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Staphylococcus aureus nasal carriers were randomized (1:1) to XF-73 or placebo nasal gel, administered 5x over ∼24hrs pre-cardiac surgery. S. aureus burden rapidly decreased after 2 doses (-2.2log 10 CFU/mL; placebo -0.01log 10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo ( P = 0.045).

Background: Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain., Methods: National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected., Results: The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group., Conclusions: The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment., (© 2024. The Author(s).)

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs., Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry., Results: This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5)., Conclusions: This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis., Trial Registration: ClinicalTrials.gov Identifier: NCT00628745., (© 2023. The Author(s).)

Background: In hereditary transthyretin amyloidosis (ATTRv), early manifestation and age at onset (AO) may vary strikingly. We assessed the disease'risk (penetrance), AO and initial features in ATTRv families to gain insights on the early disease presentation., Methods: Genealogical information, AO and first disease manifestations were collected in ATTRv families, from Sweden, Italy (Sicily), Spain (Mallorca), France, Turkey, Brazil. Penetrance was computed using a non-parametric survival method., Results: We analysed 258 TTRV30M kindreds and 84 carrying six other variants (TTRT49A, F64L, S77Y, S77F, E89Q, I107V). In ATTRV30M families, the earliest disease risk was found at age 20 years in the Portuguese and Mallorcan families and at age 30-35 years, in the French and Swedish groups. The risks were higher in men and in carriers of maternal descent. In families carrying TTR-nonV30M variants, the earliest disease risk ranged from 30 y-o in TTRT49A to 55 y-o in TTRI107V families. Peripheral neuropathy symptoms were the most frequent initial manifestations. Among patients carrying TTRnonV30M variants, about 25% had an initial cardiac phenotype, one third a mixed phenotype., Conclusion: Our work provided solid data on the risks and early features of ATTRv in a spectrum of families to enhance an early diagnosis and treatment.

We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log 10 with XF-73 compared to 0.4 log 10 CFU/mL for those who received placebo (95% CI, -2.7 to -1.5; P < .0001).

Objectives: Community representatives are key to ensuring that tuberculosis (TB) research is relevant, culturally sensitive, and appropriate. For all trials (new drugs or treatment regimens, diagnostics, or vaccines) this can result in improvement of recruitment, retention, and adherence to the trial schedule. The early engagement of the community will, later in time, support the process of implementation of new policies designed for successful products. We aim at developing a structured protocol for the early engagement of TB community representatives developed in the context of the EU-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project., Design: The EU-PEARL Innovative Medicine Initiative 2 (IMI2) project TB work package has developed a community engagement (CE) framework to ensure fair and efficient participation of the community in the design and implementation of TB clinical platform trials., Results: We showed that early engagement of the EU-PEARL community advisory board highly contributes to the process of development of a community-acceptable Master Protocol Trial and Intervention-Specific Appendixes. We identified capacity building and training as major gaps in advancing CE in the TB field., Conclusion: Developing strategies to address these needs can contribute to preventing tokenism and increase the acceptability and appropriateness of TB research., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cognitive stimulation is one of the non-pharmacological therapies recommended for dementia intervention. The present study evaluated the efficacy of an intervention based on cognitive stimulation in people with moderate Alzheimer's disease. Fifty-nine subjects with moderate dementia were randomly assigned to the stimulation group ( N = 36) and the control group ( N = 35). The treatment group received 16 intervention sessions cognitive tasks. All participants were evaluated with a battery of neuropsychological tests at three time points (pre, post, and follow-up). The treatment group showed significant increases in the three domains studied (memory, attention, and executive functions), although some of these effects were not maintained at follow-up. The control group progressively worsened. Cognitive stimulation was found to be an effective intervention for people with moderate Alzheimer's disease because it helped to maintain memory function, executive functions, and attention. However, the effects were minimized at the 3-month follow-up.

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs., Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021)., Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation., Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease., Clinicaltrials: gov Identifier: NCT00628745., (© 2022. The Author(s).)

Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies., Methods: We conducted a multicentre, international, retrospective cohort study., Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD., Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Background: Cognitive stimulation is one of the non-pharmacological therapies recommended for intervention in dementia, consisting of activities involving different cognitive domains and involving brain activation. New technologies can be very useful in this field, favoring intervention tasks., Objective: The objective of this work is to test the effectiveness of a cognitive stimulation intervention mediated with new technologies on a group of people with moderate dementia., Methods: This is a quantitative, quasi-experimental study with a control and treatment group, with three measurement times (pre, post, and follow-up months after the end of the intervention). Ninety-eight subjects with moderate dementia were randomly assigned to the treatment group (N = 50) and the control group (N = 48). The treatment group received 16 intervention sessions including attention, executive function, and memory tasks, which were presented using new technologies and the activity was conducted in a group setting. Control group remained on a waiting list. The evaluators did not know which group each subject belonged to. All participants were assessed with a battery of neuropsychological tests., Results: The results show an improvement in post-intervention outcomes in the treatment group compared to the control group on cognitive variables. No differences were found in mood depression. These results fade overtime after a few months without intervention., Conclusion: This type of intervention is useful to maintain cognitive functioning using new technologies and in a group setting, which favors the intervention. The improvements of the intervention disappear at follow-up, which would indicate the need to maintain the intervention over time.

Pulmonary nodular lymphoid hyperplasia, also known as pseudolymphoma, is an uncommon reactive lymphoproliferative disorder of unknown etiology that can be found in Sjögren's syndrome patients. Here, we present a case of a previously healthy woman in which the incidental finding of a lung mass compatible with nodular lymphoid hyperplasia led to the subsequent diagnosis of Sjögren's syndrome. We also performed a literature review for the association between both entities and described the main clinical aspects of the reported cases. Although its rarity, we consider that pulmonary nodular lymphoid hyperplasia should be considered in the differential diagnosis of lung nodules or masses among Sjögren's syndrome patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background : Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain. Methods : An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs. Results : Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€). Conclusions : Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Purpose: Cardiac rehabilitation (CR) programs decrease morbidity and mortality rates in patients with coronary artery disease, the leading cause of death in Latin America. This study was carried out to assess the characteristics and current level of CR program implementation in South America., Methods: We carried out a survey of CR programs that were identified using the directory of the South American Society of Cardiology and through an exhaustive search by the investigators., Results: We identified 160 CR programs in 9 of the 10 countries represented in the South American Society of Cardiology and 116 of those responded to our survey. On the basis of survey results from the responding programs, we estimate that the availability of CR programs in South America is extremely low, approximately 1 CR program for every 2 319 312 inhabitants. These CR programs provided services to a median of 180 patients per year (interquartile range, 60-400) and were most commonly led by cardiologists (84%) and physical therapists (72%). Phases I, II, III, and IV CR were offered in 49%, 91%, 89%, and 56% of the centers, respectively. The most commonly perceived barrier to participation in a CR program was lack of referral from the cardiologist or primary care physician, as reported by 70% of the CR program directors., Conclusions: The number of CR programs in South America appears to be insufficient for a population with a high and growing burden of cardiovascular disease. In addition, there appears to be a significant need for standardization of CR program components and services in the region.