Trapeziectomy Arthroplasty With Suture Suspension: Short- to Medium-Term Outcomes From a Single-Surgeon Experience.

PURPOSE: To describe the technique and a single-surgeon experience with a suture suspension and first dorsal compartment release treatment for thumb trapeziometacarpal (TMC) osteoarthritis. METHODS: We performed 19 procedures on 18 patients using this technique and compared results with preoperative assessment. At an average of 20 months (range, 8-45 months) after surgery, standard measures after TMC joint arthroplasty were performed. RESULTS: All patients had advanced Eaton stage III or IV osteoarthritis. Grip strength, key pinch, and thumb abduction showed statistically significant increases of 7 kg, 0.7 kg, and 4°, respectively. Seventeen of 18 patients no longer had reports of TMC joint pain on follow-up. There was one reoperation for pain because of osteophytes at the ulnar surface of the thumb metacarpal base, which resolved with proximal metacarpal excision. One case of index metacarpal fracture was treated with an orthosis. CONCLUSIONS: This surgical technique for the treatment of thumb TMC joint arthritis achieved pain relief and recreated support of the base of the metacarpal to resist proximal migration or radial deviation. This technique also provided an increase in grip strength and key pinch with return of range of motion early in the postoperative period. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Lessons Learned: Trapeziectomy and Suture Suspension Arthroplasty for Thumb Carpometacarpal Osteoarthritis.

In this study, we describe refinements of an accepted technique made by a single surgeon for trapeziectomy and suture suspension arthroplasty for thumb carpometacarpal (CMC) osteoarthritis after 220 cases over 4 years. Results are derived from 77 patients who underwent treatment using this technique comparing postoperative results with preoperative assessment and had sufficient data for inclusion. The surgical technique is described, including tips and modifications to avoid known possible complications. All patients in this study had advanced Eaton stage III or IV osteoarthritis. Grip strength and key pinch showed statistically significant improvement, and the improvement in palmar pinch approached significance. Pain scores were significantly decreased with over 50% of the patients rating their pain at 0 postoperatively. The overall complication rate was very low, and improvements in technique were made to mitigate future occurrence. This surgical technique for the treatment of thumb CMC arthritis achieved pain relief and recreated ligamentous support of the base of the first metacarpal to resist proximal migration after trapeziectomy, providing an increase in grip strength and key pinch with return of range of motion early in the postoperative period. Refinements on this technique through a large volume single surgeon experience provide technical tips for optimizing outcomes.

The role of phenotyping in chronic prostatitis/chronic pelvic pain syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a chronic pain syndrome identified by the presence of noninfectious pelvic or perineal pain lasting longer than 3 months. Current diagnoses and treatments for the syndrome solely depend on and target symptoms, respectively. Thus far, the mechanistic disturbances responsible for the pathogenesis of CP/CPPS have remained largely elusive and treatments, and therefore, continue to be ineffective. To move toward successful management and treatment of CP/CPPS, it is necessary to elicit the underlying biological mechanisms responsible for the syndrome. Therefore, a phenotyping system that is able to bridge the gap between current symptom-based diagnosis and future mechanistic approaches to diagnosis and treatment is needed. In this article, we examine current CP/CPPS phenotyping systems, analyze their utility, and make suggestions for changes in clinical approaches to the syndrome that would both promulgate a mechanistic understanding and advance treatment approaches.

Migraine Treatment.

Migraine headaches affect more than 35 million Americans and are ranked the third-highest cause of disability worldwide, resulting in decreased quality of life and serious economic consequences. There are 4 types of migraine headaches: frontal, temporal, occipital, and rhinogenic. Each type has a well-described trigger site. Migraines headaches often are refractory to medical therapy and may respond well to botulinum toxin type A. Migraine surgery is another option to release trigger sites. A systematic review of the migraine surgery literature found an average success rate of 90%, with elimination or greater than 50% improvement of migraine headaches after migraine surgery.

Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer?

