Victor M. Zaydfudim

The biology of cortical granules

An egg-that took weeks to months to make in the adult-can be extraordinarily transformed within minutes during its fertilization. This review will focus on the molecular biology of the specialized secretory vesicles of fertilization, the cortical granules. We will discuss their role in the fertilization process, their contents, how they are made, and the molecular mechanisms that regulate their secretion at fertilization. This population of secretory vesicles has inherent interest for our understanding of the fertilization process. In addition, they have import because they enhance our understanding of the basic processes of secretory vesicle construction and regulation, since oocytes across species utilize this vesicle type. Here, we examine diverse animals in a comparative approach to help us understand how these vesicles function throughout phylogeny and to establish conserved themes of function.

Implementation of a Real-time Compliance Dashboard to Help Reduce SICU Ventilator-Associated Pneumonia With the Ventilator Bundle

BACKGROUND Ventilator-associated pneumonia (VAP) causes significant morbidity and mortality in critically ill surgical patients. Recent studies suggest that the success of preventive measures is dependent on compliance with ventilator bundle parameters. HYPOTHESIS Implementation of an electronic dashboard will improve compliance with the bundle parameters and reduce rates of VAP in our surgical intensive care unit (SICU). DESIGN Time series analysis of VAP rates between January 2005 and July 2008, with dashboard implementation in July 2007. SETTING Multidisciplinary SICU at a tertiary-care referral center with a stable case mix during the study period. PATIENTS Patients admitted to the SICU between January 2005 and July 2008. MAIN OUTCOME MEASURES Infection control data were used to establish rates of VAP and total ventilator days. For the time series analysis, VAP rates were calculated as quarterly VAP events per 1000 ventilator days. Ventilator bundle compliance was analyzed after dashboard implementation. Differences between expected and observed VAP rates based on time series analysis were used to estimate the effect of intervention. RESULTS Average compliance with the ventilator bundle improved from 39% in August 2007 to 89% in July 2008 (P < .001). Rates of VAP decreased from a mean (SD) of 15.2 (7.0) to 9.3 (4.9) events per 1000 ventilator days after introduction of the dashboard (P = .01). Quarterly VAP rates were significantly reduced in the November 2007 through January 2008 and February through April 2008 periods (P < .05). For the August through October 2007 and May through July 2008 quarters, the observed rate reduction was not statistically significant. CONCLUSIONS Implementation of an electronic dashboard improved compliance with ventilator bundle measures and is associated with reduced rates of VAP in our SICU.

Direct molecular interaction of a conserved yolk granule protein in sea urchins

The regulation of yolk storage in oocytes and subsequent utilization in embryos is critical for embryogenesis. In sea urchins, the major yolk protein is made in the intestines, transported to the ovaries and accumulated in developing oocytes within membrane‐bound vesicles comprising approximately 10% of the mass of an egg. Here, a non‐yolk protein that accumulates specifically in yolk granules is reported. This protein was identified by cDNA cloning and, by use of antibodies to the recombinant protein, it was shown that this molecule is stored selectively in yolk granules of oocytes and embryos. No accumulation was seen in the accessory cells, testis, or intestines. In situ ribonucleic acid (RNA) hybridizations showed that the transcript accumulated only in oocytes, and was more highly concentrated in young oocytes. However, later in oogenesis, the messenger ribonucleic acid (mRNA) levels decreased significantly so that no signal was detectable in mature haploid eggs or at any later stage in development. However, by immunofluorescence and western blot analysis, the 30 kDa band was present throughout development. The predicted sequence of this protein shows that it is a member of the bep, HLC‐32, EBP family of sea urchin proteins, but as it does not accumulate at the cell surface, nor in the hyaline layer in the two species studied here, as do other members of the family, it has been referred to as YP30 (30 kDa protein of the yolk platelet). To address its potential function, yeast two‐hybrid analysis was performed to screen for proteins that potentially interact with YP30. It was found that it binds itself, and forms strongly interacting dimers. It is hypothesized that YP30 participates in the packaging and storage of major yolk protein during oogenesis, or in the utilization of the major yolk protein in development.

Surgical Treatment of Hepatocellular Carcinoma in North America: Can Hepatic Resection Still Be Justified?

