We made a prospective study of 43 consecutive patients treated for intraforaminal (34) or extraforaminal (9) herniations of a lumbar disc by excision through an interlaminar approach, using an operating microscope. The intraforaminal herniations were contained or extruded in 52% and sequestrated in 47%; for extraforaminal herniation the proportions were 66% and 33%, respectively. There was additional posterolateral protrusion or spinal stenosis at the level of the lateral herniation in seven and four cases, respectively. The patients were reviewed at three months and two years after surgery. Radiographs showed three grades of facetectomy: grade I, removal of 50% or less, grade II, excision of 51% to 75%, and grade III, subtotal or total facetectomy.

For intraforaminal herniations the results were excellent or good in 88% of patients when reviewed at three months and in 91% at two years. For extraforaminal herniations, there was an excellent or good outcome in 89% of patients in the short term and in all in the long term. The facetectomy had been grade I in 14 and grade II in 25; it had been grade III in four, but only one had had total facetectomy. No patient had developed vertebral hypermobility as a result of the operation.

An intralaminar approach using an operating microscope can provide adequate access to a lateral protrusion. It has the advantage of allowing the treatment of posterolateral protrusion or posterior annular bulge and of spinal stenosis at the same level.

Lateral oblique radiographs are considered important for the identification of spondylolytic lesions, but these projections will give a clear view only when the radiological beam is in the plane of the defect. We studied the variation in orientation of spondylolytic lesions on CT scans of 34 patients with 69 defects.

There was a wide variation of angle: only 32% of defects were orientated within 15° of the 45° lateral oblique plane. Lateral oblique radiographs should not be considered as the definitive investigation for spondylolysis.

We suggest that CT scans with reverse gantry angle are now more appropriate than oblique radiography for the assessment of spondylolysis. Variation in the angle of the defect may also need consideration when direct repair is being planned.

We investigated 21 pairs of twins for zygosity and idiopathic scoliosis. DNA fingerprinting confirmed that 13 pairs were monozygotic and eight were dizygotic. There was concordance for idiopathic scoliosis in 92.3% of monozygotic and 62.5% of dizygotic twins.

Of the 12 pairs of monozygotic twins concordant for idiopathic scoliosis, six showed discordant curve patterns but eight had differences in Cobb angle of less than 10°. Seven of the ten pairs of monozygotic twins had similar back shapes.

Our findings suggest that there is a genetic factor in the aetiology of idiopathic scoliosis; they also indicate that there is a genetic factor in both the severity of the curve and the general shape of the back.

Various classifications of scaphoid fractures have been based on plain radiography, but there are difficulties in defining the actual fracture line without an appreciation of the three-dimensional anatomy.

Radiological fracture lines were therefore mapped on transparent methylmethacrylate models of the bone. An analysis of 91 acute fractures showed that 11 were apparently incomplete. The other 80 showed three basic anatomical patterns: transverse through the waist, oblique in the plane of the dorsal sulcus, or of the proximal pole. There was some variation and comminution in these patterns, but no distal fractures of the body were seen.

The interpretation of different radiological projections is discussed. The findings have implications for the management and the assessment of outcome.

We report three complete ruptures and one partial rupture of the flexor pollicis longus tendon in association with the insertion of a volar plate for the treatment of fracture of the distal radius. Rupture was associated with the chronic use of steroids.

From 1987 to 1993 we treated 33 patients with 29 phalangeal and seven metacarpal fractures by external fixation using a mini-Hoffmann device. There were 27 open and 25 comminuted fractures. In 12 patients one or more tendons was involved.

The mean follow-up was 4.4 years. Complications occurred in ten fractures; two required repositioning of the fixator. All the fractures healed. The functional results after metacarpal fractures were better than those after phalangeal fractures and fractures of the middle phalanx had better recovery than those of the proximal phalanx. Twenty-eight of the 33 patients were satisfied with their result.

External fixation proved to be a suitable technique for stabilising unstable, open fractures with severe soft-tissue injuries.

We reviewed 21 patients with Mason type-III fractures of the radial head treated by resection, evaluating the results at 16 to 30 years by a standard questionnaire and clinical and radiological examination of the elbow and wrist.

Seventeen patients had an excellent result, three were good and one fair. Resection of the radial head is a satisfactory method of treatment of such fractures. Prosthetic replacement seems to be indicated only when there is valgus instability of the elbow.

