Use of in vitro-generated, stem cell-derived islets to cure type 1 diabetes: how close are we?

Recent successes in treating type 1 diabetic patients with islet transplantation portends a future need for an increase in available islets. Ductal structures of the adult pancreas contain multipotent stem cells that, under the proper in vitro conditions, can both self-renew and differentiate into functional islets of Langerhans. In vitro-generated islets exhibit temporal changes in mRNA transcripts for islet-associated markers as well as regulated insulin responses following glucose challenge. When implanted into diabetic mice, in vitro-generated islets induce neovascularization and reverse insulin-dependent diabetes. The possibility of growing functional endocrine pancreas from stem cells provides new opportunities to produce large numbers of islets, even autologous islets, for use as implants.

Management of traumatic lung injury: a Western Trauma Association Multicenter review.

BACKGROUND: Improved outcomes following lung injury have been reported using "lung sparing" techniques. METHODS: A retrospective multicenter 4-year review of patients who underwent lung resection following injury was performed. Resections were categorized as "minor" (suture, wedge resection, tractotomy) or "major" (lobectomy or pneumonectomy). Injury severity, Abbreviated Injury Scale (AIS) score, and outcome were recorded. RESULTS: One hundred forty-three patients (28 blunt, 115 penetrating) underwent lung resection after sustaining an injury. Minor resections were used in 75% of cases, in patients with less severe thoracic injury (chest AIS scores "minor" 3.8 +/- 0.9 vs. "major" 4.3 +/- 0.7, p = 0.02). Mortality increased with each step of increasing complexity of the surgical technique (RR, 1.8; CI, 1.4-2.2): suture alone, 9% mortality; tractotomy, 13%; wedge resection, 30%; lobectomy, 43%; and pneumonectomy, 50%. Regression analysis demonstrated that blunt mechanism, lower blood pressure at thoracotomy, and increasing amount of the lung resection were each independently associated with mortality. CONCLUSION: Blunt traumatic lung injury has higher mortality primarily due to associated extrathoracic injuries. Major resections are required more commonly than previously reported. While "minor" resections, if feasible, are associated with improved outcome, trauma surgeons should be facile in a wide range of technical procedures for the management of lung injuries.

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Evaluating blunt abdominal trauma with sonography: a cost analysis.

Ultrasonography (US) is becoming increasingly utilized in the United States for the evaluation of blunt abdominal trauma (BAT). The objective of this study was to assess the cost impact of utilizing US in the evaluation of patients with BAT in a major trauma center. All patients sustaining BAT during a 6-month period before US was used at our institution (Jan-Jun 1993) were compared to BAT patients from a recent period in which US has been utilized (Jan-Jun 1995). The numbers of US, computed tomography (CT), and diagnostic peritoneal lavage (DPL) were tabulated for each group. Financial cost for each of these procedures as determined by our finance department were as follows: US $96, CT $494, DPL $137. These numbers are representative of actual hospital expenditures exclusive of physician fees as calculated in 1994 U.S. dollars. Cost analysis was performed with t test and chi squared test, and significance was defined as P < 0.05. There were 890 BAT admissions in the 1993 study period and 1033 admissions in the 1995 study period. During the 1993 period, 642 procedures were performed on the 890 patients to evaluate the abdomen: 0 US, 466 CT, and 176 DPL (see table) [table: see text]. This compares to 801 procedures on the 1,033 patients in 1995: 552 US, 228 CT, and 21 DPL. Total cost was $254,316 for the 1993 group and $168,501 for the 1995 group. Extrapolated to a 1-year period, a significant (P < 0.05) cost savings of $171,630 would be realized. Cost per patient evaluated was significantly reduced from $285.75 in 1993 to $163.12 in 1995 (P < 0.05). This represents a 43 per cent reduction in per patient expenditure for evaluating the abdomen. By effectively utilizing ultrasonography in the evaluation of patients with blunt abdominal trauma, a significant cost savings can be realized. This effect results chiefly from an eight-fold reduction in the use of DPL, and a two-fold reduction in the use of CT.

Early life stress and disease among offspring and siblings of individuals with type 1 diabetes mellitus.

