The genomic origins of the Bronze Age Tarim Basin mummies.

The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000-2800 BC from the Dzungarian Basin and 13 individuals dating to around 2100-1700 BC from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early-Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria-Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.

Caregivers' concerns and supports needed to care for adults with Down syndrome.

Research regarding caregivers for individuals with Down syndrome mainly focuses on outcomes for the pediatric population and not on the experience of caregivers themselves. Our objective was to understand caregiver-reported experiences and concerns for themselves and the individual they care for through a survey of caregivers of adults with Down syndrome. We conducted a survey of N = 438 caregivers of adults with Down syndrome and asked about the perspectives of the respondents surrounding caregiving and demographics. The most common concerns among caregivers were planning for future needs (72.1%) and what happens when they (the caregiver) are gone (68.3%). Concerns they had for the individual they cared for were employment (63.2%) and friendships/relationships (63.2%). We found no significant difference in responses based on caregiver education level. Our survey identified six themes for the feedback about what clinical and research professionals should know to better serve individuals with Down syndrome, their families, and those who support them. Many caregivers discussed topics including healthcare, coordination, competence, and ability. More efforts for research into the caregiver experience for adults with Down syndrome are needed.

Doubly marginalized: the interplay of racism and disability in outcomes for minoritized people with Down syndrome.

BACKGROUND: Intersectionality, or the multidimensional influence of social identity and systems of power, may drive increased morbidity and mortality for adults of color with Down syndrome. We documented racial and ethnic differences in death and hospitalizations among Medicaid enrolled adults with Down syndrome and assessed interaction of racial-ethnic group and Down syndrome. METHODS: Our sample consisted of 119,325 adults with Down syndrome and >3.2 million adults without intellectual disability enrolled in Medicare at any point from 2011-2019. We calculated age-adjusted mortality and hospitalization rates by racial-ethnic group among those with Down syndrome. We examined additive interaction between Down syndrome and racial and ethnic group on mortality and hospitalization rates. RESULTS: Among those with Down syndrome, age-adjusted mortality rate did not differ between Black and White racial groups (rate ratio: 0.96, 95%CI: 0.92, 1.01) while mortality rate was lower for Pacific Islander (0.80), Asian (0.71), Native (0.77), and Mixed-race groups (0.50). Hospitalization rates were higher for all marginalized groups compared to the White group. When assessing the interaction between racial-ethnic group and Down syndrome, Black, Native Americans, and Mixed-race groups exhibited a negative additive interaction for mortality rate and all groups except Native Americans exhibited positive additive interaction for hospitalization. CONCLUSIONS: Increased hospitalization rates for adults with Down syndrome from marginalized racial and ethnic groups suggest worse health and healthcare. Similar mortality rates across racial and ethnic groups may result from increased infant mortality rate in marginalized groups with Down syndrome leading to reduced mortality among those surviving to adulthood.

Exotic foods reveal contact between South Asia and the Near East during the second millennium BCE.

Although the key role of long-distance trade in the transformation of cuisines worldwide has been well-documented since at least the Roman era, the prehistory of the Eurasian food trade is less visible. In order to shed light on the transformation of Eastern Mediterranean cuisines during the Bronze Age and Early Iron Age, we analyzed microremains and proteins preserved in the dental calculus of individuals who lived during the second millennium BCE in the Southern Levant. Our results provide clear evidence for the consumption of expected staple foods, such as cereals (Triticeae), sesame (Sesamum), and dates (Phoenix). We additionally report evidence for the consumption of soybean (Glycine), probable banana (Musa), and turmeric (Curcuma), which pushes back the earliest evidence of these foods in the Mediterranean by centuries (turmeric) or even millennia (soybean). We find that, from the early second millennium onwards, at least some people in the Eastern Mediterranean had access to food from distant locations, including South Asia, and such goods were likely consumed as oils, dried fruits, and spices. These insights force us to rethink the complexity and intensity of Indo-Mediterranean trade during the Bronze Age as well as the degree of globalization in early Eastern Mediterranean cuisine.

