Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92 · 3% of patients received the primer vaccine, 70 · 8% received one monovalent booster, but only 30 · 1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR = 0 · 61, p = 0 · 024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed.

Characteristics of Lung Cancer Patients With Asymptomatic or Undiagnosed SARS-CoV-2 Infections.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer. PATIENTS AND METHODS: In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection. RESULTS: Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002). CONCLUSIONS: In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.

Burden and predictors of thirty-day readmission in patients with NSTEMI: a retrospective analysis of the 2020 NRD database.

BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is an entity which was defined as a type of a coronary syndrome with positive cardiac biomarker of myocardial necrosis with no ST-segment elevation in ECG. Currently, the centers for Medicare and Medicaid services (CMS) Hospital readmission reduction program assistance risk-adjusted 30-day readmission rates for five major clinical entities which includes acute myocardial infarction. METHODS: We performed this retrospective study to look into the current burden and predictors of NSTEMI readmission. Data were obtained from the Nationwide Readmission Database for the year 2020. We analyzed data on hospital readmission of 336 620 adults who were admitted for NSTEMI. RESULTS: The 30-day readmission rate was 13.5% with NSTEMI being the most common cause of readmission. Mortality was higher in readmitted patients compared to index admission (5.4 vs 3.6%, P = 0.000). Higher risk of readmission was associated with female sex, higher Charlson comorbidity index, and longer length of stay. Lower risk of admission was seen in patients from smaller communities, patients who underwent percutaneous coronary intervention, and discharged to rehabilitation facilities. CONCLUSION: Although we found an improvement in readmission rates compared to prior studies, about 13% of patients continue to get readmitted within 30 days causing significant cost to the healthcare system and often these patients have worse outcomes. We need continuing large-scale studies to identify quality measures to prevent readmission, improve mortality during readmission, and make better use of financial resources.

Risk Factors of Acute Ischemic Stroke and Mortality Among Adults With Endocardial Fibroelastosis.

OBJECTIVES: Endocardial fibroelastosis (EFE) is a rare form of restrictive cardiomyopathy associated with high morbidity and mortality. The literature is sparse on information pertaining to risk stratification. Thus, we sought to highlight the risk factors of acute ischemic stroke (AIS) and mortality in adults with EFE. METHODS: The National Inpatient Sample (NIS) database was queried from 2001 to 2020 using the International Classification of Diseases 9th Revision (ICD-9) and 10th Revision (ICD-10) codes for adult patients with EFE. Factors associated with AIS and mortality were identified. RESULTS: In all, 18495 cases of EFE fit the inclusion criteria, of which 2370 (12.82%) had AIS. The mean ages for patients with and without AIS were 62.37 and 54.24, respectively. Multivariate regression suggested greater odds of AIS in patients with hypertension (aOR 2.329, P<0.01), dyslipidemia (aOR: 1.566, P<0.01), peripheral vascular disease (PVD) (aOR: 1.736, P<0.01), alcohol abuse (aOR: 1.817, P<0.01), age >60 y (aOR: 1.646, P<0.01), females (vs. males, aOR: 1.238, P<0.01), and smokers (aOR: 1.697, P<0.01). Patients with cirrhosis (aOR: 0.174, P<0.01), CKD (aOR: 0.369, P<0.01), COPD (aOR: 0.402, P<0.01), atrial fibrillation (aOR: 0.542, P<0.01) had lower odds of AIS. 3.1% of EFE patients with AIS died. Diabetes (aOR: 11.665, P<0.01) and COPD (aOR: 3.201, P=0.017) were associated with the greatest odds of all-cause mortality. Dyslipidemia (aOR: 0.387, P=0.010) and females (vs. males, aOR: 0.432, P=0.012) had reduced odds of all-cause mortality. CONCLUSION: Several risk factors are associated with AIS in EFE, while diabetes, COPD, and being male are associated with mortality in EFE.

Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites.

