bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognoses of “high-profile” diseases: five-year survival following hospitalization with previous cancer compared to previous heart failure
Authors: Fauchier L , Bentounes S A , Bodin A , Bisson A , Herbert J , Genet T , Angoulvant D , Ivanes F
Published: October 2022

Background

The prognostic impact of heart failure relative to that of “high-profile” disease states such as cancer within the whole population is poorly known. Some data reported 2 decades ago indicated that heart failure was as “malignant” as many common types of cancer (with the notable exception of lung cancer) and was associated with a comparable number of expected life-years lost. Whether this is also the case in more recent years is unknown.

Methods

In a nationwide cohort study including 5,123,193 patients seen in French hospitals in 2012 with at least 5 years of follow-up (or dying earlier), all patients with a first admission to any hospital with heart failure or cancer were identified. We assessed the incidence of all-cause death during follow-up (2,523,627person-years). We analysed the outcome for the most common types of cancer specific to men and women and the results were then age-adjusted in men and in women.

Results

In 2012, 409,210 men had a hospitalisation with heart failure (n=164,601) or cancer (n=244,609). Similarly, 325,410 women were admitted with heart failure (n=127,734), or cancer (n=197,676).

Heart failure was associated with a worse survival rate than urologic cancer in men and a worse survival rate than breast cancer, gynaecologic cancer and gastrointestinal cancer in women (Figure 1). On an age-adjusted basis, cancer was associated with a worse survival than heart failure in men except for urologic cancer (see adjusted hazard ratios in Table 1). Cancer was associated with a worse age-adjusted survival than heart failure in women except for breast cancer.

Conclusion

Heart failure may be as “malignant” as many common types of cancer in men and in women. However, it is possible that the prognosis of HF has improved compared to that of cancer in the 2 last decades since only breast cancer in women and urologic cancer in men had a better prognosis than heart failure in an age-adjusted analysis.

Funding Acknowledgement

Type of funding sources: None.
Does a normal electrocardiogram exclude heart failure with reduced left ventricular ejection fraction?
Authors: Auscher S , Mohamed R A , Andersen T R , Overgaard K , Egstrup K
Published: October 2022

Background

In the ESC guidelines for chronic heart failure an electrocardiogram (ECG) is part of the diagnostic set-up (1).

A normal ECG makes the diagnosis unlikely. But can a normal ECG exclude heart failure with reduced left ventricular ejection fraction (HFrEF) and be a gatekeeper to echocardiography?

Methods

Patients referred from primary care to the cardiac outpatient clinic with suspicion of heart failure were consecutively included in the study, during a period of one year. With the referral from primary care was included an ECG which was assessed by a senior cardiologist and divided into two groups: 1) Patients with normal ECG; 2) Patients with pathologically ECG.

Subsequently, an echocardiographic examination was performed in a blinded fashion and left ventricular ejection fraction (LVEF) was measured.

Results

Overall, 403 patients were included in the study. A normal ECG was present in 155 (38%) patients and a pathological ECG was present in 248 (62%) patients. In total, an echocardiographic examination identified 55 (14%) patients with an LVEF below 60% and 33 patients (8%) with LVEF below 50%. In patients with a normal ECG, only two patients had heart failure with a mildly reduced ejection fraction (41–49%), Figure 1.

Thus, the ECG had a sensitivity of 94% and a negative predictive value of 99%, Figure 2.

Conclusion

A normal electrocardiogram has a high diagnostic sensitivity and negative predictive value for excluding heart failure with reduced LVEF and could be a gatekeeping tool in the prioritization of patients referred to echocardiography examination from primary care.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): Department of Cardiovascular research, OUH, Svendborg Hospital
NT-proBNP is superior to novel plasma biomarkers for predicting adverse outcome in arrhythmogenic right ventricular cardiomyopathy
Authors: Borowiec K , Wozniak O , Wrobel A , Smigielski W , Skrzypczynska-Banasik U , Kowalik E , Lutynska A , Hoffman P , Biernacka E K
Published: October 2022

Background/Introduction

Arrhythmogenic right ventricular cardiomyopathy is a heritable heart muscle disease characterized by progressive substitution of the myocardium with fibrous and fatty tissue, which is the substrate for ventricular arrhythmia, systolic dysfunction and heart failure. Determining the optimal time for heart transplantation is challenging and, therefore, finding risk factors for disease progression is needed.

Purpose

The purpose of the study was to evaluate the role of markers of myocardial fibrosis sST2, Gal-3, MMP-2 and MMP-9, as well as NT-proBNP and hsTnT, in predicting major adverse outcomes in ARVC. Moreover, we aimed to identify other risk factors for developing end-stage heart failure.

Methods

We included 91 patients with the definite diagnosis of ARVC according to the 2010 Task Force Criteria (59 males, mean age of 47±16 years). Patients were interviewed for their medical history, electrocardiography and echocardiography were performed and plasma levels of selected biomarkers were measured. Thereafter, subjects were followed for the occurrence of the composite endpoint of death or heart transplantation (HTx) and major arrhythmic events defined as ventricular fibrillation, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator intervention.

