Post-discharge Mental Healthcare and Emergency General Surgery Readmission for Patients with Serious Mental Illness.

OBJECTIVE: To determine the association between post-discharge mental healthcare and odds of readmission after emergency general surgery (EGS) hospitalization for patients with serious mental illness (SMI). BACKGROUND DATA: A mental health visit (MHV) after medical hospitalization is associated with decreased readmissions for patients with SMI. The impact of a MHV after surgical hospitalization is unknown. METHODS: Using Medicare claims, we performed a retrospective cohort study of hospitalized EGS patients with SMI aged >65.5 (2016-2018). EGS included colorectal, general abdominal, hepatopancreatobiliary, hernia, intestinal obstruction, resuscitation, and upper gastrointestinal conditions. SMI was defined as schizophrenia spectrum, mood, or anxiety disorders. The exposure was MHV within 30 days of discharge. The primary outcome was 30-day readmission. Secondary outcomes included emergency department presentation and psychiatric admission. Inverse probability weighting was used to evaluated outcomes. RESULTS: Of 88,092 analyzed patients, 11,755 (13.3%) had a MHV within 30 days of discharge. 23,696 (26.9%) of patients were managed operatively, 64,395 (73.1%) non-operatively. After adjustment for potential confounders, patients with a post-discharge MHV had lower odds of acute care readmission than patients without a MHV in both operative (OR 0.60; 95% CI: [0.40-0.90]) and non-operative (OR 0.67; 95% CI [0.53-0.84]) cohorts. There was no association between post-discharge MHV and ED presentation or psychiatric admission in the operative or non-operative groups. CONCLUSIONS: Post-discharge MHV after EGS hospitalization was associated with decreased odds of readmission for patients with SMI managed operatively and nonoperatively. In older EGS patients with SMI, coordination of MHVs may be a mechanism to reduce readmission disparities.

Novel Program Connects Medical Students with Startups Focused on Social Determinants of Health.

BACKGROUND: Understanding health equity is critical for the development of patient-centered physicians, but few avenues exist for medical students to participate in experiential learning related to social determinants of health (SDOH). AIM: To create and evaluate the PennHealthX SDOH Accelerator Program, which pairs students with health equity startups. SETTING: The program matches medical students at our institution with startups focused on SDOH for voluntary, part-time internships. PARTICIPANTS: Medical students of all years are eligible to apply. Startups are typically early-stage (≤ 10 employees). PROGRAM DESCRIPTION: Two pre-clinical students lead the program. Startups are sourced via alumni networking, partnerships with venture capital firms, and cold outreach. Startups and students apply and are matched based on project goals and student backgrounds/skills. Upon completion, feedback is gathered through open-ended interviews with all students. PROGRAM EVALUATION: Twenty medical students were matched with 11 startups. In post-program interviews, students expressed high satisfaction. Students specifically valued the opportunity to learn about SDOH in a hands-on and solution-oriented way. DISCUSSION: This program gives students the opportunity to impact their communities and learn about addressing SDOH with innovative solutions. We are continuing to build the program at our institution and expand its impact to other medical schools.

Validation of a rodent model of episodic memory replay.

Vivid episodic memories in humans have been described as the replay of the flow of past events in sequential order. Recently, Panoz-Brown et al. Current Biology, 28, 1628-1634, (2018) developed an olfactory memory task in which rats were presented with a list of trial-unique odors in an encoding context; next, in a distinctive memory assessment context, the rats were rewarded for choosing the second to last item from the list while avoiding other items from the list. In a different memory assessment context, the fourth to last item was rewarded. According to the episodic memory replay hypothesis, the rat remembers the list items and searches these items to find the item at the targeted locations in the list. However, events presented sequentially differ in memory trace strength, allowing a rat to use the relative familiarity of the memory traces, instead of episodic memory replay, to solve the task. Here, we directly manipulated memory trace strength by manipulating the odor intensity of target odors in both the list presentation and memory assessment. The rats relied on episodic memory replay to solve the memory assessment in conditions in which reliance on memory trace strength is ruled out. We conclude that rats are able to replay episodic memories.