Major life events, recent life stressors, and childhood diseases were examined among children and adolescents who were offspring, siblings, or other relatives of persons with type 1 diabetes mellitus (DM). All youth were recruited as part of a multi-site nationwide trial on the prevention of type 1 DM; parents of 347 children (4 to 18 yr) completed measures that asked about children's life events, recent stressors, and childhood illnesses. Analyses compared age groups (young child, preadolescent, adolescent) and relative type (offspring, sibling, other relative). Findings revealed offspring and siblings did not differ from "other relatives" in terms of life events, recent life stress, and disease/illness variables. However, siblings were reported to have fewer major life events and fewer life stressors in the past 12 months than offspring; siblings also had fewer infectious diseases during the first two years of life compared to offspring. Few age-related differences were found. Overall, results suggest that offspring and siblings of persons with type 1 DM are not at a disadvantage in terms of early life stress or disease in comparison to youth who have other family members with diabetes. However, siblings may have some advantages relative to children who are offspring. The mechanisms underlying these relationships require further elucidation and study.

Timing of urgent thoracotomy for hemorrhage after trauma: a multicenter study.

HYPOTHESIS: It is possible to quantify an amount of thoracic hemorrhage, after blunt and penetrating injury, at which delay of thoracotomy is associated with increased mortality. DESIGN: A retrospective case series. SETTING: Five urban trauma centers. STUDY SELECTION: Patients undergoing urgent thoracotomy (within 48 hours of injury) for hemorrhage (excluding emergency department thoracotomy). DATA EXTRACTION: Respective registries identified patients who underwent urgent thoracotomy. Injury characteristics, initial and subsequent chest tube outputs, time before thoracotomy, and outcomes were evaluated. MAIN OUTCOME MEASURE: Death. RESULTS: One hundred fifty-seven patients (36 with blunt and 121 with penetrating injuries) underwent urgent thoracotomy for hemorrhage between January 1, 1995, and December 31, 1998. Mortality correlated with mean (+/- SD) Injury Severity Score (38 +/- 19 vs 22 +/- 12.6 for survivors; P<.01) and mechanism (24 [67%] for blunt vs 21 [17%] for penetrating injuries; P<.01). Mortality increased as total chest blood loss increased, with the risk for death at blood loss of 1500 mL being 3 times greater than at 500 mL. Blunt-injured patients waited a significantly longer time to thoracotomy than penetrating-injured patients (4.4 +/- 9.0 h vs 1.6 +/- 3.0 h; P =.02) and also had a greater total chest tube output before thoracotomy (2220 +/- 1235 mL vs 1438 +/- 747 mL; P =.001). CONCLUSIONS: The risk for death increases linearly with total chest hemorrhage after thoracic injury. Thoracotomy is indicated when total chest tube output exceeds 1500 mL within 24 hours, regardless of injury mechanism.

Efficacy of follow-up evaluation in penetrating thoracic injuries: 3- vs. 6-hour radiographs of the chest.

Pneumothorax (PTX) in patients with penetrating thoracic trauma is routinely ruled out with serial chest radiographs (CXRs). This study examined the efficacy of a shortened time period between initial and follow-up radiographs. Patients with penetrating torso injuries treated at a Level-1 trauma center received a CXR during their initial evaluation. If no pneumothorax or hemothorax was noted, and the patient did not require immediate admission to the Intensive Care Unit or operating room, a repeat chest film was taken at 3 and 6 h. Findings were treated as clinically indicated, and patients were discharged home if the last radiograph revealed no evidence of pathology. Over a 15-month period, 116 patients were evaluated for penetrating thoracic injuries (93 stabbings, 23 gunshot wounds) and had no pneumothorax detected on initial CXR. Two patients had pneumothorax detectable only by computed tomography. One patient had a normal initial CXR, but developed a PTX on the 3-h film, requiring tube thoracostomy. No patients developed a PTX on the 6-h study that was not present on the initial or 3-h CXR. In conclusion, extending the time between initial and final CXRs to 6 h in patients with penetrating thoracic trauma provided no additional information that was not available on the 3-h film.

Prospective randomized trial of two wound management strategies for dirty abdominal wounds.

