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The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 88 - 96
1 Jan 2016
Tsirikos AI Sud A McGurk SM

Aims. We reviewed 34 consecutive patients (18 female-16 male) with isthmic spondylolysis and grade I to II lumbosacral spondylolisthesis who underwent in situ posterolateral arthodesis between the L5 transverse processes and the sacral ala with the use of iliac crest autograft. Ten patients had an associated scoliosis which required surgical correction at a later stage only in two patients with idiopathic curves unrelated to the spondylolisthesis. . Methods. No patient underwent spinal decompression or instrumentation placement. Mean surgical time was 1.5 hours (1 to 1.8) and intra-operative blood loss 200 ml (150 to 340). There was one wound infection treated with antibiotics but no other complication. Radiological assessment included standing posteroanterior and lateral, Ferguson and lateral flexion/extension views, as well as CT scans. . Results. A solid posterolateral fusion was confirmed in all patients at mean latest follow-up of 4.7 years (3.4 to 9.8) beyond skeletal maturity into early adult life. Fusion of the isthmic lesion was documented in nine patients bilaterally and eight patients unilaterally. The poor fusion rate across the spondylolysis has not affected the excellent functional results of the procedure, which in our series depended on achieving a stable lumbosacral junction. . Conclusion. Quality of life assessment demonstrated significant improvement in all functional scores and high patient satisfaction with 28 patients returning to previous sports activities at an elite competitive level. Take home message: Posterolateral arthrodesis in situ with autologous iliac crest bone without instrumentation has achieved a solid fusion between the L5 transverse processes and the sacral ala in patients with grade I to II isthmic lumbosacral spondylolisthesis and this has produced excellent clinical outcomes and high patient satisfaction. Cite this article: Bone Joint J 2016;98-B:88–96


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1352 - 1356
1 Oct 2008
Suh KT Park WW Kim S Cho HM Lee JS Lee JS

Between March 2000 and February 2006, we carried out a prospective study of 100 patients with a low-grade isthmic spondylolisthesis (Meyerding grade II or below), who were randomised to receive a single-level and instrumented posterior lumbar interbody fusion with either one or two cages. The minimum follow-up was for two years. At this stage 91 patients were available for review. A total of 47 patients received one cage (group 1) and 44 two cages (group 2). The clinical and radiological outcomes of the two groups were compared. There were no significant differences between the two groups in terms of post-operative pain, Oswestry Disability Score, clinical results, complication rate, percentage of post-operative slip, anterior fusion rate or posterior fusion rate. On the other hand, the mean operating time was 144 minutes (100 to 240) for patients in group 1 and 167 minutes (110 to 270) for those in group 2 (p = 0.0002). The mean blood loss up to the end of the first post-operative day was 756 ml (510 to 1440) in group 1 and 817 ml (620 to 1730) in group 2 (p < 0.0001). Our results suggest that an instrumented posterior lumbar interbody fusion performed with either one or two cages in addition to a bone graft around the cage has a low rate of complications and a high fusion rate. The clinical outcomes were good in most cases, regardless of whether one or two cages had been used


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXI | Pages 4 - 4
1 Jul 2012
Ekman P Möller H Hedlund R
Full Access

