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BACKGROUND: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses. METHODS: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies - one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models. RESULTS: Among children, the overall effectiveness of the 10-µg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-µg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-µg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose. CONCLUSIONS: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna BNT162 , COVID-19 , Eficacia de las Vacunas , Adolescente , Niño , Humanos , Vacuna BNT162/administración & dosificación , Vacuna BNT162/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/uso terapéutico , Qatar/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Preescolar , Eficacia de las Vacunas/estadística & datos numéricosRESUMEN
BACKGROUND: The protection conferred by natural immunity, vaccination, and both against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the BA.1 or BA.2 sublineages of the omicron (B.1.1.529) variant is unclear. METHODS: We conducted a national, matched, test-negative, case-control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19). RESULTS: The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-1.1%; 95% CI, -7.1 to 4.6), but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection and two doses of BNT162b2 was 55.1% (95% CI, 50.9 to 58.9), and the effectiveness of previous infection and three doses of BNT162b2 was 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273. CONCLUSIONS: No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , COVID-19 , Inmunidad Innata , Inmunización , SARS-CoV-2 , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/uso terapéutico , Vacuna BNT162/inmunología , Vacuna BNT162/uso terapéutico , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Estudios de Casos y Controles , Humanos , Inmunidad Innata/inmunología , Inmunización Secundaria , Recurrencia , SARS-CoV-2/inmunología , VacunaciónRESUMEN
BACKGROUND: Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear. METHODS: We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19-related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models. RESULTS: In a population of 2,239,193 persons who had received at least two doses of BNT162b2 or mRNA-1273 vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19-related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273-vaccinated cohorts. CONCLUSIONS: The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19-related hospitalization and death. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna BNT162/inmunología , COVID-19 , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Cohortes , Humanos , Inmunización Secundaria , Inmunogenicidad Vacunal , Qatar/epidemiología , ARN Mensajero , Estudios Retrospectivos , SARS-CoV-2 , Eficacia de las Vacunas , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
In cancer patients, immune cells are often functionally compromised due to the immunosuppressive features of the tumor microenvironment (TME) which contribute to the failures in cancer therapies. Clinical and experimental evidence indicates that developing tumors adapt to the immunological environment and create a local microenvironment that impairs immune function by inducing immune tolerance and invasion. In this context, microenvironmental hypoxia, which is an established hallmark of solid tumors, significantly contributes to tumor aggressiveness and therapy resistance through the induction of tumor plasticity/heterogeneity and, more importantly, through the differentiation and expansion of immune-suppressive stromal cells. We and others have provided evidence indicating that hypoxia also drives genomic instability in cancer cells and interferes with DNA damage response and repair suggesting that hypoxia could be a potential driver of tumor mutational burden. Here, we reviewed the current knowledge on how hypoxic stress in the TME impacts tumor angiogenesis, heterogeneity, plasticity, and immune resistance, with a special interest in tumor immunogenicity and hypoxia targeting. An integrated understanding of the complexity of the effect of hypoxia on the immune and microenvironmental components could lead to the identification of better adapted and more effective combinational strategies in cancer immunotherapy. Clearly, the discovery and validation of therapeutic targets derived from the hypoxic tumor microenvironment is of major importance and the identification of critical hypoxia-associated pathways could generate targets that are undeniably attractive for combined cancer immunotherapy approaches.
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Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Inmunoterapia , Hipoxia/genética , Hipoxia/metabolismo , Tolerancia Inmunológica/genética , Hipoxia de la Célula/genética , Microambiente TumoralRESUMEN
BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. METHODS: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2). RESULTS: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). CONCLUSIONS: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.