Tocilizumab Associated With Survival in Patients Hospitalized for COVID-19 Acute Respiratory Distress Syndrome and Low Urine Output.

BACKGROUND: Acute respiratory distress syndrome (ARDS) with oliguria is associated with increased mortality. Interleukin-6 (IL-6) plays an integral role in the pathophysiology of both disease processes. Patients who experience severe COVID-19 have demonstrated higher IL-6 levels compared to baseline, and use of tocilizumab has demonstrated efficacy in such cohorts. We set out to investigate the relationship between tocilizumab use, COVID-19 ARDS, low urine output, and mortality. METHODS: Retrospective cohort review of adult patients aged ≥ 18 years with COVID-19 and moderate or severe ARDS, admitted to the intensive care unit (ICU) of a tertiary referral center in metropolitan Detroit. Patients were analyzed based on presence of oliguria (defined as ≤ 0.7 mL/kg/h) on the day of intubation and exposure to tocilizumab while inpatient. The primary outcome was inpatient mortality. RESULTS: One hundred and twenty-eight patients were analyzed, 103 (80%) with low urine output, of whom 30 (29%) received tocilizumab. In patients with low urine output, risk factors associated with mortality on univariate analysis included Black race (P = .028), lower static compliance (P = .015), and tocilizumab administration (P = .002). Tocilizumab (odds ratio 0.245, 95% confidence interval 0.079-0.764, P = .015) was the only risk factor independently associated with survival on multivariate logistic regression analysis. CONCLUSION: In this retrospective cohort review of patients hospitalized with COVID-19 and moderate or severe ARDS, tocilizumab administration was independently associated with survival in patients with low urine output ≤ 0.7 mL/kg/h on the day of intubation. Prospective studies are needed to investigate the impact of urine output on efficacy of interleukin-targeted therapies in the management of ARDS.

Cellular-scale sex differences in extracellular matrix remodeling by valvular interstitial cells.

Males acquire calcific aortic valve disease (CAVD) twice as often as females, yet stenotic valves from females display significantly higher levels of fibrosis compared to males with similar extent of disease. Fibrosis occurs as an imbalance between the production and degradation of the extracellular matrix (ECM), specifically type I collagen. This work characterizes ECM production and remodeling by male and female valvular interstitial cells (VICs) to better understand the fibrocalcific divergence between sexes evident in CAVD. Male and female VICs were assessed for gene and protein expression of myofibroblastic markers, ECM components, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) via qRT-PCR and western blot. Overall metabolic activity was also measured. Activity assays for collagenase and gelatinase were performed to examine degradation behavior. Male VICs produced greater levels of myofibroblastic markers while female VICs showed greater metabolic activity and collagen production. In general, females displayed a greater level of MMP expression and production than males, but no sex differences were observed in TIMP production. Male VICs also displayed a greater level of collagenase and gelatinase activity than female VICs. This work displays sex differences in ECM remodeling by VICs that could be related to the sexual dimorphism in ECM structure seen in clinical CAVD.

Relief food subsistence revealed by microparticle and proteomic analyses of dental calculus from victims of the Great Irish Famine.

Food and diet were class markers in 19th-century Ireland, which became evident as nearly 1 million people, primarily the poor and destitute, died as a consequence of the notorious Great Famine of 1845 to 1852. Famine took hold after a blight (Phytophthora infestans) destroyed virtually the only means of subsistence-the potato crop-for a significant proportion of the population. This study seeks to elucidate the variability of diet in mid-19th-century Ireland through microparticle and proteomic analysis of human dental calculus samples (n = 42) from victims of the famine. The samples derive from remains of people who died between August 1847 and March 1851 while receiving poor relief as inmates in the union workhouse in the city of Kilkenny (52°39' N, -7°15' W). The results corroborate the historical accounts of food provisions before and during the famine, with evidence of corn (maize), potato, and cereal starch granules from the microparticle analysis and milk protein from the proteomic analysis. Unexpectedly, there is also evidence of egg protein-a food source generally reserved only for export and the better-off social classes-which highlights the variability of the prefamine experience for those who died. Through historical contextualization, this study shows how the notoriously monotonous potato diet of the poor was opportunistically supplemented by other foodstuffs. While the Great Irish Famine was one of the worst subsistence crises in history, it was foremost a social disaster induced by the lack of access to food and not the lack of food availability.

