Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

AIMS: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. METHODS AND RESULTS: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). CONCLUSIONS: Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

Modifiable self-management practices impact nocturnal and morning glycaemia in type 1 diabetes.

AIMS: To identify risk factors for nocturnal/morning hypo- and hyperglycaemia in type 1 diabetes. METHODS: Data on self-management practices were obtained from 3-day records. We studied the associations between self-management practices on the first recording day and the self-reported blood glucose (BG) concentrations on the subsequent night/morning. RESULTS: Of the 1025 participants (39 % men, median age 45 years), 4.4 % reported nocturnal hypoglycaemia (<3.9 mmol/l), 9.8 % morning hypoglycaemia, 51.5 % morning euglycaemia, and 34.3 % morning hyperglycaemia (≥8.9 mmol/l). Within hypoglycaemic range, insulin pump use was associated with higher nocturnal BG concentration (B=0.486 [95 % Confidence Interval=0.121-0.852], p=0.009). HbA1c was positively (0.046 [0.028-0.065], p<0.001), while antecedent fibre intake (-0.327 [-0.543 - -0.111], p=0.003) and physical activity (PA) (-0.042 [-0.075 - -0.010], p=0.010) were inversely associated with morning BG concentration. The odds of morning hypoglycaemia were increased by previous day hypoglycaemia (OR=2.058, p=0.002) and alcohol intake (1.031, p=0.001). Previous day PA (0.977, p=0.031) and fibre intake (0.848, p=0.017) were inversely, while HbA1c (1.027, p<0.001) was positively associated with the risk of morning hyperglycaemia. CONCLUSIONS: Alcohol avoidance may prevent nocturnal hypoglycaemia, while PA and fibre intake may reduce hyperglycaemia risk. Avoidance of daytime hypoglycaemia and keeping HbA1c in control may help maintain normoglycaemia also at night-time.

The Importance of Identifying Children With Brain Injury in Schools: Speech-Language Pathologists as Crucial Partners.

PURPOSE: The purpose of this article is to describe the importance of and strategies to identify traumatic brain injury (TBI) and associated cognitive-communication disorders (CCDs) in children, a priority identified by the attendees at the Fourth International Cognitive-Communication Disorders Conference. Childhood TBI is associated with a range of difficulties, including CCDs, that can adversely impact functioning and participation into adulthood. Identifying a history of TBI in children in schools is the crucial first step to then monitor, assess, and provide evidence-based intervention and accommodations in collaboration with families and medical and educational professionals. CONCLUSION: Given that CCDs are treatable, effective identification, assessment, and management of students with TBI and resulting CCDs can reduce adverse outcomes in adult survivors of childhood TBI. Speech-language pathologists must be aware of their expertise in assessing and treating CCDs in children with TBI and advocate for programmatic and policy changes to better identify and support children with TBI.

Utilizing COVID-19 as a Model for Diagnostics Using an Electrochemical Sensor.

This paper reports a rapid and sensitive sensor for the detection and quantification of the COVID-19 N-protein (N-PROT) via an electrochemical mechanism. Single-frequency electrochemical impedance spectroscopy was used as a transduction method for real-time measurement of the N-PROT in an immunosensor system based on gold-conjugate-modified carbon screen-printed electrodes (Cov-Ag-SPE). The system presents high selectivity attained through an optimal stimulation signal composed of a 0.0 V DC potential and 10 mV RMS-1 AC signal at 100 Hz over 300 s. The Cov-Ag-SPE showed a log response toward N-PROT detection at concentrations from 1.0 ng mL-1 to 10.0 µg mL-1, with a 0.977 correlation coefficient for the phase (θ) variation. An ML-based approach could be created using some aspects observed from the positive and negative samples; hence, it was possible to classify 252 samples, reaching 83.0, 96.2 and 91.3% sensitivity, specificity, and accuracy, respectively, with confidence intervals (CI) ranging from 73.0 to 100.0%. Because impedance spectroscopy measurements can be performed with low-cost portable instruments, the immunosensor proposed here can be applied in point-of-care diagnostics for mass testing, even in places with limited resources, as an alternative to the common diagnostics methods.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BACKGROUND: Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes. METHODS: The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status. RESULTS: In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status. CONCLUSIONS: In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Anticonvulsant activity of Tetrahydrolinalool: behavioral, electrophysiological, and molecular docking approaches.

