bluuebunny/crossref_metadata_2025 huggingface dataset:
P1533 Early evaluation of global longitudinal strain and biomarkers at initiation of trastuzumab treatment in breast cancer patients
Authors: Banke A , Schou M , Dahl J , Frederiksen P , Videbaek L , Ewertz M , Cold S , Moeller J
Published: January 2020

Funding Acknowledgements

The Danish Heart Foundation, Copenhagen (grant number: 14-R97-A5188-22839 and 15-R99-A5940). The Research Fond of the Region of Southern Denmark.

Background

Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. The possibility to detect signs of acute myocardial deterioration at treatment initiation is not thoroughly investigated. Accordingly, the aim of this study was to assess changes in GLS and biomarkers within the first two weeks of trastuzumab treatment.

Methods

In a prospective cohort study 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8% (SD ± 3.6), GLS -19.9% (SD ± 2.1), 40% hypertension) were included. Examinations including echocardiography and measurement of troponin T and NT-proBrain Natriuretic Peptide were conducted before initiation of trastuzumab, at day 3, 7 and 14 and after 3, 6 and 9 months.

Results

A significant deterioration in LVEF, GLS, s’, e’ septal and s’RV occurred during the 9 months study period and was proceed by significant changes in all these parameters within the first 14 days.

After 14 days 12 patients (27%) had an increase in GLS ≥10 %, which was associated with significantly lower LVEF at nine month at 55.2% (SD ± 4.1) vs. 59.5% (SD ± 3.5) (p = 0.001) compared to patients with <10 % early increase in GLS (Figure 1). No difference in plasma concentrations of cardiac biomarkers was observed between the two groups.

Conclusion

In this cohort study deteriorations in key echocardiographic parameters were detected within the first two weeks of trastuzumab treatment, and an early 10 % increase in GLS was associated with a lower LVEF at nine months.

Abstract P1533 Figure 1
P1534 Clinical feasibility of 4D myocardial speckle tracking strain analysis in soccer referee: comparison to 2D strain
Authors: Stefani L , Leone B L , Zappelli E Z , Toncelli L T , Galanti G G
Published: January 2020

Funding Acknowledgements

no

OnBehalf

no

Background

Quantitative analysis of deformation parameters can provide evidence about the presence of disease . Speckle tracking (ST)strain is recently largely used in sports medicine, as an usefull tool to add value to the traditional echo information .Especially 4D echo-strain is emerging in this context despite not yet completely explored. The study aim to verify the feasibility of the 4D strain analysis , compared to the 2D ST strain data, in a class of international trained soccer referee. Materials and methods : a group of 25 soccer referee ( aged 45,5 ± 5) underwent to an EMT, conducted at the 85% of their effort to obtain the eligibility. An 2D echocardiographic evaluation was also performed with the measurements of the systolic-diastolic parameters . A specific investigation for the 2D and 4D strain analysis by X-Strain-Esaote software, was possible from the 2C,3C;4C apical view chambers, acquired as cine loop. The study was completed by the study of the circumferential strain calculated from short axis view, from the images of the basal and medium LV segments. Results : all 2D echo parameters were normal (LVDD: 50,56 ± 2 mm,68; LVSD: 35,4 ± 2,3 mm; EF: 65,76 ±1,78%; E/A:1,73 ± 0,35 ; RV:23,71 ± 1 mm) The 2D GLS ( -22,29 ± 2,64); Circumferential strain( Basal -22,29 ± 5,3; Apical -25,66 ± 5,8 ) were in the normal range. No statistical differences ( P:NS) were observed comparing the mean GLS(21,60 ± 2,68) to the LV 4D strain( -21,24 ± 2,75) Conclusions : 4D strain completes and strengthens the role of the 2D strain in evaluating the myocardial function contributing to exclude eventual undiscovered disease. Especially in athletes, often checked in a short time the combination of the two methods should be widely proposed .More studies will be necessary in future to confirm this hypothesis.

Abstract P1534 Figure. 4D strain
P1535 Interventricular interaction can result in right ventricular dysfunction in interventricular septum involved myocardial infarction patient
Authors: Park C S , Gwon A , Ahn H S , Kim G H , Cho J S , Youn H J
Published: January 2020

Background

Previous studies revealed that interventricular septal thickness is related to right ventricular dysfunction after anterior myocardial infarction. This finding suggest that interventricular septal function can affect right ventricular function in myocardial infarction patients. We assumed that right ventricular free wall strain values measured using dedicated software can be affected in the setting of ischemic insult on interventricular septum in long-term follow up.

Methods

The patients diagnosed as acute myocardial infarction due to left anterior descending artery disease who underwent successful revascularization were enrolled. Echocardiographic exams were performed at least 2 times, within 72 hours and 1 year after the revascularization. Strain values of interventricular septum and right ventricular free wall were derived from the raw-dicom images. The analysis was performed using the dedicated software for the measurement of right ventricular strain.

Results

Total 65 patients were enrolled. The values of global left ventricular strain were increased after the follow up. There were no changes in global longitudinal strain of the right ventricle. But longitudinal stain values acquired from right ventricular free walls were decreased even the strain values measured at left ventricle and interventricular septum were improved.

Conclusion

Interventricular septal dysfunction due to ischemic injury can affect long term right ventricular dysfunction. This finding suggests the interventricular dependence between cardiac chambers and can provide the development of heart failure in myocardial infarction patient even after the successful revascularization.

