Rotational acetabular osteotomy for hip dysplasia: spontaneous medial enlargement of the acetabulum

We followed 56 patients (63 joints) who had undergone rotational acetabular osteotomy (RAOs) between 1987 and 1993, mean 7 (5-12) years. The Merle d'Aubigné score increased by 15 points or more in 59 and decreased in 4 hips. The arthrosis progressed in 5 joints. In about 2/3 of the cases, we observed some medial and/or lateral expansion of the subchondral bone in the acetabulum 3 years postoperatively, suggesting enlargement of the load-bearing area.     

Three-dimensional kinetic simulation before and after rotational acetabular osteotomy

Background

Some reports indicate that one of major causes of clinical failure after periacetabular osteotomy is development of secondary femoroacetabular impingement (FAI). To assess the impact of range of motion (ROM) on the increase in FAI following rotational acetabular osteotomy (RAO), we performed FAI simulations before and after RAO.

Methods

We evaluated 12 hips that had undergone RAO (study group), and 12 normal hips (control group). The study group was evaluated before and after surgery. Morphological parameters were evaluated to assess acetabular coverage. The acetabular anteversion angle, anterior CE angle, alpha angle, and combined anteversion angle were also measured. Impingement simulations were performed using 3D-CT. The ROM which causes bone-to-bone impingement was evaluated in flexion (flex), abduction, external rotation at 0° flexion, and internal rotation at 90° flexion. The lesions caused by impingement were evaluated.

Results

Radiographic measurements indicated improved postoperative acetabular coverage in the study group. The crossover sign was recognized pre- and postoperatively in every case in the study group and in no cases in the control group. In the simulation study, flexion, abduction, and internal rotation at 90° flexion decreased postoperatively. Impingement occurred within 45° internal rotation at 90° flexion in two preoperative and nine postoperative cases. The impingement lesions were anterosuperior of the acetabulum in all cases. There were correlations between anterior CE angle, CE angle, acetabular anteversion angle, and hip flexion angle. There were also correlations between the anterior CE angle, combined anteversion angle, and angle of internal rotation at 90° flexion.

Conclusions

In the postoperative simulation, there was a tendency to reduce the ROM in flexion, abduction, and internal rotation at 90° flexion due to impingement. Since there were more cases which caused impingement within 45° internal rotation at 90° flexion after RAO, we consider there is a potential for increased FAI after RAO.     

Rotational acetabular osteotomy for hip dysplasia: Spontaneous medial enlargement of the acetabulum

We followed 56 patients (63 joints) who had undergone rotational acetabular osteotomy (RAOs) between 1987 and 1993, mean 7 (5-12) years. The Merle d'Aubigné score increased by 15 points or more in 59 and decreased in 4 hips. The arthrosis progressed in 5 joints. In about 2/3 of the cases, we observed some medial and/or lateral expansion of the subchondral bone in the acetabulum 3 years postoperatively, suggesting enlargement of the load-bearing area.     

Acetabular roof arc angles and anatomic biomechanical superior acetabular weight bearing area

Background:

Acetabular fracture involves whether superior articular weight bearing area and stability of the hip are assessed by acetabular roof arc angles comprising medial, anterior and posterior. Many previous studies, based on clinical, biomechanics and anatomic superior articular surface of acetabulum showed different degrees of the angles. Anatomic biomechanical superior acetabular weight bearing area (ABSAWBA) of the femoral head can be identified as radiographic subchondral bone density at superior acetabular dome. The fracture passes through ABSAWBA creating traumatic hip arthritis. Therefore, acetabular roof arc angles of ABSAWBA were studied in order to find out that the most appropriate degrees of recommended acetabular roof arc angles in the previous studies had no ABSAWBA involvement.

Materials and Methods:

ABSAWBA of femoral head was identified 68 acetabular fractures and 13 isolated pelvic fractures without unstable pelvic ring injury were enrolled. Acetabular roof arc angle was measured on anteroposterior, obturator and iliac oblique view radiographs of normal contralateral acetabulum using programmatic automation controller digital system and measurement tools.

Results:

Average medial, anterior and posterior acetabular roof arc angles of the ABSAWBA of 94 normal acetabulum were 39.09 (7.41), 42.49 (8.15) and 55.26 (10.08) degrees, respectively.

