University of Maryland Medical System

BACKGROUND: The prognosis of patients hospitalized with acute myocardial ischemia is quite variable. We examined the value of serum levels of cardiac troponin T, serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia. METHODS: We studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion at the core laboratory. We used logistic regression to assess the usefulness of baseline levels of cardiac troponin T and CK-MB and the electrocardiographic category assigned at admission-ST-segment elevation, ST-segment depression, T-wave inversion, or the presence of confounding factors that impair the detection of ischemia (bundle-branch block and paced rhythms)-in predicting outcome. RESULTS: On admission, 289 of 801 patients with base-line serum samples had elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days was significantly higher in these patients than in patients with lower levels of troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was the variable most strongly related to 30-day mortality (chi-square = 21, P < 0.001), followed by the electrocardiographic category (chi-square = 14, P = 0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels remained significantly predictive of 30-day mortality in a model that contained the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P = 0.027). CONCLUSIONS: The cardiac troponin T level is a powerful, independent risk marker in patients who present with acute myocardial ischemia. It allows further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level.

From January 1, 1985, to September 10, 1988, 210 consecutive patients with high-energy pelvic ring disruptions (exclusive of acetabular fractures) were admitted to a statewide referral center for adult multiple trauma. They were treated by one of four attending orthopaedic traumatologists per protocol as determined by their injury classification and hemodynamic status; the injury classification system was based on the vector of force involved and the quantification of disruption from that force, i.e., lateral compression, anteroposterior compression, vertical shear, and combined mechanical injury. Of the 210 patients, 162 had complete charts: 126 (78.0%) were admitted directly from the scene, 110 (67.9%) were injured in motor vehicle or motorcycle accidents, 25 (15.0%) were admitted in shock (blood pressure <90 mm Hg), the average Glasgow Coma Score was 13.2, and the average Injury Severity Score was 25.8. Treatment of the pelvic fracture included the following methods (alone or in combination): acute external fixation (45.0; 28.0%), open reduction/internal fixation (22; 13.5%), acute arterial embolization (11; 7.0%), and bedrest (68; 42.0%). Overall blood replacement averaged 5.9 units (lateral compression, 3.6 units; anteroposterior compression, 14.8 units; vertical shear, 9.2 units; combined mechanical, 8.5 units). Overall mortality was 8.6% (lateral compression, 7.0%; anteroposterior, 20.0%, vertical shear, 0%; combined mechanical, 18.0%). The cause of death was associated with the pelvic fracture in less than 50%; no patient with an isolated or vertical shear pelvic injury died. We conclude that the predictive value of our classification system (incorporating appreciation of the causative forces and resulting injury patterns) and our classification-based treatment protocols reduce the morbidity and mortality related to pelvic ring disruption.

From January 1, 1985, to September 10, 1988, 210 consecutive patients with high-energy pelvic ring disruptions (exclusive of acetabular fractures) were admitted to a statewide referral center for adult multiple trauma. They were treated by one of four attending orthopaedic traumatologists per protocol as determined by their injury classification and hemodynamic status; the injury classification system was based on the vector of force involved and the quantification of disruption from that force, i.e., lateral compression, anteroposterior compression, vertical shear, and combined mechanical injury. Of the 210 patients, 162 had complete charts: 126 (78.0%) were admitted directly from the scene, 110 (67.9%) were injured in motor vehicle or motorcycle accidents, 25 (15.0%) were admitted in shock (blood pressure less than 90 mm Hg), the average Glasgow Coma Score was 13.2, and the average Injury Severity Score was 25.8. Treatment of the pelvic fracture included the following methods (alone or in combination): acute external fixation (45.0; 28.0%), open reduction/internal fixation (22; 13.5%), acute arterial embolization (11; 7.0%), and bedrest (68; 42.0%). Overall blood replacement averaged 5.9 units (lateral compression, 3.6 units; anteroposterior compression, 14.8 units; vertical shear, 9.2 units; combined mechanical, 8.5 units). Overall mortality was 8.6% (lateral compression, 7.0%; anteroposterior, 20.0%, vertical shear, 0%; combined mechanical, 18.0%). The cause of death was associated with the pelvic fracture in less than 50%; no patient with an isolated or vertical shear pelvic injury died. We conclude that the predictive value of our classification system (incorporating appreciation of the causative forces and resulting injury patterns) and our classification-based treatment protocols reduce the morbidity and mortality related to pelvic ring disruption.