Strain values of both ventricles Left ventricle after revascularization (n = 65) 1 year later (n = 65) P values Global longitudinal strain (%) -12.84 ± 4.50 -15.62 ± 4.45 <0.001 Septal longitudinal strain (%) -10.77 ± 5.96 -14.02 ± 5.26 <0.001 Right ventricle Global longitudinal strain (%) -19.36 ± 4.57 -19.47 ± 4.83 0.872 Septal longitudinal strain (%) -14.82 ± 4.48 -16.43 ± 6.03 0.055 Free wall longitudinal strain (%) -20.23 ± 5.33 -17.82 ± 5.70 0.010

Abstract P1535 Figure. Right ventricular segmental strain
P1539 Role of global longitudinal strain diastolic index in assessment of coronary artery disease in patients with stable angina and normal or borderline ejection fraction
Authors: Bolog M I , Dumitrescu M , Pacuraru E , Romanoschi F , Rapa A
Published: January 2020

Background Previous studies demonstrated that 2 D strain imaging segmental transverse diastolic index is a marker of regional ischemia and that global longitudinal strain diastolic index (GLSDI) correlates with left ventricular (LV) filling pressures and NTproBNP. However, usefulness of GLSDI in clinical practice has to be established.

Purpose The aim of the study is to examine the utility of global longitudinal strain diastolic index in the assessment of patients with suspected ischemic heart disease (IHD).

Methods We performed 2 D standard echocardiography and strain imaging in 30 healthy subjects and in 148 patients with stable angina with indication for coronarography. Patients with severe symptoms, severe valvulopathy, arrythmia and/or ejection fraction (EF) less than 45% were excluded. Standard echocardiographic parameters, left ventricular global longitudinal strain (LVGLS) and global longitudinal strain diastolic index were analysed. The patients subsequently underwent coronary angiographic examination.

Results GLSDI was significantly lower in angina pectoris vs control group (0.41 vs 0,69, p <0.001). After coronarography patients were divided in three subgroups: 74 patients (50%) with more than 50% obstruction in any major artery, 26 patients (17.5%) with previous revascularisation but no significant obstructive lesions at present and 48 patients (32.5%) without obstructive artery disease. Average GLSDI was significantly lower in the subgroup with obstructive coronary disease vs the other two subgroups (0.32 vs 0.41 and 0.46 respectively, p < 0.05). Mean LVEF was different in subgroups but with no statistical significance (50 % vs 48 % vs 54 %, p= 0.08). Mean LVGLS was lower in the obstructive artery disease subgroup (-16.4% vs -18.2% vs -21% respectively, p< 0.05). In univariate analysis lower GLSDI was associated with a higher risk of coronary artery disease (Hazard Ratio 1.39, 95% Confidence Interval 1.09-1.49; p < 0.05 per 0.1% decrease). There was significant correlation between reduced GLSDI and the presence of coronary artery disease (r= -0,54, P < 0.05), hypertension (r=- 0.61, p < 0.05), left ventricular hypertrophy (-0.68, p < 0.05) and diastolic disfunction (-0.69, p < 0.05). GLSDI lower than 0.5 had a good sensitivity (84%) and negative predictive value (71%) and a lower specificity (40%) and positive predictive value (52%) for detection of ischemic heart disease.

Conclusions Global longitudinal strain diastolic index is significantly lower in patients with stable angina and normal or borderline reduced ejection fraction compared with normal subjects. A cut off value lower than 0.5 selects patients with a higher probability of obstructive coronary heart disease.
P1541 Left ventricular global longitudinal strain can predict the risk of ventricular arrhythmias in hypertrophic cardiomyopathy patients with preserved left ventricle function
Authors: Marinho V , Alves P , Domingues C , Ferreira J , Milner J , Antonio N , Martins R , Elvas L , Goncalves F , Goncalves L
Published: January 2020

Introduction

Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous clinical expression with increased risk of sudden cardiac death (SCD) from ventricular arrhythmias (VAs).Several studies have shown that patients with malignant arrhythmias have increased electrical dispersion and in homogeneity of intraventricular conduction. Strain by echocardiography is an excellent tool for assessing regional and global left ventricular (LV) function and mechanical dispersion reflects heterogeneous myocardial contraction. We aimed to explore the value of strain parameters in prediction of VAs in HCM with LV preserved systolic function.

Methods

Retrospective observational study including all patients with HCM and ICD implanted in setting of primary prevention in our centre. Patients with LVEF < 40% or coronary artery disease were excluded. LV GLS was defined as the average of peak longitudinal strains from a 16 LV segments model, obtained from three apical views. Time to peak strain was defined as the time from onset Q/R wave on ECG to peak negative longitudinal strain during the entire cardiac cycle. Mechanical dispersion was defined as the standard deviation of time to peak negative strain in 16 LV segments. Patients with VA (group1) and patients without VA (group2) were compared.

Results

The study population included 48 patients, 63.3% of male gender. A family history of HCM was present in 64 pts (43%). All patients were under anti arrhythmic therapy (BB in 95.6%, other anti-arrhythmic in 28.2%). VAs (sustained and non sustained) were documented in 27 (55%) patients. The study groups did not differ regarding to mean age (54 ± 12 vs 56 ± 12 years, p = 0.67), male gender (54% vs 56%, p = 0.87) and BB therapy (91% vs 96%,p = 0.07). Mean LVEF was 58% in group 1 and 61% in group 1, p = 0.56; a LVOT gradient >30mmHg was present in 52% of group 1 pts and 45% of group 2 pts, p = 0.06. Mean wall thickness was 22mm vs 18 mm, p = 0.03, respectively.

GLS was significantly lower in group 1 (- 13.9 ±3.4 vs -16.1 ±3.5, p = 0.02), mechanic dispersion was significantly higher in group 1(81 ± 14 vs 60 ± 12ms, respectively, p = 0.01. Using a multivariate logistic regression model including variables included in SCD HCM risk score proposed by ESC mechanical dispersion (OR: 1.54 (1.03–8.7), p = 0,03) was a strong and independent risk predictor of VA. Using optimal cut-off values from ROC analyses, patients with mechanical dispersion >67 ms (AUC = 0.82, p= 0.02) had more VAs.

