources) was associated with lower odds of CVH (OR 0.89 (95% CI 0.72 to 0.88), 0.89 (95% CI 0.81 to 0.98), 0.87 (95% CI 0.80 to 0.94) and 0.70 (95% CI 0.62 to 0.80), respectively). Higher trust in religious leaders, social media and traditional media (considered unofficial sources) was associated with higher odds of CVH, with respective ORs of 1.32 (95% CI 1.18 to 1.47), 1.30 (95% CI 1.19 to 1.41) and 1.08 (95% CI 0.97 to 1.22). CONCLUSION: We report findings on CVH from a national household survey in the DR and identify overall low rates of CVH but marked heterogeneity by age, gender and ethnicity. Trust in unofficial versus official sources of information is associated with increased CVH. These findings highlight and quantify the importance of trust as a key parameter when considering public health communication strategies.

ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly.

Pulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation.

Central role of ubiquitin-specific protease 8 in leptin signaling pathway in pulmonary arterial hypertension.

BACKGROUND: Leptin receptor (ObR-b) is overexpressed in pulmonary artery smooth muscle cells (PA-SMCs) from patients with pulmonary arterial hypertension (PAH) and is implicated in both mechanisms that contribute to pulmonary vascular remodeling: hyperproliferation and inflammation. Our aim was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in ObR-b overexpression in PAH. METHODS: We performed in situ and in vitro experiments in human lung specimens and isolated PA-SMCs combined with 2 different in vivo models in rodents and we generated a mouse with an inducible USP8 deletion specifically in smooth muscles. RESULTS: Our results showed an upregulation of USP8 in the smooth muscle layer of distal pulmonary arteries from patients with PAH, and upregulation of USP8 expression in PAH PA-SMCs, compared to controls. USP8 inhibition in PAH PA-SMCs significantly blocked both ObR-b protein expression level at the cell surface as well as ObR-b-dependant intracellular signaling pathway as shown by a significant decrease in pSTAT3 expression. USP8 was required for ObR-b activation in PA-SMCs and its inhibition prevented Ob-mediated cell proliferation through STAT3 pathway. USP8 inhibition by the chemical inhibitor DUBs-IN-2 protected against the development of experimental PH in the 2 established experimental models of PH. Targeting USP8 specifically in smooth muscle cells in a transgenic mouse model also protected against the development of experimental PH. CONCLUSIONS: Our findings highlight the role of USP8 in ObR-b overexpression and pulmonary vascular remodeling in PAH.

Radiological pulmonary sequelae after COVID-19 and correlation with clinical and functional pulmonary evaluation: results of a prospective cohort.

OBJECTIVES: Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. MATERIALS AND METHODS: We conducted a prospective single-center study among patients hospitalized for COVID-19 between March and May 2020. Patients with residual symptoms or admitted into intensive care units were investigated 4 months after discharge by a chest CT (CCT) and pulmonary function tests (PFTs). The primary endpoint was the rate of persistent radiological fibrotic lesions after 4 months. Secondary endpoints included further CCT evaluation at 9 and 16 months, correlation of fibrotic lesions with clinical and PFT evaluation, and assessment of predictive factors. RESULTS: Among the 1151 patients hospitalized for COVID-19, 169 patients performed a CCT at 4 months. CCTs showed pulmonary fibrotic lesions in 19% of the patients (32/169). These lesions were persistent at 9 months and 16 months in 97% (29/30) and 95% of patients (18/19) respectively. There was no significant clinical difference based on dyspnea scale in patients with pulmonary fibrosis. However, PFT evaluation showed significantly decreased diffusing lung capacity for carbon monoxide (p < 0.001) and total lung capacity (p < 0.001) in patients with radiological lesions. In multivariate analysis, the predictive factors of radiological pulmonary fibrotic lesions were pulmonary embolism (OR = 9.0), high-flow oxygen (OR = 6.37), and mechanical ventilation (OR = 3.49). CONCLUSION: At 4 months, 19% of patients investigated after hospitalization for COVID-19 had radiological pulmonary fibrotic lesions; they persisted up to 16 months. CLINICAL RELEVANCE STATEMENT: Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. The prevalence of persisting lesions after COVID-19 remains unclear. We assessed this prevalence and predictive factors leading to fibrotic lesions in a large cohort. The respiratory clinical impact of these lesions was also assessed. KEY POINTS: • Nineteen percent of patients hospitalized for COVID-19 had radiological fibrotic lesions at 4 months, remaining stable at 16 months. • COVID-19 fibrotic lesions did not match any infiltrative lung disease pattern. • COVID-19 fibrotic lesions were associated with pulmonary function test abnormalities but did not lead to clinical respiratory manifestation.

Pulmonary hypertension associated with diazoxide: the SUR1 paradox.