Engineering the aortic valve extracellular matrix through stages of development, aging, and disease.

For such a thin tissue, the aortic valve possesses an exquisitely complex, multi-layered extracellular matrix (ECM), and disruptions to this structure constitute one of the earliest hallmarks of fibrocalcific aortic valve disease (CAVD). The native valve structure provides a challenging target for engineers to mimic, but the development of advanced, ECM-based scaffolds may enable mechanistic and therapeutic discoveries that are not feasible in other culture or in vivo platforms. This review first discusses the ECM changes that occur during heart valve development, normal aging, onset of early-stage disease, and progression to late-stage disease. We then provide an overview of the bottom-up tissue engineering strategies that have been used to mimic the valvular ECM, and opportunities for advancement in these areas.

Bronze Age population dynamics and the rise of dairy pastoralism on the eastern Eurasian steppe.

Recent paleogenomic studies have shown that migrations of Western steppe herders (WSH) beginning in the Eneolithic (ca. 3300-2700 BCE) profoundly transformed the genes and cultures of Europe and central Asia. Compared with Europe, however, the eastern extent of this WSH expansion is not well defined. Here we present genomic and proteomic data from 22 directly dated Late Bronze Age burials putatively associated with early pastoralism in northern Mongolia (ca. 1380-975 BCE). Genome-wide analysis reveals that they are largely descended from a population represented by Early Bronze Age hunter-gatherers in the Baikal region, with only a limited contribution (∼7%) of WSH ancestry. At the same time, however, mass spectrometry analysis of dental calculus provides direct protein evidence of bovine, sheep, and goat milk consumption in seven of nine individuals. No individuals showed molecular evidence of lactase persistence, and only one individual exhibited evidence of >10% WSH ancestry, despite the presence of WSH populations in the nearby Altai-Sayan region for more than a millennium. Unlike the spread of Neolithic farming in Europe and the expansion of Bronze Age pastoralism on the Western steppe, our results indicate that ruminant dairy pastoralism was adopted on the Eastern steppe by local hunter-gatherers through a process of cultural transmission and minimal genetic exchange with outside groups.

Derivation and validation of the ED-SAS score for very early prediction of mortality and morbidity with acute pancreatitis: a retrospective observational study.

BACKGROUND: Existing scoring systems to predict mortality in acute pancreatitis may not be directly applicable to the emergency department (ED). The objective of this study was to derive and validate the ED-SAS, a simple scoring score using variables readily available in the ED to predict mortality in patients with acute pancreatitis. METHODS: This retrospective observational study was performed based on patient data collected from electronic health records across 2 independent health systems; 1 was used for the derivation cohort and the other for the validation cohort. Adult patients who were eligible presented to the ED, required hospital admission, and had a confirmed diagnosis of acute pancreatitis. Patients with chronic or recurrent episodes of pancreatitis were excluded. The primary outcome was 30-day mortality. Analyses tested and derived candidate variables to establish a prediction score, which was subsequently applied to the validation cohort to assess odds ratios for the primary and secondary outcomes. RESULTS: The derivation cohort included 599 patients, and the validation cohort 2011 patients. Thirty-day mortality was 4.2 and 3.9%, respectively. From the derivation cohort, 3 variables were established for use in the predictive scoring score: ≥2 systemic inflammatory response syndrome (SIRS) criteria, age > 60 years, and SpO2 < 96%. Summing the presence or absence of each variable yielded an ED-SAS score ranging from 0 to 3. In the validation cohort, the odds of 30-day mortality increased with each subsequent ED-SAS point: 4.4 (95% CI 1.8-10.8) for 1 point, 12.0 (95% CI 4.9-29.4) for 2 points, and 41.7 (95% CI 15.8-110.1) for 3 points (c-statistic = 0.77). CONCLUSION: An ED-SAS score that incorporates SpO2, age, and SIRS measurements, all of which are available in the ED, provides a rapid method for predicting 30-day mortality in acute pancreatitis.