Results

During the median follow-up of 36,4 months [29,8–41,2], 13 subjects (14%) reached the composite endpoint of death or HTx and 27 subjects (30%) experienced major arrhythmic event. Among the studied biomarkers, significantly higher levels of sST2, MMP-2, NT-proBNP and hsTnT were found in patients who achieved the composite endpoint. The remaining prognostic factors are shown in Table 1. In the multivariate analysis, three factors turned out to be significant: higher NT-proBNP levels (the cut-off point ≥890.3 pg/m), greater right ventricular end-diastolic area (the cut-off point ≥39.0 cm2) and history of atrial tachycardia. Kaplan-Meyer survival analysis depending on the number of predictors is presented in Figure 1. None of the biomarkers predicted major arrhythmic events.

Conclusions

NT-proBNP ≥890.3 pg/ml, RV area ≥39.0 cm2 and history of atrial tachycardia are independent risk factors for death or HTx in ARVC. Among the studied biomarkers, higher levels of sST2, MMP-2, NT-proBNP and hsTnT were observed in patients who reached the composite endpoint. Biomarkers had no value in predicting ventricular arrhythmias.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology, Warsaw, Poland
Proenkephalin as a novel prognostic marker in heart failure patients: a meta-analysis
Authors: Siranart N , Laohasurayotin K , Chokesuwattanaskul R , Ariyachaipanich A
Published: October 2022

Background

Proenkephalin (PENK), a novel biomarker, sequentially activates delta-opioid receptors in heart tissue causing reduced myocardial contractility, blood pressure, and heart rate. PENK has several prognostic abilities for patients with myocardial infarction, stroke, and impaired renal function. However, its prognostic value in heart failure patients is still inconclusive.

Purpose

To evaluate the association between plasma PENK level at the time of admission and all-cause mortality in patients with heart failure.

Methods

We collected studies from MEDLINE and EMBASE databases until January 2022 to perform a meta-analysis. High level of PENK is defined as plasma PENK level more than 99th percentile of the general population. Separated pooling hazard ratio (HR) for all-cause mortality among high and normal levels of PENK was performed using a random-effect model, generic inverse variance method of DerSimonian and Laird. Sources of heterogeneity including clinical and methodological variations were explored using a meta regression and subsequent subgroup analysis.

Results

A total of six observational studies composed of 6,929 patients with either acute heart failure or chronic heart failure were included in this analysis. There are five studies involving heart failure patients with both reduced ejection fraction and preserved ejection fraction and another one concerning those with only preserved ejection fraction. High level of PENK was found in 70.9% of patients. The high level of PENK compared with normal levels was associated with a higher prevalence of all-cause mortality with pooled HRs of 1.72 (95% CI, 1.62–1.84; I2=84%). The analyzed data were shown in the Figure 1.

Conclusions

This study demonstrates the association between high levels of PENK and all-cause mortality in heart failure patients. These findings suggest that the opioid system might be involved in deteriorating cardiovascular function in heart failure.

Funding Acknowledgement

Type of funding sources: None.
Selenoprotein-P deficiency is associated with higher risk of incident heart failure
Authors: Jujic A , Molvin J , Schomburg L , Struck J , Bergmann A , Melander O , Magnusson M
Published: October 2022

Background

Selenium deficiency has been associated with all-cause and cardiovascular mortality, incident cardiovascular disease (coronary artery disease, myocardial infarction and stroke), and with poor prognosis in patients with acute heart failure (HF). Furthermore, high selenium levels were recently shown to be associated with reduced mortality and reduced incidence of HF in non-smokers.

Purpose

To examine if selenoprotein-P (SELENOP), a main carrier protein of selenium, is associated with incident HF.

Methods

SELENOP concentrations were measured in 5060 randomly selected subjects from the population-based prospective cohort study “the Malmö Preventive Project” (n=18240) using a validated ELISA approach. After exclusion of subjects with prevalent HF (n=230), complete data on all co-variates was available in 4803 subjects (1400 women (29.1%), mean age 69.6±6.2 years, 885 (19.7%) current smokers). SELENOP was continously related to risk of incident HF using Cox regression models adjusted for age, sex, body mass index, systolic blood pressure, anti-hypertensive treatment, smoking status, diabetes status, low-density lipoprotein cholesterol levels, and prevalent coronary events. Further, subjects within the lowest SELENOP quintile were compared to subjects in the remaining four quintiles in an adjusted model.

Results

Each 1 SD increment in SELENOP levels was associated with lower risk of incident HF (n=436) during a median follow-up period of 14.7 years (interquartile range 10.9–15.7 years, hazard ratio (HR) 0.92, 95% confidence interval (95% CI) 0.84–0.99; p=0.049 in a model adjusted for cardiovascular risk factors. Multivariate quintile analyses revealed that the subjects in the lowest SELENOP quintile were at the highest risk of incident HF in an adjusted model (HR 1.46; 95% CI: 1.17–1.83 for incident HF; p for trend 0.039) illustrated in a Kaplan-Meier survival analysis (Figure 1). No interaction effect was seen for sex or smoking.

Conclusion

Low SELENOP levels are associated with a higher risk of incident HF supporting recent studies, which further emphasizes the need for randomly controlled trials to examine if supplementation with selenium improves prognosis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Medical Research CouncilSwedish Society of Medicine
Post systolic shortening by speckle tracking echocardiography as a predictor for cardiovascular events in patients with type 2 diabetes
Authors: Hult L , Kylhammar D , Engvall J , Ostgren C J , Nystrom F , Blomstrand P , Hedman K
Published: October 2022

Background

Post systolic shortening (PSS), measured by speckle tracking echocardiography has emerged as a novel method to evaluate left ventricular function and has been linked to adverse outcomes.

