bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial reporalization duration reflects autonomic nervous system activity in Takotsubo syndrome
Authors: Mantzouranis E , Leontsinis I , Sakalidis A , Dalakouras I , Dris E , Drogkaris S , Vlachakis P , Liatakis I , Manta E , Antonopoulos A , Fragkoulis C , Konstantinidis D , Kordalis A , Dimitriadis K , Tsioufis K
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Sympathetic overdrive has been proposed as a major precursor in Takotsubo syndrome (TTS) development. ECG changes in TTS often persist in time beyond the recovery of the cardiac systolic function and their prognostic significance remains unclear. Autonomic nervous system (ANS) fluctuations affect myocardial repolarization as well as the presence of myocardial oedema and active ischemia.

Purpose

In this study we aimed to investigate the correlation between indices of ANS activity and the degree of QT interval prolongation during the course of TTS.

Methods

We studied 30 patients (29 women, mean age: 66 ± 11 years, 17.2% history of diabetes mellitus) with a TTS diagnosis established after multimodality imaging evaluation, which included cardiac magnetic resonance imaging. Daily ECG recordings during the acute phase of the TTS were available for all patients. Both sympathetic and parasympathetic activity were evaluated with time and frequency domain indices of heart rate variability (HRV). Moreover, sympathetic tone was assessed by means of muscle sympathetic nerve activity (MSNA). All investigations were completed within 30 days of the index event. ANS indices were correlated with the maximum measured QTc interval of each patient during the acute phase of TTS.

Results

Maximal QTc interval during the acute TTS phase exhibited a linear correlation with indices of sympathetic withdrawal. Specifically, QTc duration was positively correlated with rMSSD (r=430, p=0.036) and high frequency FFT (=0,497, p=0,016) whereas it was inversely associated with MSNA results measured in oscillations/100 heart beats (r=-573, p=0,007). In a multivariate analysis model standardized for patients’ age, left ventricular ejection fraction (synchronous with ECG measurements) and the usage of beta blocker medications the aforementioned results remained statistically significant (Table 2).

Conclusion

In our population of TTS patients, increased parasympathetic activity and sympathetic withdrawal within the first month of the index event reflect increased repolarization duration during the acute phase of the syndrome.
Blood lactate levels, base excess values and lactic acidosis predict short-term and long-term survival in patients admitted to the ICU after and out-of-hospital cardiac arrest
Authors: Fasolino A , Vecchione A , Bagliani A , Baldi E , Gentile F R , Compagnoni S , Quilico F , Vicini Scajola L , Primi R , Bendotti S , Currao A , Lopiano C , Colombo C N J , Tavazzi G , Savastano S
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Global hypoperfusion causes tissue hypoxia, resulting in overproduction of lactate because of impaired mitochondrial oxidation, causing lactic acidosis (LA). Base excess (BE) is defined as the amount of acid or base required to return the pH to 7.4 in the setting of a normal Paco2 and is therefore related to the degree of acid production following injury.

Purpose

Our hypothesis was that lactate levels, BE levels and occurrence of LA on admission could help in early risk stratification in patients admitted to the ICU after an out-of-hospital cardiac arrest (OHCA).

Methods

we enrolled 171 consecutive patients resuscitated from an OHCA and admitted to ICU at our center from September 2017 to April 2021. Blood gas analysis on admission was available for 140 patients [77%male, mean age 60 (18-90) years, 54% with first shockable rhythm, median number of shocks delivered 1 (0-14), median dose of adrenaline administered 3 mg (0-12), 26% received amiodarone, median cardiac arrest duration 38 min (IQR 22-74 min)].

Patients with low lactate levels were compared with patients with high lactate levels (cutoff 2 mmol/l as per standard practice), patients with low BE levels were compared with patients with high BE levels (cutoff -8.5 mmol/l, median value) and patients with LA were compared with patients without LA (defined as pH <7.36 and lactate>2mmol/). Survival with good neurological outcome (CPC 1-2) at ICU discharge and 30-day survival were investigated for each group with chi-squared test. Then, one-year survival was investigated for each group with Kaplan-Meier analysis.

Results

Patients with low BE (< -8.5 mmol/l) had a significantly lower survival with good neurological outcome at ICU discharge (p=0.0017), lower survival at 30 days (p < 0.0001) and 365 days (p<0.0001) compared to patients with high BE (> - 8.5 mmol/l). Low lactate levels (< 2 mmol/L) were associated with higher survival with good neurological outcome at ICU discharge (p< 0.0001), higher survival at 30 days (p < 0.0001) and 365 days (p = 0.0002) compared to higher lactate levels (> 2 mmol/l). The occurrence of LA on admission was significantly associated with lower survival with good neurological outcome at ICU discharge (p=0.001), lower 30-days survival (p=0.001) and 365-days survival (p<0.0001).

