Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-life experiences with goal-directed prohemostatic therapy with fibrinogen concentrate, prothrombin complex concentrate, and recombinant factor VIIa: a retrospective study of 287 consecutive patients

Abstract The Danish Capital Region Blood Bank operates a 24/7 on-call service staffed with physicians specialized in hemostatic management to guide clinicians in hemostatic resuscitation, including administration of prohemostatic therapy (PHT). The outcome of patients who receive PHT as part of hemostatic resuscitation remains unanswered. The objective of this study was therefore to investigate clinical outcome of patients receiving PHT managed by the on-call service. We identified 287 patients who received PHT during 2015-16, of which 161 (59%) received fibrinogen concentrate (FC), 111 (39%) received prothrombin complex concentrate (PCC), and 15 (5%) received recombinant factor VIIa (rFVIIa) as the first product. Patients were critically ill with a 30-day mortality of 31%. Among FC recipients, cardiothoracic admission, non-trauma, and antithrombotics predicted survival. FC recipients had lower platelet count and thrombelastography clot strengths than the other PHT groups and within the group, these factors predicted mortality. The symptomatic thromboembolic event (TE) rate at 30 days was 5%. For PCC recipients, vitamin K antagonists predicted survival, while rivaroxaban predicted mortality. TE rate was 2%. We did not identify factors associated with survival in the small group of rFVIIa recipients. TE rate was 13%. In summary, trauma and coagulopathy predicted mortality in patients who received FC and our data suggest that optimization of PHT algorithms may be possible. Outcome of patients who received PCC was comparable to results reported elsewhere and its use may be safe in a setting as reported here. Recombinant FVIIa was rarely used but had the highest incidence of arterial thromboembolism.
Family History of Breast Cancer and Mammographic Breast Density in Premenopausal Women

Key Points Question Is family history of breast cancer (FHBC) associated with mammographic breast density in premenopausal women? Findings In this cohort study of 14 415 premenopausal women, volumetric percent density was significantly higher in women with FHBC compared with women without FHBC, and the odds of having dense breasts was significantly higher in women with FHBC compared with women without FHBC. Meaning The findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.
Differential attainment at MRCS according to gender, ethnicity, age and socioeconomic factors: a retrospective cohort study

Summary Objective A recent independent review on diversity and inclusivity highlighted concerns that barriers to surgical career progression exist for some groups of individuals and not others. Group-level differences in performance at the Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) examinations have been identified but are yet to be investigated. We aimed to characterise the relationship between sociodemographic differences and performance at MRCS. Design Retrospective cohort study. Setting Secondary care. Participants All UK MRCS candidates attempting Part A (n = 5780) and Part B (n = 2600) between 2013 and 2019 with linked sociodemographic data in the UK Medical Education Database (https://www.ukmed.ac.uk). Main outcome measures Chi-square tests established univariate associations with MRCS performance. Multiple logistic regression identified independent predictors of success, adjusted for medical school performance. Results Statistically significant differences in MRCS pass rates were found according to gender, ethnicity, age, graduate status, educational background and socioeconomic status (all p < 0.05). After adjusting for prior academic attainment, being male (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.87–2.92) or a non-graduate (OR 1.98, 95% CI 1.44–2.74) were independent predictors of MRCS Part A success and being a non-graduate (OR 1.77, 95% CI 1.15–2.71) and having attended a fee-paying school (OR 1.51, 95% CI 1.08–2.10) were independent predictors of Part B success. Black and minority ethnic groups were significantly less likely to pass MRCS Part B at their first attempt (OR 0.41, 95% CI 0.18–0.92 for Black candidates and OR 0.49, 95% CI 0.35–0.69 for Asian candidates) compared to White candidates. Conclusions There is significant group-level differential attainment at MRCS, likely to represent the accumulation of privilege and disadvantage experienced by individuals throughout their education and training. Those leading surgical education now have a responsibility to identify and address the causes of these attainment differences.
Molecular diagnosis contribution for personalized medicine