Purpose

Our aim was to assess if the presence of pathological PSS had prognostic value in the prediction of major cardiovascular events in a cohort of patients with type-II diabetes (T2D).

Method

Three-hundred-and-sixty-four patients with T2D in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes – a Prospective study in Primary care) underwent echocardiography between 2005 and 2009. All patients were evaluated with strain analysis by speckle tracking. PSS was defined as any myocardial contraction occurring after aortic valve closure (Figure 1). Pathological PSS was defined as a post systolic index (PSI) >5% where PSI was calculated as: (peak global longitudinal strain – peak systolic longitudinal strain) / (peak global longitudinal strain) x 100. The composite endpoint of any major cardiovascular event (MACE) was defined as the diagnosis of or death in heart failure, myocardial infarction, or stroke. Cox proportional hazard ratios (HR) with 95% confidence intervals were calculated and were adjusted for sex, age, body mass index, hypertension, smoking, previous cardiovascular events and HbA1c.

Results

Mean follow-up time was 11.2±2.3 years. Patients with pathological PSS had an increased unadjusted risk of MACE, (HR 3.73, 95% CI 2.06–6.76), which persisted after adjustment (HR 2.20, 95% CI 1.11–4.37) as compared to subjects without pathological PSS. When adding PSS to a risk prediction model including Global Longitudinal Strain (GLS), the adjusted HR (95% CI) for MACE was 2.94 (1.33–6.52) for subjects with reduced GLS (lower limit of normal −16%) and PSI >5%, compared to those with normal GLS and PSI ≤5%. Adverse events were more common in subjects with the combination of pathological PSS and GLS (Figure 2).

Conclusions

Our results suggest that PSS may provide important additional prognostic information in patients with T2D.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): This work was funded by grant support from FORSS, the Research Council of Southeastern Sweden and from FUTURUM, the Research Council of Jönköping.
Left atrial reservoir strain and long-term prognosis in patients with heart failure and reduced ejection fraction
Authors: Chimed S , Stassen J , Galloo X , Meucci M C , Van Der Bijl P , Marsan N A , Delgado V , Bax J J
Published: October 2022

Background

Cardiac damage in heart failure (HF) with reduced ejection fraction (HFrEF) often involves structural and functional left atrial (LA) abnormalities. Speckle-tracking echocardiography derived LA reservoir strain (LARS) is a sensitive measurement for early detection of LA dysfunction. However, the prognostic value of LARS is not well established in patients with HFrEF.

Methods

LARS was measured with speckle tracking echocardiography in patients who had a first echocardiographic diagnosis of reduced LVEF (≤45%). Patients with prior history of atrial fibrillation (AF) were excluded. The primary endpoint was newly onset AF, while the composite endpoint of newly onset AF and all-cause mortality was chosen as the secondary endpoint. The study population was divided into two groups according to the optimal threshold value of baseline LARS (derived from spline curve analysis) (Figure 1) and event-free survival rates were compared by the Kaplan-Meier method.

Results

A total of 997 patients (mean age 62±13 years, 73% men) were analyzed. At baseline, LA volume index was significantly larger (41±17 vs. 32±12 ml/m2, p<0.001), and LA reservoir function significantly more impaired (9±3.1 vs. 21±6.3%, p<0.001) in patients with LARS ≤14% compared to patients with LARS >14%. During a median follow-up of 60 months (interquartile range [IQR] 29–60 months), newly onset AF occurred in 75 patients (7.5%), while 254 patients (25.5%) experienced the composite endpoint of newly onset AF and all-cause mortality. The 5-year event-free survival rates for both endpoints were significantly lower in the LARS ≤14% group compared to LARS >14% group (Figure 1A for new onset AF and Figure 2B for the composite endpoint of newly onset AF and all-cause mortality). After adjustment for important risk factors, including HF treatments and echocardiographic predictors, baseline LARS remained independently associated with a higher risk of development of AF (HR=0.89, 95% CI 0.85–0.94, p<0.001) and the composite of newly onset AF and all-cause mortality (HR=0.93, 95% CI 0.91–0.96, p<0.001).

Conclusions

Baseline LARS is associated with long-term prognosis in patients with HFrEF and the association is independent from various clinical and echocardiographic predictors.

Funding Acknowledgement

Type of funding sources: None.
Quantitative estimation of pulmonary artery wedge pressure from chest radiographs by a regression convolutional neural network
Authors: Saito Y , Omae Y , Fukamachi D , Nagashima K , Toyotani J , Okumura Y
Published: October 2022

Introduction

Recent studies reported that a convolutional neural network (CNN; a deep learning model) can detect elevated pulmonary artery wedge pressure (PAWP) from chest radiographs, the diagnostic images most commonly used for assessing pulmonary congestion in heart failure. However, no method has been published for quantitatively estimating PAWP from such radiographs. We hypothesized that a regression CNN, an alternative type of deep learning, could be a useful tool for quantitatively estimating PAWP from chest radiographs in cardiovascular diseases.

