Cardiac rupture as a life-threatening outcome of Takotsubo syndrome: A systematic review.

BACKGROUND: Takotsubo syndrome (TS) is a reversible cause of heart failure; however, a minority of patients can develop serious complications, including cardiac rupture (CR). OBJECTIVES: Analyze case reports of CR related to TS, detailing patient characteristics to uncover risk factors and prognosis for this severe complication. METHODS: We conducted a systematic search of MEDLINE and Embase databases to identify case reports of patients with TS complicated by CR, from inception to October 2023. RESULTS: We included 44 subjects (40 females; 4 males) with a median age of 75 (IQR 71-82) years, of White/Caucasian (61%) or East Asian/Japanese (39%) ethnicity. An emotional trigger was present in 15 (34%) subjects and an apical ballooning pattern was observed in all cases (100%). ST-segment elevation was reported in 39 (93%) of 42 cases, with the anterior myocardial segments (37 [88%]) being the most compromised, followed by lateral (26 [62%]) and inferior (14 [33%]) segments. The median time to cardiac rupture was 48 (5-120) hours since admission, with the left ventricular free wall (25 [57%]) being the most frequent site of perforation. Surgery was attempted in 16 (36%) cases, and 28 (64%) patients did not survive. CONCLUSIONS: CR related to TS is a rare complication associated with high mortality and affecting elderly females, specially from White/Caucasian or East Asian/Japanese descent, presenting with anterior or lateral ST-segment elevation, and an apical ballooning pattern. Although data is limited and additional prospective studies are needed, the awareness of this life-threatening complication is crucial to early identify high-risk patients. CONDENSED ABSTRACT: Cardiac rupture is a rare complication of Takotsubo syndrome. We conducted a systematic review of cases complicated by cardiac rupture, and we identified 44 subjects (40 females and 4 males) with a median age of 75 (IQR 71-82) years, of White/Caucasian (61%) or East Asian/Japanese (39%) ethnicity, all with an apical ballooning pattern (100%). The median time to cardiac rupture was 48 (5-120) hours since admission, with the left ventricular free wall (25 [57%]) being the most frequent site of perforation. Surgery treatment was attempted in 16 (36%) cases, and 28 (64%) patients did not survive.

Interleukin Receptor Therapeutics Attenuate Inflammation in Canine Synovium following Cruciate Ligament Injury.

OBJECTIVE: In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis. DESIGN: Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n=10/group) and micromechanical testing (n=5/group) to identify changes in tissue architecture and stiffness. Additional samples (n=5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n=6 (IL1) or n=8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6). RESULTS: Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators. CONCLUSION: Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.

Collaborative practice with parents in occupational therapy for children: A scoping review.

INTRODUCTION: In childhood intervention, parent-therapist collaboration is central to the family-centred approach. Despite long-standing discussion in occupational therapy literature, the field faces challenges, including inconsistent terminology and difficulties in translating theory into practice. This paper represents the first part of a comprehensive scoping review study aimed at developing foundational concepts for collaborative practices with parents in occupational therapy for children. Therefore, this paper focusses on mapping existing practices, types, and approaches articulated in the literature. METHODS: We searched English-language sources published worldwide from 1998 to 2022 discussing collaborative practices with parents in occupational therapy for children aged 0-10 with any diagnosis, including multidisciplinary practices. Seven databases were searched. Data from peer-reviewed indexed literature, theses and dissertations, and book chapters were extracted and analysed through basic numerical and descriptive analyses before being synthesised into similar categories. The Joanna Briggs Institute Manual and the Preferred Reporting Items for Systematic reviews and Meta-Analysis-extension for Scoping Reviews were used. RESULTS: The scoping review yielded 299 papers. Parent-therapist collaboration was prominent in clinics, family homes, schools, and hospitals, particularly during therapy implementation, goal setting, and planning. Most reported practice types included 'interventions with parent engagement', 'parent-directed interventions', and 'parent education'. 'Family-centred', 'occupational-focussed', and 'client-therapist collaborative' approaches were frequently mentioned. There were inconsistencies in the terms used to describe collaborative practice characteristics. CONCLUSION: Over the past 24 years, the collaborative practice literature has expanded and evolved, with parent-therapist collaboration observed across various occupational therapy settings. Inconsistencies in this collaboration across different therapeutic stages were revealed, which could impact intervention success and sustainability. Further research is needed to explore parent-therapist collaboration mechanisms within and across stages. This scoping review also underscores the need for a common framework to guide practice and research. PLAIN LANGUAGE SUMMARY: This literature review explores how occupational therapists and parents work together in childhood intervention. Collaboration is essential for understanding and meeting children's needs within their family and community settings. However, occupational therapists and parents face challenges in applying family-centred practices and using a common language to bridge theory with practice. To address these challenges, we examined 299 papers published between 1998 and 2022 to understand how collaborative practices with parents have been described in the literature. Our review revealed that therapists and parents collaborate across various settings, such as clinics, schools, homes, and hospitals, mainly during therapy sessions, goal setting, and planning interventions. Collaborative practices take different forms. For instance, therapists often encourage parents to actively engage and take the lead in therapy, requiring therapists to recognise and respect parents' priorities and learning preferences. They often develop strategies together to support the child within family routines. While we found several studies on therapist-parent collaboration, the review outlined inconsistencies in how this practice was described and applied, which could affect its success. Therefore, more research is needed to understand the best ways in which collaboration can occur at each stage of therapy. The need for a core guideline for collaborative practice with parents in occupational therapy was also observed. While therapist-parent collaboration is used in occupational therapy for children, there is a clear need to minimise inconsistencies and gaps found in the literature, as well as to ensure a common language to promote intervention quality and success.

