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Biomedical subjects

E P Dellinger

Publications and source records attributed to E P Dellinger.

At least 19 recordsLinked to original sources

Impaired esophageal function in morbidly obese patients with gastroesophageal reflux disease: evaluation with multichannel intraluminal impedance.

BACKGROUND: Morbid obesity is associated with gastroesophageal reflux disease (GERD), and both have an independent association with motility disorders. Impaired esophageal function is thought to play a role in the development of dysphagia after fundoplication and bariatric procedures (especially restrictive procedures). The authors aimed to define both the physiology and the underlying pathophysiology of swallowing using a novel technique, multichannel intraluminal impedance (MII), which can accurately determine the clearance of a swallowed bolus through the esophagus, in combination with traditional manometry, which can measure peristalsis. METHODS: Simultaneous MII, manometry, and pH monitoring were performed for 10 asymptomatic subjects, 22 consecutive nonobese patients with GERD (GERD), and 22 consecutive morbidly obese patients with GERD (MO-GERD) who were under evaluation for antireflux and bariatric surgery at the University of Washington. In this study, MII was defined as abnormal if less than 80% of swallowed liquid boluses cleared the esophagus completely. RESULTS: All GERD and MO-GERD patients had abnormal pH monitoring. The manometric findings were similar for the GERD and MO-GERD patients. All the asymptomatic subjects had normal manometry and impedance test results. Abnormal manometry would have predicted that approximately 23% of GERD and MO-GERD patients had defective emptying. However, when measured with impedance, esophageal clearance was found to be defective in two times as many GERD and nearly three times as many MO-GERD patients. CONCLUSIONS: In patients with GERD, impedance often detects impairments in esophageal motility not identified by manometry. Morbidly obese patients with GERD have a higher incidence of impaired esophageal motility than nonobese patients with GERD. This may have implications for bariatric procedures, especially those that are restrictive.

Circadian Rhythm↗

Has misdiagnosis of appendicitis decreased over time? A population-based analysis.

CONTEXT: Misdiagnosis of presumed appendicitis is an adverse outcome that leads to unnecessary surgery. Computed tomography, ultrasonography, and laparoscopy have been suggested for use in patients with equivocal signs of appendicitis to decrease unnecessary surgery. OBJECTIVE: To determine if frequency of misdiagnosis preceding appendectomy has decreased with increased availability of computed tomography, ultrasonography, and laparoscopy. DESIGN, SETTING, AND PATIENTS: Retrospective, population-based cohort study of data from a Washington State hospital discharge database for 85 790 residents assigned International Classification of Diseases, Ninth Revision procedure codes for appendectomy, and United States Census Bureau data for 1987-1998. MAIN OUTCOME MEASURE: Population-based age- and sex-standardized incidence of appendectomy with acute appendicitis (perforated or not) or with a normal appendix. RESULTS: Among 63 707 nonincidental appendectomy patients, 84.5% had appendicitis (25.8% with perforation) and 15.5% had no associated diagnosis of appendicitis. After adjusting for age and sex, the population-based incidence of unnecessary appendectomy and of appendicitis with perforation did not change significantly over time. Among women of reproductive age, the population-based incidence of misdiagnosis increased 1% per year (P =.005). The incidence of misdiagnosis increased 8% yearly in patients older than 65 years (P<.001) but did not change significantly in children younger than 5 years (P =.17). The proportion of patients undergoing laparoscopic appendectomy who were misdiagnosed was significantly higher than that of open appendectomy patients (19.6% vs 15.5%; P<.001). CONCLUSION: Contrary to expectation, the frequency of misdiagnosis leading to unnecessary appendectomy has not changed with the introduction of computed tomography, ultrasonography, and laparoscopy, nor has the frequency of perforation decreased. These data suggest that on a population level, diagnosis of appendicitis has not improved with the availability of advanced diagnostic testing.

Adolescent↗

Common bile duct injury during laparoscopic cholecystectomy and the use of intraoperative cholangiography: adverse outcome or preventable error?

BACKGROUND: Common bile duct (CBD) injury is a serious complication of laparoscopic cholecystectomy (LC). Predictors of this adverse outcome have not been well documented. HYPOTHESIS: Surgeon experience and the use of intraoperative cholangiography (IOC) are associated with a decreased rate of major CBD injury during LC. DESIGN: A retrospective population-based cohort study. SETTING: Washington State hospital discharge database reports from 1991 through 1998. PATIENTS: Discharge reports were searched for International Classification of Diseases, Ninth Revision, procedure codes consistent with LC and then evaluated for procedure codes for CBD repair and reconstruction within 90 days of LC. MAIN OUTCOME MEASURE: The rate of CBD injury in patients undergoing LC based on the surgeon's experience and IOC use. RESULTS: In all, 30 630 LCs and 76 major CBD injuries (2.5/1000 operations) were identified in this analysis. There were no significant differences between injured and noninjured patients in demographics, disease, payer status, or hospital variables. A CBD injury occurred in 3.2 of 1000 LCs in the early case order of surgeons compared with 1.7 per 1000 at later points (P = .01) (relative risk, 1.81; 95% confidence interval, 1.44-2.88). The rate of injury in LCs performed without IOC was 3.3 per 1000 compared with 2.0 per 1000 in LCs with IOC (P = .02) (relative risk, 1.7; 95% confidence interval, 1.1-2.6). Surgeon's experience and IOC use were independent predictors of injury. CONCLUSIONS: The rate of CBD injury is significantly lower when IOC is used. This effect is magnified during the early experience of surgeons. Systematic use of IOC may significantly reduce the rate of CBD injury.

