Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

BACKGROUND: We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. METHODS: The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. RESULTS: Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. CONCLUSION: APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Ultrasound marking by gastroenterologists prior to percutaneous liver biopsy removes the need for a separate radiological evaluation.

BACKGROUND/AIM: Ultrasound marking by radiologists prior to percutaneous liver biopsy (PLB) results in biopsy site adjustment, decreased pain related complications and improved tissue yield. Minimal data exists on the impact of ultrasound marking by gastroenterologists on these parameters. The study aim was to evaluate whether ultrasound marking by gastroenterologists results in improved PLB tissue yield, fewer needle passes and decreased biopsy failure rates compared to blind biopsy, eliminating the need for a separate radiological evaluation. METHODOLOGY: All PLB performed by gastroenterologists from June 1999 to February 2003 at the University of Florida College of Medicine, Jacksonville, were reviewed retrospectively. Data collected included ultrasound marked or blind PLB, demographics, indication, number of passes performed, and specimen length, if obtained. RESULTS: Four hundred and eighty PLB were included: 328 performed with ultrasound marking and 152 blind. Ultrasound marking by gastroenterologists prior to PLB resulted in fewer passes and longer specimens as well as a decreased failure rate in ultrasound marked compared to blind PLB. CONCLUSIONS: Ultrasound marking by gastroenterologists prior to PLB provided significantly larger tissue samples, fewer needle passes and a decreased biopsy failure rate compared to blind PLB. This removes the need for a separate radiological evaluation on the procedure day.

Overuse of acid suppression therapy in hospitalized patients.

BACKGROUND: Acid suppression therapy (AST) is one of the most commonly prescribed classes of medications in hospitalized patients. Multiple studies have shown that AST is overused during inpatient admissions. However, minimal data is available regarding the frequency and patient characteristics of those discharged on unnecessary AST. The aims of the study were to examine administration of AST on admission, to characterize the patient population discharged on unnecessary AST and to determine predictive factors for inappropriate administration of AST in hospitalized patients. METHODS: A retrospective chart review of randomly selected patients admitted to the general medicine service at University of Florida Health Science Center/Jacksonville from August to October 2006 for appropriateness of AST was done. The admitting diagnosis, indications for starting AST, type of AST used, and discharge on these medications was recorded on a case by case basis. RESULTS: Seventy percent of patients were started on AST on admission. Of these, 73% were unnecessary. Stress ulcers prophylaxis in low risk patients or the concomitant use of ulcerogenic drugs motivated initiation of therapy most frequently. Sixty nine percent of patients started on inappropriate AST were discharged on the same regimen. Admitting diagnosis, age of patient, length of stay, or concomitant use of ulcerogenic drugs did not predict continuation of unnecessary AST at discharge. CONCLUSION: AST is overused in hospitalized patients. This primarily occurred in low risk patients and was compounded by continuation at discharge. This significantly increases cost to the health care system and the risk of drug interactions.

Organizational factors associated with quality of care in US teaching hospitals.

This study is unique because it uses multiple regression and data envelopment analysis (DEA) to evaluate teaching hospital quality. The results support the premise that teaching hospital leadership through the effective allocation of resources can improve the quality of care. This study has managerial implications by demonstrating the positive correlation between HMO market penetration and improved clinical quality outcomes. This would suggest that improved efficiency caused by limited HMO reimbursement and tight utilization controls encourage hospitals to cut waste as well as improve their clinical care processes. Additionally, our research found that teaching hospitals with higher levels of long-term debt also had improved quality. This shows that increased investments in facilities and advanced technology at teaching hospitals can lead to enhanced quality.

Modified technique to extract malpositioned or migrated self-expanding stents from the esophagus and stomach.

BACKGROUND AND AIM: Various methods have been used to remove self expandable stents (SES) because of either malposition or migration. The main difficulties encountered in such situations are the anatomic obstacle of the lower and upper esophageal sphincters as well as risk of mucosal injury during removal. METHODS: We describe a modified approach using an esophagogastroduodenoscope (EGD) in combination with a foreign body hood protector, rat tooth forceps and snare allowing for successful SES removal from the upper gastrointestinal tract in four cases. RESULTS: In all cases, the SES were successfully removed from upper gastrointestinal tract using this technique. No complications were noted after extraction. CONCLUSION: The foreign body hood protector combined with rat tooth forceps/snare technique is a safe and effective alternative to previously described methods for extraction of SES from the upper gastrointestinal tract. This method may be applicable for the removal of other such objects within the endoscope's reach.

Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C.

BACKGROUND & AIMS: Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens. METHODS: A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks. RESULTS: The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group. CONCLUSIONS: In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.

Extraction of hollow gastric foreign bodies by flexible upper endoscopy assisted by a through-the-scope balloon catheter for anchoring.

BACKGROUND: Various methods have been used to remove foreign bodies; hollow foreign bodies deserve special consideration. The main difficulty encountered in such situations is the anatomic obstacle of the lower and upper esophageal sphincters along with a risk of perforation. OBJECTIVE: We describe a unique approach by using an esophageal balloon dilator to anchor a hollow foreign body onto an endoscope, which allows for the successful extraction of such objects with minimal risk. DESIGN: Case series. SETTING: Shands Jacksonville and University of Florida/Jacksonville, Jacksonville, Florida. PATIENTS: Two consecutive patients with hollow foreign bodies in the stomach that required removal. INTERVENTIONS: A combined approach by using an endoscope and a 20-mm by 8-cm esophageal balloon dilator to remove hollow foreign bodies from the stomach. MAIN OUTCOME MEASUREMENTS: Nonsurgical removal of hollow gastric foreign bodies. RESULTS: Both foreign bodies were successfully removed from the stomach and extracted by mouth with this technique. There were no complications after both procedures. CONCLUSIONS: The inflated esophageal balloon that anchors a hollow foreign body onto a flexible endoscopic technique is a safe and effective alternative to previously described methods for removal of such foreign bodies in the gastric cavity. This method may be applicable to the removal of other hollow objects within the gastric lumen.

Mediastinal pancreatic pseudocyst--a case report and review of the literature.

Pancreatic pseudocyst, a common complication of acute or chronic pancreatitis, in rare instances may also extend to the mediastinum. A case of 67-year-old woman presenting with a triad of chest pain, dysphagia, and dyspnea is presented. The patient had an episode of acute alcoholic pancreatitis 1 year before presentation. Chest radiography on admission showed a retrocardiac opacity. Two-dimensional echocardiography revealed an echolucent mass compressing the left atrium. A subsequent upper gastrointestinal series for her dysphagia showed extrinsic compression of the distal esophagus. Finally a definitive diagnosis was made with computed tomography (scan), which revealed a 19 x 12 cm pseudocyst extending from the body of pancreas into the thorax and compressing the esophagus and the cardiac chambers. A mediastinal pseudocyst can cause symptoms due to compression or invasion of surrounding structures. The fluid collection may enlarge slowly and hence the symptoms can be delayed as in our patient. The pseudocyst was successfully treated using endoscopic ultrasound-guided transesophageal drainage. Approximately 50 cases of mediastinal extension of the pancreatic pseudocyst in the world literature are reported. At this time, this is only the second time that successful drainage of a mediastinal pseudocyst using a transesophageal approach under endoscopic ultrasound guidance has been reported. The literature was reviewed for clinical presentation, complications, and available treatment options for mediastinal pancreatic pseudocysts.

Impact of weight-based ribavirin with peginterferon alfa-2b in African Americans with hepatitis C virus genotype 1.

UNLABELLED: WIN-R (Weight-based dosing of pegINterferon alfa-2b and Ribavirin) was a multicenter, randomized, open-label, investigator-initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in treatment-naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG-IFN alfa-2b at 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based-dose RBV (800 mg/day for weight <65 kg, 1000 mg/day for 65-85 kg, 1200 mg/day for >85-105 kg, or 1400 mg/day for >105-<125 kg). Sustained virologic response (SVR; undetectable [<125 IU/mL] hepatitis C virus [HCV] RNA at end of follow-up) in patients > or =65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN-R was conducted to evaluate the efficacy of weight-based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight-based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight-based-dose group than in the flat-dose group. Safety and rates of drug discontinuation were similar between the 2 groups. CONCLUSION: Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1. Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups.

The impact of graduate medical education on teaching hospital efficiency.

