Linda S. Chan

Outcome of Sickle Cell Anemia: A 4-decade Observational Study of 1056 Patients

Abstract: Based on a prospective cohort study of 1056 patients with sickle cell anemia (Hb SS) initiated in 1959, we investigated the influence of calendar era, age, sex, and prior medical conditions on the subsequent development of irreversible organ damage and survival using the Cox regression model with time-dependent covariates adjusting for all prior occurrences. We studied 30 acute clinical events, and focused on 8 prototypic forms of irreversible organ damage. Childhood survival to age 20 years has improved from 79% for those born before 1975 to 89% for children born in or after 1975. Bone infarction was a significant risk factor for avascular necrosis (p = 0.01), and infantile dactylitis was a significant risk factor for stroke (p = 0.01). Prior hospitalized vaso-occlusive sickle crisis in adults was significantly associated with the increased rate of avascular necrosis (p < 0.001), leg ulcers (p < 0.001), sickle chronic lung disease (p < 0.001), renal failure (p < 0.005), and early death (p < 0.001). The diagnosis of clearly evident clinical conditions such as leg ulcer, osteonecrosis, and retinopathy predicted an increased likelihood of developing a more lethal form of organ damage and earlier death: 77% of patients with chronic lung disease, 75% of those with renal insufficiency, and 51% of those with stroke had a prior chronic condition. Of the 232 patients who died, 73% had 1 or more clinically recognized forms of irreversible organ damage. By the fifth decade, nearly one-half of the surviving patients (48%) had documented irreversible organ damage. End-stage renal disease (glomerulosclerosis), chronic pulmonary disease with pulmonary hypertension, retinopathy, and cerebral microinfarctions are manifestations of arterial and capillary microcirculation obstructive vasculopathy. The current study underscores the need for preventive therapy to ameliorate the progression of the sickle vasculopathy. Abbreviations: CVA = cerebral vascular accident.

Operative repair or endovascular stent graft in blunt traumatic thoracic aortic injuries: results of an American Association for the Surgery of Trauma Multicenter Study.

INTRODUCTION The purpose of this American Association for the Surgery of Trauma multicenter study is to assess the early efficacy and safety of endovascular stent grafts (SGs) in traumatic thoracic aortic injuries and compare outcomes with the standard operative repair (OR). PATIENTS Prospective, multicenter study. Data for the following were collected: age, blood pressure, and Glasgow Coma Scale (GCS) at admission, type of aortic injury, injury severity score, abbreviate injury scale (AIS), transfusions, survival, ventilator days, complications, and intensive care unit and hospital days. The outcomes between the two groups (open repair or SG) were compared, adjusting for presence of critical extrathoracic trauma (head, abdomen, or extremity AIS >3), GCS score </=8, systolic blood pressure <90 mm Hg, and age >55 years. Separate multivariable analysis was performed, one for patients without and one for patients with associated critical extrathoracic injuries (head, abdomen, or extremity AIS >3), to compare the outcomes of the two therapeutic modalities adjusting for hypotension, GCS score </=8, and age >55 years. RESULTS One hundred ninety-three patients met the criteria for inclusion. Overall, 125 patients (64.9%) were selected for SG and 68 (35.2%) for OR. SG was selected in 71.6% of the 74 patients with major extrathoracic injuries and in 60.0% of the 115 patients with no major extrathoracic injuries. SG patients were significantly older than OR patients. Overall, 25 patients in the SG group (20.0%) developed 32 device-related complications. There were 18 endoleaks (14.4%), 6 of which needed open repair. Procedure-related paraplegia developed in 2.9% in the OR and 0.8% in the SG groups (p = 0.28). Multivariable analysis adjusting for severe extrathoracic injuries, hypotension, GCS, and age, showed that the SG group had a significantly lower mortality (adjusted odds ratio: 8.42; 95% CI: [2.76-25.69]; adjusted p value <0.001), and fewer blood transfusions (adjusted mean difference: 4.98; 95% CI: [0.14-9.82]; adjusted p value = 0.046) than the OR group. Among the 115 patients without major extrathoracic injuries, higher mortality and higher transfusion requirements were also found in the OR group (adjusted odds ratio for mortality: 13.08; 95% CI [2.53-67.53], adjusted p value = 0.002 and adjusted mean difference in transfusion units: 4.45; 95% CI [1.39-7.51]; adjusted p value = 0.004). Among the 74 patients with major extrathoracic injuries, significantly higher mortality and pneumonia rate were found in the OR group (adjusted p values 0.04 and 0.03, respectively). Multivariate analysis showed that centers with high volume of endovascular procedures had significantly fewer systemic complications (adjusted p value 0.001), fewer local complications (adjusted p value p = 0.033), and shorter hospital lengths of stay (adjusted p value 0.005) than low-volume centers. CONCLUSIONS Most surgeons select SG for traumatic thoracic aortic ruptures, irrespective of associated injuries, injury severity, and age. SG is associated with significantly lower mortality and fewer blood transfusions, but there is a considerable risk of serious device-related complications. There is a major and urgent need for improvement of the available endovascular devices.