Six highly unstable elbows with severe bone loss due to rheumatoid arthritis were replaced by a non-constrained, unlinked prosthesis. Bone defects were filled with autogenous bone grafts. The mean follow-up was 4.5 years (2 to 8).

The clinical results were excellent in four elbows and good in two, with good varus-valgus stability in all. Radiological follow-up showed no appreciable signs of loosening, and the bone grafts had retained most of their original size, with minimal resorption. There were no major complications such as dislocation, skin necrosis, infection or ulnar neuropathy.

The study has shown that the so-called mutilans elbow can be successfully replaced using a properly selected type of non-constrained, unlinked prosthesis with bone grafting of the major defects.

We dissected 21 cadaver elbows to determine the relationship of the posterior interosseous nerve to the posterolateral approach to the elbow and head of the radius. At the distal end of the exposure the first branches at risk, those to extensor carpi ulnaris, were on average 6.0 ± 1.0 cm (4.0 to 8.4) from the articular surface of the radial head.

When using the posterolateral approach it is important that the interval between extensor carpi ulnaris and anconeus is clearly identified with the forearm fully pronated. The supinator should be released close to its ulnar border. It is safe to expose the proximal radius as far as the distal aspect of the bicipital tuberosity.

We report a prospective study of the incidence of fractures in the adult population of Edinburgh, related to age and gender. Over a two-year period, 15 293 adults, 7428 males and 7865 females, sustained a fracture, and 5208 (34.0%) required admission.

Between 15 and 49 years of age, males were 2.9 times more likely to sustain a fracture than females (95% CI 2.7 to 3.1). Over the age of 60 years, females were 2.3 times more likely to sustain a fracture than males (95% CI 2.1 to 2.4). There were three main peaks of fracture distribution: the first was in young adult males, the second was in elderly patients of both genders, mainly in metaphyseal bone such as the proximal femur, although diaphyseal fractures also showed an increase in incidence. The third increase in the incidence of fractures, especially of the wrist, was seen to start at 40 years of age in women.

Our study has also shown that ‘osteoporotic’ fractures became evident in women earlier than expected, and that they were not entirely a postmenopausal phenomenon.

We have analysed 249 consecutive fractures of the humeral shaft treated over a three-year period. The fractures were defined by their AO morphology, position, the age and gender of the patient and the mechanism of injury. Open fractures were classified using the Gustilo system and soft-tissue injury, and closed fractures using the Tscherne system.

The fractures were classified as AO type A in 63.3%, type B in 26.2% and type C in 10.4%. Most (60%) occurred in the middle third of the diaphysis with 30% in the proximal and 10% in the distal third. The severity of the fracture and soft-tissue injury was greater with increasing injury severity. Less than 10% of the fractures were open. There was a bimodal age distribution with a peak in the third decade as a result of moderate to severe injury in men and a larger peak in the seventh decade after a simple fall in women.

We carried out a randomised, controlled trial in 157 patients who had isolated severe Gustilo type-IIIa and type-IIIb fractures of the metaphysis or diaphysis of the leg to determine the prevalence of vascular injuries and the role of vascular repair. All patients had stable vital signs and clinically adequate circulation in their legs before operation. In a control group of 64 patients we performed conventional surgery with systematic debridement and primary stabilisation of the fractures. In the trial group of 93 patients the major vessels and nerves adjoining the compound fracture were routinely explored and repaired when necessary after the initial procedure.

Two of the 28 control patients (7.1%) with type-IIIb compound fractures had signs of inadequate circulation after the first operation. Both had major vascular injuries which were demonstrated at a second procedure. In the trial group, major vascular injuries were found in two of 54 patients (3.7%) with type-IIIa and 11 of 39 patients (28.2%) with type-IIIb compound fractures. Compared with the control group the trial group showed improved results at both the immediate and long-term follow-up.

Routine exploration and early repair of injured major vessels of the leg in severe compound fractures gave encouraging results.

We report a prospective, randomised, blinded clinical comparison of the use of indomethacin or radiation therapy for the prevention of heterotopic ossification (HO) in 75 adults who had open reduction and internal fixation of acetabular fractures through either a Kocher-Langenbeck, a combined ilioinguinal and Kocher-Langenbeck, or an extended iliofemoral approach. Indomethacin, 25 mg, was given three times daily for six weeks. Radiation with 800 cGy was delivered within three days of operation. Plain radiographs were reviewed and given Brooker classification scores by three independent observers who were unaware of the method of prophylaxis.