Brain metastasis of advanced breast cancer often results in deleterious consequences. Metastases to the brain lead to significant challenges in treatment options, as the blood-brain barrier (BBB) prevents conventional therapy. Thus, we hypothesized that creation of a nanoparticle (NP) that distributes to both primary tumor site and across the BBB for secondary brain tumor can be extremely beneficial. Here, we report a simple targeting strategy to attack both the primary breast and secondary brain tumors utilizing a single NP platform. The nature of these mitochondrion-targeted, BBB-penetrating NPs allow for simultaneous targeting and drug delivery to the hyperpolarized mitochondrial membrane of the extracranial primary tumor site in addition to tumors at the brain. By utilizing a combination of such dual anatomical distributing NPs loaded with therapeutics, we demonstrate a proof-of-concept idea to combat the increased metabolic plasticity of brain metastases by lowering two major energy sources, oxidative phosphorylation (OXPHOS) and glycolysis. By utilizing complementary studies and genomic analyses, we demonstrate the utility of a chemotherapeutic prodrug to decrease OXPHOS and glycolysis by pairing with a NP loaded with pyruvate dehydrogenase kinase 1 inhibitor. Decreasing glycolysis aims to combat the metabolic flexibility of both primary and secondary tumors for therapeutic outcome. We also address the in vivo safety parameters by addressing peripheral neuropathy and neurobehavior outcomes. Our results also demonstrate that this combination therapeutic approach utilizes mitochondrial genome targeting strategy to overcome DNA repair-based chemoresistance mechanisms.

Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.

AIMS: We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. METHODS AND RESULTS: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: -4780 to 5178; P = 0.93). CONCLUSIONS: In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors.

Re-evaluating the Incidence and Prevalence of Clinical Hypertrophic Cardiomyopathy: An Epidemiological Study of Olmsted County, Minnesota.

OBJECTIVE: To contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015. PATIENTS AND METHODS: A validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984. RESULTS: Two hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade. CONCLUSION: The incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period.

Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T-cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92·3% of patients received the primer vaccine, 70·8% received one monovalent booster, but only 30·1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR=0·61, P=0·024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed. Highlights: COVID-19 booster vaccinations increase antibody levels and maintain T-cell responses against SARS-CoV-2 in patients receiving various anti-cancer therapiesBooster vaccinations reduced all-cause mortality in patientsA significant proportion of patients remain unboosted and strategies are needed to encourage patients to be up-to-date with vaccinations.

Correction to "New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance".

[This corrects the article DOI: 10.1021/acscentsci.3c00286.].

New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance.

Tumor cells adapt to diverse survival strategies defying our pursuit of multimodal cancer therapy. Prostate cancer (PCa) is an example that is resistant to one of the most potent chemotherapeutics, cisplatin. PCa cells survive and proliferate using fatty acid oxidation (FAO), and the dependence on fat utilization increases as the disease progresses toward a resistant form. Using a pool of patient biopsies, we validated the expression of a key enzyme carnitine palmitoyltransferase 1 A (CPT1A) needed for fat metabolism. We then discovered that a cisplatin prodrug, Platin-L, can inhibit the FAO of PCa cells by interacting with CPT1A. Synthesizing additional cisplatin-based prodrugs, we documented that the presence of an available carboxylic acid group near the long chain fatty acid linker on the Pt(IV) center is crucial for CPT1A binding. As a result of fat metabolism disruption by Platin-L, PCa cells transition to an adaptive glucose-dependent chemosensitive state. Potential clinical translation of Platin-L will require a delivery vehicle to direct it to the prostate tumor microenvironment. Thus, we incorporated Platin-L in a biodegradable prostate tumor-targeted orally administrable nanoformulation and demonstrated its safety and efficacy. The distinctive FAO inhibitory property of Platin-L can be of potential clinical relevance as it offers the use of cisplatin for otherwise resistant cancer.

Dilated Cardiomyopathy: Beware of Diet Drugs Slimming the Heart.

