Primary Care Women's Health Screening: A Case Study of a Community Engaged Human Centered Design Approach to Enhancing the Screening Process.

PURPOSE: To apply a Human Centered Design (HCD) approach to co-designing a comprehensive women's health screening tool with community partners. DESCRIPTION: Evidenced-based health screenings for behaviors and risks are important tools in primary health care and disease prevention, especially for women. However, numerous barriers limit the effective implementation of comprehensive health screenings, and often lead to excluding important risks such as intimate partner violence (IPV). Utilizing a human centered design approach (HCD), Mountain Area Health Education Center (MAHEC, NC USA) developed a community co-designed 9-topic health screening for women. Key end-users were recruited to participate in the design process, including women who identified IPV as a health issue in their community, Spanish speaking women, domestic violence program organizers, and MAHEC staff. ASSESSMENT: A total of 21 participants collaborated during three design sessions on two specific goals: 1) creating a comprehensive women's health screening tool from the existing tools that were in use in our clinics at the time, and 2) incorporating IPV screening. Through the HCD sessions, participants highlighted the impact of what they termed "Triple T: time, trust and talk" on the effectiveness of women's health screening. CONCLUSION: Our co-designed women's health screening tool is a first step towards addressing screening barriers from both primary care provider's and community women's perspectives. Future research will explore the facilitators of and barriers to implementing the tools in different primary care settings. Future work should also more systematically examine whether and how screening processes may reinforce or contribute to women's feelings of being stereotyped, and how screening processes can be designed to avoid stereotype threat, which has the potential to reduce the effectiveness of screenings intended to promote women's health.

Chest compression fraction: A time dependent variable of survival in shockable out-of-hospital cardiac arrest.

INTRODUCTION: The role of chest compression fraction (CCF) in resuscitation of shockable out-of-hospital cardiac arrest (OHCA) is uncertain. We evaluated the relationship between CCF and clinical outcomes in a secondary analysis of the Resuscitation Outcomes Consortium PRIMED trial. METHODS: We included patients presenting in a shockable rhythm who suffered OHCA prior to EMS arrival. Multivariable logistic regression was used to determine the relationship between CCF and survival to hospital discharge, return of spontaneous circulation (ROSC), and neurologically intact survival. We also performed a secondary analysis restricted to patients without ROSC in the first 10 min of EMS resuscitation. RESULTS: Among the 2011 patients, median (IQR) age was 65 (54, 75) years, 78.2% were male, and mean (SD) CCF was 0.71 (0.14). Compared to the reference group (CCF<0.60), the odds ratio (OR) for survival was 0.49 (95% CI: 0.36, 0.68) for CCF 0.60-0.79 and 0.30 (95% CI: 0.20, 0.44) for CCF≥0.80. Results were similar for outcomes of ROSC and neurologically intact survival. Conversely, when restricted to the cohort who did not achieve ROSC during the first 10 min (n=1633), compared to the reference group (CCF<0.60), the OR for survival was 0.79 (95% CI: 0.53, 1.18) for CCF 0.60-0.79 and OR 0.88 (95% CI: 0.56, 1.36) for CCF≥0.80. CONCLUSIONS: In this study of OHCA patients presenting in a shockable rhythm, CCF was paradoxically associated with lower odds of survival. CCF is a complex measure and taken by itself may not be a consistent predictor of good clinical outcomes.

Apples to apples or apples to oranges? International variation in reporting of process and outcome of care for out-of-hospital cardiac arrest.

OBJECTIVES: Survival after out-of-hospital cardiac arrest (OHCA) varies between communities, due in part to variation in the methods of measurement. The Utstein template was disseminated to standardize comparisons of risk factors, quality of care, and outcomes in patients with OHCA. We sought to assess whether OHCA registries are able to collate common data using the Utstein template. A subsequent study will assess whether the Utstein factors explain differences in survival between emergency medical services (EMS) systems. STUDY DESIGN: Retrospective study. SETTING: This retrospective analysis of prospective cohorts included adults treated for OHCA, regardless of the etiology of arrest. Data describing the baseline characteristics of patients, and the process and outcome of their care were grouped by EMS system, de-identified, and then collated. Included were core Utstein variables and timed event data from each participating registry. This study was classified as exempt from human subjects' research by a research ethics committee. MEASUREMENTS AND MAIN RESULTS: Thirteen registries with 265 first-responding EMS agencies in 13 countries contributed data describing 125,840 cases of OHCA. Variation in inclusion criteria, definition, coding, and process of care variables were observed. Contributing registries collected 61.9% of recommended core variables and 42.9% of timed event variables. Among core variables, the proportion of missingness was mean 1.9±2.2%. The proportion of unknown was mean 4.8±6.4%. Among time variables, missingness was mean 9.0±6.3%. CONCLUSIONS: International differences in measurement of care after OHCA persist. Greater consistency would facilitate improved resuscitation care and comparison within and between communities.