This quantitative research study assesses the efficiency of university teaching hospitals in providing hospital services and graduate medical education, identifying areas in which inefficient teaching hospitals differed from their efficient counterparts. The study analyzed American Hospital Association (AHA) data from 2002 in order to examine the efficiency of Council of Teaching Hospital (COTH) hospitals. An efficiency frontier was determined using Data Envelopment Analysis, an effective method of measuring efficiency widely accepted within the health care management literature. The study found that the performance of teaching hospitals increased approximately 6.6 percent when graduate medical education (GME) was included as a key measure of output. Additionally, average excess operating expenses per hospital went from $29,447,581 without residents to $8,321,407 with residents. The average excess full-time employees decreased by 24 percent from 187 without residents to 143 with residents. Conversely, the shortage of outpatient visits increased from an average of 29,461 per hospital without residents to 36,155 with residents. This study clearly documents the need to include GME when benchmarking teaching hospitals. It also shows inefficient COTH hospitals could save approximately $1.6 billion in excess overhead expenses if they emulate the practices of the most efficient members.

Role of gastroesophageal reflux symptoms in exacerbations of COPD.

BACKGROUND AND AIMS: The impact of gastroesophageal reflux disease (GERD) on exacerbations of COPD has never been evaluated. The aims of this investigation were to determine the prevalence of gastroesophageal reflux (GER) symptoms in COPD patients and the effect of GER on the rate of exacerbations of COPD per year. METHODS: A questionnaire-based, cross sectional survey was performed. Subjects were recruited from the outpatient pulmonary clinics at the University of Florida Health Science Center/Jacksonville. Included patients had an established diagnosis of COPD. Exclusion criteria were respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger-Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those meeting criteria and agreeing to participate were asked to complete the Mayo Clinic GERD questionnaire by either personal/telephone interview. Clinically significant reflux was defined as heartburn and/or acid regurgitation weekly. Other outcome measures noted were frequency and type of COPD exacerbations. Statistical analysis was performed using the Fisher exact test for categorical data and the independent t test for interval data. RESULTS: Eighty-six patients were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for 55% of the study group. Overall, 37% of patients reported GER symptoms. The mean FEV(1) percentage of predicted was similar in those with or without GER. The rate of exacerbations of COPD was twice as high in patients with GER symptoms compared to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). CONCLUSIONS: The presence of GER symptoms appears to be associated with increased exacerbations of COPD.

A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy.

Albumin-interferon-alpha (IFN-alpha) is a novel 85.7-kDa recombinant protein consisting of IFN-alpha that is genetically fused to human serum albumin. In this Phase I/II, multicentre, open-label study, we evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics of albumin-IFN-alpha in IFN-alpha-experienced patients with chronic hepatitis C. Albumin-IFN-alpha was administered in 22 escalating doses (7-900 microg) in a single injection or in two injections 14 days apart. In the 119 patients studied, there were no discontinuations because of adverse events, and albumin-IFN-alpha had a favourable safety profile at doses up to 900 microg. The most common adverse events were headache (56%), fatigue (52%), injection site erythema (38%), arthralgias (32%) and pyrexia (27%). Reduced clearance resulted in a mean elimination half-life of 159 h, which supports dosing at 2- to 4-week intervals. Induction of the IFN-specific gene OAS1 was maintained for > or = 28 days following a single injection of albumin-IFN-alpha at doses of > or = 40 microg. Dose-dependent antiviral activity was observed in this IFN-alpha-experienced study population. Antiviral activity of > or = 1.0-log reductions in HCV RNA was observed in 47% (37/78) of patients in the 120- to 900-microg cohorts and in 59% (16/27) in the 400- to 900-microg double-injection cohorts. These results support further clinical studies of albumin-IFN-alpha for the treatment of patients with chronic hepatitis C.

Modulation of interferon-specific gene expression by albumin-interferon-alpha in interferon-alpha-experienced patients with chronic hepatitis C.

Albumin-interferon-alpha (alb-IFN) is a novel recombinant protein derived from IFN-alpha2b genetically fused to human albumin. The resulting single polypeptide combines in one molecule the antiviral properties of IFN-alpha with the long serum half-life of albumin. IFN-mediated biological responses stem from the engagement of IFN-alpha with its target receptor and subsequent modulation of IFN-specific gene (ISG) expression. To evaluate the pharmacodynamics of alb-IFN during the Phase I/II study conducted in patients with chronic hepatitis C (CHC) who had previously failed IFN-alpha-containing regimens, ISG induction was evaluated in peripheral blood and compared with antiviral response. Whole blood was obtained at day 0, day 7 and day 28 from 21 patients enrolled in the higher dose (500-900 microg) alb-IFN cohort, who received two injections on day 0 and day 14. Taqman real-time PCR was used to assess candidate ISG expression. There was sustained induction on day 7 and day 28 of the ISG's OAS1, IRF-7, IFI44 and IFI27. Although all patients showed a molecular response to alb-IFN, individual variability in pretreatment gene expression levels and fold of modulation during treatment was observed. At day 28, induction of OAS1, IFI44 and IRF7 showed pairwise correlation in individual patients (P < 0.05). Moreover, the induction of expression at day 28, and pretreatment levels of OAS1 and IFI44 correlated with hepatitis C virus RNA reduction at day 28 (P < 0.05). In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the response associated with an IFN-alpha.

