Background/Objectives: Pre-operative radiation (Pre-RT) decreases local recurrence following soft tissue sarcoma (STS) resection but carries the risk of wound healing complications (WHCs). This study evaluated skin specimens and clinical characteristics of STS patients to (1) compare patients with and without Pre-RT, (2) compare Pre-RT patients with and without WHCs, and (3) explore associations between clinical characteristics and WHCs. Methods: This retrospective study included 54 adults who underwent STS resection with primary closure (Pre-RT n = 30). A pathologist who was blinded to the clinical outcomes evaluated the skin specimens microscopically. Results: Irradiated skin had lower vessel density and was more likely to lack hair follicles and sebaceous glands, consistent with the effects of radiation. Irradiated skin was also more likely to include plasma cells. Irradiated skin demonstrated higher mean TAZ H-scores; however, within the Pre-RT subset, those patients who developed WHCs demonstrated comparatively lower TAZ. Conclusions: This novel finding may suggest that higher TAZ in irradiated skin reflects a response to injury but that comparatively lower TAZ in irradiated skin might contribute to WHCs. Future studies should consider more focused evaluation of TAZ in STS resections with Pre-RT as they may help to predict WHCs when used in combination with other histologic factors and could suggest a therapeutic target.

BACKGROUND Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. OBSERVATIONS A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as “glioneuronal tumor kinase-fused” (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. LESSONS This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.

BACKGROUND:Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. OBSERVATIONS:A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as "glioneuronal tumor kinase-fused" (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. LESSONS:This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.

BACKGROUND Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. OBSERVATIONS A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as “glioneuronal tumor kinase-fused” (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. LESSONS This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.

Cervical spine manipulation is a known risk factor for vertebral artery dissection. In this report, we present a case of fatal vertebral artery dissection that occurred as the result of self-manipulation of the cervical spine. The decedent was a 40-year-old man with no significant past medical history. He was observed to "crack his neck" while at work. Soon after, he began experiencing neck pain, then developed strokelike symptoms and became unresponsive. He was transported to a local medical center, where imaging showed bilateral vertebral artery dissection. His neurological status continued to decline, and brain death was pronounced several days later. An autopsy examination showed evidence of cerebellar and brainstem infarcts, herniation, and diffuse hypoxic-ischemic injury. A posterior neck dissection was performed to expose the vertebral arteries, which showed grossly visible hemorrhage and dilation. There was no evidence of traumatic injury to the bone or soft tissue of the head or neck. Bilateral dissection tracts were readily appreciated on microscopic examination. Death was attributed to self-manipulation of the neck, which in turn led to bilateral vertebral artery dissection, cerebellar and brainstem infarcts, herniation, hypoxic-ischemic injury, and ultimately brain death.

Journal Article Ready, Set, Screen: The Role of the Clinical Laboratory in Eliminating Chronic Hepatitis B Infection Get access Jane E Persons, Jane E Persons Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States https://orcid.org/0000-0002-2393-6886 Search for other works by this author on: Oxford Academic Google Scholar Anna E Merrill Anna E Merrill Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States Address correspondence to this author at: Department of Pathology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242, United States. E-mail anna-merrill@uiowa.edu. https://orcid.org/0000-0002-5945-5937 Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 70, Issue 3, March 2024, Pages 567–568, https://doi.org/10.1093/clinchem/hvad208 Published: 02 March 2024 Article history Received: 06 October 2023 Accepted: 02 November 2023 Published: 02 March 2024

Objectives. To examine sudden and unexpected or trauma-related deaths that occurred in the presence of law enforcement in Johnson County, Iowa, between 2011 and 2020. Methods. We identified deaths in the presence of law enforcement using definitions from the National Association of Medical Examiners. We obtained data, including demographics, cause and manner of death, toxicology results, and circumstances and location of event leading to death, from comprehensive medical examiner investigative reports. Results. There were 165 deaths that occurred in the presence of law enforcement: 114 were from a known disease, and 51 were either trauma related or the sudden, unexpected initial presentation of a previously unrecognized disease. Three deaths occurred in the context of physical restraint by law enforcement. Suicide was the leading manner of death among trauma-related deaths; the means of suicide was predictable based on in-custody (hanging) or precustody (firearm) circumstances. Conclusions. Our findings highlight the potential role of medical examiners and coroners in improving completeness of data on reporting death in the presence of law enforcement to public health agencies. ( Am J Public Health. 2024;114(6):642–650. https://doi.org/10.2105/AJPH.2024.307616 )