Conclusions

Mechanical dispersion and GLS may help to identify HCM patients with high risk of VAs and SCD.

Abstract P1541 Figure 1
P1556 Significance of combined cardiopulmonary and echocardiographic stress test to distinguish the hemodynamic and metabolic responses of hypertensive patients with or without heart failure
Authors: Pugliese N R , Mazzola M , De Biase N , Natali A , Gargani L , Pedrinelli R , Dini F L
Published: January 2020

Background

Arterial hypertension (HT) is one of the main risk factors for the development of heart failure with preserved ejection fraction (HFpEF). However, little is known regarding the hemodynamic and metabolic responses of patients with HT during the stress test.

Purpose

We assessed the hemodynamic and metabolic characteristics of HT subjects and patients with HFpEF and HT (HFpEF-HT) by combining cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE).

Methods

We studied 170 consecutive subjects, undergoing a symptom-limited graded ramp bicycle CPET-ESE: 52 stable (NYHA I-III) outpatients with HFpEF-HT (69 ± 13 years; 44 males, 85%), 86 well-controlled HT subjects (66 ± 10 years; 72 males, 84%) and 32 age and sex-matched healthy controls (59 ± 15 years; 24 males, 75%). During the exercise, we assessed oxygen consumption (VO2), cardiac output (CO) systemic vascular resistance (SVR) and arterial-venous oxygen content difference (AVO2diff).

Results

Peak systolic blood pressure was significantly more elevated in HT subjects (205.7 ± 23 mmHg) than controls (190.9 ± 29 mmHg; p = 0.005) and patients with HFpEF-HT (177.5 ± 26 mmHg; p = 0.03). HT patients exhibited a peak VO2 (18.7 ± 2 ml/min/kg) that was higher than HFpEF-HT patients (15.2 ± 2 ml/min/kg; p < 0.0001), but lower than controls (24.4 ± 7.3 ml/min/kg; p < 0.0001). Peak CO was significantly more elevated in HT (12.3 ± 0.4 ml/min) and controls (13.3 ± 0.6 ml/min) than in HFpEF-HT (9.8 ± 0.4 ml/min; p < 0.0001). Both HFpEF-HT and HT patients displayed a significantly reduced peak AVO2diff (13.3 ± 1 and 13.5 ± 1 vs 16.9 ± 1 mL/dL; p < 0.0001) and increased SVR compared to controls (1066 ± 36 and 1054 ± 33 vs 904 ± 42 dyne·s/cm; p = 0.01).

Conclusions

CPET-ESE was valuable to characterise the hemodynamic and metabolic responses of patients with HT (Figure). HT subjects present a decreased AVO2diff similar to HFpEF patients, suggesting an early peripheral dysfunction, probably related to the impaired reduction of SVR during exercise.

Abstract P1556 Figure.
P1563 A new dimension in patent foramen ovale size estimation
Authors: Demulier L , Paelinck B P , Coomans I , Hemelsoet D , De Backer J , Campens L , De Wolf D
Published: January 2020

Introduction

Detailed multidimensional assessment of patent foramen ovale (PFO) size with transesophageal echocardiography (TOE) may help to determine PFO pathogenicity in cryptogenic stroke patients and may improve the procedural outcome of percutaneous PFO closure.

Purpose

We explored the potential additive value of Live xPlane and three-dimensional (3D) TOE anatomical PFO sizing techniques.

Methods

Imaging data of 45 patients who underwent a 3D TOE-assisted PFO closure were included. The two-dimensional (2D) PFO separation distance and right to left (RL) contrast shunt magnitude were retrospectively assessed at rest and during release of a Valsalva maneuver on pre‑procedural 2D TOE recordings. Peri-procedural measurements of the triangular anatomic PFO opening (base, height and area) were performed after positioning of a stiff guidewire (SW) through the PFO, using Live xPlane imaging and 3D Zoom mode.

Results

The peri-procedural PFO SW base was on average five times larger than the pre-procedural 2D PFO separation (median difference +/- IQR : 13 +/- 5 mm ; p < 0.001), having the biggest impact on total PFO area. The width of the PFO SW base was highly variable, even for a given separation, and significantly larger in patients with a large versus a small to moderate PFO RL contrast shunt (18 versus 15 mm; p = 0.007) and in those with a spontaneous versus a provoked shunt (18 versus 14 mm; p = 0.003).

Conclusion

The PFO SW base, assessed by Live xPlane and 3D TOE, seems a more precise estimate of anatomical PFO size compared to the conventional 2D PFO separation distance. This new PFO dimension may be taken into account for optimization of device and patient selection strategies.

Abstract P1563 Figure. 3D Zoom PFO size measurement
P1571 Echocardiograms on Twitter: the good, the bad and the ugly
Authors: Irenji N , Mcaloon C
Published: January 2020

Background - Case reports are a well-established part of the medical literature presenting interesting cases which require patient consent and peer review as a prerequisite. The advent of social media platforms has changed the way knowledge is shared. Twitter is a micro-blogging site utilised by the medical profession including cardiologists and allied health care professionals (HCP), allowing sharing of interesting cases. Echocardiography is particularly complementary to the medium as images and short films can be included in Tweets. However, its immediacy means traditional safeguards are absent, meaning patients might be identifiable.

The study aim was to sample the prevalence of echocardiography cases being shared on Twitter and analyse the degree of identifiable information present.

