Systematic review and meta-analysis of external ventricular drain placement accuracy and narrative review of guidance devices.

BACKGROUND: Insertion of external ventricular drain (EVD) is one of the most common neurosurgical procedures performed worldwide. This is generally performed freehand, on the basis of anatomical landmarks. There is significant variability in the reported accuracy of freehand placement, lacking Level I evidence. We present the first meta-analysis of freehand EVD placement accuracy and technologies or techniques to enhance accuracy. METHODS: We report a systematic review of the Pubmed, Embase, and Cochrane Central databases according to MOOSE (Meta-analysis Of Observational Studies) guidelines. 37 studies were included for qualitative analysis and 19 studies (2983 cases) for quantitative analysis. RESULTS: There is substantial heterogeneity in the outcome measures used to report EVD placement accuracy. Of those nineteen studies reporting accuracy using the Kakarla grading system the mean rate of ideal ipsilateral frontal horn placement was 73% (standard deviation ±7%). The use of formal stereotaxic guidance is consistently reported to improve accuracy to >90%, although with variable outcome measures. However, the reported efficacy of other guidance devices or techniques is highly variable. The quality of studies directly comparing all existing non-stereotaxic devices with freehand EVD placement is poor and precludes any assertion of superiority to freehand insertion. CONCLUSIONS: We provide the first meta analysis of freehand placement accuracy. There is insufficient data to perform a meta-analysis of the relative efficacy of interventions to improve accuracy. Qualitative synthesis of reports of stereotaxic guidance is suggestive of higher accuracy than freehand placement.

Orthogonal external ventricular drain (EVD) trajectory from burr holes sited by junior neurosurgical staff is superior to freehand placement: An in-silico model.

External ventricular drain (EVD) or ventriculostomy placement is one of the most common neurosurgical procedures performed worldwide and is associated with complications including haemorrhage, malposition and infection. Several authors have attempted to define an ideal trajectory for placement, and scalp-mounted guidance devices have been devised to exploit the theoretical ideal orthogonal trajectory from the scalp to the lateral ventricles. However, uptake has been limited due to lack of demonstrated superiority to freehand placement. Previous modelling studies have failed to include a true-to-life sample of patients undergoing EVD insertion and excluded cases with midline shift or non-hydrocephalus indications. Further, none have attempted to model the orthogonal insertion of EVD via actual burr holes placed by junior neurosurgical staff. In our report of 58 cases of frontal EVD insertion in a low-volume Australian neurosurgical unit freehand EVD insertion resulted in acceptable placement in the ipsilateral frontal horn in 62% of cases, any ventricle in 22%, and in eloquent or non-eloquent brain in 16% of cases. The modelled orthogonal trajectory from the same burr holes, using post-procedural computed tomography scans and the S8 Stealth Station (Medtronic), resulted in superior placement; 80% in the ipsilateral frontal horn and 20% contralateral (p = 0.007). There were no significant malpositions associated with the modelled trajectories. In our series, 18% of freehand catheters required multiple placement attempts. In conclusion, our data suggests that an orthogonal trajectory may result in improved EVD positioning compared to freehand placement.

A randomized controlled trial of fixed- versus mobile-bearing total knee arthroplasty: a follow-up at a mean of ten years.

Aims: It has been suggested that mobile-bearing total knee arthroplasty (TKA) might lead to better outcomes by accommodating some femorotibial rotational mismatch, thereby reducing contact stresses and polyethylene wear. The aim of this study was to determine whether there is a difference between fixed- and mobile-bearing versions of a contemporary TKA with respect to durability, range of movement (ROM) and function, ten years postoperatively. Patients and Methods: A total of 240 patients who were enrolled in this randomized controlled trial (RCT) underwent a primary cemented TKA with one of three tibial components (all-polyethylene fixed-bearing, modular metal-backed fixed-bearing and mobile-bearing). Patients were reviewed at a median follow-up of ten years (IQR 9.2 to 10.4). Results: There was no difference in durability, as measured by survivorship free of revision for any reason, nor in mean maximal ROM at ten years (p = 0.8). There was also no difference in function, as measured by Knee Society (KS) function scores (p = 0.63) or the prevalence of patellar tilt (p = 0.12). Conclusion: In this clinical RCT, the mobile-bearing design of TKA was found to be reliable and durable, but did not provide better maximum knee flexion, function or durability ten years postoperatively compared with a posterior-stabilized, fixed-bearing design incorporating either an all-polyethylene or a modular-metal-backed tibial component. Cite this article: Bone Joint J 2018;100-B:925-9.

