Safety and efficacy of aminophylline in the prevention of bradyarrhythmia during coronary atherectomy.

Coronary calcified lesions are commonly encountered and coronary atherectomy is commonly used for lesion modification during percutaneous coronary interventions (PCI). The release of adenosine during atherectomy can result in bradyarrhythmias and aminophylline is commonly used to prevent this reaction. We identified 138 patients to evaluate the safety and efficacy of intravenous (IV) aminophylline administration prior to coronary atherectomy. A total of 159 calcified lesions were treated, and the atherectomy device was orbital atherectomy, rotational atherectomy, and both in 52 %, 42 %, and 6 %; respectively. After administration of aminophylline, 4.3 % of patients required intraprocedural insertion of a transvenous pacer (TVP), and 18.1 % of patients required administration of IV atropine. Technical success was achieved in 98.6 % of patients, and no adverse reactions to aminophylline were reported. All patients survived to discharge. In conclusion, aminophylline administration prior to coronary atherectomy was safe and effective. No adverse effects of aminophylline were seen, and the rate of bailout TVP placement was low.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Genomic alterations and transcriptional phenotypes in circulating tumor DNA and matched metastatic tumor.

Background: Profiling circulating cell-free DNA (cfDNA) has become a fundamental practice in cancer medicine, but the effectiveness of cfDNA at elucidating tumor-derived molecular features has not been systematically compared to standard single-lesion tumor biopsies in prospective cohorts of patients. The use of plasma instead of tissue to guide therapy is particularly attractive for patients with small cell lung cancer (SCLC), a cancer whose aggressive clinical course making it exceedingly challenging to obtain tumor biopsies. Methods: Here, a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent SCLC, we study cfDNA low pass whole genome (0.1X coverage) and exome (130X) sequencing in comparison with time-point matched tumor, characterized using exome and transcriptome sequencing. Results: Direct comparison of cfDNA versus tumor biopsy reveals that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor but also identifies clinically relevant resistance mechanisms and cancer driver alterations not found in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Genomic sequencing coverage of plasma DNA fragments around transcription start sites shows distinct treatment-related changes and captures the expression of key transcription factors such as NEUROD1 and REST in the corresponding SCLC tumors, allowing prediction of SCLC neuroendocrine phenotypes and treatment responses. Conclusions: These findings have important implications for non-invasive stratification and subtype-specific therapies for patients with SCLC, now treated as a single disease.

Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma.

The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to surgery or radiation therapy. Although cemiplimab shows excellent efficacy with a good tolerability profile, it can cause side effects, including potentially life-threatening endocrinopathies. We discuss the case of a 77-year-old Caucasian female with CSCC treated with only three cycles of cemiplimab who presented with altered mental status and was found to have severe hyperglycemia, hyperosmolarity, ketonemia, glucosuria, and ketonuria concerning for hyperosmolar hyperglycemic syndrome (HHS) with concurrent diabetic ketoacidosis (DKA). The patient made a rapid recovery in the hospital while on standard therapies for HHS/DKA and cemiplimab was discontinued upon discharge. While there have been reports of cemiplimab-induced DKA, to our knowledge, this is the first reported case of cemiplimab-induced HHS-DKA. This report aims to shed light on cemiplimab-induced HHS-DKA and to underscore the need to elucidate the molecular mechanisms underlying ICI-induced diabetes mellitus (ICI-DM).

Helicobacter pylori Infection and Complications of Cirrhosis.

INTRODUCTION: Helicobacter pylori is a significant contributor to conditions such as peptic ulcer disease, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and colorectal cancer. Recent studies have suggested a potential link between H. pylori and cirrhosis. However, the impact of H. pylori on cirrhosis-related mortality, inpatient outcomes, and decompensating events remains unclear. Considering the widespread availability of H. pylori testing and effective treatment options, there is a potential rationale for eradicating H. pylori in cirrhotic patients to mitigate the morbidity and mortality associated with cirrhosis. This study aims to investigate the association between H. pylori and inpatient outcomes and complications related to cirrhosis. METHODS: The National Inpatient Sample (NIS) database, a part of the Healthcare Cost & Utilization Project, was utilized for this study. Inpatient data from the years 2016 through 2019 were extracted for patients with a primary discharge diagnosis of cirrhosis and a concurrent diagnosis of H. pylori infection. The primary outcomes included inpatient mortality, length of stay, and cost of care. Secondary outcomes involved cirrhosis-related complications during hospitalization, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome. RESULTS: Over the years 2016 to 2019, 416,410 patients received a primary discharge diagnosis of cirrhosis. Among them, 990 patients (0.2%) had a secondary diagnosis of H. pylori infection. Those with both cirrhosis and H. pylori tended to be younger on average (mean age 54.25 vs. 57.18 years, p=0.01) and more frequently fell within the age range of 18-49 (33.84% vs. 24.71%, P=0.01). H. pylori-infected patients were also more likely to be male (70.71% vs. 63.11%, P<0.028), of Hispanic race (36.4% vs. 18.6%, p< 0.1), and of Black race (20.2% vs. 8.1%, p< 0.1). While H. pylori-exposed patients had lower in-hospital mortality (0.51% vs. 4.44%, p=0.007), their mean length of stay was higher (6.97 days vs. 5.75, p=0.002). The overall cost of care was comparable between the H. pylori-exposed and non-exposed groups (mean USD18,106.18 vs. $16,543.49, P=0.160). H. pylori-exposed patients had a higher overall rate of cirrhosis-related complications (84.85% vs. 67.59%, p< 0.001), gastrointestinal bleeding (48.48% vs. 27.34%, p< 0.001), and hepatorenal syndrome (70.71% vs. 46.99%, p< 0.001), and these differences persisted in multivariable analysis. Initially, rates of hepatic encephalopathy were higher in H. pylori non-exposed patients (21.57% vs. 15.66%, p=0.04), but this discrepancy was corrected after adjusting for potential confounders. CONCLUSION: While patients in this study were diagnosed with both H. pylori and cirrhosis by discharge, it cannot be definitively concluded that H. pylori was the direct cause of cirrhosis complications. Recognizing this uncertainty, further studies are needed better to understand the associations between cirrhosis and H. pylori complications. Distinguishing the causes of cirrhosis and its relationship with H. pylori may offer deeper insights into whether H. pylori is a causative factor or merely correlated in its effects on patients with cirrhosis.

Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.

Breast cancer accounts for the highest cancer cases globally, with 12% of occurrences progressing to metastatic breast cancer with a low survival rate and limited effective early intervention strategies augmented by late diagnosis. Moreover, a low concentration of prognostic and predictive markers hinders disease monitoring. Circulating and exosomal microRNAs (miRNAs) have recently shown a considerable interplay in breast cancer, standing out as effective diagnostic and prognostic markers. The primary functions are as gene regulatory agents at the genetic and epigenetic levels. An array of dysregulated miRNAs stimulates cancer-promoting mechanisms, activating oncogenes and controlling tumor-suppressing genes and mechanisms. Exosomes are vastly studied extracellular vesicles, carrying, and transporting cargo, including noncoding RNAs with premier roles in oncogenesis. Translocation of miRNAs from the circulation to exosomes, with RNA-binding proteins in stress-induced conditions, has shown significant cooperation in function to promote breast cancer. This review examines cellular and exosomal miRNA biogenesis and loading, the clinical implications of their dysregulation, their function in diagnosis, prognosis, and prediction of breast cancer, and in regulating cancer signaling pathways. The influence of cellular and exosomal miRNAs presents clinical significance on breast cancer diagnosis, subtyping, staging, prediction, and disease monitoring during treatment, hence a potent marker for breast cancer.

Endoscopic Management of Gastric Band Erosion: a Systematic Review and Meta-Analysis.

BACKGROUND: Gastric band erosion may be seen in up to 3% of patients. Endoscopic intervention has become increasingly utilized due to its minimally invasive nature. The purpose of this study was to perform a systematic review and meta-analysis to examine the role of endoscopic removal for eroded gastric bands. METHODS: Individualized search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases in accordance with PRISMA and MOOSE guidelines. Outcomes included technical success, clinical success, procedure duration, adverse events, and surgical conversion. Pooled proportions were analyzed using random effects models. Heterogeneity and publication bias was assessed with I2 statistics and funnel plot asymmetry using Egger and Begg tests. Meta-regression was also performed comparing outcomes by endoscopic tools. RESULTS: Ten studies (n=282 patients) were included in this meta-analysis. Mean age was 40.68±7.25 years with average duration of band placement of 38.49±19.88 months. Pre-operative BMI was 42.76±1.06 kg/m2 with BMI of 33.06±3.81 kg/m2 at time of band erosion treatment. Endoscopic removal was attempted in 240/282 (85.11%) of cases. Pooled technical and clinical success of the endoscopic therapy was 86.08% (95% CI: 79.42-90.83; I2=28.62%) and 85.34% (95% CI: 88.70-90.62; I2=38.56%), respectively. Mean procedure time for endoscopic removal was 46.47±11.52 min with an intra-operative adverse event rate of 4.15% (95% CI: 1.98-8.51; I2=0.00%). Post-procedure-associated adverse events occurred in 7.24% (CI: 4.46-11.55; I2=0.00%) of patients. Conversion to laparotomy/laparoscopy occurred in 10.54% (95% CI: 6.12-17.54) of cases. CONCLUSION: Endoscopic intervention is a highly effective and safe modality for the treatment of gastric band erosion.

A Meta-analysis of Standard Versus Ultrasound-Assisted Catheter-Directed Thrombolysis in the Management of Acute Pulmonary Embolism.

Background: Standard catheter-directed thrombolysis (SCDT) harnesses the therapeutic benefit of systemic thrombolytics while minimizing bleeding complications in patients presenting with pulmonary embolism (PE). Ultrasound-assisted catheter-directed thrombolysis (USAT) theoretically improves upon SCDT by disrupting fibrin and increasing the surface area exposed to thrombolytic agent. However, it is unclear if this translates into improved outcomes. Methods: A systematic search of prior publications comparing SCDT and USAT in patients with intermediate or high-risk PE was conducted. Primary outcomes of interest were bleeding events, ICU and hospital length of stay. Secondary outcomes included changes in pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (mPAP), and right ventricle to left ventricle diameter (RV/LV) ratio. Studies that lacked comparison groups were excluded. Bias assessments were performed using the Cochrane tools for randomized and nonrandomized studies. Data was collated utilizing the Cochrane Review Manager software, and all analyses assumed random effects. Results: Our search yielded 7 observational studies and 1 randomized control trial. The studies included a total of 543 patients who underwent either SCDT (n = 273) or USAT (n = 270) for intermediate or high-risk PE. The synthesized analysis showed no significant differences in bleeding between the groups. There were no differences in ICU or hospital lengths of stay, changes in PASP, or mPAP. Reductions in RV/LV ratio were greater with SCDT (mean difference, -0.16; 95% CI, -0.27 to -0.06; P = .003). Conclusions: In comparison to SCDT, USAT did not result in improved clinical or hemodynamic outcomes in patients presenting with PE. Results were limited by heterogeneity among the included studies.