Impact of age on the transmission of SARS-CoV-2 in healthcare workers : Influence of nonoccupational risk factors.

BACKGROUND: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV­2) infection was highest among older adults early in the COVID-19 pandemic; however, this pattern was later reversed with young adults showing the highest incidence. The aim of this study was to identify risk factors in healthcare workers (HCWs) associated with this evolution. METHODS: We conducted a survey nested within a prospective cohort study of 680 HCWs from a tertiary referral public hospital who received 2 doses of SARS-CoV­2 vaccine in January and February 2021 (VACCICO-VAO cohort). In October 2022 all participants were invited to participate in a survey. Risk factors were tested for association with COVID-19 ever, the number of COVID-19 episodes, and the time to the first episode. RESULTS: Among 350 respondents (51% response rate, 90% female, mean age 48.1 years), 323 COVID-19 episodes were diagnosed during the study period. Multivariable analysis revealed that age < 35 years vs. > 50 years (odds ratio, OR 2.12, 95% confidence interval, CI 1.27-3.51; P = 0.004) and not maintaining social distance at social events (OR: 1.82, 95% CI: 1.16-3.19; P = 0.011) were associated with a higher risk of COVID-19. Age < 35 years (hazard ratio, HR 1.70, 95% CI 1.14-2.54; P = 0.010), and not maintaining social distance (HR 1.34, 95% CI 1.05-1.72; P = 0.020) were also associated with the time to the first episode. CONCLUSIONS: The youngest HCWs had the highest incidence rate of COVID-19, which was not explained by occupational risk factors or health conditions. The increase in nonoccupational exposure since the end of the lockdowns in summer 2020 could by a key factor.

Translating NIA-AA criteria into usual practice: Report from the ReDeMa Project.

INTRODUCTION: Biomarker-informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA-AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS: ReDeMa (Red de Demencias de Madrid) is a regional cohort of patients attending memory and neurology clinics. Core cerebrospinal fluid biomarkers were obtained, NIA-AA diagnostic criteria were considered, and changes in diagnosis and management were evaluated. RESULTS: A total of 233 patients were analyzed (mean age 70 years, 50% women, 73% AD). The diagnostic language was modified significantly, with a majority assumption of NIA-AA definitions (69%). Confidence in diagnosis increased from 70% to 92% (p < 0.0005) and management was changed in 71% of patient/caregivers. The influence of neurologist's age or expertise on study results was minimal. DISCUSSION: The NIA-AA criteria are adequate and utile for usual practice in memory and neurology clinics, improving diagnostic confidence and significantly modifying patient management. HIGHLIGHTS: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers increase diagnostic certainty regardless of the neurologist.AD CSF biomarkers lead to changes in disease management .Biomarker-enriched, 2011 NIA-AA diagnostic criteria are adequate for usual practice.

Exploring older people's experiences of the interpersonal care relationship between nurses and patients during hospitalization in the pandemic period: A qualitative study.

AIM: This article presents the findings of a qualitative study focusing on the experiences of people aged over 70 years in the interpersonal nurse-patient care relationship in hospital settings during and after the COVID-19 pandemic. The aim was to analyse different aspects of this relationship, including nurses' behaviour and caring attitudes, the person-centred model of care, patients' involvement in their own care and communication in the hospital context. DESIGN: An exploratory qualitative study was conducted on the basis of an interpretative framework. METHODS: Six focus groups were conducted. A total of 34 participants were purposively recruited from three nursing homes in Spain, Italy and Portugal. Specific inclusion criteria were used to select participants. RESULTS: Five main categories were identified. Analysis revealed the importance of empathy and sensitivity in caring relationships, as well as the need for personalized and patient-centred care. The importance of effective communication and recognition of ageist behaviour by professionals was highlighted. In addition, independent of the pandemic, situational factors in the hospital environment were identified that influence the interpersonal care relationship. CONCLUSIONS: The study highlights the need to promote a person-centred model of care that takes into account the specific preferences and needs of older people. This is achieved by identifying elements of the interpersonal nurse-patient relationship. In addition to highlighting the disparity of opinion regarding an active or passive role in self-care and decision making, the importance of addressing ageism and improving communication is emphasized. WHAT PROBLEM DID THE STUDY ADDRESS?: The importance of the patient-nurse relationship in hospital care has been highlighted in previous studies. Critical elements of the patient care experience have been identified as empathy and effective communication. Ageism in healthcare has been recognized as a potential barrier to patient-centred care. WHAT WERE THE KEY FINDINGS?: The main findings highlight the importance of empathy and personalized care, emphasize the importance of effective communication and address ageist behaviours in the nurse-patient relationship. WHERE AND WHO WILL THE RESEARCH IMPACT?: By highlighting the need for person-centred care and improved communication strategies, particularly in the context of caring for older patients during and after the COVID-19 pandemic, this research will have an impact on healthcare professionals, policy makers and carers. REPORTING METHOD: The COREQ guideline was used. PATIENT OR PUBLIC CONTRIBUTION: This study adopted a collaborative approach to ensure that patient perspectives were integrated into the research process. We organized regular focus groups. Patients were actively involved in shaping the research questions, refining the study design and interpreting the emerging findings. Their valuable input helped us to understand the nuances of their experience and to prioritize the aspects that were critical to their well-being. In addition, their insights guided the development of practical recommendations aimed at improving the interpersonal care relationship between nurses and patients in hospital settings, ensuring that their voices were heard and reflected in the proposed interventions. This patient-centred approach fostered a sense of empowerment among the participants. It reinforced the notion that their experiences and opinions are integral to shaping healthcare practice.