Tetrahydrolinalool (THL) is an acyclic monoterpene alcohol, produced during linalol metabolism and also a constituent of essential oils. As described in the literature, many monoterpenes present anticonvulsant properties, and thus we became interested in evaluating the anticonvulsant activity of Tetrahydrolinalool using in mice model as well as in silico approaches. Our results demonstrated that THL increased latency to seizure onset and also reduced the mortality, in picrotoxin induced seizure tests. The results may be related to GABAergic regulation, which was also suggested in seizure testing induced by 3-mercapto-propionic acid. In the strychnine-induced seizure testing, none of the groups pretreated with THL modulated the parameters indicative of anticonvulsant effect. The electrophysiological results revealed that THL treatment reduces seizures induced by pentylenetetrazole. The in silico molecular docking studies showed that the interaction between THL and a GABAA receptor model formed a stable complex, in comparison to the crystaligraphic structure of diazepam, a structurally related ligand. In conclusion, all the evidences showed that THL presents effective anticonvulsant activity related to the GABAergic pathway, being a candidate for treatment of epileptic syndromes.

Actigraphy methodology in the Kids Mod PAH trial: Physical activity as a functional endpoint in pediatric clinical trials.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

Health-Related Quality of Life Across the Spectrum of Pulmonary Hypertension.

BACKGROUND: Health-related quality of life (HRQOL) is frequently impaired in pulmonary arterial hypertension. However, little is known about HRQOL in other forms of pulmonary hypertension (PH). RESEARCH QUESTION: Does HRQOL vary across groups of the World Symposium on Pulmonary Hypertension (WSPH) classification system? STUDY DESIGN AND METHODS: This cross-sectional study included patients with PH from the Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort study. HRQOL was assessed by using emPHasis-10 (e-10), the 36-item Medical Outcomes Study Short Form survey (physical component score [PCS] and mental component score), and the Minnesota Living with Heart Failure Questionnaire. Pearson correlations between HRQOL and demographic, physiologic, and imaging characteristics within each WSPH group were tested. Multivariable linear regressions compared HRQOL across WSPH groups, adjusting for demographic characteristics, disease prevalence, functional class, and hemodynamics. Cox proportional hazards models were used to assess associations between HRQOL and survival across WSPH groups. RESULTS: Among 691 patients with PH, HRQOL correlated with functional class and 6-min walk distance but not hemodynamics. HRQOL was severely depressed across WSPH groups for all measures except the 36-item Medical Outcomes Study Short Form survey mental component score. Compared with Group 1 participants, Group 2 participants had significantly worse HRQOL (e-10 score, 29 vs 24 [P = .001]; PCS, 32.9 ± 8 vs 38.4 ± 10 [P < .0001]; and Minnesota Living with Heart Failure Questionnaire score, 50 vs 38 [P = .003]). Group 3 participants similarly had a worse e-10 score (31 vs 24; P < .0001) and PCS (33.3 ± 9 vs 38.4 ± 10; P < .0001) compared with Group 1 participants, which persisted in multivariable models (P < .05). HRQOL was associated in adjusted models with survival across Groups 1, 2, and 3. INTERPRETATION: HRQOL was depressed in PH and particularly in Groups 2 and 3 despite less severe hemodynamics. HRQOL is associated with functional capacity, but the severity of hemodynamic disease poorly estimates the impact of PH on patients' lives. Further studies are needed to better identify predictors and treatments to improve HRQOL across the spectrum of PH.

Enhancing availability of services to control hypertension through a team-based care approach that includes pharmacists.

BACKGROUND: Primary care physician (PCP) shortages are expected to increase. The Michigan Medicine Hypertension Pharmacists' Program uses a team-based care (TBC) approach to redistribute some patient care responsibilities from PCPs to pharmacists for patients with diagnosed hypertension. OBJECTIVE: This evaluation analyzed whether the Michigan Medicine Hypertension Pharmacists' Program increased the availability of hypertension management services and described facilitators that addressed barriers to program sustainability and replicability. METHODS: We conducted a retrospective observational study that used a mixed methods approach. We examined the availability of hypertension management services using the number of pharmacists' referrals of patients to other services and the number of PCP appointments. We analyzed qualitative interviews with program staff and site-level quantitative data to examine the program's impact on the availability of services, the impact of TBC that engaged pharmacists, and program barriers and facilitators. RESULTS: Patients who visited a pharmacist had fewer PCP visits over 3- and 6-month periods compared to a matched comparison group that did not see a pharmacist and were 1.35 times more likely to receive a referral to a specialist within a 3-month period. Support from leaders and physicians, shared electronic health record access, and financial backing emerged as leading factors for program sustainability and replicability. CONCLUSION: Adding pharmacists to the care team reduced the number of PCP appointments per patient while increasing the availability of hypertension management services; this may in turn improve PCPs' availability. Similar models may be sustainable and replicable by relying on organizational buy-in, accessible infrastructure, and financing.

