Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study.

BACKGROUND: Procalcitonin (PCT), an inflammatory blood biomarker, is well studied in infectious diseases. Its prognostic value in unselected emergency department (ED) patients remains yet undefined. Herein, we investigated association of admission PCT levels and mortality in a large, international-multicenter ED patient cohort. METHODS: We prospectively enrolled 6970 unselected, consecutive, adult, medical patients seeking ED care in three tertiary-care hospitals in Switzerland, France and the USA. We used multivariable logistic regression models to examine association of admission PCT levels (as a continuous predictor and across cut-offs) and 30-day mortality. We also investigated subgroup effects by main diagnosis, comorbidities and clinical features at presentation. RESULTS: During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%, 13% to 15%, respectively. This association was also confirmed in a fully-adjusted model including age, gender, main symptom, main diagnosis and vital parameters on admission. Receiver operating characteristic (ROC) curve analysis showed that PCT differentiated well between survivors and non-survivors in the overall cohort (area under ROC curve [AUC] 0.75) with best results for patient with metabolic (AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved the prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other secondary endpoints including intensive care unit (ICU) admission and hospital readmission. CONCLUSIONS: In this large and heterogenous medical ED patient cohort, admission PCT was a strong and independent outcome predictor for 30-day mortality across different medical diagnoses independent of underlying infection. PCT may help to improve risk stratification in unselected medical ED patients.

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

INTRODUCTION: Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. METHOD: We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). RESULTS: During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. CONCLUSIONS: Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Granulicatella adiacens Endocarditis of a Bioprosthetic Aortic Valve.

Infective endocarditis (IE) is relatively uncommon; however, when it is diagnosed, it is usually among those with known cardiac valvular abnormalities. The most common pathogens that cause endocarditis are streptococci (mainly viridans), enterococci, and other streptococci species. An extremely rare pathogen that could cause IE is Granulicatella. This gram-positive coccus classically inhabits human mucosal surfaces and only rarely causes disease. We present an incredibly rare case of a 74-year-old female with a bioprosthetic aortic valve replacement, who presented with headache and weakness and was subsequently found to have recurrent Granulicatella adiacens infective endocarditis.

A Rare Case of Cord Compression From Extra-Medullary Hematopoiesis (EMH) in Beta Thalassemia.

Cord compression can arise from many different etiologies -- including trauma, degenerative changes, growths, neoplasms, or even abscesses. While some etiologies can cause symptoms such as weakness or motor deficits, others can simply present as pain. A rare cause of cord compression is extramedullary hematopoiesis (EMH), or the growth of blood cells outside the bone marrow. This rare, abnormal growth of cells can result in severe complications such as increased intracranial pressure and motor and sensory impairment. General clinicians should strive for early and prompt diagnosis of cord compression whenever possible, especially in patients who present with acute neurological deficits. We present a case of a 27-year-old female with beta thalassemia major (BTM) and transfusional hemosiderosis, who came in with progressive lower extremity weakness, numbness and urinary retention, and was diagnosed with acute cord compression from EMH.

Non-sustained Ventricular Tachycardia as a Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disorder with familial (autosomal dominant) predisposition and can be challenging to diagnose. Non-sustained ventricular tachycardia (NSVT) is a relatively uncommon and short-lived arrhythmia when seen in the general, healthy population. NSVT with a left bundle branch block morphology is usually idiopathic but may also be seen in ARVC. It can also be associated with poorer prognosis and increased mortality. Repetitive monomorphic ventricular ectopic beats may suggest ARVC, but could also be idiopathic. Timely diagnosis is vital due to the unpredictability and progressive nature of ARVC. We present a case of a 40-year-old Caucasian female with heart palpitations and NSVT found on an outpatient Holter monitor, and later found to have clinical and radiological features consistent with ARVC.

Correction: A Rare Case of Cord Compression From Extra-Medullary Hematopoiesis (EMH) in Beta Thalassemia.

[This corrects the article DOI: 10.7759/cureus.38520.].

Role of Checkpoint Inhibitors in the Management of Gastroesophageal Cancers.

PURPOSE: This article reviews the essential clinical trials that have led to these immunotherapy approvals and explores the use of predictive biomarkers, such as PD-L1 expression and MSI status, to identify patients who are most likely to benefit from immunotherapies. METHODS: This case review series describe findings from different clinical trials and contribute to the evolving understanding of the role of CPIs in managing advanced gastroesophageal cancers and may lead to improved treatment options and patient outcomes. Ongoing clinical trials also hold promise for expanding treatment options and improving patient outcomes in the future. METHODS: The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. A systematic literature review was conducted to identify relevant clinical trials and studies that describe the role of immune checkpoint inhibitors in managing advanced gastroesophageal cancers. Electronic database (PubMed, Clinicaltrials.gov, Society of Immunotherapy of Cancer, Aliment Pharmacology & Therapeutics, BMC cancer, Molecular Cancer Research, Nature Reviews Molecular Cell Biology, American Association for Cancer Research, Science, Nature, Cancer Discovery, Journal of the National Cancer Institute, Advanced Immunology, Oncotarget, Nature Medicine, Nature Genetics, Gut, Pathology and Oncology Research, Journal of Clinical Oncology, The New England Journal of Medicine, Gastrointestinal oncology, JAMA Oncology, Journal of Gastrointestinal Oncology, Current Oncology, Annals of Oncology, The Lancet, JCO Oncology Practice, Future Oncology, Gastric Cancer, CA: A Cancer Journal for Clinicians, American Journal of Gastroenterology, Gastroenterology, Journal of the National Cancer Institute, International Journal of Epidemiology, Helicobacter, Gastroenterology Review) were searched using a combination of relevant keywords and MESH terms. The search encompassed articles published up to 5/2023. Additionally, manual searches of reference lists of selected articles and pertinent review papers were conducted to ensure comprehensive coverage of relevant studies. Studies were included if they provided insights into clinical trials evaluating the efficacy and safety of CPIs in treating advanced gastroesophageal cancers. Relevant case reviews and trials exploring combination therapies involving CPIs were also considered. Articles discussed in the utilization of predictive biomarkers were included to assess their impact on treatment outcomes. Data from selected studies were extracted to inform the narrative review. Key findings were summarized, including clinical trial designs, patient populations, treatment regimens, response rates, progression-free survival (PFS), overall survival (OS), and adverse events. The role of predictive biomarkers, particularly PD-L1 expression and MSI status, in identifying patients likely to benefit from CPIs was critically evaluated based on study results. Ongoing clinical trials investigating novel combination strategies and exploring the broader scope of CPIs in gastroesophageal cancers were also highlighted. The collected data were synthesized to provide a comprehensive overview of the crucial clinical trials that have contributed to the approval of CPIs for advanced gastroesophageal cancers. The role of CPIs in different lines of therapy, including first-line regimens, was discussed. Furthermore, the evolving landscape of predictive biomarkers was examined, emphasizing their potential significance in optimizing patient selection for CPI therapy. Ongoing clinical trials were reviewed to underscore the continuous efforts in expanding treatment options and improving patient outcomes in the future.