BACKGROUND: Recent military experience suggests that immediate 1:1 fresh frozen plasma (FFP); red blood cells (RBC) for casualties requiring >10 units packed red blood cells (RBC) per 24 hours reduces mortality, but no clinical trials exist to address this issue. Consequently, we reviewed our massive transfusion practices during a 5-year period to test the hypothesis that 1:1 FFP:RBC within the first 6 hours reduces life threatening coagulopathy. METHODS: We queried our level I trauma center's prospective registry from 2001 to 2006 for patients undergoing massive transfusion. Logistic regression was used to evaluate the independent effect of FFP:RBC in 133 patients who received >10 units RBC in 6 hours on (1) Coagulopathy (international normalized ratio [INR] >1.5 at 6 hours), controlling for our previously described risk factors predictive of coagulopathy, as well as RBC, FFP, and platelet administration (2) Death (controlling for all variables plus age, crystalloids per 24 hours, INR >1.5 at 6 hours). RESULTS: Overall mortality was 56%; 50% died from acute blood loss in the operating room. Over 80% of the RBC transfusions were completed in the first 6 hours: (Median RBC: 18 units) Median FFP:RBC survivors, 1:2, nonsurvivors: 1:4. (p < 0.001) INR >1.5 at 6 hours occurred in 30 (23%); 81% died. Regarding mortality, logistic regression showed significant variables (p < 0.05) included: RBC per 6 hours (OR = 1.248, 95%CI: 1.957-53.255), INR at 6 hours >1.5 (OR = 10.208, 95% CI: 1.957-53.255), ED temperature <34 degrees C (OR = 15.491, 95% CI 1.376-174.396), and age >55 years (OR = 40.531, CI 5.315-309.077). The adjusted OR for FFP:RBC ratio including the quadratic term was found to follow a U-shaped association (quadratic term estimate 0.6737 +/- 0.0345, p = 0.0189). CONCLUSION: Although our data suggest that 1:1 FFP:RBC reduced coagulopathy, this did not translate into a survival benefit. Our findings indicate that the relationship between coagulopathy and mortality is more complex, and further clinical investigation is necessary before recommending routine 1:1 in the exsanguinating trauma patient.

Cervical spine fracture patterns mandating screening to rule out blunt cerebrovascular injury.

BACKGROUND: Aggressive screening for blunt cerebrovascular injury (BCVI) and prompt anticoagulation for documented injuries has resulted in a significant reduction in ischemic neurologic events. An association between vertebral artery injuries (VAIs) and specific cervical spine fracture patterns has been suggested; however, current screening guidelines would subject all patients with cervical spine fractures to imaging because no distinction has been made for carotid artery injuries (CAIs). We hypothesized that specific cervical spine fracture patterns that warrant screening evaluation exist, hence limiting unwarranted diagnostic imaging. METHODS: Patients undergoing screening for BCVI on the basis of injury patterns and mechanism have been prospectively followed at our regional trauma center since January 1996. RESULTS: During the study period from January 1996 to January 2005, there were 17,007 blunt trauma admissions. Twenty-three patients presented with symptoms of BCVI. Screening angiography was performed in 766 patients (4.5%), and diagnosed 258 (34%) patients with BCVI. One hundred twenty-five patients with BCVI had cervical spine fractures; 18 patients had isolated CAI; 84 had isolated VAI, and 23 had combined CAI and VAI. Eight patients with VAI had minor cervical fractures but underwent screening for other injury patterns. Fractures in the remaining patients with BCVI were 1 of 3 patterns. Subluxations in 56 (48%) patients, C1 to C3 cervical spine fractures in 42 (36%), or extension of the fracture through the foramen transversarium in 19 (16%). Cervical spine fractures were the sole indication for screening in 90% of the study population. Screening yield of all patients admitted with 1 of these 3 fracture patterns was 37%. CONCLUSIONS: Blunt cerebrovascular injury is associated with complex cervical spine fractures that include subluxation, extension into the foramen transversarium, or upper C1 to C3 fractures. Patients sustaining such cervical fractures should undergo prompt screening.

Case Report of Clinical Vignette: Osteopetrosis.