STUDY OBJECTIVE: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension. DESIGN: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months. SETTING: Four referral centers. PATIENTS: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema). INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics. MEASUREMENTS AND MAIN RESULTS: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system. CONCLUSIONS: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease.

The effect of intracellular ion deregulation, particularly of [Ca2+], on the events following acute cell injury and the progression of change from initiation (reversible) to maintenance (reversible-irreversible) phases and finally to cell death has been the major thrust of experimentation in our laboratory for over 20 years. Cell death, which plays an important role in both normal and pathological phenomena, has been classified into two principal types, accidental and programmed. Recent exploration of programmed cell death (or apoptosis) has revealed extensive data showing it is an important mechanism for the normal maintenance and also differentiation of a variety of cell types and organs. From the results from our laboratory and those of others, we continue to expand and refine our working hypothesis: deregulation of [Ca2+] results in a number of phenomena from activation of signaling mechanisms and alterations in cellular structure to alterations in gene expression, all of which contribute to or play a critical role in cellular toxicity, including carcinogenesis and cell death. Therefore, although much more experimentation is needed to clarify some of these phenomena, the implications of such data for understanding the mechanisms and processes involved in carcinogenesis and the chemotherapeutic killing of cancer cells are extremely exciting. These relationships between [Ca2+], cell injury, and cell death are briefly reviewed here within the framework of our hypothesis.

BACKGROUND: Spinal-cord injury is devastating; until recently, there was no medical treatment to improve recovery of the initial neurologic deficit. Studies in animals have shown that monosialotetrahexosylganglioside (GM-1) ganglioside enhances the functional recovery of damaged neurons. METHODS: A prospective, randomized, placebo-controlled, double-blind trial of GM-1 ganglioside was conducted in patients with spinal-cord injuries. Of 37 patients entered into the study, 34 (23 with cervical injuries and 11 with thoracic injuries) completed the test-drug protocol (100 mg of GM-1 sodium salt or placebo intravenously per day for 18 to 32 doses, with the first dose taken within 72 hours of the injury) and a one-year follow-up period. Neurologic recovery was assessed with the Frankel scale (comprising five categories) and the American Spinal Injury Association (ASIA) motor score (a scale of scores from 0 to 100, derived from strength tests of 20 specific muscles, each scored from 0 to 5). RESULTS: There was a significant difference between groups in the distribution of improvement of Frankel grades from base line to the one-year follow-up (improvement of 0, 1, 2, and 3 grades in 13, 4, 1, and 0 patients, respectively, in the placebo group and 8, 1, 6, and 1 patients, respectively, in the GM-1 group; P = 0.034 by the Cochran-Mantel-Haenszel chi-square test). The GM-1-treated patients also had a significantly greater mean improvement in ASIA motor score from base line to the one-year follow-up than the placebo-treated patients (36.9 vs. 21.6 points; P = 0.047 by analysis of covariance with the base-line ASIA motor score as the covariate). An analysis of individual muscle recoveries revealed that the increased recovery in the GM-1 group was attributable to initially paralyzed muscles that regained useful motor strength rather than to strengthening of paretic muscles. CONCLUSIONS: This small study provides evidence that GM-1 enhances the recovery of neurologic function after one year. A larger study must be conducted, however, before GM-1 is considered efficacious and safe in treating spinal-cord injury.