Relación entre el estreñimiento y la calidad de vida de las personas en tratamiento renal sustitutivo con hemodiálisis / Relationship between constipation and the quality of life of individuals undergoing renal replacement therapy with hemodialysis

Introducción:El estreñimiento es un problema frecuente en pacientes en hemodiálisis, asociado, entre otros aspectos a comorbilidad, polimedicación y restricciones hídricas y dieté-ticas, pudiendo llegar a afectar la calidad de vida. Objetivos: Analizar la relación del estreñimiento en la calidad de vida de pacientes en hemodiálisis, determinar la prevalen-cia del estreñimiento objetivo y subjetivo, y analizar las varia-bles más influyentes. Material y Método: Estudio observacional descriptivo trans-versal en una unidad de hemodiálisis hospitalaria. Se emplea-ron los Criterios Diagnósticos Roma IV (2016) y escala visual Bristol para evaluar el estreñimiento. Para evaluar la calidad de vida, el cuestionario CVE-20. Resultados: Se estudiaron 38 pacientes (58% hombres) con una edad media de 68,69±12,76 años, tiempo en hemodiá-lisis de 44±37,19 meses y el 31,57% eran sedentarios. La ingesta hídrica diaria fue de 1004,05±460,13 ml y diuresis 658,11±696,47 ml. El índice de Charlson fue 8,15±2,29 pun-tos. El 45% presentaron estreñimiento subjetivo y 42% obje-tivo. Los pacientes con estreñimiento fueron: 56% mujeres, con edad media de 67,81±14,88 años y tiempo en hemodiá-lisis de 40,06±32,97 meses; 12% tenían pautados opioides, 44% quelantes del fósforo, 56% hierro intravenoso y 25% laxantes. La calidad de vida fue inferior en los pacientes es-treñidos (53,06 vs 69,62 puntos); existiendo diferencias signi-ficativas en todas las dimensiones del cuestionario.Conclusiones: En los pacientes en hemodiálisis existe una importante prevalencia de estreñimiento, siendo más pre-valente en mujeres. Este estreñimiento está asociado a peor percepción de la calidad de vida (AU)

Introducción: Constipation is a frequent issue in hemodialy-sis patients, associated, among other factors, with comorbidi-ty, polypharmacy, and restrictions in fluid and dietary intake, potentially affecting the quality of life.Objectives: To analyze the relationship between constipation and the quality of life of hemodialysis patients, determine the prevalence of objective and subjective constipation, and analyze the most influential variables.Material and Method: Cross-sectional descriptive obser-vational study in a hospital hemodialysis unit. The Rome IV Diagnostic Criteria (2016) and the Bristol Visual Scale were used to assess constipation. Quality of life was evaluated using the CVE-20 questionnaire.Results: A total of 38 patients were studied (58% males) with a mean age of 68.69±12.76 years, a hemodialysis du-ration of 44±37.19 months, and 31.57% were sedentary. aily fluid intake was 1004.05±460.13 ml, and diuresis was 658.11±696.47 ml. The Charlson index was 8.15±2.29 points. Subjective constipation was present in 45%, and ob-jective constipation in 42%. Patients with constipation were 56% females, with a mean age of 67.81±14.88 years, and hemodialysis duration of 40.06±32.97 months; 12% were prescribed opioids, 44% phosphorus binders, 56% intra-venous iron, and 24% laxatives. Quality of life was lower in constipated patients (53.06 vs. 69.62 points), with significant differences in all dimensions of the questionnaire.Conclusions: Hemodialysis patients have a significant preva-lence of constipation, more prevalent in females. This consti-pation is associated with a poorer perception of quality of life (AU)

Life Satisfaction and Psychological Capital in Athletes with Physical Disabilities.