Methods - A retrospective observational study of videos of echocardiograms uploaded to Twitter under the hashtag #echofirst over 4 months (Nov 18-Feb 19) was performed in May 2019. Only English language Tweets were included. All Tweeter Demographics and Followers were manually collected by reviewing biographies. Tweets were screened for ‘direct’ (name, address, date-of-birth) and ‘indirect’ (age, gender, ethnicity, diagnosis, clinical diagnosis, date study performed) patient identifiers. Numbers of interactions (replies, likes, retweets, views) were recorded at the time of viewing tweets.

Results - 324 of screened tweets (120 unique users; 114 individuals, 6 organisations) met study criteria. 81 (67%) stated their city. 35 (29%) stated their hospital. One Tweet contained directly identifiable information. Patient consent was not mentioned in any Tweet. Table 1 demonstrates Tweets with the number of identifiers cross-referenced with Tweeters" location.

Discussion - Social media is a highly accessible method for cardiologists and allied HCP to instantly share and discuss echocardiography cases. However, our analysis potentially demonstrates that specific patients could be identified based location and identifiers. Caution must be applied when posting cases as Tweets. Specific guidelines on this practice should be considered.

Table 1 Identifiers (n) Worldwide (n = 324) Country (n = 284) City (n = 221) Hospital (n = 112) 0 98 (30%) 88 (31%) 64 (29%) 27 (24%) 1 114 (35%) 97 (34%) 77 (35%) 39 (35%) 2 50 (15%) 45 (16%) 33 (15%) 19 (17%) 3 24 (7%) 20 (7%) 15 (7%) 5 (4%) 4 36 (11%) 32 (11%) 31 (14%) 21 (19%) 5 2 (1%) 2 (1%) 1 (<1%) 1 (1%)
P1573 Late recovery of left ventricular function in patients with non-severe ischemic mitral regurgitation and multivessel disease qualified to cardiosurgery treatment
Authors: Piatkowski R , Kochanowski J , Budnik M , Grabowski M , Scislo P , Kosior D A , Opolski G
Published: January 2020

Late recovery of left ventricular function in patients with non-severe ischemic mitral regurgitation and multivessel disease qualified to cardiosurgery treatment.

Purpose

In patients (pts) after myocardial infarction (MI) with chronic left ventricle (LV) dysfunction, the presence and degree of ischemic mitral regurgitation (IMR) are predominantly related to LV remodelling and mitral valvular deformation. The aim of this study was to compare functional recovery (LVFR) as well as reverse remodelling of the left ventricle (LVRR) in pts with non-severe IMR qualified for cardiosurgical treatment - coronary artery bypass grafting alone (CABGa) or CABG with mitral repair (CABGmr in the 12-month follow-up.

Materials and methods

A total of 100 pts (mean age 64,4 ± 7,9 years) after MI, eligible for CABG, were included in a prospective study. Echo and clinical assessment were performed before and 12-months after surgery. Pts were referred for CABG a(gr.1; n = 74) or CABGmr (gr.2; n = 26) based on clinical assessment, 2D echo at rest and exercise and myocardial viability assessment (low dose dobutamine - dbx). Effective regurgitation orifice area (EROA) was used for quantitative IMR assessment. An increase in EF≥ 5% (ΔEF) from baseline value was considered as LVFR. A decrease in LV end-systolic volume > 15% from baseline value was considered as LVRR. Multivariable logistic regression analysis was used to identify the strongest factors of lack of LVFR and LVRR.

Results

An LVFR was observed, at late control, in 35 (49%) of pts in the CABGa group and in 11 (48%) of pts in CABGmr group (p = 0,948). LVRR was observed in 41 (56%) of pts in the CABGa group and in 16 (70%) of pts in CABGmr group 12 months follow-up (p = 0,5). In pts with LVFR, there was a lower incidence of at least moderate IMR at follow-up (ΔEF dbx≥5% vs ΔEFdbx < 5%:11% vs 30% pts; p = 0,05). Multivariable logistic regression analysis revealed that in both CABGa and CABGmr group only preoperative age and EF changes during stress echo remained the independent predictors of the lack of LVFR in 12 months follow-up (table 1).

Conclusions

1. LVFR and LVRR were reported in most of the pts in both analyzed groups.

2. Preoperative assessment of changes EF during dbx (ΔEFdbx)can be used to identify pts with IMR at increased risk of lack of improvement in LV function and risk of residual IMRin 12-month f-up after surgery.

Parameters Odds ratio (OR) Odds ratio (OR) p CABGa vs CABGmr 0,644 0,215 - 1,927 0,432 Age (increase by every 5 years) 1,11 1,039 - 1,879 0,003 ΔEF dbx (increase by every 5%) 0,21 0,096 - 0,46 <0,001 Table 1. Prognostic factors lack improvement in left ventricle function.
P1574 Variation in myocardial work performance after surgical and transcather aortic valve replacement: A pilot echocardiographic study
Authors: Hatam N , Donuru S , Musetti G , Lotfi S H , Spetsotaki K , Steffen H , Autschbach R , Zayat R
Published: January 2020

Funding Acknowledgements

none

Objective

Perioperative myocardial injury occurs after surgical aortic valve replacement (SAVR) as well as after transcather aortic valve replacement (TAVR). The novel non-invasive method for regional LV pressure– strain corresponds well with invasively measured myocardial work (MW) and is independent of afterload compared to ejection fraction and global longitudinal strain (GLS) . In this pilot study, we aimed to compare changes of LV-MW index (MWI) between SAVR and TAVR in the early postoperative period.

Methods

25 TAVR (Corevalve & Symetis) and 25 SAVR (Perimount) patients, scheduled for elective procedures received transthoracic echocardiography studies pre- and 7 days postoperatively. Besides routine measurements the following parameters were analyzed: MWI, global MW efficiency (MWE), global wasted myocardial work (GWMW), GLS and global strain rate (GSR).

