Hepatocellular carcinoma metastatic to the pituitary gland without an identifiable primary lesion.

Hepatocellular carcinoma is one of the most common malignancies worldwide. However, brain metastases from this cancer are incredibly rare. While the hepatocellular carcinoma mortality rate in the United States has been increasing, hepatocellular carcinoma is rare among patients without underlying liver disease. Here we present a patient with a history of left optic nerve meningioma treated with stereotactic radiosurgery who presented with acute vision loss. Magnetic resonance imaging revealed an enhancing mass lesion in the region of the sella turcica. Neurosurgical histopathology revealed a metastatic lesion consistent with hepatocellular carcinoma. Systemic workup failed to identify a primary liver lesion.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights From 2023.

This special article is the 16th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series, namely the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology. The major themes selected for 2023 are outlined in this introduction, and each highlight is reviewed in detail in the main article. The literature highlights in the specialty for 2023 begin with an update on perioperative rehabilitation in cardiothoracic surgery, with a focus on novel methods to best assess patients in the preoperative and postoperative periods, and the impact of rehabilitation on outcomes. The second major theme is focused on cardiac surgery, with the authors discussing new insights into inhaled pulmonary vasodilators, coronary revascularization surgery, and discussion of causes of coronary graft failure after surgery. The third theme is focused on cardiothoracic transplantation, with discussions focusing on bridge-to-transplantation strategies. The fourth theme is focused on mechanical circulatory support, with discussions focusing on both temporary and durable support. The fifth and final theme is an update on medical cardiology, with a focus on outcomes of invasive approaches to heart disease. The themes selected for this article are only a few of the diverse advances in the specialty during 2023. These highlights will inform the reader of key updates on various topics, leading to improved perioperative outcomes for patients with cardiothoracic and vascular disease.

Adding an extension piece to the end of the purge side arm of the Impella device can prevent the incidence of the cassette breaking and decrease the Impella device failure rate: Impact of practice change on patient outcome.

Background: Impella 5.5® with Smart Assist is a minimally invasive Left Ventricular Assist Devices (LVAD) approved by the Food and Drug Administration (FDA) for treating ongoing cardiogenic shock for up to 14 days. The Impella® intends to reduce ventricular workload and provide the circulatory support necessary for myocardial recovery.Research Question: Compared to standard practice, does adding an extension piece to the purge tube side arm of the Impella® Device decrease the incidence of device failure and positively impact the health outcome of adult patients receiving Impella® support?Study Design and Methods: A retrospective chart review of ICU patients was done at a tertiary care center from August 2018 to August 2022 to assess the differences in patient outcomes related to Impella® Device utilization before and after the implementation of the extension piece to the purge tube sidearm. Among patients reviewed, a total of 20 were included in our review, with seven not having the purge tube side arm extension added, while 13 patients had the extension.Results: The two study groups had no significant difference in patient health outcomes. Additionally, there were no instances of device failure requiring explanation without the extension tubing. However, there were no cases of the purge cassette cracking with the addition of the extension tubing.Conclusion: The addition of extension tubing to the purge cassette of the Impella® Device did not impact patient health outcomes or the incidence of device failure. There was a complete reduction in the incidence of the purge cassette cracking, which could reduce the potential for infection or device failure over a long period of mechanical support. There is a need for long-term prospective studies to confirm the results.

From numbers to medical knowledge: harnessing combinatorial data patterns to predict COVID-19 resource needs and distinguish patient subsets.

Background: The COVID-19 pandemic intensified the use of scarce resources, including extracorporeal membrane oxygenation (ECMO) and mechanical ventilation (MV). The combinatorial features of the immune system may be considered to estimate such needs and facilitate continuous open-ended knowledge discovery. Materials and methods: Computer-generated distinct data patterns derived from 283 white blood cell counts collected within five days after hospitalization from 97 COVID-19 patients were used to predict patient's use of hospital resources. Results: Alone, data on separate cell types-such as neutrophils-did not identify patients that required MV/ECMO. However, when structured as multicellular indicators, distinct data patterns displayed by such markers separated patients later needing or not needing MV/ECMO. Patients that eventually required MV/ECMO also revealed increased percentages of neutrophils and decreased percentages of lymphocytes on admission. Discussion/conclusion: Future use of limited hospital resources may be predicted when combinations of available blood leukocyte-related data are analyzed. New methods could also identify, upon admission, a subset of COVID-19 patients that reveal inflammation. Presented by individuals not previously exposed to MV/ECMO, this inflammation differs from the well-described inflammation induced after exposure to such resources. If shown to be reproducible in other clinical syndromes and populations, it is suggested that the analysis of immunological combinations may inform more and/or uncover novel information even in the absence of pre-established questions.

Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary.

Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand the cellular and molecular events shaping metastatic niches, we used a spontaneous breast cancer lung metastasis model to create a single-cell atlas spanning different metastatic stages and regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils and monocytes, followed by the accumulation of suppressive macrophages with the emergence of metastases. Spatial profiling revealed that metastasis-associated immune cells were present in the metastasis core, with the exception of TREM2+ regulatory macrophages uniquely enriched at the metastatic invasive margin, consistent across both murine models and human patient samples. These regulatory macrophages (Mreg) contribute to the formation of an immune-suppressive niche, cloaking tumor cells from immune surveillance. Our study provides a compendium of immune cell dynamics across metastatic stages and niches, informing the development of metastasis-targeting immunotherapies. SIGNIFICANCE: Temporal and spatial single-cell analysis of metastasis stages revealed new players in modulating immune surveillance and suppression. Our study highlights distinct populations of TREM2 macrophages as modulators of the microenvironment in metastasis, and as the key immune determinant defining metastatic niches, pointing to myeloid checkpoints to improve therapeutic strategies. This article is featured in Selected Articles from This Issue, p. 2489.

Association of plasma volume status with outcomes in hospitalized Covid-19 ARDS patients: A retrospective multicenter observational study.

PURPOSE: To evaluate the association of estimated plasma volume (ePV) and plasma volume status (PVS) on admission with the outcomes in COVID-19-related acute respiratory distress syndrome (ARDS) patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and these variables were analyzed for correlation with patient outcomes. RESULTS: Our analysis included 1298 patients with sequential organ failure assessment (SOFA) respiratory score ≥ 2 (PaO2/FIO2 ≤300 mmHg) and a mortality rate of 25.96%. A Cox proportional multivariate analysis showed PVS but not ePV as an independent correlation with 90-day mortality after adjusting for the covariates (HR: 1.015, 95% CI: 1.005-1.025, p = 0.002 and HR 1.054, 95% CI 0.958-1.159, p = 0.278 respectively). CONCLUSION: A lower PVS on admission correlated with a greater chance of survival in COVID-19-related ARDS patients. The role of PVS in guiding fluid management should be investigated in future prospective studies.

The transcriptional and regulatory identity of erythropoietin producing cells.

Erythropoietin (Epo) is the master regulator of erythropoiesis and oxygen homeostasis. Despite its physiological importance, the molecular and genomic contexts of the cells responsible for renal Epo production remain unclear, limiting more-effective therapies for anemia. Here, we performed single-cell RNA and transposase-accessible chromatin (ATAC) sequencing of an Epo reporter mouse to molecularly identify Epo-producing cells under hypoxic conditions. Our data indicate that a distinct population of kidney stroma, which we term Norn cells, is the major source of endocrine Epo production in mice. We use these datasets to identify the markers, signaling pathways and transcriptional circuits characteristic of Norn cells. Using single-cell RNA sequencing and RNA in situ hybridization in human kidney tissues, we further provide evidence that this cell population is conserved in humans. These preliminary findings open new avenues to functionally dissect EPO gene regulation in health and disease and may serve as groundwork to improve erythropoiesis-stimulating therapies.

Metal-rich stars are less suitable for the evolution of life on their planets.

Atmospheric ozone and oxygen protect the terrestrial biosphere against harmful ultraviolet (UV) radiation. Here, we model atmospheres of Earth-like planets hosted by stars with near-solar effective temperatures (5300 to 6300 K) and a broad range of metallicities covering known exoplanet host stars. We show that paradoxically, although metal-rich stars emit substantially less ultraviolet radiation than metal-poor stars, the surface of their planets is exposed to more intense ultraviolet radiation. For the stellar types considered, metallicity has a larger impact than stellar temperature. During the evolution of the universe, newly formed stars have progressively become more metal-rich, exposing organisms to increasingly intense ultraviolet radiation. Our findings imply that planets hosted by stars with low metallicity are the best targets to search for complex life on land.