Methods

We retrospectively enrolled 936 patients with cardiovascular diseases who had undergone right heart catheterization (RHC) and chest radiography and estimated PAWP by constructing a regression CNN based on the VGG16 model. We randomly categorized 80% of the data as training data (training group, n=748) and 20% as test data (test group, n=188). Moreover, we tuned the learning rate–one of the model parameters–by 5-hold cross-validation of the training group. Correlations between PAWP measured by RHC (ground truth [GT] PAWP) and PAWP derived from the regression CNN (estimated PAWP) were tested. To visualize how the regression CNN assessed the images, we created a regression activation map (RAM), a visualization technique for regression CNN.

Results

Estimated PAWP correlated significantly with GT PAWP in both the training (r=0.76, P<0.001) and test group (r=0.62, P<0.001). Bland-Altman plots found a mean (SEM) difference between GT and estimated PAWP of −0.23 (0.16) mm Hg in the training and −0.05 (0.41) mm Hg in the test group. The RAM showed that our regression CNN model estimated high PAWP by focusing on the cardiomegaly and pulmonary congestion. In the test group, the area under the curve (AUC) for detecting elevated PAWP (≥18 mm Hg) produced by the regression CNN model was similar to the AUC of an experienced cardiologist (0.86 vs 0.83, respectively; P=0.24).

Conclusion

This proof-of-concept study shows that regression CNN can quantitatively estimate PAWP from standard chest radiographs in cardiovascular diseases.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The Bayer Academic Support
Cardiac magnetic resonance predictors of readmission for heart failure in elderly vs not elderly patients after ST-segment elevation myocardial infarction
Authors: Merenciano-Gonzalez H , Marcos Garces V , Gabaldon-Perez A , Gavara J , Lopez-Lereu M P , Monmeneu J V , Perez N , Rios-Navarro C , De Dios E , Chorro F J , Valente F , Lorenzatti D , Ortiz-Perez J T , Rodriguez-Palomares J F , Bodi V
Published: October 2022

Background

Patients with ST-segment elevation acute myocardial infarction (STEMI) have an increased risk of re-admission for acute heart failure (AHF). However, identification of patients at higher risk of AHF is challenging, especially in elderly individuals. The implications of cardiac magnetic resonance (CMR) imaging soon after the acute event for this specific purpose are unknown.

Purpose

We aim to study the clinical and CMR predictors of AHF in elderly and not elderly patients after STEMI.

Methods

STEMI patients treated with percutaneous coronary intervention and discharged from three university hospitals were included in a multicenter registry. We registered baseline clinical characteristics, echocardiographic parameters and early (1-week) CMR parameters - left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments). Univariate and multivariate comparisons were performed in elderly (>70 years) and not elderly (≤70 years) patients to predict AHF during follow-up.

Results

The cohort was comprised of 759 patients, of which 177 (23.3%) were elderly (>70 years). During a mean follow-up of 5.23±3.54 years, 79 (10.4%) patients presented AHF. In not elderly patients, Killip class at admission (HR 2.05 [1.32–3.17], p=0.001), anterior infarction (HR 3.43 [1.13–10.36], p=0.03) and CMR-LVEF (HR 0.94 [0.91–0.98] per increased %, p=0.001) independently predicted AHF. However, a combined risk score comprising these variables was not superior to CMR-LVEF alone to predict AHF during follow-up (AUC 0.81 [0.74–0.88] vs. 0.81 [0.73–0.88], p=NS). In elderly patients, CMR-LVEF was the only predictor of AHF in the final multivariable model (HR 0.94 [0.91–0.97], p<0.001), although its predictive power was moderate (AUC 0.68 [0.56–0.80], p=0.001). Most AHF events in the not elderly subgroup occurred in patients with reduced (≤40%) CMR-LVEF (71%), while in the elderly subgroup AHF occurred more frequently in patients with preserved (≥50%, 30%) or mildly reduced (40–49%, 32%) CMR-LVEF than reduced (≤40%) CMR-LVEF (38%).

Conclusions

LVEF quantified by CMR soon after STEMI can accurately predict the risk of AHF in not elderly (≤70 years) patients and identify those individuals at higher risk (i.e. CMR-LVEF ≤40%). However, in elderly (>70 years) patients most AHF occur in patients with CMR-LVEF >40%, emphasizing the need for better predictive strategies in this population.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III and “Fondos Europeos de Desarrollo Regional FEDER” and Conselleria de Educaciόn – Generalitat Valenciana.
Cognitive impairment negatively impacts self-efficacy in patients with chronic heart failure patients: results from the Cognition.Matters-HF study
Authors: Wissel S , Frey A , Sell R , Frantz S , Stoll G , Stoerk S
Published: October 2022

Background

Cognitive impairment is highly prevalent in patients with chronic heart failure (HF), but evidence on its relationship with health-related quality of life (HRQoL) is sparse. We aimed to examine whether cognitive impairment is associated with HRQoL. We hypothesized that cognitive impairment would negatively impact HRQoL.

Methods

A total of 148 outpatients with chronic stable HF (mean LV ejection fraction 43±8%) were enrolled in the Cognition.Matters-HF prospective cohort study: mean age 64±11 years, 16% women, 77% in NYHA functional class I-II. Patients were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). Severity of cognitive deficits were categorized based on the domains affected according to neurocognitive test battery results: 0 domains (“none”, n=46 [31%]), 1–2 domains (“mild”, n=77 [52%]), and >2 domains (“severe”, n=24 [16%]). HRQoL was measured with the generic Short-Form 36 (SF-36) and the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ). Multivariable analysis of variance and regression modelling were applied to model associations between cognitive impairment and HRQoL.

