Dror Soffer

Targeted Disruption of the Mouse Caspase 8 Gene Ablates Cell Death Induction by the TNF Receptors, Fas/Apo1, and DR3 and Is Lethal Prenatally

Homozygous targeted disruption of the mouse Caspase 8 (Casp8) gene was found to be lethal in utero. The Caspase 8 null embryos exhibited impaired heart muscle development and congested accumulation of erythrocytes. Recovery of hematopoietic colony-forming cells from the embryos was very low. In fibroblast strains derived from these embryos, the TNF receptors, Fas/Apo1, and DR3 were able to activate the Jun N-terminal kinase and to trigger IkappaB alpha phosphorylation and degradation. They failed, however, to induce cell death, while doing so effectively in wild-type fibroblasts. These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development.

Can near-infrared spectroscopy identify the severity of shock in trauma patients?

BACKGROUND Our recent experimental study showed that peripheral muscle tissue oxygen saturation (StO2), determined noninvasively by near-infrared spectroscopy (NIRS), was more reliable than systemic hemodynamics or invasive oxygenation variables as an index of traumatic shock. The purpose of this study was to establish the normal range of thenar muscle StO2 in humans and the relationship between shock state and StO2 in trauma patients. METHODS This was a prospective, nonrandomized, observational, descriptive study in normal human volunteers (n = 707) and patients admitted to the resuscitation area of our Level I trauma center (n = 150). To establish a normal StO2 range, an NIRS probe was applied to the thenar eminence of volunteers (normals). Subsequently, in a group of trauma patients, an NIRS probe was applied to the thenar eminence and data were collected and stored for offline analysis. StO2 monitoring was performed continuously and noninvasively, and values were recorded at 2-minute intervals. Five moribund trauma patients were excluded. Members of our trauma faculty, blinded to StO2 values, classified each patient into one of four groups (no shock, mild shock, moderate shock, and severe shock) using conventional physiologic parameters. RESULTS Mean +/- SD thenar StO2 values for each group were as follows: normals, 87 +/- 6% (n = 707); no shock, 83 +/- 10% (n = 85); mild shock, 83 +/- 10% (n = 19); moderate shock, 80 +/- 12% (n = 14); and severe shock, 45 +/- 26% (n = 14). The thenar StO2 values clearly discriminated the normals or no shock patients and the patients with severe shock (p < 0.05). CONCLUSION Decreased thenar muscle tissue oxygen saturation reflects the presence of severe hypoperfusion and near-infrared spectroscopy may be a novel method for rapidly and noninvasively assessing changes in tissue dysoxia.

Secondary ultrasound examination increases the sensitivity of the FAST exam in blunt trauma.

INTRODUCTION Approximately one third of stable patients with significant intra-abdominal injury do not have significant intraperitoneal blood evident on admission. We hypothesized that a delayed, repeat ultrasound study (Secondary Ultrasound--SUS) will reveal additional intra-abdominal injuries and hemoperitoneum. METHODS We performed a prospective observational study of trauma patients at our Level I trauma center from April 2003 to December 2003. Patients underwent an initial ultrasound (US), followed by a SUS examination within 24 hours of admission. Patients not eligible for a SUS because of early discharge, operative intervention or death were excluded. All US and SUS exams were performed and evaluated by surgical/emergency medicine house staff or surgical attendings. RESULTS Five hundred forty-seven patients had both an initial US and a SUS examination. The sensitivity of the initial US in this patient population was 31.1% and increased to 72.1% on SUS (p < 0.001) for intra-abdominal injury or intra-abdominal fluid. The specificity for the initial US was 99.8% and 99.8% for SUS. The negative predictive value was 92.0% for the initial US and increased to 96.6% for SUS (p = 0.002). The accuracy of the initial ultrasound was 92.1% and increased to 96.7% on the SUS (p < 0.002). No patient with a negative SUS after 4 hours developed clinically significant hemoperitoneum. CONCLUSION A secondary ultrasound of the abdomen significantly increases the sensitivity of ultrasound to detect intra-abdominal injury.