INTRODUCTION: Osteopetrosis is a connective tissue disorder resulting from abnormally dense bone predisposing patients to fracture. The clinical pattern of fractures across time and space as well as suggestive radiographic findings usually raises diagnostic suspicion. Multiple genetic mutations resulting in dysfunctional osteoclasts have been implicated in the pathogenesis of osteopetrosis with variable inheritance patterns. In severe cases, usually inherited in an autosomal recessive pattern, the medullary cavity important in the production of normal blood cell progenitors is replaced by defective endochondral bone, leading to pancytopenia and consequential extramedullary hematopoiesis. MATERIALS AND METHODS: This is a case report from a patient presenting to Naval Medical Center San Diego, a large Military Treatment Facility constituting a regional referral center for Navy Medicine West and serving approximately 250,000 eligible patients with more than 6,200 military and civilian staff. The genetic analysis was performed by Connective Tissue Gene Tests (CTGT) using the CTGT Osteopetrosis NextGen sequencing panel, consisting of 13 genes associated with osteopetrosis. A literature review was performed using PUBMED and Google Scholar to identify information on osteopetrosis and mutation implications. RESULTS: We present a 19-year-old male with clinical osteopetrosis resulting from compound heterozygosity of several mutated alleles within the PLEKHM1 gene, which is important to endosomal and lysosomal vesicular function. To date, most mutations discovered involve genes coding for intracellular enzymes, like carbonic anhydrase, or cell surface transporters, such as the osteoclast H+-ATPase proton pump and the chloride channel, engaged in the acidification of bone at the interface of the osteoclastic ruffled border and the bone matrix. This case represents one of the few reports of inherited defects within the PLEKHM1 gene, resulting in defective osteoclastic ruffled border formation and consequential inadequate bone resorption. CONCLUSIONS: This patient's lack of hematologic deficiencies and survival into adulthood portend an improved long-term prognosis and may infer prognostic insight in future cases with similar genetic abnormalities. In patients presenting with skeletal abnormalities and pathologic fractures in early adulthood, the clinician should consider osteopetrosis as a potential explanatory mechanism. Genetic characterization can elucidate cellular pathophysiology and potentially guide treatment modalities. Patients are typically managed with lifestyle adjustments limiting traumatic fracture and antiresorptive medications, typified by the bisphosphonate class. Since osteoclasts derive from a hematopoietic precursor, the only definitive curative therapy present is hematopoietic stem cell transplant. In the future, novel genomic level modulation may confer the ability to correct underlying point mutations and spare individuals from the morbidity associated with bone marrow transplant.

One hundred percent fascial approximation with sequential abdominal closure of the open abdomen.

BACKGROUND: Damage-control surgery and the recognition of the abdominal compartment syndrome have improved patient outcomes but at the cost of an open abdomen. Multiple techniques have been introduced to obtain fascial closure for the open abdomen to minimize morbidity and cost of care. We performed a modification of the vacuum-assisted closure (VAC) technique that provided constant fascial tension, hypothesizing this would result in a higher rate of primary fascial closure. METHODS: After initial temporary closure of the abdomen after post-injury damage control or decompressive laparotomy for abdominal compartment syndrome, we began the sequential closure technique. The technique begins by covering the bowel with the multiple white sponges overlapped like patchwork, and the fascia is placed under moderate tension over the white sponges with #1-PDS sutures. Large black VAC sponges are placed on top of the white sponges and affixed with an occlusive dressing and standard suction tubing is placed. Patients are returned to the operating room for sequential fascial closure and replacement of the sponge sandwich every 2 days, with a resulting decrease in the fascial defect. RESULTS: Fourteen patients underwent sequential abdominal closure during the study period: 9 owing to damage control surgery and 5 owing to secondary abdominal compartment syndrome. Average time to closure was 7.5 +/- 1.0 days (range 4-16) and average number of laparotomies to closure was 4.6 +/- 0.5 (range 3-8). All patients attained primary fascial closure. CONCLUSION: We propose a modification of the previously described vacuum-assisted closure technique that achieves 100% fascial approximation in our limited experience. Further application and refinement of this technique may eliminate the need for delayed complex and costly reconstructive abdominal wall procedures for the open abdomen.

Carotid artery stents for blunt cerebrovascular injury: risks exceed benefits.