Conclusion

high blood lactate levels, low base excess and lactic acidosis predict short-term and long-term survival in patients admitted to the ICU after an OHCA. These results could help clinician in the identification of populations with different risk profile with the first blood gas analysis obtained at ICU admission.
Protective role of chronic beta-blocker intake against the appearance of complex ventricular arrhythmias in acute coronary syndrome
Authors: Barea Gonzalez C , Jurado Vinteno V , Arroyo Monino D F , Gonzalez Gomez A , Hidalgo Urbano R F , Garcia Rubira J C
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Although the presence of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) in the context of acute coronary syndromes (ACS) has decreased in the era of early reperfusion, their occurrence may lead to fatal consequences. However, clear predisposing or protective factors have not been identified yet.

Purpose

Our purpose is to describe the prevalence of ventricular arrhythmias before reperfusion treatment in a population of patients hospitalized due to ACS, as well as the possible protective role of chronic intake of beta-blockers, among other factors.

Material and methods

Retrospective, single-center and observational registry of patients admitted to a Coronary Care Unit from July 2011 to September 2022 with a diagnosis of ACS. The baseline characteristics were described, as well as factors related to diagnosis and treatment. A multivariate analysis was performed to study possible predictors of arrhythmic events.

Results

A total of 3123 patients diagnosed with ACS were included. 682 patients (21.8%) had beta- blockers as a chronic treatment and 201 patients (7.1%) presented ventricular arrhythmias. In Table 1 we can see the baseline characteristics of both groups, as well as the differences between them.

Previous intake of beta-blockers was associated with a lower incidence of ventricular arrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) (11% vs 6%, p 0.002), while no differences were observed between patients without ST-segment elevation myocardial infarction (NSTEMI) (2.3% vs 1.6%, p = 0.435). As shown in the multivariate analysis (Table 2), prior intake of beta-blockers turned out to be a protective factor against the development of ventricular arrhythmias, while ST elevation and worse initial Killip were risk factors.

Conclusion

Chronic intake of beta-blockers could be a protective factor against the development of ventricular arrhythmias before revascularization in patients diagnosed with acute coronary syndrome, specially those with STEMI.
Culprit-only versus immediate multi-vessel revascularization in patients with AMI complicated by advanced cardiogenic shock undergoing VA-ECMO
Authors: Choi K H , Yang J H , Park T K , Lee J M , Song Y B , Hahn J Y , Choi S H , Ahn C M , Yu C W , Gwon H C
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by unrestricted grants from the Korean Society of Interventional Cardiology.

Aims

Despite the benefit of culprit-only percutaneous coronary intervention (PCI) in the CULPRIT-SHOCK trial, the optimal revascularization strategy for a refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit-only and immediate multi-vessel PCI strategies in patients with acute myocardial infarction (AMI) complicated by CS who underwent venoarterial-extracorporeal membrane oxygenation (VA-ECMO).

Methods and Results

This study was patient-pooled data from the RESCUE and SMC-ECMO registries. A total of 408 AMI patients with multi-vessel disease who underwent VA-ECMO due to refractory CS were included in this analysis. The study population was classified into culprit-only versus immediate multi-vessel PCI according to non-culprit lesion (NCL) treatment strategies. The co-primary endpoints were 30-day mortality or renal-replacement therapy and 12-month follow-up mortality. Among the study population, 241 (59.1%) underwent culprit-only PCI and 167 (40.9%) underwent immediate multi-vessel PCI. Compared with culprit-only PCI, immediate multi-vessel PCI was associated with significantly lower risks of 30-day mortality or renal-replacement therapy (66.8% vs. 54.5%, p=0.02) and all-cause mortality during 12 months of follow-up (59.5% vs. 47.8%, hazard ratio [HR] 0.70; 95% confidence interval [CI] 0.53–0.92, p=0.01) in patients with AMI and CS who underwent VA-ECMO. These results were also consistent in the 290 pairs of propensity score-matched population (55.6% vs. 46.1%, HR 0.71; 95% CI 0.51–0.98, p=0.04).

Conclusion

Among AMI patients with multi-vessel disease complicated by advanced CS, immediate multi-vessel PCI might be associated with improved clinical outcomes in those undergoing VA-ECMO.
Timing of surgery for patients with infective endocarditis complicated by stroke
Authors: Tao M , Manikantan P , Despotidis G , Alkhalil A , Parikh P , Pyo R
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Infective endocarditis (IE) is a disease associated with high risk of morbidity and mortality. Recent literature suggests that early surgery may be performed without increased risk of mortality, however this association in patients with IE complicated by cerebral infarction (CI) remains unclear.

Purpose

The purpose of this meta-analysis is to assess the association between early surgery after CI and mortality in patients with IE complicated by CI.

Methods

We performed a literature search for studies reporting an association between early surgery and study endpoints. The primary endpoint was in-hospital mortality. The secondary endpoint was long-term mortality. Early surgery was defined as surgery within 14 days of CI event. Conventional therapy was defined as surgery after 14 days of CI event. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status.

