Suzana Erico Tanni

Scopus Publications

Influence of CReatine Supplementation on mUScle Mass and Strength After Stroke (ICaRUS Stroke Trial): A Randomized Controlled Trial
Juli T. Souza, Marcos F. Minicucci, Natália C. Ferreira, Bertha F. Polegato, Marina P. Okoshi, Gabriel P. Modolo, Filipe W. Leal-Pereira, Bethan E. Phillips, Philip J. Atherton, Kenneth Smith,et al.
MDPI AG
Background/Objectives: The acute phase of stroke is marked by inflammation and mobility changes that can compromise nutritional status. This study was a randomized, double-blind, placebo-controlled trial evaluating the effectiveness of creatine supplementation for older people during seven days of hospitalization for stroke compared to usual care. Method: The primary outcome measures were changes in functional capacity, strength, muscle mass, and muscle degradation. The secondary outcomes were changes in serum biomarkers related to inflammation, fibrosis, anabolism, and muscle synthesis. In addition, a follow-up 90 days after the stroke verified functional capacity, strength, quality of life, and mortality. Following admission for an acute stroke, participants received either creatine (10 g) or a visually identical placebo (10 g) orally twice daily. Both groups received supplementation with protein to achieve the goal of 1.5 g of protein/kg of body weight/day and underwent daily mobility training during seven days of hospitalization. Results: Thirty older people were included in two similar groups concerning baseline attributes (15—treatment/15—placebo). Conclusions: Creatine supplementation did not influence functional capacity, strength, or muscle mass during the first 7 days or outcomes 90 days after stroke. There were no serious adverse events associated with creatine supplementation. However, it decreased progranulin levels, raising a new possibility of creatine action. This finding needs further exploration to understand the biological significance of creatine–progranulin interaction.

Sepsis management in pre-hospital care – the earlier, the better?
Taline Lazzarin, Raquel Simões Ballarin, Leonardo Zornoff, Suzana Erico Tanni, Sergio Alberto Rupp de Paiva, Paula Schmidt Azevedo, and Marcos Ferreira Minicucci
Springer Science and Business Media LLC

Salivary Metabolomics in Patients with Long COVID-19 Infection
Luiz Machado, Robson Prudente, Estefânia Franco, Mariana Gatto, Gustavo Mota, Luana Pagan, Luís Brizola, Maércio dos Santos, Thulio Cunha, Robinson Sabino-Silva,et al.
MDPI AG
Background: Long COVID-19 has been characterized by the presence of symptoms lasting longer than 4 weeks after the acute infection. The pathophysiology of clinical manifestations still lacks knowledge. Objective: The objective of this paper was to evaluate metabolite abundance in the saliva of long COVID patients 60 days after hospital discharge. Methods: A convenience sample was composed of 30 post-discharge patients with long COVID and seven non-COVID-19 controls. All COVID-19 patients were evaluated by demographic characteristics, spirometry, 6 min walk test (6mWT), Saint George Respiratory Questionnaire (SGRQ), and body composition. Metabolomics was performed on saliva. Results: The long COVID-19 patients were 60.4 ± 14.3 years-old, and 66% male. Their lean body mass was 30.7 ± 7.3 kg and fat mass, 34.4 ± 13.7 kg. Spirometry evaluation showed forced vital capacity (FVC) of 3.84 ± 0.97 L with 96.0 ± 14.0% of the predicted value, and forced expiratory volume in the first second (FEV1) of 3.11 ± 0.83 L with 98.0 ± 16.0 of the predicted value. The long COVID-19 patients had reduced maximal inspiratory (90.1 ± 31.6 cmH2O) and maximal expiratory (97.3 ± 31.0 cmH2O) pressures. SGRQ showed domain symptoms of 32.3 ± 15.2, domain activities of 41.9 ± 25.6, and domain impact 13.7 ± 11.4, with a mean of 24.3 ± 14.9%. Physical capacity measured by distance covered in the 6mWT was 418.2 ± 130 m with a 73.3% (22.3–98.1) predictive value. The control group consisted of 44.1 ± 10.7-year-old men with a body mass index of 26.5 ± 1.66 Kg/m2. Metabolomics revealed 19 differentially expressed metabolites; expression was lower in 16 metabolites, and 2 metabolites were absent in the COVID-19 patients compared to controls. Calenduloside G methyl ester (p = 0.03), Gly Pro Lys (p = 0.0001), and creatine (p = 0.0001) expressions were lower in patients than controls. Conclusions: Long COVID-19 patients present less abundance of calenduloside G methyl ester, Gly Pro Lys, and creatine in saliva than healthy controls. Lower creatine abundance may be related to reduced physical capacity and fatigue

