Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients.

Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 .

Higher-Order Intrinsic Brain Network Trajectories After Antipsychotic Treatment in Medication-Naïve Patients With First-Episode Psychosis.

BACKGROUND: Intrinsic brain network connectivity is already altered in first-episode psychosis (FEP), but the longitudinal trajectories of network connectivity, especially in response to antipsychotic treatment, remain poorly understood. The goal of this study was to investigate how antipsychotic medications affect higher-order intrinsic brain network connectivity in FEP. METHODS: Data from 87 antipsychotic medication-naïve patients with FEP and 87 healthy control participants were used. Medication-naïve patients received antipsychotic treatment for 16 weeks. Resting-state functional connectivity (FC) of the default mode, salience, dorsal attention, and executive control networks were assessed prior to treatment and at 6 and 16 weeks after treatment. We evaluated baseline and FC changes using linear mixed models to test group × time interactions within each network. Associations between FC changes after 16 weeks and response to treatment were also evaluated. RESULTS: Prior to treatment, significant group differences in all networks were found. However, significant trajectory changes in FC were found only in the default mode and executive control networks. Changes in FC in these networks were associated with treatment response. Several sensitivity analyses showed a consistent normalization of executive control network FC in response to antipsychotic treatment. CONCLUSIONS: Here, we found that alterations in intrinsic brain network FC were not only alleviated with antipsychotic treatment, but the extent of this normalization was also associated with the degree of reduction in symptom severity. Taken together, our data suggest modulation of intrinsic brain network connectivity (mainly frontoparietal connectivity) as a mechanism underlying antipsychotic treatment response in FEP.

The additive effects of anaemia and transfusion on long-term survival after coronary artery bypass surgery.

OBJECTIVES: To compare the independent and combined effects of anaemia and red blood cell transfusion on late survival after isolated coronary artery bypass grafting (CABG). METHODS: Retrospective analysis of 5243 consecutive patients undergoing primary isolated CABG, performed from 2000 to 2015, in a Portuguese Academic Hospital. We identified 1649 patients with preoperative anaemia (A+) and 1422 patients who received a perioperative transfusion (T+) - the four possible combinations allowed for the creation of four subgroups (A-/T-, A-/T+, A+/T-, and A+/T+). The primary endpoint was all-cause mortality at ten years. We employed inverse probability weighting to control for confounding variables. RESULTS: Thirty-one percent of the patients had preoperative anaemia, and 27.0% had at least one packed red blood cell transfusion. Inverse probability weighting was effective in eliminating differences in all significant baseline characteristics. The primary endpoint of all-cause mortality at ten years occurred in 568 patients (20.5%) in the A-/T- group, as compared with 204 (24.4%) in the A-/T+ group (HR, 1.14; 95% CI, 1.00 to 1.31; p = 0.053), 358 (33.8%) in the A+/T- group (HR, 1.53; 95% CI, 1.38 to 1.71; p < 0.001), 254 (43.6%) in the A+/T+ group (HR, 2.25; 95% CI, 1.97 to 2.56; p < 0.001). CONCLUSIONS: This longitudinal, population-level study emphasises the adverse long-term outcomes of preoperative anaemia and perioperative RBC transfusion. It stresses the importance of an evidence-based, multimodal, and multidisciplinary approach to conserving blood resources and optimising outcomes in patients at high risk for transfusion.

Body mass index effect on long-term survival after coronary artery bypass surgery: a competing risk analysis.