Results

A total of 6 studies with 747 participants (318 with early surgery vs 429 with conventional therapy) were included. The mean duration of follow-up was 36 months (ranging between 12 to 62 months). Early surgery was not associated with increased risk of in-hospital or long-term mortality compared to conventional therapy (OR 1.21, 95% CI 0.59, 2.49; P=0.6; OR 0.65, 95% CI 0.06, 7.22; P=0.72). Heterogeneity was moderate: Chi2 = 7.26, I2 = 45%.

Conclusions

Early surgery within 14 days of CI is not associated with increased risk of in-hospital or long-term mortality in patients with IE complicated by CI.
Surgery versus medical therapy in patients with infective endocarditis and surgical indication: a retrospective study
Authors: Bernardo M , Martins Moreira I , Carvalho C , Carvalho P , Monteiro J , Mateus P , Carvalho S , Moreira J I
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Infective endocarditis is a condition associated with poor outcomes. Even though we have guidelines that establish which patients could benefit from surgery, the decision to perform it is not straightforward and there are many factors to be considered before we decide surgical approach.

Purpose

To establish the impact of surgery versus medical treatment in patients with surgical indication according to the ESC guidelines, in our population. The primary outcome was a composite of death, embolic events, and recurrence of infective endocarditis.

Methods

We performed a retrospective study of the patients admitted to our center between 2000 and 2020, with the diagnosis of infective endocarditis. After selecting the patients with surgical indication, according to ESC guidelines, we divided them in two groups: group A (submitted to surgery) and group B (medical therapy only).

Results

A total of 70 patients (65.7% males, 34.3% females, mean age 68.5 ± 15.2) were included. Of these 51.4% were submitted to surgery and 48.6 % received only medical therapy. The group A patients were significantly younger (mean age 63.03 ± 16.03 versus 75.52 ± 10.40, p<0.001). There were no statistically significant differences in terms of previous history of heart failure (p=0.09), valvular heart disease (p=0.83), ischemic heart disease (p=0.47), diabetes (p=0.50), obesity (p=0.17), chronic kidney disease (p=0.68). In terms of local complications, group A had a higher prevalence of severe valvular regurgitation (72.2% vs 36.4%, p= 0.003), with no statistically significant differences in abscess, aneurysm, fistula.

During a mean follow-up of 28.66 ± 39.07 months, 42 pts (60%) experienced the composite endpoint. Group A had significantly better outcomes compared to group B (47.2% versus 26.5%, p= 0.016).

In a multivariate regression analysis, after adjusting for all the possible confounders, including age, not performing surgery was an independent predictor of the composite endpoint (HR 2.23 95% CI: 1.16-4.55, p=0.02).

Conclusion

In patients with surgical indication, surgery was associated with a significant improvement in prognosis. In our population, older patients were more likely to receive medical therapy. However, surgery was associated with better outcomes, independently of age, which suggests that this shouldn’t be the only factor that determines whether surgery is performed or not.
Stent restenosis: identifying predictors
Authors: Paralta De Figueiredo M , Carias M , Picarra B , Rocha De Almeida A , Claudio F , Rocha R , Trinca M
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Despite advancements in stent technology, such as the appearance of the drug-eluting stents, stent restenosis remains a common post-procedure complication and is associated with a higher morbimortality. These patients frequently need repeat revascularisation and pose a therapeutic challenge.

Purpose

This study aims to characterize if it is possible to identify clinical predictors of stent restenosis.

Methods

We retrospectively observed a population of 9815 patients (D) admitted with acute coronary syndrome (ACS) and divided them into two groups: those who had stent restenosis (D1), and those who did not (D2). We then compared both groups regarding age, sex, personal history of smoking (both current or former smokers), hypertension, dyslipidaemia, diabetes mellitus, stroke/TIA, chronic kidney disease and stent location.

Results

D1 consisted of 2,9% of the population. Both groups had similar age (D1: 67,95±10,35 years vs. D2: 68,56±11,57years) and were predominantly of the male sex (75,9% vs. 73,3%). D1 had a significantly higher prevalence of diabetes (3,1% vs 2,7%, p=0,008; odds ratio: 1,183, 95% CI [1,044;1,340]); dyslipidaemia (72,4% vs 59,0%, p<0,001; odds ratio: 1,821, 95% CI [1,586;2,092]); hypertension (86,4% vs 80,8%, p<0,001; odds ratio: 1,507, 95% CI [1,259;1,805]); smoking (38,1% vs 33,6%, p=0,003; odds ratio: 1,215, 95% CI [1,069;1,381]); and chronic kidney disease (12,1% vs 10,0%, p=0,003; odds ratio 1,235, 95% CI [1,020;1,495]) than D2. When comparing stent location, restenosis was more frequently observed in the right coronary artery (4,5% vs 2,3%, p<0,001; odds ratio 2,016, 95% CI [1,775;2,289]), with no significant differences in relation to other segments. There were no statistically relevant differences regarding stroke/TIA between the groups.