A phase-specific neuroimmune model of clinical depression.

Immune dysfunction and pro-inflammatory states in particular have been implicated in the aetiology and pathogenesis of depression. Whilst the onset of an episode and certain symptoms of depression appear well explained by this inflammatory model, the underpinnings of the episodic and progressive nature, as well as relapse and remission status in depression require attention. In this review it is suggested that additional immune factors beyond pro- and anti-inflammatory cytokines may effectively contribute to the understanding of the neurobiology of clinical depression. Considering neurobiological effects of immunomodulatory factors such as T cells, macrophages, microglia and astrocytes relevant to depression, we suggest a neuroimmune model of depression underpinned by dynamic immunomodulatory processes. This perspective paper then outlines a neuroimmune model of clinical phases of depression in an attempt to more adequately explain depression-like behaviours in pre-clinical models and the dynamic nature of depression in clinical populations. Finally, the implications for immunomodulatory treatments of depression are considered.

Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies.

The search for immune biomarkers in psychiatric disorders has primarily focused on pro-inflammatory cytokines. Other immune proteins including chemokines have been relatively neglected in such studies. Recent evidence has implicated chemokines in many neurobiological processes potentially relevant to psychiatric disorders, beyond their classical chemotactic functions. These may include neuromodulator effects, neurotransmitter-like effects, and direct/indirect regulation of neurogenesis. This systematic review presents the existing early evidence which supports an association of many chemokines with the psychiatric disorders: depression, bipolar disorder, schizophrenia, mild cognitive impairment and Alzheimer's disease. The non-specific association of chemokines including CXCL8 (IL-8), CCL2 (MCP-1), CCL3 (MIP-1α) and CCL5 (RANTES) with these disorders across diagnostic categories implies a generalised involvement of many chemokine systemic with psychiatric disease. Additional chemokines with great mechanistic relevance including CXCL12 (SDF-1) and CX3CL1 (fractalkine) have been rarely reported in the existing human literature and should be included in future clinical studies. The potential utility of these proteins as pathologically relevant biomarkers or therapeutic targets should be considered by future clinical and translational research.

Heme induces endothelial tissue factor expression: potential role in hemostatic activation in patients with hemolytic anemia.

OBJECTIVES: We explored the possibility that heme, an inflammatory mediator and a product of intravascular hemolysis in patients with hemolytic anemia including sickle cell disease, could modulate hemostasis by an effect on endothelial tissue factor (TF) expression. METHODS: Levels of TF mRNA, protein and procoagulant activity were measured in heme-treated endothelial cells. RESULTS: Heme induces TF expression on the surface of both macrovascular and microvascular endothelial cells in a concentration-dependent manner, with 12-fold to 50-fold induction being noted (enzyme-linked immunosorbent assay) between 1 and 100 microm heme (P < 0.05). Complementary flow cytometry studies showed that the heme-mediated endothelial TF expression was quantitatively similar to that of tumor necrosis factor-alpha (TNF-alpha). Heme also upregulated the expression of TF mRNA (8-fold to 26-fold), protein (20-fold to 39-fold) and procoagulant activity (5-fold to 13-fold) in endothelial cells in a time-dependent manner. The time-course of heme-mediated TF antigen expression paralleled the induction of procoagulant activity, with antibody blocking studies demonstrating specificity for TF protein. Interleukin (IL)-1alpha, and TNF-alpha are not involved in mediating the heme effect, as antibodies against these cytokines and IL-1-receptor antagonist failed to block heme-induced TF expression. Inhibition of heme-induced TF mRNA expression by sulfasalazine and curcumin suggested that the transcription factor nuclear factor kappaB is involved in mediating heme-induced TF expression in endothelial cells. CONCLUSIONS: Our results demonstrate that heme induces TF expression by directly activating endothelial cells, and that heme-induced endothelial TF expression may provide a pathophysiologic link between the intravascular hemolytic milieu and the hemostatic perturbations previously noted in patients with hemolytic anemia including sickle cell disease.