Structural comparison of ColH and ColG collagen-binding domains from Clostridium histolyticum.

Clostridium histolyticum secretes collagenases, ColG and ColH, that cause extensive tissue destruction in myonecrosis. The C-terminal collagen-binding domain (CBD) of collagenase is required for insoluble collagen fibril binding and subsequent collagenolysis. The high-resolution crystal structures of ColG-CBD (s3b) and ColH-CBD (s3) are reported in this paper. The new X-ray structure of s3 was solved at 2.0-Å resolution (R = 17.4%; R(free) = 23.3%), while the resolution of the previously determined s3b was extended to 1.4 Å (R = 17.9%; R(free) = 21.0%). Despite sharing only 30% sequence identity, the molecules resemble one another closely (root mean square deviation [RMSD] C(α) = 1.5 Å). All but one residue, whose side chain chelates with Ca(2+), are conserved. The dual Ca(2+) binding site in s3 is completed by an unconserved aspartate. Differential scanning calorimetric measurements showed that s3 gains thermal stability, comparable to s3b, by binding to Ca(2+) (holo T(m) = 94.1°C; apo T(m) = 70.2°C). holo s3 is also stabilized against chemical denaturants urea and guanidine HCl. The three most critical residues for collagen interaction in s3b are conserved in s3. The general shape of the binding pocket is retained by altered loop structures and side chain positions. Small-angle X-ray scattering data revealed that s3 also binds asymmetrically to minicollagen. Besides the calcium-binding sites and the collagen-binding pocket, architecturally important hydrophobic residues and the hydrogen-bonding network around the cis-peptide bond are well conserved within the metallopeptidase subfamily M9B. CBDs were previously shown to bind to the extracellular matrix of various tissues. Compactness and extreme stability in physiological Ca(2+) concentration possibly make both CBDs suitable for targeted growth factor delivery.

Adding chemoprophylaxis to sequential compression might not reduce risk of venous thromboembolism in bariatric surgery patients.

BACKGROUND: Anticoagulation, the use of sequential compression devices on the lower extremities perioperatively, and early ambulation are thought to reduce the incidence of venous thromboembolism (VTE) postoperatively and are recommended to reduce VTE risk. However, the evidence on which this recommendation has been based is not particularly strong. We have demonstrated that even a large, multicenter cohort with carefully collected prospective data is inadequate to provide sufficient evidence to support, or refute, this recommendation. METHODS: Longitudinal Assessment of Bariatric Surgery participants from 10 centers in the United States who underwent their first bariatric surgery between March 2005 and December 2007 constituted the study group. We examined the ability to address the question of whether anticoagulation therapy, in addition to sequential compression, reduces the 30-day incidence of VTE or death sufficiently to recommend the use of prophylactic anticoagulation, a therapy that is not without risk. RESULTS: Of 4416 patients, 396 (9.0%) received sequential compression alone, and 4020 also received anticoagulation therapy. The incidence of VTE within 30 days of surgery was low (.25% among those receiving sequential compression alone and .47% when anticoagulation therapy was added), and the 30-day incidence of death was also low (.25% versus .34%, respectively, P = .76, for sequential compression alone versus sequential compression plus anticoagulation therapy). Estimates of the number of cases required to address the question of whether a difference exists in the outcome related to VTE chemoprophylaxis or whether the outcome rates are equivalent have ranged from 13,680 to ≥ 35,760 patients, depending on whether superiority or equivalence was being analyzed. CONCLUSION: Sufficient evidence from a clinical trial study to determine whether prophylactic anticoagulation added to compression devices further prevents VTE is not available, and such a trial is likely to be impractical. The data presented are insufficient to make a final recommendation concerning prophylactic treatment to prevent VTE in the 30 days after bariatric surgery.

