Christina Holcroft

Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

PURPOSEnDiffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.nnnPATIENTS AND METHODSnWe determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation.nnnRESULTSnIn the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations.nnnCONCLUSIONnAssessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

Abdominal versus laparoscopic hysterectomies for benign diseases: evaluation of morbidity and mortality among 465,798 cases

Hysterectomy is the most common major gynecological surgery performed in women. The aim of this study was to compare major morbidity and mortality between abdominal hysterectomy (AH) and laparoscopic hysterectomy (LH) for benign diseases. We performed a retrospective cohort study using the data from Health Cost and Utilization Project Nationwide Inpatient Sample. Women were admitted for hysterectomy for benign diseases between the years 2002 and 2008. In-hospital morbidities and mortalities were identified using the diagnostic and procedural codes classified according to the International Classification of Disease, Ninth Revision, and Clinical Modification. Logistic regression analysis was used to estimate the relationship between the type of hysterectomy and the development of major morbidity and mortality. Of a total 465,798 cases, 389,189 women (83.6xa0%) underwent AH and the remainders underwent LH (76,609, 16.4xa0%). The LH group was younger and more likely to be Caucasian than those who underwent AH. Although major morbidities and mortalities were rare, women who underwent LH were less likely to develop thromboembolic events (0.68xa0% vs. 0.84xa0%, odds ratio (OR) 0.85 (0.77–0.93)), require blood transfusions (2.4xa0% vs. 4.7xa0%, OR 0.58 (0.55–0.61)), and sustain bowel perforation (0.07xa0% vs. 0.13xa0%, OR 0.56 (0.42–0.74)). The mortality rate was also lower in the LH group (0.01xa0%) compared with the AH group (0.03xa0%, OR 0.48 (0.24–0.95)). Our conclusion was that for benign diseases, laparoscopic hysterectomy is associated with a lower complication rate than abdominal hysterectomy. When possible, hysterectomy performed for benign diseases should be performed with minimally invasive technique.

Elevated plasma gas6 levels are associated with venous thromboembolic disease

Growth arrest-specific 6 (gas6), a novel vitamin K-dependent protein, has been demonstrated to have a role in thrombus stabilization as gas6 null mice are resistant to lethal venous and arterial thrombosis. However, the association between gas6 and venous thromboembolism has not been elucidated in humans. The present study aims to assess the role of gas6 in human venous thromboembolic (VTE) disease. Using a highly specific ELISA method, we measured plasma levels of gas6 in plasma samples obtained from 279 patients with VTE and 79 healthy volunteers. Medication history, comorbid conditions and VTE characteristics were documented. Mean gas6 levels were higher in patients with VTE as compared to healthy volunteers, being 46xa0±11xa0ng/ml and 35xa0±6.4xa0ng/ml respectively (Pxa0<xa00.001). Odds ratios (OR) for VTE given elevated (≥90th percentile of healthy volunteers) gas6 levels were estimated in regression models in the whole study population. After adjustment for age, sex, medications and comorbidity, subjects with elevated gas6 had an increased risk of VTE (OR of 16.3 (95% CI 5.8–45.7, Pxa0<xa00.001) compared to those with lower levels of gas6. This association remains significant even among patients with a comparable age distribution. Among patients with VTE, mean gas levels showed a trend of higher levels in those with more extensive thrombi. There was no correlation between elevated gas6 levels and recurrent VTE. In conclusion, we demonstrate an association between VTE and elevated gas6 levels consistent with in vivo murine models of thrombosis. This constitutes a potential novel mechanism for thrombosis in humans and may aid in the understanding of the pathophysiology of VTE.