Conclusions:

Less than 39°, 42° and 55° of medial, anterior and posterior acetabular roof arc angles involve ABSAWBA of the femoral head. Application of the study results showed that 45°, 45° and 62° from the previous studies are the most appropriate medial, anterior and posterior acetabular roof arc angles without involvement of the ABSAWBA respectively.     

Hip-shelf procedure in the treatment of osteonecrosis of the transpositioned acetabulum after rotational acetabular osteotomy

Necrosis of the transpositioned acetabulum after rotational acetabular osteotomy (RAO) is a major complication characteristic of this procedure. This complication, although rare, has been thought difficult to treat. We report a patient with acetabular osteonecrosis and subsequent collapse after RAO that was effectively treated with a shelf operation, providing satisfactory remodeling of the hip joint. A 16-year-old female had undergone RAO for the treatment of developmental acetabular dysplasia. Postoperative radiography showed that the osteotomized acetabular fragment was unusually thin, and that the osteotome entered the hip joint during the surgery. Five months after the RAO, X-rays revealed significant collapse of the transpositioned acetabulum, and femoral head subluxation caused by postoperative osteonecrosis. Seven months after the RAO, the patient underwent a hip-shelf procedure. The remaining acetabular fragment was used in this procedure, according to the Spitzy method. Seven years after the second operation, favorable remodeling of the hip joint was observed; however, early osteoarthritic changes, including slight joint space narrowing, bone sclerosis of the new acetabulum, and bone cysts within the femoral head, were seen. Received: November 30, 2000 / Accepted: April 16, 2001     

Prophylaxis of secondary osteoarthrosis with spherical osteotomy in residual acetabular dysplasia

The aim of this study was to evaluate whether or not spherical acetabular osteotomy prevents progression of osteoarthrosis in hip joints with residual dysplasia and which radiological parameters can be used postoperatively as predictive factors concerning the outcome. Sixty-eight out of 78 joints were re-investigated with a mean follow-up of 11.2 years after the index operation. Twenty-three Wagner type 1 and 45 type II osteotomies were performed. At surgery, the mean age of the patients was 26 years; 90% of joints showed no or mild degenerative changes, 26% presented with a good or excellent Harris hip score. At follow-up, 28% of patients had improved in function, mean Harris hip score rated 75 points. The mean center-edge (CE) angle improved from -4 degrees to 18 degrees, and the anterior center-edge (ACE) angle from -4 degrees to 26 degrees. The weight-bearing zone of the acetabulum showed an acetabular index (AC) angle of 27 degrees preoperatively and 14 degrees postoperatively. Statistical analysis proved a significant correlation between the normal postoperative values of the acetabulum/femoral-head index of Heyman and Herndon and the absence of degenerative joint changes at follow-up. 73.5% of the hips had not markedly progressed to secondary osteoarthrosis, but 26.5% of joints had deteriorated: 7.4% of them due to perioperative complications and early postoperative trauma. In 8.8% (severe dysplasia) only partial reorientation was possible, which explains the progression of arthrosis, but 10.2% progressed despite sufficient correction.     

Growth disorders of the acetabular roof after acetabuloplasty in congenital hip dysplasia

PURPOSE: The aim of this long-term study was to evaluate whether the Lance acetabuloplasty for congenital dysplasia of the hip causes a growth disturbance of the acetabular roof during or after puberty. METHOD: 71 hips of 58 patients were followed clinically and radiologically over a maximum time of 16 years after the operative procedure of a Lance acetabuloplasty. The average age of the patients at the time of operation was 2.8 years (1-6 years). In order to assess the growth of the acetabulum in the early and long-term postoperative phase quantitative parameters (acetabular index of Hilgenreiner, CE angle of Wiberg, ACM angle of Idelberger) as well as qualitative parameters (disturbance of the ossification of the acetabulum and the femoral head) were determined in standardized X-rays of the pelvis, done routinely 6 months, 3 years, 5 years, 8 years and at an average of 11 years as the last follow-up examination after the operation. The assessment of these metrical parameters were carried out in accordance to the classification of the study-group "hip dysplasia" of the DGOT (normal--slight pathological--serious pathological) respecting the different age-groups and degrees of dysplasia. RESULTS: Although in the early postoperative phase the acetabular roof showed a positive development (65% of the CE angles could be considered normal 3 years after operation), the further growth of the acetabulum was disturbed in the period of puberty (8 years after operation only 33% of the CE angles could be considered normal, 51% were extremely pathological). And also in the last X-ray control after an average follow-up time of 11 years a significant retardation of the acetabular roof was seen in 51% of all cases. CONCLUSION: The Lance acetabuloplasty seems to damage the Ossa acetabuli, which are as centers of ossification the essential anatomic structures for the growth of the acetabular rim in adolescence. CLINICAL RELEVANCE: Other procedures such as the Salter osteotomy are to be preferred for the therapy of hip dysplasia.     