This study reports 3-year outcomes for clients who had been treated in the five outpatient sites of Project MATCH, a multisite clinical trial designed to test a priori client treatment matching hypotheses. The main purpose of this study was to characterize the status of the matching hypotheses at the 3-year follow-up. This entailed investigating which matching findings were sustained or even strengthened across the 3-year study period, and whether any hypotheses that were not supported earlier eventually emerged at 3 years, or conversely, whether matching findings discerned earlier dissipated at this later time. This research also examines the prognostic effects of the client matching attributes, characterizes the overall outcomes at 37 to 39 months, and explores differential effects of the three treatments at extended follow-up. With regard to the matching effects, client anger demonstrated the most consistent interaction in the trial, with significant matching effects evident at both the 1-year and 3-year follow-ups. As predicted, clients high in anger fared better in Motivational Enhancement Therapy (MET) than in the other two MATCH treatments: Cognitive-Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Among subjects in the highest third of the anger variable, clients treated in MET had on average 76.4% abstinent days, whereas their counterparts in the other two treatments (CBT and TSF) had on average 66% abstinent days. Conversely, clients low in anger performed better after treatment in CBT and TSF than in MET. Significant matching effects for the support for drinking variable emerged in the 3-year outcome analysis, such that clients whose social networks were more supportive of drinking derived greater benefit from TSF treatment than from MET. Among subjects in the highest third of the support for drinking variable, TSF participants were abstinent 16.1% more days than MET participants. At the lower end of this variable, difference in percent days abstinent between MET and TSF was 3%, with MET clients having more abstinent days. A significant matching effect for psychiatric severity that appeared in the first year posttreatment was not observed after 3 years. Of the 21 client attributes used in testing the matching hypotheses, 11 had prognostic value at 3 years. Among these, readiness-to-change and self-efficacy emerged as the strongest predictors of long-term drinking outcome. With regard to the overall outcomes, the reductions in drinking that were observed in the first year after treatment were sustained over the 3-year follow-up period: almost 30% of the subjects were totally abstinent in months 37 to 39, whereas those who did report drinking nevertheless remained abstinent an average of two-thirds of the time. As in the 1-year follow-up, there were few differences among the three treatments, although TSF continued to show a possible slight advantage.

OBJECTIVE: To assemble an international panel of experts to develop consensus recommendations on selected important issues on the use of ultrasonography (US) in trauma care. SETTING: R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Md. The conference was held on December 4, 1997. PARTICIPANTS: A committee of two co-directors and eight faculty members, in the disciplines of surgery and emergency medicine, representing four nations. Each faculty member had made significant contributions to the current understanding of US in trauma. RESULTS: Six broad topics felt to be controversial or to have wide variation in practice were discussed using the ad hoc process: (1) US nomenclature and technique; (2) US for organ-specific injury; (3) US scoring systems; (4) the meaning of positive and negative US studies; (5) US credentialing issues; and (6) future applications of US. Consensus recommendations were made when unanimous agreement was reached. Majority viewpoints and minority opinions are presented for unresolved issues. CONCLUSION: The consensus conference process fostered an international sharing of ideas. Continued communication is needed to advance the science and technology of US in trauma care.

OBJECTIVE: To evaluate the effects of long-term-intravenous infusion of prostacyclin on exercise capacity, hemodynamics, and survival in patients with primary pulmonary hypertension. DESIGN: Open, multicenter, uncontrolled trial. SETTING: Four referral centers. PATIENTS: 18 patients with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients. INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pumps. All patients were treated with anticoagulant agents. MEASUREMENTS AND MAIN RESULTS: With the 6-minute walk used to evaluate exercise capacity, patients could walk on average more than 100 meters farther after prostacyclin therapy was initiated (distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 meters at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 months: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02), and mean pulmonary artery pressure and total pulmonary resistance decreased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in cardiac index and total pulmonary resistance were maintained at 12 months (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9.7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuous prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institutes of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, respectively, compared with 77.4%, 51.6%, and 40.6% for the historical control group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious complications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients. CONCLUSIONS: Continuous intravenous prostacyclin resulted in sustained clinical and hemodynamic improvement and probably in improved survival in patients with severe primary pulmonary hypertension. Despite potentially serious complications, long-term prostacyclin may be especially helpful in seriously ill patients awaiting transplantation.