The Social Contagion Potential of Pro-Vaccine Messages on Black Twitter.

Black Americans in the US not only suffered from disproportionately high hospitalization and death rates throughout the pandemic but also from the consequences of low COVID-19 vaccination rates. This pattern of disparity is linked to distrust of public health systems that originates from a history of medical atrocities committed against Black people. For that reason, mitigation of race-based inequity in COVID-19 impacts might find more success in grassroots information contagion than official public health campaigns. While Black Twitter is well-positioned as a conduit for such information contagion, little is known about message characteristics that would afford it. Here, we tested the impact of four different message frames (personalization, interactive, fear appeal, neutral) on the social contagion potential of bi-modal social media messages promoting COVID-19 vaccinations and finding personalized messages to be the most shareable. Wary of recommending personalization as the blueprint for setting a social contagion health campaign in motion, we probed further to understand the influence of individual-level variables on the communicability of personalized messages. Subsequently, regression models and focus group data were consulted, revealing that thinking styles, vaccine confidence levels, and attitudes toward social media were significant factors of influence on the contagion potential of personalized messages. We discussed the implications of these results for health campaigns.

Technical considerations for replantation: from bony fixation to soft tissue coverage.

Digital replantation is a challenging and at-time tedious operation, but if approached thoughtfully and with reasonable expectations can be a reliable and rewarding undertaking. This article summarizes technical considerations for digital replantations involving flexor tendon zone II. The article has been ordered according to the recommended sequence of a structure-by-structure repair in a non-thumb digit. Special considerations are described for thumb, multiple digits, and heterotopic replantation.

Weight status and meeting the physical activity, sleep, and screen-time guidelines among Texas children: results from a population based, cross-sectional analysis.

BACKGROUND: Evidence suggests that the interactive effects of physical activity, screen-time and sleep are stronger than independent effects of these behaviors on pediatric obesity. However, this hypothesis has not been fully examined among samples of young school-aged children. The aim of this study is to determine the association of weight status with meeting the physical activity, screen-time, and sleep guidelines, independently and concurrently, among 2nd grade children. METHODS: The Texas School Physical Activity and Nutrition Project collected parent-reported physical activity, screen-time, and sleep, and measured body height and weight on a statewide representative weighted sample (n = 320,005) of children. Weighted multivariable logistic regressions were used to assess associations of weight status (classified using age- and sex-specific body weight [kg]/height [m]2, based on International Obesity Task Force cutoffs) with meeting the physical activity, screen-time, and sleep guidelines, while controlling for relevant covariates (age, sex, race/ethnicity, comorbidities etc.). RESULTS: A greater proportion of healthy weight children (9.9%) met the physical activity, screen-time, and sleep guidelines concurrently compared to children who are thin (3.3%), or children with overweight (5.7%), obese (3.5%), and morbid obesity (1.0%). Children who were thin (adjusted odds ratio [aOR]:0.40, 95% confidence interval [CI]: 0.10, 1.50), overweight (aOR = 0.75, CI: 0.33, 1.70), obese (aOR = 0.53, CI: 0.15, 1.81), and morbidly obese (aOR = 0.10, CI: 0.02, 0.28) had lower odds of concurrently meeting the guidelines compared to children with healthy weight. CONCLUSIONS: Among this representative sample of Texas children, weight status was associated with meeting physical activity, screen-time, and sleep guidelines. Future studies should aim to evaluate causal relations between these behaviors and weight status.

Intracranial hemangioma-associated cranial nerve VII palsy treated with propranolol in an infant with possible PHACE syndrome.

A 2-week-old infant with a large vascular birthmark involving her right face presented with right-sided facial paralysis. MRI of the brain revealed multiple intracranial hemangiomas, and the hemangioma within the right temporal bone impinged on the facial nerve, which resulted in paralysis. Cranial nerve palsies are a rare neurological manifestation of PHACE syndrome. We report successful treatment of the facial nerve palsy with oral propranolol.

