Hallucinations are common in psychiatric disorders, and are also experienced by many individuals who are not mentally ill. Here, in 153 participants, we investigate brain structural markers that ...predict the occurrence of hallucinations by comparing patients with schizophrenia who have experienced hallucinations against patients who have not, matched on a number of demographic and clinical variables. Using both newly validated visual classification techniques and automated, data-driven methods, hallucinations were associated with specific brain morphology differences in the paracingulate sulcus, a fold in the medial prefrontal cortex, with a 1 cm reduction in sulcal length increasing the likelihood of hallucinations by 19.9%, regardless of the sensory modality in which they were experienced. The findings suggest a specific morphological basis for a pervasive feature of typical and atypical human experience.
Complete revascularization of coronary artery disease has been linked to improved outcomes in patients with preserved left ventricular (LV) function.
This study sought to identify the impact of ...complete revascularization in patients with severe LV dysfunction.
Patients enrolled in the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial were eligible if baseline/procedural angiograms and viability studies were available for analysis by independent core laboratories. Anatomical and viability-guided completeness of revascularization were measured by the coronary and myocardial revascularization indices (RIcoro and RImyo), respectively, where RIcoro = (change in British Cardiovascular Intervention Society Jeopardy score BCIS-JS) / (baseline BCIS-JS) and RImyo= (number of revascularized viable segments) / (number of viable segments supplied by diseased vessels). The percutaneous coronary intervention (PCI) group was classified as having complete or incomplete revascularization by median RIcoro and RImyo. The primary outcome was death or hospitalization for heart failure.
Of 700 randomized patients, 670 were included. The baseline BCIS-JS and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were 8 (Q1-Q3: 6-10) and 22 (Q1-Q3: 15-29), respectively. In those patients assigned to PCI, median RIcoro and RImyo values were 67% and 85%, respectively. Compared with the group assigned to optimal medical therapy alone, there was no difference in the likelihood of the primary outcome in those patients receiving complete anatomical or viability-guided revascularization (HR: 0.90; 95% CI: 0.62-1.32; and HR: 0.95; 95% CI: 0.66-1.35, respectively). A sensitivity analysis by residual SYNTAX score showed no association with outcome.
In patients with severe LV dysfunction, neither complete anatomical nor viability-guided revascularization was associated with improved event-free survival compared with incomplete revascularization or treatment with medical therapy alone. (Revascularization for Ischemic Ventricular Dysfunction) REVIVED-BCIS2; NCT01920048)
Explaining individual differences in vocabulary in autism is critical, as understanding and using words to communicate are key predictors of long-term outcomes for autistic individuals. Differences ...in audiovisual speech processing may explain variability in vocabulary in autism. The efficiency of audiovisual speech processing can be indexed via amplitude suppression, wherein the amplitude of the event-related potential (ERP) is reduced at the P2 component in response to audiovisual speech compared to auditory-only speech. This study used electroencephalography (EEG) to measure P2 amplitudes in response to auditory-only and audiovisual speech and norm-referenced, standardized assessments to measure vocabulary in 25 autistic and 25 nonautistic children to determine whether amplitude suppression (a) differs or (b) explains variability in vocabulary in autistic and nonautistic children. A series of regression analyses evaluated associations between amplitude suppression and vocabulary scores. Both groups demonstrated P2 amplitude suppression, on average, in response to audiovisual speech relative to auditory-only speech. Between-group differences in mean amplitude suppression were nonsignificant. Individual differences in amplitude suppression were positively associated with expressive vocabulary through receptive vocabulary, as evidenced by a significant indirect effect observed across groups. The results suggest that efficiency of audiovisual speech processing may explain variance in vocabulary in autism.
Our understanding of the past shapes our sense of the present and the future: this is historical consciousness. While academic history, public history, and the study of collective memory are thriving ...enterprises, there has been only sparse investigation of historical consciousness itself, in a way that relates it to the policy questions it raises in the present. WithTheorizing Historical Consciousness, Peter Seixas has brought together a diverse group of international scholars to address the problem of historical consciousness from the disciplinary perspectives of history, historiography, philosophy, collective memory, psychology, and history education.
Historical consciousness has serious implications for international relations, reparations claims, fiscal initiatives, immigration, and indeed, almost every contentious arena of public policy, collective identity, and personal experience. Current policy debates are laced with mutually incompatible historical analogies, and identity politics generate conflicting historical accounts. Never has the idea of a straightforward 'one history that fits all' been less workable.Theorizing Historical Consciousnesssets various theoretical approaches to the study of historical consciousness side-by-side, enabling us to chart the future study of how people understand the past.
Large studies comparing totally minimally invasive oesophagectomy (TMIE) with laparoscopically assisted (hybrid) oesophagectomy are lacking. Although randomized trials have compared TMIE invasive ...with open oesophagectomy, daily clinical practice does not always resemble the results reported in such trials. The aim of the present study was to compare complications after totally minimally invasive, hybrid and open Ivor Lewis oesophagectomy in patients with oesophageal cancer.
The study was performed using data from the International Esodata Study Group registered between February 2015 and December 2019. The primary outcome was pneumonia, and secondary outcomes included the incidence and severity of anastomotic leakage, (major) complications, duration of hospital stay, escalation of care, and 90-day mortality. Data were analysed using multivariable multilevel models.