One patient died from unrelated causes and two were lost to follow-up, leaving 72, 33 in the radiation group and 39 in the indomethacin group, available for evaluation at a mean of 12 months (6 to 48). There was no significant difference in the two groups in terms of age, gender, injury severity score, estimated blood loss, delay to surgery, head injury, presence of femoral head dislocation, or operating time, and no complications due to either method of treatment. The final extent of HO was already present by six weeks in all patients who were followed up.

Three patients in the radiation group and five who received indomethacin developed HO of Brooker grade III. Two patients in the indomethacin group developed Brooker IV changes; both had failed to receive proper doses of the drug. Cochran-Armitage analysis showed no significant difference between the two treatment groups as regards the formation of HO.

Indomethacin and single-dose radiation therapy are both safe and effective for the prevention of HO after operation for acetabular fractures. Radiation therapy is, however, approximately 200 times more expensive than indomethacin therapy at our institution and has other risks.

A 61-year-old woman was seen with diastasis of the symphysis pubis and insufficiency fractures of the wings of both ilia after irradiation for carcinoma of the cervix. The characteristics and treatment of these fractures are discussed.

One concern about the fixation of HA-coated implants is the possible disintegration of the surface, with the migration of HA granules into the joint space, producing third-body wear.

We report a study of six revisions of HA-coated polyethylene RM cups at 9 to 14 years after successful primary arthroplasty. In all six hips, we found HA granules embedded in the articulating surface of the polyethylene, with abrasive wear of the cup and the metal femoral head. The cup had loosened in four hips and three showed severe osteolysis of the proximal femur.

Third-body wear due to HA particles from implant coating may produce severe clinical problems with few early warning signs. Further clinical, radiological and histological observations are needed to determine the possible incidence of this late complication in the various types of coating of a variety of substrates.

We report a prospective study of the use of intramedullary bone blocks to improve the fixation of a matt-finish femoral stem in Charnley low-friction arthroplasties. There were 379 patients (441 hips), but at a minimum follow-up of ten years there were 258 arthroplasties in 221 patients including some which had been revised. The mean age at surgery was 41 years (17 to 51) and the mean follow-up was 13.4 years (1 to 20 including the early revisions).

Nine stems (3.5%) had been revised for aseptic loosening, but there were no stem fractures. Survivorship of stems was 99.2% at ten years and 94.35% at 15 and 20 years. We found that the patient’s gender, the position of the stem and the experience of the surgeon all influenced the outcome.

Our findings suggest that using our method of stem fixation, follow-up of over 11 years was needed to reveal the effects of endosteal cavitation of the femur, and of over 13 years to assess any divergence between the clinical and the radiological outcomes of stem fixation.

We investigated 42 patients who were being considered for primary total hip arthroplasty (THA), but in whom it was uncertain whether the hip was the source of their pain. They were given an injection of local anaesthetic into the joint space.

Of 33 patients who gained pain relief from their injection, 32 subsequently had successful THA. The remaining patient has not had surgery. The intra-articular injection of local anaesthetic is thus at least 96% sensitive. Of the nine patients who had no or only minimal pain relief from injection, one has had an unsuccessful THA, three have been successfully treated for other conditions and five have unresolved pain for which no organic basis has been established.

We believe that the injection of local anaesthetic into the hip is a reliable test, with low morbidity. In difficult cases it will aid in the clarification of the cause of pain which possibly arises from the hip.

In a frail elderly patient a pathological fracture of the femur at the lower end of a loose femoral stem was treated by the retrograde insertion of an intramedullary nail over the tip of the prosthesis.

We compared two methods of reconstruction of the abductor mechanism in 15 patients after prosthetic replacement of the upper femur, to assess abductor strength and function.

Six patients in group I had direct fixation of the gluteus medius tendon and a segment of the original bone to the prosthesis. Nine patients in group 2 had the abductor tendon fixed to the iliotibial band. We assessed clinical function, isometric muscle strength and muscle cross-sectional area for each patient.