Childhood lymphomatoid papulosis Type D, a rare and challenging diagnosis.

A 10-year-old female with a several-year history of pityriasis lichenoides (PL) presented with a new, asymptomatic, large, and necrotic ulcer of her right upper arm. Skin biopsy was consistent with lymphomatoid papulosis (LyP) Type D, a recently recognized subtype of LyP that is distinguished histologically by marked epidermotropism and a perivascular infiltrate of medium-sized pleomorphic lymphocytes with a cytotoxic phenotype (CD3+, CD8+). This is only the sixth reported case of LyP Type D in a child, and while the prognosis in children appears favorable, with no reports of progression to lymphoma to date, more experience in children with longer-term follow-up is needed. Our case highlights both the challenging clinical diagnosis, since in our patient the longstanding clinical presentation was indistinguishable from PL, as well as histopathologic diagnosis, which required expert opinion and consensus.

Developing a Qualification and Verification Strategy for Digital Tissue Image Analysis in Toxicological Pathology.

Digital tissue image analysis is a computational method for analyzing whole-slide images and extracting large, complex, and quantitative data sets. However, as with any analysis method, the quality of generated results is dependent on a well-designed quality control system for the entire digital pathology workflow. Such system requires clear procedural controls, appropriate user training, and involvement of specialists to oversee key steps of the workflow. The toxicologic pathologist is responsible for reporting data obtained by digital image analysis and therefore needs to ensure that it is correct. To accomplish that, they must understand the main parameters of the quality control system and should play an integral part in its conception and implementation. This manuscript describes the most common digital tissue image analysis end points and potential sources of analysis errors. In addition, it outlines recommended approaches for ensuring quality and correctness of results for both classical and machine-learning based image analysis solutions, as adapted from a recently proposed Food and Drug Administration regulatory framework for modifications to artificial intelligence/machine learning-based software as a medical device. These approaches are beneficial for any type of toxicopathologic study which uses the described end points and can be adjusted based on the intended use of the image analysis solution.

Stereology of the Peripheral Nervous System.

Qualitative histopathology has been the gold standard for evaluation of morphological tissue changes in all organ systems, including the peripheral nervous system. However, the human eye is not sensitive enough to detect small changes in quantity or size. Peripheral nervous system toxicity can manifest as subtle changes in neuron size, neuron number, axon size, number of myelinated or unmyelinated axons, or number of nerve fibers. Detection of these changes may be beyond the sensitivity of the human eye alone, necessitating quantitative approaches in some cases. Although 2-dimensional (2D) histomorphometry can provide additional information and is more sensitive than qualitative evaluation alone, the results are not always representative of the entire tissue and assumptions about the tissue can lead to bias, or inaccuracies, in the data. Design-based stereology provides 3D estimates of number, volume, surface area, or length, and stereological principles can be applied to peripheral nervous system tissues to obtain accurate and precise estimates, such as neuron number and size, axon number, and total intraepidermal nerve fiber length. This review describes practical stereological approaches to 3 compartments of the peripheral nervous system: ganglia, peripheral nerves, and intraepidermal nerve fibers.

Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats.

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.

Society of Toxicologic Pathology Digital Pathology and Image Analysis Special Interest Group Article*: Opinion on the Application of Artificial Intelligence and Machine Learning to Digital Toxicologic Pathology.

Toxicologic pathology is transitioning from analog to digital methods. This transition seems inevitable due to a host of ongoing social and medical technological forces. Of these, artificial intelligence (AI) and in particular machine learning (ML) are globally disruptive, rapidly growing sectors of technology whose impact on the long-established field of histopathology is quickly being realized. The development of increasing numbers of algorithms, peering ever deeper into the histopathological space, has demonstrated to the scientific community that AI pathology platforms are now poised to truly impact the future of precision and personalized medicine. However, as with all great technological advances, there are implementation and adoption challenges. This review aims to define common and relevant AI and ML terminology, describe data generation and interpretation, outline current and potential future business cases, discuss validation and regulatory hurdles, and most importantly, propose how overcoming the challenges of this burgeoning technology may shape toxicologic pathology for years to come, enabling pathologists to contribute even more effectively to answering scientific questions and solving global health issues. [Box: see text].