Prevention of venous thromboembolism after injury: an evidence-based report--part II: analysis of risk factors and evaluation of the role of vena caval filters.

OBJECTIVE In part II, we describe the results of the literature search and data analysis concerning risk factors for venous thromboembolism and the role of vena caval filters (VCF) in preventing pulmonary embolism. METHODS The methodology used in part I was used in part II. RESULTS Spinal fractures and spinal-cord injuries increase the risk for development of deep venous thrombosis (DVT) by twofold and threefold, respectively. Patients with DVT were an average of 9 years older than patients without DVT. No specific age cut-off point for increased risk could be established because data could not be combined across studies. Patients with prophylactically inserted VCF had a lower incidence of pulmonary embolism (0.2%) compared with concurrently managed patients without VCF (1.5%) or historical controls without VCF (5.8%). These results are reported on uncontrolled studies with observational design. CONCLUSION Spinal injuries, spinal cord injuries, and age are risk factors for development of DVT. Prophylactic placement of VCF in selected trauma patients may decrease the incidence of pulmonary embolism. Future research with well-designed studies is required to provide definitive answers.

Diagnosis and treatment of blunt thoracic aortic injuries: changing perspectives.

BACKGROUND The diagnosis and management of blunt thoracic aortic injuries has undergone many significant changes over the last decade. The present study compares clinical practices and results between an earlier prospective multicenter study by the American Association for the Surgery of Trauma completed in 1997 (AAST1) and a new similar study completed in 2007 (AAST2). METHODS The AAST1 study included 274 patients from 50 participating centers over a period of 30 months. The AAST2 study included 193 patients from 18 centers, over a period of 26 months. The comparisons between the two studies included the method of definitive diagnosis of the aortic injury [computed tomography (CT) scan, aortography, transesophageal echocardiogram (TEE) or magnetic resonance imaging], the method of definitive aortic repair (open repair vs. endovascular repair, clamp and sew vs. bypass techniques), the time from injury to procedure (early vs. delayed repair), and outcomes (survival, procedure-related paraplegia, other complications). RESULTS There was a major shift of the method of definitive diagnosis of the aortic injury, from aortography in the AAST1 to CT scan in AAST2, and a nearly complete elimination of aortography and TEE in the AAST2 study. In the AAST2 study the diagnosis was made by CT scan in 93.3%, aortography in 8.3%, and TEE in 1.0% of patients when compared with 34.8%, 87.0%, and 11.9%, respectively, in the AAST1 study (p < 0.001). The mean time from injury to aortic repair increased from 16.5 hours in the AAST1 study to 54.6 hours in the AAST2 study (p < 0.001). In the AAST1 study, all patients were managed with open repair, whereas in the AAST2 study only 35.2% were managed with open repair and the remaining 64.8% were managed with endovascular stent-grafts. In the patients managed with open repair, the use of bypass techniques increased from 64.7% to 83.8%. The overall mortality, excluding patients in extremis, decreased significantly from 22.0% to 13.0% (p = 0.02). Also, the incidence of procedure-related paraplegia in patients with planned operation, decreased from 8.7% to 1.6% (p = 0.001). However, the incidence of early graft-related complications increased from 0.5% in the AAST1 to 18.4% in the AAST2 study. CONCLUSIONS Comparison between the two AAST studies in 1997 and 2007 showed a major shift in the diagnosis of the aortic injury, with the widespread use of CT scan and the almost complete elimination of aortography and TEE. The concept of delayed definitive repair has gained wide acceptance. Endovascular repair has replaced open repair to a great extent. These changes have resulted in a major reduction of mortality and procedure-related paraplegia but also a significant increase of early graft-related complications.

Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial.

ObjectiveTo evaluate the effect of early optimization in the survival of severely injured patients. Summary Background DataIt is unclear whether supranormal (“optimal”) hemodynamic values should serve as endpoints of resuscitation or simply as markers of the physiologic reserve of critically injured patients. The failure of optimization to produce improved survival in some randomized controlled trials may be associated with delays in starting the attempt to reach optimal goals. There are limited controlled data on trauma patients. MethodsSeventy-five consecutive severely injured patients with shock resulting from bleeding and without major intracranial or spinal cord trauma were randomized to resuscitation, starting immediately after admission, to either normal values of systolic blood pressure, urine output, base deficit, hemoglobin, and cardiac index (control group, 35 patients) or optimal values (cardiac index >4.5 L/min/m2, ratio of transcutaneous oxygen tension to fractional inspired oxygen >200, oxygen delivery index >600 mL/min/m2, and oxygen consumption index >170 mL/min/m2; optimal group, 40 patients). Initial cardiac output monitoring was done noninvasively by bioimpedance and, subsequently, invasively by thermodilution. Crystalloids, colloids, blood, inotropes, and vasopressors were used by predetermined algorithms. ResultsOptimal values were reached intentionally by 70% of the optimal patients and spontaneously by 40% of the control patients. There was no difference in rates of death (15% optimal vs. 11% control), organ failure, sepsis, or the length of intensive care unit or hospital stay between the two groups. Patients from both groups who achieved optimal values had better outcomes than patients who did not. The death rate was 0% among patients who achieved optimal values compared with 30% among patients who did not. Age younger than 40 years was the only independent predictive factor of the ability to reach optimal values. ConclusionsSeverely injured patients who can achieve optimal hemodynamic values are more likely to survive than those who cannot, regardless of the resuscitation technique. In this study, attempts at early optimization did not improve the outcome of the examined subgroup of severely injured patients.

Diagnosis, Microbial Epidemiology, and Antibiotic Treatment of Acute Otitis Media in Children: A Systematic Review

CONTEXT Acute otitis media (AOM) is the most common condition for which antibiotics are prescribed for US children; however, wide variation exists in diagnosis and treatment. OBJECTIVES To perform a systematic review on AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology. DATA SOURCES PubMed, Cochrane Databases, and Web of Science, searched to identify articles published from January 1999 through July 2010. STUDY SELECTION Diagnostic studies with a criterion standard, observational studies and randomized controlled trials comparing AOM microbiology with and without PCV7, and randomized controlled trials assessing antibiotic treatment. DATA EXTRACTION Independent article review and study quality assessment by 2 investigators with consensus resolution of discrepancies. RESULTS Of 8945 citations screened, 135 were included. Meta-analysis was performed for comparisons with 3 or more trials. Few studies examined diagnosis; otoscopic findings of tympanic membrane bulging (positive likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI, 6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness. CONCLUSIONS Otoscopic findings are critical to accurate AOM diagnosis. AOM microbiology has changed with use of PCV7. Antibiotics are modestly more effective than no treatment but cause adverse effects in 4% to 10% of children. Most antibiotics have comparable clinical success.

Selective Nonoperative Management in 1,856 Patients With Abdominal Gunshot Wounds: Should Routine Laparotomy Still Be the Standard of Care?