The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with heritable pulmonary arterial hypertension. Conversely, activation of SUR1 and SUR2 leads to the relaxation of pulmonary arteries and reduces cell proliferation and migration. Diazoxide, a SUR1 activator, has been shown to alleviate experimental PH, suggesting its potential as a therapeutic option. However, there are paradoxical reports of diazoxide-induced PH in infants. This review explores the role of SUR1/2 in the pathophysiology of PH and the contradictory effects of diazoxide on the pulmonary vascular bed. Additionally, we conducted a comprehensive literature review of cases of diazoxide-associated PH and analysed data from the World Health Organization pharmacovigilance database (VigiBase). Significant disproportionality signals link diazoxide to PH, while no other SUR activators have been connected with pulmonary vascular disease. Diazoxide-associated PH seems to be dose-dependent and potentially related to acute effects on the pulmonary vascular bed. Further research is required to decipher the differing pulmonary vascular consequences of diazoxide in different age populations and experimental models.

Using Regional Sero-Epidemiology SARS-CoV-2 Anti-S Antibodies in the Dominican Republic to Inform Targeted Public Health Response.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT80 for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

Clinical Phenotype and Outcomes of Pulmonary Hypertension Associated with Myeloproliferative Neoplasms: A Population-based Study.

Rationale: Precapillary pulmonary hypertension (PH) is a rare and largely unrecognized complication of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF). Objectives: To describe characteristics and outcomes of MPN-associated PH. Methods: We report clinical, functional, and hemodynamic characteristics, classification, and outcomes of patients with PV, ET, or primary MF in the French PH registry. Measurements and Main Results: Ninety patients with MPN (42 PV, 35 ET, 13 primary MF) presented with precapillary PH with severe hemodynamic impairment, with a median mean pulmonary arterial pressure and pulmonary vascular resistance of 42 mm Hg and 6.7 Wood units, respectively, and impaired clinical conditions, with 71% in New York Heart Association functional classes III/IV and having a median 6-minute-walk distance of 310 m. Half of the patients were diagnosed with chronic thromboembolic PH (CTEPH); the other half were considered to have group 5 PH. MF was preferentially associated with group 5 PH, whereas PV and ET were generally related to CTEPH. Proximal lesions were diagnosed in half of the patients with CTEPH. Thromboendarterectomy was performed in 18 selected patients with high risk of complications (5 early deaths). Overall survival at 1, 3, and 5 years was 67%, 50%, and 34% in group 5 PH and 81%, 66%, and 42% in CTEPH, respectively. Conclusions: PH is a life-threatening condition potentially occurring in MPN. There are multiple mechanisms, with equal diagnoses of CTEPH and group 5 PH. Physicians should be aware that PH strongly affects the burden of patients with MPN, especially in group 5 PH, with unknown pathophysiological mechanisms.

[Post-COVID-19 syndrome]. / Syndrome post-COVID-19.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.

International use of objective structured clinical examinations in respiratory training: a European Respiratory Society early career member survey.

This international overview of the use of objective structured clinical examinations (OSCEs) in respiratory training highlights the heterogeneity in use between countries as well as the positive experience of OSCEs amongst users https://bit.ly/3Zee6zP.

Sleep Assessment in Critically Ill Patients With Acute Hypoxemic Respiratory Failure.

BACKGROUND: Sleep deprivation alters respiratory muscle performance and may precipitate respiratory failure. This study aimed to assess sleep in subjects admitted to ICU for acute hypoxemic respiratory failure and its role in the risk of intubation. METHODS: This was a prospective observational single-center cohort study including subjects admitted to ICU for de novo acute hypoxemic respiratory failure defined as breathing frequency ≥ 25 breaths/min or clinical signs of respiratory distress and PaO2 /FIO2 < 300 mm Hg while receiving high-flow nasal oxygen. Subjects with altered consciousness, central nervous or psychiatric disorders, continuous sedation or neuroleptic medication, or were uncooperative were excluded. Sleep was assessed by complete polysomnography (PSG) the night following ICU admission. The main outcome was to assess sleep among subjects with acute hypoxemic respiratory failure and to compare sleep between subjects who eventually required intubation to those who did not. RESULTS: Over a 24-month inclusion period, 34 subjects had complete PSG, among whom 5 (15%) required intubation in the ICU. Total sleep time was 4.2 h in median (interquartile range 2.9-6.8); deep-sleep duration was 70 min (34-127), and rapid eye movement (REM) sleep duration was 9 min (0-28). Among them, 13 subjects (38%) had no REM sleep. Total sleep time and duration of deep and REM sleep stages did not differ between subjects who required intubation and those successfully treated with high-flow nasal oxygen. CONCLUSIONS: Whereas total sleep time remained relatively preserved in critically ill subjects with acute hypoxemic respiratory failure, REM sleep time was uncommon or completely absent in a large number of subjects. Sleep did not differ between subjects who required intubation and those who did not. However, given a trend toward an increased risk of intubation in subjects with a complete absence of REM sleep, further studies are needed to better explore the impact of REM sleep on the risk of intubation.