BACKGROUND: The advantages of early fracture fixation in patients with multiple injuries have been challenged recently, particularly in patients with head injury. External fixation (EF) has been used to stabilize pelvic fractures after multiple injury. It potentially offers similar benefits to intramedullary nail (IMN) in long-bone fractures and may obviate some of the risks. We report on the use of EF as a temporary fracture fixation in a group of patients with multiple injuries and with femoral shaft fractures. METHODS: Retrospective review of charts and registry data of patients admitted to our Level 1 trauma center July of 1995 to June of 1998. Forty-three patients initially treated with EF of the femur were compared to 284 patients treated with primary IMN of the femur. RESULTS: Patients treated with EF had more severe injuries with significantly higher Injury Severity Scores (26.8 vs. 16.8) and required significantly more fluid (11.9 vs. 6.2 liters) and blood (1.5 vs. 1.0 liters) in the initial 24 hours. Glasgow Coma Scale score was lower (p < 0.01) in those treated with EF (11 vs. 14.2). Twelve patients (28%) had head injuries severe enough to require intracranial pressure monitoring. All 12 required therapy for intracranial pressure control with mannitol (100%), barbiturates (75%), and/or hyperventilation (75%). Most patients had more than one contraindication to IMN, including head injury in 46% of cases, hemodynamic instability in 65%, thoracoabdominal injuries in 51%, and/or other serious injuries in 46%, most often multiple orthopedic injuries. Median operating room time for EF was 35 minutes with estimated blood loss of 90 mL. IMN was performed in 35 of 43 patients at a mean of 4.8 days after EF. Median operating room time for IMN was 135 minutes with an estimated blood loss of 400 mL. One patient died before IMN. One other patient with a mangled extremity was treated with amputation after EF. There was one complication of EF, i.e., bleeding around a pin site, which was self-limited. Four patients in the EF group died, three from head injuries and one from acute organ failure. No death was secondary to the fracture treatment selected. One patient who had EF followed by IMN had bone infection and another had acute hardware failure. CONCLUSION: EF is a viable alternative to attain temporary rigid stabilization in patients with multiple injuries. It is rapid, causes negligible blood loss, and can be followed by IMN when the patient is stabilized. There were minimal orthopedic complications.

OBJECTIVES: Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint. METHODS: ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shaped to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus. RESULTS: Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight, and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for re-alignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) or pharmacological. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (e.g., prescription glucosamine sulfate and/or chondroitin sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intra-articular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before surgery are represented by weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult-to-manage alternative when surgery is contraindicated. CONCLUSIONS: The proposed treatment algorithm may represent a new framework for the development of future guidelines for the management of OA, more easily accessible to physicians.

OBJECTIVE: This study compares an initial group of patients undergoing laparoscopic live donor nephrectomy to a group of patients undergoing open donor nephrectomy to assess the efficacy, morbidity, and patient recovery after the laparoscopic technique. SUMMARY BACKGROUND DATA: Recent data have shown the technical feasibility of harvesting live renal allografts using a laparoscopic approach. However, comparison of donor recovery, morbidity, and short-term graft function to open donor nephrectomy has not been performed previously. METHODS: An initial series of patients undergoing laparoscopic live donor nephrectomy were compared to historic control subjects undergoing open donor nephrectomy. The groups were matched for age, gender, race, and comorbidity. Graft function, intraoperative variables, and clinical outcome of the two groups were compared. RESULTS: Laparoscopic donor nephrectomy was attempted in 70 patients and completed successfully in 94% of cases. Graft survival was 97% versus 98% (p = 0.6191), and immediate graft function occurred in 97% versus 100% in the laparoscopic and open groups, respectively (p = 0.4961). Blood loss, length of stay, parenteral narcotic requirements, resumption of diet, and return to normal activity were significantly less in the laparoscopic group. Mean warm ischemia time was 3 minutes after laparoscopic harvest. Morbidity was 14% in the laparoscopic group and 35% in the open group. There was no mortality in either group. CONCLUSIONS: Laparoscopic live donor nephrectomy can be performed with morbidity and mortality comparable to open donor nephrectomy, with substantial improvements in patient recovery after the laparoscopic approach. Initial graft survival and function rates are equal to those of open donor nephrectomy, but longer follow-up is necessary to confirm these observations.