BACKGROUND: Carotid stenting has been advocated in patients with grade III blunt carotid artery injuries (hereafter referred to as "blunt CAIs") because of the persistence of the pseudoaneurysm and concern for subsequent embolization or rupture. HYPOTHESIS: Carotid stenting is safe and effective for blunt CAIs. DESIGN: Analysis of a prospective database of all patients with blunt CAIs. SETTING: A state-designated, level I, urban trauma center. PATIENTS AND METHODS: In January 1, 1996, we initiated comprehensive screening for blunt CAIs with angiography based on injury patterns. Patients without contraindications receive anticoagulation therapy immediately for documented lesions. Patients with persistent pseudoaneurysms on a second angiography at 7 to 10 days after injury are candidates for stent placement. RESULTS: During the study period (January 1, 1996, to May 1, 2004), 46 patients sustained blunt carotid pseudoaneurysms; 23 (50%) underwent carotid stent placement. There were 4 complications in patients undergoing carotid stent placement: 3 strokes and 1 subclavian dissection. Follow-up angiography was performed in 38 patients (18 patients with stents who received antithrombotic agents, 20 patients who received antithrombotic agents alone); 8 patients had poststent carotid occlusion despite having received concurrent anticoagulation therapy. Carotid occlusion rates were significantly different (45% in patients with stents vs 5% in those who received antithrombotic agents alone). In the patients not undergoing stent placement, the only complication was a middle cerebral artery stroke in a patient not treated with antithrombotic therapy. CONCLUSIONS: Patients who have carotid stents placed for blunt carotid pseudoaneurysms have a 21% complication rate and a documented occlusion rate of 45%. In contrast, patients treated with antithrombotic agents alone had an occlusion rate of 5%; no asymptomatic patient treated with antithrombotic agents for their injury had a stroke. Antithrombotic therapy remains the recommended therapy for blunt CAIs, but the role of intraluminal stents remains to be defined.

Screening for blunt cerebrovascular injuries is cost-effective.

BACKGROUND: Recent reports have argued that screening for blunt carotid injury is futile and have called for a cost analysis. Our data previously supported screening asymptomatic trauma patients for blunt cerebrovascular injury (BCVI) to prevent associated neurologic sequelae. Our hypothesis is that aggressive angiographic screening for BCVI based on a patient's injury pattern and symptoms allows for early diagnosis and treatment and is cost-effective because it prevents ischemic neurological events (INEs). METHODS: Beginning in January 1996, we began comprehensive screening using 4-vessel cerebrovascular angiography based on injury patterns; these patients have been followed-up prospectively. Patients without contraindications received antithrombotic therapy immediately for documented BCVI. RESULTS: From January 1996 through June 2004, there were 15,767 blunt-trauma patient admissions to our state-designated level I urban trauma center, of which 727 patients underwent screening angiography. Twenty-one patients presented with signs or symptoms of neurologic ischemia before diagnosis. BCVI was identified in 244 patients (34% screening yield); the majority were men (68%) with a mean age of 35 +/- 3.7 years and mean Injury Severity Score of 28 +/- 3.8. Asymptomatic patients (n = 187) were treated (heparin in 117, low molecular-weight heparin in 11, and antiplatelet in 59); 1 patient had a stroke (0.5%). Using estimated stroke rate by grade of injury, we averted neurologic events in 32 asymptomatic patients with antithrombotic treatment. Of the 48 asymptomatic patients who did not receive adequate anticoagulation, 10 (21%) had an INE. Patients with BCVI-related neurologic events had a statistically higher percentage requiring discharge to rehabilitation facilities (50% vs. 77% for carotid artery injury [CAI]), a higher percentage requiring rehabilitation for BCVI-related stroke (0% vs. 55% for CAI), and a higher stroke-related mortality rate (0% vs. 21% for CAI and 0% vs. 17% for vertebral artery injury) than those without neurologic events. CONCLUSIONS: The cost of long-term rehabilitation care and human life after BCVI-associated neurologic events is substantial. Surgeons caring for the multiply injured should screen for carotid and vertebral artery injuries in high-risk patients.

Can we afford to do laparoscopic appendectomy in an academic hospital?