Results

Cognitive impairment was not associated with overall scores of SF-36 and KCCQ nor any of the subscales, with the exception of the self-efficacy scale of the KCCQ. Self-efficacy represents the ability of patients to care for themselves; it quantifies a patient's unterstanding of how to prevent heart failure exacerbations and manage arising complications. Self-efficacy was negatively associated with cognitive impairment (beta=−0.242; p=0.004) and was rated 15% lower (B=−0.148) per increment in cognitive deficit category. The association of self-efficacy with cognitive impairment remained significant after adjustment for duration and severity of HF, age, and sex (p<0.001).

Conclusions

With the exception of self-efficacy, the severity of cognitive impairment was not associated with lower HRQoL in patients with chronic HF. The self-efficacy scale of the KCCQ is a promising tool potentially suited to detect individuals, who are unable to adhere to a proper HF treatment regimen. These patients may benefit from enhanced care, e.g. in the frame of a HF nurse led management program.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF
The real-world safety profile of SGLT2 inhibitors among adults 75 years or older: a retrospective, pharmacovigilance study
Authors: Goldman A , Fishman B , Raschi E , Cukierman-Yaffe T , Dankner R , Ben-Zvi I , Maor E
Published: October 2022

Introduction

As indications for sodium-glucose co-transporter-2 (SGLT2) inhibitors treatment are expanding, more older adults become candidates for treatment. However, data regarding the treatment's safety profile in the older population are limited.

Methods

A retrospective, pharmacovigilance study of the FDA's global database of safety reports (7/1/2014–6/30/2021). To assess reporting of pre-specified adverse events following SGLT2-inhibitors treatment among adults (18≥age<75) and older adults (age≥75), we performed disproportionality analysis using the reporting odds ratio (ROR).

Results

Of 10,526,408 patients in the full database, 279,619 eligible patients with non-insulin-dependent diabetes mellitus were identified (mean age 63.4 [SD 13.0] years, 54,791 [19.6%] aged ≥75 years), among whom 29,431 receiving SGLT-2 inhibitors. Compared to other non-insulin anti-diabetics, SGLT2-inhibitors were significantly associated with amputations (ROR=127.87 [95% CI: 111.31–146.90] vs ROR=74.91 [49.99–112.25]), Fournier gangrene (ROR=53.27 [44.38–63.92] vs ROR=33.33 [20.33–54.64]), diabetes ketoacidosis (ROR=39.25 [37.20–41.42] vs ROR=58.46 [49.41–69.1]), genitourinary infections (ROR=4.36 [4.12–4.61] vs ROR=5.08 [4.45–5.79]), nocturia (ROR=2.81 [2.13–3.73] vs ROR=3.51 [1.84–6.68]), and dehydration (ROR=2.22 [2.05–2.40] vs ROR=2.33 [1.93–2.81]) in both adults and older adults, respectively. The relative reporting of these safety signals was consistent between age groups (all P interaction >0.05). Acute kidney injury was associated with SGLT2-inhibitors treatment in adults (ROR=1.47 [1.40–1.54]) but not older adults (ROR=0.84 [0.72–0.98]). No new safety signals were observed in older adults. Falls, fractures, hypotension, and syncope were not associated with SGLT2-inhibitors among either adults or older adults.

Conclusion

In this global post-marketing study, treatment with SGLT-2 inhibitors in older adults was associated with increased reporting of amputations, Fournier gangrene, DKA, genitourinary infections, and dehydration. Nevertheless, the relative reporting was consistent between adults and older adults, and no new safety signals were found in the older population.

Funding Acknowledgement

Type of funding sources: None.
Efficacy of sodium glucose cotransporter 2 inhibitors for heart failure with preserved and mildly reduced ejection fraction: a systematic review and meta-analysis
Authors: Cordovez R A B , Denila R A , Rivera K , Patricio M
Published: October 2022

Background

SGLT2 inhibition has been a breakthrough approach in the treatment for heart failure. A recent guideline has recommended SGLT2i for the treatment of patients with HFrEF to reduce the risk of HF hospitalization and death, regardless of presence of type 2 diabetes (1). However, its benefit in HFpEF and HFmrEF have yet to be established.

Purpose

We evaluated the cardiovascular outcomes of SGLT2i for HFpEF and HFmrEF.

Methods

Randomized controlled trials on SGLT2i versus placebo in patients with left ventricular ejection fraction of more than 40% reporting CV outcomes were searched using Pubmed, CENTRAL, and ScienceDirect. Primary outcome was the composite of hospitalization for heart failure or CV death. Secondary outcomes were the individual HHF, CV death, as well as all-cause mortality. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model.

Results

Six studies were included with a total of 10,450 patients. In the combined HFmrEF and HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.79, 95% CI 0.71–0.88, p<0.0001) compared to placebo, driven by a significant reduction in heart failure hospitalization (HR 0.73, 95% CI 0.63–0.84, p<0.00001). In the distinct HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.75, 95% CI 0.63–0.88, p=0.0007) compared to placebo.

