bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population
Authors: Chen Mo , Xu Wen-Mao , Wang Gui-Yang , Hou Ya-Xuan , Tian Ting-Ting , Li Yu-Qing , Qi Hong-Jiao , Zhou Meng , Kong Wei-Jia , Lu Mei-Xia
Published: October 2021

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case–control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3’-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e−8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02–1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.
Task-relevant representations and cognitive control demands modulate functional connectivity from ventral occipito-temporal cortex during object recognition tasks
Authors: Branzi Francesca M , Martin Clara D , Paz-Alonso Pedro M
Published: October 2021

The left ventral occipito-temporal cortex (vOTC) supports extraction and processing of visual features. However, it has remained unclear whether left vOTC-based functional connectivity (FC) differs according to task-relevant representations (e.g., lexical, visual) and control demands imposed by the task, even when similar visual-semantic processing is required for object identification. Here, neural responses to the same set of pictures of meaningful objects were measured, while the type of task that participants had to perform (picture naming versus size-judgment task), and the level of cognitive control required by the picture naming task (high versus low interference contexts) were manipulated. Explicit retrieval of lexical representations in the picture naming task facilitated activation of lexical/phonological representations, modulating FC between left vOTC and dorsal anterior-cingulate-cortex/pre-supplementary-motor-area. This effect was not observed in the size-judgment task, which did not require explicit word-retrieval of object names. Furthermore, retrieving the very same lexical/phonological representation in the high versus low interference contexts during picture naming increased FC between left vOTC and left caudate. These findings support the proposal that vOTC functional specialization emerges from interactions with task-relevant brain regions.
Ultraviolet-C Light Evaluation as Adjunct Disinfection to Remove Multidrug-Resistant Organisms
Authors: Rock Clare , Hsu Yea Jen , Curless Melanie S , Carroll Karen C , Ross Howard Tracy , Carson Kathryn A , Cummings Stephanie , Anderson Michael , Milstone Aaron M , Maragakis Lisa L
Published: October 2021

Background

Our objective was to determine if the addition of ultraviolet-C (UV-C) light to daily and discharge patient room cleaning reduces healthcare-associated infection rates of vancomycin-resistant enterococci (VRE) and Clostridioides difficile in immunocompromised adults.

Methods

We performed a cluster randomized crossover control trial in 4 cancer and 1 solid organ transplant in-patient units at the Johns Hopkins Hospital, Baltimore, Maryland. For study year 1, each unit was randomized to intervention of UV-C light plus standard environmental cleaning or control of standard environmental cleaning, followed by a 5-week washout period. In study year 2, units switched assignments. The outcomes were healthcare-associated rates of VRE or C. difficile. Statistical inference used a two-stage approach recommended for cluster-randomized trials with <15 clusters/arm.

Results

In total, 302 new VRE infections were observed during 45787 at risk patient-days. The incidence in control and intervention groups was 6.68 and 6.52 per 1000 patient-days respectively; the unadjusted incidence rate ratio (IRR) was 0.98 (95% confidence interval [CI], .78 − 1.22; P = .54). There were 84 new C. difficile infections observed during 26118 at risk patient-days. The incidence in control and intervention periods was 2.64 and 3.78 per 1000 patient-days respectively; the unadjusted IRR was 1.43 (95% CI, .93 − 2.21; P = .98).

Conclusions

When used daily and at post discharge in addition to standard environmental cleaning, UV-C disinfection did not reduce VRE or C. difficile infection rates in cancer and solid organ transplant units.
Resistance in Enterobacterales Is Higher Among People Living With Human Immunodeficiency Virus
Authors: Henderson Heather I , Napravnik Sonia , Gower Emily W , Aiello Allison E , Kinlaw Alan C , Williams Billy , Wohl David A , van Duin David
Published: October 2021

Background

Multidrug-resistant Enterobacterales (MDR-E) are important pathogens. People living with human immunodeficiency virus (HIV; PLWH) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities.

Methods

We analyzed data from 36 521 patients in a healthcare system in North Carolina who had a clinical culture with growth of an Enterobacterales species from 2000 to 2018; 440 were PLWH. We used generalized linear models to estimate prevalence ratios and differences, contrasting PLWH and people not living with HIV (PNLWH) for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models.

Results

The overall prevalence of MDR-E was higher among PLWH (21.5%; 95% confidence interval [CI], 18.2%–25.1%) vs PNLWH (16.5%; 95% CI, 16.2%–16.9%), with an adjusted prevalence ratio of 1.38 (95% CI, 1.14–1.65). PLWH had higher rates of antimicrobial resistance than PNLWH for all antibiotic classes analyzed, including penicillins, penicillin/beta lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PLWH than PNLWH throughout the study period based on the 5-year moving average.