Relationship between chest compression rates and outcomes from cardiac arrest.

BACKGROUND: Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions per minute. Animal and human studies have reported that blood flow is greatest with chest compression rates near 120/min, but few have reported rates used during out-of-hospital (OOH) cardiopulmonary resuscitation or the relationship between rate and outcome. The purpose of this study was to describe chest compression rates used by emergency medical services providers to resuscitate patients with OOH cardiac arrest and to determine the relationship between chest compression rate and outcome. METHODS AND RESULTS: Included were patients aged ≥ 20 years with OOH cardiac arrest treated by emergency medical services providers participating in the Resuscitation Outcomes Consortium. Data were abstracted from monitor-defibrillator recordings during cardiopulmonary resuscitation. Multiple logistic regression analysis assessed the association between chest compression rate and outcome. From December 2005 to May 2007, 3098 patients with OOH cardiac arrest were included in this study. Mean age was 67 ± 16 years, and 8.6% survived to hospital discharge. Mean compression rate was 112 ± 19/min. A curvilinear association between chest compression rate and return of spontaneous circulation was found in cubic spline models after multivariable adjustment (P=0.012). Return of spontaneous circulation rates peaked at a compression rate of ≈ 125/min and then declined. Chest compression rate was not significantly associated with survival to hospital discharge in multivariable categorical or cubic spline models. CONCLUSIONS: Chest compression rate was associated with return of spontaneous circulation but not with survival to hospital discharge in OOH cardiac arrest.

Intraoperative sentinel lymph node analysis in melanoma.

BACKGROUND: The objective of this retrospective cohort study was to evaluate the sensitivity and specificity of touch preparation cytology (TPC) and frozen section (FS) histology in the intraoperative staging of melanoma. METHODS: The cohort was identified from all patients with clinically node negative melanoma undergoing a SLN biopsy using Technetium and/or blue dye mapping from 1/1998 to 10/2008. TPC and FS analysis was performed utilizing Diff-quick and compared to permanent section interpretation with H&E. RESULTS: Of 271 patients undergoing SLN biopsy, 163 underwent intraoperative analysis of the sentinel node (125 underwent TPC alone, 15 underwent FS alone, 23 underwent both TPC and FS), and 108 underwent no intraoperative analysis. Thirty-three patients undergoing intraoperative analysis of the SLN were found to have positive nodes (20%) on permanent histology. There were no false positives identified (specificity = 100%). The overall sensitivity for all methods of intraoperative analysis was 61% (20/33). On a per patient basis, the sensitivity was 47% (9/19) for TPC alone, 75% (3/4) for FS alone, and 80% (8/10) for both TPC and FS. CONCLUSIONS: There were no false positives identified suggesting TPC and FS can be used safely to identify the majority of SLN that harbor metastases from melanoma.

Outcomes of laparoscopic adjustable gastric banding in patients with low body mass index.

BACKGROUND: The current National Institutes of Health guidelines have recommended bariatric surgery for patients with a body mass index (BMI) >40 kg/m(2) or BMI >35 kg/m(2) with significant co-morbidities. However, some preliminary studies have shown that patients with a BMI that does not meet these criteria could also experience similar weight loss and the benefits associated with it. METHODS: An institutional review board-approved protocol was obtained to study the effectiveness of laparoscopic adjustable gastric banding in patients with a low BMI. A total of 66 patients with a BMI of 30-35 kg/m(2) and co-morbidities (n = 22) or a BMI of 35-40 kg/m(2) without co-morbidities (n = 44) underwent laparoscopic adjustable gastric banding. These patients were compared with 438 standard patients who had undergone laparoscopic adjustable gastric banding who met the National Institutes of Health criteria for bariatric surgery. The excess weight loss at 3, 6, 12, and 18 months and the status of their co-morbidities were compared between the 2 groups. RESULTS: The average BMI for the study group was 36.1 +/- 2.6 kg/m(2) compared with 46.0 +/- 7.3 kg/m(2) for the control group. Both groups had significant co-morbidities, including hypertension, diabetes, hyperlipidemia, arthritis, gastroesophageal reflux disease, stress incontinence, and obstructive sleep apnea. The mean percentage of excess weight loss was 20.3% +/- 9.0%, 28.5% +/- 14.0%, 44.7% +/- 19.3%, and 42.2% +/- 33.7% at 3, 6, 12, and 18 months, respectively. This was not significantly different from the excess weight loss in the control group, except for at 12 months. Both groups showed similar improvement of most co-morbidities. CONCLUSION: Moderately obese patients whose BMI is less than the current guidelines for bariatric surgery will have similar weight loss and associated benefits. Laparoscopic adjustable gastric banding is a safe and effective treatment for patients with a BMI of 30-35 kg/m(2).