Neurophysiologic influences on hamstring flexibility: a pilot study.

OBJECTIVE: To examine the potential contribution of neurologic influences on hamstring length during passive range of motion. DESIGN: Prospective study. SETTINGS: Academic sports medicine center. PATIENTS: 15 subjects undergoing arthroscopic surgery for unilateral knee injuries without previous injury to the contralateral knee. INTERVENTIONS: Subjects received: 1) spinal anesthesia with bupivacaine, 2) epidural anesthesia with lidocaine, 3) general anesthesia, or 4) femoral nerve block of injured leg only. MAIN OUTCOME MEASURES: Noninjured leg popliteal angle preoperatively, intraoperatively under anesthesia, and postoperatively after recovery from anesthesia. RESULTS: The overall mean popliteal angle was 132.5 +/- 3.1 degrees preoperatively, 134.31 +/- 11.6 degrees intraoperatively, and 130.7 +/- 10.2 degrees postoperatively. Overall, the intraoperative angle was significantly greater than the postoperative angle (p = 0.02). The mean change in popliteal angle was 8.1 +/- 2.2 degrees (Group 1), -0.4 +/- 1.9 degrees (Group 2), 0.9 +/- 1.4 degrees (Group 3), and -2.4 +/- 3.8 degrees (Group 4). There was no significant change in pre- to postoperative popliteal angle in relation to postoperative pain. Females had a greater mean popliteal angle (139.84 degrees ) compared with males (128.84 degrees ) (p = 0.04). CLINICAL RELEVANCE: Understanding the neuromuscular influences on muscle flexibility will assist in the development of new rehabilitative and injury preventative techniques. CONCLUSION: The present pilot study implicates neural contributions to muscle flexibility. Further studies are needed to delineate the relative contributions of neural and muscular components and to facilitate new techniques in the rehabilitation and prevention of injury.

Total knee arthroplasty in patients with isolated patellofemoral arthritis.

The current study evaluated the results of total knee arthroplasty for the treatment of isolated patellofemoral degenerative arthritis. Between 1980 and 1997, 31 total knee arthroplasties were done in 24 patients with advanced, isolated patellofemoral arthritis. The average followup was 5.2 years (range, 2-12 years). There was a significant improvement in the mean preoperative Knee Society pain and function scores. Twenty-one knees required a lateral retinacular release and three knees required additional formal proximal realignment at the time of the total knee arthroplasty. There were three reoperations in this series including, manipulation for poor motion in one patient; revision of a loose patellar component in one patient; and extensor mechanism realignment in the third patient. At midterm followup, total knee arthroplasty proved to be reliable and durable in alleviating pain and improving function in this group of patients with isolated, advanced patellofemoral arthritis. Surgeons should be made aware, however, that resurfacing of the patella and balancing the extensor mechanism for patients with isolated patellofemoral arthritis can be demanding technically as evidenced by the high rate of asymmetrically resurfaced patellas, the high rate of lateral retinacular release, and formal realignment procedures.

Thrombophilia in sickle cell disease: the red cell connection.