Conclusions

In a large clinical study population in the southeastern United States from 2000 to 2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PLWH than PNLWH. These data highlight the importance of identifying and mitigating the factors that contribute to antimicrobial resistance in PLWH, given the potential clinical consequences of these resistant pathogens.
Point-of-care Intestinal Ultrasound in IBD Patients: Disease Management and Diagnostic Yield in a Real-world Cohort and Proposal of a Point-of-care Algorithm
Authors: Bots S , De Voogd F , De Jong M , Ligtvoet V , Löwenberg M , Duijvestein M , Ponsioen C Y , D’Haens G , Gecse K B
Published: October 2021

Introduction

Intestinal ultrasound [IUS] is useful for assessment of inflammation, complications, and treatment follow-up in inflammatory bowel disease [IBD] patients. We aimed to study outcomes and impact on disease management for point-of-care [POC] IUS in IBD patients.

Methods

Two patient cohorts undergoing POC IUS [January 2016–July 2018 and October 2019–December 2019] were included retrospectively. Disease management after IUS was analysed and IUS outcomes were compared with symptoms, biomarkers, and additional imaging within 8 weeks from IUS. To study differences in use of IUS over time, cohorts were compared.

Results

In total, 345 examinations (280 in Crohn’s disease [CD]/65 in ulcerative colitis [UC]) were performed. Present inflammation on IUS was comparable between symptomatic and asymptomatic CD [67.6% vs 60.5%; p = 0.291]. In 60%, IUS had impact on disease management with change in medication in 47.8%. Additional endoscopy/magnetic resonance imaging [MRI] was planned after 32.8% examinations, showing good correlation with IUS in 86.3% [ρ = 0.70, p <0.0001] and 80.0% [ρ = 0.75, p <0.0001] of cases, respectively. Faecal calprotectin was higher in active versus inactive disease on IUS [664 µg/g vs 79 µg/g; p <0.001]. Over the years, IUS was performed more frequently to monitor treatment response and the use of MRI was reduced within the cohort.

Conclusions

POC IUS affects clinical decision making and could detect preclinical relapse in CD patients, with potential to reduce additional endoscopy or MRI. In addition, the paradigm expands towards monitoring treatment and close follow-up for IUS. Based on our results, we propose a POC IUS algorithm for follow-up of IBD patients.
Speckle-tracking-based global longitudinal and circumferential strain detect early signs of antibody-mediated rejection in heart transplant patients
Authors: Ciarka Agnieszka , Cordeiro Filipa , Droogne Walter , Van Cleemput Johan , Voigt Jens-Uwe
Published: October 2021

Aims

Acute rejection is an important cause of mortality after heart transplant (HTx), but symptoms develop only when myocardial damage is already extensive. We sought to investigate if echocardiographic parameters can detect and predict an acute cellular rejection (ACR) or antibody-mediated rejection (AMR) episode in HTx patients.

Methods and results

Data of 403 consecutive HTx recipients between 2003 and 2020 from our centre were reviewed. Patients with severe ACR (n = 10) and AMR (n = 7) were identified. Each HTx patient presenting with rejection was matched to a control HTx patient. Echocardiographic variables from the moment of rejection and 3, 6, and 12 months before were analysed and compared among groups. At acute rejection episode, patients with rejection had lower values of global longitudinal strain (GLS), global circumferential strain (GCS), and left ventricular ejection fraction (LVEF) compared to controls. HTx patients with AMR showed a progressive decline of GLS and GCS in the months preceding acute rejection, while controls and ACR patients had stable strain values except for the moment of rejection. In our cohort, a GLS cut-off lower than 15.5% and a GCS cut-off lower than 15.2% could distinguish with a sensitivity and specificity of 100.0% AMR from controls 3 months before rejection. LVEF and other conventional echo parameters could not differentiate among groups.

Conclusion

GLS and GCS show a progressive decrease months before AMR becomes clinically apparent. Our data suggest that global strain assessment by echocardiography allows an early detection of a developing AMR, which could improve the clinical management of HTx patients.
CAD-RADS may underestimate coronary plaque progression as detected by serial CT angiography
Authors: Szilveszter Bálint , Vattay Borbála , Bossoussou Melinda , Vecsey-Nagy Milán , Simon Judit , Merkely Béla , Maurovich-Horvat Pál , Kolossváry Márton
Published: October 2021

Aims

We wished to assess whether different clinical definitions of coronary artery disease (CAD) [segment stenosis and involvement score (SSS, SIS), Coronary Artery Disease—Reporting and Data System (CAD-RADS)] affect which patients are considered to progress and which risk factors affect progression.