BACKGROUND: Multiple studies have shown laparoscopic appendectomy to be safe for both acute and perforated appendicitis, but there have been conflicting reports as to whether it is superior from a cost perspective. Our academic surgical group, who perform all operative cases with resident physicians, has been challenged to reduce expenses in this era of cost containment. We recognize resident training is an expensive commodity that is poorly reimbursed, and hypothesized laparoscopic appendectomy was too expensive to justify resident teaching of this procedure. The purpose of this study was to determine if laparoscopic appendectomy is more expensive than open appendectomy. METHODS: From April 2003 to April 2004, all patients undergoing appendectomy for presumed acute appendicitis at our university-affiliated teaching hospital were reviewed; demographic data, equipment charge, minutes in the operating room (OR), hospital length of stay, and total hospital charge were analyzed. OR minute charges were gradated based on equipment use and level of skilled nursing care. Conversions to open appendectomy were included in the laparoscopic group for analysis. RESULTS: During the study period, 247 patients underwent appendectomy for preoperative diagnosis of acute appendicitis, with 152 open (113 inflamed, 37 perforated, 2 normal), 88 laparoscopic (69 inflamed, 12 perforated, 7 normal), and 7 converted (2 inflamed, 4 perforated, 1 normal) operations performed. The majority were men (67%) with a mean age of 31.4 +/- 2.2 years. Overall, there was significant difference (P < .05) in intraoperative equipment charge (125.32 dollars +/- 3.99 dollars open versus 1,078.70 dollars +/- 24.06 dollars lap), operative time charge (3,022.16 dollars +/- 57.51 dollars versus 4,065.24 dollars +/- 122.64 dollars), and total hospital charge (12,310 dollars +/- 772 dollars versus 16,773 dollars +/- 1,319 dollars) but no significant difference in operative minutes (56.3 +/- 1.3 versus 57.4 +/- 2.3), operating room minutes (90.5 +/- 1.7 versus 95.7 +/- 2.5), or hospital days (2.6 versus 2.2). In subgroup analysis of patients with uncomplicated appendicitis, open and laparoscopic groups had equivalent hospital days (1.47 versus 1.49) but significantly different hospital charges (9,632.44 dollars versus 14,251.07 dollars). CONCLUSIONS: Although operative time was similar between the 2 groups, operative and total hospital charges were significantly higher in the laparoscopic group. Unless patient factors warrant a laparoscopic approach (questionable diagnosis, obesity), we submit open appendectomy remains the most cost-effective procedure in a teaching environment.

Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects.

We present a noninvasive method to measure the venous oxygen saturation (Sv(O(2))) in tissues using near-infrared spectroscopy (NIRS). This method is based on the respiration-induced oscillations of the near-infrared absorption in tissues, and we call it spiroximetry (the prefix spiro means respiration). We have tested this method in three piglets (hind leg) and in eight human subjects (vastus medialis and vastus lateralis muscles). In the piglet study, we compared our NIRS measurements of the Sv(O(2)) (Sv(O(2))-NIRS(resp)) with the Sv(O(2)) of blood samples. Sv(O(2))-NIRS(resp) and Sv(O(2)) of blood samples agreed well over the whole range of Sv(O(2)) considered (20-95%). The two measurements showed an average difference of 1.0% and a standard deviation of the difference of 5.8%. In the human study, we found a good agreement between Sv(O(2))-NIRS(resp) and the Sv(O(2)) values measured with the NIRS venous occlusion method. Finally, in a preliminary test involving muscle exercise, Sv(O(2))-NIRS(resp) showed an expected postexercise decrease from the initial baseline value and a subsequent recovery to baseline.

Anticoagulation is the gold standard therapy for blunt carotid injuries to reduce stroke rate.