The patients in group 1 had better clinical and functional results (p = 0.059), with average peak torques for hip abduction of 92% of that in the non-operated leg in group 1, and of 57% in group 2. Group 1 had a mean muscle cross-sectional area of 69% and a mean value of strength per cross-sectional area of 134% when compared with the control side. The respective values for group 2 were 52% and 91%.

Direct fixation of the abductor muscles to the prostheses gave improved function and higher isometric abductor muscle force.

We treated 90 patients with an isolated injury to the anterior cruciate ligament (ACL) by reconstruction using a patellar tendon autograft and interference screw fixation.

Of these, 82 (91%) were available for review at 24 months. Two grafts and two contralateral ACLs had ruptured during sport and there was one case of atraumatic graft resorption. Using the assessment of the International Knee Documentation Committee (IKDC), 86% of the remaining patients were normal or nearly normal. The median Lysholm knee score was 95/100 and 84% of patients were participating in moderate to strenuous activity. All had grade-0 or grade-1 Lachman, pivot-shift and anterior-drawer tests. Measurement with the KT1000 arthrometer gave a side-to-side difference of < 3 mm of anterior tibial displacement in 90%. Sixty-six radiographs were IKDC grade A and one was grade B. Pain on kneeling was present in 31% and graft site pain in 44%.

At 24 months after operation all patients had excellent knee stability, a high rate of return to sport and minimal radiological evidence of degenerative change. Our series therefore represents a basis for comparison of results using other techniques and after more severe injuries.

To assess migration of the tibial component we used roentgen stereophotogrammetric analysis in 40 patients who had had a total knee arthroplasty after failure of a closing wedge osteotomy and compared them with 40 matched patients after primary total knee arthroplasty.

We found no difference in migration over time or in the tendency for continuous migration between the two groups. There were no differences in alignment or position of the knee prosthesis or in the clinical outcome.

Our findings show that revision of a failed high tibial osteotomy to a total knee arthroplasty is effective.

Lipoma arborescens is a rare intra-articular lesion, characterised by diffuse replacement of the subsynovial tissue by mature fat cells, producing prominent villous transformation of the synovium. The aetiology of this benign condition is unknown.

We describe six cases involving the knee discussing the symptoms, diagnosis and treatment.

The Blauth prosthesis is a hinged total knee replacement. We have evaluated 422 consecutive primary total knee arthroplasties using this design in 330 patients with a maximum follow-up of 20 years (mean 6). The mean age of the patients at the time of operation was 70 years (29 to 87).

Using endpoints of infection, removal because of aseptic loosening, removal for any cause, and the worst case as definitions of failure, the cumulative rates of survival at 20 years were 93.6%, 96.0%, 94.4% and 86.8%, respectively. The cumulative rate of survival of the patients themselves was 14.4% (24% in patients with osteoarthritis and 9% in these with rheumatoid arthritis) after 20 years.

Our survivorship analysis shows that hinged knee prostheses, when they are biomechanically well designed, can yield a satisfactory long-term outcome, similar to those of the best prostheses of the resurfacing type. Hinged knee prostheses continue to be of value in patients with severe deformity or instability of the knee.

We compared the prognostic value of the Catterall grouping, the Salter-Thompson grading, the arthrographic shape of the femoral head, and the Herring lateral pillar grouping during the fragmentation stage of Perthes’ disease in 73 patients with 81 affected hips. Radiographs were available for study from the onset of the disease until skeletal maturity. We used the Stulberg classification to assess outcome.

The Herring grade and arthrographic sphericity proved to be the best predictors of final outcome. Combining these two values further increased the predictive value. All but one patient in Herring group A achieved an excellent outcome. In Herring group B, the age of the child and the sphericity of the femoral head influenced the end result. If the child was less than seven years old at the onset of symptoms the prognosis was invariably good and all spherical hips in group B had a good outcome with Stulberg grades 1 or 2. Moderately and severely deformed hips on arthrography resulted in Stulberg 3 and 4 hips. None of the hips in Herring group C had a normal appearance at maturity and the outcome was not significantly influenced by the age at onset or the arthrographic appearance.

We examined 50 patients with diastrophic dysplasia both clinically and radiologically. Two legally aborted fetuses were dissected. The mean age of the patients was 16.2 years (newborn to 38) and the mean follow-up was 11.4 years (3 months to 34 years).