Venous thromboembolism among physically active young adult females.

Background: Young adult females are at risk of venous thromboembolism (VTE) due to various acquired and transient factors. In recent years, a growing number of females have engaged in strenuous physical activity, but its role as a risk factor for VTE is uncertain. Objectives: To determine the incidence of VTE in young adult females engaged in strenuous physical activity. Methods: A large national cohort of female individuals enlisted in the Israeli Defense Forces between 2012 and 2019 was analyzed. The study group consisted of participants undergoing strenuous physical training during their military service, while the control group maintained regular activity levels. We compared the incidence of VTE between the groups and adjusted for potential risk factors using a multivariate Cox analysis. Results: The cohort included 160,718 female individuals aged 18 to 21years, of whom 11,745 engaged in strenuous physical activity and 148,973 served as controls. During a mean follow-up of 1.7 years, VTE occurred in 5 individuals (0.04%) in the strenuous activity group and 47 individuals (0.03%) in the control group. The incidence per 10,000 person-years was 2.41 (95% CI, 0.78-5.62) for the strenuous activity group and 1.82 (95% CI, 1.34-2.42) for the controls. Strenuous activity did not increase the risk for VTE in univariate or multivariate regression, with a hazard ratio (HR) of 1.27 (95% CI, 0.49-4.22). Use of oral contraceptives was the only significant risk factor, demonstrating dose effect; HR 1.95 (95% CI, 1.06-3.57) for low dose and HR 3.62 (95% CI, 1.40-9.37) for medium estrogen dose contraceptives. Conclusion: Strenuous physical activity did not increase the risk for VTE among a large cohort of young adult female individuals.

Supporting Young Children With Disabilities During the COVID-19 Pandemic: Evidence From Caregivers in Virginia.

Early care and education (ECE) experiences shape children's developmental trajectories, particularly for children who have or may have disabilities. However, caregivers of children with disabilities have faced considerable challenges finding care for their children, which have increased during the COVID-19 pandemic. Using survey data from nearly 3,000 caregivers of preschool-age children in Virginia collected in December 2020 and January 2021, we find that caregivers of children with disabilities were less likely to find ECE programs that met their needs, more likely to experience high levels of stress, and more likely to be concerned about their children's development than were caregivers of children without disabilities. Concerns about child development were particularly pronounced among caregivers of children with disabilities in remote instructional settings. Our findings suggest a disproportionate impact of ECE disruption on caregivers of children with disabilities and the need for targeted supports for these caregivers moving forward.

Unexpected Candidal Hyphae in Oral Mucosa Lesions-A Clinico-Pathological Study.

Background: Oral mucosal biopsies might harbor candidal hyphae (CH) in the absence of any clinical signs or symptoms. Aim: To assess oral mucosa biopsies for the frequency of unexpected CH and characterize their clinico-pathological features. Materials and Methods: All biopsy reports (2004−2019) were searched using CH/candida/candidiasis as key words. Cases with clinical diagnosis of oral candidiasis (OC) were excluded. Demographic data, health status, smoking habits, clinical features and diagnoses were collected. Statistical analysis included the chi-square test; significance was set at p < 0.05. Results: Of all the biopsies, 100 (1.05%) reported microscopical evidence of CH without typical clinical signs/symptoms of OC. Fifteen cases were from healthy, non-smoking patients. CH was common on buccal mucosa (38%) and lateral tongue (23%). The tip of tongue (OR = 54.5, 95% CI 9.02−329.4, p < 0.001) and lateral tongue (OR = 3.83, 95% CI 2.4−6.09, p < 0.001) were more likely to harbor CH-positive lesions. CH-positive lesions were diagnosed as epithelial hyperplasia (55%) and exophytic reactive lesions (30%). No correlation was found between CH and the grade of epithelial dysplasia. Conclusions: Microscopic evidence of CH embedded into oral epithelium without typical signs/symptoms of OC is rare, especially in healthy, non-smokers. Since CH was occasionally found in oral sites prone to local trauma and in association with reactive lesions, in absence of host co-morbidities, the contribution of local mechanical forces to CH embedment cannot be ruled out.

The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response.

