James C. Hebert

Treatment of intra-abdominal infection with granulocyte colony-stimulating factor.

Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Implementation of resident work hour restrictions is associated with a reduction in mortality and provider-related complications on the surgical service: a concurrent analysis of 14,610 patients.

Objective:To determine the effect of implementation of work hour restrictions on the rates of morbidity, mortality, and provider-related complications in surgical patients and to determine the incremental personnel costs associated with implementation. Summary Background Data:In 2003, the Accreditation Council for Graduate Medical Education enacted resident work hour restrictions (RWHR) to improve patient safety by decreasing errors attributed to resident fatigue. There are no quantitative data on surgical patients to validate whether this objective has been achieved and, if so, at what cost. Methods:Retrospective observational cohort analysis of data gathered concurrently with patient care for 30 days after admission or surgical intervention before implementation (prerestriction: July 2001–June 2003) and after (postrestriction: July 2005–June 2007). Main outcome measures: mortality, surgical complications, percentage of complications judged to be provider-related, and incremental personnel costs (salary and fringe of providers). Results:A total of 14,610 patients were admitted during the 2 periods. Compared with the prerestriction period, there was a significant reduction in the percentage of complications attributed to providers (pre: 48.3%; post: 38.6%, P < 0.001) and a significant reduction in mortality rate (pre: 1.9%; post: 1.1%, P = 0.002) in the postrestriction period. Postrestriction the clinical care hours provided by attending surgeons increased significantly and was associated with a 1250% increase in the RVU-82 billing modifier (“no qualified resident available”) from 523 RVUs pre-RWHR to 6542 post-RWHR. There was an increase in annual personnel costs postrestriction of

Effect of thymosin alpha one on specific antibody response and susceptibility to infection in young and aged mice

1.466 million. Conclusions:Implementation of RWHR was associated with reduced provider-related complications and mortality suggesting improved patient safety. This was likely due to several factors including reduced resident fatigue and greater attending involvement in clinical care.

Frequency of Inappropriate Continuation of Acid Suppressive Therapy After Discharge in Patients Who Began Therapy in the Surgical Intensive Care Unit

The antibody response to a variety of antigens has been shown to diminish with age. We investigated the capacity for Thymosin Alpha One (T alpha 1) treatment to augment antibody production in tetanus toxoid (TT) and pneumococcal capsular polysaccharide (PN) inoculated young and old mice. We also measured survival of these immunized mice after aerosol exposure to Streptococcus pneumoniae. As predicted antibody response to TT, but not PN, was significantly reduced in the old animals and T alpha 1 augmented antitetanus antibody in both young and old mice. T alpha 1 did not have an effect on anti pneumococcal antibody production. All mice that had received PN did have an antibody response, yet survival after exposure to the organism was strikingly less in the old animals. Our data support the contention that antibody response to T-dependent antigens (such as tetanus toxoid) falls with aging but can be reconstituted somewhat by thymic factors. Furthermore, for T-independent antigen (such as pneumococcal capsular antigens) the age-related changes are less evident. In the latter situation, the presence of a brisk antibody response after vaccination was not sufficient to prevent pneumonia and death in old animals.

Post-traumatic upper airway obstruction secondary to a lingual artery hematoma.

Study Objective. To determine the frequency with which patients who begin to receive stress ulcer prophylaxis in the surgical intensive care unit (SICU) are discharged receiving inappropriate acid suppressive therapy (AST).

Serum levels of prophylactic cefazolin during cardiopulmonary bypass surgery

An accident victim presented with maxillofacial trauma complicating a head injury. After the airway was secured by tracheostomy, surgical exploration revealed a lingual artery hematoma. This case illustrates the progressive airway occlusion seen with this disorder and the importance of repeated oral examinations.