Conclusions

In patients with ACS, stent restenosis seems to be associated with a significantly higher prevalence of diabetes, hypertension, dyslipidaemia, history of smoking and chronic kidney disease. Right coronary artery stenting also seems to be associated with a higher rate if restenosis when compared to other revascularised segments. These characteristics could help predict which patients are at a higher risk and need closer monitoring, potentially improving outcomes. Further developing a score with these predictors could be of interest.
Thrombosis of Chiari’s network in the setting of non-bacterial thrombotic endocarditis occurring under non-vitamin K antagonist oral anticoagulation: a case report
Authors: Zaher Wael , Balland Amandine , De Cubber Michael , Sorgente Antonio
Published: May 2023

Background

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition characterized by sterile thrombi on undamaged valves. We herein report a case of NBTE involving the Chiari’s network and the mitral valve, related to a metastatic cancer, and occurring under non-vitamin K antagonist oral anticoagulant (NOAC).

Case summary

A 74-year-old patient with metastatic pulmonary cancer was diagnosed with a right atrium mass during pre-treatment cardiovascular check-up. Transoesophageal echocardiography and cardiac magnetic resonance concluded that the mass was a Chiari’s network. Two months later, the patient was admitted for a pulmonary embolism and started rivaroxaban. At 1-month follow-up, the patient underwent a new echocardiography, which showed an increased size of the right atrium mass and the presence of two new masses on the mitral valve. She suffered an ischaemic stroke. Infectious work-up was negative. Coagulation factor VIII was 419%. A NBTE with Chiari’s network thrombosis and mitral valve involvement was suspected in the setting of a hypercoagulable state related to the active cancer, and intravenous heparin was started, bridged to vitamin K antagonist (VKA) after 3 weeks. All the lesions were fully resolved on follow-up echocardiography at 6 weeks.

Discussion

This case highlights an atypical association of thrombosis on right and left heart chamber with systemic and pulmonary embolism, related to a hypercoagulable state. Chiari’s network is an embryonic remnant with no clinical significance and is exceptionally thrombosed. Failure of treatment by NOAC highlights the complexity of cancer-related thrombosis, particularly in NBTE, and the necessity of heparin and VKA in our case.
The dog, valves’ best friend: infective endocarditis due to Capnocytophaga canimorsus—a case report
Authors: Salazar Rodríguez Daniel Jesús , Plata Ciézar Antonio José , Gaitán Román Daniel , Urbano Carrillo Cristóbal Antonio
Published: May 2023

Background

Capnocytophaga canimorsus is a Gram-negative bacillus found in the oral microbiota of dogs. It is a very rare cause of endocarditis. We hereby present a case of aortic valve endocarditis due to this microorganism.

Case Summary

A 39-year-old male was admitted to hospital with a history of intermittent fever and exertion dyspnoea and showed signs of heart failure on physical examination. Transthoracic and transoesophageal echocardiography confirmed the presence of a vegetation in the non-coronary cusp of the aortic valve, aortic root pseudoaneurysm, and left ventricle-to-right atrium fistula (Gerbode defect). The patient underwent aortic valve replacement with a biological prosthesis. The fistula was closed with a pericardial patch, although a dehiscence of the patch was detected in post-operative echocardiogram. The post-operative period was complicated by acute mediastinitis and cardiac tamponade secondary to a pericardial abscess, requiring emergent surgery. The patient made a good recovery afterwards and was discharged 2 weeks later.

Discussion

Capnocytophaga canimorsus is a very rare cause of endocarditis, although it can be very aggressive, with high degree of valve damage, necessity of surgery, and high mortality. It mainly affects young men with no previous structural heart disease. Due to its slow growth, blood cultures can be negative, so other microbiological techniques such as 16S RNA sequencing or matrix-assisted laser desorption/ionization and time-of-flight (MALDI-TOF) can be helpful for diagnosis.
Improved paradoxical splitting of the second heart sound after cardiac resynchronization therapy
Authors: Arakaki Tomohiro , Hirata Kazuhito , Kakazu Masanori , Oba Kageyuki
Published: May 2023

The outcome of paradox splitting of the second heart sound (S2) after cardiac resynchronization therapy (CRT) has not been well defined. We present a case of right ventricular pacing induced heart failure with prominent paradox splitting of S2 which markedly improved after upgrading to CRT.
Coronary artery calcium among patients with heterozygous familial hypercholesterolaemia
Authors: Tada Hayato , Kojima Nobuko , Yamagami Kan , Nomura Akihiro , Nohara Atsushi , Usui Soichiro , Sakata Kenji , Hayashi Kenshi , Fujino Noboru , Takamura Masayuki , Kawashiri Masa-aki
Published: May 2023

Aims

We aimed to determine if coronary artery calcium (CAC) is associated with cardiovascular disease (CVD) events, defined as CVD-related death, unstable angina, myocardial infarction, or staged revascularization among patients with heterozygous familial hypercholesterolaemia (HeFH) under primary prevention settings.

