Outcomes of Pregnancy in Sickle Cell Disease Patients: Results from the Prospective ESCORT-HU Cohort Study.

Sickle cell disease (SCD) refers to a group of inherited hemoglobin disorders in which sickle red blood cells display altered deformability, leading to a significant burden of acute and chronic complications, such as vaso-occlusive pain crises (VOCs). Hydroxyurea is a major therapeutic agent in adult and pediatric sickle cell patients. This treatment is an alternative to transfusion in some complications. Indeed, it increases hemoglobin F and has an action on the endothelial adhesion of red blood cells, leukocytes, and platelets. Although the safety profile of hydroxyurea (HU) in patients with sickle cell disease has been well established, the existing literature on HU exposure during pregnancy is limited and incomplete. Pregnancy in women with SCD has been identified as a high risk for the mother and fetus due to the increased incidence of maternal and non-fetal complications in various studies and reports. For women on hydroxyurea at the time of pregnancy, transfusion therapy should probably be initiated after pregnancy. In addition, there is still a significant lack of knowledge about the incidence of pregnancy, fetal and maternal outcomes, and management of pregnant women with SCD, making it difficult to advise women or clinicians on outcomes and best practices. Therefore, the objective of this study was to describe pregnancy outcomes (n = 128) reported in the noninterventional European Sickle Cell Disease COhoRT-HydroxyUrea (ES-CORT-HU) study. We believe that our results are important and relevant enough to be shared with the scientific community.

Evaluating the Effectiveness of Community and Hospital Medical Record Integration on Management of Behavioral Health in the Emergency Department.

This study evaluated the correlation of an emergency department embedded care coordinator with access to community and medical records in decreasing hospital and emergency department use in patients with behavioral health issues. This retrospective cohort study presents a 6-month pre-post analysis on patients seen by the care coordinator (n=524). Looking at all-cause healthcare utilization, care coordination was associated with a significant median decrease of one emergency department visit per patient (p < 0.001) and a decrease of 9.5 h in emergency department length of stay per average visit per patient (p<0.001). There was no significant effect on the number of hospitalizations or hospital length of stay. This intervention demonstrated a correlation with reducing emergency department use in patients with behavioral health issues, but no correlation with reducing hospital utilization. This under-researched approach of integrating medical records at point-of-care could serve as a model for better emergency department management of behavioral health patients.

When Is It Safe to Return to Driving After Spinal Surgery?

Study Design Prospective study. Objective Surgeons' recommendations for a safe return to driving following cervical and lumbar surgery vary and are based on empirical data. Driver reaction time (DRT) is an objective measure of the ability to drive safely. There are limited data about the effect of cervical and lumbar surgery on DRT. The purpose of our study was to use the DRT to determine when the patients undergoing a spinal surgery may safely return to driving. Methods We tested 37 patients' DRT using computer software. Twenty-three patients (mean 50.5 ± 17.7 years) received lumbar surgery, and 14 patients had cervical surgery (mean 56.7 ± 10.9 years). Patients were compared with 14 healthy male controls (mean 32 ± 5.19 years). The patients having cervical surgery were subdivided into the anterior versus posterior approach and myelopathic versus nonmyelopathic groups. Patients having lumbar spinal surgery were subdivided by decompression versus fusion with or without decompression and single-level versus multilevel surgery. The patients were tested preoperatively and at 2 to 3, 6, and 12 weeks following the surgery. The use of opioids was noted. Results Overall, the patients having cervical and lumbar surgery showed no significant differences between pre- and postoperative DRT (cervical p = 0.49, lumbar p = 0.196). Only the patients having single-level procedures had a significant improvement from a preoperative DRT of 0.951 seconds (standard deviation 0.255) to 0.794 seconds (standard deviation 0.152) at 2 to 3 weeks (p = 0.012). None of the other subgroups had a difference in the DRT. Conclusions Based on these findings, it may be acceptable to allow patients having a single-level lumbar fusion who are not taking opioids to return to driving as early as 2 weeks following the spinal surgery.