Interleukin 1β improves survival following cecal ligation and puncture

BACKGROUND Controversy exists regarding the appropriate prophylactic dose of cefazolin for coronary artery bypass grafting (CABG) surgery requiring cardiopulmonary bypass (CPB) because the effect of CPB on serum drug levels is poorly understood. Current standards of prophylaxis are based primarily on empiric studies. Few studies have attempted to quantify serum cefazolin levels in either cardiac or noncardiac surgeries. This study was conducted to measure and assess the adequacy of the intraoperative serum levels of prophylactic cefazolin in CPB surgery. METHODS This prospective study serially measured six intraoperative serum cefazolin levels in 10 subjects undergoing elective and urgent CABG surgery. We compared the serum levels with the minimum inhibitory concentrations (MIC90) for the most common organisms causing postoperative infection. RESULTS Serum-free cefazolin levels fluctuated considerably during the operation but remained above the MIC90, for Staphylococcus aureus and S. epidermidis. The serum levels fell below the MIC90 for Enterobacter, Serratia, Escherichia coli, and Proteus mirabilis. CONCLUSIONS Serum cefazolin levels during CPB remained consistently above the MIC for two of the three main organisms causing postoperative infection but were suboptimal for the remainder. Additional studies are needed to assess the intraoperative serum levels of single-dose cefazolin prophylaxis and to explore alternate dosing methods that minimize intraoperative fluctuations in serum cefazolin levels.

Pursuing Professional Accountability An Evidence-Based Approach to Addressing Residents With Behavioral Problems

Abstract Despite antibiotic therapy intra-abdominal sepsis following major surgery is a significant cause of mortality. We sought to determine if interleukin-1β (IL-1) could improve survival in a murine model of intra-abdominal infection. Groups of 10 BDF 1 mice received a single subcutaneous (sc) injection of recombinant human IL-1β 24 hr prior to cecal ligation and puncture (CLP) and were assessed twice daily for survival. Mice that received a single injection of IL-1β 24 hr prior to CLP had a dose-dependent improval in survival compared to controls. The beneficial effect of IL-1 treatment may have been related to its ability to stimulate myelopiesis. The addition of indomethacin, in an effort to limit possible toxicity of IL-1, did not further improve survival. Appropriate timing of specific immunomodulators may provide an additional strategy for the treatment of infections.

Augmentation of alveolar macrophage phagocytic activity by granulocyte colony stimulating factor and interleukin-1 : influence of splenectomy

OBJECTIVE To develop an evidence-based approach to the identification, prevention, and management of surgical residents with behavioral problems. DESIGN The American College of Surgeons and Southern Illinois University Department of Surgery hosted a 1-day think tank to develop strategies for early identification of problem residents and appropriate interventions. Participants read a selection of relevant literature before the meeting and reviewed case reports. SETTING American College of Surgeons headquarters, Chicago, Illinois. PARTICIPANTS Medical and nursing leaders in the field of resident education; individuals with expertise in dealing with academic law, mental health issues, learning deficiencies, and disruptive physicians; and surgical residents. MAIN OUTCOME MEASURES Evidence-based strategies for the identification, prevention, and management of problem residents. RESULTS Recommendations based on the literature and expert opinions have been made for the identification, remediation, and reassessment of problem residents. CONCLUSIONS It is essential to set clear expectations for professional behavior with faculty and residents. A notice of deficiency should define the expected acceptable behavior, timeline for improvement, and consequences for noncompliance. Faculty should note and address systems problems that unintentionally reinforce and thus enable unprofessional behavior. Complaints, particularly by new residents, should be investigated and addressed promptly through a process that is transparent, fair, and reasonable. The importance of early intervention is emphasized.

Do general surgery residency programs adequately train surgeons to perform anorectal surgery

The use of cytokines and other naturally occurring substances as biopharmaceuticals for modulating the host response to trauma and infection offers new therapeutic possibilities. Cytokine pretreatment protects animals in a variety of experimental models, including splenectomized mice following pneumococcal aerosol challenge. Since splenectomy appears to affect alveolar macrophage function, we postulated that pretreatment with interleukin 1 (IL-1) and granulocyte colony stimulating factor (G-CSF) improved survival in mice following aerosol challenge of live pneumococci by activating alveolar macrophages. Alveolar macrophage bactericidal and phagocytic function was slightly, but consistently, depressed following splenectomy. Interleukin-1 and G-CSF pretreatment had pronounced effects on macrophage phagocytic and bactericidal activity, and these effects were quite different depending upon whether the mice were eusplenic or asplenic. Splenectomy augmented the effects of IL-1 on alveolar macrophage bactericidal function compared with eusplenic mice (p < 0.001), while more pronounced effects on macrophage function following G-CSF treatment were seen in mice with intact spleens (p < 0.001). The use of cytokines and other substances to modify the host response to infection has great potential. Individuals with deficits such as splenectomy will have a different net response to therapy. It is important that we be able to predict these responses accurately in most patients in order to use these substances more effectively.