Methods and results

Data of patients with FH admitted to Kanazawa University Hospital between 2000 and 2020, who underwent CAC measurement and were followed up (n = 622, male = 306, mean age = 54 years), were retrospectively reviewed. Risk factors for CVD events were determined using the Cox proportional hazard model. The median follow-up duration was 13.2 years (interquartile range: 9.8–18.4 years). We observed 132 CVD events during the follow-up period. The event rate per 1000 person-years for CAC scores of 0 [n = 283 (45.5%)], 1–100 [n = 260 (41.8%)], and >100 [n = 79 (12.7%)] was 1.2, 17.0, and 78.8, respectively. Log (CAC score + 1) was a significant predictor of the occurrence of CVD events (hazard ratio: 3.24; 95% confidence interval: 1.68–4.80; P < 0.0001) in the multivariate Cox regression analysis, independent of other factors. The risk discrimination of CVD events was enhanced by adding CAC information to other conventional risk factors (C-statistics: 0.833–0.934; P < 0.0001).

Conclusion

The CAC score helps in further risk stratification in patients with HeFH.
The role of site-2-proteases in bacteria: a review on physiology, virulence, and therapeutic potential
Authors: Kristensen Sofie S , Diep Dzung B , Kjos Morten , Mathiesen Geir
Published: May 2023

Site-2-proteases are a class of intramembrane proteases involved in regulated intramembrane proteolysis. Regulated intramembrane proteolysis is a highly conserved signaling mechanism that commonly involves sequential digestion of an anti-sigma factor by a site-1- and site-2-protease in response to external stimuli, resulting in an adaptive transcriptional response. Variation of this signaling cascade continues to emerge as the role of site-2-proteases in bacteria continues to be explored. Site-2-proteases are highly conserved among bacteria and play a key role in multiple processes, including iron uptake, stress response, and pheromone production. Additionally, an increasing number of site-2-proteases have been found to play a pivotal role in the virulence properties of multiple human pathogens, such as alginate production in Pseudomonas aeruginosa, toxin production in Vibrio cholerae, resistance to lysozyme in enterococci and antimicrobials in several Bacillus spp, and cell-envelope lipid composition in Mycobacterium tuberculosis. The prominent role of site-2-proteases in bacterial pathogenicity highlights the potential of site-2-proteases as novel targets for therapeutic intervention. In this review, we summarize the role of site-2-proteases in bacterial physiology and virulence, as well as evaluate the therapeutic potential of site-2-proteases.
High frequency attenuation of S waves in alluvial deposits of the central Po Plain (northern Italy)
Authors: Franceschina Gianlorenzo , Tento Alberto
Published: May 2023

Estimation of local seismic response plays a key role in assessing local seismic hazard and particularly in the design of shaking scenarios. Modelling local seismic response involves knowing of the shear wave velocity (VS) and quality factor (QS) profiles for the site in question. The many techniques that have been developed to assess VS in surface deposits produce reliable measurements of VS, but these rarely correspond to direct measurements of QS. The latter is often considered through damping measures from laboratory tests on small-scale soil samples, which can provide information primarily on intrinsic attenuation, neglecting the contribution of scattering effects. In this paper, using seismic recordings obtained at the surface and in boreholes at 100 m depth, we estimate an average value of QS of some characteristic alluvial deposits of the Po Plain (northern Italy). Data come from a microseismic network which sampled an almost uniform lithology in the central Po Plain and consisted of three surface and four borehole stations with an interstation distance of about 2 km. The average value of QS of the shallowest 100 m of the sedimentary strata, QS,100, is estimated by considering: (1) the high-frequency attenuation of seismic waves due to propagation through the corresponding stratigraphy and (2) the interference between incident and surface-reflected waves observed at borehole stations. We parametrize the first through $\Delta k_{0_{ {100}}}$, the difference between the values of the spectral decay parameter kappa (k) estimated at the surface and at the boreholes depth, respectively. We use the second in order to compute VS,100, the time-averaged VS referred to the uppermost 100 m stratigraphy. We obtain: $\Delta k_{0_{ {100}}} = (11 \pm 3)\,$ ms, ${V_{S,100}} \, =\, (309\, \pm \, 11)\,$ m s−1 and ${Q_{S,100}} \, =\, 31 \pm 10$. At the surface, the estimated values of the site-specific kappa, k0, are found to range from 75 to 79 ms. As expected, these results are in good agreement with studies performed in other sites characterized by sandy or clayey lithologies, and can be usefully used in site response analysis at sites where the rigidity is mainly controlled by lithostatic pressure.
S

treptococcus pneumoniae serotyping and antimicrobial susceptibility:

a

ssessment for

v

accine

e

fficacy in Canada after the introduction of PCV13
Authors: Zhanel George G , Lynch Joseph P , Adam Heather J
Published: May 2023

Background

Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries.

Objectives

To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines.

Methods

SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada—National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation.

Results

The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011–2020).

Conclusions

The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.
Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011–2020
Authors: Alford Morgan A , Karlowsky James A , Adam Heather J , Baxter Melanie R , Schellenberg John , Golden Alyssa R , Martin Irene , Demczuk Walter , Mulvey Michael R , Zhanel George G
Published: May 2023

Objectives

To assess the antimicrobial susceptibility of 14 138 invasive Streptococcus pneumoniae isolates collected in Canada from 2011 to 2020.