OBJECTIVE: To determine the optimal method of wound closure for dirty abdominal wounds. SUMMARY BACKGROUND DATA: The rate of wound infection for dirty abdominal wounds is approximately 40%, but the optimal method of wound closure remains controversial. Three randomized studies comparing delayed primary closure (DPC) with primary closure (PC) have not conclusively shown any advantage of one method over the other in terms of wound infection. METHODS: Fifty-one patients with dirty abdominal wounds related to perforated appendicitis, other perforated viscus, traumatic injuries more than 4 hours old, or intraabdominal abscesses were enrolled. Patients were stratified by cause (appendicitis vs. all other causes) and prospectively randomized to one of two wound management strategies: E/DPC (wound packed with saline-soaked gauze, evaluated 3 days after surgery for closure the next day if appropriate) or PC. In the E/DPC group, wounds that were not pristine when examined on postoperative day 3 were not closed and daily dressing changes were instituted. Wounds were considered infected if purulence discharged from the wound, or possibly infected if signs of inflammation or a serous discharge developed. RESULTS: Two patients were withdrawn because they died less than 72 hours after surgery. The wound infection rate was greater in the PC group than in the E/DPC group. Lengths of hospital stay and hospital charges were similar between the two groups. CONCLUSION: A strategy of DPC for appropriate dirty abdominal wounds 4 days after surgery produced a decreased wound infection rate compared with PC without increasing the length of stay or cost.

Outcome after major renovascular injuries: a Western trauma association multicenter report.

BACKGROUND: Major renal vascular injuries are uncommon and are frequently associated with a poor outcome. In addition to renal dysfunction, posttraumatic renovascular hypertension may result, although the true incidence of this complication is unknown. The objective of this study was to describe the factors contributing to outcome after major renovascular trauma. We hypothesized that the highest percentage of renal salvage would be achieved by minimizing the time from injury to repair. METHODS: This was a retrospective chart review over a 16-year period conducted at six university trauma centers of patients with American Association for the Surgery of Trauma grade IV/V renal injuries surviving longer than 24 hours. Postinjury renal function with poor outcome was defined as renal failure requiring dialysis, serum creatinine greater than or equal to 2 mg/dL, renal scan showing less than 25% function of the injured kidney, postinjury hypertension requiring treatment, or delayed nephrectomy. Data collected for analysis included demographics, mechanism of injury, presence of shock, presence of hematuria, associated injuries, type of renal injury (major artery, renal vein, segmental artery), type of repair (primary vascular repair, revascularization, observation, nephrectomy), time from injury to definitive renal surgery, and type of surgeon performing the operation (urologist, vascular surgeon, trauma surgeon). RESULTS: Eighty-nine patients met inclusion criteria; 49% were injured from blunt mechanisms. Patients with blunt injuries were 2.29 times more likely to have a poor outcome compared with those with penetrating injuries. Similarly, the odds ratio of having a poor outcome with a grade V injury (n = 32) versus grade IV (n = 57) was 2.2 (p = 0.085). Arterial repairs had significantly worse outcomes than vein repairs (p = 0.005). Neither the time to definitive surgery nor the operating surgeon's specialty significantly affected outcome. Ten percent (nine patients) developed hypertension or renal failure postoperatively: three had immediate nephrectomies, four had arterial repairs with one intraoperative failure requiring nephrectomy, and two were observed. Of the 20 good outcomes for grade V injuries, 15 had immediate nephrectomy, 1 had a renal artery repair, 1 had a bypass graft, 1 underwent a partial nephrectomy, and 2 were observed. CONCLUSION: Factors associated with a poor outcome following renovascular injuries include blunt trauma, the presence of a grade V injury, and an attempted arterial repair. Patients with blunt major vascular injuries (grade V) are likely to have associated major parenchymal disruption, which contributes to the poor function of the revascularized kidney. These patients may be best served by immediate nephrectomy, provided that there is a functioning contralateral kidney.

Blunt splenic injury in adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma.

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (>15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p < 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) < 15 and 46.6% of patients with ISS > 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.

Effect of a curfew law on juvenile trauma.