全髋置换术中应用髋臼内壁环形截骨术治疗成人髋臼发育不良

目的评价全髋置换中应用髋臼内壁环形截骨固定非骨水泥髋臼杯治疗成人髋臼发育不良的疗效。方法对29例髋臼发育不良继发骨性关节炎患者(29髋)在全髋置换术中应用髋臼内壁环形截骨术。手术指征为术前X线髋臼覆盖率70%。非骨水泥髋臼杯全部安放在真臼位置,附加操作:软组织松解17髋,治疗性股骨截骨2髋,结构性植骨1髋,股骨短缩3髋。手术前后进行临床及X线参数评价。结果患者均获得随访,时间4~8年。Harris评分从术前36~75(68.4±8.49)分提高到85~100(92.2±4.05)分(P0.05);其中优25髋,良4髋。影像学观察髋臼内壁截骨处愈合时间3~5个月,术后6~12个月时骨重塑。X线检查显示没有无菌性松动和透亮线,真臼固定稳定。结论在非骨水泥全髋置换术治疗髋关节发育不良中,应用髋臼内壁环形截骨术可以提供良好的髋臼位置、足够的髋臼覆盖及保留足够内壁厚度,并且无需植骨。     

Bombelli's valgus-extension osteotomy for osteoarthritis due to acetabular dysplasia: results at 10 to 14 years

Severe osteoarthritis due to acetabular dysplasia (n = 17) was treated with valgus-extension osteotomy, and the patients' clinical outcomes 10–14 years after operation were evaluated according to clinical factors (Japanese Orthopaedic Association hip score; JOA score) and by roentgenography. The mean JOA score 10 years or later had improved by 22 points compared with the preoperative score. On roentgenography, joints which had preoperative roof osteophyte had better postoperative formation of roof osteophyte. The JOA score was higher in the 12 joints which had osteophyte 5 mm or longer than in those joints with osteophyte that was 5 mm or shorter. Postoperative joint space widening occurred in 15 joints (88.2%) 3–6 months postoperatively, and it reached the maximum at 3–5 years. In patients who had a large bone cyst in the femoral head preoperatively, the cyst collapsed, and deformation of femoral head occurred after operation, but remodeling of the joint surface occurred naturally and the congruity improved. In the 6 joints in which the preoperative acetabular head index was less than 60% and the acetabular angle was larger than 30°, the JOA score at 10 years or later was lower than that of the other joints. Based on these findings, valgus-extension osteotomy was evaluated as a useful surgical method for advanced or terminal osteoarthritis in young or middle-aged patients. Predictive factors for long-term prognosis would be the preoperative length of roof osteophyte, joint space widening, and the degree of femoral head covering. Received: December 1, 1999 / Accepted: May 29, 2000     

V形镍钛合金支架植入治疗犬髋臼发育不良的实验研究

目的 探讨Ｖ形镍钛合金（记忆合金）支架植入髋臼顶部后,对其髋臼发育不良的矫正及对其髋臼发育的影响。方法 选用髋臼发育不良的幼犬１０只,随机分为２组,在髋臼顶部距臼缘上０．５ｃｍ处用弧形骨刀做与髋臼弧度一致的截骨,其截骨深达Ｙ形软骨,将截骨后的骨瓣向下扳压,在骨瓣上方植入２￣３只Ｖ形镍钛合金支架,术后４、１２周行双髋关节Ｘ线摄片,进行大体及组织学观察。结果 术后１２周髋臼顶部由术前斜坡形恢复为弧形,     