Methods

Antimicrobial susceptibility testing was performed using the CLSI M07 broth microdilution reference method. MICs were interpreted using 2022 CLSI M100 breakpoints.

Results

In 2020, 90.1% and 98.6% of invasive pneumococci were penicillin-susceptible when MICs were interpreted using CLSI meningitis or oral and non-meningitis breakpoints, respectively; 96.9% (meningitis breakpoint) and 99.5% (non-meningitis breakpoint) of isolates were ceftriaxone-susceptible, and 99.9% were levofloxacin-susceptible. Numerically small, non-temporal, but statistically significant differences (P < 0.05) in the annual percentage of isolates susceptible to four of the 13 agents tested was observed across the 10-year study: chloramphenicol (4.4% difference), trimethoprim-sulfamethoxazole (3.9%), penicillin (non-meningitis breakpoint, 2.7%) and ceftriaxone (meningitis breakpoint, 2.7%; non-meningitis breakpoint, 1.2%). During the same period, annual differences in percent susceptible values for penicillin (meningitis and oral breakpoints) and all other agents did not achieve statistical significance. The percentage of isolates with an MDR phenotype (resistance to ≥3 antimicrobial classes) in 2011 and 2020 (8.5% and 9.4%) was not significantly different (P = 0.109), although there was a significant interim decrease observed between 2011 and 2015 (P < 0.001) followed by a significant increase between 2016 and 2020 (P < 0.001). Statistically significant associations were observed between resistance rates to most antimicrobial agents included in the MDR analysis (penicillin, clarithromycin, clindamycin, doxycycline, trimethoprim/sulfamethoxazole and chloramphenicol) and patient age, specimen source, geographic location in Canada or concurrent resistance to penicillin or clarithromycin, but not biological sex of patients. Given the large isolate collection studied, statistical significance did not necessarily imply clinical or public health significance in some analyses.

Conclusions

Invasive pneumococcal isolates collected in Canada from 2011 to 2020 generally exhibited consistent in vitro susceptibility to commonly tested antimicrobial agents.
Clinical use of artificial intelligence requires AI-capable organizations
Authors: Novak Laurie Lovett , Russell Regina G , Garvey Kim , Patel Mehool , Thomas Craig Kelly Jean , Snowdon Jane , Miller Bonnie
Published: May 2023

Artificial intelligence-based algorithms are being widely implemented in health care, even as evidence is emerging of bias in their design, problems with implementation, and potential harm to patients. To achieve the promise of using of AI-based tools to improve health, healthcare organizations will need to be AI-capable, with internal and external systems functioning in tandem to ensure the safe, ethical, and effective use of AI-based tools. Ideas are starting to emerge about the organizational routines, competencies, resources, and infrastructures that will be required for safe and effective deployment of AI in health care, but there has been little empirical research. Infrastructures that provide legal and regulatory guidance for managers, clinician competencies for the safe and effective use of AI-based tools, and learner-centric resources such as clear AI documentation and local health ecosystem impact reviews can help drive continuous improvement.
Red, Green, and Blue Model-Based Assessment and Principles of White Analytical Chemistry to Robust Stability-Indicating Chromatographic Estimation of Thiocolchicoside and Diclofenac Sodium
Authors: Prajapati Pintu , Pulusu Veera Shakar , Shah Shailesh
Published: May 2023

Background

White analytical chemistry (WAC) is a recent approach for evaluating analytical procedures based on their effectiveness in validating results, capacity to be environmentally friendly, and economic effectiveness.

Objective

The detection of diclofenac sodium (DCF) and thiocolchicoside (THC) simultaneously has been established using a WAC-driven stability-indicating chromatographic method (SICM).

Methods

For the concurrent stability study of THC and DCF, the suggested chromatographic technique was developed employing safe and environmentally acceptable organic solvents. To identify critical analytical method parameters (AMPs) and analytical quality attributes (AQAs), a design of experiments (DoE)-based screening design was applied. For the DoE-based response surface modelling (RSM) of critical AMPs and AQAs, the Box–Behnken design (BBD) was employed.

Results

A robust SICM was developed by navigating the analytical design space for simultaneous estimation of THC and DCF. IR, NMR, and mass spectral data were used to characterize the degradation products. Red, green, and blue (RGB) models were used to evaluate the suggested method's validation effectiveness, greenness power, and economic efficiency and compared to published chromatographic techniques. The effectiveness of the chromatographic method's validation concerning the International Council for Harmonization (ICH) Q2 (R1) guideline was evaluated using the red model. The analytical greenness (AGREE) evaluation tool and eco-scale assessment (ESA) approach were used to evaluate the green model's methodology. The blue model-based assessment was carried out for comparison of simplicity of instruments handling, cost, and time during sample analysis. The red, blue, and green scores of the techniques were averaged to arrive at the white score of the suggested and reported methods.