Corrigendum to “Development of an international glossary for clinical guidelines collaboration” “[Journal of Biomechanics 158 (2023) 84-91]”, (S089543562300077X), (10.1016/j.jclinepi.2023.03.026)
Rachel E. Christensen, Michael D. Yi, Bianca Y. Kang, Sarah A. Ibrahim, Noor Anvery, McKenzie Dirr, Stephanie Adams, Yasser S. Amer, Alexandre Bisdorff, Lisa Bradfield,et al.
Elsevier BV

Clinical and Physiological Variables in Patients with Post-COVID-19 Condition and Persistent Fatigue
Maércio Santos, Mariana Dorna, Estefânia Franco, Jéssica Geronutti, Luís Brizola, Letícia Ishimoto, Yasmin Barros, Adriele Costa, Carolina Breda, Caroline Marin,et al.
MDPI AG
Background/Objectives: Post-COVID-19 condition can manifest through various symptoms such as dyspnea, cognitive disturbances, and fatigue, with mechanisms related to these symptoms, particularly those related to fatigue, still requiring further clarification. Therefore, our aim was to assess the clinical and physiological variables in patients with post-COVID-19 condition and persistent fatigue. Methods: After one year post-COVID-19 infection, the patients underwent a comprehensive evaluation, including a complete blood count, a metabolic panel, complete spirometry, and assessments of dyspnea, quality of life, anxiety and depression, physical capacity, body composition, muscle strength, comorbidities, and medications. The participants were categorized into two groups: G1—fatigue and G2—non-fatigue. Results: Seventy-seven patients (53% female; 55 ± 11.8 years) were included, 37 in G1 and 40 in G2. As for clinical markers and symptoms of illness, in those with persistent fatigue symptoms, a greater sensation of dyspnea [BDI score: 7.5 (6–9) vs. 12 (9–12), p < 0.001; mMRC score: 1 (1–2) vs. 0 (0–1), p = 0.002], worse quality of life [SGRQ total score: 1404 (1007–1897) vs. 497 (274–985); p < 0.001], higher levels of anxiety [HADS-A score: 8 (5–9) vs. 3 (0.5–4); p < 0.001], and a reduction in peripheral and inspiratory muscle strength [handgrip strength: 34 (28–40) vs. 40 (30–46.5) kgf, p = 0.044; MIP: −81 ± 31 vs. −111 ± 33 mmHg, p < 0.001)] were observed. Conclusions: Those with persistent fatigue exhibited a greater sensation of dyspnea, higher levels of anxiety, reduced peripheral and inspiratory muscle strength, and a greater impairment of quality of life. The severity of fatigue was influenced by the worsening quality of life, heightened anxiety levels, and decreased peripheral muscle strength. Additionally, the worse quality of life was associated with a higher sensation of dyspnea, lower muscle strength, and reduced physical capacity.

