Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years.

Pediatric to adult primary care transition for medically complex youth: A tale of learning from challenges experienced implementing a pilot project during COVID-19.

Purpose: The aim of our article is to describe our learning based on challenges encountered implementing two related pediatric to adult primary care transition pilots for medically complex adolescents and young adults as part of the Children with Medical Complexity Collaborative for Improvement and Innovation Network.

Design: We undertook two sequential pilot projects. The first focused on supporting the transfer stage for an older group of medically complex young adults to facilitate their establishment with an adult primary care provider.

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans ( = 374 at baseline and = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; = 275), brain morphology (hippocampal subfield volume and cortical thickness; = 280), neurocognitive functioning ( = 337), and genetic variation ( = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI.

For whom the bell tolls: psychopathological and neurobiological correlates of a DNA methylation index of time-to-death.

Psychopathology is a risk factor for accelerated biological aging and early mortality. We examined associations between broad underlying dimensions of psychopathology (reflecting internalizing and externalizing psychiatric symptoms), PTSD, and age-adjusted GrimAge ("GrimAge residuals"), a DNA methylation biomarker of mortality risk relative to age. We also examined neurobiological correlates of GrimAge residuals, including neurocognitive functioning, blood-based biomarkers (of inflammation, neuropathology, metabolic disease), and cortical thickness.

Photodermatitis following knee intra-articular hylan G-F 20 injection for osteoarthritis: two cases.

Hyaluronic acid (HA) intra-articular injections are increasingly used for the treatment of knee osteoarthritis. Described adverse reactions of HA intra-articular injections include injection site pain or swelling. A 71-year-old man and a 65-year-old woman independently presented with photodistributed lesions shortly after receiving a repeat HA injection (hylan G-F 20) intra-articularly.

Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume.

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures.

A novel program to enhance pediatric emergency medicine training in Thailand.

Background: In Thailand, there are few pediatric emergency medicine (PEM) fellowship-trained providers, and emergency departments (EDs) are staffed by pediatricians and emergency physicians. Our pediatric ED collaborated with Thailand's largest private hospital system to develop a training program designed to improve emergency care for children.

Objective: The objective was to develop, implement, and assess the efficacy of a curriculum to improve PEM care by emergency providers in a Thai health system.

Progression-free survival by investigator versus blinded independent central review in newly diagnosed patients with high-grade serous ovarian cancer: Analysis of the VELIA/GOG-3005 trial.

Objective: In the phase 3 VELIA/GOG-3005 trial, veliparib added to carboplatin-paclitaxel and continued as maintenance improved progression-free survival (PFS) compared to carboplatin-paclitaxel alone in patients with newly diagnosed ovarian carcinoma. Primary analysis of PFS was by investigator (INV) assessment, with a supplemental analysis of PFS by blinded independent central review (BICR).

Methods: Patients received veliparib or placebo with carboplatin-paclitaxel (6 cycles) and as maintenance (30 additional cycles).

Apolipoprotein E (APOE) ε4 moderates the relationship between c-reactive protein, cognitive functioning, and white matter integrity.

Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle-aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -0.

Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population.

Apolipoprotein E () ε4 Status Moderates the Relationship Between Close-Range Blast Exposure and Cognitive Functioning.

Objectives: Recent studies suggest that close-range blast exposure (CBE), regardless of acute concussive symptoms, may have negative long-term effects on brain health and cognition; however, these effects are highly variable across individuals. One potential genetic risk factor that may impact recovery and explain the heterogeneity of blast injury's long-term cognitive outcomes is the inheritance of an apolipoprotein (APOE) ε4 allele, a well-known genetic risk factor for Alzheimer's disease. We hypothesized that APOE ε4 carrier status would moderate the impact of CBE on long-term cognitive outcomes.

Interpersonal early life trauma is associated with increased cerebral perfusion and poorer memory performance in post-9/11 veterans.

Background: Cerebral blood flow (CBF) is critically important in the overall maintenance of brain health, and disruptions in normal flow have been linked to the degradation of the brain's structural integrity and function. Recent studies have highlighted the potential role of CBF as a link between psychiatric disorders and brain integrity. Although interpersonal early life trauma (IP-ELT) is a risk factor for the development of psychiatric disorders and has been linked to disruptions in brain structure and function, the mechanisms through which IP-ELT alters brain integrity and development remain unclear.

Cerebral perfusion is associated with blast exposure in military personnel without moderate or severe TBI.

Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion.

Shorter survival and later stage at diagnosis among unmarried patients with cutaneous melanoma: A US national and tertiary care center study.

Background: Addressing risk factors of delayed melanoma detection minimizes disparities in outcome.

Objective: To elucidate the significance of marital status in melanoma outcomes across anatomic sites.

Methods: Retrospective cohort study of 73,558 patients from the Surveillance, Epidemiology, and End Results (SEER) program and 2992 patients at Johns Hopkins University.

Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial.

Importance: Neoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer.

Objectives: To prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC).

Design, Setting, And Participants: This prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia.

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium).

Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial.

Introduction: The ability of breast magnetic resonance imaging (MRI) to predict pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) varies across biological subtypes. We sought to determine how well breast MRI findings following initial treatment on the phase III BrighTNess trial correlated with pCR in patients with triple negative breast cancer (TNBC).

Methods: Baseline and mid-treatment imaging and pathologic response data were available in 519 patients with stage II-III TNBC who underwent NST as per protocol.

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer.

Background: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma.

Methods: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout).

The PPM1F gene moderates the association between PTSD and cortical thickness.

Background: Evidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in serotonergic signaling and stress response pathways moderate associations between PTSD and cortical thickness. This study examined a genetic regulator of these pathways, the PPM1F gene, which has also been implicated in mechanisms of stress responding and is differentially expressed in individuals with comorbid PTSD and depression compared to controls.

Methods: Drawing from a sample of 240 white non-Hispanic trauma-exposed veterans, we tested 18 SNPs spanning the PPM1F gene for association with PTSD and cortical thickness.

Correction: A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.

The original version of this article contained an error in Figure 1a. The number of patients at risk listed in the Veliparib arm of Figure 1a should have read "65" instead of "35".An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Close-Range Blast Exposure Is Associated with Altered White Matter Integrity in Apolipoprotein ɛ4 Carriers.

Evidence suggests that blast exposure has profound negative consequences for the health of the human brain, and that it may confer risk for the development of neurodegenerative diseases such as chronic traumatic encephalopathy and Alzheimer's disease (AD). Although the molecular mechanisms linking blast exposure to subsequent neurodegeneration is an active focus of research, recent studies suggest that genetic risk for AD may elevate the risk of neurodegeneration following traumatic brain injury (TBI). However, it is currently unknown if blast exposure also interacts with AD risk to promote neurodegeneration.