NMR characterization of copper and lipid interactions of the C2B domain of synaptotagmin I-relevance to the non-classical secretion of the human acidic fibroblast growth factor (hFGF-1).

Human fibroblast growth factor (hFGF-1) is a approximately 17 kDa heparin binding cytokine. It lacks the conventional hydrophobic N-terminal signal sequence and is secreted through non-classical secretion routes. Under stress, hFGF-1 is released as a multiprotein complex consisting of hFGF-1, S100A13 (a calcium binding protein), and p40 synaptotagmin (Syt1). Copper (Cu(2+)) is shown to be required for the formation of the multiprotein hFGF-1 release complex (Landriscina et al. ,2001; Di Serio et al., 2008). Syt1, containing the lipid binding C2B domain, is believed to play an important role in the eventual export of the hFGF-1 across the lipid bilayer. In this study, we characterize Cu(2+) and lipid interactions of the C2B domain of Syt1 using multidimensional NMR spectroscopy. The results highlight how Cu(2+) appears to stabilize the protein bound to pS vesicles. Cu(2+) and lipid binding interface mapped using 2D (1)H-(15)N heteronuclear single quantum coherence experiments reveal that residues in beta-strand I contributes to the unique Cu(2+) binding site in the C2B domain. In the absence of metal ions, residues located in Loop II and beta-strand IV contribute to binding to unilamelar pS vesicles. In the presence of Cu(2+), additional residues located in Loops I and III appear to stabilize the protein-lipid interactions. The results of this study provide valuable information towards understanding the molecular mechanism of the Cu(2+)-induced non-classical secretion of hFGF-1.

Predicting survival after out-of-hospital cardiac arrest: role of the Utstein data elements.

STUDY OBJECTIVE: Survival after out-of-hospital cardiac arrest depends on the links in the chain of survival. The Utstein elements are designed to assess these links and provide the basis for comparing outcomes within and across communities. We assess whether these measures sufficiently predict survival and explain outcome differences. METHODS: We used an observational, prospective data collection, case-series of adult persons with nontraumatic out-of-hospital cardiac arrest from December 1, 2005, through March 1, 2007, from the multisite, population-based Resuscitation Outcomes Consortium Epistry-Cardiac Arrest. We used logistic regression, receiver operating curves, and measures of variance to estimate the extent to which the Utstein elements predicted survival to hospital discharge and explained outcome variability overall and between 7 Resuscitation Outcomes Consortium sites. Analyses were conducted for all emergency medical services-treated cardiac arrests and for the subset of bystander-witnessed patient arrests because of presumed cardiac cause presenting with ventricular fibrillation or ventricular tachycardia. RESULTS: Survival was 7.8% overall (n=833/10,681) and varied from 4.6% to 14.7% across Resuscitation Outcomes Consortium sites. Among bystander-witnessed ventricular fibrillation or ventricular tachycardia, survival was 22.1% overall (n=323/1459) and varied from 12.5% to 41.0% across sites. The Utstein elements collectively predicted 72% of survival variability among all arrests and 40% of survival variability among bystander-witnessed ventricular fibrillation. The Utstein elements accounted for 43.6% of the between-site survival difference among all arrests and 22.3% of the between-site difference among the bystander-witnessed ventricular fibrillation subset. CONCLUSION: The Utstein elements predict survival but account for only a modest portion of outcome variability overall and between Resuscitation Outcomes Consortium sites. The results underscore the need for ongoing investigation to better understand characteristics that influence cardiac arrest survival.

Chest compression fraction determines survival in patients with out-of-hospital ventricular fibrillation.