Results

In the TAVR group, 17 patients received transfermoral, 8 patients transapical TAVR. As expected, EuroSCORE II was significantly higher in the TAVR group (p = 0.015). GLS was significantly lower (better) in the SAVR group compared to the TAVR group preoperatively (-13.4 + 4.9 vs.-16.7 ± 4.2, p = 0.027). Postoperative GLS increased (worsened) in the SAVR group, though no significant difference was detected between the groups (-12.7 ± 5.1% vs. -10.4 ± 3.4%, p = 0.215) postoperatively. MWI was significantly lower in the TAVR group preoperatively (p = 0.033). Within the TAVR group MWI did not decrease significantly postoperatively (1242 mmHg% vs. 1108 mmHg%, p = 0.476). However, postoperative MWI decreased significantly in the SAVR group (1632 mmHg% vs. 1267mmHg%, p = 0.043). MWE and GWMW did not differ between the groups or within the groups comparing pre- and postoperative values.

Conclusion

Despite better GLS values in SAVR patients preoperatively, we could detect a better preservation of GMWI in TAVR Patients postoperatively. To evaluate the clinical impact of MWI, further studies with larger cohort and correlation with biomarkers of myocardial injury and follow-up assessments are required.

Abstract P1574 Figure. Myocardial work changes after TAVI
Subxiphoid approach for robotic single-site-assisted thymectomy
Authors: Park Seong Yong , Han Kook Nam , Hong Jeong In , Kim Hyun Koo , Kim Dae Joon , Choi Young Ho
Published: January 2020

OBJECTIVES

We previously reported a transthoracic approach using the da Vinci Single-Site™ platform. This study describes the outcomes of robotic single-site thymectomy via a subxiphoid approach based on our previous experiences.

METHODS

This study included patients, who underwent single-site robotic thymectomy via the subxiphoid approach between September 2018 and October 2019. A 3- to 4-cm vertical incision was made over the subxiphoid area, and the Lapsingle port with CO2 gas was introduced. After docking at the single site, a 5-mm curved cannula, 5-mm cardiere grasper and Maryland bipolar forceps or permanent cautery hook was inserted. The single-site robotic platform was used to conduct all surgical procedures except the dissection around the inferior portion of the thymic tissue performed via a thoracoscopic approach through the same incision.

RESULTS

Overall, 13 patients, including 2 with myasthenia gravis, were enrolled. The mean duration of the surgery and chest drainage were 167.3 ± 52.8 (range 73–253) min and 2.2 ± 0.9 (range 1–5) days, respectively. All surgeries were successfully completed without conversion to an open surgery, and there were no major post-surgical complications. The diagnoses based on histopathology included thymoma in 10 patients, thymolipoma in 2 patients and atypical carcinoid tumour in 1 patient with free resection margin.

CONCLUSIONS

This study demonstrated that robotic single-site-assisted thymectomy via the subxiphoid approach is a safe and technically feasible procedure. Although this initial series comprised relatively simple cases, more advanced and complex procedures can soon be performed with the advent of single-port robotic platform.
Outcomes of non-elective coronary artery bypass grafting performed on weekends
Authors: Beller Jared P , Chancellor William Z , Mehaffey J Hunter , Hawkins Robert B , Krebs Elizabeth D , Speir Alan M , Quader Mohammed A , Yarboro Leora T , Ailawadi Gorav , Teman Nicholas R
Published: January 2020

OBJECTIVES

A weekend effect with increased mortality has previously been reported in surgical patients and those with acute myocardial infarction (MI). We hypothesized that a similar phenomenon may exist in coronary artery bypass grafting (CABG).

METHODS

Patients undergoing non-elective isolated CABG (2011–2017) were included from a multicentre regional Society of Thoracic Surgeons database. Patients were stratified by weekend versus weekday operations and further analysed by specific day of the week.

RESULTS

A total of 14 374 patients underwent urgent or emergency isolated CABG with 410 (2.9%) operated on over the weekend. Weekend operations were more often emergency (36.1% vs 5.0%, P < 0.001) and more likely to be in the setting of MI (70.0% vs 51.2%, P < 0.001). Cardiopulmonary bypass times were similar [91 min (71-114) vs 94 min (74-117), P = 0.0749] and the frequency of complete revascularization equivalent (83.4% vs 85.3%, P = 0.284) between weekend and weekday operations. In risk-adjusted analyses, there was no increased odds for mortality in patients operated on over the weekend [odds ratio (OR) 1.07, P = 0.811]; however, there was an increased odds of major morbidity (OR 1.37, P = 0.034). Furthermore, compared with Monday, morbidity increased as the operative day approached the weekend (Tuesday 0.98, P = 0.828; Wednesday 1.07, P = 0.469; Thursday 1.12, P = 0.229; Friday 1.19, P = 0.041; weekend 1.47, P = 0.014).

CONCLUSIONS

While patients requiring surgery on the weekend are higher risk, there is no independent effect of weekend surgery on mortality. However, these patients are at increased risk for major morbidity, the causes of which require further investigation.
Childhood Misfortune and Late-Life Stroke Incidence, 2004–2014
Authors: Zaborenko Callie J , Ferraro Kenneth F , Williams-Farrelly Monica M
Published: January 2020

Background and Objectives

Although most strokes occur in later life, recent studies reveal that negative exposures decades earlier are associated with stroke risk. The purpose of this study was to examine whether accumulated and/or specific domains of early misfortune are related to stroke incidence in later life.