OBJECTIVES: The aim of this sudy was to investigate the presence of an obesity paradox on the long-term mortality of patients undergoing primary isolated coronary artery bypass surgery and to uncover whether any discrepancy found could be attributable to cardiovascular or noncardiovascular causes. METHODS: Retrospective analysis of 5242 consecutive patients with body mass index (BMI) over 18.5 kg/m2 undergoing primary isolated coronary artery bypass surgery, performed from 2000 to 2015, in a Portuguese level III Hospital. The primary end point was long-term all-cause mortality. Secondary outcomes were long-term cause-specific mortality (cardiovascular and noncardiovascular). We fitted overall, and cause-specific hazard models, with BMI forced both as a categorical (using World Health Organization predefined cutoffs) and as a continuous variable. RESULTS: Follow-up was 99.7% complete. The median follow-up time was 12.79 years (interquartile range, 9.51-16.61). The cumulative incidence functions failed to uncover any difference in 15-year all-cause (log-rank test, P = 0.400), cardiovascular (Gray's test, P = 0.996) and noncardiovascular mortality (Gray's test, P = 0.305) between BMI categories. Likewise, extensive multivariable-adjusted Cox regression and cause-specific hazards models failed to demonstrate in-between category differences, with BMI forced as a categorical variable. On the other hand, using BMI as a continuous variable, the model identified the optimal BMI as between 25.8 and 30.3 kg/m2 (nadir around 28.9 kg/m2), albeit this was dependent on the definition of the reference value. CONCLUSIONS: In this longitudinal, population-level analysis of patients undergoing isolated primary coronary artery bypass grafting, we could not attest to any protective effect of obesity on long-term survival.

Ventricular Pseudoaneurysm After Myocardial Infarction: A Case Report.

A 66-year-old female patient was admitted to hospital care in March 2021 due to aggravating fatigue and dyspnoea. Her past medical history was relevant for chronic anaemia, smoking, dyslipidaemia, antiphospholipid syndrome and lupus-like mixed connective tissue disease, for which she was taking corticosteroids. She had suffered an acute coronary syndrome in August 2020, complicated with postinfarction pericarditis; at the time, coronariography diagnosed moderate disease of the anterior descending artery and occlusion of the circumflex artery. Echocardiography showed a discontinuity in the lateral and posterior walls of the left ventricle to a thin walled, loculated cavity, with doppler blood flow (Figure 1). A diagnosis of pseudoaneurysm was assumed, and the patient was transferred to our centre for surgical treatment.

Hippocampal Hyperconnectivity to the Visual Cortex Predicts Treatment Response.

BACKGROUND: Converging lines of evidence point to hippocampal dysfunction in psychosis spectrum disorders, including altered functional connectivity. Evidence also suggests that antipsychotic medications can modulate hippocampal dysfunction. The goal of this project was to identify patterns of hippocampal connectivity predictive of response to antipsychotic treatment in 2 cohorts of patients with a psychosis spectrum disorder, one medication-naïve and the other one unmedicated. HYPOTHESIS: We hypothesized that we would identify reliable patterns of hippocampal connectivity in the 2 cohorts that were predictive of treatment response and that medications would modulate abnormal hippocampal connectivity after 6 weeks of treatment. STUDY DESIGN: We used a prospective design to collect resting-state fMRI scans prior to antipsychotic treatment and after 6 weeks of treatment with risperidone, a commonly used antipsychotic medication, in both cohorts. We enrolled 44 medication-naïve first-episode psychosis patients (FEP) and 39 unmedicated patients with schizophrenia (SZ). STUDY RESULTS: In both patient cohorts, we observed a similar pattern where greater hippocampal connectivity to regions of the occipital cortex was predictive of treatment response. Lower hippocampal connectivity of the frontal pole, orbitofrontal cortex, subcallosal area, and medial prefrontal cortex was predictive of treatment response in unmedicated SZ, but not in the medication-naïve cohort. Furthermore, greater reduction in hippocampal connectivity to the visual cortex with treatment was associated with better clinical response. CONCLUSIONS: Our results suggest that greater connectivity between the hippocampus and occipital cortex is not only predictive of better treatment response, but that antipsychotic medications have a modulatory effect by reducing hyperconnectivity.

Dorsal striatial hypoconnectivity predicts antipsychotic medication treatment response in first-episode psychosis and unmedicated patients with schizophrenia.

INTRODUCTION: The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico-striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response. METHODS: Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication-naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls). Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response. RESULTS: This dysconnectivity was also predictive of treatment response in both cohorts. DISCUSSION: These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico-striatal dysconnectivity.

Results of Surgery in Lung Cancer - A Retrospective Study of a Single Center Experience.