Despite their key regulatory role and therapeutic potency, the molecular signatures of interactions between T cells and antigen-presenting myeloid cells within the tumor microenvironment remain poorly characterized. Here, we systematically characterize these interactions using RNA sequencing of physically interacting cells (PIC-seq) and find that CD4+PD-1+CXCL13+ T cells are a major interacting hub with antigen-presenting cells in the tumor microenvironment of human non-small cell lung carcinoma. We define this clonally expanded, tumor-specific and conserved T-cell subset as T-helper tumor (Tht) cells. Reconstitution of Tht cells in vitro and in an ovalbumin-specific αß TCR CD4+ T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht-dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.

Positive impacts of a strengths-based family program on Latino kindergarteners' narrative language abilities.

Narrative language abilities are foundational to literacy development and are a culturally grounded measure of early literacy for Latino children. This study evaluates the impacts on narrative language abilities and the costs of a 4-week, strengths-based program that leverages two valued sociocultural practices with built-in benefits, personal narratives, and family food routines (e.g., grocery shopping), for improving Latino kindergarteners' learning outcomes in the United States. Two-hundred and 34 children (M age = 67 months; 51% girls; 13 schools) and their parents participated in a cluster randomized trial. Children produced personal narratives at three time points: pretest, end-of-treatment, and 5-month follow-up. Four narrative features were measured: narrative coherence, elaborations, word types, and literate language features. Large positive impacts were observed on all four narrative features at the end-of-treatment posttest (d = 1.21-1.76). There was suggestive evidence of moderate impacts on one narrative feature (i.e., narrative coherence) at the 5-month follow-up (d = .59). The costs required to implement the family program were relatively low. Findings highlight the potential value of implementing this strengths-based program in schools serving Latino kindergarteners using a rigorous evaluation of its effectiveness. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A strengths-based, culturally responsive family intervention improves Latino kindergarteners' vocabulary and approaches to learning.

Food routines are an ecocultural asset of Latino families. This cluster-randomized trial with 248 children (Mage  = 67 months; 50% girls; 13 schools) investigated the impact of a 4-week family program designed to capitalize on food routines in improving Latino kindergarteners' outcomes in the United States. There were moderate-to-large impacts on child vocabulary (especially food-related) at end-of-treatment and the 5-month follow-up, and suggestive evidence of moderate impacts on approaches to learning (ATL; including ATL math) and executive function at the 5-month follow-up (d = .38-.95). There were no statistically significant impacts on children's math or literacy skills. A strengths-based, culturally responsive family intervention that is integrated into Latino family life can improve the skills needed to succeed in school.

Relationship between religiosity, spirituality and physical and mental outcomes in fibromyalgia patients.

OBJECTIVES: The coping mechanisms utilised by patients with the fibromyalgia syndrome (FM) pose a crucial focus of treatment. Previous research points to the positive effects of religiosity and spirituality (R/S) as tools for coping with illness. The role of these factors in coping with chronic pain in FM has not previously been studied. The aim of this study was to evaluate the link between R/S and FM outcomes. METHODS: Fifty-five FM patients (ACR criteria) attending a tertiary rheumatology clinic completed a packet of questionnaires assessing demographic data, levels of religiosity and spirituality (SpREUK) and locus of control (LOC). These variables were then individually assessed for influence on FM outcome measures, using the Fibromyalgia Impact Questionnaire (FIQ), the SF-36, and the Beck Depression Index (BDI). RESULTS: A high score on SpREUK I (search for meaningful support) was negatively correlated with the Role-Physical (p=0.032) and Role-Emotional (p<0.005) scales on SF-36. Secular patients scored higher on SF-36 domains of "Role limitation due to emotional health" and "General health" (p<0.05). Employment demonstrated a positive correlation with the FIQ (p<0.01), the BDI (p<0.001), and the SF-36 (p<0.05). Physical activity correlated positively with BDI scores (p=0.012) and better scores on SF-36: energy/fatigue (p=0.024), social-functioning (p=0.014) and physical-functioning (p<0.01). No significant correlation was found between LOC (internal versus external) and FM outcomes. No significant correlation was found between SpREUK domains and the BDI. CONCLUSIONS: FM patients do not appear to benefit from high levels of R/S. Physicians should be aware of the impact of R/S on well-being in this population.

The Kindergarten Hotspot: Literacy Skill Convergence Between Boston Prekindergarten Enrollees and Nonenrollees.