Athletes with physical disabilities practice fewer sports than people without disabilities due to the difficulties and barriers they face in their daily lives. Sports are a powerful tool offering multiple physical, psychological and social benefits and act as a facilitator in their societal integration and inclusion. Today, more and more studies are analysing the psychological strengths of athletes, as well as their well-being. This research aimed to describe the levels of life satisfaction and psychological capital in a sample of physically disabled athletes according to the following variables: age, gender, degree of dependence, type of disability and level of competition. A structured questionnaire was distributed to 101 federated athletes with physical disabilities in the Basque Autonomous Community, with a valid return rate of 79 participants. A study of the relationship between variables was conducted using student's t-test and ANOVA. A stepwise hierarchical multiple linear regression was also performed to assess the predictive capabilities of the analysed variables on life satisfaction. The findings showed that gender, degree of dependence and level of competition correlated with the psychological capital and life satisfaction of athletes with disabilities; male athletes scored higher in the self-efficacy and hope dimensions of psychological capital; athletes with lower levels of dependence scored higher on life satisfaction; and international athletes scored higher on psychological capital, specifically on the self-efficacy dimension. Finally, psychological capital and degree of dependence also had a significant influence on athletes' life satisfaction.

Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients. A TMRG and GINECO group study.

OBJECTIVE: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges. METHODS: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015. RESULTS: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS. CONCLUSION: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment.

¿Cómo evaluar la sepsis neonatal de inicio precoz? Estudio comparativo de tres estrategias de detección / How to assess early-onset neonatal sepsis? Comparison of three detection strategies

Introducción: La sepsis neonatal de inicio precoz puede causar morbimortalidad importante, sobre todo si se retrasa su identificación. La disminución de su incidencia en las últimas décadas motiva que sea importante encontrar un equilibrio entre reducir las pruebas complementarias y seguir detectando los pacientes afectos. Comparamos 3 estrategias de detección en pacientes con factores de riesgo: E1. Cribado analítico; E2. Calculadora de riesgo de sepsis neonatal; E3. Observación clínica. Pacientes y métodos: Estudio observacional retrospectivo, en recién nacidos con edad gestacional ≥34 semanas y con factores de riesgo o sintomatología compatible con sepsis neonatal de inicio precoz. Se analizaron los resultados de nuestra unidad con cribado analítico (E1) y se comparó con las otras 2 estrategias (E2 y E3) para valorar modificar nuestro protocolo. Resultados: Se incluyeron 754 pacientes cuyos factores de riesgo más frecuentes fueron la rotura prologada de membranas (35,5%) y la colonización materna por Streptococcus agalactiae (38,5%). Las E2 y E3 disminuirían la realización de analíticas (E1 56,8% de los pacientes; E2 9,9%; E3 22,4%; p<0,01), los ingresos hospitalarios (E1 11%; E2 6,9%; E3 7,9%; p<0,01) y la administración de antibioterapia (E1 8,6%; E2 6,7%; E3 6,4%; p<0,01). Trece pacientes se diagnosticaron de sepsis, las cuales se hubieran detectado con E2 y E3, salvo un paciente con bacteriemia asintomática por Enterococcusfaecalis. Ningún paciente con clínica leve y autolimitada en que no se inició antibioterapia, se diagnosticó posteriormente de sepsis. Conclusiones: La observación clínica estrecha parece una opción segura y podría disminuir la realización de pruebas complementarias, la tasa de hospitalización y el uso de antibioterapia innecesaria. Mantener una conducta expectante en pacientes con sintomatología leve y autolimitada en las primeras horas de vida parece no relacionarse con la no identificación de sepsis. (AU)