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis.

BACKGROUND: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. METHODS: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. RESULTS: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. CONCLUSIONS: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.

An exploration of the attitudes and perceptions of the UK public towards self-care for minor ailments.

AIMS AND OBJECTIVES: the purpose of this pilot study was to explore the attitudes and perceptions of members of the UK public towards self-care for minor ailments. BACKGROUND: with an ageing and increasing population, and an NHS under extreme pressure, methods to reduce demand on health services are vital. Increasing the use of self-care for minor ailments is one way in which this pressure could be alleviated. DESIGN AND METHOD: this study used qualitative methods including semi-structured telephone interviews. The data were then evaluated, and key themes drawn out using thematic analysis. FINDINGS: the results showed that the public are aware of the notion of self-care, and some are engaging with it. However, for a number of reasons, patients are still likely to want a face-to-face appointment despite the use of online and telephone advice services. CONCLUSION: the study highlighted that there are multifactorial aspects impacting on a patient's likelihood of engaging in self-care when faced with a minor illness. The results are not generalisable to every member of the public, but interesting questions are raised with regard to the usefulness of current public health messages in various media when there appears to be a lack of desire from the public to use some recommended services.

Social Media Programs for Outreach and Recruitment Supporting Aging and Alzheimer Disease and Related Dementias Research: Longitudinal Descriptive Study.

BACKGROUND: Social media may be a useful method for research centers to deliver health messages, increase their visibility in the local community, and recruit study participants. Sharing examples of social media-based community outreach and educational programs, and evaluating their outcomes in this setting, is important for understanding whether these efforts have a measurable impact. OBJECTIVE: The aim of this study is to describe one center's social media activities for community education on topics related to aging, memory loss, and Alzheimer disease and related dementias, and provide metrics related to recruitment into clinical research studies. METHODS: Several social media platforms were used, including Facebook, X (formerly Twitter), and YouTube. Objective assessments quantified monthly, based on each platform's native dashboard, included the number of followers, number of posts, post reach and engagement, post impressions, and video views. The number of participants volunteering for research during this period was additionally tracked using a secure database. Educational material posted to social media most frequently included content developed by center staff, content from partner organizations, and news articles or resources featuring center researchers. Multiple educational programs were developed, including social media series, web-based talks, Twitter chats, and webinars. In more recent years, Facebook content was occasionally boosted to increase visibility in the local geographical region. RESULTS: Up to 4 years of page metrics demonstrated continuing growth in reaching social media audiences, as indicated by increases over time in the numbers of likes or followers on Facebook and X/Twitter and views of YouTube videos (growth trajectories). While Facebook reach and X/Twitter impression rates were reasonable, Facebook engagement rates were more modest. Months that included boosted Facebook posts resulted in a greater change in page followers and page likes, and higher reach and engagement rates (all P≤.002). Recruitment of participants into center-affiliated research studies increased during this time frame, particularly in response to boosted Facebook posts. CONCLUSIONS: These data demonstrate that social media activities can provide meaningful community educational opportunities focused on Alzheimer disease and related dementias and have a measurable impact on the recruitment of participants into research studies. Additionally, this study highlights the importance of tracking outreach program outcomes for evaluating return on investment.

Revolutionizing Nurse Practitioner Training: Integrating Virtual Reality and Large Language Models for Enhanced Clinical Education.

This project introduces an innovative virtual reality (VR) training program for student Nurse Practitioners, incorporating advanced 3D modeling, animation, and Large Language Models (LLMs). Designed to simulate realistic patient interactions, the program aims to improve communication, history taking, and clinical decision-making skills in a controlled, authentic setting. This abstract outlines the methods, results, and potential impact of this cutting-edge educational tool on nursing education.