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Neoplasias de Células Epitelioides Perivasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias de Células Epitelioides Perivasculares/terapia , Neoplasias de Células Epitelioides Perivasculares/mortalidad , Neoplasias de Células Epitelioides Perivasculares/cirugía , Anciano , Adulto Joven , Adolescente , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
BACKGROUND: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear. METHODS: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021. RESULTS: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months. CONCLUSIONS: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna BNT162/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Eficacia de las Vacunas , Vacuna nCoV-2019 mRNA-1273 , Adulto , Anciano , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/mortalidad , Vacunas contra la COVID-19 , Estudios de Casos y Controles , Femenino , Humanos , Inmunización Secundaria , Masculino , Persona de Mediana Edad , Qatar/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Health care routinely fails Indigenous peoples and anti-Indigenous racism is common in clinical encounters. Clinical training programs aimed to enhance Indigenous cultural safety (ICS) rely on learner reported impact assessment even though clinician self-assessment is poorly correlated with observational or patient outcome reporting. We aimed to compare the clinical impacts of intensive and brief ICS training to control, and to assess the feasibility of ICS training evaluation tools, including unannounced Indigenous standardized patient (UISP) visits. METHOD: Using a prospective parallel group three-arm randomized controlled trial design and masked standardized patients, we compared the clinical impacts of the intensive interactive, professionally facilitated, 8- to10-h Sanyas ICS training; a brief 1-h anti-bias training adapted to address anti-Indigenous bias; and control continuing medical education time-attention matched to the intensive training. Participants included 58 non-Indigenous staff physicians, resident physicians and nurse practitioners from family practice clinics, and one emergency department across four teaching hospitals in Toronto, Canada. Main outcome measures were the quality of care provided during UISP visits including adjusted odds that clinician would be recommended by the UISP to a friend or family member; mean item scores on patient experience of care measure; and clinical practice guideline adherence for NSAID renewal and pain assessment. RESULTS: Clinicians in the intensive or brief ICS groups had higher adjusted odds of being highly recommended to friends and family by standardized patients (OR 6.88, 95% CI 1.17 to 40.45 and OR 7.78, 95% CI 1.05 to 58.03, respectively). Adjusted mean item patient experience scores were 46% (95% CI 12% to 80%) and 40% (95% CI 2% to 78%) higher for clinicians enrolled in the intensive and brief training programs, respectively, compared to control. Small sample size precluded detection of training impacts on clinical practice guideline adherence; 100% of UISP visits were undetected by participating clinicians. CONCLUSIONS: Patient-oriented evaluation design and tools including UISPs were demonstrated as feasible and effective. Results show potential impact of cultural safety training on patient recommendation of clinician and improved patient experience. A larger trial to further ascertain impact on clinical practice is needed. TRIAL REGISTRATION: Clinicaltrials.org NCT05890144. Retrospectively registered on June 5, 2023.
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Antiinflamatorios no Esteroideos , Servicio de Urgencia en Hospital , Humanos , Estudios Prospectivos , Canadá , FamiliaRESUMEN
Hydrogen storage by cryoadsorption on porous materials has the advantages of low material cost, safety, fast kinetics, and high cyclic stability. The further development of this technology requires reliable data on the H2 uptake of the adsorbents, however, even for activated carbons the values between different laboratories show sometimes large discrepancies. So far no reference material for hydrogen cryoadsorption is available. The metal-organic framework ZIF-8 is an ideal material possessing high thermal, chemical, and mechanical stability that reduces degradation during handling and activation. Here, we distributed ZIF-8 pellets synthesized by extrusion to 9 laboratories equipped with 15 different experimental setups including gravimetric and volumetric analyzers. The gravimetric H2 uptake of the pellets was measured at 77â K and up to 100â bar showing a high reproducibility between the different laboratories, with a small relative standard deviation of 3-4 % between pressures of 10-100â bar. The effect of operating variables like the amount of sample or analysis temperature was evaluated, remarking the calibration of devices and other correction procedures as the most significant deviation sources. Overall, the reproducible hydrogen cryoadsorption measurements indicate the robustness of the ZIF-8 pellets, which we want to propose as a reference material.
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BACKGROUND: Redo-transcatheter aortic valve replacement (TAVR) is a promising treatment for transcatheter aortic valve degeneration, becoming increasingly relevant with an aging population. In redo-TAVR, the leaflets of the initial (index) transcatheter aortic valve (TAV) are displaced vertically when the second TAV is implanted, creating a cylindrical cage that can impair coronary cannulation and flow. Preventing coronary obstruction and maintaining coronary access is essential, especially in young and low-risk patients undergoing TAVR. This study aimed to develop a new leaflet modification strategy using laser ablation to prevent coronary obstruction and facilitate coronary access after repeat TAVR. METHODS: To evaluate the feasibility of the leaflet modification technique using laser ablation, the initial phase of this study involved applying a medical-grade ultraviolet laser for ablation through pericardial tissue. Following this intervention, computational fluid dynamics simulations were utilized to assess the efficacy of the resulting perforations in promoting coronary flow. These simulations played a crucial role in understanding the impact of the modifications on blood flow patterns, ensuring these changes would facilitate the restoration of coronary circulation. RESULTS: Laser ablation of pericardium leaflets was successful, demonstrating the feasibility of creating openings in the TAV leaflets. Flow simulation results show that ablation of index valve leaflets can effectively mitigate the flow obstruction caused by sinus sequestration in redo-TAVR, with the extent of restoration dependent on the number and location of the ablated openings. CONCLUSIONS: Laser ablation could be a viable method for leaflet modification in redo-TAVR, serving as a new tool in interventional procedures.
