Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Pulmonary artery capacitance is a relatively novel measurement associated with adverse outcomes in pulmonary arterial hypertension. We sought to determine if preoperative indexed pulmonary artery capacitance was related to outcomes in paediatric heart transplant recipients, describe the changes in indexed pulmonary artery capacitance after transplantation, and compare its discriminatory ability to predict outcomes as compared to conventional predictors.

This was a retrospective study of paediatric patients who underwent heart transplant at our centre from July 2014 to May 2022. Variables from preoperative and postoperative clinical, catheterisation, and echo evaluations were recorded. The primary composite outcome measure included postoperative mortality, postoperative length of stay in the top quartile, and/or evidence of end organ dysfunction.

Of the 23 patients included in the analysis, 11 met the composite outcome. There was no statistical difference between indexed pulmonary artery capacitance values in patients who met the composite outcome [1.8 ml/mmHg/m2 (interquartile 0.8, 2.4)] and those who did not [1.4 (interquartile 0.9, 1.7)], p = 0.17. There were no significant signs of post-operative right heart failure in either group. There was no significant difference between pre-transplant and post-transplant indexed pulmonary artery capacitance or indexed pulmonary vascular resistance.

Preoperative pulmonary artery capacitance was not associated with our composite outcome in paediatric heart transplant recipients. It did not appear to be additive to pulmonary vascular resistance in paediatric heart transplant patients. Pulmonary vascular disease did not appear to drive outcomes in this group.

Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Whole genome sequencing (WGS) can help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time intensive. Given recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource approach providing accurate WGS-pathogen comparison within a time frame allowing for infection prevention and control (IPC) interventions.

WGS was prospectively performed on pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecaller. Potential transmission was assessed via Ridom SeqSphere+ for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cutoff values. The accuracy of our ONT pipeline was determined relative to Illumina.

Over a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold standard, our ONT pipeline achieved a mean identity score of Q60 for assembled genomes, even with a coverage rate as low as 40×. The mean time from initiating DNA extraction to complete analysis was 2 days (IQR 2–3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of sequenced strains). Integrating ONT with epidemiological data, >70% (15/21) of putative transmission cluster isolates originated from patients with potential healthcare transmission links.

Via a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in IPC efforts.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

We conducted a quantitative analysis of the microbial burden and prevalence of epidemiologically important pathogens (EIP) found on long-term care facilities (LTCF) environmental surfaces.

Microbiological samples were collected using Rodac plates (25cm2/plate) from resident rooms and common areas in five LTCFs. EIP were defined as MRSA, VRE, C. difficile and multidrug-resistant (MDR) Gram-negative rods (GNRs).

Rooms of residents with reported colonization had much greater EIP counts per Rodac (8.32 CFU, 95% CI 8.05, 8.60) than rooms of non-colonized residents (0.78 CFU, 95% CI 0.70, 0.86). Sixty-five percent of the resident rooms and 50% of the common areas were positive for at least one EIP. If a resident was labeled by the facility as colonized with an EIP, we only found that EIP in 30% of the rooms. MRSA was the most common EIP recovered, followed by C. difficile and MDR-GNR.

We found frequent environmental contamination with EIP in LTCFs. Colonization status of a resident was a strong predictor of higher levels of EIP being recovered from his/her room.

Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours lacking a standardised timeline for treatment initiation post-diagnosis. Delays beyond 60 days are linked to poorer outcomes and higher recurrence risk.

A retrospective review was conducted on patients over 18 with HNSCC treated with (chemo)radiation at a rural tertiary care centre (September 2020–2022). Data on patient demographics, oncologic characteristics, treatment details and delay causes were analysed using SPSS.

Out of 93 patients, 35.5% experienced treatment initiation delays (TTIs) over 60 days. Median TTI was 73 days for delayed cases, compared to 41.5 days otherwise. No significant differences in demographics or cancer characteristics were observed between groups. The primary reasons for the delay were care coordination (69.7%) and patient factors (18.2%). AJCC cancer stage showed a trend towards longer delays in advanced stages.

One-third of patients faced delayed TTI, primarily due to care coordination and lack of social support. These findings highlight the need for improved multidisciplinary communication and patient support mechanisms, suggesting potential areas for quality improvement in HNSCC treatment management.

In decision-making, especially for sustainability, choosing the right assessment tools is crucial but challenging due to the abundance of options. A new method is introduced to streamline this process, aiding policymakers and managers. This method involves four phases: scoping, cataloging, selection, and validation, combining data analysis with stakeholder engagement. Using the food system as an example, the approach demonstrates how practitioners can select tools effectively based on input variables and desired outcomes to address sustainability risks. This method can be applied across various sectors, offering a systematic way to enhance decision-making and manage sustainability effectively.

Decision making frequently entails the selection and application of assessment tools. For sustainability decisions there are a plethora of tools available for environmental assessment, yet no established and clear approach to determine which tools are appropriate and resource efficient for application. Here we present an extensive inventory of tools and a novel taxonomic method which enables efficient, effective tool selection to improve decision making for policymakers and managers. The tool selection methodology follows four main phases based on the divergence-convergence logic; a scoping phase, cataloging phase, selection phase and validation phase. This approach combines elements of data-driven analysis with participatory techniques for stakeholder engagement to achieve buy-in and to ensure efficient management of progress and agile course correction when needed. It builds on the current limited range and scope of approaches to tool selection, and is flexible and Artificial Intelligence-ready in order to facilitate more rapid integration and uptake. Using the food system as a case study, we demonstrate how practitioners can use available input variables and desired output metrics to select the most appropriate tools to manage sustainability risks, with the approach having wide applicability to other sectors.

New method simplifies tool selection for sustainable decisions, aiding policymakers & managers. #Sustainability #DecisionMaking

Identifying thrombus formation in Fontan circulation has been highly variable, with reports between 17 and 33%. Initially, thrombus detection was mainly done through echocardiograms. Delayed-enhancement cardiac MRI is emerging as a more effective imaging technique for thrombus identification. This study aims to determine the prevalence of occult cardiac thrombosis in patients undergoing clinically indicated cardiac MRI.

A retrospective chart review of children and adults in the Duke University Hospital Fontan registry who underwent delayed-enhancement cardiac MRI. Individuals were excluded if they never received a delayed-enhancement cardiac MRI or had insufficient data. Demographic characteristics, native heart anatomy, cardiac MRI measurements, and thromboembolic events were collected for all patients.

In total, 119 unique individuals met inclusion criteria with a total of 171 scans. The median age at Fontan procedure was 3 (interquartile range 1, 4) years. The majority of patients had dominant systemic right ventricle. Cardiac function was relatively unchanged from the first cardiac MRI to the third cardiac MRI. While 36.4% had a thrombotic event by history, only 0.5% (1 patient) had an intracardiac thrombus detected by delayed-enhancement cardiac MRI.

Despite previous echocardiographic reports of high prevalence of occult thrombosis in patients with Fontan circulation, we found very low prevalence using delayed-enhancement cardiac MRI. As more individuals are reaching adulthood after requiring early Fontan procedures in childhood, further work is needed to develop thrombus-screening protocols as a part of anticoagulation management.

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally.

We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation.

Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups

The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Profiling patients on a proposed ‘immunometabolic depression’ (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.

Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001–0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01–0.22, I2 = 23.91%), with a higher – but still small – effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.

Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.