Clinical Characteristics and Mortality Risks Among Patients With Culture-Proven Coccidioidomycosis Who Are Critically Ill: A Multicenter Study in an Endemic Region.

Background: Coccidioidomycosis is an endemic mycosis in the southwestern United States. While most infections are mild, severe cases can be devastating. We aimed to describe the clinical characteristics and mortality risks of patients in the intensive care unit (ICU) with culture-proven coccidioidomycosis. Methods: We performed a retrospective chart review of patients in the ICU with positive Coccidioides spp culture in a large health care system in Arizona between 1 October 2017 and 1 July 2022. All data were entered into REDCap. Results: An overall 145 patients were identified and included. The median age was 51 years, with the majority male (69%) and non-Hispanic White (39%). Most patients (n = 104, 72%) had pulmonary coccidioidomycosis, and 41 had extrapulmonary disease (17 meningitis, 13 fungemia, 10 musculoskeletal disease, and 4 pericardial or aortic involvement). Seventy patients (48%) died during hospitalization, and most (91%) received antifungal therapy during hospitalization. In the multivariate logistic regression model, age ≥60 years (odds ratio [OR], 7.0; 95% CI, 2.6-18.8), cirrhosis (OR, 13.1; 95% CI, 1.6-108.8), and mechanical ventilation or vasopressor support (OR, 15.4; 95% CI, 3.9-59.6) were independently associated with increased all-cause mortality, but pre-ICU antifungal use had a statistically insignificant mortality risk association (OR, 0.5; 95% CI, .2-1.2). Conclusions: In our study of patients in the ICU with coccidioidomycosis and multiple comorbidities, the mortality rate was high. Older age, cirrhosis, and mechanical ventilation or vasopressor support were significantly associated with high mortality. Future studies are recommended to evaluate those risk factors and the efficacy of rapid diagnosis and early therapy in patients at high risk.

Alzheimer Dementia Among Individuals With Down Syndrome.

Importance: With the advancement in administrative data as a research tool and the reliance on public health insurance for individuals with Down syndrome, population-level trends in Alzheimer dementia in this population are beginning to be understood. Objective: To comprehensively describe the epidemiology of Alzheimer dementia in adults with Down syndrome in a full US Medicare and Medicaid sample. Design, Setting, and Participants: This cohort study included 132 720 adults aged 18 years or older with Medicaid and/or Medicare claims data with an International Statistical Classification of Diseases and Related Health Problems code for Down syndrome. Data were collected from January 1, 2011, to December 31, 2019, and analyzed from August 2023 to May 2024. Main Outcomes and Measures: The main outcome was prevalence of Alzheimer dementia in each calendar year and during the 9-year period. Alzheimer dementia incidence rates by calendar year and age and stratified for race or ethnicity as well as time to death after Alzheimer dementia diagnosis were also assessed. Results: There were 132 720 unique adults with Down syndrome from 2011 to 2019: 79 578 (53.2%) were male, 17 090 (11.7%) were non-Hispanic Black, 20 777 (15.7%) were Hispanic, 101 120 (68.8%) were non-Hispanic White, and 47 692 (23.3%) had ever had an Alzheimer dementia diagnosis. Incidence was 22.4 cases per 1000 person-years. The probability of an incident Alzheimer dementia diagnosis over 8 years was 0.63 (95% CI, 0.62-0.64) for those entering the study between ages 55 to 64 years. Mean (SD) age at incident diagnosis was 54.5 (7.4) years and median (IQR) age was 54.6 (9.3) years. Mean (SD) age at death among those with Alzheimer dementia was 59.2 (6.9) years (median [IQR], 59.0 [8.0] years). The mean (SD) age at onset for the Hispanic group was 54.2 (9.2) years, 52.4 (7.8) years for the American Indian or Alaska Native group, and 52.8 (8.2) years for the mixed race groups compared with 55.0 (7.8) years for the White non-Hispanic group. For age at death, there were no differences by sex. The mean (SD) age at death was later for the White non-Hispanic group (59.3 [6.8] years) compared with the Hispanic group (58.5 [7.8] years), Native American group (57.8 [7.1] years), and mixed race group (58.2 [7.0] years). Conclusions and Relevance: In this cohort study of adults with Down syndrome who were enrolled in Medicaid and Medicare, Alzheimer dementia occurred at high rates. Consistency with clinical studies of dementia in Down syndrome supports the use of administrative data in Down syndrome-Alzheimer dementia research.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