Research Design and Methods

A decade of longitudinal data from stroke-free participants 50 years or older in the Health and Retirement Study were analyzed (N = 12,473). Incident stroke was defined as either self-reported first incident stroke or death due to stroke between 2004 and 2014.

Results

Analyses revealed that accumulated misfortune was associated with increased stroke risk, but the relationship was moderated by wealth. Examining specific domains of childhood misfortune revealed that stroke incidence was greater for persons with behavioral/psychological risks, but that this relationship also was moderated by higher wealth for those with only one behavioral/psychological risk.

Discussion and Implications

Accumulated childhood misfortune and adolescent depression heighten the risk of stroke in later life, but the influence is remediable through adult wealth. Reducing poverty in later life may decrease stroke incidence for persons exposed to negative childhood exposures.
Crystal structures of a β-trefoil lectin from Entamoeba histolytica in monomeric and a novel disulfide bond-mediated dimeric forms
Authors: Khan Farha , Kurre Devanshu , Suguna K
Published: January 2020

β-Trefoil lectins are galactose/N-acetyl galactosamine specific lectins, which are widely distributed across all kingdoms of life and are known to perform several important functions. However, there is no report available on the characterization of these lectins from protozoans. We have performed structural and biophysical studies on a β-trefoil lectin from Entamoeba histolytica (EntTref), which exists as a mixture of monomers and dimers in solution. Further, we have determined the affinities of EntTref for rhamnose, galactose and different galactose-linked sugars. We obtained the crystal structure of EntTref in a sugar-free form (EntTref_apo) and a rhamnose-bound form (EntTref_rham). A novel Cys residue-mediated dimerization was revealed in the crystal structure of EntTref_apo while the structure of EntTref_rham provided the structural basis for the recognition of rhamnose by a β-trefoil lectin for the first time. To the best of our knowledge, this is the only report of the structural, functional and biophysical characterization of a β-trefoil lectin from a protozoan source and the first report of Cys-mediated dimerization in this class of lectins.
Calpain-1 ablation partially rescues disease-associated hallmarks in models of Machado-Joseph disease
Authors: Weber Jonasz J , Haas Eva , Maringer Yacine , Hauser Stefan , Casadei Nicolas L P , Chishti Athar H , Riess Olaf , Hübener-Schmid Jeannette
Published: January 2020

Proteolytic fragmentation of polyglutamine-expanded ataxin-3 is a concomitant and modifier of the molecular pathogenesis of Machado–Joseph disease (MJD), the most common autosomal dominant cerebellar ataxia. Calpains, a group of calcium-dependent cysteine proteases, are important mediators of ataxin-3 cleavage and implicated in multiple neurodegenerative conditions. Pharmacologic and genetic approaches lowering calpain activity showed beneficial effects on molecular and behavioural disease characteristics in MJD model organisms. However, specifically targeting one of the calpain isoforms by genetic means has not yet been evaluated as a potential therapeutic strategy. In our study, we tested whether calpains are overactivated in the MJD context and if reduction or ablation of calpain-1 expression ameliorates the disease-associated phenotype in MJD cells and mice. In all analysed MJD models, we detected an elevated calpain activity at baseline. Lowering or removal of calpain-1 in cells or mice counteracted calpain system overactivation and led to reduced cleavage of ataxin-3 without affecting its aggregation. Moreover, calpain-1 knockout in YAC84Q mice alleviated excessive fragmentation of important synaptic proteins. Despite worsening some motor characteristics, YAC84Q mice showed a rescue of body weight loss and extended survival upon calpain-1 knockout. Together, our findings emphasize the general potential of calpains as a therapeutic target in MJD and other neurodegenerative diseases.
Genome-wide scan identifies novel genetic loci regulating salivary metabolite levels
Authors: Nag Abhishek , Kurushima Yuko , Bowyer Ruth C E , Wells Philippa M , Weiss Stefan , Pietzner Maik , Kocher Thomas , Raffler Johannes , Völker Uwe , Mangino Massimo , Spector Timothy D , Milburn Michael V , Kastenmüller Gabi , Mohney Robert P , Suhre Karsten , Menni Cristina , Steves Claire J
Published: January 2020

Saliva, as a biofluid, is inexpensive and non-invasive to obtain, and provides a vital tool to investigate oral health and its interaction with systemic health conditions. There is growing interest in salivary biomarkers for systemic diseases, notably cardiovascular disease. Whereas hundreds of genetic loci have been shown to be involved in the regulation of blood metabolites, leading to significant insights into the pathogenesis of complex human diseases, little is known about the impact of host genetics on salivary metabolites. Here we report the first genome-wide association study exploring 476 salivary metabolites in 1419 subjects from the TwinsUK cohort (discovery phase), followed by replication in the Study of Health in Pomerania (SHIP-2) cohort. A total of 14 distinct locus-metabolite associations were identified in the discovery phase, most of which were replicated in SHIP-2. While only a limited number of the loci that are known to regulate blood metabolites were also associated with salivary metabolites in our study, we identified several novel saliva-specific locus-metabolite associations, including associations for the AGMAT (with the metabolites 4-guanidinobutanoate and beta-guanidinopropanoate), ATP13A5 (with the metabolite creatinine) and DPYS (with the metabolites 3-ureidopropionate and 3-ureidoisobutyrate) loci. Our study suggests that there may be regulatory pathways of particular relevance to the salivary metabolome. In addition, some of our findings may have clinical significance, such as the utility of the pyrimidine (uracil) degradation metabolites in predicting 5-fluorouracil toxicity and the role of the agmatine pathway metabolites as biomarkers of oral health.
Statistical inference in matched case–control studies of recurrent events
Authors: Cheung Yin Bun , Ma Xiangmei , Lam K F , Li Jialiang , Yung Chee Fu , Milligan Paul , Mackenzie Grant
Published: January 2020

Background

The concurrent sampling design was developed for case–control studies of recurrent events. It involves matching for time. Standard conditional logistic-regression (CLR) analysis ignores the dependence among recurrent events. Existing methods for clustered observations for CLR do not fit the complex data structure arising from the concurrent sampling design.