The fetal hips and MRI of newborn infants showed congruity and no significant joint deformity. Flexion contracture of the hip became evident later in 93% and was progressive. The radiological appearance of the proximal femoral ossific nuclei was delayed and in 17% of males and 28% of females the ossific nuclei had not appeared by the age of 12 years.

Radiological measurements differed considerably from reference values and were related to the rapid and progressive restriction of rotational movement and the increase in flexion contracture. The typical findings were flattening and inferomedial bulking of the femoral head and a double-hump deformation. The changes in the hip led to secondary osteoarthritis before early middle age. We describe the clinical and radiological measurements which define the early degeneration of the joint.

Ultrasonography of the hip was performed sequentially by two different examiners in 75 infants. The ultrasound strips were reviewed twice by three paediatric orthopaedic surgeons and classified by the Graf method. The intraobserver and interobserver agreement between the interpretations was analysed using simple and weighted kappa coefficients calculated for agreement on the Graf classification and for grouping as normal (types 1A to 2A), and abnormal requiring treatment (types 2B to 4).

When examining the same ultrasound strip, intraobserver agreement for the Graf classification was substantial (mean kappa 0.61), but interobserver agreement was only moderate (kappa 0.50).

For the grouping into normal and abnormal, the mean kappa value for intraobserver agreement was 0.67 and for interobserver agreement 0.57. Because of the significant differences in agreement between normal and abnormal hips, we analysed a subgroup of those with at least one abnormal interpretation. Intraobserver agreement within this subgroup showed moderate reliability (kappa 0.41), but interobserver agreement was only fair (kappa 0.28).

Interpretations of two different strips performed sequentially showed significantly lower agreement with an intraobserver kappa value of 0.29 and an interobserver value of 0.28. In the subgroup with at least one abnormal reading, the intraobserver kappa was 0.09 and the interobserver 0.1.

Our findings suggest that both the technique of performing ultrasonography and the interpretation of the image may influence the result.

Recurrent dislocation of peroneal tendons is uncommon and there are few reports of the long-term results after repair. The Singapore operation, first described in 1985, is an anatomical repair based on the Bankart-like lesion seen in the superior peroneal retinaculum.

We reviewed 21 patients after a mean follow-up of 9.3 years, and found no recurrence. Eighteen had good functional results and had returned to their previous levels of vocational and sports activities. The three fair results were due to painful scars or neuromas.

We performed 52 cemented ankle arthroplasties for painful osteoarthritis (OA) (25) or rheumatoid arthritis (RA) (27) using an ankle prosthesis with a near-anatomical design.

We assessed the patients radiologically and clinically for up to 14 years using an ankle scoring system. The preoperative median scores were 29 for the OA group and 25 for the RA group and at ten years were 93.5 and 83, respectively. Six ankles in the OA group and five in the RA group required revision or arthrodesis.

Survivorship analysis of the two groups showed no significant differences with 72.7% survival for the OA group and 75.5% for the RA group at 14 years.

Between 1985 and 1994, 1223 patients with malleolar fractures of the ankle were treated by open reduction and internal fixation with absorbable pins and screws, of whom 74 (6.1%) had an obvious inflammatory foreign-body reaction to the implants. Of these 74, ten later developed moderate to severe osteoarthritis of the ankle despite no evidence of incongruity of the articular surface. The implants used in these patients were made from polyglycolide, polylactide or glycolidelactide copolymer.

The joint damage seemed to be due to polymeric debris entering the articular cavity through an osteolytic extension of an implant track. The ten patients had a long clinical course which included a vigorous local foreign-body reaction, synovial irritation and subsequent degeneration. At a follow-up of three to nine years, ankle arthrodesis had been necessary in two patients and is being considered for another two.

The incidence of these changes in the whole series was 0.8%, which is not high, but awareness of this possible late complication is essential.

Ultra-high-molecular-weight polyethylene (UHMWPE) components for total joint replacement generate wear particles which cause adverse biological tissue reactions leading to osteolysis and loosening. Sterilisation of UHMWPE components by gamma irradiation in air causes chain scissions which initiate a long-term oxidative process that degrades the chemical and mechanical properties of the polyethylene. Using a tri-pin-on-disc tribometer we studied the effect of ageing for ten years after gamma irradiation in air on the volumetric wear, particle size distribution and the number of particles produced by UHMWPE when sliding against a stainless-steel counterface.