Introduction: Early-onset neonatal sepsis can cause significant morbidity and mortality, especially if it is not detected early. Given the decrease in its incidence in the past few decades, it is important to find a balance between reducing the use of diagnostic tests and continuing to detect affected patients. We compared 3 detection strategies in patients with risk factors (RFs) for infection: laboratory screening (S1), the neonatal sepsis risk calculator (S2) and clinical observation (S3). Patients and methods: Retrospective observational study in neonates born at 34 weeks or gestation or later and with RFs or symptoms compatible with early-onset neonatal sepsis. We analysed outcomes in our unit with the use of laboratory screening (S1) and compared them with the other two strategies (S2 and S3) to contemplate whether to modify our protocol. Results: The study included 754 patients, and the most frequent RFs were prolonged rupture of membranes (35.5%) and maternal colonization by Streptococcus agalactiae (38.5%). Strategies S2 and S3 would decrease the performance of laboratory tests (S1, 56.8% of patients; S2, 9.9%; S3, 22.4%; P<.01), hospital admissions (S1, 11%; S2, 6.9%; S3, 7.9%; P<.01) and the use of antibiotherapy (S1, 8.6%; S2, 6.7%; S3, 6.4%; P<.01). Sepsis was diagnosed in 13 patients, and it would have been detected with S2 and S3 except in 1 patient who had asymptomatic bacteriemia by Enterococcusfaecalis. No patient with mild and self-limited symptoms in whom antibiotherapy was not started received a diagnosis of sepsis later on. Conclusions: Close clinical observation seems to be a safe option and could reduce the use of diagnostic tests, hospital admission and unnecessary antibiotherapy. The watchful waiting approach in patients with mild and self-limiting symptoms in the first hours post birth does not appear to be associated with failure to identify sepsis. (AU)

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Methodology of the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: This article describes the methodology used for The Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). The PALLIC-2 sought to develop evidence-based clinical recommendations and when evidence was lacking, expert-based consensus statements and research priorities for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: Electronic searches were conducted using PubMed, Embase, and Cochrane Library (CENTRAL) databases from 2012 to March 2022. STUDY SELECTION: Content was divided into 11 sections related to PARDS, with abstract and full text screening followed by data extraction for studies which met inclusion with no exclusion criteria. DATA EXTRACTION: We used a standardized data extraction form to construct evidence tables, grade the evidence, and formulate recommendations or statements using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. DATA SYNTHESIS: This consensus conference was comprised of a multidisciplinary group of international experts in pediatric critical care, pulmonology, respiratory care, and implementation science which followed standards set by the Institute of Medicine, using the GRADE system and Research And Development/University of California, Los Angeles appropriateness method, modeled after PALICC 2015. The panel of 52 content and four methodology experts had several web-based meetings over the course of 2 years. We conducted seven systematic reviews and four scoping reviews to cover the 11 topic areas. Dissemination was via primary publication listing all statements and separate supplemental publications for each subtopic that include supporting arguments for each recommendation and statement. CONCLUSIONS: A consensus conference of experts from around the world developed recommendations and consensus statements for the definition and management of PARDS and identified evidence gaps which need further research.

How to assess early-onset neonatal sepsis? Comparison of three detection strategies.

INTRODUCTION: Early-onset neonatal sepsis (EONS) can cause significant morbidity and mortality, especially if it is not detected early. Given the decrease in its incidence in the past few decades, it is important to find a balance between reducing the use of diagnostic tests and continuing to detect affected patients. We compared 3 detection strategies in patients with risk factors (RFs) for infection: laboratory screening (S1), the Neonatal Sepsis Risk Calculator (S2) and clinical observation (S3). PATIENTS AND METHODS: Retrospective observational study in neonates born at 34 weeks of gestation or later and with RFs or symptoms compatible with EONS. We analysed outcomes in our unit with the use of laboratory screening (S1) and compared them with the other two strategies (S2 and S3) to contemplate whether to modify our protocol. RESULTS: The study included 754 patients, and the most frequent RFs were prolonged rupture of membranes (35.5%) and maternal colonization by Streptococcus agalactiae (38.5%). Strategies S2 and S3 would decrease the performance of laboratory tests (S1, 56.8% of patients; S2, 9.9%; S3, 22.4%; P < 0.01), hospital admissions (S1, 11%; S2, 6.9%; S3, 7.9%; P < 0.01) and the use of antibiotherapy (S1, 8.6%; S2, 6.7%; S3, 6.4%; P < 0.01). Sepsis was diagnosed in 13 patients, and it would have been detected with S2 and S3 except in 1 patient who had asymptomatic bacteriemia by Enterococcus faecalis. No patient with mild and self-limited symptoms in whom antibiotherapy was not started received a diagnosis of sepsis later on. CONCLUSION: Close clinical observation seems to be a safe option and could reduce the use of diagnostic tests, hospital admission and unnecessary antibiotherapy. The watchful waiting approach in patients with mild and self-limiting symptoms in the first hours post birth does not appear to be associated with failure to identify sepsis.