[Complement deficiencies and human diseases]. / Déficits en protéines du complément et pathologies humaines.

The complement system is a complex system involving serum and membrane proteins interacting in a regulated manner. The complement system plays a major role in antibacterial immunity, in inflammation, and in immune complex processing. Therefore, deficiencies in complement proteins are associated with increased susceptibility to bacterial infections and autoimmune diseases. These deficiencies can be inherited or acquired. Most of them can be screened by simple laboratory tests but require a diagnosis in a specialized laboratory. All sequences of complement genes are known, and the discovery of a deficiency must lead to genetic testing. The discovery of a congenital deficiency requires a familial study and a prophylaxis. In this article, we review the complement cascade, the laboratory tests to explore it, and the main diseases associated with complement deficiencies.

Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign?

Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association.

Arthroscopic versus open shoulder stabilization: current practice patterns in the United States.

PURPOSE: The purpose of this study was to investigate current trends in arthroscopic and open shoulder stabilization in the United States. METHODS: Patients who underwent arthroscopic shoulder stabilization (Current Procedural Terminology code 29806) or open stabilization (Current Procedural Terminology codes 23455 [open Bankart repair], 23460 [anterior bone block], and 23462 [coracoid transfer]) were identified using a national database of insurance billing records during the years 2004 through 2009. Demographic data were recorded for each patient. RESULTS: From 2004 through 2009, there were 23,096 cases of shoulder stabilization, of which 84% (19,337) were arthroscopic and 16% (3,759) were open procedures. There were 17,241 male patients (75%) and 5,855 female patients (25%). The incidence of arthroscopic shoulder stabilization nearly doubled during the period studied, increasing from 11.8 cases for every 10,000 patients in 2004 to 22.9 cases for every 10,000 patients in 2009. The percentage of arthroscopic stabilizations increased from 71% of stabilization procedures in 2004 to 89% in 2009, whereas the percentage of open stabilizations decreased from 29% in 2004 to 11% in 2009 (P < .0001). Among open procedures, a significant decline in the incidence of open Bankart repair was observed, from 4.5 cases for every 10,000 patients in 2004 to 2.2 cases for every 10,000 patients in 2009 (P < .0001), whereas the performance of open coracoid transfer increased from 0.17 cases per 10,000 patients in 2004 to 0.40 cases per 10,000 patients in 2009 (P < .0001). For both arthroscopic and open stabilization, the group aged 10 to 19 years had the highest rate of surgery (29%), followed by the group aged 20 to 29 years (25%). CONCLUSIONS: The current data indicate that arthroscopic stabilization is performed in nearly 90% of shoulder stabilization surgeries and nearly doubled in incidence from 2004 to 2009 in the United States. Additional research is needed to further investigate the long-term clinical outcomes of this practice pattern. LEVEL OF EVIDENCE: Level IV, retrospective database review.

Functional evaluation of factor H genetic and acquired abnormalities: application for atypical hemolytic uremic syndrome (aHUS).

The atypical hemolytic uremic syndrome (aHUS) is a paradigm of a disease, caused by overactivation of the alternative complement pathway secondary to a not well-understood trigger event. About 60 % of the patients present genetic or acquired abnormalities in the proteins of the alternative complement pathway. In 40 % of the cases the affected protein is the complement regulator Factor H (FH)-30 % due to mutations and 10 % because of anti-FH autoantibodies. Here we describe the detailed protocol for a rapid test to analyse the functional defect associated with genetic or acquired FH-related abnormalities. It can be applied for the characterization of the underlying complement defect in aHUS, based on spontaneous lysis of non-sensitized sheep erythrocytes in contact with patients' plasma or serum.

Anti-factor H autoantibodies assay.

