A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies.

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.

The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies.

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.

Adverse childhood experiences, gender, and suicidality among Florida high school students: Examining intervening mechanisms.

BACKGROUND: Adverse childhood experiences (ACEs) represent a key risk factor for suicidal thoughts and behaviors among adolescents. However, the intervening mechanisms linking ACEs and suicidality, and whether such processes vary by gender, remain underexplored. OBJECTIVE: The present study examines whether the relationships between ACEs and the likelihood of experiencing suicidal thoughts and attempting suicide are indirect through depressive symptoms and low self-control. This study also investigates whether these direct and indirect paths might be moderated by gender. PARTICIPANTS AND SETTING: The analyses make use of data on a statewide representative sample of students enrolled in public high schools in Florida (N = 23,078) from the 2022 Florida Youth Substance Abuse Survey (FYSAS). METHODS: Generalized structural equation modeling (GSEM) was used to estimate the direct and indirect effects of ACEs on the likelihood of suicidal thoughts and attempting suicide. The indirect effects were assessed using bootstrapping, and between-gender differences in the coefficients were tested. RESULTS: ACEs has direct associations with depressive symptoms, low self-control, and both suicidality outcomes. The effects of ACEs on suicidal thoughts are indirect through both depressive symptoms and low self-control, and the effects of ACEs on suicide attempts are indirect through depressive symptoms. Limited gender differences in these pathways emerge. CONCLUSIONS: For male and female youth, ACEs are associated with heightened depression symptoms and reduced self-control, and both of these factors partially explain the previously established relationship between ACEs and suicidality.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

Update on corneal crosslinking for keratoconus and corneal ectasia.

PURPOSE OF REVIEW: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations. RECENT FINDINGS: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients. SUMMARY: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.

Rice bran arabinoxylan compound as a natural product for cancer treatment - an evidence-based assessment of the effects and mechanisms.

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA.

Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense, Caenorhabditis elegans Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1's helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

Chronic Idiopathic Ulcers Mimicking Cecal Carcinoma: A Case Report.

Chronic idiopathic ulcers of the colon pose diagnostic challenges due to their elusive etiology and potential resemblance to other intestinal pathologies, such as cecal carcinoma. This case report outlines the clinical course of a 68-year-old female patient who presented to the emergency department (ED) with persistent right lower quadrant pain. Despite multiple hospital visits yielding varied diagnoses, a definitive diagnosis was only made following a laparoscopic partial colectomy, which revealed chronic idiopathic ulcers with transmural scarring and adhesions to adjacent small intestine loops. Histological examination demonstrated a substantial ulcer bed populated by inflammatory cells, including large stellate and spindled stromal cells within the granulation tissue, alongside lymphoid hyperplasia and scar tissue extending into the muscularis propria. The initial presentation of this case could easily be mistaken for appendicitis, diverticulitis, carcinoma, or irritable bowel syndrome, highlighting the significance of considering chronic idiopathic ulcers in the differential diagnosis of patients presenting with cecal masses.

DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract.

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Long-distance dispersal in the short-distance dispersing house sparrow (Passer domesticus).

The house sparrow (Passer domesticus) is a small passerine known to be highly sedentary. Throughout a 30-year capture-mark-recapture study, we have obtained occasional reports of recoveries far outside our main metapopulation study system, documenting unusually long dispersal distances. Our records constitute the highest occurrence of long-distance dispersal events recorded for this species in Scandinavia. Such long-distance dispersals radically change the predicted distribution of dispersal distances and connectedness for our study metapopulation. Moreover, it reveals a much greater potential for colonization than formerly recorded for the house sparrow, which is an invasive species across four continents. These rare and occasional long-distance dispersal events are challenging to document but may have important implications for the genetic composition of small and isolated populations and for our understanding of dispersal ecology and evolution.

Asian koel rapidly locates host breeding in novel nest sites.

