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.

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.