OBJECTIVES: Surgery provides the best chance for cure in patients with non-small-cell lung cancer stage I or II, but only a small portion of all new cases diagnosed are eventually suitable for surgical resection. Our goal was to appraise the surgical outcomes including survival and progression rates in patientswith histological diagnosis of lung cancer. METHODS: Between 1st August 2012 and 30th June 2018, the patients with histological lung cancer diagnosis that underwent surgical resection with a curative intent at the department of Cardiothoracic Surgery of Centro Hospitalar Univer- sitário de São João were included. RESULTS: The majority of patients were pathological stage I and the most performed surgery was a lobectomy (90.6%). The hospitality mortality was 1,3% and the rate of complication was 26,1%. Patients with forced expiratory volume in 1 second (FEV1) less than 80% had higher (statistically significant difference) frequency of complications. Active smokers, Eastern Co- operative Oncology Group Performance Status (ECOG PS)value different than 0 and FEV1 inferior to 80% had a higher mean length of drainage and higher mean length of stay (statistically significant difference). The overall survival was 92,6% at 1 year, 87,7 % in 2 years and 79,1% in 5 years. The overall survival according to pathological stages were similar when compared with the literature. CONCLUSIONS: Ours results are similar to international centers and we should be more alert to preoperative assessment.

Long-term survival of female versus male patients after coronary artery bypass grafting.

BACKGROUND: Several of the most extensively used risk prediction tools for coronary artery bypass grafting outcomes include female sex as an independent risk factor for postoperative outcomes. It is not clear whether this putative increased surgical risk impacts long-term survival. This study aimed to assess sex differences in 10-year all-cause mortality. METHODS: Retrospective analysis of 5340 consecutive patients undergoing primary isolated coronary artery bypass surgery, performed from 2000 to 2015, in a Portuguese level III Hospital. The primary endpoint was all-cause mortality at ten years. We employed an overlap weighting algorithm to minimize confounding. Its target population highlights patients with the most overlap in their observed characteristics, and its corresponding estimand is the average treatment effect in the overlap population. RESULTS: We identified that 5340 patients underwent isolated CABG: 1104 (20.7%) were female, and 4236 (79.3%) were male. Sixteen patients were lost to follow-up (0.3%). The median follow-up time was 12.79 (IQR, 9.52-16.66) years: 12.68 (IQR, 9.48-16.54) years for the male patient group and 13.13 (IQR, 9.75-16.98) years for the female patient group. The primary endpoint of all-cause mortality at ten years occurred in 1106 patients (26.1%) in the male patient group, compared with 315 (28.5%) in the female patient group. The unweighted survival analysis for both groups reveals the worst long-term prognosis for the female cohort (hazard ratio, 1.22; 95% CI, 1.10 to 1.35; p < 0.001), while in the overlap weighted survival analysis, such long-term difference in prognosis disappears (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; p = 0.693). CONCLUSION: In this longitudinal, population-level analysis of patients undergoing primary, isolated CABG, we demonstrated that the female sex is not associated with increased long-term all-cause mortality compared to their male counterparts. Thus, sex should not influence the undertaking of an adequate revascularization strategy.

An overlap-weighted analysis on 10-year survival of off-pump versus on-pump coronary artery grafting in multivessel coronary artery disease.

BACKGROUND AND OBJECTIVE: The introduction of off-pump coronary artery bypass surgery intended to overcome some of the conventional on-pump procedure limitations by avoiding potentially harmful adverse effects of extracorporeal circulation and aortic cross-clamping. However, the doubt remains on whether it is associated with worse long-term outcomes. To compare long-term survival in patients with multivessel ischemic heart disease undergoing off-pump versus on-pump coronary artery bypass grafting. METHODS: Retrospective analysis of 4788 consecutive patients undergoing primary isolated multivessel coronary artery bypass grafting surgery, performed from 2000 to 2015, in Northern Portugal. Among the study population, we identified 1616 and 3172 patients that underwent off-pump and on-pump coronary artery grafting, respectively. We employed a propensity-score-based overlap weighting (OW) algorithm to restrict confounding by indication. The primary endpoint was all-cause mortality at 10 years. RESULTS: The mean age of the study population was 63.9 (±9.8) years, and 951 (19.9%) were females. OW was effective in eliminating differences in all major baseline characteristics. Follow-up was 100% complete. The median follow-up time was 12.80 (9.62, 16.62) years. The primary endpoint of all-cause mortality at 10 years occurred in 431 patients (26.7%) in the off-pump group, as compared with 863 (27.2%) in the on-pump group (hazard ratio, 0.93; 95% confidence interval, 0.83-1.04; p = .196). CONCLUSIONS: In this longitudinal, population-level comparison of off-pump versus on-pump coronary artery bypass surgery for treating multivessel coronary artery disease, the primary outcome of long-term mortality was identical among both patients' groups.