There have been rare reports of dilated cardiomyopathy from chronic use of phentermine/topiramate, although very limited data are available. Phentermine is an atypical amphetamine analog that has been contraindicated in patients with a history of cardiovascular disease. We present a case of nonischemic dilated cardiomyopathy in the setting of chronic phentermine/topiramate use, which is the most likely cause of her dilated cardiomyopathy.

Yamaguchi syndrome - An updated review article of electrocardiographic and echocardiographic findings.

Apical hypertrophic cardiomyopathy (ApHCM) is thought to be an uncommon variant of hypertrophic cardiomyopathy (HCM). This article is a literature review focusing on the characteristic electrocardiogram (EKG) and 2D echocardiogram findings as currently there are no specific ACC/AHA/ESC guidelines set as diagnostic criteria for ApHCM.

Serratia endocarditis, uncommon organism, with significant complications.

Serratia marcescens is an aerobic, Gram-negative bacillus predominantly seen in patients with intravenous drug use, immunosuppression, previous antibiotic exposure, and indwelling catheterization. Gram-negative organism causing infective endocarditis (IE) is rare. Serratia marcescens IE is uncommon and is reported to be seen in 0.14% of all cases. In this report, we discuss in detail about a 38-year-old man with a history of intravenous drug abuse presenting with S. marcescens related prosthetic valve IE.

Trends, Burden, and Impact of Arrhythmias on Cardiac Transplant Recipients: A 16-year Nationwide Study.

Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and allograft rejection may result in an increased prevalence of arrhythmias in transplanted hearts. We aim to describe the trends, distribution, and the clinical impact of arrhythmias in patients with transplanted hearts. We queried the National Inpatient Sample with administrative codes for cardiac transplant patients using procedure ICD-9-CM codes 37.5 and 33.6. Arrhythmias were extracted using validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis. There were a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States of which 1,6342 (54.4%) had an arrhythmia. The frequency of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. Transplant patients with arrythmias was not associated with significantly higher inpatient mortality (7.72% vs 6.90%, P = 0.225). The most common arrythmia was atrial fibrillation ([AF]26.83%) followed by ventricular tachycardia (22.86%). Trends in mortality associated with arrhythmias following heart transplant has been decreasing from 12.3% in 1999 to 8.9% in 2014 (P = 0.04). Subgroup analysis of ventricular arrythmias (VA) following heart transplant were associated with increased mortality (8.61% vs 6.94%, P = 0.0229). Over half of patients develop 1 or more cardiac arrhythmia after heart transplant. There is an increasing secular trend in the frequency of arrhythmias post cardiac transplant with atrial fibrillation determined to be the most common arrhythmia.

Critical Stenosis in Left Anterior Descending Artery: Beware of T- Wave Inversions.

Wellens' syndrome (WS) is a pattern on an electrocardiogram (ECG) characterized by biphasic T waves or deeply inverted T waves in leads V2-V3 with a recent clinical history of angina. Wellens' pattern on the ECG is particular for critical left anterior descending artery (LAD) stenosis. Wellens' sign and WS have been used interchangeably in the literature. However, the typical patterns of ECG changes noted are mostly represented by Wellens' sign. These ECG changes have been crucial in identifying this subset of patients with severe LAD disease.

Brugada Sign in a Cardiac Transplant Donor.

Brugada syndrome (BrS) is a rare entity represented by the Brugada sign on an electrocardiogram (EKG) and is associated with sudden cardiac death (SCD). There is little data to guide the management of donor Brugada syndrome in the setting of cardiac transplantation. A 31-year-old male sustained out-of-hospital cardiac arrest secondary to polysubstance use and was found asystole. Bystander cardiopulmonary resuscitation (CPR) with advanced cardiovascular life support (ACLS) protocol was initiated. Return of spontaneous circulation (ROSC) was achieved and the patient was taken to the emergency room (ER) in sinus rhythm with an initial presenting EKG showing the Brugada sign. A toxicological screen for cocaine was positive. The patient was eventually declared brain dead and underwent angiographic and echocardiographic evaluation as a donor heart for cardiac transplantation and was accepted for transplantation. Cardiac arrest in a young patient with a Brugada sign on EKG is a concern for BrS. Cocaine exerts a sodium channel blockade that can unmask BrS. Genetic testing for sodium voltage-gated channel alpha subunit 5 (​​​​​​SCN5A) gene mutation was negative, however, only 15% to 30% of patients carry the mutation. We proceeded with cardiac transplantation and suggested an implantable cardioverter defibrillator (ICD) for primary prevention in the recipient, should further specialized testing reveal a continued concern for BrS. We suggest the necessity for further data to guide decisions in patients with BrS undergoing cardiac transplantation.