Methods

We propose to break the matches, apply unconditional logistic regression with adjustment for time in quintiles and residual time within each quintile, and use a robust standard error for observations clustered within persons. We conducted extensive simulation to evaluate this approach and compared it with methods based on CLR. We analysed data from a study of childhood pneumonia to illustrate the methods.

Results

The proposed method and CLR methods gave very similar point estimates of association and showed little bias. The proposed method produced confidence intervals that achieved the target level of coverage probability, whereas the CLR methods did not, except when disease incidence was low.

Conclusions

The proposed method is suitable for the analysis of case–control studies with recurrent events.
Evaluation of a community pharmacy-led test-and-treat service for women with uncomplicated lower urinary tract infection in England
Authors: Thornley Tracey , Kirkdale Charlotte L , Beech Elizabeth , Howard Philip , Wilson Peter
Published: January 2020

Background

Uncomplicated lower urinary tract infections (UTIs) are common in women consulting primary healthcare, taking up GP resources. Delayed consultation can increase the risk of serious infections such as pyelonephritis or bacteraemia.

Objectives

To evaluate the effectiveness and uptake of a lower UTI test-and-treat service for women presenting with urinary symptoms within a community pharmacy in supporting self-care and appropriate use of antibiotics and reducing demand on other NHS resources.

Methods

The service was aligned to national guidelines to diagnose and treat lower UTI in women aged 16–64 years and used national resources to provide safety-netting and self-care advice. Consultation included clinical assessment and a urine dipstick test alongside a novel smartphone app, with diagnosis informed by test results. Women were provided with safety-netting advice and either advised on self-care, supplied with antibiotics or referred to their GP.

Results

Data were analysed for 764 women who presented to 23 pharmacies during December 2018 to April 2019. Lower UTI was found to be likely in 372/496 (75.0%) women, most of whom purchased antibiotics on the same day. Had the service not been available, approximately three-quarters of women who had completed the service and responded to the question would have visited their GP (214/301) and more than one-third would have used self-care with or without going to see their GP (116/301).

Conclusions

A community pharmacy-led UTI test-and-treat service for women aged 16–64 years presenting with urinary symptoms provided accessible and timely care aligned to national guidance, with 75.0% of consultations requiring antibiotic treatment.
Impact of added copper, alone or in combination with chlortetracycline, on growth performance and antimicrobial resistance of fecal enterococci of weaned piglets
Authors: Capps Kaylen M , Amachawadi Raghavendra G , Menegat Mariana B , Woodworth Jason C , Perryman Kurt , Tokach Mike D , Dritz Steve S , DeRouchey Joel M , Goodband Robert D , Bai Jianfa , Apley Mike D , Lubbers Brian V , Nagaraja Tiruvoor G
Published: January 2020

Studies suggest a link between added copper (Cu) and co-selection of antimicrobial resistance (AMR) in Enterococcus spp., but data are inconsistent. This study aimed to assess the impact of added Cu, alone or with a feed-grade antimicrobial, on growth performance, transferable Cu resistance gene (tcrB) prevalence, abundance of tcrB in fecal community DNA, and AMR in fecal enterococci in weaned piglets. A total of 320 barrows (DNA 200 × 400, DNA Genetics) weaned at approximately 21 d of age with 7.4 kg (7.4 ± 0.06 kg) BW were used in a 28-d study. Piglets were fed a common non-medicated diet for 7 d of acclimation. Treatments were arranged in a 2 × 2 factorial design with main effects of added Cu (0 vs. 200 mg/kg Cu from Cu sulfate) and chlortetracycline (0 vs. 440 mg/kg CTC). Growth performance and fecal samples were obtained on days 0, 14, and 28. There was no evidence (P > 0.05) for Cu and CTC interaction in growth performance. Pigs fed diets with added Cu had increased (P < 0.05) ADG and ADFI from days 0 to 14, with no evidence for differences (P > 0.05) from days 15 to 28 and 0 to 28. Pigs fed diets with CTC had improved (P < 0.01) ADG, ADFI, and G:F from days 0 to 28. Prevalence of tcrB-positive enterococci was not affected by the addition of Cu and/or CTC (P > 0.05). Prevalence of tcrB-positive enterococci was higher on day 14 than other sampling days (P = 0.002). Prevalence of tetracycline resistance gene [tet(M)]-positive enterococci was not affected by treatments or day (P > 0.05). Prevalence of macrolide resistance gene [erm(B)]-positive enterococci had a significant treatment and sampling day interaction (P = 0.021). The abundance of the tcrB gene in feces, quantified by PCR, was not affected by Cu treatment. The median Cu minimum inhibitory concentrations (MIC) of tcrB-negative and -positive isolates were 3 and 20 mM, respectively (P < 0.001). For day 0 and day 28, all Enterococcus isolates were susceptible to gentamicin, kanamycin, streptomycin, daptomycin, and tigecycline, with a majority of isolates resistant to chloramphenicol, erythromycin, lincomycin, linezolid, tetracycline, tylosin tartrate, and Synercid. In conclusion, 200 mg/kg added Cu or 440 mg/kg CTC in nursery diets improved growth performance of nursery pigs. Added Cu, with or without a selection pressure of CTC, did not increase Cu-resistant enterococci and did not co-select resistance to antibiotics.
Neuropathology of Speech Network Distinguishes Bulbar From Nonbulbar Amyotrophic Lateral Sclerosis
Authors: Shellikeri Sanjana , Keith Julia , Black Sandra E , Zinman Lorne , Yunusova Yana
Published: January 2020