HYPOTHESIS: Aggressive screening, early angiographic diagnosis, and prompt anticoagulation for blunt carotid artery injuries (CAIs) improves neurologic outcome. DESIGN: From January 1, 1996, through December 31, 2002, there were 13 280 blunt trauma admissions to our level I center, of which 643 underwent screening angiography for blunt CAI on the basis of a protocol including injury patterns and symptoms. Patients without contraindications underwent anticoagulation immediately for documented lesions. SETTING: A state-designated, level I urban trauma center. PATIENTS: Of the 643 patients undergoing screening angiography, 114 (18%) had confirmed CAI. INTERVENTION: Early angiographic diagnosis and prompt anticoagulation. MAIN OUTCOME MEASURES: Diagnosis, stroke rate, and complications stratified by method of intervention. RESULTS: A CAI was identified in 114 patients during the 7-year study period; the majority were men (71%), with a mean +/- SD age of 34 +/- 1.3 years and a mean +/- SD Injury Severity Score of 29 +/- 1.5. Seventy-three patients underwent anticoagulation after diagnosis (heparin in 54, low-molecular-weight heparin in 2, antiplatelet agents in 17); none had a stroke. Of the 41 patients who did not receive anticoagulation (because of a contraindication in 27, symptoms before diagnosis in 9, and carotid coil or stent in 5), 19 patients (46%) developed neurologic ischemia. Ischemic neurologic events occurred in 100% of patients who presented with symptoms before angiographic diagnosis and those receiving a carotid coil or stent without anticoagulation. CONCLUSIONS: Our prospective evaluation of blunt CAIs suggests that early diagnosis and prompt anticoagulation reduce ischemic neurologic events and their disability. The optimal anticoagulation regimen, however, remains to be established.

Multiple organ dysfunction during resuscitation is not postinjury multiple organ failure.

HYPOTHESIS: Multiple organ dysfunction (MOD) within 48 hours of injury is a reversible physiologic response to tissue injury and resuscitation. DESIGN: A prospective 10-year inception cohort study ending September 2003. SETTING: Regional academic level I trauma center. PATIENTS: One thousand two hundred seventy-seven consecutive trauma patients at risk for postinjury multiple organ failure (MOF). Inclusion criteria were being 16 years and older, being admitted to the trauma intensive care unit, having an Injury Severity Score higher than 15, and surviving more than 48 hours after injury. Isolated head injuries were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Development of postinjury MOD as defined by a Denver MOF score of 4 or higher within 48 hours of injury and MOF as defined by a Denver MOF score of 4 or higher more than 48 hours after injury. RESULTS: Postinjury MOD and MOF were diagnosed in 209 (16%) and 300 (23%) patients, respectively. Age, Injury Severity Score, and 12-hour blood transfusion requirements were significantly higher among patients who developed MOD and MOF. Of the 209 patients who developed MOD, 134 (64%) progressively developed MOF while 75 (36%) had MOD resolve within 48 hours. CONCLUSION: Multiple organ dysfunction during resuscitation is a reversible response to severe injury and often resolves during the resuscitation period.

Is emergency department resuscitative thoracotomy futile care for the critically injured patient requiring prehospital cardiopulmonary resuscitation?

BACKGROUND: Documented prehospital asystole justifies termination of resuscitation, but recently it has been proposed to extend this policy to patients in the field with pulseless electrical activity. Consequently, we questioned whether resuscitative thoracotomy is warranted in the critically injured patient who fails to respond to prehospital CPR. STUDY DESIGN: A prospective database of all emergency department resuscitative thoracotomies (EDT) performed at our Level I trauma center has been maintained since January 1977. These registry data were augmented by a review of prehospital paramedic records for all survivors of EDT to verify length of CPR. RESULTS: During the 26-year study period, 959 patients underwent EDT. Of the 62 patients who survived to leave the hospital, 26 (42%) required prehospital CPR. The injury mechanism in these 26 patients was stab wounds in 18 (69%), gunshot wounds in 4 (15%), and blunt trauma in 4 (15%). The duration of prehospital CPR ranged from 3 to 15 minutes and in 7 patients CPR exceeded 10 minutes. Five survivors had asystole documented at the time of EDT; four of these patients had good functional outcomes at discharge. Each of these patients had pericardial tamponade from ventricular stab wounds. Patients with blunt trauma had uniformly dismal neurologic outcomes. CONCLUSIONS: EDT after prehospital CPR can be used to salvage select critically injured patients. Based on these data, we propose that resuscitative thoracotomy is futile care in patients with blunt trauma requiring prehospital CPR longer than 5 minutes, and in patients with penetrating trauma with more than 15 minutes of prehospital CPR. EDT is warranted in those patients with penetrating trauma with less than 15 minutes of prehospital CPR, and should be performed despite documented asystole on arrival if pericardial tamponade is the proximate event.