Methods and results

We enrolled 115 subsequent patients (60.1 ± 9.6 years, 27% female) who underwent serial coronary computed tomography angiography (CTA) imaging with >1year between the two examinations. CAD was described using SSS, SIS, and CAD-RADS. Linear mixed models were used to investigate the effects of risk factors on the overall amount of CAD and the effect on annual progression rate of different definitions. Coronary plaque burdens were SSS 4.63 ± 4.06 vs. 5.67 ± 5.10, P < 0.001; SIS 3.43 ± 2.53 vs. 3.89 ± 2.65, P < 0.001; CAD-RADS 0:8.7% vs. 0.0% 1:44.3% vs. 40.9%, 2:34.8% vs. 40.9%, 3:7.0% vs. 9.6% 4:3.5% vs. 6.1% 5:1.7% vs. 2.6%, P < 0.001, at baseline and follow-up, respectively. Overall, 53.0%, 29.6%, and 28.7% of patients progressed over time based on SSS, SIS, and CAD-RADS, respectively. Of the patients who progressed based on SSS, only 54% showed changes in CAD-RADS. Smoking and diabetes increased the annual progression rate of SSS by 0.37/year and 0.38/year, respectively (both P < 0.05). Furthermore, each year increase in age raised SSS by 0.12 [confidence interval (CI) 0.05–0.20, P = 0.001] and SIS 0.10 (CI 0.06–0.15, P < 0.001), while female sex was associated with 2.86 lower SSS (CI −4.52 to −1.20, P < 0.001) and 1.68 SIS values (CI −2.65 to −0.77, P = 0.001).

Conclusion

CAD-RADS could not capture the progression of CAD in almost half of patients with serial CTA. Differences in CAD definitions may lead to significant differences in patients who are considered to progress, and which risk factors are considered to influence progression.
Late primary angioplasty (beyond 12 h): are we sure it should be avoided?
Authors: Bolognese Leonardo
Published: October 2021

Optimal management for patients with ST-segment elevation myocardial infarction (STEMI) who arrive at a hospital late remains uncertain since evidence and real-world data are limited. Patients who present late with a STEMI are a heterogeneous population, and the clinical decision regarding percutaneous coronary intervention (PCI) should not be the same for all. One randomized clinical trial, multiple mechanistic studies, and contemporary registries suggest a presumed benefit for a prompt restoration of coronary flow even in late presenting STEMI. Crucial elements in decision-making are the presence of haemodynamic or electrical instability, and ongoing ischaemic signs or symptoms to tip the scales toward PCI. Among clinically stable, late-presenting patients, myocardial viability assessment and functional testing can identify yet another subgroup that may benefit from late PCI
New prevention scenarios: polygenic risk
Authors: Boccanelli Alessandro , Bottà Giordano
Published: October 2021

Although coronary heart disease is a highly preventable disease, it is still the leading cause of morbidity and mortality in developed countries. This is also due to the fact that the risk models used in clinical practice have proved ineffective in identifying people at risk: up to 30% of cases of myocardial infarction do not have traditional risk factors used in risk estimation models. Although the genetic component of myocardial infarction has been known for many years, with an inheritance rate of between 40% and 60%, it is not yet used as a risk factor in primary prevention models such as the Heart Card or the European SCORE. Recent advances in genomics and the use of clinical big data have allowed the development of genetic risk scores called Polygenic Risk Score (PRS), capable of identifying populations with average LDL-C levels, but with the same risk of heart attack of carriers of hypercholesterolaemia. The clinical usefulness of the PRS lies precisely in identifying high-risk individuals who are invisible to traditional models. The clinical applications of PRS for coronary artery disease are discussed in this report.
Mitral valve prolapse with ventricular arrhythmias: does it carries a worse prognosis?
Authors: Coutsoumbas Gloria Vassilikì , Di Pasquale Giuseppe
Published: October 2021