Non-Shiga-toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy which associates hemolytic anemia, thrombocytopenia, and acute renal failure. In 10 % of cases the disease is linked to presence of autoantibodies directed against Factor H (FH), the main plasmatic alternative complement pathway regulatory protein. Their presence induces an acquired functional FH deficiency. The anti-FH autoantibodies screening must be performed at the very onset of the disease in all cases of HUS, in order, first, to make the proper diagnosis as early as possible, and second to support an appropriate therapy including early plasma exchanges and immunosuppressive treatments. Thus, anti-CFH IgG represents a diagnostic marker and the titer determination is useful for assessing disease evolution, because changes precede clinical symptoms, and for monitoring of treatment. Presence of anti-FH IgG has been recently reported to be associated with other clinical context such as C3 glomerulopathies, but their pathogenicity in these conditions remains to be assessed. Here we describe the ELISA assay allowing the detection of these autoantibodies and report the analysis which can be performed concomitantly to improve the diagnosis.

Standardisation of the factor H autoantibody assay.

The screening of all atypical haemolytic uraemic syndrome (aHUS) patients for factor H autoantibodies is best practice. However, there is no consensus assay for the reporting of factor H autoantibody titres. In this study, three European complement laboratories with expertise in the field of autoantibody testing address this by systematically evaluating several ELISA methods used for the detection of factor H autoantibodies. All methods tested adequately detect high titre samples. However, this study recommends the Paris method for the detection and reporting of factor H autoantibodies to be used when setting up a factor H autoantibody screen. The importance of individual sample background subtraction in these ELISA tests was established. The use of a relative or arbitrary unit index with a common positive and negative serum allowed for consistent comparison of findings from different test centres. Therefore, it is recommended that a standard arbitrary unit scale based on a titration curve from a common positive anti-serum be adopted to allow future establishment of the relative importance of particular titres of factor H autoantibodies in aHUS. Systematic assay for the presence of factor H autoantibodies in patients using the Paris method will provide the longitudinal analysis needed to fully establish the importance of factor H autoantibodies in disease. This will feed into additional research to clarify whether additional factors have a bearing on the phenotype/outcome of autoimmune aHUS.

C3 nephritic factor associated with C3 glomerulopathy in children.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF. METHODS: We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes. RESULTS: Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases. CONCLUSIONS: C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.

Trends in the surgical treatment of articular cartilage defects of the knee in the United States.

PURPOSE: The purpose of this study was to evaluate trends in surgical treatment of articular cartilage defects of the knee in the United States. METHODS: The current procedural terminology (CPT) billing codes of patients undergoing articular cartilage procedures of the knee were searched using the PearlDiver Patient Record Database, a national database of insurance billing records. The CPT codes for chondroplasty, microfracture, osteochondral autograft, osteochondral allograft, and autologous chondrocyte implantation (ACI) were searched. RESULTS: A total of 163,448 articular cartilage procedures of the knee were identified over a 6-year period. Microfracture and chondroplasty accounted for over 98% of cases. There was no significant change in the incidence of cartilage procedures noted from 2004 (1.27 cases per 10,000 patients) to 2009 (1.53 cases per 10,000 patients) (p = 0.06). All procedures were performed more commonly in males (p < 0.001). This gender difference was smallest in patients undergoing chondroplasty (51 % males and 49% females) and greatest for open osteochondral allograft (61% males and 39% females). Chondroplasty and microfracture were most commonly performed in patients aged 40-59, while all other procedures were performed most frequently in patients <40 years old (p < 0.001). CONCLUSIONS: Articular cartilage lesions of the knee are most commonly treated with microfracture or chondroplasty in the United States. Chondroplasty and microfracture were most often performed in middle-aged patients, whereas osteochondral autograft, allograft, and ACI were performed in younger patients, and more frequently in males. LEVEL OF EVIDENCE: Cross-sectional study, Level IV.

Synergistic effect of bone morphogenetic proteins 2 and 7 by ex vivo gene therapy in a rat spinal fusion model.

