20966 research outputs found
Sort by
Lacerate and Macerate: The BASILICA-LLAMACORN/UNICORN Combination to Optimize Bioprosthetic Bileaflet Modification
No full textWorld vitiligo day: a model for grassroots medical activism and pharmaceutical innovation
No full textSequential decreases in basolateral amygdala response to threat predict failure to recover from PTSD
No full textAmygdala hyperreactivity early-post trauma has been a demonstrable neurobiological correlate of future posttraumautic stress disorder (PTSD). The basolateral amygdala (BLA) particularly is vital for fear memory and threat processing, but BLA functional dynamics following a traumatic event are unexplored. BLA reactivity to threat may be a trait that can predict PTSD and persist over time. Alternatively, BLA responsivity to threat cues may change over time and be related to PTSD severity. As part of a larger, multisite study, AURORA, participants 18-75 years old were enrolled in an emergency department (ED) within 72 h of a traumatic event (N = 304, 199 female). At 2-weeks and 6-months post-trauma, PTSD symptoms, BLA responses to threat (fearful\u3eneutral faces), and functional connectivity (FC) during fMRI were assessed. Generalizability of findings was assessed in an external replication sample of ED patients (n = 33). Two weeks post-trauma right BLA reactivity positively predicted later PTSD severity. However, left BLA reactivity to threat at 6 months post-trauma was negatively associated with PTSD severity at that timepoint (ΔPseudo-R(2) = 0.04, IRR = 0.38, p \u3c 0.001). In addition, a decrease in BLA reactivity from 2-weeks to 6-months predicted greater PTSD severity at 6 months (ΔPseudo-R(2) = 0.03, IRR = 0.58, p \u3c 0.001). This replicated in the external sample. A reduction in left BLA FC with the dorsal attention network predicted increased PTSD severity over time. These findings support a shift in BLA function within the first 6 months post-trauma that predicts PTSD pathology and stand in contrast to prior conceptualizations of amygdala hyperreactivity as a trait-like PTSD risk factor
Management of alcohol use disorder in alcohol-related liver disease
No full textAlcohol-related liver disease (ArLD) is a leading cause of liver-related morbidity and mortality worldwide and is fundamentally connected to alcohol use disorder (AUD). ArLD develops in a subset of heavy drinkers, with progression from steatosis to cirrhosis. Despite the proven benefits of AUD treatment in halting ArLD progression, fewer than 20% of patients with AUD and ArLD receive treatment, and less than 2% are prescribed pharmacotherapy. Hepatology and gastroenterology practitioners are often not confident to manage coexistent AUD and ArLD. This article examines the relationship between AUD and ArLD, evaluates treatment options and highlights the role of integrated care in improving outcomes. Medical addiction therapy significantly reduces binge drinking, hospitalisations and the risk of hepatic decompensation. Several pharmacotherapies are viable in ArLD, but require specific consideration of hepatotoxicity, renal excretion and central nervous system effects. Psychotherapy is associated with lower rates of hepatic decompensation and improved liver-related outcomes. Integrated care models that embed AUD treatment within liver clinics improve engagement, abstinence rates and clinical outcomes compared with standard referrals. AUD treatment is fundamental in ArLD management. Increased use of pharmacological and psychological therapies, alongside integrated care models, may improve patient outcomes and reduce the burden of ArLD. Further research is needed to optimise treatment strategies in this high-risk population
American Radium Society Appropriate Use Criteria for the Workup and Treatment of Local Intraprostatic Recurrence of Prostate Cancer Following Definitive Radiotherapy
No full textBACKGROUND AND OBJECTIVE: Local intraprostatic radiorecurrence of prostate cancer (IPR-PC) can be associated with an aggressive natural history and impact long-term disease-specific survival. While appropriate local salvage intervention can be curative, best practices for workup and local salvage of intraprostatic recurrence are poorly defined. The American Radium Society (ARS) Genitourinary Appropriate Use Criteria Committee sought to develop evidence-based recommendations to address this gap.
METHODS: PubMed and Embase were searched to retrieve a comprehensive set of relevant peer-reviewed articles on four topics relevant to the workup and treatment of IPR-PC. The literature was evaluated and summarized by three investigators, and clinical variants were created for each of the four topics. The ARS Genitourinary AUC multidisciplinary expert panel voted on the most appropriate procedures for each variant, and a modified Delphi approach was used to summarize recommendations.
KEY FINDINGS AND LIMITATIONS: The panel concluded that radiographic staging via prostate-specific membrane antigen positron emission tomography (PSMA PET) and multiparametric magnetic resonance imaging should be performed to exclude patients with metastatic disease and identify the local extent of radiorecurrence. Biopsy is required before local salvage to avoid excessive toxicity in patients whose radiographic recurrence represents a treatment effect. Consideration of local salvage is preferred in lieu of noncurative hormonal manipulation alone, although shared decision-making is critical. Salvage reirradiation approaches are recommended to limit toxicity. Hormonal therapy may be beneficial for radiosensitization when radiotherapeutic salvage is pursued, but only of short duration, and classic androgen deprivation therapies are preferred over novel hormonal agents. Focal salvage should be pursued when confidence in focal recurrence can be confirmed via multiple radiographic and tissue sampling modalities, although the toxicity associated with whole-gland salvage appears to be very tolerable. Several radiotherapeutic salvage regimens exist, most of which can be carried out in six or fewer fractions. The data informing this guideline are limited to individuals initially treated with conventionally fractionated external beam radiotherapy and with workup for recurrence before the PSMA PET era.
