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.

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.

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.

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.