BACKGROUND: Previous studies have suggested that the co-expression of two different bone morphogenetic protein (BMP) genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP-2 and BMP-7 gene transfer was performed ex vivo to compare the resulting new bone formation with that of single-BMP gene transfer in a rat spinal fusion model. METHODS: Forty-four athymic rats underwent posterolateral fusion at L4-L5 and were implanted with a collagen sponge containing human adipose-derived stem cells. Group A received untreated cells, and the remaining groups received cells transfected with various genes in a lentivirus vector. The transferred genes were GFP (green fluorescent protein) in Group B, BMP-2 in Group C, BMP-7 in Group D, and both BMP-2 and BMP-7 in Group E. In vitro production of BMP-2 and BMP-7 was quantified by means of an enzyme-linked immunosorbent assay (ELISA) specific to BMP-2 or BMP-7. Osseous fusion was quantified with use of radiography and microcomputed tomography. RESULTS: ELISA demonstrated that Group E, which was treated with both BMP-2 and BMP-7, produced less than one-fourth as much BMP as the groups treated with a single transfected BMP (Groups C and D). Radiographs showed that all of the spines in Groups C, D, and E appeared to be fused by eight weeks; the spines in Groups A and B showed minimal evidence of new bone formation. Measurements confirmed that the mean bone formation area was significantly greater in Groups C, D, and E compared with Groups A and B (p < 0.001). In addition, the bone formation area was significantly greater in Group E compared with Groups C and D (p < 0.001). CONCLUSIONS: Combined BMP-2 and BMP-7 ex vivo gene transfer was found to be significantly more effective for inducing new bone formation compared with ex vivo gene transfer of an individual BMP in a rat spinal fusion model. CLINICAL RELEVANCE: Combined BMP-2 and BMP-7 therapy may lead to efficient bone regeneration.

Cross-sectional analysis of trends in meniscectomy and meniscus repair.

Knee arthroscopy to address meniscus tears is among the most common orthopedic procedures performed, and technical advances in the treatment of meniscus tears have affected the treatment options available to orthopedic surgeons. The purpose of this study was to perform a large cross-sectional analysis of orthopedic patients to investigate trends in arthroscopic meniscectomy and meniscus repair in the United States. Patients who underwent arthroscopic meniscectomy (Current Procedural Terminology codes 29881 and 29880) and arthroscopic meniscus repair (Current Procedural Terminology codes 29882 and 29883) were identified using the PearlDiver Patient Record Database, which is a national database of insurance records. The authors identified 187,607 arthroscopic medial or lateral meniscectomies and repairs performed between 2004 and 2009. Ninety-six percent of patients underwent meniscectomy and 4% underwent repair. No change occurred in the incidence of medial or lateral meniscectomy. The incidence of medial meniscus repair decreased from 5.3 cases per 10,000 patients in 2004 to 3.8 in 2009 (P<.001), although no significant change occurred in the incidence of lateral meniscus repair. Medial meniscectomy was most commonly performed in patients aged 50 to 59 years, whereas lateral meniscectomy demonstrated a bimodal age distribution. Conversely, meniscus repairs were most frequently performed in patients aged 10 to 19 years. Sex differences were more pronounced with meniscus repair (63% male vs 37% female) compared with meniscectomy (53% male vs 47% female). A high frequency of meniscus debridement can be expected in arthroscopic knee surgery. Despite advances in meniscus repair techniques and devices, no increase occurred in the performance of meniscus repair compared with meniscectomy.

Analysis of rotator cuff repair trends in a large private insurance population.