Effects of NMDA antagonist dizocilpine (MK-801) are modulated by the number of distractor stimuli in the rodent odor span task of working memory.

The rodent odor span task (OST) uses an incrementing non-matching to sample procedure in which a series of odors is presented and selection of the session-novel odor is reinforced. An OST is frequently used to test the effects of neurobiological variables on memory capacity as the number of odors to remember increases during the course of the session. In this regard, one important finding has been that NMDA receptor antagonists selectively impair OST performance at doses that spare accuracy on control tasks. However, in many versions of the odor span task the number of stimuli to remember is confounded with the number of distractor odors presented to the rat on each trial. The present study compared the effects of the NMDA antagonist dizocilpine when the number of choices was held constant at two (one novel odor-S+ and one previously presented distractor odor-S-) and when the number of choice stimuli was permitted to increase up to 10 (one S+ and 9 S-). Dizocilpine impaired OST accuracy at doses that had no effect on a reference memory control task in both 2-choice and 10-choice conditions; however, the dose-response function was shifted to the left in the 10-choice tests. The impairments produced by dizocilpine were exacerbated as the memory load increased in both 2- and 10-choice conditions. These findings support the hypothesis that NMDA antagonism reduces the number of stimuli that rats can remember accurately, but the interaction between the effective DZP dose and the number of distractors shows that drug effects on OST performances may involve attentional factors in addition to memory capacity. The findings also demonstrate that variations in number of OST distractors can be used to alter sensitivity of the task.

Pharmacological evidence of medicinal cannabis in oncology: a systematic review.

PURPOSE: This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology. METHODS: A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology. RESULTS: Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified. CONCLUSIONS: There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.

Classic pseudoxanthoma elasticum in a girl with sickle cell disease.

A pseudoxanthoma elasticum (PXE)-like phenotype develops in a subset of patients with inherited hemoglobinopathies. Although PXE tissue changes are thought to develop in the absence of ABCC6 mutations in patients with beta-thalassemia, ABCC6 mutations have not been well evaluated among sickle cell disease patients with PXE-like disease. To our knowledge, we describe the first patient with sickle cell disease, PXE skin findings, and two confirmed pathogenic ABCC6 mutations. This case suggests that ABCC6 testing is warranted for sickle cell disease patients with the PXE-like phenotype and that the pathogenesis of PXE manifestations in beta-thalassemia and sickle cell disease may differ.

Incidental spatial memory in the domestic dog (Canis familiaris).

We built upon previous work by Fujita et al. (2012, Animal Cognition, 15(6), 1055-1063) to create an experiment that investigated the presence of incidental memory for the spatial location of uneaten food in the domestic dog. Here, we dissociated potentially incidental spatial memory from the incidental memory for the characteristics of objects, in this case, food bowls. Eighteen household domestic dogs of various breeds and age were presented with four bowls. Each bowl contained either a novel object, treats the dog could consume, treats it could not consume, or it was left empty. Following a delay, the dogs returned to the laboratory and were presented with empty bowls in the same spatial orientation as the initial exposure and could move freely between bowls. This experiment required no previous training outside of basic obedience and so avoids the possibility that performance on the test was a conditioned response. We hypothesized that domestic dogs would be able to remember the location of uneaten food when presented with an unexpected memory test. We found that dogs in this study showed no evidence that they encoded spatial location in the absence of other cues that could be used to distinguish food bowls at specific locations. This suggests that dogs in previous experiments were more dependent on incidentally encoding the "what" and "in what" of this task than the "where," in the absence of features making each location distinct.

Prevalence of Concomitant Acute Bacterial Meningitis in Neonates with Febrile Urinary Tract Infection: A Retrospective Cross-Sectional Study.