髋臼旋转截骨术治疗髋臼发育不良

目的探讨髋臼旋转截骨术治疗髋臼发育不良的疗效。方法应用髋臼旋转截骨术治疗髋臼发育不良16例（18髋）,截骨线距臼周缘2 cm,做穹隆状截骨,凿断后再用弧度骨凿将髋臼向前外下方旋转。髋臼矫正到较正常位置后,截骨间隙呈楔形状,用类似间隙大小的楔形同种异体骨块嵌入,并用可注射状人工骨填满间隙,最后用2枚可吸收螺钉固定。测定并比较术前和术后JOA评分、CE角和Sharp角。结果16例均获随访,时间442个月。术后摄片髋关节复位位置好,股骨头及髋臼形状基本正常。髋臼旋转截骨及植入骨块2个月后骨性愈合,6个月后髋关节功能恢复正常17髋,较差1髋,无患髋的骨性关节炎病变继续恶化。JOA评分：术前为75.2分±3.1分,术后为93.5分±3.5分;CE角：术前为15.8°±1.3°,术后为33.4°±1.7°;Sharp角：术前为47.3°±2.5°,术后为29.8°±2.1°。JOA评分术后增加18.3分;CE角增加17.6°,Sharp角减少17.5°,差异有统计学意义（P〈0.05）。结论髋臼旋转截骨术可矫正头臼间异常的匹配关系,使疼痛得到缓解,并使骨性关节炎的过程得到有效遏制,是治疗髋臼发育不良合并早、中期骨性关节炎的理想术式。     

Diagnosing childhood acetabular dysplasia using the lateral margin of the sourcil

The purpose of this study was to evaluate the lateral edge of the acetabulum and locate the most accurate marking point on a plain radiograph when measuring the acetabular index (AI) and the center-edge (CE) angle. We studied the radiographs of 53 patients with unilateral developmental dysplasia of the hip (DDH), all of whom were treated by closed reduction. In addition to plain radiographs, eight patients had magnetic resonance imaging (MRI) studies, 16 had three-dimensional computed tomography (3-DCT) studies, and six underwent arthrographic studies. We found that the most lateral bony margin of the acetabular roof on plain radiograph represents the anterolateral portion of the acetabulum. The lateral end of the sourcil indicates the lateral margin of the mid-superior portion of the acetabulum. To reduce intra- and interobserver errors, we suggest that when measuring the AI and the CE angle, physicians clearly indicate in the medical records which of the two marking points was used.     

Viability of the acetabular bone bed at revision surgery following cemented primary arthroplasty

Loosening of total hip replacements is often associated with severe loss of periprosthetic bone. The notion exists that the remaining bone is sclerotic, avascular, and displays little osteogenic activity, and that it therefore potentially compromises the revitalization of bone grafts used to restore bony defects. To verify this opinion we studied the bone characteristics in acetabular bone biopsies taken at primary total hip arthroplasty (PTH) and revision total hip arthroplasty (RTH) for a cemented PTH. In 6 PTH patients and in 10 RTH patients, acetabular bone biopsies were taken from the roof, the center, and the lower rim of each acetabulum. Specimens were evaluated by light microscopy and histomorphometrically measured for specimen size, bone area, perimeter, active osteoid perimeter, number of vessels, and osteoclasts. The vascularity and vitality appeared to be comparable in the RTH and PTH bone biopsies. However, the trabecular organization of the RTH bone differed from that of the PTH biopsies. In the PTH biopsies, the trabeculae were running perpendicular to the subchondral bone layer, whereas in the RTH biopsies the layers of bone were oriented parallel to the implant surface. There was abundant remodeling activity in the RTH bone, with large quantities of active osteoid and osteoclasts. These histologic parameters differed, but not statistically significant, from the PTH biopsies. In conclusion, we found that at revision, the acetabular bone was viable with sufficient vascularity and remodeling activity to provide an acceptable recipient host bone bed for revision surgery combined with bone grafting.     

Rotational acetabular osteotomy for acetabular dysplasia of the hip with a giant acetabular bone cyst: a case report

In acetabular dysplasia of the hip joint accompanied by a giant acetabular bone cyst, rotational acetabular osteotomy may cause serious complications, such as bone necrosis after surgery or fracture of the fragile acetabulum during the operation. In a patient with this condition, we performed a two-stage operation: first, autogenous bone grafting supplemented with hydroxyapatite filling, then rotational acetabular osteotomy (after new bone formation had been assured). Radiographs and CT scans showed favorable fusion of the grafted bone. Some 18 months after the second operation, arthrograms showed no inflow of contrast medium from the articular cavity into the bone cyst region, although this had been observed before treatment. Thus, an effective remodeling of bony congruency was indicated in the mobile acetabulum 5 years after the second operation. This two-stage operation appears to be useful for correcting acetabular dysplasia accompanied by a giant bone cyst and to carry a reduced risk of serious complications, such as deterioration of the articular surface of the acetabulum or necrosis of the translocated acetabulum.     