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Fuchsine acid serves as a supramolecular dye in Masson's trichrome stain, finding extensive applications in histology. It is also utilized with picric acid in Van Gieson's method to reveal red collagen fibers and in Masson's trichrome to highlight smooth muscle in contrast to collagen. Beyond these applications, it plays a crucial role in electronic fields and photonic devices as an organic semiconductor. Therefore, investigating and predicting the complex molecular structure of fuchsine acid becomes essential, serving as the foundation for understanding its physicochemical features. This article employs topological modeling, specifically a connection number edge partition, to explore the supramolecular nature of fuchsine acid. Closed formulae for key degree-based molecular descriptors are derived, aiming to illuminate the effectiveness of these descriptors for QSAR and QSPR analyses.
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OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.
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COVID-19 , Educación a Distancia , Personal de Salud , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Personal de Salud/educación , Educación a Distancia/métodos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Competencia Clínica , SARS-CoV-2 , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Transition of care refers to the continuity of health care during the movement from one healthcare setting to another as care needs change during a chronic illness. We sought to describe social, demographic, and clinical factors related to successful transition in a tertiary urban care facility in patients with CHD. Patients were identified utilising the electronic medical record. Inclusion criteria were patients with CHDs aged ≥15 years seen in the paediatric cardiology clinic between 2013 and 2014. Deceased patients were excluded. Clinical and demographic variables were collected. Patient charts were reviewed in 2015-2021 to determine if included patients were a) still in paediatric cardiology care, b) transitioned to adult cardiology/adult CHD, or were c) lost to follow-up. A total of 322 patients, 53% male (N:172), 46% female (N:149) were included. Majority had moderately complex lesions (N:132, 41%). Most patients had public insurance (N:172, 53%), followed by private insurance (N:67, 21%), while 15% of patients (N:47) were uninsured. Only 49% (N = 159) had successful transition, while 22% (N = 70) continued in care with paediatric cardiology, and 29% (N = 93) were lost to follow-up. Severity of CHD (p = 0.0002), having healthcare insurance (p < .0001), presence of a defibrillator (p = 0.0028), and frequency of paediatric cardiology visits (p = 0.0005) were significantly associated with successful transition. Most patients lost to follow-up (N:42,62%) were either uninsured or had public insurance. Lack of successful transition is multifactorial, and further efforts are needed to improve the process in patients with CHD.
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Cardiología , Cardiopatías Congénitas , Transición a la Atención de Adultos , Adulto , Niño , Humanos , Masculino , Femenino , Transferencia de Pacientes , Cardiopatías Congénitas/terapia , Cardiopatías Congénitas/complicaciones , Atención a la Salud , CiclofosfamidaRESUMEN
INTRODUCTION: Vascular access-related aneurysms (VARA) are a complication of arteriovenous fistulas. Repair techniques have been described in the literature with varied outcomes. MATERIALS AND METHODS: We conducted a prospective cohort study on patients who had VARA repair over 41 months. The indication for repair was an aneurysmal arteriovenous fistula (AVF) at risk of haemorrhage or difficulty in cannulation. Pseudoaneurysms, infected AVF and bleeding VARA were excluded. All patients underwent outflow stenosis treatment when present, followed by aneurysmorrhaphy. They were monitored periodically over 12 months, measuring functional primary and cumulative patency and access flow. We studied the patient demography, access flow and presence of outflow stenosis. Access flow was measured from the brachial artery (Qa) as a surrogate using ultrasonography. A Kaplan-Meier survival analysis was used to predict the primary and cumulative patency at 12 months and factors contributing to 12-month patency were analysed. RESULTS: A total of 64 patients were recruited for this study, of whom 58 completed the study. Most of the participants were male (67%) with a median age of 45 years. Forty-six patients (79.3%) had brachiocephalic fistula (BCF) aneurysms. Thirty-nine (67.2%) had preexisting outflow stenoses that required intervention. All patients underwent an aneurysmorrhaphy, of whom 12% had a cephalic arch vein transposition due to severe stenosis. Primary patency at 12 months was 86%, whereas the cumulative patency rate was 95%. Patency was significantly associated with younger age and showed a positive trend with higher preintervention Qa. Symptomatic recurrent stenosis developed in 17.2% of the cohort. CONCLUSION: Improving the patency of VARA entails the treatment of outflow stenosis and aneurysmorrhaphy. Surveillance is important to detect and treat recurrent outflow stenoses. The outcome is better among younger patients with pre-interventional access flow as measured in the brachial artery as a surrogate.