PURPOSE: The purpose of this study was to identify current trends in open and arthroscopic surgical treatment of rotator cuff tears across sex, age, and region in the United States. METHODS: Using the PearlDiver Patient Record Database (PearlDiver, Fort Wayne, IN), a publicly available national database of insurance records, patients who underwent rotator cuff repair from 2004 through 2009 were identified. The number of open (CPT codes 23410, 23412, 23420) and arthroscopic (CPT code 29827) rotator cuff repairs were quantified in isolation and in combination with acromioplasty (CPT codes 23415, 29826). The type of procedure, date, sex, and region of the country was identified for each patient. Trend tests (χ(2) and Cochran-Armitage) were used to determine statistical significance. RESULTS: There were 151,866 rotator cuff repair procedures identified in the database from 2004 through 2009, which represented an incidence of 13.6 for every 1,000 patients assigned an orthopaedic International Classification of Diseases, Ninth Revision (ICD-9) or Current Procedural Terminology (CPT) code. Male patients accounted for 60% of the repairs and female patients for 40%. There were 98,174 arthroscopic cuff repairs (65%) and 53,692 open repairs (35%). The annual percentage of arthroscopic cases increased from 48.8% in 2004 to 74.3% in 2009, whereas the percentage of open cases decreased from 51.2% in 2004 to 25.7% in 2009 (P < .0001). Acromioplasty was also performed in 47.3% of cases, and the rate showed only a slight increase (from 46.6% to 47.8%) between 2004 and 2009 (P < .01). All regions of the United States showed similar surgical trends and trends for sex and age distributions. CONCLUSIONS: Our analysis shows that the majority of rotator cuff repairs in the United States are now performed arthroscopically (>74%) and there has been a recent steady decline in performance of open rotator cuff repair. Concomitant acromioplasty is performed approximately half the time, and this trend is increasing slightly. These findings were consistent across age, sex, and region in the United States. LEVEL OF EVIDENCE: IV, cross-sectional study.

Trends and demographics in hip arthroscopy in the United States.

PURPOSE: The purpose of this study was to evaluate the trends and report on the demographics of patients undergoing hip arthroscopy in the United States. METHODS: Patients who underwent hip arthroscopy from 2004 to 2009 were identified by searching Current Procedural Terminology codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopaedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 10,000 patients searched in the database. RESULTS: In total, 3,447 cases of hip arthroscopy were identified between 2004 and 2009. The incidence of procedures increased significantly over the study period, from 1.20 cases per 10,000 patients in 2004 to 5.58 in 2009 (P < .001). Hip arthroscopy was performed most commonly in patients aged 20 to 39 years (P < .05), with an incidence of 4.45 cases in each age group. In contrast to other common arthroscopic procedures searched, no gender differences were observed, with a male-to-female ratio of 0.89 (P = .18). The greatest incidence of hip arthroscopy was observed in the Western region with an incidence of 5.24 cases identified compared with 2.94, 2.70, and 2.56 in the Northeast, Midwest, and South, respectively (P < .001). CONCLUSIONS: A 365% increase in the rate of hip arthroscopy was observed in the examined cohort of patients between 2004 and 2009. The majority of cases were performed in patients aged 20 to 39 years, with no difference in gender. The Western region of the United States was found to have a higher incidence of hip arthroscopy compared with the Midwest, South, and Northeast. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults.

BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti-factor H antibodies. RESULTS: Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P<0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups. CONCLUSION: Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.

Complications of arthroscopic meniscectomy in the older population.

BACKGROUND: Complications of arthroscopic meniscectomy in the older population have not been established. PURPOSE: To determine the risk and relative risk of developing pyogenic arthritis (PA), a deep vein thrombosis (DVT), and pulmonary embolism (PE) in an older population of patients who have undergone arthroscopic meniscectomy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Men and women ≥65 years old who underwent procedures coded as CPT-29880 (medial and lateral meniscectomy) and CPT-29881 (medial or lateral meniscectomy) were identified in the Medicare Standard Analytic Files database from 2005 to 2008. Identified patients were analyzed for gender and postoperative complications, including PA, DVT, and PE, occurring within 90 days of the index operation. RESULTS: Overall, 314,578 patients (119,814 men and 194,764 women) were identified. With respect to the Current Procedural Terminology codes, 131,420 patients were coded 29880 and 183,158 patients were coded 29881. In the study population, 0.4% (1107 patients) developed PA, 0.8% (2507 patients) developed a DVT, and 0.3% (982 patients) developed a PE. Among male patients, 0.4% developed PA, 0.7% developed a DVT, and 0.2% developed a PE. Among female patients, 0.3% developed PA, 0.8% developed a DVT, and 0.3% developed a PE. Overall, men had a statistically significant higher relative risk of PA and women had a statistically significant higher relative risk of DVT and PE. CONCLUSION: Postoperative complications, including PA, DVTs, and PEs, are rare in patients ≥65 years old. However, gender-specific differences in the rate and type of postoperative complications may exist. Further studies in this population are warranted.