CONCLUSIONS AND CLINICAL IMPLICATIONS: This consensus guideline provides evidence-based guidance on the appropriate procedures for workup and treatment of IPR-PC. Prospective evidence to enrich these guidelines is eagerly anticipated.
PATIENT SUMMARY: We summarize evidence for the best workup and treatment for patients with local recurrence of prostate cancer after radiotherapy. A panel of experts evaluated previous studies and voted on the procedures that should be performed and those that should be avoided. This guideline is a useful tool for helping doctors to discuss the best treatment options that maximize the chance of cure while minimizing side effects
A Response to the Letter to the Editor: Can We Refine Criteria for the First-Line Treatment for Patients With Advanced ALK-Positive NSCLC in the Real World?
No full textMolecular Characterization and Clinical Outcomes of Pancreatic Neuroendocrine Neoplasms Harboring PAK4-NAMPT Alterations
No full textPURPOSE: The mammalian target of rapamycin (mTOR) inhibitor everolimus is US Food and Drug Administration-approved for advanced pancreatic neuroendocrine neoplasms (pNENs), yet resistance is common, necessitating the identification of resistance mechanisms for effective treatment strategies. Previous studies suggest that targeting the aberrant expression of mTOR regulators p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) sensitizes pNENs to everolimus. In this study, we queried a large real-world data set of pNENs, characterizing the molecular and immune landscapes, as well as the clinical outcomes associated with aberrant PAK4 and NAMPT expression.
METHODS: Two-hundred and ninety-four pNEN cases were analyzed using next-generation sequencing and whole-exome/whole-transcriptome sequencing. We stratified patients into clusters on the basis of median cutoff.
RESULTS: High expression of genes activated in response to mTOR activation was found in NAMPT-high and PAK4-high groups. Enrichment of PI3K/AKT/mTOR and glycolysis pathways was observed in these tumors. Higher mutation rates in multiple endocrine neoplasia type 1, alpha thalassemia/mental retardation syndrome X-linked, TSC2, SETD2, and CCNE1 were observed in high NAMPT and PAK4 clusters. Immune analysis revealed enrichment in inflammatory response pathways, IL2/STAT5 signaling, and immune checkpoint genes. Increased neutrophils, natural killer cells, and macrophages were found in PAK4-high/NAMPT-high tumors. Analysis of real-world patient data revealed that high PAK4 (P = .0428) or NAMPT (P = .0002) expression individually correlated with lower overall survival in all neuroendocrine neoplasms (NEN) cohorts, while the combined high expression of both was associated with the worst outcomes (P = .0002). Similar trends were observed in pancreatic NEN cohorts.
CONCLUSION: Our study demonstrates that PAK4-high/NAMPT-high pNENs are associated with distinct molecular and immune profiles. Further investigation is warranted to determine if dual PAK4 and NAMPT blockade enhances the efficacy of immunotherapeutics
Perioperative Management of Oral Anticoagulation in Patients with Venous Thromboembolism
No full textPerioperative management of anticoagulation for patients with history of venous thromboembolism (VTE) is based on the patient\u27s individual recurrent VTE risk and procedural bleeding risk. The American College of Chest Physicians (ACCP) guidelines can help in estimating VTE recurrence risk. For warfarin, holding 5 days prior to a procedure, and restarting the night of or morning after is suggested. For direct oral anticoagulants, holding for 1 calendar day (as opposed to 24 hours) in low-to-moderate bleeding risk procedures, and 2 days for high bleeding risk procedures has been shown to be safe and is supported by the ACCP guidelines
Leukemia Cutis With Concomitant Seborrheic Keratosis as the Presenting Symptom of Chronic Lymphocytic Leukemia: A Case Report
No full textLeukemia cutis is a term used to describe a dermatologic manifestation of hematologic malignancies. It represents a wide range of identifiable cutaneous lesions that result from the infiltration of neoplastic leukocytes in patients with leukemia or lymphoma. We report a case involving an initial solitary lesion without systemic symptoms, but a biopsy revealed a seborrheic keratosis in the epidermis with lymphoid infiltration in the dermis. Flow cytometry studies confirmed a B-cell chronic lymphocytic leukemia, and an additional investigation with fluorescence in situ hybridization demonstrated a chromosomal deletion in the long arm of chromosome 13 at position 14, indicating a favorable prognosis. The patient was referred to a hematologist, who determined that no pharmacologic treatment was necessary at that time. The patient continues to follow up for monitoring of his disease