Foundational concepts of collaborative practice with parents in occupational therapy for children.

INTRODUCTION: In occupational therapy for children, collaborative practice with parents is crucial for meaningful family-centred interventions, yet it remains undefined and inconsistently addressed. This study aimed to establish foundational concepts for collaborative practice with parents in occupational therapy for children in progressing the field with a universal description. METHODS: This paper encompasses the second dataset of a larger scoping review and a preliminary validation of findings by an advisory panel. Data were gathered from indexed sources on collaborative practice with parents in occupational therapy for children (ages 0-10) using MedLine, PsychInfo, ERIC, Embase, OTSeeker, Scopus, and ProQuest Central. Data were extracted, charted, and descriptively analysed by paired independent reviewers. The Joanna Briggs Institute Manual and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-extension for Scoping Reviews were used. A draft definition of collaborative practices, developed based on preliminary review findings and an operational definition, was validated by an advisory panel of 13 experienced Australian occupational therapists, whose input was integrated into a final, comprehensive description of collaborative practice. RESULTS: The scoping review encompassed 299 sources, revealing three major components of collaborative practice: 'collaborative practice aims', 'parent-therapist partnership', and 'strategies for collaboration'. The advisory panel endorsed the draft definition, confirmed its professional relevance, and suggested some modifications. CONCLUSION: The major outcome of this study is an evidence-based and discipline-specific preliminary description of collaborative practice with parents in occupational therapy for children. This description provides a common language and foundational concepts for the future development of a collaborative practice framework to guide practice and research. Future studies can explore specific components, exploring their mechanisms and significance. Further expanded validation is required, incorporating the perspectives of a wider community of occupational therapists and families to enhance the description's applicability.

Unveiling contrasts in microbiota response: A1c control improves dysbiosis in low-A1c T2DM, but fails in high-A1c cases-a key to metabolic memory?

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with dysbiosis in the gut microbiota (MB). Individually, each medication appears to partially correct this. However, there are no studies on the response of the MB to changes in A1c. Therefore, we investigated the MB's response to intensive glycemic control. RESEARCH DESIGN AND METHODS: We studied two groups of patients with uncontrolled T2DM, one group with an A1c <9% (18 patients-G1) and another group with an A1c >9% (13 patients-G2), aiming for at least a 1% reduction in A1c. We collected A1c and fecal samples at baseline, 6, and 12 months. G1 achieved an average A1c reduction of 1.1%, while G2 a reduction of 3.13%. RESULTS: G1's microbiota saw a decrease in Erysipelotrichaceae_UCG_003 and in Mollicutes order (both linked to metabolic syndrome and associated comorbidities). G2, despite having a more significant reduction in A1c, experienced an increase in the proinflammatory bacteria Megasphaera and Acidaminococcus, and only one beneficial genus, Phascolarctobacterium, increased, producer of butyrate. CONCLUSION: Despite a notable A1c outcome, G2 could not restore its MB. This seeming resistance to change, leading to a persistent inflammation component found in G2, might be part of the "metabolic memory" in T2DM.