During the past two decades selective nonoperative management (SNOM) has been used with increasing frequency for abdominal trauma. Many injuries previously managed exclusively by surgery are now being observed closely in the absence of peritonitis or hemodynamic instability. SNOM is considered the standard of care for blunt injuries and stab wounds and has decreased the rate of unnecessary laparotomy, shortened the length of hospital stay, and produced significant cost savings. 1,2 However, abdominal gunshot wounds have been excluded from this advancement. Identically to the way abdominal blunt injuries and stabbings were managed 20 years ago, abdominal gunshot wounds are still managed by routine laparotomy in most trauma centers around the world. 3,4 The reasons cited for this are three: first, the incidence of significant intraabdominal injuries after abdominal gunshot wounds is more than 90%; second, an unnecessary laparotomy is a harmless procedure; and third, clinical examination is unreliable. The high-volume level 1 trauma center at the Los Angeles County and University of Southern California Medical Center admits many patients with abdominal gunshot wounds every year. Because we believe that all three of the above arguments in favor of routine laparotomy are invalid, we manage our patients by SNOM. 5,6 In this study, we describe our experience with abdominal gunshot wounds during the past 8 years with the intent of offering a convincing argument about the advantages of SNOM over routine laparotomy. Our hypothesis is that SNOM is safe and cost-effective, prevents unnecessary negative laparotomies, and decreases the hospital length of stay and therefore should become the standard of care for the management of abdominal gunshot wounds.

A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction

Background:Multiple outcome studies have been published on the use of acellular dermal matrix (ADM) in breast reconstruction with disparate results. The purpose of this study was to conduct a systematic review and meta-analysis to determine an aggregate estimate of risks associated with ADM-assisted breast reconstruction. Methods:The MEDLINE, Web of Science, and Cochrane Library databases were queried, and relevant articles published up to September 2010 were analyzed based on specific inclusion criteria. Seven complications were studied including seroma, cellulitis, infection, hematoma, skin flap necrosis, capsular contracture, and reconstructive failure. A pooled random effects estimate for each complication and 95% confidence intervals (CI) were derived. For comparisons of ADM and non-ADM, the pooled random effects odds ratio (OR) and 95% CI were derived. Heterogeneity was measured using the I2 statistic. Results:Sixteen studies met the inclusion criteria. The pooled complication rates were seroma (6.9%; 95% CI, 5.3%–8.8%), cellulitis (2.0%; 95% CI, 1.2%–3.1%), infection (5.7%; 95% CI, 4.3%–7.3%), skin flap necrosis (10.9%; 95% CI, 8.7%–13.5%), hematoma (1.3%; 95% CI, 0.6%–2.4%), capsular contracture (0.6%; 95% CI, 0.1%–1.7%), and reconstructive failure (5.1%; 95% CI, 3.8%–6.7%). Five studies reported findings for both the ADM and non-ADM patients and were used in the meta-analysis to calculate pooled OR. ADM-assisted breast reconstructions had a higher likelihood of seroma (pooled OR, 3.9; 95% CI, 2.4–6.2), infection (pooled OR, 2.7; 95% CI, 1.1–6.4), and reconstructive failure (pooled OR, 3.0; 95% CI, 1.3–6.8) than breast reconstructions without the use of ADM. The relation of ADM use to hematoma (pooled OR, 2.0; 95% CI, 0.8–5.2), cellulitis (pooled OR, 2.0; 95% CI, 0.9–4.3), and skin flap necrosis (pooled OR, 1.9; 95% CI, 0.6–5.4) was inconclusive. Conclusions:In the studies evaluated, ADM-assisted breast reconstructions exhibited a higher likelihood of seroma, infection, and reconstructive failure than prosthetic-based breast reconstructions using traditional musculofascial flaps. ADM is associated with a lower rate of capsular contracture. A careful risk/benefit analysis should be performed when choosing to use ADM in implant-based breast reconstruction.

Coagulopathy in severe traumatic brain injury: a prospective study.