ABSTRACT In this report, we present an unusual and multifactorial case of severe hyponatremia with important clinical implications. The decedent was a 42-year-old woman who was discovered at her place of residence with altered mental status and profuse watery diarrhea. The scene was significant for numerous empty water bottles. She was transported to the emergency department of a local medical center and rapidly became obtunded. Imaging demonstrated cerebral edema with impending herniation. Serum chemistry was significant for severe hyponatremia (116 mEq/L) with decreased serum osmolality (245 mOsm/kg), suggestive of water overload. Over a brief course of hospitalization, she continued to deteriorate and brain death was pronounced. After brain death, she underwent organ donation. Subsequent autopsy examination demonstrated global cerebral edema with evidence of herniation. Toxicology examination of antemortem blood was positive for methamphetamine (1900 ng/mL) and amphetamine (100 ng/mL). An incidentally identified colon polyp was submitted for microscopic evaluation, which revealed the presence of Cryptosporidium, the likely cause of her diarrheal illness. Death was attributed to severe hyponatremia through the combined effects of excessive water consumption and loss of fluid and electrolytes from cryptosporidiosis, in turn leading to cerebral edema and brain herniation. Acute methamphetamine intoxication was a contributing condition.

Methamphetamine is a psychostimulant that exerts its euphoric and stimulant effects by increasing cytosolic monoamine concentration at the nerve terminal. In addition to its known systemic cardiovascular effects, there is compelling evidence to suggest a direct neurotoxic effect of methamphetamine; however, the existing body of literature includes very few human tissue studies. This exploratory analysis used postmortem human brain specimens to examine histologic and immunohistochemical features associated with chronic methamphetamine use. This retrospective cohort study included 60 decedents who were autopsied at the University of Iowa Hospitals and Clinics between the years 2015 and 2021. Logistic regression models demonstrated no definite pathologic changes in the hippocampi of individuals with a history of chronic methamphetamine use. Decedents with a history of methamphetamine use had a marginally increased odds of basal ganglia arteriosclerosis, which did not reach statistical significance (odds ratio, 3.33; 95% confidence interval, 0.6-19.2; P = 0.17), which may be independent of the systemic hypertensive effects of methamphetamine. Future studies that include targeted examination of brain regions of interest, such as the basal ganglia and specifically the striatum, may prove revealing.

Bipolar disorder is typified by episodes of manic/hypomanic and depressive symptoms, either distinctly or concurrently as mixed symptoms. While depressive symptoms are the major driver of risk, it is unclear whether specific combinations of manic and anxiety symptoms contribute differentially to suicidal ideation and behavior in individuals with bipolar disorder during a depressive state. This study uses a quantitative application of Rothman's theoretical framework of causation, or 'causal pies' model. Data were obtained from the National Network of Depression Centers Mood Outcomes Program for 1028 visits from 626 individuals with bipolar disorder with current moderate-to-severe depressive symptoms, operationalized as a Patient Health Questionnaire-8 (PHQ-8) score ≥10. Mania symptoms were captured using the Altman Self-Rating Mania scale (ASRM) and anxiety symptoms were captured using the Generalized Anxiety Disorder-7 scale (GAD-7). The outcome of suicidal ideation or behavior was captured using the Columbia Suicide Severity Rating Scale (C-SSRS). In this cohort of individuals with bipolar disorder and at least moderate depressive symptoms, we found no increased risk of suicidal ideation or behavior attributable to manic and anxiety symptom clusters in individuals with bipolar disorder during depressive state. A small amount (4%) of risk was attributable to having severe depressive symptoms. These findings, however, may be influenced by limitations in sample size and measurement instruments. Future studies would benefit from larger samples and more rigorous assessments, including clinician-rated measures.

OBJECTIVE:Acceptance and Commitment Therapy (ACT) is a behavioral intervention demonstrating sustained improvements in anxiety in individuals with chronic anxiety and psychological distress. Because anxiety disorders are associated with the development of cardiovascular disease (CVD), we hypothesized that a novel 1-day ACT workshop would both lower anxiety and improve vascular function in persons with moderate/high anxiety. METHODS:In a randomized controlled study, 72 adults (age 33.9 ± 8.6 (SD) years) with baseline moderate/high anxiety completed a one-day ACT intervention (n = 44, age 33.9 ± 8.7 years) or control (n = 28, age 37.1 ± 10.1 years). Pre-specified secondary outcomes were measured over 12 weeks: aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]), forearm vascular endothelial function (post-ischemic peak forearm blood flow [FBF] via plethysmography), and brachial artery flow-mediated dilation (FMD). Carotid artery stiffness (β-stiffness index), and inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) were also explored. RESULTS:Although the intervention had a significant and sustained effect on the primary outcome of anxiety as measured by the Beck Anxiety Inventory, the 1-day ACT workshop was not associated with improvement in vascular or inflammatory endpoints. The intervention was unexpectedly associated with increases in β-stiffness index that were also associated with changing trait anxiety. CONCLUSION:Anxiety improvements did not translate into improvements in any of the vascular function outcomes. This may reflect a less-than-robust effect of the intervention on anxiety, failure in design to select those with vascular dysfunction, or not intervening on a relevant causal pathway. (Trial registration NCT02915874 at www.clinicaltrials.gov).