BACKGROUND: CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus-1 (HIV-1). Recently, an inactive CCR5 allele (designated here as CCR5-2) was identified that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. The reports conflict on the effect of heterozygous CCR5-2 on HIV-1 susceptibility, and race and risk levels have not yet been fully analyzed. Here we report our independent identification of CCR5-2 and test its effects on HIV-1 pathogenesis in individuals with contrasting clinical outcomes, defined race, and quantified risk. MATERIALS AND METHODS: Mutant CCR5 alleles were sought by directed heteroduplex analysis of genomic DNA from random blood donors. Genotypic frequencies were then determined in (1) random blood donors from North America, Asia, and Africa; (2) HIV-1+ individuals; and (3) highly exposed-seronegative homosexuals with quantified risk. RESULTS: CCR5-2 was the only mutant allele found. It was common in Caucasians, less common in other North American racial groups, and not detected in West Africans or Tamil Indians. Homozygous CCR5-2 frequencies differed reciprocally in highly exposed-seronegative (4.5%, n = 111) and HIV-1-seropositive (0%, n = 614) Caucasians relative to Caucasian random blood donors (0.8%, n = 387). This difference was highly significant (p < 0.0001). By contrast, heterozygous CCR5-2 frequencies did not differ significantly in the same three groups (21.6, 22.6, and 21.7%, respectively). A 55% increase in the frequency of heterozygous CCR5-2 was observed in both of two cohorts of Caucasian homosexual male, long-term nonprogressors compared with other HIV-1+ Caucasian homosexuals (p = 0.006) and compared with Caucasian random blood donors. Moreover, Kaplan-Meier estimates indicated that CCR5-2 heterozygous seroconvertors had a 52.6% lower risk of developing AIDS than homozygous wild-type seroconvertors. CONCLUSIONS: The data suggest that homozygous CCR5-2 is an HIV-1 resistance factor in Caucasians with complete penetrance, and that heterozygous CCR5-2 slows the rate of disease progression in infected Caucasian homosexuals. Since the majority (approximately 96%) of highly exposed-seronegative individuals tested are not homozygous for CCR5-2, other resistance factors must exist. Since CCR5-2 homozygotes have no obvious clinical problems, CCR5 may be a good target for the development of novel antiretroviral therapy.

BACKGROUND AND OBJECTIVES: This study set out to determine the incidence of hypoglycemia in patients with chronic kidney disease (CKD), with and without diabetes, and the association of hypoglycemia with mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort analysis of 243,222 patients who had 2,040,206 glucose measurements and were cared for at the Veterans Health Administration. CKD was defined as an estimated GFR of <60 ml/min per 1.73 m(2). Hypoglycemia was set at <70 mg/dl. Mortality was measured 1 day after glucose measurement. RESULTS: The incidence of hypoglycemia was higher in patients with CKD versus without CKD. Among patients with diabetes, the rate was 10.72 versus 5.33 per 100 patient-months and among patients without diabetes was 3.46 versus 2.23 per 100 patient-months, for CKD versus no CKD, respectively. The odds of 1-d mortality were increased at all levels of hypoglycemia but attenuated in CKD versus no CKD. Adjusted odds ratios for 1-d mortality that were associated with glucose values of <50, 50 to 59, and 60 to 69 mg/dl, respectively, versus glucose of >or=70 mg/dl were 6.09, 4.10, and 1.85 for inpatient records from patients with CKD; 9.95, 3.79, and 2.54 for inpatients records from patients without CKD; 6.84, 3.28, and 3.98 for outpatient records from patients with CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients without CKD. CONCLUSIONS: CKD is a risk for hypoglycemia, with or without diabetes. The excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD.