OBJECTIVE: As a method of crime reduction among teenagers, several cities, counties, and states across the country have enacted, or attempted to enact, curfew laws. A curfew law was successfully implemented in Dade County, Florida, in January of 1996. Although its efficacy for crime reduction has been questioned, its benefit for trauma prevention may be real. METHODS: Trauma registry data was collected retrospectively and prospectively from Dade County's Level I trauma center for all trauma victims 5 to 16 years of age. The time period spanned the 2 years before the institution of the curfew law (January 1, 1996) and the 2 years after. Total adult and pediatric trauma volumes during the 4-year period were used as comparisons, as well as juvenile traumas occurring during noncurfew hours. RESULTS: Total trauma volume did not change significantly across the 4-year period, nor did the volume among the curfew age group during noncurfew hours. The predominant mechanisms of injury during curfew hours were motor vehicle crashes and gunshots. Neither the patterns of mechanisms nor ages changed significantly during the precurfew and postcurfew eras. However, the volume of cases seen at the trauma center among the curfew age group was significantly lower with the curfew law in effect (mean, 7.0/month) than before it was in effect (mean, 9.5/month, p = 0.043). CONCLUSION: Although the overall trauma admissions and juvenile trauma admissions during the noncurfew hours remained relatively stable, juvenile trauma admissions during curfew hours dropped significantly in the 2 years after enforcement of the curfew law compared with the 2 years before the curfew law. This finding suggests that attempts to prevent late-night nonproductive street presence among teens can decrease the incidence of trauma occurrences.

A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients.

BACKGROUND: Amphotericin B is the agent of choice for most invasive fungal infections in critically ill patients. It is associated with at least a 50% incidence of nephrotoxicity, despite prophylactic measures such as sodium loading. Newer formulations of amphotericin B are available but are costly and have unknown bioavailability in critically ill patients. Previous trials in neutropenic and critically ill patients have demonstrated that mixing amphotericin B with 20% lipid solution (Intralipid; Clintec Nutrition, Deerfield, III) may decrease nephrotoxicity. METHODS: In this randomized, prospective clinical trial, patients with positive fungal blood cultures, tracheal/sputum cultures or peritoneal cavity cultures were randomized to receive either 0.5 mg/kg per day of amphotericin B dextrose or 1.0 mg/kg per day of amphotericin B lipid emulsion. Duration of therapy was determined by the primary care team. Weekly 24-hour creatinine clearance was measured until 2 weeks after amphotericin B therapy was completed. RESULTS: The two groups were similar based on age, white blood cell count, serum creatinine, and creatinine clearance at the beginning of therapy. The group receiving amphotericin B lipid emulsion had significantly less decrease in creatinine clearance compared with controls, despite receiving significantly more amphotericin B. CONCLUSION: Amphotericin B lipid emulsion can be given at a higher total cumulative dose than amphotericin B dextrose with less nephrotoxicity.

Patterns of maxillofacial injuries in powered watercraft collisions.

Because of the widespread popularity of water sports, plastic and reconstructive surgeons can expect to manage an increasing number of injuries associated with these activities, particularly those related to powered watercraft vehicles. Although seat belts for motorists and helmets for motorcyclists may be efficacious, such devices currently do not serve a similar role in powered watercraft sports. In this study, a retrospective chart review of 194 consecutive patients who presented to the University of Miami/Jackson Memorial Hospital (Level I trauma center) as a result of powered watercraft collisions is presented. The purpose of this investigation was to assess the incidence, cause, demographics, and available management options for head and neck injuries secondary to powered watercraft. Identified were 194 patients who presented because of watersports-related injuries during the period January 1, 1991, through December 31, 1996. From this group, 81 patients (41.8 percent) sustained injuries directly attributable to powered watercraft collisions, including 41 personal watercraft collisions (50.6 percent), 39 boat collisions (48.1 percent), and 1 airboat collision (1.2 percent). The patient population, as expected, tended to be young and male with an average age of 29 years (range, 8 to 64 years old). Interestingly, 41 of the patients (50.6 percent) who presented to this trauma center as a result of powered watercraft collisions also sustained associated head and neck trauma. Of 74 injuries 24 were facial fractures (32.4 percent), 18 were facial lacerations (24.3 percent), 14 were closed head injuries (18.9 percent), 8 were skull fractures (10.8 percent), 4 were scalp lacerations (5.4 percent), 4 were C-spine fractures (5.4 percent), 1 was an ear laceration (1.4 percent), and 1 was a fatality (1.4 percent). Le Fort fractures were the most commonly identified facial fracture in this series. The number of these injuries seen in hospital emergency rooms will most likely increase in the future as the popularity of water-related recreational activities becomes even more widespread. Based on these findings, it is strongly recommended that future efforts be directed toward the prevention of these injuries through patient education and the eventual development of efficacious and safe protective equipment.