Study design. A prospective study on predictive factors for the outcome of 164 patients with adult isthmic spondylolisthesis operated on with fusion between 1990 and 2003. Purpose. In view of the need to better select patients for fusion we investigated the use of the pain drawing (PD) and other potential factors for predicting the outcome of fusion. Background. Results on predictive factors of outcome after spinal fusion have been contradictory and large, well defined, patient samples with adequate observation times are lacking. Methods. QuestionnairesF including possible predictive factors as well as PDs were obtained preoperatively. Degree and level of slip were documented. Outcome was quantified by measurement of pain (VAS), Disability Rating Index (DRI), the Oswestry Disability Index and global assessment by the patient into “much better”, “better”, “unchanged” or “worse”. The 2-year follow up rate was 160/164 (98%). Results. In the total sample 49% of patients were much better, 25% better, 14% unchanged and 12% worse. Most factors investigated did not correlate with the outcome including; degree of slip, level of slip, fusion technique, age, smoking, drinking habits, weight, BMI, sciatica, laminectomy, marital status, level of education, type of domicile, possible immigrant status, dominant hand, births and number of children. The following preoperative factors correlated to a worse outcome in the univariate analysis: Not working, no regular exercise, female gender, shortness in stature and a non-organic PD. The multivariate regression analysis showed that work status was the main determinant of outcome. Gender and exercise had less but significant impact (p=0.004 and 0.02, respectively), whereas the PD was of borderline significance (p=0.06). These factors, however, explained only 22% of the variability of outcome. Conclusion. Prediction of outcome after fusion is difficult. Only a limited number of predictive factors were identified, with working preoperatively being the strongest predictor. Also male gender and regular exercise are indicators of a better outcome. Female patients not working, not exercising, or with a non-organic pain drawing, should be informed about their suboptimal chances of an excellent outcome after fusion


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXI | Pages 31 - 31
1 Jul 2012
Schlenzka D Ylikoski M Yrjönen T Lund T Österman H Laine T Poussa M
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The purpose was to analyze preoperative symptoms, curve characteristics, and outcome of surgery in patients operated on for isthmic spondylolisthesis with concomitant scoliosis. Overall, 151(9.1%) of 1667 scoliosis patients had spondylolisthesis treated surgically in 21 (13.9%)(19 females, 2 males; 11 low-, 10 high-grade). Patients' age at admission was 13.5(10-17)y. Preoperatively, 5/21 were pain-free (1 high-grade, 4 low-grade), 7 (2 high-grade) had LBP, 2 (both high-grade) radiating pain, and 7 (5 high-grade) had both. Hamstring tightness was present in 5/10 high-grades. Scoliosis was primary thoracic in 3/11 low-grade and secondary lumbar with oblique rotated take-off of L5 in 8/11 low-grade patients. Of the high-grades, 7/10 had sciatic curves and 3 secondary lumbar. In low-grades, the main indication for surgery was pain in 3/11 and lumbar curve progression or the intent to prevent it in 7/11. The operative technique was uninstrumented posterolateral fusion in 8/11, instrumented L4-S1 fusion with reduction of L4-tilt in 2, and direct repair in 1 patient. High-grades were fused to prevent further slipping regardless of subjective symptoms (uninstrumented anterior 5, combined 2, instrumented reduction 3). Selective thoracic fusion for scoliosis was performed in 3 patients. None of the lumbar curves needed fusion. All sciatic curves resolved. The follow-up time was 10.6(2-21)y. Of the low-grade patients, 5 were pain-free, 4 had moderate pain, and 2 had a severe chronic pain syndrome. One had broken pedicle screws without sequelae. Of the high-grade patients, 4 were pain-free, 6 had moderate pain. One had a pain-free peroneal weakness after slip reduction


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 240 - 244
1 Mar 1999
Ishida Y Ohmori K Inoue H Suzuki K

We reviewed the radiographs of 325 unselected patients with defects in the pars interarticularis of L5 to study whether the incidence of vertebral slip in spondylolysis of L5 remained unchanged after the age of 20 years. MRI was also carried out on 111 of the patients to investigate the relationship between the shape of the transverse process of L5 and the degeneration of the discs adjacent to this level. The incidence of spondylolisthesis increased with age from 17% in the second decade to 51% in the sixth. The transverse process was significantly more slender in patients with less degeneration at L4/5 and advanced degeneration at L5/S1 than in patients with advanced degeneration at L4/5 and less degeneration at L5/S1. Vertebral slip secondary to an isthmic defect of L5 after the age of 20 years was confirmed and the adjacent disc degeneration was significantly related to the vertical thickness of the transverse process of L5