Conclusion

For the concurrent stability study of THC and DCF, the suggested technique was shown to be validated, environmentally friendly, and cost effective. The suggested approach could be a cost-effective and environmentally friendly analytical technique for determining the stability and monitoring the quality of fixed-dose combinations (FDC) of THC and DCF.

Highlights

Stability-indicating HPTLC method was developed for concomitant analysis of THC and DCF using concepts of DoE and WAC.
Movement Lawyering and theCaring SocietyLitigation
Authors: Hernandez Julia , Levesque Anne
Published: May 2023

In 2016, the Canadian Human Rights Tribunal issued a landmark ruling in First Nations Child and Family Caring Society of Canada v. Canada finding that the government of Canada was racially and ethnically discriminating against First Nations children and their families in its funding and delivery of child welfare services to them. This ruling did not result from an isolated legal case; it was the result of litigation that was part of a broader social campaign with active supporters from all over the world. The litigation was driven by, and supported, a dynamic movement for sovereignty for First Nations Peoples around child welfare. This article examines the Caring Society case through the lens of movement lawyering—using the law to bring about transformative social change.

Section 2 examines movement lawyering as an approach to lawyering. Movement lawyering involves a range of practices, advocacy and mobilizing that seek to dismantle architectures of subordination. Section 3 provides an overview of the Caring Society litigation and the social campaign within which the case was litigated. The I am a Witness campaign, a dynamic education and grassroots social campaign that engaged Indigenous and non-Indigenous children and sought to make the litigation accessible to the public, is examined in detail. Section 4 analyses Caring Society as a study of movement lawyering. It examines how three elements of movement lawyering; integrated advocacy; accountability to social movements; and willingness to address the root causes of structural oppression were at play in the litigation and related campaigns.

In conclusion, the authors contend that Caring Society and the I am a Witness campaign constitute a successful example of movement lawyering as they properly recognize litigation, and the role of lawyers, as one piece of the mosaic of efforts needed to advance transformative social change.
Regorafenib inhibits growth, survival and angiogenesis in nasopharyngeal carcinoma and is synergistic with Mcl-1 inhibitor
Authors: Li Jiangping , Hua Qingquan
Published: May 2023

Objectives

Regorafenib is an oral multi-kinase inhibitor approved for various metastatic/advanced cancers, and has been investigated in clinical trials in many other tumour entities. The purpose of this study was to evaluate the therapeutic potential of regorafenib for nasopharyngeal carcinoma (NPC).

Methods

Cellular proliferation, survival, apoptosis and colony formation assays were performed and combination index was determined. NPC xenograft tumour models were established. In vitro and In vivo angiogenesis assays were performed.

Key findings

Regorafenib is effective against a panel of NPC cell lines regardless of cellular origin and genetic profiling while sparing normal nasal epithelial cells. The predominant inhibitory effects of regorafenib in NPC are anchorage-dependent and anchorage-independent growth rather than survival. Apart from tumour cells, regorafenib potently inhibits angiogenesis. Mechanistically, regorafenib inhibits multiple oncogenic pathways including Raf/Erk/Mek and PI3K/Akt/mTOR. Regorafenib decreases Bcl-2 but not Mcl-1 level in NPC cells. The in vitro observations are evident in in vivo NPC xenograft mouse model. The combination of Mcl-1 inhibitor with regorafenib is synergistic in inhibiting NPC growth without causing systemic toxicity in mice.

Conclusions

Our findings also support further clinical investigation of regorafenib and Mcl-1 inhibitor for NPC treatment.
An experimental evaluation of a stopping rule aimed at maximizing cost-quality trade-offs in surveys
Authors: Wagner James , Zhang Xinyu , Elliott Michael R , West Brady T , Coffey Stephanie M
Published: May 2023

Surveys face difficult choices in managing cost-error trade-offs. Stopping rules for surveys have been proposed as a method for managing these trade-offs. A stopping rule will limit effort on a select subset of cases to reduce costs with minimal harm to quality. Previously proposed stopping rules have focused on quality with an implicit assumption that all cases have the same cost. This assumption is unlikely to be true, particularly when some cases will require more effort and, therefore, more costs than others. We propose a new rule that looks at both predicted costs and quality. This rule is tested experimentally against another rule that focuses on stopping cases that are expected to be difficult to recruit. The experiment was conducted on the 2020 data collection of the Health and Retirement Study (HRS). We test both Bayesian and non-Bayesian (maximum-likelihood or ML) versions of the rule. The Bayesian version of the prediction models uses historical data to establish prior information. The Bayesian version led to higher-quality data for roughly the same cost, while the ML version led to small reductions in quality with larger reductions in cost compared to the control rule.
Surgical management of a giant hepatic metastasis from a cranial meningioma 10 years after resection
Authors: Feltracco Haley , Matar Abraham J , Smith Savannah A , Blair Catherine , Sarmiento Juan M
Published: May 2023