OBJECTIVES: To evaluate the results and complications of Ilizarov bone transport in the treatment of tibial bone defects. DESIGN: Retrospectively reviewed consecutive series. METHODS: Nineteen patients with tibial bone defects were treated by the Ilizarov bone transport method. The mean bone defect was ten centimeters, and there were eight soft-tissue defects. The mean external fixation time was sixteen months. Ten patients required debridement of the bone ends and/or bone grafting of the docking site at the end of transport. RESULTS: Union was achieved in all cases. One refracture of the docking site required retreatment with the Ilizarov apparatus to achieve union. There was one residual leg length discrepancy greater than 2.5 centimeters and two angular deformities greater than 5 degrees. There were no recurrent or residual infections. Seven of the eight soft-tissue defects were closed by soft-tissue transport; the eighth required a free-vascularized flap. The bone results were graded as fifteen excellent, three good, and one fair. The functional results were graded as twelve excellent, six good, and one poor. There were twenty-two minor complications, sixteen major complications without residual sequelae, and three major complications with residual sequelae. To treat the bone defect and the complications, a mean of 2.9 operations per patient was required. CONCLUSIONS: Our results compare favorably with those for other methods of bone grafting as well as with those from other published accounts of the Ilizarov method, especially considering the large defect size in this series. The main disadvantage of the Ilizarov method is the lengthy external fixation time.

OBJECTIVES: The purpose of this study was to examine the success rate of nonoperative management of blunt splenic injury in an institution using splenic embolization. METHODS: We conducted a retrospective review of all patients admitted to a Level I trauma center with blunt splenic injury. Data review included patient demographics, computed tomographic (CT) scan results, management technique, and patient outcomes. RESULTS: A total of 648 patients with blunt splenic injury were admitted, 280 of whom underwent immediate surgical management. Three hundred sixty-eight underwent planned nonoperative management, and 70 patients were treated with observation, serial abdominal examination, and follow-up abdominal CT scanning. All were hemodynamically stable, with a 100% salvage rate. One hundred sixty-six patients had a negative angiogram, with a nonoperative salvage rate of 94%, and 132 patients underwent embolization, with a nonoperative salvage rate of 90%. Overall salvage rates decreased with increasing injury grade; however, over 80% of grade 4 and 5 injuries were successfully managed nonoperatively. The salvage rate was similar for main coil embolization versus selective or combined embolization techniques. Admission abdominal CT scan correlated with splenic salvage rates. Significant hemoperitoneum, extravasation, and pseudoaneurysm had acceptable salvage rates, whereas arteriovenous fistula had a high failure rate, even after embolization. CONCLUSION: Splenic embolization is a valuable adjunct to splenic salvage in our experience, allowing for the increased use of nonoperative management and higher salvage rates for American Association for the Surgery of Trauma splenic injury grades when compared with prior studies. Main coil embolization has a similar salvage rate when compared with other angiographic techniques. An arteriovenous fistula as a CT finding was predictive of a 40% nonoperative failure rate.

BACKGROUND: Ten to 15 percent of all RBCs are used in the care of injury. Understanding patterns of RBC use is important. Routine resource allocation, planning for mass casualty situations, designing research, and optimizing triage all can be usefully informed. STUDY DESIGN AND METHODS: Blood Bank and Trauma Registry records were linked to produce a transfused blood product list for each patient directly admitted from the scene of injury to a large Level 1 trauma center in calendar year 2000. Categorical associations between demographic data, Injury Severity Score, transfused products, and outcome were sought. Special attention was paid to the groups receiving uncross-matched RBCs and more than 10 units of RBCs. RESULTS: Eight percent (479/5645) of acute trauma patients received RBCs, using 5219 units and sustaining an overall mortality of 27 percent. Sixty-two percent of RBCs were given in the first 24 hours of care. Three percent of patients (147 injured) received more than 10 units and received 71 percent of all RBCs given. Mortality in this cohort was 39 percent. Ninety percent of the patients who received more than 10 units of RBCs received plasma, and 71 percent received PLTs. CONCLUSIONS: A small number of patients receives most of the blood products used in the treatment of injury. Transfusion of more than 10 units of RBCs identifies a subgroup where most patients received plasma and PLTs to treat actual or anticipated dilutional coagulopathy. There is no clear threshold beyond which blood use is futile.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow caused primarily by failure of normal homeostatic mechanisms to prevent the expansion of postgerminal center plasma cells. We have examined the molecular mechanisms that promote the survival of MM cells and have identified a key role for myeloid cell factor-1 (Mcl-1), an antiapoptotic member of the Bcl-2 family. These experiments were initiated by the observation that MM cells were exquisitely sensitive to culture in the presence of actinomycin D: caspase activation occurred within 3 hours of treatment and cells were not protected by interleukin-6, the main MM cell growth and survival factor. Actinomycin D-induced apoptosis was blocked by proteasome inhibitors, suggesting that a labile protein was required for MM cell survival. Further analysis demonstrated that Mcl-1 was likely to be the labile factor governing MM cell survival. Mcl-1 protein levels decreased rapidly after culture in the presence of actinomycin D in concordance with effector caspase activation, but addition of proteasome inhibitors reversed the loss of Mcl-1 and maintained cell viability. The levels of other antiapoptotic proteins, including Bcl-2 and members of the inhibitors-of-apoptosis family, were unaffected by these interventions. Furthermore, Mcl-1 antisense oligonucleotides caused a rapid down-regulation of Mcl-1 protein levels and the coincident induction of apoptosis, whereas overexpression of Mcl-1 delayed actinomycin D-induced apoptosis with kinetics that correlated with expression levels of Mcl-1. These data indicate that Mcl-1 expression is required for the survival of MM cells and may represent an important target for future therapeutics.

