Publications
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Chronic autonomic symptom burden in long-COVID: a follow-up cohort study.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
2025
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Abstract
Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an established online cohort of participants with LC to assess duration and severity of autonomic dysfunction, impact on quality of life, risk factors of autonomic diagnoses including postural tachycardia syndrome (POTS), and efficacy of common treatments.Our international cohort included 526 adults with LC aged 20-65 years who previously completed baseline evaluations of LC symptoms, autonomic symptom burden, and quality of life. Participants repeated survey instruments and completed new instruments assessing risk factors and symptom mitigation strategies. A subset of individuals completed a 10-min active stand test. Multivariable logistic regression identified predictors of autonomic symptom burden and incident autonomic diagnoses including POTS.A total of 71.9% of participants with LC had a Composite Autonomic Symptom Score-31 (COMPASS-31) score ≥ 20, suggestive of moderate-to-severe autonomic dysfunction. The median symptom duration was 36 [30-40] months, and 37.5% of participants could no longer work or had to drop out of school due to their illness. In addition, 40.5% of individuals with autonomic dysfunction were newly diagnosed with POTS, representing 33% of the total LC cohort. Female sex and joint hypermobility were associated with an increased risk of autonomic dysfunction.Evidence of chronic moderate-to-severe autonomic dysfunction was seen in most participants with LC in our cohort and was significantly associated with reduced quality of life and functional disability. POTS was the most common post-COVID autonomic diagnosis.
View details for DOI 10.1007/s10286-025-01111-1
View details for PubMedID 39907931
View details for PubMedCentralID 9639503
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Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data.
Vaccines
2024; 12 (12)
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Abstract
COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed.We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484).Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort.Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC.
View details for DOI 10.3390/vaccines12121427
View details for PubMedID 39772087
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Correction: Cloud-Based Machine Learning Platform to Predict Clinical Outcomes at Home for Patients With Cardiovascular Conditions Discharged From Hospital: Clinical Trial.
JMIR cardio
2024; 8: e68825
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Abstract
[This corrects the article DOI: .].
View details for DOI 10.2196/68825
View details for PubMedID 39658002
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Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data
VACCINES
2024; 12 (12)
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View details for DOI 10.3390/vaccines12121427
View details for Web of Science ID 001385630200001
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A novel label-free biosensor for myocardial ischemia biomarker detection via CRISPR/12a.
Biosensors & bioelectronics
2024; 270: 116954
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Abstract
Myocardial infarction (MI) is the leading cause of death worldwide. Here, we present a novel, label-free biosensor for detecting myocardial ischemia biomarkers via CRISPR/Cas12a. This system utilizes the unique properties of CRISPR/Cas12a and G-quadruplex-ThT-based biosensors, enabling sensitive and specific detection of ATP, a crucial biomarker in cardiovascular diseases, at concentrations as low as 23 nM. Our method demonstrates substantial improvements over traditional ATP detection techniques, such as high-performance liquid chromatography and enzymatic assays, which often require complex sample preparation methods and costly equipment. The feasibility of the biosensor was further demonstrated in various models, including heart failure in mice and hypoxic conditions in cardiomyocytes. This successfully showcased its ability to function as a practical tool for diagnosing and monitoring diseases characterized by ATP dysregulation, highlighting its effectiveness in real-world clinical scenarios. This biosensor is notable for its rapid response, ease of use, and potential for integration into point-of-care diagnostics. These features offer significant advantages for the early diagnosis and management of ischemic heart disease and other conditions where ATP serves as a key metabolic biomarker. This technology also offers significant potential for early diagnosis and monitoring of myocardial ischemia and cardiovascular diagnostics. These findings underscore the biosensor's capacity for real-time ATP monitoring, offering crucial insights into mitochondrial function and disease progression, particularly in cardiovascular and inflammatory diseases.