A standardized approach to evaluation and reporting of synovial histopathology in two surgically induced murine models of osteoarthritis.

OBJECTIVE: Synovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for reporting of synovial histopathology in mouse models of OA. METHODS: Coronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T-Blue), and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations. Inter-reader agreement of each feature score was determined. RESULTS: There was acceptable to very good agreement when using 3-4 individual readers. After DMM and PMX, expected medial predominant changes in hyperplasia and cellularity were observed, with fibrosis noted at 12 weeks post-PMX. Synovial changes were consistent from section to section in the mid-joint area. When comparing stains, H&E and T-blue resulted in better agreement compared to Saf-O stain. CONCLUSIONS: To account for the pathologic and anatomic variability in synovial pathology and allow for a more standardized evaluation that can be compared across studies, we recommend evaluating a minimum set of 3 pathological features at standardized anatomic areas. Further, we suggest reporting individual feature scores separately before relying on a single summed "synovitis" score. H&E or T-blue are preferred, inter-reader agreement for each feature should be considered.

Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients.

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients. Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCC in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Additionally, serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. The TERT promoter mutation frequency was also remarkably high in the Hispanic cohort. Cell cycles and liver functions were identified as positively- and negatively-enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in the serum samples of HCC patients. Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. The subtype with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. It also had higher levels of immune checkpoint and immune exhaustion markers. Conclusions: Our study revealed some specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management of HCC and provides a unique resource for studying Hispanic HCC.

Chronic consumption of orange juice modifies urinary excretion of flavanone gut-derived metabolites through gut microbiota modulation.

The metabolism and absorption of citrus flavanones are intrinsically linked to the gut microbiota, creating a bidirectional relationship where these compounds influence the microbiome, and in turn, the microbiota affects their metabolism. This study evaluates the effect of acute and chronic consumption of orange juice (OJ) on the urinary excretion of gut-derived flavanone metabolites and the gut microbiota. Health volunteers ingested 500 mL of OJ for 60 days in a single-arm human intervention study. Blood and feces were collected at baseline and after 60 days, with an additional 24-hour urine collection after a single dose on day 1 and day 63. LC-MS/MS analyzed urinary flavanone metabolites, while 16S rRNA sequencing characterized gut microbiota. Total urinary hesperetin conjugates excretion significantly decreased over 60 days, while gut-derived total phenolic acids, particularly three hydroxybenzoic acids, increased. Moreover, the heterogeneity of the total amount of flavanone conjugates, initially categorizing individuals into high-, medium- and low- urinary excretor profiles, shifted towards medium-excretor, except for five individuals who remained as low-excretors. This alteration was accompanied by a decrease in intestinal ß-glucosidase activity and a shift in the relative abundance of specific genera, such as decreases in Blautia, Eubacterium hallii, Anaerostipes, and Fusicatenibacter, among which, Blautia was associated with higher urinary flavanone conjugates excretion. Conversely, an increase in Prevotella was observed. In summary, chronic OJ consumption induced transient changes in gut microbiota and altered the metabolism of citrus flavanones, leading to distinct urinary excretion profiles of flavanone metabolites.

Skin assessment in congenital untreated isolated GH deficiency.

PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

The vector-symbiont affair: a relationship as (im)perfect as it can be.

Vector-borne diseases are globally prevalent and represent a major socioeconomic problem worldwide. Blood-sucking arthropods transmit most pathogenic agents that cause these human infections. The pathogens transmission to their vertebrate hosts depends on how efficiently they infect their vector, which is particularly impacted by the microbiota residing in the intestinal lumen, as well as its cells or internal organs such as ovaries. The balance between costs and benefits provided by these interactions ultimately determines the outcome of the relationship. Here, we will explore aspects concerning the nature of microbe-vector interactions, including the adaptive traits required for their establishment, the varied outcomes of symbiotic interactions, as well as the factors influencing the transition of these relationships across a continuum from parasitism to mutualism.

Influence of simultaneous comorbidities on COVID-associated acute respiratory distress syndrome mortality in people with diabetes.