BACKGROUND:It has not been established that suicide risk with mixed symptoms is any greater than the depressive component or if there is synergy between depressive and manic symptoms in conveying suicide risk.METHODS:The National Network of Depression Centers Mood Outcomes Program collected data from measurement-based care for 17,179 visits from 6,105 unique individuals with clinically diagnosed mood disorders (998 bipolar disorder, 5,117 major depression). The Patient Health Questionaire-8 (PHQ-8) captured depressive symptoms and the Altman Self-Rating Mania scale (ASRM) measured hypomanic/manic symptoms. Generalized linear mixed models assessed associations between depressive symptoms, manic symptoms, and their interaction (to test for synergistic effects of mixed symptoms) on the primary outcome of suicidal ideation or behavior (secondarily suicidal behavior only) from the Columbia-Suicide Severity Rating Scale (C-SSRS). Moderation was assessed.RESULTS:PHQ-8 scores were strongly associated with suicide-related outcomes across diagnoses. ASRM scores showed no association with suicidal ideation/behavior in bipolar disorder and an inverse association in major depression. There was no evidence of synergy between depressive and manic symptoms. There was no moderation by sex, race, or mood disorder polarity. Those over 55 years of age showed a protective effect of manic symptoms, which was lost when depressive symptoms were also present (mixed symptoms).DISCUSSION:Mixed depressive and manic symptoms convey no excess risk of suicidal ideation or behavior beyond the risk conveyed by the depressive symptoms alone. Depressive symptoms are strongly linked to suicidal ideation and suicidal behavior and represent an important and potentially modifiable risk factor for suicide.

Objectives: Suicide is an ongoing public health problem in the United States. The purpose of this epidemiologic investigation was to characterize and identify populations at risk of suicide, which in turn may lead to targeted intervention and improvements in suicide prevention. Study design: This is a descriptive analysis of 657 suicide decedents autopsied by the University of Iowa Hospitals and Clinics between 7/1/2003 and 6/30/2018 (180 months, 15 years). Methods: Data were obtained via autopsy report abstraction. Chi-squared tests were used for categorical variables and Wilcoxon rank-sum tests were used for continuous variables. Statistical analyses were conducted using SAS 9.3. Results: Decedents were primarily white (88.2%) and male (75.7%). Average age was 43 years. Suicides were more likely to occur at a residence (69.3%), earlier in the week, and in the late night to early morning hours. Suicides were most likely to occur in spring and least likely to occur in winter. The most common method was a firearm (44.6%), most often a handgun (61.3% of firearm suicides). Less than one-half (42.8%) of decedents communicated intent to end their life. Approximately one-quarter (22.1%) of suicides were without a known identified life stressor or a known inciting event, a phenomenon that was markedly more common among men. Conclusions: More than one-half of decedents left no communication of intent to commit suicide, and one-quarter-more commonly men-had no known life stressor or other specifically identified motivating factor. While women were more likely to have a known mental health condition, prior contact with mental health care, or prior suicidal behavior, we found that, statistically speaking, the typical profile of a completed suicide is a white male who used a firearm in his place of residence. Future studies should seek to further elucidate factors leading to suicide in this at-risk population. (C) 2019 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The inflammatory marker C-reactive protein has been linked to anxiety across a number of studies. This paper uses data for 1,439 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2004 to examine the association between anxiety and C-reactive protein (CRP), and the potential for moderation by body mass index. No association was found between anxiety or depression and CRP in unadjusted or multivariable-adjusted logistic regression analyses, nor was there evidence of moderation by continuous BMI, BMI class, or obesity. Future studies on the relationship between anxiety and CRP should utilize larger general population samples or populations with a high prevalence of anxiety. There is also a need for prospective studies in this area to better discern the temporal relationships between anxiety and inflammation.