The aged and irradiated material produced six times more volumetric wear and 34 times more wear particles per unit load per unit sliding distance than non-sterilised UHMWPE. Our findings indicate that oxidative degradation of polyethylene after gamma irradiation in air with ageing produces more wear.

We used radiostereometric analysis to compare wear rates between uncemented porous sockets and cemented all-polyethylene sockets in a series of 102 hips randomised for either a Harris-Galante or a Charnley cup. Wear was evaluated in 95 hips at a mean of five years (2 to 7). All hips had a cemented, 22 mm head mono-bloc Charnley stem.

The mean annual wear rate was 0.09 mm in the Charnley sockets and 0.10 mm in the Harris-Galante sockets, with no statistically significant differences in wear, migration or rotation.

We conclude that, up to five years, the wear characteristics of the modular and porous Harris-Galante socket resemble that of the Charnley socket.

We performed a biomechanical study on human cadaver spines to determine the effect of three different interbody cage designs, with and without posterior instrumentation, on the three-dimensional flexibility of the spine. Six lumbar functional spinal units for each cage type were subjected to multidirectional flexibility testing in four different configurations: intact, with interbody cages from a posterior approach, with additional posterior instrumentation, and with cross-bracing. The tests involved the application of flexion and extension, bilateral axial rotation and bilateral lateral bending pure moments. The relative movements between the vertebrae were recorded by an optoelectronic camera system.

We found no significant difference in the stabilising potential of the three cage designs. The cages used alone significantly decreased the intervertebral movement in flexion and lateral bending, but no stabilisation was achieved in either extension or axial rotation. For all types of cage, the greatest stabilisation in flexion and extension and lateral bending was achieved by the addition of posterior transpedicular instrumentation. The addition of cross-bracing to the posterior instrumentation had a stabilising effect on axial rotation. The bone density of the adjacent vertebral bodies was a significant factor for stabilisation in flexion and extension and in lateral bending.

Previous studies of the Ilizarov procedure have concentrated on musculoskeletal assessments rather than the opinions of patients. In a prospective trial of 25 consecutive patients, we evaluated the effect of Ilizarov reconstruction of post-traumatic deformity on general health status using the SF36 and Nottingham Health Profile (NHP).

The patients had very low preoperative scores, which remained low during treatment and correction, but increased postoperatively. The mean overall SF36 score improved from 36 ± 3 to 58 ± 7 (p = 0.031) and the NHP score from 39 ± 11 to 67 ± 10 (p = 0.002). The improvements in scores were not limited to the physical components and were equal or better than the improvements reported for other orthopaedic procedures, including total joint arthroplasty.

Ilizarov-type reconstruction of deformity of the lower limb not only restores bony configuration, but also produces a large improvement in the general health status of patients.

Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia of muscle. We have attempted to use the direct measurement of muscle blood flow for diagnosis since the assessment of intracompartmental pressure does not provide accurate knowledge of the vascular state. We recorded simultaneously continuous measurements of the laser Doppler flow (LDF) in muscle and the intracompartment pressure (ICP) after exercise in seven patients with CCS, and in seven control subjects.

The mean ICP was 74.1 ± 4.4 mmHg in CCS patients and 24.2 ± 3.4 mmHg in control subjects one minute after exercise, decreasing to 34.6 ± 2.3 mmHg and 15.0 ± 1.6 mmHg at 20 min, respectively. The LDF was 0.80 ± 0.11 arbitrary units (AU) in control subjects and 1.09 ± 0.14 AU in CCS patients one minute after exercise, and 0.41 ± 0.11 AU and 0.27 ± 0.04 AU, respectively, at the end of the recovery period.

The ICP showed a progressive decrease over time in both groups. The LDF decreased sharply during the first minutes of recovery in control subjects, but in patients with CCS there was a delayed hyperaemic peak with blood flow reaching 0.84 ± 0.10 AU at nine minutes as against 0.33 ± 0 .06 AU for control subjects (p < 0.01). The ICP increased in both control subjects and CCS patients after exercise with no clear cut-off point between the groups. By contrast, changes in muscle blood flow over time were clearly different between control subjects and patients with CCS.

For this reason, LDF should be investigated further as a technique for the diagnosis of CCS.