Some 8640 patients were included between 2015 and 2019. Patients undergoing TMIE had a lower incidence of pneumonia than those having hybrid (10.9 versus 16.3 per cent; odds ratio (OR) 0.56, 95 per cent c.i. 0.40 to 0.80) or open (10.9 versus 17.4 per cent; OR 0.60, 0.42 to 0.84) oesophagectomy, and had a shorter hospital stay (median 10 (i.q.r. 8-16) days versus 14 (11-19) days (P = 0.041) and 11 (9-16) days (P = 0.027) respectively). The rate of anastomotic leakage was higher after TMIE than hybrid (15.1 versus 10.7 per cent; OR 1.47, 1.01 to 2.13) or open (15.1 versus 7.3 per cent; OR 1.73, 1.26 to 2.38) procedures.
Compared with hybrid and open Ivor Lewis oesophagectomy, TMIE resulted in a lower pneumonia rate, a shorter duration of hospital stay, but higher anastomotic leakage rates. Therefore, no clear advantage was seen for either TMIE, hybrid or open Ivor Lewis oesophagectomy when performed in daily clinical practice.
Focal But Not Diffuse Fibrosis Burden Predicts CRT Remodeling Response
Introduction
Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization ...therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT.
Methods and Results
In a prospective study of 48 consecutive patients (27 ischemic cardiomyopathy, 21 dilated cardiomyopathy) LV scar burdens were quantified (scar core and gray zone using late gadolinium enhancement LGE CMR; interstitial fibrosis using T1 mapping) before CRT implant. LV RR was defined by a ≥ 15% reduction in LV end‐systolic volume 6 months postimplant. Twenty‐seven (56%) patients were responders with RR. Association between scar quantification and LV RR was assessed using the Poisson regression model. Univariate analysis showed that QRS duration/morphology, scar core, and gray zone volumes expressed as % of LV mass and extracellular volume index (ECV) (a measure of interstitial fibrosis from T1 mapping) to be significant predictors of LV RR. Multivariable‐adjusted analyses demonstrated scar core quantification (≥13.7% LV mass) to be the only independent predictor of LV RR (prevalence ratio 0.40, P = 0.038).
Conclusions
Focal scar burden detected by LGE CMR is associated with a poor response to CRT. Diffuse interstitial fibrosis assessment by T1 mapping, however, is not independently predictive of CRT response.
Activation of the phosphoinositide-3 kinase (PI3K) pathway is a resistance mechanism to anti-human epidermal growth factor receptor 2 (HER2) therapy. This phase Ib trial was conducted to determine ...the maximum tolerated dose (MTD) of copanlisib, an intravenous (IV) pan-class I PI3K inhibitor, combined with trastuzumab.
Patients with advanced HER2-positive breast cancer and disease progression following at least one prior line of HER2 therapy in the metastatic setting were treated with copanlisib (45 or 60 mg) IV on days 1, 8 and 15 of a 28-day cycle with a fixed dose of trastuzumab 2 mg/kg weekly.
Twelve patients were enrolled. The MTD was determined as copanlisib 60 mg plus trastuzumab 2 mg/kg weekly. The most common adverse events of any grade occurring in more than two patients were hyperglycaemia (58%), fatigue (58%), nausea (58%) and hypertension (50%). Stable disease was confirmed at 16 weeks in six participants (50%).
mutations were detected in archival tumour of six participants (50%).
hotspot mutations, were detectable in pre- and on-treatment plasma of all participants. Pre- and post-treatment tumour biopsies for two patients identified temporal genomic heterogeneity, somatic mutations in the
gene, which encodes a PI3K-like protein kinase, and emergent somatic mutations related to protein kinase signalling.
Copanlisib and trastuzumab can be safely administered with fair overall tolerability. Preliminary evidence of tumour stability was observed in patients with heavily pre-treated, metastatic HER2 positive breast cancer. Several potential biomarkers were identified for further study in the current phase 2 clinical trial. NCT: 02705859.
Introduction
The role of implantable cardioverter defibrillators (ICDs) in nonischemic cardiomyopathy is unclear and better risk‐stratification is required. We sought to determine if T1 mapping ...predicts appropriate defibrillator therapy in patients with nonischemic cardiomyopathy. We studied a mixed cohort of ischemic and nonischemic patients to determine whether different cardiac magnetic resonance (CMR) applications (T1 mapping, late gadolinium enhancement, and Grayzone) were selectively predictive of therapies for the different arrhythmic substrates.
Methods and results
We undertook a prospective longitudinal study of consecutive patients receiving defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CMR scar assessment before device implantation. QRS duration and fragmentation on the surface electrocardiogram were also assessed. The primary endpoint was appropriate defibrillator therapy. One‐hundred thirty patients were followed up for a median of 31 months (IQR ± 9 months). In nonischemic patients, T1_native was the sole predictor of the primary endpoint (hazard ratio HR 1.12 per 10 millisecond increment in value 95% confidence interval CI 1.04–1.21; P ≤ 0.01). In ischemic patients, Grayzone_2SD‐3SD was the strongest predictor of appropriate therapy (HR 1.34 per 1% left ventricular increment in value 95% CI 1.03–1.76; P = 0.03). QRS fragmentation correlated well with myocardial scar core (receiver operating characteristic area under the curve ROC AUC 0.64; P = 0.02) but poorly with T1_native (ROC AUC 0.4) and did not predict appropriate therapy.
Conclusions
In the medium–long term, T1_native mapping was the only independent predictor of therapy in nonischemic patients, whereas Grayzone was a better predictor in ischemic patients. These findings suggest a potential role for T1_native mapping in the selection of patients for ICDs in a nonischemic population.
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease ...(AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
Abstract
There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This ...has led to calls for “precision medicine” or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.
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