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Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk

Brosnahan, Shari B; Chen, Xian Jie Cindy; Chung, Juri; Altshuler, Diana; Islam, Shahidul; Thomas, Sarun V; Winner, Megan D; Greco, Allison A; Divers, Jasmin; Spiegler, Peter; Sterman, Daniel H; Parnia, Sam
BACKGROUND:Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES/OBJECTIVE:The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS:A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS:= 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE/UNASSIGNED:Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
PMID: 34180274
ISSN: 1542-6270
CID: 4926192

A Rare Cause of Biliary Obstruction: Intrabiliary Rupture of a Hepatic Hydatid Cyst [Meeting Abstract]

Forman, Jacqueline; Jimada, Ismail; Shapiro, Daniel; Friedel, David; Klein, Natalie; Cunha, Burke; Winner, Megan
ISSN: 0002-9270
CID: 3897712

Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection

Elliott, Irmina A; Epelboym, Irene; Winner, Megan; Allendorf, John D; Haigh, Philip I
CONTEXT/BACKGROUND:Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. OBJECTIVE:To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. DESIGN/METHODS:We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. MAIN OUTCOME MEASURES/METHODS:Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI ≥ 2, p < 0.01). Distal resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p < 0.01; HR = 0.54, p < 0.01, respectively). CONCLUSION/CONCLUSIONS:In a large population-based database, the rates of postpancreatectomy endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.
PMID: 28406793
ISSN: 1552-5775
CID: 3486992

Liver-Directed Therapy in Metastatic Colorectal Cancer

Wilson, Ana; Ronnekliev-Kelly, Sean; Winner, Megan; Pawlik, Timothy M.
Approximately 50-70 % of patients with colorectal cancer ultimately develop colorectal liver metastases. Determining which patients may benefit from aggressive treatment has historically been achieved through clinical predictive models. However, factors such as radiographic response to neoadjuvant therapy should also be taken into consideration. Recently, molecular markers have emerged as an adjunct to clinical-pathologic factors and provide a surrogate for tumor biology. With improved understanding of tumor biology, the likelihood of recurrence can be better predicted. However, when feasible, the best chance for cure entails surgical resection as a part of multimodal therapy, and select patients can achieve prolonged median survival. Alternatively, ablation techniques may be used in conjunction with surgery or as isolated therapy in patients who are not candidates for surgical resection. Transarterial therapy may also provide clinical benefit in certain patient subsets with unresectable disease. These strategies have allowed for a more tailored approach to patients with colorectal liver metastases.
ISSN: 1556-3790
CID: 3502202

The Level of Estrogen and Progesterone Receptor Immunoreactivity Correlates With Time to Disease Recurrence in Hormone Receptor-Positive Breast Cancer [Meeting Abstract]

Winner, Megan; Rosman, Martin; Mylander, Charles; Jackson, Rubie Sue; Pozo, Marcos; Umbricht, Christopher; Tafra, Lorraine
ISSN: 1068-9265
CID: 3502212

Associations Between Patient Perceptions of Communication, Cure, and Other Patient-Related Factors Regarding Patient-Reported Quality of Care Following Surgical Resection of Lung and Colorectal Cancer

Ejaz, Aslam; Kim, Yuhree; Winner, Megan; Page, Andrew; Tisnado, Diana; Dy, Sydney E Morss; Pawlik, Timothy M
BACKGROUND:The objective of the current study was to analyze various patient-related factors related to patient-reported quality of overall and surgical care following surgical resection of lung or colorectal cancer. METHODS:Between 2003 and 2005, 3,954 patients who underwent cancer-directed surgery for newly diagnosed lung (30.3%) or colorectal (69.7%) cancer were identified from a population- and health system-based survey of participants from multiple US regions. Factors associated with patient-perceived quality of overall and surgical care were analyzed with multivariable logistic regression models. RESULTS:Overall, 56.7% of patients reported excellent quality of overall care and 67.9% of patients reported excellent quality of surgical care; there was no difference by cancer type (P > 0.05). Factors associated with lower likelihood to report excellent quality of overall and surgical care included female sex, minority race, and the presence of multiple comorbidities (all odds ratio [OR] <1, all P < 0.05). Patients who had higher levels of education (overall quality: OR 1.62; surgical quality: OR 1.26), higher annual income (overall quality: OR 1.29; surgical quality: OR 1.23), and good physical function (overall quality: OR 1.35; surgical quality: OR 1.24) were all more likely to report excellent quality of overall and surgical care (all P < 0.05). Furthermore, patients who reported their physician as having excellent communication skills (overall quality: OR 6.49; surgical quality: OR 3.74) as well as patients who perceived their cancer as likely curable (overall quality: OR 1.17; surgical quality: OR 1.11) were more likely to report excellent quality of overall and surgical care (all P < 0.05). CONCLUSION/CONCLUSIONS:Patient-reported quality of care is associated with several factors including race, income, and educational status, as well as physician communication and patient perception of likelihood of cure. Future studies are needed to more closely examine patient-physician relationships and communication barriers, particularly among minority patients and those with lower income and educational status.
PMID: 26608194
ISSN: 1873-4626
CID: 3502232