Copper Deficiency-Induced Neuropathy After Bariatric Surgery Disguised as Demyelinating Disease: A Case Report.

Neuropathy may arise from many different etiologies - from diabetes and nerve compression to viral infections and chemotherapy side effects; many patients suffer from neuropathic symptoms. While some etiologies produce irreversible neuropathy, others, such as vitamin and mineral deficiencies, lead to a possibly reversible disease process once treated. General clinicians should strive for early and prompt diagnosis of copper deficiency neuropathy whenever possible, especially in patients with normal vitamin B12 levels who present with a subacute gait disorder or prominent sensory ataxia. We present a case of a 73-year-old female with a surgical history of Roux-en-Y gastric bypass (RYGB) 20 years prior, who presented with difficulty with ambulation due to sensory ataxia and bilateral, ascending, sensory neuropathy, who was diagnosed with acquired copper deficiency-induced myeloneuropathy.

Combination of the National Early Warning Score (NEWS) and inflammatory biomarkers for early risk stratification in emergency department patients: results of a multinational, observational study.

OBJECTIVES: The National Early Warning Score (NEWS) helps to estimate mortality risk in emergency department (ED) patients. This study aimed to investigate whether the prognostic value of the NEWS at ED admission could be further improved by adding inflammatory blood markers (ie, white cell count (WCC), procalcitonin (PCT) and midregional-proadrenomedullin (MR-proADM). DESIGN: Secondary analysis of a multinational, observational study (TRIAGE study, March 2013-October 2014). SETTING: Three tertiary care centres in France, Switzerland and the USA. PARTICIPANTS: A total of 1303 adult medical patients with complete NEWS data seeking ED care were included in the final analysis. NEWS was calculated retrospectively based on admission data. MAIN OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcome was intensive care unit (ICU) admission. We used multivariate regression analyses to investigate associations of NEWS and blood markers with outcomes and area under the receiver operating curve (AUC) as a measure of discrimination. RESULTS: Of the 1303 included patients, 54 (4.1%) died within 30 days. The NEWS alone showed fair prognostic accuracy for all-cause 30-day mortality (AUC 0.73), with a multivariate adjusted OR of 1.26 (95% CI 1.13 to 1.40, p<0.001). The AUCs for the prediction of mortality using the inflammatory markers WCC, PCT and MR-proADM were 0.64, 0.71 and 0.78, respectively. Combining NEWS with all three blood markers or only with MR-proADM clearly improved discrimination with an AUC of 0.82 (p=0.002). Combining the three inflammatory markers with NEWS improved prediction of ICU admission (AUC 0.70vs0.65 when using NEWS alone, p=0.006). CONCLUSION: NEWS is helpful in risk stratification of ED patients and can be further improved by the addition of inflammatory blood markers. Future studies should investigate whether risk stratification by NEWS in addition to biomarkers improve site-of-care decision in this patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study.

INTRODUCTION: The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. METHODS: We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. RESULTS: Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75-1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). CONCLUSIONS: Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out).

Predictors for Delayed Emergency Department Care in Medical Patients with Acute Infections - An International Prospective Observational Study.

INTRODUCTION: In overcrowded emergency department (ED) care, short time to start effective antibiotic treatment has been evidenced to improve infection-related clinical outcomes. Our objective was to study factors associated with delays in initial ED care within an international prospective medical ED patient population presenting with acute infections. METHODS: We report data from an international prospective observational cohort study including patients with a main diagnosis of infection from three tertiary care hospitals in Switzerland, France and the United States (US). We studied predictors for delays in starting antibiotic treatment by using multivariate regression analyses. RESULTS: Overall, 544 medical ED patients with a main diagnosis of acute infection and antibiotic treatment were included, mainly pneumonia (n = 218; 40.1%), urinary tract (n = 141; 25.9%), and gastrointestinal infections (n = 58; 10.7%). The overall median time to start antibiotic therapy was 214 minutes (95% CI: 199, 228), with a median length of ED stay (ED LOS) of 322 minutes (95% CI: 308, 335). We found large variations of time to start antibiotic treatment depending on hospital centre and type of infection. The diagnosis of a gastrointestinal infection was the most significant predictor for delay in antibiotic treatment (+119 minutes compared to patients with pneumonia; 95% CI: 58, 181; p<0.001). CONCLUSIONS: We found high variations in hospital ED performance in regard to start antibiotic treatment. The implementation of measures to reduce treatment times has the potential to improve patient care.