BACKGROUND: Quality cardiopulmonary resuscitation contributes to cardiac arrest survival. The proportion of time in which chest compressions are performed in each minute of cardiopulmonary resuscitation is an important modifiable aspect of quality cardiopulmonary resuscitation. We sought to estimate the effect of an increasing proportion of time spent performing chest compressions during cardiac arrest on survival to hospital discharge in patients with out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia. METHODS AND RESULTS: This is a prospective observational cohort study of adult patients from the Resuscitation Outcomes Consortium Cardiac Arrest Epistry with confirmed ventricular fibrillation or ventricular tachycardia, no defibrillation before emergency medical services arrival, electronically recorded cardiopulmonary resuscitation before the first shock, and a confirmed outcome. Patients were followed up to discharge from the hospital or death. Of the 506 cases, the mean age was 64 years, 80% were male, 71% were witnessed by a bystander, 51% received bystander cardiopulmonary resuscitation, 34% occurred in a public location, and 23% survived. After adjustment for age, gender, location, bystander cardiopulmonary resuscitation, bystander witness status, and response time, the odds ratios of surviving to hospital discharge in the 2 highest categories of chest compression fraction compared with the reference category were 3.01 (95% confidence interval 1.37 to 6.58) and 2.33 (95% confidence interval 0.96 to 5.63). The estimated adjusted linear effect on odds ratio of survival for a 10% change in chest compression fraction was 1.11 (95% confidence interval 1.01 to 1.21). CONCLUSIONS: An increased chest compression fraction is independently predictive of better survival in patients who experience a prehospital ventricular fibrillation/tachycardia cardiac arrest.

Regional variation in out-of-hospital cardiac arrest incidence and outcome.

CONTEXT: The health and policy implications of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined. OBJECTIVE: To evaluate whether cardiac arrest incidence and outcome differ across geographic regions. DESIGN, SETTING, AND PATIENTS: Prospective observational study (the Resuscitation Outcomes Consortium) of all out-of-hospital cardiac arrests in 10 North American sites (8 US and 2 Canadian) from May 1, 2006, to April 30, 2007, followed up to hospital discharge, and including data available as of June 28, 2008. Cases (aged 0-108 years) were assessed by organized emergency medical services (EMS) personnel, did not have traumatic injury, and received attempts at external defibrillation or chest compressions or resuscitation was not attempted. Census data were used to determine rates adjusted for age and sex. MAIN OUTCOME MEASURES: Incidence rate, mortality rate, case-fatality rate, and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation. RESULTS: Among the 10 sites, the total catchment population was 21.4 million, and there were 20,520 cardiac arrests. A total of 11,898 (58.0%) had resuscitation attempted; 2729 (22.9% of treated) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator; and 954 (4.6% of total) were discharged alive. The median incidence of EMS-treated cardiac arrest across sites was 52.1 (interquartile range [IQR], 48.0-70.1) per 100,000 population; survival ranged from 3.0% to 16.3%, with a median of 8.4% (IQR, 5.4%-10.4%). Median ventricular fibrillation incidence was 12.6 (IQR, 10.6-5.2) per 100,000 population; survival ranged from 7.7% to 39.9%, with a median of 22.0% (IQR, 15.0%-24.4%), with significant differences across sites for incidence and survival (P<.001). CONCLUSION: In this study involving 10 geographic regions in North America, there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome.

Resuscitation Outcomes Consortium (ROC) PRIMED cardiac arrest trial methods part 2: rationale and methodology for "Analyze Later vs. Analyze Early" protocol.

OBJECTIVE: The primary objective of the trial is to compare survival to hospital discharge with modified Rankin score (MRS) < or =3 between a strategy that prioritizes a specified period of CPR before rhythm analysis (Analyze Later) versus a strategy of minimal CPR followed by early rhythm analysis (Analyze Early) in patients with out-of-hospital cardiac arrest. METHODS: Design-Cluster randomized trial with cluster units defined by geographic region, or monitor/defibrillator machine. Population-Adults treated by emergency medical service (EMS) providers for non-traumatic out-of-hospital cardiac arrest not witnessed by EMS. Setting-EMS systems participating in the Resuscitation Outcomes Consortium and agreeing to cluster randomization to the Analyze Later versus Analyze Early intervention in a crossover fashion. Sample size-Based on a two-sided significance level of 0.05, a maximum of 13,239 evaluable patients will allow statistical power of 0.996 to detect a hypothesized improvement in the probability of survival to discharge with MRS < or =3 rate from 5.41% after Analyze Early to 7.45% after Analyze Later (2.04% absolute increase in primary outcome). CONCLUSION: If this trial demonstrates a significant improvement in survival with a strategy of Analyze Later, it is estimated that 4000 premature deaths from cardiac arrest would be averted annually in North America alone.