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Aneurisma , Derivación Arteriovenosa Quirúrgica , Grado de Desobstrucción Vascular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Aneurisma/cirugía , Aneurisma/etiología , Estudios Prospectivos , Adulto , Derivación Arteriovenosa Quirúrgica/efectos adversos , AncianoRESUMEN
Ischemic stroke is a leading cause of disability and there is a paucity of therapeutic strategies that promote functional recovery after stroke. Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as a tool to reduce infarct size in animal models of hyperacute stroke. In chronic stroke, tVNS paired with limb movements has been shown to enhance neurological recovery. In this review, we summarize the current evidence for tVNS in preclinical models and clinical trials in humans. We highlight the mechanistic pathways involved in the beneficial effects of tVNS. We critically evaluate the current gaps in knowledge and recommend the key areas of research required to translate tVNS into clinical practice in acute and chronic stroke.
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Accidente Cerebrovascular Isquémico , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Animales , Humanos , Nervio Vago/fisiologíaRESUMEN
BACKGROUND: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD. METHODS: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): (1) d-looped Transposition of the Great Arteries (d-TGA); (2) Tetralogy of Fallot (TOF); (3) single ventricle (SV) physiology; and (4) "other moderately or severely complex CHD." Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory. CONCLUSIONS: MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.
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COVID-19 , Cardiopatías Congénitas , Enfermedades no Transmisibles , Transposición de los Grandes Vasos , Adulto Joven , Humanos , Adulto , Niño , Cardiopatías Congénitas/epidemiología , Transposición de los Grandes Vasos/complicaciones , Estudios Transversales , Pandemias , Proyectos Piloto , Calidad de Vida , COVID-19/complicacionesRESUMEN
Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and additional clinical features not previously reported to be associated with PCH1, including dilated cardiomyopathy. On assessment, failure to thrive, microcephaly, distinctive facial features, and bluish sclera, were noted. Whole-exome sequencing was performed and revealed a novel homozygous missense variant c.547C > T (p.Arg183Trp) in the EXOSC1 gene. Functional studies in a budding yeast model that expresses the human EXOSC1 variant Arg183Trp show a slow-growth phenotype, whereas the previously identified PCH1F allele EXOSC1-Ser35Leu is lethal, indicating impaired exosome function for both of these variants. The protein levels of both EXOSC1 variants are reduced compared with wild-type when expressed in budding yeast. Herein, we ascertain the second case of PCH associated with a EXOSC1 variant that causes defects in RNA exosome function and provide a model organism system to distinguish between benign and pathogenic variants in EXOSC1.
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Enfermedades Cerebelosas , Microcefalia , Malformaciones del Sistema Nervioso , Atrofias Olivopontocerebelosas , Humanos , Femenino , Lactante , Microcefalia/genética , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/genética , Atrofias Olivopontocerebelosas/genética , Mutación , Complejo Multienzimático de Ribonucleasas del Exosoma/genética , Proteínas de Unión al ARN/genéticaRESUMEN
The present study investigates the complex topological characteristics of DNA networks, with a specific emphasis on the innovative metric known as Connection Number (CN) as a key factor in determining network structure. The Connection Number, represented as CN(v) for a vertex v, measures the count of unique paths that link v to every other vertex in the network. By employing rigorous mathematical modeling and analysis techniques, we are able to reveal the profound implications of CN (complex networks) in characterizing the structural robustness and dynamics of information flow within DNA networks. The study of how the theory of graphs and chemicals interact is known as chemical graph theory. This paper, computing the hyper Zagreb connection index, augmented connection index, inverse sum connection index, harmonic connection index, symmetric division connection index, geometric arithmetic connection index, and atom bond connectivity connection index, of two significant types of backbone DNA and Barycentric subdivision of backbone DNA networks. Direct method computation is used to produce these Connection-based topological descriptors.