Effects of exercise-based pulmonary rehabilitation on lung function, muscle strength and functional capacity in post-COVID-19 patients
Roberta Munhoz Manzano, Alessandro Domingues Heubel, and Suzana Erico Tanni
Springer Science and Business Media LLC

Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial
Suzana Margareth Lobo, Gaétan Plantefève, Girish Nair, Adilson Joaquim Cavalcante, Nara Franzin de Moraes, Estevao Nunes, Otis Barnum, Claudio Marcel Berdun Stadnik, Maria Patelli Lima, Muriel Lins,et al.
Elsevier BV

Long-term oxygen therapy to reduce length of hospital stay in COVID-19
Douglas Inomata Cardoso da Silva, Letícia Yumi Ishimoto, Estefânia Aparecida Thomé Franco, Maércio Souza Cícero dos Santos, Luís Fernando Pereira Brizola, Camila Aparecida Colombo, Edris Guardiano Savadkouhi, Luiz Henrique Soares Machado, Suzana Erico Tanni, and Robson Prudente
FapUNIFESP (SciELO)
SUMMARY OBJECTIVE: The aim of this study was to evaluate the efficacy of long-term oxygen therapy as a strategy to reduce hospitalization time in patients affected by COVID-19. METHODS: Between April and December 2021, COVID-19 patients with stable clinical conditions needing supplementary oxygen therapy during hospitalization were oriented to have hospital discharge with long-term oxygen therapy and reassessment after 15 days. RESULTS: A total of 62 patients were evaluated and, 15 days after discharge, 69% of patients had suspended long-term oxygen therapy, with no difference between the groups admitted to the intensive care unit or the ward (p=0.319). Among the individuals who needed to maintain long-term oxygen therapy, in addition to worse P/F ratio (265±57 vs. 345±51; p<0.001) and lower partial pressure of oxygen (55±12 vs. 72±11 mmHg; p<0.001), were those more obese (37±8 vs. 30±6 kg/m2; p=0.032), needed more time for invasive mechanical ventilation (46±27 vs. 20±16 days; p=0.029), had greater persistence of symptoms (p<0.001), and shorter time between the onset of symptoms and the need for hospitalization (7 [2–9] vs. 10 [6–12] days; p=0.039). CONCLUSION: Long-term oxygen therapy is an effective strategy for reducing hospitalization time in COVID-19 patients, regardless of gravity. Additionally, more obese patients with persistence of respiratory symptoms, faster disease evolution, and more days of invasive mechanical ventilation needed to maintain the long-term oxygen therapy longer.

Metal in biological samples from electronic cigarette users and those exposed to their second-hand aerosol: a narrative review
Diane Rezende Batista, Liana Sousa Coelho, Suzana Erico Tanni, and Irma de Godoy
Frontiers Media SA
IntroductionElectronic nicotine delivery systems (ENDS) are gradually becoming more popular, particularly, among today’s youth. Despite being marketed as safe by the tobacco industry, the notable absence of regulation in their composition is evident. Both the generated fluids and aerosol exhibit a wide variety of substances that are not yet fully identified. In addition to additives, the aerosol contains metals, the presence of which can be attributed to the excessive heating of metallic filaments used in vaporizing the liquid.ObjectiveThis review aimed to identify and describe studies that have assessed metal levels in biological samples obtained from electronic cigarette users and those exposed to their second-hand aerosol. This involved detailing the types and concentrations of metals identified and the biological samples in which the metals were detected.MethodsTwo independent researchers conducted searches in the MEDLINE and EMBASE databases to identify studies that measured the metal levels in human non-invasive biological samples from electronic cigarette users and second-hand exposure. Data were presented as a narrative review.ResultsIn total, 18 articles were included in this review. Overall active and passive exposure to ENDS was related to higher levels of many metals, including lead and cadmium, in biological samples. ENDS users, in general, have lower metal concentrations in biological samples compared to the users of combustible cigarettes.ConclusionThe exposure to primary and second-hand e-cigarette aerosol is related to higher metal concentrations in the biological samples. The adverse effects of this exposure on long-term users are yet to be determined.