Bulbar amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative subtype affecting speech and swallowing motor functions as well as associated with the burden of cognitive deficits. The neuroanatomical underpinnings of bulbar ALS are not well understood. The aim of this study was to compare neuropathology of the speech network (SpN) between 3 cases of bulbar-onset ALS (bALS), 3 cases of spinal-onset ALS (sALS) with antemortem bulbar ALS (sALSwB) against 3 sALS without antemortem bulbar ALS (sALSnoB) and 3 controls. Regional distribution and severity of neuronal loss, TDP-43 (transactive response DNA-binding protein of 43 kDa), and tau proteinopathy were examined. All 3 bALS cases showed marked neuronal loss and severe proteinopathy across most SpN regions; sALSwB cases showed no neuronal loss but mild and variable TDP-43 pathology in focal regions; sALSnoB cases demonstrated an absence of pathology. Two bALS cases had coexisting tauopathy in SpN regions, which was not noted in any sALS cases. The findings suggested that bALS may have a distinct neuropathological signature characterized by marked neuronal loss and polypathology in the SpN. Milder TDP-43 pathology in the SpN for sALSwB cases suggested a link between severity of bulbar ALS and SpN damage. Findings support a clinicopathologic link between bulbar symptoms and pathology in the SpN.
Linear Polyubiquitin Chain Modification of TDP-43-Positive Neuronal Cytoplasmic Inclusions in Amyotrophic Lateral Sclerosis
Authors: Nakayama Yoshiaki , Tsuji Kazumi , Ayaki Takashi , Mori Megumi , Tokunaga Fuminori , Ito Hidefumi
Published: January 2020

Neuronal cytoplasmic inclusions (NCIs) containing TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and are known to be ubiquitinated. Eight linkage types of polyubiquitin chains have been reported, each type of chain exerting different intracellular actions. The linkage type of polyubiquitin chain involved in the formation of NCIs in sporadic ALS (sALS), however, has not yet been elucidated. We performed immunohistochemical study of the spinal cords of 12 patients with sALS and on those of 6 control subjects. Virtually all ubiquitinated NCIs were immunolabeled with lysine 48-linked polyubiquitin chain (K48-Ub). Although the majority of NCIs were triple-immunoreactive for K48-Ub, linear polyubiquitin chain (L-Ub), and lysine 63-linked polyubiquitin chain (K63-Ub), thin parts of K48-Ub-immunopositive NCIs were not labeled for K63-Ub or L-Ub. We also detected HOIP and SHARPIN, components of linear ubiquitin chain assembly complex, colocalizing with L-Ub on NCIs. Moreover, the immunosignal of optineurin, an autophagy receptor working with L-Ub, and that of activated NF-κB p65, were observed to be colocalizing with L-Ub on certain parts of NCIs. The L-Ub modification of TDP-43-positive NCIs may function as an inducer of autophagic clearance of NCIs, neuroinflammation, and neurodegeneration in sALS.
Mutations in orthologous PETALOSA TOE-type genes cause a dominant double-flower phenotype in phylogenetically distant eudicots
Authors: Gattolin Stefano , Cirilli Marco , Chessa Stefania , Stella Alessandra , Bassi Daniele , Rossini Laura
Published: January 2020

The double-flower phenotype has been selected by humans for its attractiveness in various plant species and it is of great commercial value for the ornamental market. In this study we investigated the genetic determinant of the dominant double-flower trait in carnation, petunia, and Rosa rugosa, and identified mutant alleles of TARGET OF EAT (TOE)-type genes characterized by a disruption of the miR172 target sequence and of the C-terminal portion of the encoded protein. Despite the phylogenetic distance between these eudicots, which diverged in the early Cretaceous, the orthologous genes carrying these mutations all belong to a single TOE-type subgroup, which we name as PETALOSA (PET). Homology searches allowed us to identify PET sequences in various other species. To confirm the results from naturally occurring mutations, we used CrispR-Cas9 to induce lesions within the miR172 target site of Nicotiana tabacum PET genes, and this resulted in the development of supernumerary petaloid structures. This study describes pet alleles in economically important ornamental species and provides evidence about the possibility of identifying and engineering PET genes to obtain the desirable double-flower trait in different plants.
The WAGGS project-III. Discrepant mass-to-light ratios of Galactic globular clusters at high metallicity
Authors: Dalgleish H , Kamann S , Usher C , Baumgardt H , Bastian N , Veitch-Michaelis J , Bellini A , Martocchia S , Da Costa G S , Mackey D , Bellstedt S , Pastorello N , Cerulo P
Published: January 2020

Observed mass-to-light ratios (M/L) of metal-rich globular clusters (GCs) disagree with theoretical predictions. This discrepancy is of fundamental importance since stellar population models provide the stellar masses that underpin most of extragalactic astronomy, near and far. We have derived radial velocities for 1622 stars located in the centres of 59 Milky Way GCs – 12 of which have no previous kinematic information – using integral-field unit data from the WAGGS project. Using N-body models, we determine dynamical masses and M/LV for the studied clusters. Our sample includes NGC 6528 and NGC 6553, which extend the metallicity range of GCs with measured M/L up to [Fe/H] ∼ −0.1 dex. We find that metal-rich clusters have M/LV more than two times lower than what is predicted by simple stellar population models. This confirms that the discrepant M/L–[Fe/H] relation remains a serious concern. We explore how our findings relate to previous observations, and the potential causes for the divergence, which we conclude is most likely due to dynamical effects.