Identification of Quality of Care Deficiencies in Elderly Surgical Patients by Measuring Adherence to Process-Based Quality Indicators

BACKGROUNDnThe ability to measure surgical quality of care is important and can lead to improvements in patient safety. As such, processes should be carried out in an identical fashion for all patients, regardless of how vulnerable or complex they are. Our objectives were to assess quality of surgical care delivered to elderly patients and to determine the association between patient characteristics and quality of care.nnnSTUDY DESIGNnThis is a retrospective pilot cohort study, conducted in a single university-affiliated hospital. Using the institutions National Surgical Quality Improvement Program (NSQIP) database (2009 to 2010), 143 consecutive patients 65 years or older, undergoing elective major abdominal surgery, were selected. Adherence to 15 process-based quality indicators (QIs) was measured, and a pass rate was calculated for each individual QI. The association between patient characteristics (age, sex, Charlson Comorbidity Index, functional status, wound class) and patient quality score was assessed using multiple linear regression.nnnRESULTSnQuality indicators with the lowest pass rates included postoperative delirium screening (0%), level of care documentation (0.7%), cognition and functional assessment at discharge (4.9%), oral intake documentation (12.6%), and pressure ulcer risk assessment (35.0%). The mean patient quality score was 46.8% ± 10.7% (range 16.7% to 75.0%). No association was found between patient characteristics and patient quality score.nnnCONCLUSIONSnQuality of care delivered to elderly patients undergoing major surgery at our institution was generally poor and independent of patient characteristics. Although quality appears to be uniform across different patients, these results provide targets for quality improvement initiatives.

Comparison of outcomes among patients aged 80 and over and younger patients with diffuse large B-cell lymphoma: a population based study

Abstract In this retrospective cohort study of 174 consecutive, newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL), clinical and pathological variables, treatment, response and survival were compared for patients aged 80 and over (n = 40) to those under 80. Eastern Cooperative Oncology Group (ECOG) status and International Prognostic Index (IPI) were significantly worse among older patients. Standard treatment was given to only 32.5% of older versus 86.6% of younger patients, and 65% of the elderly did not receive standard therapy. At 12 months, overall and event-free survival were 51.3% (95% confidence interval [CI]: 35–66%) vs. 93% (CI: 88–97%) and 41.9% (CI: 25–58%) vs. 84.8% (CI: 77–90%), for older versus younger patients, respectively. Choice of therapy was significantly associated with survival in the elderly, and low albumin but not comorbidity score was associated with not receiving standard therapy. Patients with DLBCL aged 80 and over are distinct from all other age groups with regard to treatment tolerance. A minority can receive standard therapy, but for the majority, novel therapeutic options are needed.

Association between quality of care and complications after abdominal surgery.

BACKGROUNDnMeasuring the quality of surgical care is essential to identifying areas of weakness in the delivery of effective surgical care and to improving patient outcomes. Our objectives were to (1) assess the quality of surgical care delivered to adult patients; and (2) determine the association between quality of surgical care and postoperative complications.nnnMETHODSnThis retrospective, pilot, cohort study was conducted at a single university-affiliated institution. Using the institutions National Surgical Quality Improvement Program database (2009-2010), 273 consecutive patients ≥18xa0years of age who underwent elective major abdominal operations were selected. Adherence to 10 process-based quality indicators (QIs) was measured and quantified by calculating a patient quality score (no. of QIs passed/no. of QIs eligible). A pass rate for each individual QI was also calculated. The association between quality of surgical care and postoperative complications was assessed using an incidence rate ratio, which was estimated from a Poisson regression.nnnRESULTSnThe mean overall patient quality score was 67.2xa0±xa014.4% (range, 25-100%). The mean QI pass rate was 65.9xa0±xa026.1%, which varied widely from 9.6% (oral intake documentation) to 95.6% (prophylactic antibiotics). Poisson regression revealed that as the quality score increased, the incidence of postoperative complications decreased (incidence rate ratio, 0.19; Pxa0=xa0.011). A sensitivity analysis revealed that this association was likely driven by the postoperative ambulation QI.nnnCONCLUSIONnHigher quality scores, mainly driven by early ambulation, were associated with fewer postoperative complications. QIs with unacceptably low adherence were identified as targets for future quality improvement initiatives.