Avian brood parasites depend upon locating host nests to lay their eggs. However, how brood parasites locate host nests and select the nests for parasitism remains poorly studied. Here, we examined how a non-evicting brood parasite, the Asian koel (Eudynamys scolopaceus) were able to locate host nests in locally novel nest sites. We provided a set of novel nest sites (i.e., nestboxes, n = 100) to the common myna (Acridotheres tristis), a regular host of the Asian koel, at a field site in Central Bangladesh. We found that common myna quickly utilized the novel breeding sites (n = 99 nests across 59 boxes) and similarly, 21.2% of these nests were parasitized by the Asian koel. Unsurprisingly, none of the inactive nest boxes were parasitized, neither were empty nests of common myna (i.e., either predated or fledged clutches, thus lack of parental activity, n = 83). Our results provide an experimental demonstration of the Asian koel ability to rapidly locate nests in locally novel nest sites, potentially facilitated by close monitoring of host activity and behavior around the nest site. However, the underlying mechanisms for this rapid adjustment to novel nest sites remain unresolved.

Titration of Medications after Acute Heart Failure is Safe, Tolerated, and Effective Regardless of Risk.

BACKGROUND: Guideline-directed medical therapy decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF, high intensity care (HIC) in the form of rapid uptitration of heart failure (HF) guideline-directed medical therapy (GDMT) was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. OBJECTIVES: To assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable Meta-Analysis Global Group in Chronic (MAGGIC) HF risk score. METHODS: In STRONG-HF, 1078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) versus usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at Day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. RESULTS: Among 1062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC versus UC group and did not differ by MAGGIC risk score tertiles (interaction non-significant). The incidence of all-cause death or HF readmission at Day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1-3. The HIC arm was at lower risk of all-cause death or HF readmission at Day 180 (HR 0.66, 95% CI 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR 0.51, 0.62, 0.68 in tertile 1, 2, and 3, respectively, (interaction non-significant) for all comparisons) and continuous (p-interaction=NS) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction non-significant). CONCLUSIONS: HIC led to better use of GDMT and lower HF-related morbidity and mortality compared to UC regardless of underlying HF risk profile.

Characteristics, treatment, and outcomes of early vs. late enrollees of the STRONG-HF trial.

BACKGROUND: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist. METHODS: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736). RESULTS: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73). CONCLUSIONS: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03412201.

Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs.

One critical mechanism through which prostate cancer (PCa) adapts to treatments targeting androgen receptor (AR) signaling is the emergence of ligand-binding domain-truncated and constitutively active AR splice variants, particularly AR-V7. While AR-V7 has been intensively studied, its ability to activate distinct biological functions compared to the full-length AR (AR-FL), and its role in regulating the metastatic progression of castration-resistant PCa (CRPC), remains unclear. Our study found that, under castrated conditions, AR-V7 strongly induced osteoblastic bone lesions, a response not observed with AR-FL overexpression. Through combined ChIP-seq, ATAC-seq, and RNA-seq analyses, we demonstrated that AR-V7 uniquely accesses the androgen-responsive elements in compact chromatin regions, activating a distinct transcription program. This program was highly enriched for genes involved in epithelial-mesenchymal transition and metastasis. Notably, we discovered that SOX9, a critical metastasis driver gene, was a direct target and downstream effector of AR-V7. Its protein expression was dramatically upregulated in AR-V7-induced bone lesions. Moreover, we found that Ser81 phosphorylation enhanced AR-V7's pro-metastasis function by selectively altering its specific transcription program. Blocking this phosphorylation with CDK9 inhibitors impaired the AR-V7-mediated metastasis program. Overall, our study has provided molecular insights into the role of AR splice variants in driving the metastatic progression of CRPC.

Number of Older Biological Siblings and Early-Onset Colorectal Cancer Risk.

Colorectal cancer (CRC) is the third most common cancer in the United States.1 Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).1 By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.2 To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.3 Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.

Status epilepticus in Auckland, New Zealand: Treatment patterns and determinants of outcome in a prospective population-based cohort.

OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE). METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously. RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups. SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.