BACKGROUND The incidence of hepatocellular cancer (HCC) is increasing dramatically worldwide. Optimal management remains undefined, especially for well-compensated cirrhosis and HCC. STUDY DESIGN This retrospective analysis included 5 US liver cancer centers. Patients with surgically treated HCC between 1990 and 2011 were analyzed; demographics, tumor characteristics, and survival rates were included. RESULTS There were 1,765 patients who underwent resection (n = 884, 50.1%) or transplantation (n = 881, 49.9%). Overall, 248 (28.1%) resected patients were transplant eligible (1 tumor <5 cm or 2 to 3 tumors all <3 cm, no major vascular invasion); these were compared with 496 transplant patients, matched based on year of transplantation and tumor status. Overall survivals at 5 and 10 years were significantly improved for transplantation patients (74.3% vs 52.8% and 53.7% vs 21.7% respectively, p < 0.001), with greater differences in disease-free survival (71.8% vs 30.1% at 5 years and 53.4% vs 11.7% at 10 years, p < 0.001). Ninety-seven of the 884 (11%) resected patients were within Milan criteria and had cirrhosis; these were compared with the 496 transplantation patients, with similar results to the overall group. On multivariate analysis, type of surgery was an independent variable affecting all survival outcomes. CONCLUSIONS The increasing incidence of HCC stresses limited resources. Although transplantation results in better long-term survival, limited donor availability precludes widespread application. Hepatic resection will likely remain a standard therapy in selected patients with HCC. In this large series, only about 10% of patients with cirrhosis were transplant-eligible based on tumor status. Although liver transplantation results are significantly improved compared with resection, transplantation is available only for a minority of patients with HCC.

The effect of health insurance status on the treatment and outcomes of patients with colorectal cancer

Uninsured and underinsured cancer patients often have delayed diagnosis and inferior outcomes. As healthcare reform proceeds in the US, this disparity may gain increasing importance. Our objective was to investigate the impact of health insurance status on the presentation, treatment, and survival among colorectal cancer (CRC) patients.

Lack of emergency hand surgery: discrepancy between elective and emergency hand care.

Wrist, hand, and finger trauma are the most common injuries presenting to emergency departments. Shortage of emergency hand care is an emerging problem, as on-call hand coverage declines. This study evaluates the availability of elective and emergency hand surgery services in Tennessee, with the use of telephone surveys administered to emergency department and operating facility management. One hundred eleven Tennessee hospitals completed the surveys (93% response rate). In all, 77% of hospitals offer elective hand surgery, 58% offer basic emergency hand services, 18% offer occasional hand specialist call coverage and only 7% of hospitals have 24/7 hand specialist call coverage. Hospitals with hand specialists have significantly more payer charges from commercial insurance than hospitals without hand specialists (26.1% vs. 16.1%, P < 0.001). Our results strongly support the need for increased emergency hand coverage. Solutions include creating multihospital coordinated call schedules, increasing incentives for call coverage, and training more hand specialists.

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria.

Objectives: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria. Background: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center. Methods: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. Results: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5–12.9 cm vs. median 4.1, IQR: 3.4–5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001). Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ⩽ 0.017). Conclusions: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

Management of Biliary Cystic Tumors: A Multi-institutional Analysis of a Rare Liver Tumor