The association of mitral valve prolapse (MVP) with ventricular arrhythmias has long been known and has generally been considered a benign condition. In recent years, however, a small but not negligible risk of malignant ventricular arrhythmias and sudden cardiac death has been documented in the large population of subjects with MVP. The main predictors of major arrhythmic risk identified so far include history of syncope, ventricular repolarization abnormalities in the inferior-lateral electrocardiogram leads, right bundle branch block morphology of ventricular ectopic beats, finding of areas of myocardial fibrosis on cardiac magnetic resonance, and mitral annular disjunction (MAD) on echocardiogram, as well as a possible pro-arrhythmic genetic substrate. The stratification of arrhythmic risk, with the active search for red flags and in particular of MAD, is important to identify patients with the malignant arrhythmic variant of MVP in whom to implement closer surveillance and possible therapeutic interventions.
Recurrent pericarditis is less scary: the new therapeutic solutions
Authors: Del Pinto Rita , Ferri Claudio
Published: October 2021

Pericarditis is a common inflammatory disease affecting the pericardial sac, resulting from a variety of stimuli that trigger a stereotyped immune response. Generally self-limiting, this condition can be burdened by a significant risk of acute complications and relapses, with recurrence rates affecting up to 30% of patients, especially in the case of diagnostic and therapeutic delay. Therapeutic options in recurrent forms, initially based only on the use of traditional drugs such as colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids, have recently been enriched with new molecules, such as interleukin 1 blockers anakinra and rilonacept, particularly indicated in refractory forms dependent on corticosteroids. Other medically relevant therapeutic possibilities in refractory disease include azathioprine, methotrexate, and intravenous immunoglobulins. This brief review aims to summarize the treatment strategies of recurrent pericarditis in light of the most up-to-date evidence and recommendations.
Transthyretin amyloidosis in aortic stenosis: clinical and therapeutic implications
Authors: Fabbri Gioele , Serenelli Matteo , Cantone Anna , Sanguettoli Federico , Rapezzi Claudio
Published: October 2021

About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.
Atrial fibrillation in advanced renal failure: are there alternative solutions to warfarin-dicumarol?
Authors: Rossini Roberta , Casula Matteo , Ferlini Marco
Published: October 2021

Patients with atrial fibrillation (AF) and chronic renal failure (CRF) represent a growing population in epidemiological terms since both conditions increase with advancing age. The association of AF and CRF is burdened with a poor prognosis and with a high risk of adverse events, both ischaemic and haemorrhagic. Oral anticoagulant therapy, in these patients, is more problematic, especially due to the concomitant increased risk of bleeding. The use of direct oral anticoagulants (DOACs) in patients with non-severe renal insufficiency appears to be safe and effective. Since all currently available DOACs are at least partially eliminated by the kidney (dabigatran is the direct anticoagulant with the highest rate of renal elimination, approximately 80%), periodic monitoring of renal function is recommended to evaluate possible need for dosage adjustment. In patients with advanced renal insufficiency, the use of DOAC appears controversial, given the small number of clinical studies that have tested its efficacy and safety. It is known, however, that oral anticoagulation therapy with vitamin K antagonists (VKAs) is associated with an increase in nephropathy and renal-vascular calcification. From this point of view, therapy with DOAC could be more advantageous than VKAs. Data from clinical studies would seem to show that the use of dabigatran and rivaroxaban in these patients may lead to a reduction in the inevitable deterioration of renal function.
Clinical impact of myocardial fibrosis in severe aortic stenosis
Authors: Castrichini Matteo , Vitrella Giancarlo , De Luca Antonio , Altinier Alessandro , Korcova Renata , Pagura Linda , Radesich Cinzia , Sinagra Gianfranco
Published: October 2021

The pressure overload due to the progressive narrowing of the valve area determines the development of the left ventricular hypertrophy which characterizes aortic stenosis (AS). The onset of myocardial fibrosis marks the inexorable decline of an initially compensatory response towards heart failure. However, myocardial fibrosis does not yet represent a key element in the prognostic and therapeutic framework of AS. In this context, cardiac magnetic resonance imaging plays a major role by highlighting both the focal irreversible fibrotic replacement, using the late gadolinium enhancement (LGE) technique, and the earlier diffuse reversible interstitial fibrosis, using the T1 mapping techniques. For this reason, the presence of myocardial fibrosis would be useful to identify a subgroup of patients at greater risk of events among the subjects with severe AS. Actually, more and more evidences seem to identify the presence of LGE as a powerful prognostic factor to be used to optimize the timing of prosthetic valve replacement. Randomized clinical trials, such as the EVoLVeD trial currently underway, will be needed to better define the importance of myocardial fibrosis assessment in the management of patients with AS.
What we have learned: is pulmonary vein isolation still the cornerstone of atrial fibrillation ablation?
Authors: Metzner Andreas , Kuck Karl-Heinz , Chun Julian K R
Published: October 2021

Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. The cornerstone of all ablation strategies is electrical isolation of the pulmonary veins (PVs). Ablation strategies going beyond PV isolation (PVI) might be considered in the setting of recurrent AF despite durably isolated PVs. The lack of persistent PVI, however, limits the opportunities to perceive the real impact of this endpoint on AF suppression and to fully understand the benefit of extended ablation strategies going beyond. To overcome this limitation, novel and innovative ablation systems have been developed to facilitate acute PVI and to increase its durability. These systems include balloon-based ablation devices incorporating different energy sources such as cryo energy, laser, or radiofrequency current, but also new energy sources such as pulsed field ablation as a non-thermal energy source. These technologies could advance catheter ablation of AF to an early stage of the disease and to the primary treatment tool. The current manuscript focuses on the past, the present, and the future value of PVI as the cornerstone for interventional treatment of AF and on how to achieve durable PVI during the first procedure and to further improve the clinical success rates of AF ablation. It also analyses extended ablation strategies going beyond PVI and their impact.
Antibiotic dispensing during the COVID-19 pandemic: analysis of Welsh primary care dispensing data
Authors: Wasag Diana R , Cannings-John Rebecca , Hughes Kathryn , Ahmed Haroon
Published: October 2021

Background

The COVID-19 pandemic led to rapid changes in demand and delivery of primary care services that could have led to increases in antibiotic prescribing.

Objective

We investigated the impact of the COVID-19 pandemic on oral antibiotic dispensing rates in primary care in Wales using longitudinal analysis of monthly oral antibiotic dispensing data from 1 April 2018 to 30 April 2021.

Methods

We used All-Wales primary care dispensing data. We examined trends in oral antibiotic dispensing per 1,000 people for Wales and for individual Health Boards. We used interrupted time series analysis to estimate changes in trends pre- and post-April 2020 to assess the impact of the first and subsequent lockdowns.

Results

Between April 2020 and April 2021, antibiotic dispensing in Wales was lower compared with the same period in 2018 and 2019, with an average monthly decrease of 14.00 dispensed items per 1,000 registered patients (95% confidence interval 19.89–8.11). The overall prepandemic monthly antibiotic dispensing rate ranged from 48.5 to 67.4 antibiotic items per 1,000 registered patients. From the onset of the pandemic, it ranged from 40.3 to 49.07 antibiotic items per 1,000 registered patients. This reduction was primarily driven by narrow-spectrum antibiotics. Statistically significant reductions were also observed for antibiotics commonly dispensed for the treatment of respiratory tract infections. Dispensing of antibiotics primarily used for urinary and skin infections remained stable.

Conclusions

Despite complexities of consulting during the COVID-19 pandemic in primary care we found no evidence of an increase in antibiotic dispensing during this time.
Age-Related Differences in T-Cell Subsets in a Nationally Representative Sample of People Older Than Age 55: Findings From the Health and Retirement Study
Authors: Thyagarajan Bharat , Faul Jessica , Vivek Sithara , Kim Jung K , Nikolich-Žugich Janko , Weir David , Crimmins Eileen M
Published: October 2021

Though T-cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T-cell subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the United States. We evaluated the counts of T-cell subsets including total, CD4+, and CD8+ T cells and their naïve (Tn), effector memory (Tem), and effector subsets, in the context of age, sex, and exposure to cytomegalovirus (CMV) infection among 8 848 Health and Retirement Study participants, a nationally representative study of adults older than 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV-seropositive and CMV-seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV-seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T-cell subsets by age and sex in a national sample of US adults older than the age of 55 years. Understanding T-cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.
Clinical Features and Risk Factors for Mortality Among Long-term Care Facility Residents Hospitalized Due to COVID-19 in Spain
Authors: Ramos-Rincón José-Manuel , Bernabeu-Wittel Máximo , Fiteni-Mera Isabel , López-Sampalo Almudena , López-Ríos Carmen , García-Andreu María-del-Mar , Mancebo-Sevilla Juan-José , Jiménez-Juan Carlos , Matía-Sanz Marta , López-Quirantes Pablo , Rubio-Rivas Manuel , Paredes-Ruiz Diana , González-San-Narciso Candela , González-Vega Rocío , Sanz-Espinosa Pablo , Hernández-Milián Almudena , Gonzalez-Noya Amara , Gil-Sánchez Ricardo , Boixeda Ramon , Alcalá-Pedrajas José-Nicolás , Palop-Cervera Marta , Cortés-Rodríguez Begoña , Guisado-Espartero María-Esther , Mella-Pérez Carmen , Gómez-Huelgas Ricardo ,   SEMI-COVID-19 Network
Published: October 2021

Background

COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents.