The role of computed tomography in selective management of gunshot wounds to the abdomen and flank.

OBJECTIVE: To determine whether computed tomography (CT) is an accurate diagnostic modality for the triage of hemodynamically stable patients with gunshot wounds of the abdomen and flank. METHODS: A chart review of 83 trauma patients for whom abdominal CT was used as initial screening. RESULTS: In 53 patients, CT revealed no evidence of peritoneal penetration, and in 15 patients, there was evidence of either peritoneal penetration or liver injury. There were no false results in these patients. Among 15 patients with questionable peritoneal penetration, cavitary endoscopy was performed in 11 and exploratory laparotomy was performed in 3, and 1 patient was initially observed and subsequently underwent exploratory surgery for a missed colonic injury. CONCLUSION: In selected centers and in hemodynamically stable patients with abdominal and flank gunshot wounds, abdominal CT can be an effective and safe initial screening modality to document the presence or absence of peritoneal penetration and to manage nonoperatively stable patients with liver injuries. If there is any question of peritoneal penetration, cavitary endoscopy should be part of the protocol of nonoperative management.

Laryngeal injuries after short- versus long-term intubation.

Forty-five patients were seen over a 5-year period with laryngeal injuries following endotracheal intubation (ETI). The mean duration of ETI was 5.6 days (2 hours to 37 days). Patients intubated for less than 24 hours were most likely to present with a vocal fold immobility or an anterior glottic web. Long-term intubation was associated with the development of subglottic stenoses and granulomas. Patients with vocal fold immobility were seen more often after ETI for surgical reasons and had a significantly higher incidence of previous intubation and tobacco usage. Subglottic stenoses were seen in younger patients intubated for medical reasons and associated with nasogastric tubes and longer periods of intubation.

Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy.

OBJECTIVES: Pneumococcal polysaccharide vaccine is given after emergency splenectomy for trauma to lessen the risk of overwhelming postsplenectomy sepsis. This study was undertaken to determine optimal timing of vaccine administration as determined by serum type-specific polysaccharide antibody concentration titer and functional activity of the resulting antibodies. METHODS: Fifty-nine consecutive patients undergoing splenectomy after trauma were randomized to receive pneumococcal vaccine postoperatively at 1, 7, or 14 days. Immunoglobulin G serum antibody concentrations against serogroup 4 and serotypes 6B, 19F, and 23F were measured before vaccination and 4 weeks postvaccination. Antibody concentrations were determined by enzyme-linked immunosorbent assay, and functional antibody by opsonophagocytosis. Results were compared with a normal adult control group (n = 12). RESULTS: Postvaccination enzyme-linked immunosorbent assay immunoglobulin G antibody concentrations for all serogroups and serotypes studied were not significantly different in splenectomized patients and control subjects. Postvaccination functional antibody activity was significantly reduced in early vaccination groups (serotype 6B excepted). However, with the exception of 19F, all titers for the 14-day group approached those of the control subjects (p > 0.05). Fold-increases of opsonophagocytic titers for serogroup 4 and serotypes 6B and 19F showed progressive increases with delay in vaccination. Except for serotype 23F, the number of postsplenectomy patients with opsonophagocytic titers <64 significantly decreased with a delay in vaccination (14 days). CONCLUSIONS: Postvaccination immunoglobulin G serum antibody concentrations were not significantly different from normal control subjects regardless of the time of vaccination (1, 7, or 14 days). Although concentrations approach normal, functional antibody activity was significantly lower. Better functional antibody responses against the serogroup and serotypes studied seemed to occur with delayed (14-day) vaccination.