OBJECTIVE To characterize clinical and radiological features associated with biliary cystic tumors (BCTs) of the liver, and to define recurrence-free and overall survival. BACKGROUND Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare tumors that arise in the liver. METHODS Between 1984 and 2013, 248 patients who underwent surgical resection of BCA or BCAC were identified. Clinical and outcome data were analyzed. RESULTS Median total bilirubin, CA19-9, and carcinoembryonic antigen (CEA) levels were 0.6 mg/dL, 15.0 U/mL, and 2.7 ng/mL, respectively. Preoperative imaging included computed tomography only (62.5%), magnetic resonance imaging only (6.9%), or CT + MRI (18.5%). Features on cross-sectional imaging included multiloculation (56.9%), mural nodularity (16.5%), and biliary ductal dilatation (17.7%). The presence of these factors did not reliably predict BCAC versus BCA (sensitivity, 81%; specificity, 21%). Median biliary cyst size was 10.0 cm (interquartile range, 7-13 cm). Operative interventions included unroofing/partial excision of the lesion (14.1%), less than hemihepatectomy (48.8%), or hemi-/extended hepatectomy (36.3%). On pathology most lesions were BCA (89.1%), whereas 27 (10.9%) were BCAC. At last follow-up, there were 46 (18.3%) recurrences; 2 patients who initially had BCA recurred with BCAC. Median overall survival was 18.1 years; 1-year, 3-year, and 5-year survival was 95.0%, 86.8%, and 84.2%, respectively. Long-term outcomes were associated with BCAC versus BCA, as well as the presence of spindle cell/ovarian stroma (both P < 0.05). CONCLUSIONS Among patients undergoing surgery for BCT, associated malignancy was uncommon (10%) and no preoperative findings reliably predicted underlying BCAC. After excision of BCA, long-term outcomes were good; however, patients with BCAC had a worse long-term prognosis.

Evaluation of living kidney donors: variables that affect donation.

Approximately 10000 deceased donor organs are available yearly for 85 000 US patients awaiting kidney transplant. Living kidney donation is essential to close this gap and offers better survival rates. However, nationally, 80% of potential donors evaluated fail to donate. Nurse coordinators who perform predonation screening and education need additional insight into the large number of potential donors who fail to complete the donation process. Reasons for nondonation in donor candidates undergoing medical evaluation, and variables affecting nondonation at Vanderbilt University Medical Center between 2004 and 2009 are examined. Multivariable logistic regression models are used to test the effects of age and race on donation status and reasons for nondonation. Summary data are frequencies, percentages, and means (SD). The sample included 706 candidates (63% female, 80% white; mean age, 40 [SD, 12] years). Almost half (46%) received clearance to donate. Undiagnosed hypertension (14%), abnormal glucose tolerance (10%), and proteinurea (9%) were the most prevalent medical reasons for nondonation. About 13% of candidates changed their minds during evaluation. Analyses demonstrated an increased likelihood of older candidates (P < .001) and a decreased likelihood of white candidates (P = .007) being excluded from donation. Within the nondonation group, increased age was associated with undiagnosed hypertension and abnormal glucose tolerance (both race-adjusted, P = .01). Younger candidates (race-adjusted, P = .003) and African Americans (age-adjusted, P = .04) were more likely to decide against donation. The most prevalent medical reasons for nondonation could be identified through enhanced prescreening, and improved preevaluation education could decrease nondonation rates.

Improving treatment and survival: a population‐based study of current outcomes after a hepatic resection in patients with metastatic colorectal cancer

BACKGROUND Population-based studies historically report underutilization of a resection in patients with colorectal metastases to the liver. Recent data suggest limitations of the methods in the historical analysis. The present study examines trends in a hepatic resection and survival among Medicare recipients with hepatic metastases. METHODS Medicare recipients with incident colorectal cancer diagnosed between 1991 and 2009 were identified in the SEER(Surveillance, Epidemiology and End Results)-Medicare dataset. Patients were stratified into historical (1991-2001) and current (2002-2009) cohorts. Analyses compared treatment, peri-operative outcomes and survival. RESULTS Of 31.574 patients with metastatic colorectal cancer to the liver, 14,859 were in the current cohort treated after 2002 and 16,715 comprised the historical control group. The overall proportion treated with a hepatic resection increased significantly during the study period (P < 0.001) with pre/post change from 6.5% pre-2002 to 7.5% currently (P < 0.001). Over time, haemorrhagic and infectious complications declined (both P ≤ 0.047), but 30-day mortality was similar (3.5% versus 3.9%, P = 0.660). After adjusting for predictors of survival, the use of a hepatic resection [hazard ratio (HR) = 0.40, 95% confidence interval (CI): 0.38-0.42, P < 0.001] and treatment after 2002 (HR = 0.88, 95% CI: 0.86-0.90, P < 0.001) were associated with a reduced risk of death. CONCLUSIONS Case identification using International Classification of Diseases, 9th Revision (ICD-9) codes is imperfect; however, comparison of trends over time suggests an improvement in multimodality therapy and survival in patients with colorectal metastases to the liver.