Methylene blue in sepsis and septic shock: a systematic review and meta-analysis
Raquel Simões Ballarin, Taline Lazzarin, Leonardo Zornoff, Paula Schmidt Azevedo, Filipe Welson Leal Pereira, Suzana Erico Tanni, and Marcos Ferreira Minicucci
Frontiers Media SA
BackgroundMethylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock.MethodsThe authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470.ResultsDuring the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD −1.58; 95%CI −2.97, −0.20; I2 = 25%; p = 0.03), decreased days on mechanical ventilation (MD −0.72; 95%CI −1.26, −0.17; I2 = 0%; p = 0.010), and a shorter time to vasopressor discontinuation (MD −31.49; 95%CI −46.02, −16.96; I2 = 0%; p &lt; 0.0001). No association was found with methemoglobinemia.ConclusionAdministering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis
Luiz Vicente Ribeiro Ferreira da Silva Filho1, Rodrigo Abensur Athanazio2, Carolina Rodrigues Tonon3, Juliana Carvalho Ferreira2, and Suzana Erico Tanni3
Sociedade Brasileira de Pneumologia e Tisiologia
Objective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

Effectiveness of wearing masks during the COVID-19 outbreak in cohort and case-control studies: a systematic review and meta-analysis
Idevaldo Floriano1, Antônio Silvinato1,2, Hélio Arthur Bacha3, Alexandre Naime Barbosa4, Suzana Tanni5, Wanderley Marques Bernardo2, and 6
Sociedade Brasileira de Pneumologia e Tisiologia
Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = -0.21 (95% CI, -0.34 to -0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats
Eder Anderson Rodrigues, Camila Moreno Rosa, Dijon Henrique Salome Campos, Felipe Cesar Damatto, Gilson Masahiro Murata, Lidiane Moreira Souza, Luana Urbano Pagan, Mariana Gatto, Jessica Yumi Brosler, Hebreia Oliveira Almeida Souza,et al.
Springer Science and Business Media LLC
Abstract Background Sodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established. Objective To evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM. Methods Male Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results DM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM. Conclusion Long-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.

Organizing pneumonia and COVID-19
Carolina Rodrigues Tonon, Suzana Erico Tanni, Juliana Rocha, Irma Godoy, Bertha Furlan Polegato, Filipe Welson Leal Pereira, Danilo Martins, Robson Aparecido Prudente, Estefania Thome Franco, Fernando Brizola,et al.
Elsevier BV

Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API)
Alexandre Naime Barbosa, Alberto Chebabo, Carlos Starling, Clevy Pérez, Clóvis Arns Cunha, David de Luna, Estevão Portela Nunes, Gabriela Zambrano, Juliana Carvalho Ferreira, Julio Croda,et al.
Springer Science and Business Media LLC
Abstract Background Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. Methods Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. Results Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. Conclusion This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

Influence of CReatine supplementation on mUScle mass and strength after stroke (ICaRUS Stroke Trial): study protocol for a randomized controlled trial
Juli Thomaz de Souza, Marcos F. Minicucci, Natália C. Ferreira, Bertha F. Polegato, Marina Politi Okoshi, Gabriel P. Modolo, Bethan E. Phillips, Philip J. Atherton, Kenneth Smith, Daniel Wilkinson,et al.
Springer Science and Business Media LLC
Abstract Background Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life. Methods Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life. Discussion The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover. Trial registration The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4. Registered on 21 January 2019.

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium
Francesca Sperotto, Alba Gutiérrez-Sacristán, Simran Makwana, Xiudi Li, Valerie N. Rofeberg, Tianxi Cai, Florence T. Bourgeois, Gilbert S. Omenn, David A. Hanauer, Carlos Sáez,et al.
Elsevier BV

Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study
Arianna Dagliati, Zachary H. Strasser, Zahra Shakeri Hossein Abad, Jeffrey G. Klann, Kavishwar B. Wagholikar, Rebecca Mesa, Shyam Visweswaran, Michele Morris, Yuan Luo, Darren W. Henderson,et al.
Elsevier BV

Correction to: DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach (Advances in Therapy, (2023), 40, 10, (4282-4297), 10.1007/s12325-023-02583-1)
Dave Singh, Diego Litewka, Rafael Páramo, Adrian Rendon, Abdullah Sayiner, Suzana E. Tanni, Sudeep Acharya, Bhumika Aggarwal, Afisi S. Ismaila, Raj Sharma,et al.
Springer Science and Business Media LLC