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ADNRESUMEN
Survival of patients after repair of coarctation of Aorta (CoA) has improved significantly over the decades, but patients have decreased life expectancy as compared to the general population. This has been attributed to increased hypertension, cerebrovascular disease, and coronary artery disease. There has also been an increasing concern of overweight and obesity in patients with adult congenital heart disease. While there have been studies looking at the impact of long-term hypertension on myocardial performance and outcomes in this population, this study aims to assess the impact of obesity in these patients on their myocardial performance. Ventriculo-arterial coupling is used as a measure of myocardial performance which reflects the interaction between cardiac contractility and arterial elastance. Patients after CoA repair are known to have hypertension affecting the arterial elastance. Obesity affects cardiac contractility as well. This study demonstrated that in a group of young patients after CoA repair, body mass index (BMI) has a relationship with left ventricular (LV) contractility and myocardial performance. This relationship was independent of blood pressure. BMI itself was not seen to affect the determinants of diastolic function in this study, suggesting that LV contractility may be affected before one can notice a change in the diastolic function secondary to BMI.
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Patients with single ventricle cardiac disease palliated with Fontan procedures inevitably develop Fontan-Associated Liver Disease (FALD), which poses a significant risk for hepatocellular carcinoma (HCC). Standard imaging criteria for the diagnosis of cirrhosis are not reliable due to parenchymal heterogeneity of FALD. We present 6 cases to demonstrate our center's experience and the challenges in diagnosing HCC within this patient population.
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Carcinoma Hepatocelular , Procedimiento de Fontan , Neoplasias Hepáticas , Corazón Univentricular , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiologíaRESUMEN
OBJECTIVE: This study was aimed to examine the impact of daily self-weighing via remote monitoring on postpartum weight loss. STUDY DESIGN: This was a secondary analysis of a nonrandomized controlled trial comprised of postpartum women with diagnosed hypertensive-related disorders in pregnancy who received a tablet device linked to Bluetooth-enabled equipment including a scale and blood pressure cuff. In addition to blood pressure monitoring, participants were instructed to perform daily self-weighing. The primary outcome of this study was to determine whether postpartum women who performed daily self-weighing lost more weight than those who did not, with a 42-day endpoint based on a 6-week postpartum visit weight. RESULTS: Overall, 214 women participated in this program and 214 received usual care. Median weight loss for women participating in the remote blood pressure monitoring system was 23.0 (interquartile range [IQR]: 17-30) pounds versus 23.0 (IQR: 17-29) pounds among controls. Weight loss did not vary by prepregnancy obesity (median: 20 pounds [IQR: 17-28 pounds] for nonobese and 23 [IQR: 17-30] pounds for women with obesity, p = 0.16). Women who weighed themselves more than half of follow-up days lost a median of 24 pounds (IQR: 17-30 pounds) compared with 20.5 pounds (IQR: 14-29 pounds), p = 0.06. Women who weighed themselves more than half of follow-up days lost a mean of 11.4% (standard deviation [SD] = 0.41%) of body weight compared with 9.1% (SD = 0.74%; p = 0.01). The amount of weight loss in the telehealth group was correlated with the number of daily weights performed (Pearson's correlation coefficient 0.164, p = 0.025). Postpartum weight loss for daily self-weighing participants was most notable in the first 2 weeks with ongoing weight loss up to the 42-day (6-week) endpoint of this secondary analysis. CONCLUSION: Daily self-weighing alone may be insufficient to promote postpartum weight loss. However, there was a slight trend toward more weight loss with more frequent weighing. KEY POINTS: · Daily self-weighing is insufficient for postpartum weight loss.. · Women who weighed themselves more lost slightly more weight.. · Weight loss was the most notable in the first 2 weeks.. · Its use as one part of a program may be worth studying..