Comparative effectiveness of two interventions to increase colorectal cancer screening among females living in the rural Midwest.

PURPOSE: To assess the comparative effectiveness of a tailored, interactive digital video disc (DVD) intervention versus DVD plus patient navigation (PN) intervention versus usual care (UC) on the uptake of colorectal cancer (CRC) screening among females living in Midwest rural areas. METHODS: As part of a larger study, 663 females (ages 50-74) living in rural Indiana and Ohio and not up-to-date (UTD) with CRC screening at baseline were randomized to one of three study groups. Demographics , health status/history, and beliefs and attitudes about CRC screening were measured at baseline. CRC screening was assessed at baseline and 12 months from medical records and self-report. Multivariable logistic regression was used to determine whether females in each group were UTD for screening and which test they completed. RESULTS: Adjusted for covariates, females in the DVD plus PN group were 3.5× more likely to complete CRC screening than those in the UC group (odds ratio [OR] 3.62; 95% confidence interval [CI]: 2.09, 6.47) and baseline intention to receive CRC screening (OR 3.45, CI: 2.21,5.42) at baseline. Adjusting for covariates, there was no difference by study arm whether females who became UTD for CRC screening chose to complete a colonoscopy or fecal occult blood test/fecal immunochemical test. CONCLUSIONS: Many females living in the rural Midwest are not UTD for CRC screening. A tailored intervention that included an educational DVD and PN improved knowledge, addressed screening barriers, provided information about screening test options, and provided support was more effective than UC and DVD-only to increase adherence to recommended CRC screening.

A National Approach to Promoting Health Equity in Cardiovascular Disease Prevention: Implementation Science Strengths, Opportunities, and a Changing Chronic Disease Context.

In the USA, structural racism contributes to higher rates of cardiovascular disease (CVD) including hypertension, heart disease, and stroke among African American persons. Evidence-based interventions (EBIs), which include programs, policies, and practices, can help mitigate health inequities, but have historically been underutilized or misapplied among communities experiencing discrimination and exclusion. This commentary on the special issue of Prevention Science, "Advancing the Adaptability of Chronic Disease Prevention and Management Through Implementation Science," describes the Centers for Disease Control and Prevention, Division for Heart Disease and Stroke Prevention's (DHDSP's) efforts to support implementation practice and highlights several studies in the issue that align with DHDSP's methods and mission. This work includes EBI identification, scale, and spread as well as health services and policy research. We conclude that implementation practice to enhance CVD health equity will require greater coordination with diverse implementation science partners as well as continued innovation and capacity building to ensure meaningful community engagement throughout EBI development, translation, dissemination, and implementation.

Predicted versus observed activity of PCB mixtures toward the ryanodine receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs and similar compounds toward RyR1 activation and related neurotoxicity.

Ambulatory 7-day mechanical circulatory support in sheep model of pulmonary hypertension and right heart failure.

BACKGROUND: Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure. METHODS: In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7 days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed. RESULTS: Six subjects underwent the chronic disease model for 56 to 71 days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit. CONCLUSIONS: Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.

¿Qué hay de nuevo en el diagnóstico de amiloidosis? / What is new in diagnosis of amyloidosis?

La amiloidosis siempre ha representado un desafío diagnóstico. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA), confeccionó la Guía de Práctica Clínica para el Diagnóstico de Amiloidosis. Nuevas líneas de investigación se han desarrollado posteriormente. Esta revisión narrativa tiene como intención explorar el estado del arte en el diagnóstico de la amiloidosis. En pacientes con amiloidosis se recomienda la tipificación de la proteína mediante espectrometría de masa, técnica de difícil ejecución por requerir de microdisectores láser para la preparación de la muestra. Algunas publicaciones recientes proponen otros métodos para obtener la muestra de amiloide que se va a analizar, permitiendo prescindir de la microdisección. Por otra parte, en pacientes con Amiloidosis ATTR confirmada, la recomendación de secuenciar el gen amiloidogénico se encontraba destinada a los casos sospechosos de ATTR hereditaria (ATTRv,), pero actualmente esta se ha extendido a todos los pacientes sin importar la edad. En lo que respecta a los estudios complementarios orientados al diagnóstico de compromiso cardíaco, se ha propuesto el uso de la inteligencia artificial para su interpretación, permitiendo la detección temprana de la enfermedad y el correcto diagnóstico diferencial. Para el diagnóstico de neuropatía, las últimas publicaciones proponen el uso de la cadena ligera de neurofilamento sérica, que también podría resultar un indicador útil para seguimiento. Finalmente, con referencia a la amiloidosis AL, la comunidad científica se encuentra interesada en definir qué características determinan el carácter amiloidogénico de las cadenas livianas. La N-glicosilación de dichas proteínas impresiona ser uno de los determinantes en cuestión. (AU)

