Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
BACKGROUND:Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS:In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS:The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS:In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19
BACKGROUND:Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS:In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS:The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS:In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).
Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19
OBJECTIVE:<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS:Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.
Identifying high-risk features for readmission in patient with metastatic solid tumor malignancies at an academic community hospital. [Meeting Abstract]
Cancer Antigen 72-4 for the Monitoring of Advanced Tumors of the Gastrointestinal Tract, Lung, Breast and Ovaries
BACKGROUND:Cancer antigen CA72-4 is a tumor marker found to be elevated in a variety of human adenocarcinomas. Using the DRG TM-CA72-4, we quantified the elevation of CA72-4 compared to current United States Food And Drug Administration-approved tumor markers in various cancer types. MATERIALS AND METHODS:We conducted a prospective, single-center study enrolling 96 patients between March 2013 and August 2016 with different locally advanced, unresectable or metastatic cancer known to express CA72-4. Quantification of CA72-4 was performed according to the manufacturer's instructions using the DRG TM-CA72-4 enzyme-linked immunosorbent assay kit and the positivity rates were calculated. RESULTS:CA72-4 expression varied with tumoral site of origin, with the highest positivity rates found in pancreatic and ovarian malignancies. Correlation with clinical activity was also noted in some patients. CONCLUSION:CA72-4 may have a potential role as an adjunct to conventional biomarkers in disease monitoring of pancreatic, ovarian and colorectal carcinomas.
Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma [Case Report]
We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.
Coronary Calcium Scanning in Patients after Adjuvant Radiation for Early Breast Cancer and Ductal Carcinoma In situ
BACKGROUND AND OBJECTIVE/OBJECTIVE:Radiation therapy (RT) is part of standard adjuvant treatment for breast cancer. Earlier studies demonstrated increased cardiac morbidity and mortality from this. Coronary Calcium scanning utilizing Multidetector Computed Tomography (MDCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcifications. In our study we employed these tools to detect occult atherosclerosis at least 5â€‰years following breast RT. METHODS:We evaluated 20 asymptomatic patients, <60â€‰years old, treated with RT at least 5â€‰years prior to enrollment. Nine received RT to the left and 11 to the right chest wall. The median interval between RT and calcium scan was 8â€‰years. All patients were treated with external beam RT using tangential technique. All patients underwent MDCT to compute volumetric and Agatston calcium scores of the coronary arteries and the aorta. RESULTS:Eleven patients had RT to the right chest wall, and eight had a calcium score of 0, while two had minimally elevated scores and one patient had a significantly elevated score. Meanwhile nine patients had RT to the left chest wall, and seven had a calcium score of 0. None had significantly elevated scores. In the aorta, 11 of 20 patients had a score of 0, while 8 of 20 had minimally elevated scores. CONCLUSION/CONCLUSIONS:In contrast to studies demonstrating increased cardiovascular morbidity, our pilot study did not detect significant occult atherosclerosis using MDCT of the coronaries and aorta of patients assessed five or more years following radiation for treatment of breast cancer.
Sex hormone receptors in breast cancer
The dependency of certain breast cancers on estrogen is undeniably one of the most important observations in oncology. Since this early observation, there has been a tremendous effort to define the precise roles of the estrogen receptor (ER) in the pathogenesis of breast cancer. Estrogen signaling pathways can also be exploited as effective targets for cancer treatment. Both ligand-dependent and ligand-independent receptor activation pathways have been successfully blocked by hormonal therapies including selective ER modulators such as tamoxifen, by blocking and accelerating the degradation of ER (fulvestrant), and by depleting tissue levels of estrogen (aromatase inhibitors). Because of the immense prognostic and predictive value of the ER and PR receptor, accurately defining hormone dependency is also of paramount importance. Despite this avalanche of discovery and development resulting in improved outcome for the patient, resistance to these therapies, both intrinsic and acquired, is well known. Uncovering the various mechanisms of resistance has deepened scientific understanding of posttranslational modifications of these receptors, as well as their cross talk with other receptor families such as the HER-2/neu receptor. The recent discovery that orphan estrogen-related receptors may also play an important role in breast cancer is just starting to be appreciated. A clear understanding of the historical perspective and the intricacies of ER structure and function is required to improve current therapeutic strategies for breast cancer.
Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer
Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.
Successful desensitization in a patient with lenalidomide hypersensitivity [Letter]