Purpose of review The purpose of the current review is to highlight the most recent findings in molecular allergy and its applicability in precision medicine for allergic patients. Recent findings Molecular allergy provides useful information in areas of respiratory allergy (house dust mites, pet dander and pollen allergy), food allergy (tree nuts, peanuts, fruits and vegetables), hymenoptera venom allergy and others, in order to improve management of patients. Regional differences in sensitization profiles, assay characteristics and interpretation of molecular sensitization in relation to whole extracts and total immunoglobulin E need to be taken into account. Studies of the impact of such strategies are needed. Summary Molecular allergy diagnosis represents a major contribution for personalized medicine. It aids in the assesment of risk prediction, disease severity, genuine/cross-reactive sensitization, and finally to apply precise management strategies.
Posterior corneal vesicles are not associated with the genetic variants that cause posterior polymorphous corneal dystrophy

Posterior corneal vesicles (PCVs) have clinical features that are similar to posterior polymorphous corneal dystrophy (PPCD). To help determine whether there is a shared genetic basis, we screened 38 individuals with PCVs for changes in the three genes identified as causative for PPCD.
The role of probiotics on slowing down the aging process.

The gastrointestinal (GI) microbiota is one of the most complex ecosystems in nature that are mainly comprised of bacteria and other microbes like fungi, protozoa, and viruses. More than 1000 bacterial species have been reported in the gut microbiome, of which most of these species belong to Firmicutes (31.1%), Proteobacteria (29.5%), Actinobacteria (25.9%), or Bacteroidetes (7.1%) phylum. A symbiotic relationship, which plays a critical role in host health, exists between intestinal microflora and its host. With aging, the intestinal microbiota profile changes are observed, generally characterized by the decrease in biodiversity, carriage of commensals, and enrichment of opportunistic pathogens. The dysbiosis associated with aging in the gut microbiota increases the risk of several diseases. Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” and play crucial functions in improving gut health and disease in all age groups, particularly the elderly induvial. This review focuses on the promising effects of probiotics on slowing down the aging process, treating age-related diseases, and improving the quality of life in light of the current clinical studies.
Reply to: Comment on: Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure

1. Pérez-Belmonte LM, Sanz-C anovas J, Mill an-G omez M, et al. Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure. J Am Geriatr Soc. 2022; 70(3):862-871. doi:10.1111/jgs.17585 2. Ida S, Kaneko R, Imataka K, Murata K. Relationship between frailty and mortality, hospitalization, and cardiovascular diseases in diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol. 2019;18:1-13. 3. Sinclair AJ, Abdelhafiz A, Dunning T, et al. An international position statement on the management of frailty in diabetes mellitus: summary of recommendations 2017. J Frailty Aging. 2018;7:10-20.
Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection

Abstract Background The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. Methods We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. Results Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 97% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer–BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) — considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. Conclusions Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.)
Lung-borne systemic inflammation in mechanically ventilated infant rats due to high PEEP, oxygen, and hypocapnia.

BACKGROUND Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response. METHODS Fourteen-day old Wistar rat pups were randomized to the following groups: (a) "control" with tidal volume ~8 mL/kg, PEEP 5 cmH2O, FiO2 0.4, RR 90 min-1, (b) "PEEP 1", (c) "PEEP 9" (d) "FiO2 0.21", (e) "FiO2 1.0", (f) "hypocapnia" with RR of 180 min-1, and (g) "hypercapnia" with RR of 60 min-1. Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment. RESULTS Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were driven by FiO2 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH2O, P<0.05) and hypocapnia (P<0.05), and TNF-α was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected. CONCLUSION Alterations of PEEP, FiO2, and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants.
Coeliac disease in the COVID-19 pandemic: does HLA have a protective effect?