Operational Definitions Related to Pediatric Ventilator Liberation.

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. INTERPRETATION: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome.

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.

Randomized clinical trial to assess the impact of oral intervention with cetylpyridinium chloride to reduce salivary SARS-CoV-2 viral load.

AIM: Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus. The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride (CPC) to reduce the viral load in the saliva of Coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: In this multi-centre, single-blind, randomized, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomized to two groups, namely test (n = 40) and placebo (n = 40). Saliva samples were collected at baseline and 2 h after rinsing. The samples were analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay test specific for the nucleocapsid (N) protein of SARS-CoV-2. RESULTS: With RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 h after a single rinse, N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus. CONCLUSIONS: The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.

A Network Meta-analysis of Dexamethasone for Preventing Postextubation Upper Airway Obstruction in Children.

Rationale: Periextubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. Objectives: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. Methods: MEDLINE, CINAHL, and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 h before extubation) and the dose (high dose: ⩾0.5 mg/kg/dose). We performed Bayesian network meta-analysis with studies grouped into four regimens: high dose, early use (HE); low dose, early use (LE); high dose, late use (HL); and low dose, late use. Results: Eight trials (n = 903) were included in the analysis. For preventing UAO (odds ratio; 95% credible interval), HE (0.13; 0.04-0.36), HL (0.39; 0.19-0.74), and LE (0.15; 0.04-0.58) regimens appear to be more effective than no dexamethasone (low certainty). HE and LE had the highest probability of being the top-ranked regimens for preventing UAO (surface under the cumulative ranking curve 0.901 and 0.808, respectively). For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared with no dexamethasone (very low certainty). HE and LE were the top-ranked regimens (surface under the cumulative ranking curve 0.803 and 0.720, respectively) for preventing reintubation. Sensitivity analysis showed that regimens that started >12 hours before extubation were likely more effective than regimens started >6 hours before extubation. Conclusions: Periextubation dexamethasone can prevent postextubation UAO in children, but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 h before extubation) appears to be more important than the dose of dexamethasone. Ultimately, the specific steroid strategy should be personalized, considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.

Concealed Inherited Cardiomyopathies Detected in Cardio-Oncology Screening.

INTRODUCTION: Basal cardiovascular risk assessment in cardio-oncology is essential. Integrating clinical information, ECG and transthoracic echocardiogram can identify concealed inherited cardiomyopathies (ICMPs) with potential added risk of cardiotoxicity. We aimed to evaluate the impact of our Cardio-Oncology Unit design in detecting concealed ICMPs. METHODS: We carried out a retrospective study of all consecutive breast cancer patients referred to the Cardio-Oncology Unit for cardiac evaluation (2020-2022). ICMPs diagnosis was provided according to ESC guidelines and underwent genetic testing. ICMPs prevalence in this cohort was compared to the highest and lowest frequency reported in the general population. RESULTS: Among 591 breast cancer patients, we identified eight patients with ICMPs: one arrhythmogenic cardiomyopathy (ACM), three familial non-ischemic dilated cardiomyopathy (DCM), three hypertrophic cardiomyopathy (HCM) and one left ventricular non-compaction cardiomyopathy (LVNC), which has now been reclassified as non-dilated left ventricular cardiomyopathy. The number of ICMPs identified was within the expected range (neither overdiagnosed nor overlooked): ACM 0.0017 vs. 0.0002-0.001 (p 0.01-0.593); DCM 0.0051 vs. 0.002-0.0051 (p 0.094-0.676); HCM 0.005 vs. 0.0002-0.002 (p < 0.001-0.099); LVCN 0.0017 vs. 0.00014-0.013 (p 0.011-0.015). Genetic testing identified a pathogenic FLNC variant and two pathogenic TTN variants. CONCLUSION: Opportunistic screening of ICMPs during basal cardiovascular risk assessment can identify high-risk cancer patients who benefit from personalized medicine and enables extension of prevention strategies to all available relatives at concealed high cardiovascular risk.

The Arabidopsis ATP-Binding Cassette E protein ABCE2 is a conserved component of the translation machinery.