Meningiomas are the most common type of primary brain tumor; they have a low risk for extracranial metastases, which are primarily associated with increased tumor grade. Hepatic metastases from cranial meningiomas are extremely rare, with only a paucity of cases reported in the literature and no standardized approach to management. Herein, we report a case of an incidentally discovered giant (>20 cm) metastatic meningioma to the liver treated with surgical resection 10 years following resection of a low-grade cranial meningioma. This report also highlights the use of (68Ga) DOTATATE PET/CT as the diagnostic imaging modality of choice when evaluating for meningioma metastases. To our knowledge, this report describes the largest hepatic metastasis from a cranial meningioma to undergo surgical resection in the literature.
Prevention of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice by a synbiotic approach using probiotic and lactulose
Authors: Hu Gege , Liu Shaoli , Zeng Hong , Yi Ruokun , Zhao Xin , Yang Zhennai
Published: May 2023

In this research, the synbiotic effects of the probiotic Lactiplantibacillus plantarum YW11 and lactulose on intestinal morphology, colon function, and immune activity were evaluated in a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed that L. plantarum YW11 in combination with lactulose decreased the severity of colitis in mice and improved the structure of the damaged colon, as assessed using colon length and disease condition. Moreover, colonic levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-12, TNF-α, and IFN-γ) were significantly lower and anti-inflammatory factors (IL-10) were significantly higher following the synbiotic supplementation. The synbiotic also exerted antioxidant effects by up-regulating SOD and CAT levels and down-regulating MDA levels in colon tissue. It could also reduce the relative expression of iNOS mRNA and increase the relative expression of nNOS and eNOS mRNA. Western blot confirmed the increased expression of c-Kit, IκBα, and SCF and significantly reduced expression of the NF-κB protein. Therefore, the combination of L. plantarum YW11 and lactulose exerted therapeutic effects mainly through the NF-κB anti-inflammatory pathway, which represented a novel synbiotic approach in the prevention of colonic inflammation.
Magnetic field measurement from the Davis–Chandrasekhar–Fermi method employed with atomic alignment
Authors: Pavaskar Parth , Yan Huirong , Cho Jungyeon
Published: May 2023

The Davis–Chandrasekhar–Fermi (DCF) method is widely employed to estimate the mean magnetic field strength in astrophysical plasmas. In this study, we present a numerical investigation using the DCF method in conjunction with a promising new diagnostic tool for studying magnetic fields: the polarization of spectral lines resulting from the atomic alignment effect. We obtain synthetic spectropolarimetry observations from 3D magnetohydrodynamic (MHD) turbulence simulations and estimate the mean magnetic field projected onto the plane of the sky using the DCF method with ground-state-alignment (GSA) polarization maps and a modification to account for the driving scale of turbulence. We also compare the method to the classical DCF approach using dust polarization observations. Our observations indicate that the modified DCF method correctly estimates the plane-of-sky projected magnetic field strengths for sub-Alfvénic turbulence using a newly proposed correction factor of ξ′ ∈ 0.35–0.75. We find that the field strengths are accurately obtained for all magnetic field inclination and azimuth angles. We also observe a minimum threshold for the mean magnetic field inclination angle with respect to the line of sight, θB ∼ 16°, for the method. The magnetic field dispersion traced by the polarization from the spectral lines is comparable in accuracy to dust polarization, while mitigating some of the uncertainties associated with dust observations. The measurements of the DCF observables from the same atomic/ionic line targets ensure the same origin for the magnetic field and velocity fluctuations and offer a possibility of tracing the 3D direction of the magnetic field.
Three dimensional magnetorotational core-collapse supernova explosions of a 39 solar mass progenitor star
Authors: Powell Jade , Müller Bernhard , Aguilera-Dena David R , Langer Norbert
Published: May 2023

We perform three-dimensional simulations of magnetorotational supernovae using a $39\, {\rm M}_{\odot }$ progenitor star with two different initial magnetic field strengths of 1010  and 1012 G in the core. Both models rapidly undergo shock revival, and their explosion energies asymptote within a few hundred milliseconds to values of ≳2 × 1051 erg after conservatively correcting for the binding energy of the envelope. Magnetically collimated, non-relativistic jets form in both models, though the jets are subject to non-axisymmetric instabilities. The jets do not appear crucial for driving the explosion, as they only emerge once the shock has already expanded considerably. Our simulations predict moderate neutron star kicks of about 150 km s−1, no spin-kick alignment, and rapid early spin-down that would result in birth periods of about 20 ms, too slow to power an energetic gamma-ray burst jet. More than $0.2\, {\rm M}_\odot$ of iron-group material is ejected, but we estimate that the mass of ejected 56Ni will be considerably smaller as the bulk of this material is neutron-rich. Explosive burning does not contribute appreciable amounts of 56Ni because the burned material originates from the slightly neutron-rich silicon shell. The iron-group ejecta also showed no pronounced bipolar geometry by the end of the simulations. The models thus do not immediately fit the characteristics of observed hypernovae, but may be representative of other transients with moderately high explosion energies. The gravitational-wave emission reaches high frequencies of up to 2000 Hz and amplitudes of over 100 cm. The gravitational-wave emission is detectable out to distances of ∼4 Mpc in the planned Cosmic Explorer detector.