Cholangiography↗

Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intraabdominal infections.

OBJECTIVE: Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy. SUMMARY BACKGROUND DATA: Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity. METHODS: This prospective, randomized, double-blind trial was conducted to compare clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections. RESULTS: Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin. CONCLUSIONS: The results of this study clearly demonstrate the safety and efficacy of clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances.

Abdomen↗

Can one use biologic modifiers to prevent multiple organ dysfunction syndrome after abdominal infections?

Postoperative or trauma-induced intra-abdominal infections can result in sepsis and multiple organ dysfunction syndrome (MODS). Enteric bacteria and endotoxin released from the gut into the peritoneal cavity in response to injury can directly stimulate the inflammatory cascade responsible for the development of systemic inflammation and subsequent MODS. Therapeutic strategies, such as biologic modifiers that are aimed at blocking or enhancing specific mediators of the inflammatory response, have been developed and tested in animal models with varying efficacy in preventing mortality. Specific therapies that have shown beneficial effects in animal models have not proved successful in prospective, randomized human studies, and it is as yet unclear whether cytokine-based therapies will ultimately have a role in preventing MODS. Testing novel therapies in appropriate animal models that closely simulate human intra-abdominal infection is crucial in developing drugs that will be beneficial in preventing sepsis-induced mortality in critically ill patients.

Abdomen↗

Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group.

BACKGROUND: Postoperative infections remain common after high-risk gastrointestinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Worcester, Mass), derived from yeast cell walls, promotes phagocytosis and intracellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antibiotics to reduce mortality in rat peritonitis. HYPOTHESIS: We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent. DESIGN: Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata. SETTING: Thirty-nine medical centers throughout the United States. PATIENTS: Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors. INTERVENTIONS: PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preoperatively and 3 times postoperatively. All patients received standardized antibiotic prophylaxis. MAIN OUTCOME MEASURES: Serious infection or death within 30 days. RESULTS: All randomized patients revealed no difference in serious infections and deaths in the treated groups compared with placebo groups (15% vs 14%, P>.90). In the prospectively defined noncolorectal stratum (n = 391), PGG-glucan administration was associated with a statistically significant relative reduction (39%) in serious infections and death (placebo, 46 [36%] of 129 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P<.02). PGG-glucan reduced postoperative infection or death in malnourished patients having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan group; P<.001). Study drug was stopped owing to adverse effects more frequently for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the placebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, respectively, P<.003). CONCLUSION: Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Adjuvants, Immunologic↗

Current guidelines for antibiotic prophylaxis of surgical wounds.

Appropriately administered antibiotic prophylaxis reduces the incidence of surgical wound infection. Prophylaxis is uniformly recommended for all clean-contaminated, contaminated and dirty procedures. It is considered optional for most clean procedures, although it may be indicated for certain patients and clean procedures that fulfill specific risk criteria. Timing of antibiotic administration is critical to efficacy. The first dose should always be given before the procedure, preferably within 30 minutes before incision. Readministration at one to two half-lives of the antibiotic is recommended for the duration of the procedure. In general, postoperative administration is not recommended. Antibiotic selection is influenced by the organism most commonly causing wound infection in the specific procedure and by the relative costs of available agents. In certain gastrointestinal procedures, oral and intravenous administration of agents with activity against gram-negative and anaerobic bacteria is warranted, as well as mechanical preparation of the bowel. Cefazolin provides adequate coverage for most other types of procedures.

Anti-Bacterial Agents↗

The role of oral antimicrobials for the management of intra-abdominal infections.