Incidence and management of enteric leaks after gastric bypass for morbid obesity during a 10-year period.

BACKGROUND: To describe the incidence, etiology, outcomes, and management of enteric leaks in patients who had undergone open or laparoscopic gastric bypass. METHODS: From November 1996 to November 2006, 1133 patients underwent primary gastric bypass at Columbia University, New York-Presbyterian Hospital. A retrospective review of our prospective bariatric surgery registry identified 17 patients (1.5%) who developed a clinically apparent enteric leak after surgery. The demographic and outcome data were studied. RESULTS: The mean body mass index was 52 kg/m(2) (range 35-65), and 15 (88%) of the 17 patients were women. The mean number of co-morbidities per patient was 1.3 and included hypertension in 11, diabetes in 9, and sleep apnea in 6. Ten patients had previously undergone abdominal surgery. The enteric leak was diagnosed by radiographic studies in 12 patients (9 of 12 by upper gastrointestinal series and 3 of 6 by computed tomography); the remaining 5 patients were diagnosed at re-exploration. Of the 17 patients, 12 (70%) were treated by laparoscopy and 5 (29%) by laparotomy. The mean time from completion of the index procedure to the diagnosis of the leak was 2 days (range 1-5) for patients treated by laparoscopy versus 4 days (range 1-6) for patients treated by laparotomy (P <.05). The patients treated by laparoscopy experienced a shorter hospital stay, but the difference was not statistically significant (mean 11.4 days, range 6-36, versus 18 days, range 7-33; P >.05). One of the laparoscopic patients (5.9%) died. CONCLUSION: Enteric leak is a significant complication after gastric bypass. Prompt treatment should be based on clinical suspicion, because contrast and cross-sectional imaging studies might not be reliable diagnostic tests. A laparoscopic index procedure might be associated with an earlier diagnosis.

An evidence based alcohol screening, brief intervention and referral to treatment (SBIRT) curriculum for emergency department (ED) providers improves skills and utilization.

OBJECTIVE: Emergency Departments (EDs) offer an opportunity to improve the care of patients with at-risk and dependent drinking by teaching staff to screen, perform brief intervention and refer to treatment (SBIRT). We describe here the implementation at 14 Academic EDs of a structured SBIRT curriculum to determine if this learning experience improves provider beliefs and practices. METHODS: ED faculty, residents, nurses, physician extenders, social workers, and Emergency Medical Technicians (EMTs) were surveyed prior to participating in either a two hour interactive workshops with case simulations, or a web-based program (www.ed.bmc.org/sbirt). A pre-post repeated measures design assessed changes in provider beliefs and practices at three and 12 months post-exposure. RESULTS: Among 402 ED providers, 74% reported < 10 hours of prior professional alcohol-related education and 78% had < 2 hours exposure in the previous year. At 3-month follow-up, scores for self-reported confidence in ability, responsibility to intervene, and actual utilization of SBIRT skills all improved significantly over baseline. Gains decreased somewhat at 12 months, but remained above baseline. Length of time in practice was positively associated with SBIRT utilization, controlling for gender, race and type of profession. Persistent barriers included time limitations and lack of referral resources. CONCLUSIONS: ED providers respond favorably to SBIRT. Changes in utilization were substantial at three months post-exposure to a standardized curriculum, but less apparent after 12 months. Booster sessions, trained assistants and infrastructure supports may be needed to sustain changes over the longer term.

The level of viral antigen presented by hepatocytes influences CD8 T-cell function.