Rotational acetabular osteotomies: a rabbit model

We investigated the morphological changes in the articular cartilage after rotational acetabular osteotomy in 16 adolescent rabbits. Radiological and histological studies were conducted at 12 and 24 weeks postoperatively. The radiological evaluations at 12 and 24 weeks showed significantly increased femoral head coverage. No cases of osteonecrosis of the acetabulum or femoral head nor narrowing of the joint space was observed. The histology of the articular cartilage at 12 weeks postoperatively showed cloning and hypercellularity of the chondrocytes in the medial portion of the acetabular roof, indicating remodelling due to the increased weight-bearing stress caused by the osteotomy. The histology at 24 weeks postoperatively showed less cloning of the chondrocytes, indicating that the remodelling process in the articular cartilage induced by this procedure was almost complete at 24 weeks. Degeneration of the articular cartilage was not observed within 24 weeks of the operation.     

A new method to optimize the adhesion between bone cement and acetabular bone in total hip arthroplasty

AIM: In cemented total hip arthroplasty cup loosening occurs earlier than stem loosening in most of the cases. This is mainly caused by the lack of stabile adhesion between the hydrophobic bone cement and the hydrophilic bone surface of the acetabulum. The aim of this study was to develop a multilayer amphiphilic bonding system which prevents the hydrolytic debonding at the bone cement-bone interface, thus optimizing the compound stability. METHOD: In a first series of tests a standardized three-point-bending test was performed to determine the compound stability of the bone cement-bone interface. The bony test specimens were immersed into physiologic NaCl solution to simulate the hydrolytic in situ conditions and contaminated with blood to simulate the intraoperative bleeding of prepared acetabular bone surfaces. In a second series of tests polyethylene cups were implanted into the acetabular cavity of sheep using the current cementing technique. Acetabular bone stock was prepared differently (subchondral sclerotic zone preserved vs. removed, additional drilling into the acetabular roof, with vs. without the multilayer bonding system) in intra-individual comparison of both acetabular sides. To ascertain the bone cement-bone stability a torsional-turn out test was performed on an universal testing machine. RESULTS: In the three-point-bending tests the compound stability between bone cement and bone was 50- to 100-times higher with the use of the multilayer system. In the torsional-turn out tests the compound stability showed in mean a 1.8-fold increase of the interface strength in case of preconditioned acetabular cavities with the multilayer bonding system. CONCLUSION: The developed multilayer bonding system optimizes the interface strength between acetabular bone stock and bone cement significantly for cemented cups in total hip arthroplasty. In contrast to cementing techniques with complete removal of the subchondral sclerotic zone (in order to optimize micro-interlocking) the biologically effective and load bearing acetabular bone stock can be preserved using the newly developed multilayer bonding system. This aspect might be highly important especially with regard to possible acetabular bone defects caused by the process of aseptic cup loosening.     

髋臼卵圆窝在实现术前预期髋臼杯外展角中的参考价值

  目的 探讨髋臼卵圆窝的解剖及影像学特点,评价其在实现术前预期髋臼杯外展角中的作用。方法 在16具正常成人骨盆标本上标记髋臼卵圆窝 中轴线,观察卵圆窝中轴线走行特点及其与卵圆窝顶和髋臼骨性边缘交点在标准骨盆正位X线片上的对应关系。通过模板测量观察预期外展角度的髋臼杯中轴线 与髋臼卵圆窝顶点之间的对应关系。于骨盆标本两侧髋臼施行生物髋臼杯植入术,一侧采用卵圆窝参照法,对侧采用髋臼定位器法,在标准骨盆正位X线片上比 较两侧手术前后髋臼杯外展角偏差的差异。结果 卵圆窝中轴与卵圆窝顶和髋臼骨性边缘的交点是较为恒定的解剖标志,在标准骨盆正位X线上分别对应髋臼顶部 关节面软骨下骨的内缘和外缘。髋臼卵圆窝顶点与40°±5°外展角度的髋臼杯中轴线密切相关。卵圆窝参照组手术前后髋臼杯外展角偏差为0.19° ±3.14°（-6°~5°）,髋臼定位器组为2.75°±2.89°（-2°~8°）,两组差异有统计学意义（t=－2.453,Ρ=0.027）。结论 对于患者髋臼解剖相对正常的 初次全髋关节置换,依据术前模板测量获得的预期髋臼杯位置与卵圆窝顶点的关系,可较精确地获得预期髋臼杯外展位置。     