BACKGROUND: Oral therapy for patients with complicated intra-abdominal infections has been very limited because those patients are frequently ill and need surgery. In addition, at the time of diagnosis and initial treatment, the infection is often accompanied by ileus, gastrointestinal tract function is frequently unknown, and many patients cannot tolerate oral intake. The use of oral antimicrobials in this setting is a recent advance resulting from the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. This is the first prospective blinded study of oral therapy to provide data on the characteristics of patients eligible for oral treatment and the consequences of such treatment. STUDY DESIGN: In blinded fashion, patients with complicated intra-abdominal infections were randomized to either i.v. ciprofloxacin plus metronidazole or i.v. imipenem throughout their treatment course, or i.v. ciprofloxacin plus metronidazole and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ i.v./oral). Physicians could switch the patient to oral therapy between 3 and 8 days after the start of i.v. treatment. RESULTS: One hundred fifty-five of 330 (47%) patients were switched to active or placebo oral therapy. Patients who received i.v./oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. Of 46 CIP/MTZ i.v./oral patients (active oral arm), treatment failure occurred in 2 patients (4%) compared with 41 patients (23%) who were not switched to oral agents. No patient or disease features, such as Acute Physiology and Chronic Health Evaluation II score, severity of illness at study entry, organ source of infection, or duration of treatment were identified as predictors of conversion to oral treatment. CONCLUSIONS: In this first prospective examination of sequential i.v./oral therapy for complicated intra-abdominal infections, conversion to oral therapy with ciprofloxacin plus metronidazole appears as effective as continued i.v. therapy for patients able to tolerate oral feedings. Patients who can tolerate oral intake may be treated with appropriate oral antimicrobials and are not at any significant increased risk for failure.

APACHE↗

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group.

OBJECTIVE: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. RESULTS: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.

Abdomen↗

Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group.

OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. CONCLUSIONS: These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.

Abdomen↗

Duration of antibiotic treatment in surgical infections of the abdomen. Undesired effects of antibiotics and future studies.

Effects of antibiotic administration other than bacterial killing are common and include drug interactions, toxic, and allergic reactions. Effective antibiotics do release endotoxin from enteric bacteria, but the clinical significance of this effect is uncertain, and present knowledge does not support alteration of clinical practice based on this information. The duration of antibiotic administration that is necessary for prophylactic purposes is short, probably 12 hours or less in all cases. The duration of administration that is necessary for treatment of established infections is not known in most cases. It is likely that current clinical practice errs on the side of continuing antibiotics longer than necessary. Prospective studies to find out the necessary duration of antibiotic treatment are needed. The design and interpretation of these studies will be difficult. Studies of a decision rule for stopping antibiotics are probably preferable to studies of arbitrary duration.

Anti-Bacterial Agents↗

Definition of the role of enterococcus in intraabdominal infection: analysis of a prospective randomized trial.

BACKGROUND: The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial. METHODS: A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America. RESULTS: In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation. CONCLUSIONS: This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

Abscess↗

Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.

We report a large pedigree in which pancreatic cancer is inherited in an autosomal dominant fashion. Diabetes and exocrine insufficiency was observed in all family members who eventually developed pancreatic cancer. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those people who had inherited the predisposing allele and who were thus at high risk for the development of malignancy. This family shows that genetic factors can have a striking effect on the development of pancreatic malignancy and diabetes mellitus. Moreover, preclinical diagnosis of pancreatic cancer in family members provided a unique opportunity to study early molecular changes that accompany the development of human pancreatic cancer. Finally, the molecular approach applied here to the early diagnosis of pancreatic cancer may prove valuable in this family for identification of subjects at risk.

Adenocarcinoma↗

Assessment of hepatitis B virus immunization status among North American surgeons.

OBJECTIVE: We hypothesized that many surgeons have not been vaccinated against hepatitis B virus (HBV), despite the existence of effective recombinant vaccines. Prevalence of HBV vaccination among surgeons, attitudes of those not vaccinated, estimated HBV infection rates, and respondents' knowledge of the epidemiology of HBV exposure were determined. DESIGN: Survey conducted by mail just before implementation of mandatory HBV vaccination for health care workers. SETTING: Private and academic general surgical, trauma and transplantation practices. PARTICIPANTS: Two thousand one hundred twenty-five surgeons received the survey. Response rates are as follows: in the Surgical Infection Society, 196 (50%) of 393 surgeons; in the American Association for the Surgery of Trauma, 223 (52%) of 433 surgeons; in the American Society of Transplant Surgeons, 194 (44%) of 438 surgeons; and among the Fellows of the American College of Surgeons, 403 (47%) of 861 surgeons. MAIN OUTCOME MEASURES: Prevalence of HBV exposure and active immunization by specialty and society. RESULTS: Prevalence of HBV exposure was 19.6%, was higher among trauma and transplantation surgeons compared with general surgeons (P < .0001), and increased significantly with age in all groups (P < .05). Despite greater exposure, probable immunity was lower at an older age because young surgeons (age, < 46 years) are more likely to be vaccines (P < .05). Most surgeons (55%) were vaccinated more than 5 years ago; many recipients of recombinant vaccines (26%) received an inadequate amount of vaccine or were improperly vaccinated. Knowledge of the epidemiology was uniformly poor, with rates of correct responses to the three questions below 50%. CONCLUSIONS: Vaccination does not equal immunity. Between 38% and 50% of practicing surgeons may not have adequate immunity to HBV.

Adult↗