Left Main Coronary Artery Disease: The Forgotten Lead of Electrocardiogram Is Predictive.

An ST segment depression in eight or more leads along with ST segment elevation in lead aVR or V1, especially occurring during ischemic symptoms, has a very high predictive accuracy of left main or three-vessel disease, or tight proximal left anterior descending (LAD) coronary artery stenosis. We describe a classic case of a patient who presented with ST elevation in the lead aVR with diffuse ST segment depression during anginal symptoms and was found to have severe disease in the distal left main, ostial circumflex, and left anterior descending artery on an emergent coronary angiogram.

Machine learning predicting mortality in sarcoidosis patients admitted for acute heart failure.

Background: Sarcoidosis with cardiac involvement, although rare, has a worse prognosis than sarcoidosis involving other organ systems. Objective: We used a large dataset to train machine learning models to predict in-hospital mortality among sarcoidosis patients admitted with heart failure (HF). Method: Utilizing the National Inpatient Sample, we identified 4659 patients hospitalized with a primary diagnosis of HF. In this cohort, we identified patients with a secondary diagnosis of sarcoidosis using International Statistical Classification of Disease, Tenth Revision (ICD-10) codes. Patients were separated into a training group and a testing group in a 7:3 ratio. Least absolute shrinkage and selection operator regression was used to select variables to prevent model overfitting or underfitting. For machine learning models, logistic regression, random forest, and XGBoosting were applied in the training group. Parameters in each of the models were tuned using the GridSearchCV function. After training, all models were further validated in the testing group. Models were then evaluated using the area under curve (AUC) score, sensitivity, and specificity. Results: A total of 2.3% of sarcoidosis patients died in HF admission. Our machine learning model analysis found the RF model to have the highest AUC score and sensitivity. Feature analysis found that comorbid arrhythmias and fluid electrolyte disorders were the strongest factors in predicting in-hospital mortality. Conclusion: Machine learning methods can be useful in identifying predictors of in-hospital mortality in a given dataset.

Controlled release nanoplatforms for three commonly used chemotherapeutics.

In order to combat an evolving, multidimensional disease such as cancer, research has been aimed at synthesizing more efficient and effective versions of popular chemotherapeutic drugs. Despite these efforts, there remains a necessity for the development of suitable delivery vehicles that can both harness the chemotherapeutic effects meanwhile reducing some of the known issues when using these drugs such as unwanted side-effects, acquired drug resistance, and associated difficulties with drug delivery. Synthetic drug discovery approaches focusing on modification of the native structure of these chemotherapeutic drugs often face challenges such as loss of efficacy, as well as a potential worsening of side-effects. Synthetic chemists are then left with increasingly narrow choices for possible chemistry they could implement to achieve the desired therapy. The emergence of targeted therapies using controlled-release nanomaterials can provide many opportunities for conventional chemotherapeutic drugs to be delivered to specific target sites, ultimately leading to reduced side-effects and improved efficacy. Logically, it may prove advantageous to consider nano-delivery systems as a likely candidate for circumventing some of the barriers associated with creating viable drug therapies. In this review, we summarize controlled release nanoformulations of the three most widely used and approved chemotherapeutics, doxorubicin, paclitaxel, and cisplatin as an alternative therapeutic approach against different cancer types.