Conclusion

SGLT2i provides significant risk reduction in HF hospitalization or CV death among patients with HFpEF compared to placebo.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of liver damage assessed by direct bilirubin and skeletal muscle weakness in patients with heart failure
Authors: Noda T , Kamiya K , Hamazaki N , Nozaki K , Ichikawa T , Yamashita M , Uchida S , Maekawa E , Yamaoka-Tojo M , Matsunaga A , Ako J
Published: October 2022

Background

Patients with heart failure (HF) have a high prevalence of liver function abnormalities such as bilirubin abnormalities. However, the relationship between abnormalities of direct bilirubin (DB), a fraction of total bilirubin, and dynapenia are unclear, and the effect of the coexistence of both on the prognosis of patients with HF remains unclear.

Purpose

This study investigated the association between total/direct bilirubin and dynapenia, a muscle weakness syndrome. Moreover, we considered the effect of the combination of high DB and dynapenia on increased mortality.

Methods

In this retrospective cohort study, we reviewed patients with HF for whom we assessed total bilirubin, DB, handgrip strength, and leg strength at discharge, which were further evaluated to determine the presence of dynapenia. Dynapenia was defined by the lower handgrip strength and leg strength. Low handgrip strength was defined as <26 kg for males and <18 kg for females, and low leg strength assessed by the maximal quadriceps isometric strength was defined as <45% body mass (%BM) for males and <35% BM for females. Multiple linear and multivariate logistic regression analyses were used to examine the association between DB with muscle weakness and dynapenia. In addition, we examined the prognostic value of comorbid DB abnormalities (≥0.5) and dynapenia. The endpoint was all-cause mortality.

Results

Among 853 inpatients enrolled, high DB was identified in 147 and dynapenia in 377 (44.2%) patients. Multiple regression analysis showed that high DB was independently associated with decreased grip and leg strengths (grip strength, P=0.027; leg strength, P=0.002). Furthermore, after adjusting for covariates, the high DB group (odds ratio: 1.800, 95% confidence interval [CI]: 1.203–2.695, P=0.004) was significantly associated with dynapenia compared to the low DB group. During the follow-up period, 189 patients died (median, 1.77 years; interquartile range, 0.64–3.81 years). The risk of death was significantly higher in the high DB/dynapenia group than in the low DB group, even after adjusting for the severity of HF (hazard ratio: 2.610, 95% CI: 1.680–4.051, P<0.001).

Conclusions

High DB is associated with muscle weakness in patients with HF and affects patient prognosis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): This work was partially supported by JSPS KAKENHI.
Experiences of German health care professionals with spiritual history taking in primary care: a mixed-methods process evaluation of the HoPES3 intervention
Authors: Huperz Carolin , Sturm Noemi , Frick Eckhard , Mächler Ruth , Stolz Regina , Schalhorn Friederike , Valentini Jan , Joos Stefanie , Straßner Cornelia
Published: October 2022

Background

Spiritual needs gain importance in old age but are often ignored in health care. Within the ‘Holistic care program for elderly patients to integrate spiritual needs, social activity and self-care into disease management in primary care (HoPES3)’ a complex intervention was evaluated in a cluster-randomized trial. The aim of this study was to explore the acceptability, feasibility, benefits, and harms of a spiritual history taken by general practitioners (GPs) as part of the complex intervention.

Methods

In this mixed-methods study telephone interviews with 11 German GPs and 12 medical assistants (MAs) of the HoPES3 intervention group were conducted and analysed using a content-analytical approach. Furthermore, GPs were asked to complete a questionnaire after each spiritual history. One hundred and forty-one questionnaires from 14 GPs were analysed descriptively.

Results

GPs considered the spiritual history very/quite helpful for the patient in 27% (n= 38) and very/quite stressful in 2% (n = 3) of the cases. Interviews indicated that GPs found discussing spiritual history easier than anticipated. GPs and MAs saw a difficulty in that many patients associated spirituality with religion or church and reacted with surprise or rejection. Benefits for patients were seen in the opportunity to talk about non-medical topics, and increased awareness of their own resources. Benefits for GPs mainly related to information gain and an intensified patient–physician relationship.

Conclusions

A spiritual history in general practice has the potential to reveal important information about patients’ lives and to improve the patient–physician relationship. Implementation barriers identified in this study have to be considered and addressed.
Cognitive Effort-Based Decision-Making Across Experimental and Daily Life Indices in Younger and Older Adults
Authors: Crawford Jennifer L , English Tammy , Braver Todd S
Published: October 2022

Objectives

The study investigated whether cognitive effort decision-making measured via a neuroeconomic paradigm that manipulated framing (gain vs. loss outcomes), could predict daily life engagement in mentally demanding activities in both younger and older adults.

Method

Younger and older adult participants (N = 310) completed the Cognitive Effort Discounting paradigm (Cog-ED), under both gain and loss conditions, to provide an experimental index of cognitive effort costs for each participant in each framing condition. A subset of participants (N = 230) also completed a 7-day Ecological Momentary Assessment (EMA) protocol measuring engagement in mentally demanding daily life activities.

Results

In a large, online sample, we replicated a robust increase in cognitive effort costs among older, relative to younger, adults. Additionally, costs were found to be reduced in the loss relative to gain frame, although these effects were only reliable at high levels of task difficulty and were not moderated by age. Critically, participants who had lower effort costs in the gain frame tended to report engaging in more mentally demanding daily life activities, but the opposite pattern was observed in the loss frame. Further analyses demonstrated the specificity of reward-related cognitive motivation in predicting daily life mentally demanding activities.