Hyperammonemia Secondary to 5-Fluorouracil.

5-fluorouracil (5-FU) is one of the most common adjuvant antineoplastic agents used in the treatment of localized and metastatic colon cancer. Frequent side effects of 5-FU include myelosuppression, mucositis, nausea, vomiting, and diarrhea. However, hyperammonemic encephalopathy is a rare neurologic toxicity that can occur after 5-FU chemotherapy administration. Patients with 5-FU-induced hyperammonemic encephalopathy often exhibit symptoms of altered mental status with no radiologic abnormalities or laboratory abnormalities except for significantly elevated ammonia levels with occasional lactic acidosis and respiratory alkalosis. We report a case of a patient with stage IV colon adenocarcinoma who experienced altered state of consciousness due to hyperammonemia during the administration of palliative chemotherapy with 5-FU, bevacizumab, and leucovorin. On cycle 1 day 2 of chemotherapy, the patient became drowsy and confused at home, prompting a visit to the emergency department and ultimately hospital admission. Laboratory tests revealed an elevated blood ammonia level (838 µg/dL). After an extensive negative workup, his altered state of consciousness was thought to be secondary to 5-FU-induced hyperammonemia. Upon admission, 5-FU was immediately discontinued and the patient was treated with lactulose enemas, intravenous fluids, rifaximin, and continuous renal replacement therapy with gradual recovery to baseline mental status. It is crucial for advanced practitioners to be aware of this rare side effect to ensure prompt diagnosis and maximize treatment effectiveness.

Examining Miliary Disease Etiology in a Coccidioides-Endemic Center: A Retrospective Cohort Study.

Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential causes of miliary chest imaging patterns to improve workup and empiric therapy selection. The secondary aims are to discern the predictors of miliary disease etiology and to determine whether appropriate empiric antimicrobial therapies were given. Study Design and Methods: In this retrospective cohort study, we searched a radiology database for patients with chest imaging studies described by the word "miliary". Subjects were excluded if they were under 18 years of age and if there were insufficient objective data to support a miliary disease etiology. A radiologist independently reviewed all imaging studies, and studies that did not appear to have a true miliary pattern were excluded. The collected data include patient demographics, immunocompromising risk factors, conditions associated with miliary disease, ß-D-glucan levels, serum eosinophil count, and empiric therapies received. Results: From our 41-patient cohort, 22 patients (53.7%) were clinically diagnosed with coccidioidomycosis, 8 (19.5%) with TB, 7 (17.1%) with metastatic solid cancer, 1 (2.4%) with lymphoma, 1 (2.4%) with other (Mycobacterium simiae), and 3 (7.3%) with unknown diseases (the sum equals 42 patients because one individual was diagnosed with both coccidioidomycosis and TB). All six patients with greater than 500 eosinophils/µL were diagnosed with coccidioidomycosis. Of the 22 patients diagnosed with coccidioidomycosis, 20 (90.91%) were empirically treated with an antifungal regimen. Of the eight patients with TB, six were empirically treated for TB. Interpretation: Based on our data from a Coccidioides-endemic region with close proximity to tuberculosis-endemic areas, the leading cause of miliary disease is coccidioidomycosis, although TB and cancer are also common etiologies. Serum eosinophilia and elevated ß-D-glucan levels were strongly predictive of coccidioidomycosis in our patient cohort with a miliary chest imaging pattern.