Objectives: This study analyzed the influence of 23 comorbidities on COVID-associated acute distress respiratory syndrome (CARDS) mortality in people with a history of diabetes mellitus. Methods: An observational, analytical, cross sectional study was utilized to investigate data from 6723 health services in Brazil, comprising 5433 people with diabetes. Adjusted logistic regression models for demographic factors such as age, sex, and race were used to analyze the association between CARDS mortality and comorbidities. Results: Persons with two (p < 0.001), three (p < 0.001), four (p < 0.001), and five (p < 0.001) simultaneous comorbidities had a higher chance of dying. We identified that diabetes patients who had concomitant metabolic diseases (p = 0.019), neurological disorders (p < 0.001), or were smokers (p < 0.001) had a higher predicted mortality risk based on CADRS. Conclusion: The number of comorbidities plays a determining role in CARDS mortality in people with diabetes, especially those who suffer from smoking and neurological diseases simultaneously.

Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). METHODS: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. RESULTS: Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. CONCLUSION: Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Decreasing Perioperative Opiate Use During Pancreaticoduodenectomy Using Transversus Abdominus Plane Blocks: A Review of the Literature.

BACKGROUND: Pancreatoduodenectomy is a highly complex surgical procedure associated with high postoperative morbidity and mortality. Treatment of postoperative pain is crucial to preventing chronic pain and further complications. Opioids are the leading treatment modality for acute postoperative pain for all surgical procedures in the US, contributing to the opioid epidemic, a crisis causing death and lifelong impairment in many patients. Multimodal analgesia techniques, such as the transversus abdominis plane (TAP) block, are suggested to reduce perioperative opioid usage. This exploratory literature review aims to investigate the use of TAP block in postoperative pain and opioid use in patients undergoing pancreatoduodenectomy. MATERIALS AND METHODS: A search strategy developed from Cochrane best practice recommendations was applied to a comprehensive search of PubMed, Scopus, and PsycINFO databases, yielding three articles of relevance in patients having pancreatic surgery. RESULTS: Previous research demonstrates TAP block efficacy in decreasing opiate consumption after major abdominal surgery; however, there is a paucity of data regarding opioid consumption in pancreatoduodenectomy patients. CONCLUSION: Research in relation to TAP block analgesia is varied given the variety of approaches, techniques, and timing of the TAP block procedure. Future research should seek to elucidate the role of TAP blocks in reducing postoperative pain and opioid consumption in pancreatoduodenectomy patients.

The Gut Microbiome in the First One Thousand Days of Neurodevelopment: A Systematic Review from the Microbiome Perspective.

Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and neurodegenerative disorders. Here, we conduct a systematic review of gut microbiome assessments on infants (both healthy and with conditions that affect brain development) during the first thousand days of life, associated with neurodevelopmental outcomes, with the aim of investigating key microbiome players and mechanisms through which the gut microbiome affects the brain. Bacteroides and Bifidobacterium were associated with non-social fear behavior, duration of orientation, cognitive and motricity development, and neurotypical brain development. Lachnospiraceae, Streptococcus, and Faecalibacterium showed variable levels of influence on behavior and brain development. Few studies described mechanistic insights related to NAD salvage, aspartate and asparagine biosynthesis, methanogenesis, pathways involved in bile acid transformation, short-chain fatty acids production, and microbial virulence genes. Further studies associating species to gene pathways and robustness in data analysis and integration are required to elucidate the functional mechanisms underlying the role of microbiome-gut-brain axis in early brain development.

Prevalence of moderate-severe aortic stenosis in patients with cardiac amyloidosis in a referral center.

BACKGROUND: Aortic stenosis (AS) is currently the most common valvular disease, with an estimated prevalence of over 4% in octogenarians. OBJECTIVE: To describe the prevalence of moderate-severe aortic stenosis (AS) in patients with wild type transthyretin amyloidosis (ATTRwt). Also, describe the clinical features, echocardiographic characteristics and clinical evolution. METHOD: Retrospective cohort of patients with diagnosis of ATTRwt, belonging to Hospital Italiano de Buenos Aires Institutional Amyloidosis Registry, from 30/11/2007 to 31/05/2021. Patients follow up was carried out through the institution clinical history. The prevalence of moderate-severe AE was estimated and presented as a percentage with its 95% confidence interval (95% CI). The characteristics were compared by groups according to whether or not they had moderate-severe AS. RESULTS: 104 patients with ATTRwt were included. Median follow up was 476 days [interquartile range: 192-749]. Moderate-severe AS prevalence at the ATTRwt time of diagnosis was 10.5% (n = 11; 95% CI: 5-18%). The median age of patients with AS moderate-severe at the time of diagnosis of ATTRwt was 86 years [78-91] and the male sex predominated (82%). Most of the patients had a history of heart failure (n = 8) and atrial fibrillation (n = 8) prior to the diagnosis of ATTRwt. Most of the patients were subclassified as low flow low gradient severe AS group (n = 7). Four patients underwent some intervention on the aortic valve. During follow-up, 5 patients (46%) were hospitalized for decompensated heart failure and 4 (36%) died. CONCLUSIONS: In our cohort, the coexistence of both pathologies had a similar prevalence as reported in the international literature. It was an elderly population with a high percentage of atrial fibrillation and history of heart failure. Most of the patients presented with severe AS with low flow low gradient.