A stress analysis of acetabular reconstruction in protrusio acetabuli

We are reporting the results of a finite-element analysis of acetabular reconstruction for total hip replacement in the presence of protrusio acetabuli. In a protruded acetabulum, cortical bone stresses on the medial part of the pelvic wall increase with medial placement of the acetabular component, while normal placement of the component (more lateral placement) reduces these stresses. Metal backing of a polyethylene acetabular component causes a reduction in the peak cement and trabecular-bone stresses. A metal protrusio ring about only the periphery of the acetabular component increases stress levels within the lateral part of the pelvic cortex and has little effect on stresses in the medial part of the pelvic wall. A complete metal protrusio cup increases stresses in the lateral part of the pelvic cortex while decreasing substantially the stresses in the medial part of the cortex and the trabecular bone. Prosthetic reinforcement of the medial part of the acetabular wall has little effect on stress patterns in the acetabular region. Clinical Relevance: The major long-term problem with cemented total hip prostheses is loosening. Loosening is probably related in part to the stress state in the cement and surrounding bone. The protruded acetabulum is particularly difficult to reconstruct in a manner that ensures longevity of the total hip replacement. In patients with protrusio acetabuli, the prosthetic acetabulum should be placed in a normal and not in a protruded position. A metal-backed acetabular component or a complete metal cup incorporated within the cement reduces stress levels within the medial aspect of the pelvic bone and thus may reduce the incidence of loosening.     

Evaluation of acetabular coverage of the femoral head with anteroposterior and false profile radiographs of hip joint

To assess the three-dimensional acetabular coverage of the femoral head, we focused on Wiberg's center-edge (CE) angle on anteroposterior radiographs and Lequesne's vertical-center-anterior margin (VCA) angle on false profile radiographs of the hip joint. The study analyzed 566 hip joints of 283 subjects with coxarthrosis (mean age, 34 years). We examined three-dimensional coverage using a calculation program for determining acetabular coverage from anteroposterior radiographs of the hip. There was a significant correlation between acetabular coverage, the CE angle, and the VCA angle (P<0.001). The relationship between the VCA angle (X₁), the CE angle (X₂), and the acetabular coverage (Y) on multiple regression analysis was: Y=47.8+0.06 X₁+1.03 X₂ (r=0.97;P<0.001) We investigated patients showing normal CE and Sharp angles, despite having clinical symptoms, but abnormal VCA angles. This was the finding for 11 joints (10.9%). Therefore, to assess acetabular coverage, it is important to examine not only the CE angle but also the VCA angle. The VCA angle reflects both anterior coverage and pelvic tilt in the standing position. This technique makes it possible to estimate acetabular coverage without special facilities and may be useful for the mass screening of hip joints for detecting acetabular dysplasia. No benefits in any form have been received or will be received from a commercial party related, directly or indirectly, to the subject of this article. No funds were received in support of this study.     

The acetabular opening angle in Perthes' disease. Radiographic study of 62 unilateral cases.

Pelvis AP radiographs in 62 patients with unilateral Perthes' disease were studied in search of changes of the acetabulum throughout the active stages of this disease. The length of the acetabular roof, the diameter of the acetabulum, and the opening angle of the acetabulum, were compared with the contralateral hip. The length of the acetabular roof did not change, but the opening angle and the diameter of the acetabulum increased. This increase began in the earliest stage of the disease in half of the cases; it reached a maximum during the resorptive and the reconstructive stages, then it decreased to reach normal values at skeletal maturity. These changes were related to the extent of the epiphyseal necrosis. Probable causes were local hyperemia and a mechanical adaptation of the acetabulum to a cartilaginous coxa magna. The opening angle has a prognostic value and influences our choice of therapy.