CD8 T cells exert their antiviral function through cytokines and lysis of infected cells. Because hepatocytes are susceptible to noncytolytic mechanisms of viral clearance, CD8 T-cell antiviral efficiency against hepatotropic viruses has been linked to their capacity to produce gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). On the other hand, intrahepatic cytokine production triggers the recruitment of mononuclear cells, which sustain acute and chronic liver damage. Using virus-specific CD8 T cells and human hepatocytes, we analyzed the modulation of virus-specific CD8 T-cell function after recognition peptide-pulsed or virally infected hepatocytes. We observed that hepatocyte antigen presentation was generally inefficient, and the quantity of viral antigen strongly influenced CD8 T-cell antiviral function. High levels of hepatitis B virus production induced robust IFN-gamma and TNF-alpha production in virus-specific CD8 T cells, while limiting amounts of viral antigen, both in hepatocyte-like cells and naturally infected human hepatocytes, preferentially stimulated CD8 T-cell degranulation. Our data document a mechanism where virus-specific CD8 T-cell function is influenced by the quantity of virus produced within hepatocytes.

The learning curve measured by operating times for laparoscopic and open gastric bypass: roles of surgeon's experience, institutional experience, body mass index and fellowship training.

BACKGROUND: Surgeons must overcome a substantial learning curve before mastering laparoscopic Roux-en-Y gastric bypass (LRYGBP). This learning curve can be defined in terms of mortality, morbidity or length of surgery. The aim of this study was to compare the learning curves in terms of surgical time for the first 3 surgeons performing LRYGBP in our hospital with the length of surgery for open gastric bypass (CONTROLS). METHODS: We compared 494 primary LRYGBPs performed by 3 surgeons (393 by 1st SURGEON, 57 by 2nd SURGEON and 44 by 3rd SURGEON) to 159 open vertical banded gastroplasty-Roux-en-Y gastric bypasses (CONTROLS). Data for LRYGBP patients were prospectively obtained. Factors that significantly affected the length of surgery were identified by univariate and multivariate linear regression analysis. RESULTS: LRYGBP and CONTROL patients were similar in age, height, weight and BMI, although more CONTROLS were male. Median time for the 1st SURGEON performing LRYGBP dropped for each subsequent 100 operations: 1st 100 - 190 min, 2nd 100 - 135 min, 3rd 100 - 110 min and 4th 100 - 100 min. Median time for 2nd SURGEON performing LRYGBP was 120 min, 3rd SURGEON 173 min and CONTROLS 64 min. Length of surgery significantly correlated with surgical experience in terms of numbers of operations and BMI of patient. Times for 2nd SURGEON, a fellowship trained laparoscopic surgeon, started significantly faster than 1st SURGEON's, but did not significantly improve with experience. 3rd SURGEON's initial times were similar to 1st SURGEON's, but his times improved more rapidly with experience. Times for CONTROLS were significantly faster than all laparoscopic groups and did not correlate with operation number or patient BMI. CONCLUSIONS: The length of surgery for LRYGBPs continued to shorten beyond 400 operations for the first surgeon performing LRYGBP in our hospital. Previous fellowship training in LRYGBP shortened surgical times during initial clinical experience as an attending for the second surgeon. The learning curve was truncated because of the already established LRYGBP program.

Patient characteristics impacting excess weight loss following laparoscopic adjustable gastric banding.

BACKGROUND: Weight loss is more variable after laparoscopic adjustable gastric banding (LAGB) than after gastric bypass. Subgroup analysis of patients may offer insight into this variability. The aim of our study was to identify preoperative factors that predict outcome. METHODS: Demographics, co-morbid conditions and follow-up weight were collected for our 1st 200 LapBand patients. Linear regression determined average %EWL. Logistic regression analysis identified factors that impacted %EWL. RESULT: 200 patients returned for 778 follow-up visits. Median age was 44 years (21-72) and median BMI 45 kg/m2 (31-76). 140 (80%) were women. Average %EWL was y % = 0.007 %/day (days since surgery) + 0.12% (correlation coef. 0.4823; P<0.001). %EWL at 1 year was 37%. The best-fit logistic regression model found 7 factors that significantly changed the odds of achieving average %EWL. Older patients, diabetic patients and patients with COPD had greater odds of above average %EWL. Female patients, patients with larger BMIs, asthmatic patients and patients with hypertension had increased odds of below average %EWL. CONCLUSION: Specific patient characteristics and comorbid conditions significantly altered the odds of achieving satisfactory %EWL following gastric banding.