ANTECEDENTES: La estenosis aórtica (EA) es actualmente la enfermedad valvular más frecuente, con una prevalencia estimada de más del 4 % en octogenarios. OBJETIVO: Describir la prevalencia de estenosis aórtica (EA) moderada-grave en pacientes con amiloidosis por transtiretina wild type (ATTRwt). Además, describir las características clínicas, ecocardiográficas y la evolución en este grupo de pacientes. MÉTODO: Estudio de cohorte retrospectiva de pacientes con diagnóstico de ATTRwt, pertenecientes al Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, en el periodo del 30/11/2007 al 31/05/2021. El seguimiento de los pacientes se realizó a través de la historia clínica electrónica de la institución. Se estimó la prevalencia de EA moderada-grave, que se presenta como porcentaje con su intervalo de confianza del 95% (IC 95%). Se compararon las características por grupos según tuvieran o no EA moderada-grave. RESULTADOS: Se incluyeron 104 pacientes con diagnóstico de ATTRwt. La mediana de seguimiento fue de 476 días [rango intercuartílico: 192-749]. La prevalencia de EA moderada-grave al momento del diagnóstico de ATTRwt fue del 10.5% (n = 11; IC95%: 5-18%). La mediana de edad de los pacientes con EA fue de 86 años [78-91] y predominó el sexo masculino (81.8%). La mayoría de los pacientes tenían el antecedente de insuficiencia cardiaca (n = 8) y fibrilación auricular (n = 8). Predominaron los pacientes con EA grave de bajo flujo y bajo gradiente (n = 7). Cuatro pacientes fueron sometidos a alguna intervención en la válvula aórtica. Durante el seguimiento, 5 pacientes (46%) tuvieron internaciones por insuficiencia cardiaca descompensada y 4 (36%) fallecieron. CONCLUSIONES: En nuestra cohorte, la coexistencia de ambas patologías tuvo una prevalencia similar a la reportada en la literatura internacional. Se trató de una población añosa con alto porcentaje de fibrilación auricular y antecedente de insuficiencia cardiaca. La mayoría presentaron EA grave de bajo flujo y bajo gradiente.

Midlife sensory and motor functions improve prediction of blood-based measures of neurodegeneration and Alzheimer's disease in late middle-age.

INTRODUCTION: We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10-year changes in biomarkers of neurodegeneration and Alzheimer's disease. METHODS: Longitudinal data of N = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5-year, and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10-year incidence of biomarker positivity of serum-based neurofilament light chain (NfL) and amyloid beta (Aß)42/Aß40 using logistic regression. RESULTS: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved NfL and Aß42/Aß40 positivity predictions in adults above the age of 55. DISCUSSION: Including midlife sensory and motor function improved long-term biomarker positivity predictions. Non-invasive sensory and motor assessments could contribute to cost-effective screening tools that identify individuals at risk for neurodegeneration early to target interventions and preventions. Highlights: Sensory and motor measures improve risk prediction models of neurodegenerative biomarkersSensory and motor measures improve risk prediction models of AD biomarkersPrediction improvements were strongest in late midlife (adults >55 years of age)Sensory and motor assessments may help identify high-risk individuals early.