Postinjury abdominal compartment syndrome does not preclude early enteral feeding after definitive closure.

BACKGROUND: Critically injured patients are susceptible to the abdominal compartment syndrome (ACS), which requires decompressive laparotomy with delayed abdominal closure. Previous work by the University of Texas Houston group showed impaired gut function after resuscitation-associated gut edema. The purpose of this study was to determine if enteral nutrition was precluded by the intra-abdominal hypertension and bowel edema of the ACS. METHODS: Patients developing postinjury ACS from January 1996 to August 2003 at our level-I trauma center were reviewed. Patient demographics, time to definitive abdominal closure, and institution and tolerance of enteral nutrition were evaluated. RESULTS: Thirty-seven patients developed postinjury ACS during the study period; 26 men and 11 women with a mean age of 36 +/- 4 and injury severity score of 33 +/- 4. Mean intra-abdominal pressure before decompression was 32 +/- 3 mm Hg, and concurrent mean peak airway pressure was 50 +/- 4 cm oxygen. Enteral feeding was never started in 12 patients; 4 died within 48 hours of admission, 7 required vasoactive agents until their death, and 1 developed an enterocutaneous fistula requiring parenteral nutrition. Enteral feeding was initiated in the remaining 25 patients: 13 had feeds started within 24 hours of abdominal closure; 5 were fed with open abdomens; and 7 had a delay because of vasopressors (n = 2), multiple trips to the operating room (n = 2), paralytics (n = 2), and increased intra-abdominal pressures (n = 1). Once advanced, enteral feeding was tolerated in 23 (92%) of the 25 patients with attainment of goal feeds in a mean of 3.1 +/- 1 days. CONCLUSIONS: Despite the bowel edema and intra-abdominal hypertension related to the ACS, early enteral feeding is feasible after definitive abdominal closure.

Shape-based reprofiling of FDA-approved drugs for the H1 histamine receptor.

Reprofiling of existing drugs to treat conditions not originally targeted is an attractive means of addressing the problem of a decreasing stream of approved drugs. To determine if 3D shape similarity can be used to rationalize an otherwise serendipitous process, we employed 3D shape-based virtual screening to reprofile existing FDA-approved drugs. The study was conducted in two phases. First, multiple histamine H(1) receptor antagonists were identified to be used as query molecules, and these were compared to a database of approved drugs. Second, the hits were ranked according to 3D similarity and the top drugs evaluated in a cell-based assay. The virtual screening methodology proved highly successful, as 13 of 23 top drugs tested selectively inhibited histamine-induced calcium release with the best being chlorprothixene (IC(50) 1 nM). Finally, we confirmed that the drugs identified using the cell-based assay were all acting at the receptor level by conducting a radioligand-binding assay using rat membrane.

Using Self-Guided Treatment Software (ePST) to Teach Clinicians How to Deliver Problem-Solving Treatment for Depression.

Problem-solving treatment (PST) offers a promising approach to the depression care; however, few PST training opportunities exist. A computer-guided, interactive media program has been developed to deliver PST electronically (ePST), directly to patients. The program is a six-session, weekly intervention modeled on an evidence-based PST protocol. Users are guided through each session by a clinician who is presented via hundreds of branching audio and video clips. Because expert clinician behaviors are modeled in the program, not only does the ePST program have the potential to deliver PST to patients but it may also serve as a training tool to teach clinicians how to deliver PST. Thirteen social workers and trainees used ePST self-instructionally and subsequently attended a day-long workshop on PST. Participants' PST knowledge level increased significantly from baseline to post-ePST (P = .001) and did not increase significantly further after attending the subsequent workshop. Additionally, attending the workshop did not significantly increase the participants' skill at performing PST beyond the use of the ePST program. Using the ePST program appears to train novices to a sufficient level of competence to begin practicing PST under supervision. This self-instructional training method could enable PST for depression to be widely disseminated, although follow-up supervision is still required.