Discussion

Together, these results suggest that cognitive effort costs, as measured through behavioral choice patterns in a neuroeconomic decision-making task, can be used to predict and explain engagement in mentally demanding activities during daily life among both older and younger adults.
The Tuchyn Pogrom: The Names and Faces Behind the Violence, Summer 1941
Authors: McBride Jared
Published: October 2022

On the night of July, 6, 1941, under the cover of darkness, a group of Ukrainian assailants armed with bats, shovels, and other weapons attacked their Jewish neighbors in Tuchyn, a small town just outside of Rivne, killing dozens and wounding more. Through the testimony of perpetrators, victims, and local witnesses, this article not only reestablishes the events leading up to, during, and following the pogrom against Tuchyn’s Jews, but also provides biographical sketches of the local perpetrators and those in the community who enabled it. While there has been increasingly sophisticated work on the summer 1941 pogroms in Eastern Europe, scholars have yet to identify and thoroughly analyze local participants. From a deeper probe into local perpetrators’ organizational affiliations, social networks, and their place in the quickly changing and dynamic political situation, this article questions the analytical categories we use to frame local perpetrators, as well as the pogroms. In doing so it offers new insights on the participants, while demonstrating the possibilities for new more dynamic avenues for future research on pogrom violence.
An exponentially convergent discretization for space–time fractional parabolic equations using hp-FEM
Authors: Markus Melenk Jens , Rieder Alexander
Published: October 2022

We consider a space–time fractional parabolic problem. Combining a sinc quadrature-based method for discretizing the Riesz–Dunford integral with $hp$-FEM in space yields an exponentially convergent scheme for the initial boundary value problem with homogeneous right-hand side. For the inhomogeneous problem, an $hp$-quadrature scheme is implemented. We rigorously prove exponential convergence with focus on small times $t$, proving robustness with respect to startup singularities due to data incompatibilities.
Effects of resveratrol and its derivative pterostilbene on hepatic injury and immunological stress of weaned piglets challenged with lipopolysaccharide
Authors: Li Yue , Zhang Hao , Tu Feng , Cao Jing , Hou Xiang , Chen Yanan , Yan Junshu
Published: October 2022

The present study was to investigate the protective effects of resveratrol (RSV) and its 3,5-dimethylether derivative pterostilbene (PT) against liver injury and immunological stress of weaned piglets upon lipopolysaccharide (LPS) challenge. Seventy-two weaned piglets were divided into the following groups: control group, LPS-challenged group, and LPS-challenged groups pretreated with either RSV or PT for 14 d (n = 6 pens, three pigs per pen). At the end of the feeding trial, piglets were intraperitoneally injected with either LPS or an equivalent amount of sterile saline. After 6 h of sterile saline or LPS injection, plasma and liver samples were collected. LPS stimulation caused massive apoptosis, activated inflammatory responses, and incited severe oxidative stress in the piglet livers while also promoting the nuclear translocation of nuclear factor kappa B (NF-κB) p65 (P < 0.001) and the protein expression of Nod-like receptor pyrin domain containing 3 (NLRP3; P = 0.001) and cleaved caspase 1 (P < 0.001). PT was more effective than RSV in alleviating LPS-induced hepatic damage by decreasing the apoptotic rate of liver cells (P = 0.045), inhibiting the transcriptional expression of interleukin 1 beta (P < 0.001) and interleukin 6 (P = 0.008), and reducing myeloperoxidase activity (P = 0.010). The LPS-induced increase in hepatic lipid peroxidation accumulation was also reversed by PT (P = 0.024). Importantly, inhibiting protein phosphatase 2A (PP2A) activity in a hepatocellular model largely blocked the ability of PT to prevent tumor necrosis factor alpha-induced increases in NF-κB p65 protein phosphorylation (P = 0.043) and its nuclear translocation (P = 0.029). In summary, PT is a promising agent that may alleviate liver injury and immunological stress of weaned piglets via the PP2A/NF-κB/NLRP3 signaling pathway.
Improvement in Platelet Product Wastage and Reduction of Costs through Implementation of the Pan Genera Detection Test
Authors: Munyikwa Ru , Walker LeeAnn , Rajendran Rajkumar
Published: October 2022

Objective

The aim of this study was to evaluate the effects of Pan Genera Detection (PGD) testing on reducing platelet product wastage and transfusion service costs.

Methods

We conducted a retrospective cross-sectional study comparing the number of platelet apheresis units wasted before (March 2017 to February 2019) and after (March 2019 to February 2021) PGD implementation. The PGD testing was performed before transfusion on days 6 and 7. Cost analysis considered the costs of platelet units wasted ($500.00/unit) and PGD test supplies and performance (estimated $26.50 per test). Paired samples t-test was used to compare platelet wastage pre- and post-PGD implementation.

Results

The number of wasted platelet units decreased from pre-PGD (419) to post-PGD (195), representing a significant decrease in platelet wastage from 17.5% to 9.2% (P < .0001). During the post-PGD period, 366 and 133 units were tested on days 6 and 7, with 28 and 36 units discarded each day, allowing transfusion of an additional 302 platelet units. Costs from platelet wastage decreased from $209,500.00 pre-PGD to $97,500.00 post-PGD.