Methods

This is a cross-sectional analysis within a retrospective cohort of hospitalized patients ≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis.

Results

Of 6 189 patients ≥75 years, 1 185 (19.1%) were LTCF residents and 4 548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs 82.1 years), mostly female (61.6% vs 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p < .001). Mortality risk factors in LTCF residents were severe functional dependence (adjusted odds ratios [aOR]: 1.79; 95% confidence interval [CI]: 1.13–2.83; p = .012), dyspnea (1.66; 1.16–2.39; p = .004), SatO2 < 94% (1.73; 1.27–2.37; p = .001), temperature ≥ 37.8°C (1.62; 1.11–2.38; p = .013); qSOFA index ≥ 2 (1.62; 1.11–2.38; p = .013), bilateral infiltrates (1.98; 1.24–2.98; p < .001), and high C-reactive protein (1.005; 1.003–1.007; p < .001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR: 0.74, 95%CI: 0.62–0.87; p < .001).

Conclusion

Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.
Prediction–variance relation in a state-space fish stock assessment model
Authors: Breivik Olav Nikolai , Nielsen Anders , Berg Casper W
Published: October 2021

The state-space assessment model (SAM) is extended by allowing a functional relationship between observation variance and the corresponding prediction. An estimated relationship between observation variance and predicted value for each individual observation allows the model to assign smaller (or larger) variance to predicted larger log-observations. This relation is different from the usual assumption of constant variance of log-observations within age groups. The prediction–variance link is implemented and compared to the usual constant variance assumption for the official assessments of North East Arctic cod and haddock. For both of these stocks, the prediction–variance link is found to give a significant improvement.
Is it time to incorporate hands-on simulation into the cardiothoracic surgery curriculum?
Authors: Hussein Nabil , Zientara Alicja , Gollmann-Tepeköylü Can , Loubani Mahmoud
Published: October 2021

The COVID pandemic has had huge implications for training in cardiothoracic surgery. The reduction in training opportunities has led to concerns from trainees globally regarding the impact on their learning and their training progression. Surgical simulation is effective in the development of technical skills in cardiothoracic surgery with numerous examples of low and high-fidelity simulators. Despite this the incorporation of such methods into training curricula worldwide is seldom. Core fundamentals are required to successfully implement surgical simulation into training programmes, which includes; commitment from trainers, regular sessions and structured feedback. Few programmes have demonstrated the successful incorporation of surgical simulation and there is a growing acceptance of its place in the speciality. As we recover from this challenging period it may be the right opportunity to evolve how we train our current and future trainees by incorporating hands-on simulation as a fundamental part of the cardiothoracic curriculum.
The Choice of Either Quetiapine or Aripiprazole as Augmentation Treatment in a European Naturalistic Sample of Patients With Major Depressive Disorder
Authors: Bartova Lucie , Fugger Gernot , Dold Markus , Kautzky Alexander , Swoboda Marleen Margret Mignon , Rujescu Dan , Zohar Joseph , Souery Daniel , Mendlewicz Julien , Montgomery Stuart , Fabbri Chiara , Serretti Alessandro , Kasper Siegfried
Published: October 2021

Background

Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce.

Methods

In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy.

Results

Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine.

Conclusions

Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.
Creation of a synthesis-friendly inflammation-inducible promoter suitable for cell therapy
Authors: Jadav Anish , Truong Kevin
Published: October 2021

The development of ‘smart’ cell-based therapeutics requires cells that first recognize conditions consistent with disease (e.g. inflammation) and then subsequently release therapeutic proteins, thereby reducing potential toxicity from otherwise continuous expression. Promoters containing NF-κB response elements are often used as reporters of inflammation; however, endogenous promoters have crosstalk with other pathways, and current synthetic promoters have many exact sequence repeats of NF-κB response elements which make them both difficult to synthesize and inherently genetically unstable. Herein, a synthesis-friendly inflammation-inducible promoter (named SFNp) was created by the packing of 14 NF-κB response elements, which have no repeats >9 bp, followed by a minimal cytomegalovirus promoter. In stably expressing human embryonic kidney 293 cells, we assessed the ability of SFNp to inducibly transcribe genes for reporting expression, changing cell morphology, and performing cell fusion. These experiments represent simple milestones for potentially using SFNp in the development of cell-based therapeutics. As strongly repeated DNA can compromise the long-term stability of genetic circuits, new designs used in ‘smart’ cell therapy will become more reliant on synthesis-friendly components like SFNp.
Reporting Security: Postcolonial Governmentality in the United Nations’ Trusteeship System
Authors: Bonacker Thorsten
Published: October 2021