Long-term survival of single versus bilateral internal mammary artery grafting in patients under 70.

OBJECTIVES: As definitive data from randomized controlled trials comparing the effect on long-term survival of using single internal mammary artery (SIMA) or bilateral internal mammary artery (BIMA) grafting are not yet available, observational studies allow for long-term follow-up in large and representative populations, which might complement the information potentially derived from randomized trials. To compare long-term survival in patients under 70 years of age undergoing SIMA or BIMA grafting. METHODS: Retrospective analysis of 3384 consecutive patients under 70 years undergoing primary isolated coronary artery bypass grafting, performed from 2000 to 2015, in a Portuguese level III Hospital. We identified 2176 and 1208 patients from the study population who underwent SIMA and BIMA grafting, respectively. The primary end point was all-cause mortality at 10 years. We employed inverse probability weighting to restrict confounding by indication. RESULTS: The mean age of the study population was 59.4 (± 7.6) years, and 567 (16.8%) were females. Inverse probability weighting was effective in eliminating differences in all significant baseline characteristics. Follow-up was 99.88% complete. The median follow-up time was 12.82 (interquartile range, 9.65, 16.74) years: the primary end point of all-cause mortality at 10 years occurred in 463 patients (21.3%) and 166 (13.7%) in the SIMA and BIMA grafting groups, respectively (hazard ratio, 0.78; 95% confidence interval, 0.66-0.92; P = 0.004). CONCLUSIONS: Bilateral internal mammary grafting is associated with lower long-term mortality than single internal mammary grafting. Moreover, this survival benefit comes at no increased perioperative morbidity or mortality cost.

Contrasting Frontoparietal Network Connectivity in Antipsychotic Medication-Naive First-Episode Psychosis Patients Who Do and Do Not Display Features of the Deficit Syndrome.

BACKGROUND: The deficit syndrome is a clinical subtype of schizophrenia that is characterized by enduring negative symptoms. Several lines of evidence point to frontoparietal involvement, but the frontoparietal control network (FPCN) and its subsystems (FPCNA and FPCNB) proposed by Yeo et al. have not been systematically characterized at rest in patients with the deficit syndrome. METHODS: We used resting-state fMRI to investigate the FPCN and its subnetworks in 72 healthy controls and 65 antipsychotic medication-naive, first-episode psychosis patients (22 displayed deficit syndrome features, 43 did not). To assess whole-brain FPCN connectivity, we used the right posterior parietal cortex as the seed region. We then performed region of interest analyses in FPCN subsystems. RESULTS: We found that patterns of FPCN dysconnectivity to the whole brain differed in patients who displayed deficit syndrome features compared with those who did not. Examining the FPCN on a more granular level revealed reduced within-FPCN(A) connectivity only in patients displaying deficit features. FPCNB connectivity did not differ between patient groups. DISCUSSION: Here, we describe a neurobiological signature of aberrant FPCN connectivity in antipsychotic-naive, first-episode patients who display clinical features of the deficit syndrome. Importantly, frontoparietal subnetwork connectivity differentiated subgroups, where the FPCNA is selectively involved in patients with deficit features. Our findings add to the growing body of literature supporting a neurobiological distinction between two clinical subtypes of schizophrenia, which has the potential to be leveraged for patient stratification in clinical trials and the development of novel treatments.

Traumatic Aortic Valve Injury After Blunt Chest Trauma.