OBJECTIVE: To describe the frequency of concomitant acute bacterial meningitis (ABM) in neonates with febrile urinary tract infection (UTI). STUDY DESIGN: This was a retrospective cross-sectional study from 2005 to 2013 of infants ≤30 days old evaluated in the emergency department of a quaternary care children's hospital with fever and laboratory-confirmed UTI. Definite ABM was defined as cerebrospinal fluid (CSF) culture with growth of pathogenic bacteria and probable ABM if pleocytosis with ≥ 20 white blood cell was present in an antibiotic-pretreated patient. The timing of lumbar puncture and first antibiotic dose was recorded to assess for antibiotic pretreatment. RESULTS: A total of 236 neonates with UTI were included. Mean age was 18.6 days (SD 6.2); 79% were male infants. Twenty-three (9.7%) had bacteremia. Fourteen (6%) were pretreated. No neonate (0%; 95% CI 0%-1.6%) had definite ABM and 2 (0.8%; 95% CI 0.1%-3.0%) neonates with bloody CSF had probable ABM. CSF white blood cell count was 25 and 183 for these 2 infants, and CSF red blood cell count was 3100 and 61 932, respectively. Another neonate had herpes simplex virus meningoencephalitis. CONCLUSIONS: The frequency of ABM in neonates with febrile UTI is low. Further prospective studies are needed to evaluate the safety of a tiered approach to evaluate for serious bacterial infection, in which lumbar puncture potentially could be avoided in well-appearing febrile neonates with suspected UTI.

Amnestic drugs in the odor span task: Effects of flunitrazepam, zolpidem and scopolamine.

The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABAA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABAA receptor modulator zolpidem and the cholinergic receptor antagonist scopolamine only impaired odor span at doses that produced more global impairment, including decreased accuracy in the control discrimination and increased response omissions in the both the odor span and control discrimination procedures. Even though the effects of flunitrazepam were selective to odor span performance, they did not depend on the number of stimuli to remember-the same degree of impairment occurred regardless of the memory load. These findings suggest that flunitrazepam interfered selectively with conditional discrimination performance rather than working memory and tentatively suggest that flunitrazepam's selective effects in the odor span task relative to the control odor discrimination are mediated by one or more non-alpha1 GABAA receptor subtypes.

The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory.

Chemotherapy is widely used to treat patients with systemic cancer. The efficacy of cancer therapies is frequently undermined by adverse side effects that have a negative impact on the quality of life of cancer survivors. Cancer patients who receive chemotherapy often experience chemotherapy-induced cognitive impairment across a variety of domains including memory, learning, and attention. In the current study, the impact of paclitaxel, a taxane derived chemotherapeutic agent, on episodic memory, prior learning, new learning, and reversal learning were evaluated in rats. Neurogenesis was quantified post-treatment in the dentate gyrus of the same rats using immunostaining for 5-Bromo-2'-deoxyuridine (BrdU) and Ki67. Paclitaxel treatment selectively impaired reversal learning while sparing episodic memory, prior learning, and new learning. Furthermore, paclitaxel-treated rats showed decreases in markers of hippocampal cell proliferation, as measured by markers of cell proliferation assessed using immunostaining for Ki67 and BrdU. This work highlights the importance of using multiple measures of learning and memory to identify the pattern of impaired and spared aspects of chemotherapy-induced cognitive impairment.

Meeting Report: Tissue-based Image Analysis.

Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives. The added value of quantitative IA in pathology includes confirmation of equivocal findings noted by a pathologist, increasing the sensitivity of feature detection, quantification of signal intensity, and improving efficiency. There is no denying that quantitative IA is part of the future of pathology; however, there are also several potential pitfalls when trying to estimate volumetric features from limited 2-dimensional sections. This continuing education session on quantitative IA offered a broad overview of the field; a hands-on toxicologic pathologist experience with IA principles, tools, and workflows; a discussion on how to apply basic stereology principles in order to minimize bias in IA; and finally, a reflection on the future of IA in the toxicologic pathology field.