Methylene Blue Prevents Pulmonary Injury after Intestinal Ischemia-reperfusion

OBJECTIVE To investigate the effect of methylene blue, an inhibitor of oxygen radicals, on lung injury caused by reperfusion of ischemic tissue. METHODS Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 1 hour. Thereafter, the experimental group was administered 1% methylene blue intraperitoneally and the control group received saline. After 4 hours, pulmonary histopathologic features were assessed, and lung wet-weight to dry-weight ratios and tissue xanthine oxidase were determined. RESULTS The control group suffered from severe pulmonary parenchymal damage, compared with slight damage in the experimental group. The number of sequestered neutrophils was significantly higher in the control group (319 +/- 60 polymorphonuclear cells per 10 high-power fields) than in the methylene blue-treated group (91 +/- 8 polymorphonuclear cells per 10 high-power fields; p < 0.001). The wet-weight to dry-weight ratio was significantly increased in the saline-treated rats compared with the methylene blue-treated group (6.19 +/- 0.28 vs. 5.07 +/- 0.21; p < 0.001). Xanthine oxidase activity was similar in both groups. CONCLUSION Methylene blue attenuated lung injury after intestinal ischemia-reperfusion. Inhibition of oxygen free radicals may be the protective mechanism.

An interventional study to improve the quality of analgesia in the emergency department.

OBJECTIVE We sought to document the adequacy of acute pain management in a high-volume urban emergency department and the impact of a structured intervention. METHODS We conducted a prospective, single-blind, pre- and postintervention study on patients who suffered minor-to-moderate trauma. The intervention consisted of structured training sessions on emergency department (ED) analgesia practice and the implementation of a voluntary analgesic protocol. RESULTS Preintervention data showed that only 340 of 1000 patients (34%) received analgesia. Postintervention data showed that 693 of 700 patients (99%) received analgesia, an absolute increase of 65% (95% CI 61%-68%), and that delay to analgesia administration fell from 69 (standard deviation [SD] 54) minutes to 35 (SD 43) minutes. Analgesics led to similar reductions in visual analog pain scale ratings during the pre- and postintervention phases (4.5 cm, SD 2.0 cm, and 4.3 cm, SD 3.0 cm, respectively). CONCLUSION Our multifaceted ED pain management intervention was highly effective in improving quality of analgesia, timeliness of care and patient satisfaction. This protocol or similar ones have the potential to substantially improve pain management in diverse ED settings.

Functions and principles in the management of bombing mass casualty incidents: lessons learned at the Tel-Aviv Souraski Medical Center.

Mass casualty incidents (MCI) resulting from terrorist bombings pose special problems and may overwhelm even the most experienced trauma centre. Although role assignments for MCI management and control are documented, we would like to share several aspects that we have found to be crucial for the management of terrorist bombing MCI. Twelve topics and possible answers were brought up and discussed extensively in MCI debriefing sessions in our institution. They were of two main categories: assignments and functions of key personnel, and principles and definitions. The first category includes the Triage Officer, the Medical Director, the Administrative Director, the Head Nurse, the Emergency Medical System Coordinator, the Blood Bank Liaison, and the trauma teams. The second category encompasses the concept of triage hospital, the unidirectional patient flow, ancillary evaluation during MCI, the consultancy, and tertiary survey. All were identified as critical for proper event handling. The integration and implementation of the topics discussed throughout the medical system may enable emergency departments to handle MCI resulting from terrorist bombings better.

Is there an optimal time for laparoscopic cholecystectomy in acute cholecystitis

BackgroundLaparoscopic cholecystectomy (LC) is safe in acute cholecystitis, but the exact timing remains ill-defined. This study evaluated the effect of timing of LC in patients with acute cholecystitis.MethodsProspective data from the hospital registry were reviewed. All patients admitted with acute cholecystitis from June 1994 to January 2004 were included in the cohort.ResultsLaparoscopic cholecystectomy was attempted in 1,967 patients during the study period; 80% were women, mean patient age was 44 years (range, 20–73 years). Of the 1,967 LC procedures, 1,675 were successful, and 292 were converted to an open procedure (14%). Mean operating time for LC was 1 h 44 min (SD ± 50 min), versus 3 h 5 min (SD ± 79 min) when converted to an open procedure. Average postoperative length of stay was 1.89 days (± 2.47 days) for the laparoscopic group and 4.3 days (± 2.2 days) for the conversion group. No clinically relevant differences regarding conversion rates, operative times, or postoperative length of stay were found between patients who were operated on within 48 h compared to those patients who were operated on post-admission days 3–7.ConclusionsThe timing of laparoscopic cholecystectomy in patients with acute cholecystitis has no clinically relevant effect on conversion rates, operative times, or length of stay.