Preschool improves children's kindergarten readiness, but the cognitive outcomes of preschool enrollees and nonenrollees tend to converge partially or fully in elementary school. In older programs, most of this convergence occurs in kindergarten (Li et al., 2016), but evidence from today's programs is sparse. Using data on 4,971 children who applied to the Boston Public School Prekindergarten program and a quasi-experimental approach, we examine convergence in kindergarten through third grade (K-3) literacy outcomes of prekindergarten enrollees and nonenrollees. Consistent with previous literature, most of the convergence in K-3 literacy outcomes occurred in kindergarten. Our findings suggest that detailed investigations into the kindergarten teaching and learning context may be particularly important for solving the widely noted preschool convergence pattern.

Anticoagulant and antiplatelet treatment in cancer patients with thrombocytopenia.

A B S T R A C T Antithrombotic therapy (anticoagulation or antiplatelet therapy) is frequently prescribed in cancer patients for prior or new indications such as venous thromboembolism, secondary prevention of arterial thrombosis or atrial fibrillation. Therefore, it is not uncommon for thrombocytopenic cancer patients to have an indication for antithrombotic therapy. Thrombocytopenia does not reduce the risk of recurrent thrombosis. The bleeding risk with anticoagulation appears to increase when platelets are <50×109/L, but individual platelet counts are poor predictors of bleeding. Management options when platelets are <50×109/L include no change, temporarily withholding antithrombotic therapy, reducing dose, changing the regimen, and increasing the platelet transfusion threshold. There are currently no data on use of direct oral anticoagulants when platelets are below 50×109/L, and there is reason in restricting their use. Little is known on antiplatelet therapy in this setting, although recent data suggest the prognostic importance and apparent safety of aspirin in acute myocardial infarction and thrombocytopenia. This paper will review the evidence, guidelines, current practice and ongoing studies on anticoagulation and antiplatelet therapy in thrombocytopenic patients with cancer.

Massive Pulmonary Hemorrhage from Bronchial Varix.

Bronchial varix is a rare pulmonary disorder which may lead to life-threatening hemorrhage. Diagnosis is difficult because of the subtle abnormalities on radiographic and bronchoscopic examination. We present a case of massive hemoptysis from a bleeding bronchial varix. In the absence of immediate complex endobronchial therapy in the island of Guam, this case was initially managed with nebulized and intravenous tranexamic acid. This was followed by endobronchial blockade of the bleeding airway with endobronchial epinephrine instillation. Selective bronchial artery embolization alleviated the acute-phase bleeding. Prone positioning was initiated due to severe hypoxia after blood clots compromised the patency of bilateral bronchial airways. Prone ventilation was employed for 17 hours for 2 consecutive days with intermittent bronchoscopic forceps extraction of airway blood clots while in the prone position. These maneuvers resulted to improved lung ventilation and oxygenation. The patient underwent bronchial sleeve resection surgery for definitive management.

Anticoagulation in thrombocytopenic patients with hematological malignancy: A multinational clinical vignette-based experiment.

BACKGROUND: Thrombocytopenia in cancer patients with an indication for anticoagulation poses a unique clinical challenge. There are guidelines for the setting of venous thromboembolism but not atrial fibrillation (AF). Evidence is lacking and current practice is unclear. OBJECTIVE: To identify patient and physician characteristics associated with anticoagulation management in hematological malignancy and thrombocytopenia. METHODS: A clinical vignette-based experiment was designed. Eleven hematologists were interviewed, identifying 5 relevant variable categories with 2-5 options each. Thirty hypothetical vignettes were generated. Each physician received 5 vignettes and selected a management strategy (hold anticoagulation; no change; transfuse platelets; modify type/dose). The survey was distributed to hematologists and thrombosis specialists in 3 countries. Poisson regression models with cluster robust variance estimates were used to calculate relative risks for using one management option over the other, for each variable in comparison to a reference variable. RESULTS: 168 physicians answered 774 cases and reported continuing anticoagulation for venous thromboembolism or AF in 607 (78%) cases, usually with dose reduction or platelet transfusion support. Overall, management was affected by platelet count, anticoagulation indication, time since indication, type of hematological disease and treatment, and prior major bleeding, as well as physician demographics and practice setting. The CHA2DS2-VASc score and time since AF diagnosis affected anticoagulation management in AF. CONCLUSION: This study indicates what the widely accepted management strategies are. These strategies, and possibly others, should be assessed prospectively to ascertain effectiveness. The decision process is intricate and compatible with current venous thromboembolism guidelines.