BACKGROUND The incidence and risk factors for traumatic brain injury (TBI)-associated coagulopathy after severe TBI (sTBI) and the effect of this complication on outcomes have not been evaluated in any large prospective studies. METHODS Prospective study of all patients admitted to the surgical intensive care unit (ICU) of an urban, Level I trauma center from June 2005 through May 2007 with sTBI (head Abbreviated Injury Scale score of >or=3). Criteria for TBI-coagulopathy included a clinical condition consistent with coagulopathy, i.e. sTBI, in conjunction with a platelet count <100,000 mm3 and/or elevated international normalized ratio and/or activated partial thromboplastin time. The following potential risk factors with p < 0.2 on bivariate analysis were included in a stepwise logistic regression analysis to identify independent risk factors for TBI coagulopathy and its association with mortality: age, mechanism of injury (blunt [B] or penetrating [P]), presence of hypotension upon admission, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), head and other body area Abbreviated Injury Scale, isolated head injury, diffuse axonal injury, cerebral edema, intracranial hemorrhage (intraventricular, parenchymal, subarachnoid, or subdural), pneumocephalus, and presence of midline shift. RESULTS A total of 436 patients (392 blunt, 44 penetrating) met study criteria, of whom 387 patients had isolated SHI. TBI coagulopathy occurred in 36% of all patients (B: 33%, P: 55%; p < 0.0075) and in 34% of patients with isolated head injury (B: 32%, P: 54%; p = 0.0062). Independent risk factors for TBI-coagulopathy in isolated sTBI were found to include a GCS score of <or=8, ISS >or=16, presence of cerebral edema, subarachnoid hemorrhage, and midline shift. ICU lengths of stay were significantly longer in SHI patients who developed TBI coagulopathy (12.7 vs. 8.8 days; p = 0.006). The development of TBI coagulopathy in SHI was associated with increased mortality, adjusted odds ratio (95% confidence interval): 9.61 (4.06-25.0); p < 0.0001. CONCLUSION The incidence of TBI coagulopathy in SHI is high, especially in penetrating injuries. Independent risk factors for coagulopathy in isolated head injuries include GCS score of <or=8, ISS >or=16, hypotension upon admission, cerebral edema, subarachnoid hemorrhage, and midline shift. The development of TBI coagulopathy is associated with longer ICU length of stay and an almost 10-fold increased risk of death.

Maternal and infant complications in high and normal weight infants by method of delivery

Objective To estimate the population risks of maternal and infant complications with the birth of macrosomic (at least 4000 g) compared with normal weight infants. Methods Term, singleton infants were identified from the state of Washingtons birth event records database for 1990. Diagnosis codes from the Internal Classification of Diseases (9th revision) were used to identify delivery method and previously defined complications. We adjusted for maternal demographic and clinical factors using multivariable logistic regression to derive the risk of each maternal and infant complication. Results The incidence of macrosomia was 13% (8815 of 66,086). Vaginal birth of macrosomic infants was associated with low incidence of complications except for shoulder dystocia (11%) and postpartum hemorrhage (5%). Postpartum infection was the most common complication for women who had cesarean delivery after labor (5%), and complications for women who had cesarean without labor were rare (less than 3%). Neonatal complications were rare. Among infants with shoulder dystocia, the risks of asphyxia (adjusted relative risk [RR] 1.2, 95% confidence interval [CI] 0.6, 2.3), birth trauma (RR 0.6, 95% CI 0.2, 1.6), long-bone injury (RR 1.2, 95% CI 0.6, 2.4), seizures (RR 1.0, 95% CI 0.0, 25.0), and facial palsy (RR 2.2, 95% CI 0.2, 44.4) were not significantly different for macrosomic and normal weight infants; however, macrosomic infants had a significantly increased risk of Erb palsy (RR 3.5, 95% CI 1.8, 7.5). Conclusion This population-based study showed that most macrosomic infants are delivered vaginally with low rates of maternal and neonatal complications. Macrosomic infants have higher rates of Erb palsy, but similar rates of other serious complications of shoulder dystocia when compared with normal weight infants.