Reply to Patient perceptions regarding the likelihood of cure after surgical resection of lung and colorectal cancer [Letter]

Winner, Megan; Kim, Yuhree; Pawlik, Timothy M
PMID: 26335580
ISSN: 1097-0142
CID: 3502222

Patient perceptions regarding the likelihood of cure after surgical resection of lung and colorectal cancer

Kim, Yuhree; Winner, Megan; Page, Andrew; Tisnado, Diana M; Martinez, Kathryn A; Buettner, Stefan; Ejaz, Aslam; Spolverato, Gaya; Morss Dy, Sydney E; Pawlik, Timothy M
BACKGROUND:The objective of the current study was to characterize the prevalence of the expectation that surgical resection of lung or colorectal cancer might be curative. The authors sought to assess patient-level, tumor-level, and communication-level factors associated with the perception of cure. METHODS:Between 2003 and 2005, a total of 3954 patients who underwent cancer-directed surgery for lung (30.3%) or colorectal (69.7%) cancer were identified from a population-based and health system-based survey of participants from multiple US regions. RESULTS:Approximately 80.0% of patients with lung cancer and 89.7% of those with colorectal cancer responded that surgery would cure their cancer. Even 57.4% and 79.8% of patients with stage IV lung and colorectal cancer, respectively, believed surgery was likely to be curative. On multivariable analyses, the odds ratio (OR) of the perception of curative intent was found to be higher among patients with colorectal versus lung cancer (OR, 2.27). Patients who were female, with an advanced tumor stage, unmarried, and having a higher number of comorbidities were less likely to believe that surgery would cure their cancer; educational level, physical function, and insurance status were not found to be associated with perception of cure. Patients who reported optimal physician communication scores (reference score, 0-80; score of 80-100 [OR, 1.40] and score of 100 [OR, 1.89]) and a shared role in decision-making with their physician (OR, 1.16) or family (OR, 1.17) had a higher odds of perceiving surgery would be curative, whereas patients who reported physician-controlled (OR, 0.56) or family-controlled (OR, 0.72) decision-making were less likely to believe surgery would provide a cure. CONCLUSIONS:Greater focus on patient-physician engagement, communication, and barriers to discussing goals of care with patients who are diagnosed with cancer is needed.
PMID: 26094729
ISSN: 1097-0142
CID: 3502092

The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms

Winner, Megan; Sethi, Amrita; Poneros, John M; Stavropoulos, Stavros N; Francisco, Peter; Lightdale, Charles J; Allendorf, John D; Stevens, Peter D; Gonda, Tamas A
CONTEXT/BACKGROUND:Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS:We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS:Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS:In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.
PMID: 25791547
ISSN: 1590-8577
CID: 3486792

Neoadjuvant therapy for non-metastatic pancreatic ductal adenocarcinoma

Winner, Megan; Goff, Stephanie L; Chabot, John A
Treatment of pancreatic cancer is increasingly multimodal, with patients receiving chemotherapy, radiation, and surgical extirpation in hope of long-term cure. There is ongoing debate over the timing, sequence, and necessity of these treatments as they pertain to the spectrum of local-regional disease. Current guidelines support a neoadjuvant strategy in patients with locally advanced and borderline resectable disease. Although there is currently no high-level evidence to recommend neoadjuvant therapy for all patients, there are data to suggest that wider application of neoadjuvant therapy may be beneficial. Random-assignment prospective trials are ongoing. In this review we examine the literature addressing a neoadjuvant approach to potentially resectable, borderline resectable, and locally advanced pancreatic cancer and highlight the outcomes of preoperative emergence of latent metastatic disease, attempted resection rates, margin negative resection rates, and pathologic response to treatment.
PMID: 25726054
ISSN: 1532-8708
CID: 3502082