This article examines the political rationality and governance practices that emerged in the course of the international politics of decolonization. It focuses primarily on the UN trusteeship system, within which the former League of Nations mandates were continued by the trusteeship powers. In this process, the trustees' policies were placed under international scrutiny. The article ties in with International Political Sociology's increased interest in historical perspectives. In particular, it asks how the political rationality of the trusteeship system differs from colonial governmentality. Two arguments are put forward: first, international governing, as can be seen from the trusteeship system, is characterized by a postcolonial governmentality that continues central elements of colonial governmentality, but transfers them to the international level. Second, following Latour, it is argued that trusteeship governance is constituted by forms of knowledge production and the bureaucratic circulation of information that continue to shape the governance of international organizations today. To this end, the article takes up in particular the reporting system of the trusteeship system as well as its central instruments of knowledge production: the visiting missions, the petition system, and the collection of data through questionnaires.
The International Responsibility to Protect in a Post-Liberal Order
Authors: Pattison James
Published: October 2021

This article considers the implications of a post-liberal order for the international responsibility to protect. It focuses on two questions. First, what challenges will the international responsibility to protect face in a post-liberal order? Second, in light of these challenges, how would the requirements of the international responsibility to protect differ in the post-liberal order? In response to the first question, the article argues that in a post-liberal order the international responsibility to protect is likely to be subject to the “Influence Challenge,” whereby its ability to constrain and influence states decreases. In response to the second question, it argues that the requirements of the international responsibility to protect would be affected in several ways, including necessitating greater consideration of questions of prioritization and requiring a re-evaluation, and potential abandonment, of the currently predominant approach to the responsibility to protect.
Indirect Genetic Effects: A Cross-disciplinary Perspective on Empirical Studies
Authors: Baud Amelie , McPeek Sarah , Chen Nancy , Hughes Kimberly A
Published: October 2021

Indirect genetic effects (IGE) occur when an individual’s phenotype is influenced by genetic variation in conspecifics. Opportunities for IGE are ubiquitous, and, when present, IGE have profound implications for behavioral, evolutionary, agricultural, and biomedical genetics. Despite their importance, the empirical study of IGE lags behind the development of theory. In large part, this lag can be attributed to the fact that measuring IGE, and deconvoluting them from the direct genetic effects of an individual’s own genotype, is subject to many potential pitfalls. In this Perspective, we describe current challenges that empiricists across all disciplines will encounter in measuring and understanding IGE. Using ideas and examples spanning evolutionary, agricultural, and biomedical genetics, we also describe potential solutions to these challenges, focusing on opportunities provided by recent advances in genomic, monitoring, and phenotyping technologies. We hope that this cross-disciplinary assessment will advance the goal of understanding the pervasive effects of conspecific interactions in biology.
South Europe perspective of COVID-19 impact on travel medicine
Authors: Gobbi Federico , Noharet Roxane , Abreu Cândida , del Mar Lago Nuñez Maria , Canale Alice , Oñorbe Mar Faraco , Muñoz José , Rossanese Andrea , Atouguia Jorge
Published: October 2021

The COVID-19 crisis has drastically impacted the travel medicine field worldwide. In this perspective we have captured the challenges faced by travel clinicians in three Southern European countries: Italy, Spain and Portugal. Current practices, solutions and areas for improvement in these specific countries are discussed.
HDFN Resulting from Anti-U: Alternatives to Allogeneic Intrauterine Transfusion
Authors: Caudill Jamie L , Gillard Laurie
Published: October 2021

Hemolytic disease of the fetus and newborn (HDFN) carries significant fetal mortality risks. Although anti-D as a source of HDFN has been prevented for decades using D-specific immunoglobulin to prevent alloimmunization between fetus and mother, minor blood groups may still result in disease, with potentially disastrous consequences if left untreated. Strategies such as intrauterine transfusion, early delivery, and vigilant serologic monitoring of fetal anemia have been the standards of care for alloimmunized patients, but beyond this not much more is possible. Mothers with rare phenotypes who are alloimmunized against extremely common red blood cell antigens may find access to rare antigen-negative blood units limited. This case study presents a healthy G10P6 woman with known anti-U presenting for treatment via intrauterine transfusion in the second trimester and follows the patient through successful delivery. Difficulties in obtaining rare blood for the patient because of concomitant delivery events involving 2 patients with anti-U at the facility opened discussions about the difficulties of and alternatives to intrauterine transfusion where rare blood phenotypes are involved.
Precision in high resolution absorption line modelling, analytic Voigt derivatives, and optimization methods
Authors: Webb John K , Carswell Robert F , Lee Chung-Chi
Published: October 2021