Abstract Background The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by a novel coronavirus (SARS-CoV-2), is emerging as a worldwide public health emergency. Several scientific contributions reported the potential relevance of human leukocyte antigen (HLA) polymorphism and susceptibility to viruses, such as SARS-CoV. In our study, we examined a population of coeliac subjects presenting the HLA haplotype DQ2 and/or DQ8. Our aim was to evaluate whether HLA DQ2 and/or DQ8 haplotype play a role in SARS-CoV-2-infection. The aim was also to evaluate the difficulty in following the gluten-free diet due to all the adversities produced by the pandemic, such as the food supply disruption, and the difficulties in managing the clinical follow-up. Methods 191 consecutive coeliac patients completed a questionnaire on their current clinical status, psychological effects, and management of the gluten-free diet experienced during the COVID-19 pandemic and questions regarding possible SARS-CoV-2 infection. Results Out of the 191 patients who participated in the study, 42 were full-blown coeliac and 149 were in remission. From the answers provided, 84.8% of patients declared that they no longer consider themselves vulnerable to COVID-19 as they suffer from coeliac disease; 94.2% of patients did not encounter any difficulties in managing the gluten-free diet or in acquiring specific foods and 64.9% of patients in our study underwent diagnostic testing for SARS-CoV-2. Out of this number, 31.5% did so due to contacts with subjects affected by COVID-19, 26.6% for work related reasons, 11.3% due to flu-like symptoms and 30.6% for other reasons. Only 5.8% of the enrolled patients received a diagnosis of COVID-19. Out of all the patients in our population who were diagnosed with COVID-19, 94.8% developed no symptoms and none of them needed hospitalization or intensive care. Conclusion The hypothesis that the HLADQ2 and/or DQ8 haplotype plays a protective role against SARS-CoV-2 infection, as against other viral infections, is intriguingly suggestive. KEY MESSAGES COVID-19 as a public health emergency; SARS-CoV-2 and possible complications in coeliac disease; Role of HLA DQ2 and/or DQ8 in SARS-CoV-2 infection.
The effect of gestational age at BNT162b2 mRNA vaccination on maternal and neonatal SARS-CoV-2 antibody levels

Abstract Background COVID-19 during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of SARS-CoV-2 vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies. Methods Maternal and cord blood sera were collected from mother/newborn dyads (n=402), following term delivery after antenatal two-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)-specific IgG levels were evaluated in the samples collected. Results Median anti-S and anti-RBD-specific IgG levels in maternal sera at the time of delivery were lowest following 1 st trimester vaccination (n=90) (anti-S IgG: 76 AU/mL, anti-RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the 2 nd trimester (n=124) (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1263 AU/mL), and highest after 3 rd trimester vaccination (n=188) (anti-S IgG: 240 AU/mL, anti-RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the 1 st trimester (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the 1 st trimester (n=30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels. Conclusions These results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose, hints to its potential benefit in those who completed the two-dose vaccine series at early pregnancy or prior to conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.
Altered features of body composition in older adults with type 2 diabetes and prediabetes compared with matched controls

Ageing is accompanied by muscle loss and fat gain, which may elevate the risk of type 2 diabetes (T2D). However, there is a paucity of data on the distribution of regional lean and fat tissue in older adults with T2D or prediabetes compared with healthy controls. The objective of this study was to compare regional body composition [by dual‐energy x‐ray absorptiometry (DXA)], muscle and subcutaneous adipose tissue (SAT) thicknesses (by ultrasound), and ultrasound‐based muscle texture features in older adults with T2D or prediabetes compared with normoglycaemic controls.
Through A Glass Darkly: New Questions (And Answers) About IMF Programs