Combination of Serum Biomarkers to Differentiate Malignant From Benign Ovarian Tumours

OBJECTIVEnTo investigate biomarkers and clinical parameters to distinguish ovarian cancers from benign ovarian tumours.nnnMETHODSnSerum biomarkers (CAu202f125, human epididymis protein 4 [HE 4], interleukin-18 [IL-18], leptin, macrophage migration inhibitory factor [MIF], fibroblast growth factor 2 [FGF-2], insulin-like growth factor, osteopontin, prolactin) and the risk of malignancy indexes I and II (RMI-I and RMI-II) scores were obtained prior to surgery in 52 patients with ovarian tumours (37 malignant and 15 benign). ROC curves were built for each individual marker, for logistic regression models using all markers, and for models combining both biomarkers and RMI scores.nnnRESULTSnThe model with nine biomarkers performed well (specificity 93%, sensitivity 84%) and was more reliable than the RMI-I or RMI-II alone. A regression model combining RMI-II and six of the biomarkers (CA 125, HEu202f 4, IL-18, leptin, MIF, and FGF-2) allowed differentiation between the cancer and non-cancer cases in this pilot study.nnnCONCLUSIONnThe regression models using biomarkers combined with clinical scoring systems warrant further investigation to improve triage of patients with ovarian tumours to enhance utilization of resources and optimize patient care.

The Risk of Venous Thrombosis, Including Cerebral Vein Thrombosis, Among Women With Thrombophilia and Oral Contraceptive Use A Meta-Analysis

Several small studies have reported an elevated risk of venous thrombosis (VT) with thrombophilia and oral contraceptive (OCP) use. We aimed to summarize the risk of VT among women with thrombophilia and OCP use and to assess the interaction between the 2 factors. We selected 15 studies that assessed the prevalence of OCP use and thrombophilia among reproductive-aged women. Odds ratios (ORs) were calculated for each study and pooled using the random effects model. We found an increased risk of VT among women with OCP use (pooled OR 3.0, 95% confidence interval [CI] 1.9-4.5) and with thrombophilia (pooled OR 4.5, CI 3.4-5.9), respectively. Heterogeneity was significant (I 2 >80%). Women with both thrombophilia and OCP use had a 14-fold risk of VT compared to healthy OCP nonusers (pooled OR 14.25, CI 6.2-32.8). Oral contraceptive use and thrombophilia similarly increase VT risk. Our study confirms an interaction between OCP use and thrombophilia.

Early Improvement in Serial Echocardiographic Studies in Heart Failure Patients Predicts Long Term Survival—A Pilot Study

BACKGROUNDnSeveral echocardiographic measures have prognostic value in heart failure (HF). However, no definitive data exist on how changes in these parameters with treatment affect survival in this patient population. We hypothesized that early improvement on echocardiography could predict long-term survival.nnnMETHODS AND RESULTSnWe conducted a retrospective review of 404 patients seen in the HF clinic from 2002 to 2008 (6.5 years). Patients had one echocardiogram ≤1 year before and another ≥1 month (10 ± 7 months) after treatment onset. We studied changes in standard echocardiographic parameters, including left (LV) and right (RV) ventricular size and/or function (systolic and/or diastolic), valvular (mitral and tricuspid) function, and pulmonary artery pressure. Survival curves and hazard ratios were generated for patients showing improvement on the 2nd echocardiogram versus those who did not. Multivariable analyses were performed adjusting for age, sex, ischemic etiology, and significant baseline echocardiographic parameters. Average follow-up was 2.9 ± 1.5 years. Improvement in LV end-systolic dimension, RV function, and mitral regurgitation were independent predictors of 5-year survival (P < .05) and, importantly, more predictive than baseline values of these parameters alone (higher hazard ratios).nnnCONCLUSIONSnEarly echocardiographic improvement is strongly associated with 5-year survival in patients with HF. Serial echocardiography may aid in stratifying patient care.