Conclusion

Our results showed that PGD testing effectively reduced platelet wastage, extended platelet availability, and reduced transfusion service costs.
A Novel INS Mutation in the C-Peptide Region Causing Hyperproinsulinemic Maturity Onset Diabetes of Youth Type 10
Authors: Schlegel Amnon , Petersen Whitney C , Holbrook Alexandra A , Iverson Leslie K , Graham Timothy E
Published: October 2022

Monogenetic diabetes mellitus (DM) describes a collection of single-gene diseases marked by hyperglycemia presenting in childhood or adulthood and the absence of immunological markers of type 1 DM. Mutations in the human insulin gene INS give rise to two separate clinical syndromes: permanent neonatal DM, type 4 (PNDM4), and maturity-onset diabetes of youth, type 10 (MODY10); the former presents shortly after birth and the latter presents in childhood and adulthood. We describe a 40-year-old man in a kindred with high prevalence of DM who presented with severe hyperglycemia but not ketoacidosis or hypertriglyceridemia. Twelve years after initial presentation, the patient had elevated proinsulin and normal plasma C-peptide when nearly euglycemic on treatment with insulin glargine. A novel INS mutation, Gln65Arg, within the C-peptide region was identified. The INS (p.Gln65Arg) mutation may cause MODY10 by disrupting proinsulin maturation.
Application of a Near-infrared Spectroscope by an Extreme Forward Medical Team for the Triage of Casualties With Traumatic Brain Injury
Authors: Joubert Christophe , Sellier Aurore , Beucler Nathan , Desse Nicolas , Delmas Jean-Marc , Bordes Julien , Dulou Renaud , Dagain Arnaud
Published: October 2022

Background

During deployment of military medical teams similarly to prehospital practice, without immediate computed tomography scan access, identifying patients requiring neuro-specific care to manage pragmatic triage proves crucial. We assessed the contribution of this portable near-infrared spectroscope (NIRS) handheld device, Infrascanner Model 2000 (InfraScan Inc.; Philadelphia, PA), to screen patients suspected to require specific neurosurgical care.

Materials and methods

This single-center retrospective analysis was based on the data from the medical records of the traumatic brain injured patients. We analyzed all the patients strictly over 18 years old presenting a clinical history of traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) < 15.

Results

Thirty-seven medical records of patients admitted for TBI met the inclusion criteria for our analysis. The median GCS was 9 [3-14]. Eight patients (21.6%) underwent neurosurgery and 25 (67.6%) required intensive care unit (ICU) admission, after initial assessment and resuscitation. The NIRS was the most sensible to detect intracranial hematoma (n = 21), intracranial hematoma leading to surgery (n = 8), and intracranial hematoma leading to admission in ICU (n = 25). Its negative predictive value was 100% regarding hematomas leading to surgery. False-positive results were encountered in 10 cases (27.0%). Excluding cases harboring confounding extracranial hematomas, parietal area was still the most represented (n = 3).

Conclusion

The NIRS was relevant to detect hematoma leading to prompt surgery in our study. The lack of specificity in a nonselected cohort of patients underlines the need to associate simple clinical feature such as neurological deficit and NIRS results to perform rational triage.
Spontaneous Pneumomediastinum Resulting From Passionate Cheering at a Soccer Match
Authors: Talmy Tomer , Izhaki Ziv , Gendler Sami , Aviram Eliad
Published: October 2022

Spontaneous pneumomediastinum is a rare and self-limiting clinical entity, often triggered by activities causing acute changes in intrathoracic pressure such as childbirth, strenuous exercise, vomiting, and coughing. We present a case of a young male soldier who developed spontaneous pneumothorax following persistent yelling while attending a soccer match. Spontaneous pneumomediastinum may be preceded by a variety of strenuous activities, and clinicians should be aware of this entity when performing the evaluation of patients with nonspecific symptoms such as chest pain and dyspnea. Patients diagnosed with pneumomediastinum but presenting with additional findings such as vomiting and pleural effusion should be thoroughly evaluated to rule out potentially life-threatening mediastinal organ injury. Return to military duty should be determined by clinical reevaluation and follow-up imaging findings.
Does integrated information theory make testable predictions about the role of silent neurons in consciousness?
Authors: Bartlett Gary
Published: October 2022

Tononi et al. claim that their integrated information theory of consciousness makes testable predictions. This article discusses two of the more startling predictions, which follow from the theory’s claim that conscious experiences are generated by inactive as well as active neurons. The first prediction is that a subject’s conscious experience at a time can be affected by the disabling of neurons that were already inactive at that time. The second is that even if a subject’s entire brain is “silent,” meaning that all of its neurons are inactive (but not disabled), the subject can still have a conscious experience. A few authors have noted the implausibility of these predictions—which I call the disabling prediction and the silent brain prediction—but none have considered whether they are testable. In this article, I argue that they are not. In order to make this case, I first try to clarify the distinction between active, inactive (i.e. silent), and inactivated (i.e. disabled) neurons. With this clarification in place, I show that, even putting aside practical difficulties, it is impossible to set up a valid test of either the disabling prediction or the silent brain prediction. The conditions of the tests themselves are conditions under which a response from the subject could not reasonably be interpreted as evidence of consciousness or change in consciousness.