Prevalencia de estenosis aórtica moderada-grave en pacientes con amiloidosis cardiaca en un centro de referencia / Prevalence of moderate-severe aortic stenosis in patients with cardiac amyloidosis in a referral center

Resumen Antecedentes: La estenosis aórtica (EA) es actualmente la enfermedad valvular más frecuente, con una prevalencia estimada de más del 4 % en octogenarios. Objetivo: Describir la prevalencia de estenosis aórtica (EA) moderada-grave en pacientes con amiloidosis por transtiretina wild type (ATTRwt). Además, describir las características clínicas, ecocardiográficas y la evolución en este grupo de pacientes. Método: Estudio de cohorte retrospectiva de pacientes con diagnóstico de ATTRwt, pertenecientes al Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, en el periodo del 30/11/2007 al 31/05/2021. El seguimiento de los pacientes se realizó a través de la historia clínica electrónica de la institución. Se estimó la prevalencia de EA moderada-grave, que se presenta como porcentaje con su intervalo de confianza del 95% (IC 95%). Se compararon las características por grupos según tuvieran o no EA moderada-grave. Resultados: Se incluyeron 104 pacientes con diagnóstico de ATTRwt. La mediana de seguimiento fue de 476 días [rango intercuartílico: 192-749]. La prevalencia de EA moderada-grave al momento del diagnóstico de ATTRwt fue del 10.5% (n = 11; IC95%: 5-18%). La mediana de edad de los pacientes con EA fue de 86 años [78-91] y predominó el sexo masculino (81.8%). La mayoría de los pacientes tenían el antecedente de insuficiencia cardiaca (n = 8) y fibrilación auricular (n = 8). Predominaron los pacientes con EA grave de bajo flujo y bajo gradiente (n = 7). Cuatro pacientes fueron sometidos a alguna intervención en la válvula aórtica. Durante el seguimiento, 5 pacientes (46%) tuvieron internaciones por insuficiencia cardiaca descompensada y 4 (36%) fallecieron. Conclusiones: En nuestra cohorte, la coexistencia de ambas patologías tuvo una prevalencia similar a la reportada en la literatura internacional. Se trató de una población añosa con alto porcentaje de fibrilación auricular y antecedente de insuficiencia cardiaca. La mayoría presentaron EA grave de bajo flujo y bajo gradiente.

Abstract Background: Aortic stenosis (AS) is currently the most common valvular disease, with an estimated prevalence of over 4% in octogenarians. Objective: To describe the prevalence of moderate-severe aortic stenosis (AS) in patients with wild type transthyretin amyloidosis (ATTRwt). Also, describe the clinical features, echocardiographic characteristics and clinical evolution. Method: Retrospective cohort of patients with diagnosis of ATTRwt, belonging to Hospital Italiano de Buenos Aires Institutional Amyloidosis Registry, from 30/11/2007 to 31/05/2021. Patients follow up was carried out through the institution clinical history. The prevalence of moderate-severe AE was estimated and presented as a percentage with its 95% confidence interval (95% CI). The characteristics were compared by groups according to whether or not they had moderate-severe AS. Results: 104 patients with ATTRwt were included. Median follow up was 476 days [interquartile range: 192-749]. Moderate-severe AS prevalence at the ATTRwt time of diagnosis was 10.5% (n = 11; 95% CI: 5-18%). The median age of patients with AS moderate-severe at the time of diagnosis of ATTRwt was 86 years [78-91] and the male sex predominated (82%). Most of the patients had a history of heart failure (n = 8) and atrial fibrillation (n = 8) prior to the diagnosis of ATTRwt. Most of the patients were subclassified as low flow low gradient severe AS group (n = 7). Four patients underwent some intervention on the aortic valve. During follow-up, 5 patients (46%) were hospitalized for decompensated heart failure and 4 (36%) died. Conclusions: In our cohort, the coexistence of both pathologies had a similar prevalence as reported in the international literature. It was an elderly population with a high percentage of atrial fibrillation and history of heart failure. Most of the patients presented with severe AS with low flow low gradient.

Erosive Hand Osteoarthritis: Recent Advances and Future Treatments.

PURPOSE OF THE REVIEW: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis that leads to significant disability, and recent data suggests that it is increasing in prevalence. This review provides an update of our current understanding of epidemiology, genetic associations, biomarkers, pathogenesis, and treatment of EHOA, with particular focus on studies published within the last 5 years. RECENT FINDINGS: New studies of EHOA have identified new genetic loci associated with disease, including variants in genes involved in inflammation and bone remodeling. Preclinical studies implicate pathways of innate immunity, including some that may be causal in the condition. Recent novel studies showed that inflammatory features identified by ultrasound and MRI are associated with development of erosive lesions over time on conventional radiography. In the future, these imaging modalities may be useful in identifying patients at risk of adverse outcomes. Promising new findings in genetics, biomarkers, and treatment targets will hopefully allow for future therapeutic options for this debilitating condition.