Functional respiratory complaints among COVID-19 survivors: a prospective cohort study.

Background: Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear. Methods: We assessed the proportion and characteristics of patients with "functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET). Findings: In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease. Interpretation: FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.

[Physiopathology and treatment of pulmonary arterial hypertension]. / Physiopathologie et traitements de l'hypertension artérielle pulmonaire.

Pulmonary arterial hypertension (PAH) is a rare disease affecting mainly the pre-capillary pulmonary vascular bed. However, some forms of the disease have venous/capillary involvement. It is an obstructive remodelling of the pulmonary arterioles coupled with vascular pruning, increasing right ventricular afterload and leading to right heart failure. PAH has a complex pathogeny that is detailed in this review. Current specific treatments target endothelial dysfunction, and primarily aim at vasodilatation. Promising innovative treatments targeting the pulmonary artery remodelling are under development.

Title: Physiopathologie et traitements de l'hypertension artérielle pulmonaire. Abstract: L'hypertension artérielle pulmonaire (HTAP) est une maladie rare affectant principalement le lit vasculaire pulmonaire pré-capillaire. Certaines formes de la maladie présentent néanmoins une atteinte veinulaire/capillaire. Il s'agit d'un remodelage obstructif des artérioles pulmonaires couplé à une raréfaction vasculaire, augmentant la post-charge ventriculaire1 droite et conduisant à une insuffisance cardiaque droite. La physiopathologie de l'HTAP est complexe. Les traitements spécifiques actuels ciblent la dysfonction endothéliale, avec une action essentiellement vasodilatatrice. Des traitements innovants prometteurs ciblant le remodelage vasculaire pulmonaire sont en cours de développement.

Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

Diagnostic Performance of Pulsed Doppler Ultrasound of the Common Femoral Vein to Detect Elevated Right Atrial Pressure in Pulmonary Hypertension.

Right atrial pressure (RAP) is an important prognostic criterion in pulmonary hypertension (PH). The main goals were to evaluate the following: (i) the accuracy of Doppler assessment of common femoral vein flow waveform to detect elevated RAP and (ii) the diagnostic accuracy of RAP assessed by echocardiography (eRAP). Fifty-seven patients, addressed for right heart catheterization, were included in a retrospective cross-sectional study during a 6-month period. Forty-five patients (78.9%) had PH confirmed by RHC. Elevated RAP was defined by RAP ≥ 10 mmHg. Femoral venous stasis index (FVSI) was highly correlated to RAP on both univariate (p < 0.001) and multivariate analysis (p = 0.003), and showed good diagnostic performances to detect elevated RAP (specificity: 92.3% [80.0-99.3], diagnosis accuracy: 90.4 [77.4-97.3], positive likelihood ratio: 12.5 [3.01-51.97]). Diagnosis accuracy of eRAP was only 51.2% (36.2-66.1). FVSI is independently correlated to RAP and a useful tool to predict elevated RAP in PH patients.

SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.

Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. Funding: This study was funded by the US CDC.

Influence of environmental and dietary exposures on metals accumulation among the residents of a major industrial harbour (Fos-sur-Mer, France).

OBJECTIVES: We sought to determine whether the residents living closer to the core industrial zone (Fos-sur-Mer) had higher trace metals blood and urinary levels than residents who lived further away (Saint-Martin-de-Crau). MATERIALS AND METHODS: As part of The INDEX study, we measured the following trace metals into blood and urine samples of 138 participants (80 in the core industrial zone and 58 in the reference area): Antimony, Arsenic, Cadmium, Chromium, Cobalt, Mercury, Nickel, Lead and Vanadium. Participants were recruited using a stratified random sampling method and had to meet the following inclusion criteria: 30-65 years old, living in the area since at least 3 years, not working in the industrial sector, non-smoker. We used single-pollutant multivariate linear regression models, using substitution when censored data were under 15 % and Tobit models alternatively, adjusting for personal physiological, social, dietary, housing characteristics and leisure activities. We also measured these trace metals in samples of lichens (Xanthoria parietina) and atmospheric particles (PM2.5). RESULTS: We showed higher lichen and air levels of several metals (Cd, Cr, Co, Ni and Pb) in the exposed area. Living close to the core industrial zone was significantly associated with an increase in blood levels of lead (adjusted geometric mean = 17.2 [15.8-18.7] vs 15.1 [13.7-16.7] µg.L-1, p < 0.05). We report significant increase of some metals urinary levels among residents of the industrial port zone, as the result of the use of the environment, itself contaminated by industrial activities: dietary history of self-consumption of vegetables (Cadmium), eggs and poultries (Vanadium). However, Vanadium levels were greater among self-consumers of poultry in the reference area and gardeners had circulatory levels of Lead greater than non-gardeners only in the reference area. Consumption of non-local sea-products increased the level of Cadmium. CONCLUSIONS: These results brought interesting clues, in complement to national programs, regarding the exposure to trace metals of residents living in a major industrial harbor.

COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.