Complex pertubations of hemostasis occur in sickle cell disease (SCD). Although the procoagulant property of sickle erythrocytes in vitro is tied to exposure of phosphatidylserine (PS), no study has directly linked this PS positivity to in vivo thrombin generation. This study was designed to determine if thrombin generation in SCD correlates with erythrocyte PS, or whether platelets play a significant role. PS was quantified on erythrocytes and platelets from 40 patients with SCD (SS genotype = 25; SC genotype = 15) and 11 controls. Markers of thrombin generation (prothrombin fragment F1.2; thrombin-antithrombin or TAT complexes) and fibrin dissolution (D-dimer; plasmin-antiplasmin or PAP complexes) were also evaluated. Thrombin generation and activation of fibrinolysis occurred with elevations in F1.2, TAT, and D-dimer. Although numbers of both PS-positive erythrocytes and platelets were elevated, there was no correlation between PS-positive platelets and any hemostatic markers. In contrast, correlations were noted between PS-positive erythrocytes and F1.2 (P <.0002), D-dimer (P <.000002), and PAP (P <.01). Correlations between F1.2 and D-dimer (P <.0001) demonstrated that fibrinolysis was secondary to thrombin generation. In patients with the SC genotype, abnormalities in coagulation, although present, were of a lesser magnitude than in SS disease. This study suggests that the sickle erythrocyte is the cell responsible for the thrombophilic state in SCD because associations between erythrocyte PS and thrombin generation were observed. No such relationship with platelet PS was noted. The use of erythrocyte PS as a surrogate marker in trials testing new therapeutic modalities may provide insights into the vascular complications of SCD.

Fetal hemoglobin in sickle cell anemia: relationship to erythrocyte adhesion markers and adhesion.

To assess whether fetal hemoglobin (HbF) modulates the adhesion of sickle erythrocytes to endothelium, children with homozygous sickle cell anemia (SS disease) were studied, using this physiologically crucial period to evaluate the relationships between HbF and the major erythrocyte adhesion markers. The mean level of CD36(+) erythrocytes was 2.59% +/- 2.15% (+/- SD, n = 40) with an inverse relationship between CD36 positivity and F cells (R = -0.76, P < .000 00 002). In univariate analyses, significant correlations with various hematologic parameters and age were noted. Multiple regression analyses, however, revealed a relationship solely with F cells. Minimal levels of very late activation antigen-4(+) (VLA4(+)) erythrocytes (0.31% +/- 0.45%, n = 40) with relationships similar to those noted for CD36(+) cells were also observed. The subpopulation of strongly adhesive stress reticulocytes was further assessed, using CD71 as their marker. The mean level of CD71(+) erythrocytes was 5.81% +/- 4.21%, with statistical correlates in univariate and multivariate analyses similar to those discussed above. When adhesion ratios were evaluated, inverse correlations were noted between basal and plasma-induced adhesion and F-cell numbers (R = -0.54, P < .0005; R = -0.53, P < .0006, n = 39). In addition, in analyses where basal or plasma-induced adhesion was the dependent variable and the independent variables included F cells and the various adhesion-related parameters, significant relationships solely with F cells were noted. The results demonstrate that SS patients with higher levels of F cells have concomitant decreases in the numbers of CD36(+), VLA4(+), and CD71(+) erythrocytes and that these findings translate into less adherent erythrocytes. These findings extend knowledge regarding the protective effects of HbF in the pathophysiology of sickle cell disease.

Acute chest syndrome of sickle cell disease: new light on an old problem.

The pulmonary findings of acute chest syndrome of sickle cell disease have been well characterized in numerous studies. Whereas a third of patients have a documented infection associated with this syndrome, and fat embolism from necrotic marrow is the etiologic factor in another approximately 10%, no cause is discovered in the majority of patients. In most patients, however, the underlying pathophysiology is the presence of a hypoxia-driven, adhesion-related occlusive event in the pulmonary microcirculation. This may be accompanied by a decrease in the levels of normal cytoprotective and anti-adhesive mediators such as nitric oxide. In the patient with sickle cell disease, the lung is also a uniquely vulnerable target organ because its vasculature constricts with hypoxia in contrast to other vascular beds. This review will establish the links between known etiologic agents and the pathophysiology of this syndrome. An additional section of this review will deal with experimental therapies. The use of inhaled nitric oxide will be explored in depth because advances in this area are current and uniquely relevant to acute chest syndrome.

Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease.

High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.

Hemostatic alterations in sickle cell disease: relationships to disease pathophysiology.

The protean manifestations of sickle cell disease (SCD), especially, microvessel involvement in the vaso-occlusive process, is classically ascribed to the phenomena of erythrocyte sickling and enhanced red cell-endothelial adherence. Pertubations in various hemostatic systems occurs in SCD, both in steady state and during vaso-occlusion, with the intravascular generation of thrombin. The etiology(s) of thrombin generation in SCD will be described. Whether the activation of the cellular and plasmatic phases of hemostasis is causative or occurs as a result of vascular injury will be discussed.

Treatment of periprosthetic tibial fractures.

Periprosthetic fractures of the tibia are less commonly encountered and have received less attention than periprosthetic fractures of the patella and distal femur. In contrast with distal femoral fractures, tibial fractures frequently are encountered with loose implants and treatment often requires simultaneous revision knee surgery to address the loose prosthesis, the fracture, and any associated bone deficiencies. In some instances, fractures associated with well-fixed and satisfactorily positioned knee components may be treated by traditional methods of operative or nonoperative fracture management. A classification system, which accounts for the anatomic location of the fracture, the status of prosthesis fixation, and timing of the fracture is helpful in description of the various fracture patterns and direction of the appropriate treatment approach.

Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation.

In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children with SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thrombin generation. F cells correlated inversely with both microvesicles and PS positivity (P <.000001) in SS disease. Multiple regression analyses using various hematologic parameters as independent variables, and either microvesicles or PS positivity as the dependent variable, showed a strong relationship only with F cells. Additionally, plasma prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated with both PS positivity (P <.001) and F cells (P <.01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microvesicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers may provide valuable insights into the biology and consequences of in vivo sickling.

A commonsense approach to shoulder problems.

Shoulder pain is a common entity in a primary care physician's practice. The unique anatomy of the shoulder allows for almost unrestrained motion in all planes. A thorough history and physical examination are important to ensure efficient patient evaluation. Further assessment may include radiographic and diagnostic laboratory tests. This article presents an organized approach to the anatomy, physiology, and pathology of common shoulder disorders for the primary care physician. The distinction between disorders that are intrinsic or extrinsic to the shoulder joint is discussed. Treatment and the need for appropriate referral are described.

Biomechanical evaluation of a proximal tibial opening-wedge osteotomy plate.

This biomechanical study evaluated the static response of a new opening-wedge osteotomy plate to compression and torsion loads in a human cadaver model. This plate incorporates a metal block that distracts the medial tibial cortices to ensure precise correction and prevent bone collapse. The 15-mm plate was inserted into 23 fresh cadaver specimens using a standard surgical technique. Axial loading of 13 specimens (compression) and external rotation loading of 10 specimens (torsion) was performed using a servohydraulic-testing machine. Compression loading resulted in failure at a mean of 1810 N due to bone collapse, fracture, or translation. Torsional loading resulted in failure at a mean of 10 Nm due to fracture of the lateral tibial cortex in all specimens. The ratio of the experimental failure load to the calculated estimate of the knee joint forces during gait were 1.07 in axial compression and 0.925 in torsion. This opening-wedge osteotomy plate construct appears marginally strong enough to withstand the estimated axial load on the proximal tibia during gait. Estimated torsional load on the knee during level walking slightly exceeds the failure load prior to osteotomy healing. This information can be used to guide further experimental protocols for static and dynamic testing of this device to determine the appropriate rehabilitation guidelines following opening-wedge proximal tibial osteotomy.