Morbidity associated with MDMA (ecstasy) abuse: A survey of emergency department admissions

Methods: We conducted a prospective, representative-sample nationwide study on morbidity related to 3,4, methylenedioxymethamphetamine (MDMA; ‘ecstasy’) as determined from admissions to 5 geographically representative emergency departments (EDs) and from data from the poison information center (PIC). MDMArelated ED admissions were analyzed over a 7-month period and the records of all PIC calls were reviewed. Results: There were 52 (age 15—44 years, 32 males) ecstasy-related ED admissions during the study period. Most (68%) admissions presented to the ED at night, 52% on weekends and 44% consumed the drug at clubs and parties. Forty-six percent of the patients took between 1/2 to 3 tablets and 29 patients (56%) had taken ecstasy before. Twenty-two subjects (42%) reported poly-drug use. Fifteen subjects (29%) required hospitalization, six of them (11%) to the intensive care unit. The most common manifestations were restlessness, agitation, disorientation, shaking, high blood pressure, headache and loss of consciousness. More serious complications were hyperthermia, hyponatremia, rhabdomyolysis, brain edema and coma. Conclusion: The image of ecstasy as a safe party drug is spurious. The results of this study confirm that the drug bears real danger of physical harm and of behavioral, psychological and psychiatric disturbances.

Peritoneal cultures and antibiotic treatment in patients with perforated appendicitis.

OBJECTIVE To question the common practice of sending material for microbiological examination during appendicectomy for perforated appendixes. DESIGN Uncontrolled retrospective study. SETTING Teaching hospital, Israel. SUBJECTS 89 patients who had their perforated appendixes removed. INTERVENTIONS Appendicectomy and antibiotic treatment. MAIN OUTCOME MEASURE Whether a change in antibiotic regimen was required after bacteriological identification of bacteria isolated during the operation. RESULTS In only 43 of the cultures (48%) taken during the operation were bacteria grown, and these were mainly Escherichia coli. In 65 patients (73%) there was no need to change the previously initiated antibiotic regimen, and in 23 (26%) it was changed purely on clinical grounds. In only one patient (1%) was the change the consequence of microbiological testing, as the organisms identified in 42 of the 43 cultures (98%) were sensitive to at least one of the antibiotics that had already been given. CONCLUSION The practice of culturing samples taken from a ruptured appendix is redundant, because the antibiotic that has already been initiated is effective in most of the patients and the decision to modify the therapeutic regimen is dominated by clinical considerations.

Tumour Necrosis Factor Mediates Bacterial Translocation After Haemorrhagic Shock and Endotoxaemia

OBJECTIVE To assess the extent of bacterial translocation after haemorrhagic shock and reperfusion, and the involvement of tumour necrosis factor (TNF) in its mediation. DESIGN Controlled, randomised prospective experiment. SUBJECTS 87 rats in 7 groups. INTERVENTIONS Haemorrhagic shock was induced in rats for 1 hour. Endotoxaemia was induced in a second group by the injection of lipopolysaccharide. A third group was injected with exogenous TNF. Some of the animals were further treated with anti-TNF. MEASUREMENTS After 24 hours, bacterial translocation in blood and in several remote organs, and serum TNF concentrations were measured. RESULTS High bacterial counts were found in all remote organs of rats with haemorrhagic shock or endotoxaemia. Their serum TNF concentrations were significantly higher than in the corresponding sham-operated controls. Anti-TNF significantly reduced the extent of bacterial translocation. Rats, the only treatment of which was exogenous TNF, developed substantial bacterial translocation. CONCLUSION Bacterial translocation is associated with increased serum TNF, and can be minimised by anti-TNF. This, and the triggering of translocation in unprovoked animals by TNF alone, suggest that TNF may be the stimulator, and not the consequence, of bacterial translocation.