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 115 - 115
1 Apr 2012
Rajagopal T Marshall R McKenzie J Archibald C
Full Access

Retrospective analysis of radiology reports of conventional MRI in 100 patients with definite spinal stenosis to determine the incidence of reported “foraminal stenosis”. Prospective study of MRI including T2 coronal and T2 STIR coronal sequences in 57 patients with suspected stenosis. Three surgeons and one radiologist independently compared the diagnoses on conventional and coronal scans. Patients with suspected spinal stenosis undergoing MRI. Incidence of “foraminal stenosis” on radiologists' reports. Diagnoses obtained by different scanning methods. Retrospective analysis: “foraminal stenosis” called by radiologists in 46% using conventional axial and sagittal sequences. Prospective study - 57 patients: conventional sequences diagnosed lateral recess stenosis well but also suggested foraminal stenosis in 33%. However, coronal sequences clearly showed no foraminal nerve compression. In degenerative spondylolisthesis conventional scans suggested foraminal stenosis in 8 of 11 cases. Coronals showed no foraminal stenosis. Excellent correlation was found in normal spines and in disc herniation. In far lateral disc herniation and isthmic spondylolisthesis, true foraminal stenosis was confirmed by conventional and coronal imaging. Additional coronal MRI sequences prove that foraminal stenosis is over-diagnosed and is rare in spinal stenosis, but true foraminal nerve compression occurs in isthmic spondylolisthesis and far lateral disc herniation


Bone & Joint Open
Vol. 4, Issue 8 | Pages 573 - 579
8 Aug 2023
Beresford-Cleary NJA Silman A Thakar C Gardner A Harding I Cooper C Cook J Rothenfluh DA

Aims

Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.

Methods

As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 543 - 550
1 May 2023
Abel F Avrumova F Goldman SN Abjornson C Lebl DR

Aims

The aim of this study was to assess the accuracy of pedicle screw placement, as well as intraoperative factors, radiation exposure, and complication rates in adult patients with degenerative disorders of the thoracic and lumbar spines who have undergone robotic-navigated spinal surgery using a contemporary system.

Methods

The authors reviewed the prospectively collected data on 196 adult patients who had pedicle screws implanted with robot-navigated assistance (RNA) using the Mazor X Stealth system between June 2019 and March 2022. Pedicle screws were implanted by one experienced spinal surgeon after completion of a learning period. The accuracy of pedicle screw placement was determined using intraoperative 3D fluoroscopy.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 662 - 670
9 Aug 2024
Tanaka T Sasaki M Katayanagi J Hirakawa A Fushimi K Yoshii T Jinno T Inose H

Aims

The escalating demand for medical resources to address spinal diseases as society ages is an issue that requires careful evaluation. However, few studies have examined trends in spinal surgery, especially unscheduled hospitalizations or surgeries performed after hours, through large databases. Our study aimed to determine national trends in the number of spine surgeries in Japan. We also aimed to identify trends in after-hours surgeries and unscheduled hospitalizations and their impact on complications and costs.

Methods

We retrospectively investigated data extracted from the Diagnosis Procedure Combination database, a representative inpatient database in Japan. The data from April 2010 to March 2020 were used for this study. We included all patients who had undergone any combination of laminectomy, laminoplasty, discectomy, and/or spinal arthrodesis.


Bone & Joint Open
Vol. 2, Issue 3 | Pages 163 - 173
1 Mar 2021
Schlösser TPC Garrido E Tsirikos AI McMaster MJ

Aims

High-grade dysplastic spondylolisthesis is a disabling disorder for which many different operative techniques have been described. The aim of this study is to evaluate Scoliosis Research Society 22-item (SRS-22r) scores, global balance, and regional spino-pelvic alignment from two to 25 years after surgery for high-grade dysplastic spondylolisthesis using an all-posterior partial reduction, transfixation technique.