Amyloidosis has always represented a diagnostic challenge. In 2020, the Amyloidosis Study Group (ASG) developed the "Clinical Practice Guideline for the Diagnosis of Amyloidosis". New lines of research have subsequently emerged. This narrative review aims to explore the state of the art in the diagnosis of amyloidosis diagnosis. In patients with amyloidosis, protein typing by mass spectrometry is recommended, a technique hard to perform because it requires laser microdissection for sample preparation. Recent publications propose other methods to obtain the amyloid sample to be analyzed, making it possible to dispense with microdissection. On the other hand, in patients with confirmed TTR amyloidosis (aTTR), the recommendation to sequence the amyloidogenic gene was intended for suspected cases of hereditary aTTR but has now been extended to all patients regardless of age. (AU)

¿Qué hay de nuevo en el tratamiento de amiloidosis por cadenas livianas? Parte 1: cadenas livianas / What is new in light chain amyloidosis treatment? Part 1: lightweight chains

La amiloidosis AL es una enfermedad debida al depósito, en órganos y tejidos, de fibrillas formadas por cadenas livianas producidas de forma patológica por plasmocitos clonales. Su tratamiento actualmente está orientado a erradicar el clon de células plasmáticas; este históricamente se extrapoló de tratamientos disponibles y estudiados para otras discrasias sanguíneas. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA) confeccionó distintas guías de práctica clínica para el tratamiento de la amiloidosis AL. Desde entonces se han publicado ensayos clínicos que arrojan contundencia al conocimiento disponible hasta el momento, y están en desarrollo nuevas líneas de investigación que robustecen y estimulan el estudio en el área. En esta revisión se realiza una actualización de las guías existentes en lo que respecta al tratamiento de la amiloidosis por cadenas livianas.Como evidencia de relevancia, en el último año estuvieron disponibles resultados de ensayos clínicos que respaldan el uso de esquemas basados en daratumumab (un anticuerpo monoclonal anti-CD38+) para pacientes con diagnóstico reciente de amiloidosis AL como primera línea. Además, para el tratamiento de la amiloidosis AL refractaria o recaída, la disponibilidad de bibliografía respaldatoria es escasa y extrapolada del tratamiento del mieloma múltiple; sin embargo, actualmente existe evidencia de calidad para recomendar el uso de ixazomib, un inhibidor de proteosoma reversible por vía oral disponible en la Argentina desde 2020. Por último, se mencionan algunas líneas de investigación con otros anticuerpos monoclonales y terapéuticas basadas en el uso de CAR-T cells. (AU)

AL amyloidosis is a disease caused by the deposit in different organs and tissues of protein fibrils formed by light chains synthetized by pathological clonal plasma cells. Its treatment is currently aimed at eradicating this plasma cell clone and it has been historically extrapolated from available and validated treatments for other blood dyscrasias. In 2020, the Amyloidosis Study Group prepared different clinical practice guidelines for the treatment of AL amyloidosis.Since then, clinical trials have been published that confirm and strengthen the knowledge available up to now, and new lines of research are being developed that stimulate study in the area. In this review, an update of the existing guidelines regarding the treatment of AL amyloidosis is made. As relevant evidence, in the last year, results of clinical trials have been made available that support the use of regimens based on Daratumumab (an anti-CD38+ monoclonal antibody) for patients with newly diagnosed AL amyloidosis as first line therapy. In addition, for the treatment of refractory or relapsed AL amyloidosis, where the availability of supporting literature is scant and extrapolated from the treatment of multiple myeloma, there is currently quality evidence to recommend the use of ixazomib, an oral reversible proteasome inhibitor, only available in Argentina since 2020. Finally, some research lines exploring the efficacy of other monoclonal antibodies and therapeutic experiments based on the use of CAR-T cells are mentioned. (AU)

Policy implementation strategies to address rural disparities in access to care for stroke patients.