Traumatic aortic valve regurgitation is a rare but potentially fatal complication of blunt chest trauma. We present the case of a 68-year-old woman who suffered from severe traumatic aortic valve regurgitation after a car accident. The patient was successfully treated by surgical replacement of the aortic valve with a biologic prosthesis.

Infective aortitis after self-expanding transcatheter valve implantation: a case report of a new reality for cardiac surgeons.

A 62-year-old female patient was admitted to hospital care due to an ischaemic stroke and fever of unknown origin, 6 months after a transfemoral aortic valve implantation for symptomatic aortic stenosis. Further study resulted in the diagnosis of infective aortitis, and clinical course deemed prosthesis explantation necessary. In this case report, we describe the technique used to explant the partially endothelized aortic valve and review the alternatives found in literature for safe prosthesis removal.

Hippocampal Dysconnectivity and Altered Glutamatergic Modulation of the Default Mode Network: A Combined Resting-State Connectivity and Magnetic Resonance Spectroscopy Study in Schizophrenia.

BACKGROUND: Converging lines of evidence point to hippocampal dysfunction in schizophrenia. It is thought that hippocampal dysfunction spreads across hippocampal subfields and to cortical regions by way of long-range efferent projections. Importantly, abnormalities in the excitation/inhibition balance could impair the long-range modulation of neural networks. The goal of this project was twofold. First, we sought to identify replicable patterns of hippocampal dysconnectivity in patients with a psychosis spectrum disorder. Second, we aimed to investigate a putative link between glutamatergic metabolism and hippocampal connectivity alterations. METHODS: We evaluated resting-state hippocampal functional connectivity alterations in two cohorts of patients with a psychosis spectrum disorder. The first cohort consisted of 55 medication-naïve patients with first-episode psychosis and 41 matched healthy control subjects, and the second cohort consisted of 42 unmedicated patients with schizophrenia and 41 matched control subjects. We also acquired measurements of glutamate + glutamine in the left hippocampus using magnetic resonance spectroscopy for 42 patients with first-episode psychosis and 37 healthy control subjects from our first cohort. RESULTS: We observed a pattern of hippocampal functional hypoconnectivity to regions of the default mode network and hyperconnectivity to the lateral occipital cortex in both cohorts. We also show that in healthy control subjects, greater hippocampal glutamate + glutamine levels predicted greater hippocampal functional connectivity to the anterior default mode network. Furthermore, this relationship was reversed in medication-naïve subjects with first-episode psychosis. CONCLUSIONS: These results suggest that an alteration in the relationship between glutamate and functional connectivity may disrupt the dynamic of major neural networks.

Salience network glutamate and brain connectivity in medication-naïve first episode patients - A multimodal magnetic resonance spectroscopy and resting state functional connectivity MRI study.

BACKGROUND: Salience network (SN) connectivity is altered in schizophrenia, but the pathophysiological origin remains poorly understood. The goal of this multimodal neuroimaging study was to investigate the role of glutamatergic metabolism as putative mechanism underlying SN dysconnectivity in first episode psychosis (FEP) subjects. METHODS: We measured glutamate + glutamine (Glx) in the dorsal anterior cingulate cortex (dACC) from 70 antipsychotic-naïve FEP subjects and 52 healthy controls (HC). The dACC was then used as seed to define positive and negative resting state functional connectivity (FC) of the SN. We used multiple regression analyses to test main effects and group interactions of Glx and FC associations. RESULTS: dACC Glx levels did not differ between groups. Positive FC was significantly reduced in FEP compared to HC, and no group differences were found in negative FC. Group interactions of Glx-FC associations were found within the SN for positive FC, and in parietal cortices for negative FC. In HC, higher Glx levels predicted greater positive FC in the dACC and insula, and greater negative FC of the lateral parietal cortex. These relationships were weaker or absent in FEP. CONCLUSIONS: Here, we found that positive FC in the SN is already altered in medication-naïve FEP, underscoring the importance of considering both correlations and anticorrelations for characterization of pathology. Our data demonstrate that Glx and functional connectivity work differently in FEP than in HC, pointing to a possible mechanism underlying dysconnectivity in psychosis.