This paper describes the optimization theory on which vpfit, a non-linear least-squares program for modelling absorption spectra, is based. Particular attention is paid to precision. Voigt function derivatives have previously been calculated using numerical finite difference approximations. We show how these can instead be computed analytically using Taylor series expansions and look-up tables. We introduce a new optimization method for an efficient descent path to the best fit, combining the principles used in both the Gauss–Newton and Levenberg–Marquardt algorithms. A simple practical fix for ill-conditioning is described, a common problem when modelling quasar absorption systems. We also summarize how unbiased modelling depends on using an appropriate information criterion to guard against overfitting or underfitting. The methods and the new implementations introduced in this paper are aimed at optimal usage of future data from facilities such as ESPRESSO/VLT and HIRES/ELT, particularly for the most demanding applications such as searches for space–time variations in fundamental constants and attempts to detect cosmological redshift drift.
Velocity-imaging the rapidly precessing planetary disc around the white dwarf HE 1349–2305 using Doppler tomography
Authors: Manser Christopher J , Dennihy Erik , Gänsicke Boris T , Debes John H , Gentile Fusillo Nicola P , Hermes J J , Hollands Mark , Izquierdo Paula , Kaiser B C , Marsh T R , Reding Joshua S , Rodríguez-Gil Pablo , Veras Dimitri , Wilson David J
Published: October 2021

The presence of planetary material in white dwarf atmospheres, thought to be accreted from a dusty debris disc produced via the tidal disruption of a planetesimal, is common. Approximately 5 per cent of these discs host a co-orbital gaseous component detectable via emission from atomic transitions  –  usually the 8600 Å Ca ii triplet. These emission profiles can be highly variable in both morphology and strength. Furthermore, the morphological variations in a few systems have been shown to be periodic, likely produced by an apsidally precessing asymmetric disc. Of the known gaseous debris discs, that around HE 1349–2305 has the most rapidly evolving emission-line morphology, and we present updated spectroscopy of the Ca ii triplet of this system. The additional observations show that the emission-line morphologies vary periodically and consistently, and we constrain the period to two aliases of 459 ± 3 and 502 ± 3 d. We produce images of the Ca ii triplet emission from the disc in velocity space using Doppler tomography  –  only the second such imaging of a white dwarf debris disc. We suggest that the asymmetric nature of these velocity images is generated by gas moving on eccentric orbits with radially dependent excitation conditions via photoionization from the white dwarf. We also obtained short-cadence (≃4 min) spectroscopy to search for variability on the time-scale of the disc’s orbital period (≃hours) due to the presence of a planetesimal, and rule out variability at a level of ≃1.4 per cent.
On measuring the Hubble constant with X-ray reverberation mapping of active galactic nuclei
Authors: Ingram Adam , Mastroserio Guglielmo , van der Klis Michiel , Nathan Edward , Connors Riley , Dauser Thomas , García Javier A , Kara Erin , König Ole , Lucchini Matteo , Wang Jingyi
Published: October 2021

We show that X-ray reverberation mapping can be used to measure the distance to type 1 active galactic nuclei (AGNs). This is because X-ray photons originally emitted from the ‘corona’ close to the black hole irradiate the accretion disc and are reemitted with a characteristic ‘reflection’ spectrum that includes a prominent ∼6.4 keV iron emission line. The shape of the reflection spectrum depends on the irradiating flux, and the light-crossing delay between continuum photons observed directly from the corona and the reflected photons constrain the size of the disc. Simultaneously modelling the X-ray spectrum and the time delays between photons of different energies therefore constrains the intrinsic reflected luminosity, and the distance follows from the observed reflected flux. Alternatively, the distance can be measured from the X-ray spectrum alone if the black hole mass is known. We develop a new model of our reltrans X-ray reverberation mapping package, called rtdist, that has distance as a model parameter. We simulate a synthetic observation that we fit with our new model, and find that this technique applied to a sample of ∼25 AGNs can be used to measure the Hubble constant with a 3σ statistical uncertainty of ${\sim} 6\,{\rm km}\,{\rm s}^{-1}\, {\rm Mpc}^{-1}$. Since the technique is completely independent of the traditional distance ladder and the cosmic microwave background radiation, it has the potential to address the current tension between them. We discuss sources of modelling uncertainty, and how they can be addressed in the near future.