ATP-Binding Cassette E (ABCE) proteins dissociate cytoplasmic ribosomes after translation terminates, and contribute to ribosome recycling, thus linking translation termination to initiation. This function has been demonstrated to be essential in animals, fungi, and archaea, but remains unexplored in plants. In most species, ABCE is encoded by a single-copy gene; by contrast, Arabidopsis thaliana has two ABCE paralogs, of which ABCE2 seems to conserve the ancestral function. We isolated apiculata7-1 (api7-1), the first viable, hypomorphic allele of ABCE2, which has a pleiotropic morphological phenotype reminiscent of mutations affecting ribosome biogenesis factors and ribosomal proteins. We also studied api7-2, a null, recessive lethal allele of ABCE2. Co-immunoprecipitation experiments showed that ABCE2 physically interacts with components of the translation machinery. An RNA-seq study of the api7-1 mutant showed increased responses to iron and sulfur starvation. We also found increased transcript levels of genes related to auxin signaling and metabolism. Our results support for the first time a conserved role for ABCE proteins in translation in plants, as previously shown for the animal, fungal, and archaeal lineages. In Arabidopsis, the ABCE2 protein seems important for general growth and vascular development, likely due to an indirect effect through auxin metabolism.

In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy.

Prostate cancer (PCa), one of the leading causes of cancer-related deaths, currently lacks effective treatment for advanced-stage disease. Paclitaxel (PTX) is a highly active chemotherapeutic drug and the first-line treatment for PCa; however, conventional PTX formulation causes severe hypersensitivity reactions and limits PTX use at high concentrations. In the pursuit of high molecular weight, biodegradable, and pH-responsive polymeric carriers, one conjugates PTX to a polyacetal-based nanocarrier to yield a tert-Ser-PTX polyacetal conjugate. tert-Ser-PTX conjugate provides sustained release of PTX over 2 weeks in a pH-responsive manner while also obtaining a degree of epimerization of PTX to 7-epi-PTX. Serum proteins stabilize tert-Ser-PTX, with enhanced stability in human serum versus PBS (pH 7.4). In vitro efficacy assessments in PCa cells demonstrate IC50 values above those for the free form of PTX due to the differential cell trafficking modes; however, in vivo tolerability assays demonstrate that tert-Ser-PTX significantly reduces the systemic toxicities associated with free PTX treatment. tert-Ser-PTX also effectively inhibits primary tumor growth and hematologic, lymphatic, and coelomic dissemination, as confirmed by in vivo and ex vivo bioluminescence imaging and histopathological evaluations in mice carrying orthotopic LNCaP tumors. Overall, the results suggest the application of tert-Ser-PTX as a robust antitumor/antimetastatic treatment for PCa.

Acute Hypoxemic Respiratory Failure in Children at the Start of COVID-19 Outbreak: A Nationwide Experience.

STUDY DESIGN: This is a prospective, multicenter, and observational study with the aim of describing physiological characteristics, respiratory management, and outcomes of children with acute hypoxemic respiratory failure (AHRF) from different etiologies receiving invasive mechanical ventilation (IMV) compared with those affected by SARS-CoV-2. METHODS AND MAIN RESULTS: Twenty-eight patients met the inclusion criteria: 9 patients with coronavirus disease 2019 (COVID-19) and 19 patients without COVID-19. Non-COVID-19 patients had more pre-existing comorbidities (78.9% vs. 44.4%) than COVID-19 patients. At AHRF onset, non-COVID-19 patients had worse oxygenation (PaO2/FiO2 = 95 mmHg (65.5-133) vs. 150 mmHg (105-220), p = 0.04), oxygenation index = 15.9 (11-28.4) vs. 9.3 (6.7-10.6), p = 0.01), and higher PaCO2 (48 mmHg (46.5-63) vs. 41 mmHg (40-45), p = 0.07, that remained higher at 48 h: 54 mmHg (43-58.7) vs. 41 (38.5-45.5), p = 0.03). In 12 patients (5 COVID-19 and 7 non-COVID-19), AHRF evolved to pediatric acute respiratory distress syndrome (PARDS). All non-COVID-19 patients had severe PARDS, while 3 out of 5 patients in the COVID-19 group had mild or moderate PARDS. Overall Pediatric Intensive Care Medicine (PICU) mortality was 14.3%. CONCLUSIONS: Children with AHRF due to SARS-CoV2 infection had fewer comorbidities and better oxygenation than patients with non-COVID-19 AHRF. In this study, progression to severe PARDS was rarely observed in children with COVID-19.