Management of the mucin filled bile duct. A complication of intraductal papillary mucinous tumor of the pancreas.

CONTEXT: Biliary obstruction secondary to intrabiliary mucin is a relatively rare presentation of malignant intraductal pancreatic mucinous tumor. We report a case of unresectable intraductal pancreatic mucinous tumor associated with obstructive jaundice secondary to intrabiliary mucin. This case and a review of the literature, highlight the difficulty in obtaining sustained palliation from jaundice using endoscopically placed biliary stents or percutaneously placed biliary catheters due to rapid occlusion with thick mucin secreted by the tumor. Furthermore, this case differs from that commonly seen in the setting of pancreatic adenocarcinoma, where endoscopic or percutaneous biliary drainage is usually successful at long-term palliation from jaundice. CASE REPORT: Case report We report a case of obstructive jaundice secondary to invasive intraductal pancreatic mucinous tumor associated with dilated bile ducts containing copious amounts of mucin. The diagnosis of intraductal pancreatic mucinous tumor was established based on diagnostic findings on computed tomography scan and endoscopic retrograde cholangiopancreatography. The tumor was unresectable due to vascular invasion. Attempts at endoscopic biliary drainage proved unhelpful with the patient experiencing rapid occlusion of the biliary stents with thick mucinous material leading to recurrent cholangitis. The patient eventually underwent a choledochojejunostomy leading to complete and sustained resolution of the cholestasis. CONCLUSION: If intraductal pancreatic mucinous tumor in association with intrabiliary mucinous obstruction is deemed unresectable, surgical biliary bypass seems to be superior to endoscopic biliary drainage and should be performed on initial presentation. This is due to rapid occlusion of biliary stents with thick mucin leading to frequent stent changes and recurrent cholestasis.

Fatal cholestatic liver failure associated with gemcitabine therapy.

Drug-induced hepatotoxicity accounts for more than a third of the cases of acute liver failure in the United States. In complex medical conditions, the diagnosis of drug-induced liver injury may be confounding and, specifically, the potential hepatotoxicity of chemotherapeutic agents may be easily overlooked. Two fatal cases of cholestatic hepatotoxicity have been previously reported, clearly implicating gemcitabine therapy. We report a third fatal case of cholestatic liver failure that we think is strongly linked to the use of gemcitabine. This chemotherapeutic agent is a fluorine analog with broad-spectrum antitumor activity commonly used in the treatment of breast, lung, prostate, and cervical cancer. The case we report is of a 45-year-old woman with a history of metastatic breast cancer to her spine. The patient was in remission for two years before she presented with a compensated mixed hepatitis of mild to moderate severity. Inpatient work-up found metastases to the right humerus and inferior pubic ramus, but none in the liver. Gemcitabine and carboplatin therapy was initiated for relapse of breast cancer. The patient's liver enzyme elevation diminished, but did not normalize before the start of chemotherapy. She received four courses of gemcitabine/carboplatin and subsequently presented with decompensated, severe cholestatic hepatitis. Transjugular liver biopsy displayed marked cholestasis and hepatocellular injury consistent with drug-induced hepatoxicity. Gemcitabine has been extensively studied in the oncology literature and at this time is thought to be a low-risk hepatotoxin causing hepatic adaptation and transient, reversible liver enzyme elevation, rarely leading to termination of gemcitabine therapy for solid tumors. We believe that gemcitabine therapy, particularly in the setting of preexisting liver injury or metastases to the liver, increases the relative risk of severe and potentially fatal hepatic injury possibly by idiosyncratic and dose-dependent mechanisms. We recommend careful monitoring and dose adjustment of gemcitabine in patients with abnormal liver function tests or evidence of hepatic metastases until further study clarifies this issue.