View details for DOI 10.1016/j.bios.2024.116954
View details for PubMedID 39577179
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Wideband radiofrequency pulse sequence for evaluation of myocardial scar in patients with cardiac implantable devices
FRONTIERS IN RADIOLOGY
2024; 4: 1327406
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Abstract
Cardiac magnetic resonance is a useful clinical tool to identify late gadolinium enhancement in heart failure patients with implantable electronic devices. Identification of LGE in patients with CIED is limited by artifact, which can be improved with a wide band radiofrequency pulse sequence.The authors hypothesize that image quality of LGE images produced using wide-band pulse sequence in patients with devices is comparable to image quality produced using standard LGE sequences in patients without devices.Two independent readers reviewed LGE images of 16 patients with CIED and 7 patients without intracardiac devices to assess for image quality, device-related artifact, and presence of LGE using the American Society of Echocardiography/American Heart Association 17 segment model of the heart on a 4-point Likert scale. The mean and standard deviation for image quality and artifact rating were determined. Inter-observer reliability was determined by calculating Cohen's kappa coefficient. Statistical significance was determined by T-test as a p {less than or equal to} 0.05 with a 95% confidence interval.All patients underwent CMR without any adverse events. Overall IQ of WB LGE images was significantly better in patients with devices compared to standard LGE in patients without devices (p = 0.001) with reduction in overall artifact rating (p = 0.05).Our study suggests wide-band pulse sequence for LGE can be applied safely to heart failure patients with devices in detection of LV myocardial scar while maintaining image quality, reducing artifact, and following routine imaging protocol after intravenous gadolinium contrast administration.
View details for DOI 10.3389/fradi.2024.1327406
View details for Web of Science ID 001294434000001
View details for PubMedID 39175870
View details for PubMedCentralID PMC11339872
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Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial.
JAMA internal medicine
2024
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Abstract
There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms.This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration.Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade.The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.ClinicalTrials.gov Identifier: NCT05576662.
View details for DOI 10.1001/jamainternmed.2024.2007
View details for PubMedID 38848477
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CARDIODIAGNOSTIC FINDINGS IN PATIENTS WITH CHEST PAIN IN A LONGITUDINAL POST-ACUTE COVID SYNDROME CLINIC
ELSEVIER SCIENCE INC. 2024: 660
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View details for Web of Science ID 001291434300661
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CARDIODIAGNOSTIC FINDINGS IN PATIENTS WITH CHEST PAIN IN A LONGITUDINAL POST-ACUTE COVID SYNDROME CLINIC
ELSEVIER SCIENCE INC. 2024: 660
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View details for Web of Science ID 001324901500661
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Cloud-Based Machine Learning Platform to Predict Clinical Outcomes at Home for Patients With Cardiovascular Conditions Discharged From Hospital: Clinical Trial.
JMIR cardio
2024; 8: e45130
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Abstract
Hospitalizations account for almost one-third of the US
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New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series.
Cureus
2023; 15 (12): e51286
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Abstract
Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity. Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.
View details for DOI 10.7759/cureus.51286
View details for PubMedID 38288178
View details for PubMedCentralID PMC10823305
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Sex Influences the Safety and Therapeutic Efficacy of Cardiac Nanomedicine Technologies.
Small (Weinheim an der Bergstrasse, Germany)
2023: e2305940
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Abstract
Nanomedicine technologies are being developed for the prevention, diagnosis, and treatment of cardiovascular disease (CVD), which is the leading cause of death worldwide. Before delving into the nuances of cardiac nanomedicine, it is essential to comprehend the fundamental sex-specific differences in cardiovascular health. Traditionally, CVDs have been more prevalent in males, but it is increasingly evident that females also face significant risks, albeit with distinct characteristics. Females tend to develop CVDs at a later age, exhibit different clinical symptoms, and often experience worse outcomes compared to males. These differences indicate the need for sex-specific approaches in cardiac nanomedicine. This Perspective discusses the importance of considering sex in the safety and therapeutic efficacy of nanomedicine approaches for the prevention, diagnosis, and treatment of CVD.
View details for DOI 10.1002/smll.202305940
View details for PubMedID 37803920
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Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
2023; 166: 115373
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Abstract
With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and β receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.
View details for DOI 10.1016/j.biopha.2023.115373
View details for PubMedID 37647693
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.
Frontiers in neurology
2023; 14: 1090747
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Abstract
The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined.We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) phenotype.The median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS, majority were female, and obesity (BMI > 30 Kg/m2) (P = 0.00377895) and worse functional status (P = 0.0110474) were significantly associated with ME/CFS.Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.
View details for DOI 10.3389/fneur.2023.1090747
View details for PubMedID 36908615
View details for PubMedCentralID PMC9998690
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Microvascular Obstruction Identifies a Subgroup of Patients Who Benefit from Stem Cell Therapy Following ST-Elevation Myocardial Infarction.
American heart journal
2023
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Abstract
Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction.We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multi-center French BONAMI trial and SWISS-AMI trials. A total of 327g patients had paired imaging data at one year. All patients received 100 - 150 million intracoronary autologous BMCs or placebo / control 3 - 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n=210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n=146) (p < 0.01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7%; p < 0.05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo.The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy.
View details for DOI 10.1016/j.ahj.2023.02.004
View details for PubMedID 36796572