Context: Stroke systems of care (SSOC) promote access to stroke prevention, treatment, and rehabilitation and ensure patients receive evidence-based treatment. Stroke patients living in rural areas have disproportionately less access to emergency medical services (EMS). In the United States, rural counties have a 30% higher stroke mortality rate compared to urban counties. Many states have SSOC laws supported by evidence; however, there are knowledge gaps in how states implement these state laws to strengthen SSOC. Objective: This study identifies strategies and potential challenges to implementing state policy interventions that require or encourage evidence-supported pre-hospital interventions for stroke pre-notification, triage and transport, and inter-facility transfer of patients to the most appropriate stroke facility. Design: Researchers interviewed representatives engaged in implementing SSOC across six states. Informants (n = 34) included state public health agency staff and other public health and clinical practitioners. Outcomes: This study examined implementation of pre-hospital SSOCs policies in terms of (1) development roles, processes, facilitators, and barriers; (2) implementation partners, challenges, and solutions; (3) EMS system structure, protocols, communication, and supervision; and (4) program improvement, outcomes, and sustainability. Results: Challenges included unequal resource allocation and EMS and hospital services coverage, particularly in rural settings, lack of stroke registry usage, insufficient technologies, inconsistent use of standardized tools and protocols, collaboration gaps across SSOC, and lack of EMS stroke training. Strategies included addressing scarce resources, services, and facilities; disseminating, training on, and implementing standardized statewide SSOC protocols and tools; and utilizing SSOC quality and performance improvement systems and approaches. Conclusions: This paper identifies several strategies that can be incorporated to enhance the implementation of evidence-based stroke policies to improve access to timely stroke care for all patient populations, particularly those experiencing disparities in rural communities.

Reduction of SARS-CoV-2 viral load in saliva after rinsing with mouthwashes containing cetylpyridinium chloride: a randomized clinical study.

Background: Symptomatic patients with COVID-19 typically have a high SARS-CoV-2 viral load in their saliva. Procedures to reduce the viral load in their oral cavity are important for mitigating the viral transmission. Methods: This randomized clinical trial investigated the impact of two mouthwashes (0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC+Zn) (n = 32), and 0.075% cetylpyridinium chloride (CPC) (n = 31)) on the viral load of SARS-CoV-2 in saliva when compared to the distilled water negative control (n = 32). Saliva was collected before (T0) and after (5 min, T1; 30 min, T2; and 60 min, T3) the intervention. Viral load in saliva was measured by qRT-PCR assays. The data in both groups was normalized for T0 and Negative Control, resulting in fold change values. Results: CPC+Zn oral solution reduced the viral load in saliva by 6.34-fold at T1, 3.6-fold at T2 and 1.9-fold at T3. Rinsing with the CPC mouthwash reduced the viral load in saliva by 2.5-fold at T1, 1.9-fold at T2 and 2.0-fold at T3. Conclusion: CPC+Zn mouthwash or with the CPC mouthwash reduced the viral load in saliva of COVID-19 patients immediately after rinsing. These reductions extended up to 60 min.

Trasplante cardíaco y autólogo de células progenitoras hematopoyéticas en pacientes con amiloidosis AL / Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis

Resumen Objetivo: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. Método: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. Resultados: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. Conclusiones: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Abstract Objective: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. Method: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. Results: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. Conclusions: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

Breaking the Link Between Negative Emotion and Unhealthy Eating: the Role of Emotion Regulation.

Stressful experiences frequently lead to increased consumption of unhealthy foods, high in sugar and fat yet low in nutrients. Can emotion regulation help break this link? In a laboratory experiment (N = 200), participants were encouraged to ruminate on a current, distressing personal problem, followed by instruction to use a specific emotion regulation strategy for managing feelings around that problem (challenge appraisal, relaxation/distraction, imagined social support, no-instruction control). Participants then spent 15 min on an anagram task in which 80% of items were unsolvable-a frustrating situation offering a second, implicit opportunity to use the regulation strategy. During the anagram task they had free access to a snack basket containing various options. Analyses revealed significant differences among regulation conditions in consumption of candy versus healthy snack options; challenge appraisal led to the healthiest snack choices, imagined social support to the least healthy snack choices. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00190-5.