OBJECTIVE: The Treatment-Resistant Depression Registry investigated whether adjunctive vagus nerve stimulation (VNS) with treatment as usual in depression has superior long-term outcomes compared with treatment as usual only. METHOD: This 5-year, prospective, open-label, nonrandomized, observational registry study was conducted at 61 U.S. sites and included 795 patients who were experiencing a major depressive episode (unipolar or bipolar depression) of at least 2 years' duration or had three or more depressive episodes (including the current episode), and who had failed four or more depression treatments (including ECT). Patients with a history of psychosis or rapid-cycling bipolar disorder were excluded. The primary efficacy measure was response rate, defined as a decrease of ≥50% in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score at any postbaseline visit during the 5-year study. Secondary efficacy measures included remission. RESULTS: Patients had chronic moderate to severe depression at baseline (the mean MADRS score was 29.3 [SD=6.9] for the treatment-as-usual group and 33.1 [SD=7.0] for the adjunctive VNS group). The registry results indicate that the adjunctive VNS group had better clinical outcomes than the treatment-as-usual group, including a significantly higher 5-year cumulative response rate (67.6% compared with 40.9%) and a significantly higher remission rate (cumulative first-time remitters, 43.3% compared with 25.7%). A subanalysis demonstrated that among patients with a history of response to ECT, those in the adjunctive VNS group had a significantly higher 5-year cumulative response rate than those in the treatment-as-usual group (71.3% compared with 56.9%). A similar significant response differential was observed among ECT nonresponders (59.6% compared with 34.1%). CONCLUSIONS: This registry represents the longest and largest naturalistic study of efficacy outcomes in treatment-resistant depression, and it provides additional evidence that adjunctive VNS has enhanced antidepressant effects compared with treatment as usual in this severely ill patient population.

To reduce the burden of cardiovascular disease (CVD), management strategies are increasingly focusing on preventive measures following early detection of markers of atherosclerosis. This review focuses on microalbuminuria, which is gaining recognition as a simple marker of an atherogenic milieu. Prospective and epidemiologic studies have found that microalbuminuria is predictive, independently of traditional risk factors, of all-cause and cardiovascular mortality and CVD events within groups of patients with diabetes or hypertension, and in the general population. The pathophysiologic mechanism underlying the association between albumin excretion and CVD is not fully defined. One hypothesis is that microalbuminuria may be a marker of CVD risk because it reflects subclinical vascular damage in the kidneys and other vascular beds. It may also signify systemic endothelial dysfunction that predisposes to future cardiovascular events. Based on this theory, periodic screening for microalbuminuria could allow early identification of vascular disease and help stratify overall cardiovascular risk, especially in patients with risk factors such as hypertension or diabetes. A positive test for urinary albumin excretion could signify the need for an intensive multifactorial intervention strategy, including behavior modification and targeted pharmacotherapy, aimed at preventing further renal deterioration and improving the overall CVD risk factor profile. Data from intervention studies suggest that treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, statins, and/or strict glycemic control (in diabetics) offer significant reductions in cardiovascular and/or renal morbidity in patients with albuminuria. Use of this (old) marker may allow improved use of medications and strategies for secondary prevention.