Recent research on the International Monetary Fund has focused on the adoption, implementation and impact of their lending programs and their political dimensions. This paper evaluates this literature and suggests promising areas of future work. The first area to be surveyed deals with the initiation of a Fund program, which has been shown to be influenced by political and institutional variables. The record also shows that in some cases governments borrow from the Fund on a continuing basis. A second focus of research analyzes the design and implementation of Fund supported polices, since many programs are often not successfully completed. Political economy models attribute the incomplete implementation to a lack of domestic support for reform measures, and empirical studies provide evidence is support of this hypothesis. The third issue that is addressed is the impact of IMF policies on the economy of the borrowing government. Most of the empirical work finds that these policies improve the balance of payments but may have a negative impact on growth and income distribution. Finally, there are no signs of a catalytic effect on Fund programs on private capital flows to program countries, but some evidence of moral hazard.
Left atrial appendage exclusion in patients with atrial fibrillation: Should it become standard of care?

Atrial Fibrillation (AF) is the most common arrhythmia affecting the general population, with the prevalence projected to reach 12.1 million cases in 2030. Recently, attention has focused on the role of the Left Atrial Appendage (LAA) and its association with the most feared complication of AF: thromboembolism. Common sense indicates that the LAA should be excluded in all patients with AF; however, procedures to exclude the LAA have yet to become the standard of care. Recent studies in the cardiac surgery literature , , indicate a clear benefit of LAA exclusion amongst patients with AF undergoing cardiac surgery. Interestingly, this benefit was found to extend well beyond the postoperative period, in cohorts that were equally anticoagulated and had similar CHA2DS2-VASC scores. It appears reasonable that our medical community should strongly consider initiating a prospective randomized trial in an effort to fully elucidate the need for routine LAA exclusion in this patient population.
Effects of Ownership Text Message Wording and Reminders on Receipt of an Influenza Vaccination

Key Points Question Does a text message telling patients that “a flu shot has been reserved for you” increase vaccination rates? Findings In a randomized clinical trial of 11 188 patients, a “reserved for you” text message produced vaccination rates that were significantly higher than no message. There was no statistically significant difference in comparison with a message stating that flu shots were available. Meaning These findings suggest that text messaging encourages vaccination; more research is needed to evaluate the potential benefits of messages conveying ownership sent before a primary care visit.
DEVELOPMENT OF A MINIMUM REPORTING SET OF CONTEXTUAL FACTORS FOR REHABILITATION STUDIES: A DELPHI STUDY

Objective To identify the most important categories of the International Classification of Service Organization in Rehabilitation (ICSO-R 2.0) for a minimum reporting data set. Methods A 2-step Delphi survey was used. Rehabilitation experts from all world regions including physicians, nurses, neuropsychologists, physiotherapists, and others, were invited to participate. In the first round, all participants were asked to rate the categories and subcategories of the ICSO-R 2.0 with the following criteria: Being relevant for study outcomes; Being distinctive among different rehabilitation settings; Being feasible to use and reported by objective figures or other clear characterization. All categories that were rated relevant, distinctive and feasible by more than 60% of respondents from the first round were included in the second round. Results The most important and relevant factors for the minimum reporting set in rehabilitation services regarding the provider were: human resources, context, technical resources, quality assurance and management, location of provider, and ownership. Regarding the service delivery, the most important and relevant factors were: target group, rehabilitation team, aspect of time and intensity, setting, location of service delivery, modes of referral, facility and reporting and documentation. Conclusion Several categories were identified, and reduction in these through discussions and iterative voting at workshops and consensus conferences is needed before finalizing the reporting set. LAY ABSTRACT A goal of this Delphi study was to identify the most important parameters of the International Classification of Service Organization in Rehabilitation (ICSO-R 2.0), to characterize rehabilitation services and identify important missing categories needed in a minimum reporting set. The most important and relevant factors for developing a minimum reporting set regarding the provider were: human resources, context, technical resources, quality assurance and management, location of provider, and ownership. Regarding service delivery the most important and relevant factors were: target group, rehabilitation team, aspect of time and intensity, setting, location of service delivery, modes of referral, facility and reporting and documentation. These factors should be discussed further, and a final set should be developed in workshops through discussion and iterative voting.