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach
Dave Singh, Diego Litewka, Rafael Páramo, Adrian Rendon, Abdullah Sayiner, Suzana E. Tanni, Sudeep Acharya, Bhumika Aggarwal, Afisi S. Ismaila, Raj Sharma,et al.
Springer Science and Business Media LLC

Efficacy of BREATHOX<sup>®</sup> Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial
Suzana Tanni, Fernando Wehrmeister, Robson Prudente, Felipe Damatto, Carlos Breda Neto, Leiliane Oliveira, Luana Pagan, Mariana Gatto, Letícia Vieira, Liana Coelho,et al.
MDPI AG
(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, particles size between 1–10 μm), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06–3.81; Group 2: HR 2.17, 95% CI 1.17–4.04]. No differences between the groups for the reported symptoms’ resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20–3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.

Dual and Poly Use of Tobacco Products in a Sample of Pregnant Smokers: A Cross-sectional Study
André Luís Bertani, Suzana Erico Tanni, and Irma Godoy
Springer Science and Business Media LLC
Abstract Objectives Our aim was to assess the use of dual/poly tobacco in a sample of pregnant women. Design: cross-sectional survey. Methods Twenty prenatal care units in Botucatu, Sao Paulo, Brazil. We evaluated 127 high-risk pregnant smokers during prenatal care. Those who were 12–38 weeks pregnant and were currently smoking conventional cigarettes. The study enrollment took place between January 2015 and December 2015. The dual/poly prevalence of tobacco products during pregnancy and the characteristics related to smoking in pregnant smokers through a specific questionnaire containing questions related to sociodemographic characteristics, comorbidities, gestational history, smoking history, secondhand smoke exposure, nicotine dependence, motivation stage and use of alternative forms of tobacco. Results Mean age was 26.9 ± 6.6 years, most had only elementary education and belonged to lower income economic groups. Twenty-five (19.7%) smoked conventional cigarettes only while 102 used conventional and alternative forms of tobacco products. Smoking pack-years was significantly lower in those only smoking conventional cigarettes than in dual/poly users. Proportion of patients with elevated degree of nicotine dependence was higher in conventional cigarettes users. On the other side, alcohol intake was higher in dual/poly smokers when compared to conventional cigarettes group. The alternative forms of smoking were associated with significantly higher occurrences of comorbidities as pulmonary, cardiovascular and cancer. Conclusions for Practice The prevalence of alternative forms users of smoking products is high during pregnancy. These data reinforce the importance of a family approach towards smoking in pregnant women and education about the risks of alternative forms of tobacco.

Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients
Hellen Christina Neves Rodrigues, Mikaelly Luiz Silva, Milena dos Santos Mantovani, Juliana Medeiros da Silva, Marielle Fernanda Panelli Domingues, Suzana Érico Tanni, Paula Schmidt Azevedo, Marcos Ferreira Minicucci, Marina Nogueira Berbel Buffarah, Amanda Gomes Pereira,et al.
Elsevier BV

Development of an international glossary for clinical guidelines collaboration
Rachel E. Christensen, Michael D. Yi, Bianca Y. Kang, Sarah A. Ibrahim, Noor Anvery, McKenzie Dirr, Stephanie Adams, Yasser S. Amer, Alexandre Bisdorff, Lisa Bradfield,et al.
Elsevier BV

Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation
Mariana L. Lafetá, Vitor C. Souza, Thaís C.F. Menezes, Carlos G.Y. Verrastro, Frederico J. Mancuso, André Luis P. Albuquerque, Suzana E. Tanni, Meyer Izbicki, Júlio P. Carlstron, Luiz Eduardo Nery,et al.
European Respiratory Society (ERS)
RationalePost-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation.MethodsThis prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis.Measurements and main results87 patients were evaluated; mean±sdpeak oxygen consumption was 19.5±5.0 mL·kg−1·min−1, and the tertiles were ≤17.0, 17.1–22.2 and ≥22.3 mL·kg−1·min−1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg−1·min−1reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg−1·min−1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption.ConclusionsExercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.

Suzana Erico Tanni

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