Methods

SRS-22r and full-spine lateral radiographs were collected for the 28 young patients (age 13.4 years (SD 2.6) who underwent surgery for high-grade dysplastic spondylolisthesis in our centre (Scottish National Spinal Deformity Service) between 1995 and 2018. The mean follow-up was nine years (2 to 25), and one patient was lost to follow-up. The standard surgical technique was an all-posterior, partial reduction, and S1 to L5 transfixation screw technique without direct decompression. Parameters for segmental (slip percentage, Dubousset’s lumbosacral angle) and regional alignment (pelvic tilt, sacral slope, L5 incidence, lumbar lordosis, and thoracic kyphosis) and global balance (T1 spino-pelvic inclination) were measured. SRS-22r scores were compared between patients with a balanced and unbalanced pelvis at final follow-up.


The Bone & Joint Journal
Vol. 101-B, Issue 12 | Pages 1526 - 1533
1 Dec 2019
Endler P Ekman P Berglund I Möller H Gerdhem P

Aims

Chronic low back pain due to degenerative disc disease is sometimes treated with fusion. We compared the outcome of three different fusion techniques in the Swedish Spine Register: noninstrumented posterolateral fusion (PLF), instrumented posterolateral fusion (IPLF), and interbody fusion (IBF).

Patients and Methods

A total of 2874 patients who were operated on at one or two lumbar levels were followed for a mean of 9.2 years (3.6 to 19.1) for any additional lumbar spine surgery. Patient-reported outcome data were available preoperatively (n = 2874) and at one year (n = 2274), two years (n = 1958), and a mean of 6.9 years (n = 1518) postoperatively and consisted of global assessment and visual analogue scales of leg and back pain, Oswestry Disability Index, EuroQol five-dimensional index, 36-Item Short-Form Health Survey, and satisfaction with treatment. Statistical analyses were performed with competing-risks proportional hazards regression or analysis of covariance, adjusted for baseline variables.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1359 - 1367
3 Oct 2020
Hasegawa K Okamoto M Hatsushikano S Watanabe K Ohashi M Vital J Dubousset J

Aims

The aim of this study is to test the hypothesis that three grades of sagittal compensation for standing posture (normal, compensated, and decompensated) correlate with health-related quality of life measurements (HRQOL).

Methods

A total of 50 healthy volunteers (normal), 100 patients with single-level lumbar degenerative spondylolisthesis (LDS), and 70 patients with adult to elderly spinal deformity (deformity) were enrolled. Following collection of demographic data and HRQOL measured by the Scoliosis Research Society-22r (SRS-22r), radiological measurement by the biplanar slot-scanning full body stereoradiography (EOS) system was performed simultaneously with force-plate measurements to obtain whole body sagittal alignment parameters. These parameters included the offset between the centre of the acoustic meatus and the gravity line (CAM-GL), saggital vertical axis (SVA), T1 pelvic angle (TPA), McGregor slope, C2-7 lordosis, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), PI-LL, sacral slope (SS), pelvic tilt (PT), and knee flexion. Whole spine MRI examination was also performed. Cluster analysis of the SRS-22r scores in the pooled data was performed to classify the subjects into three groups according to the HRQOL, and alignment parameters were then compared among the three cluster groups.


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1115 - 1121
1 Sep 2019
Takenaka S Makino T Sakai Y Kashii M Iwasaki M Yoshikawa H Kaito T

Aims

The aim of this study was to explore risk factors for complications associated with dural tear (DT), including the types of DT, and the intra- and postoperative management of DT.

Patients and Methods

Between 2012 and 2017, 12 171 patients with degenerative lumbar diseases underwent primary lumbar spine surgery. We investigated five categories of potential predictors: patient factors (sex, age, body mass index, and primary disease), surgical factors (surgical procedures, operative time, and estimated blood loss), types of DT (inaccessible for suturing/clipping and the presence of cauda equina/nerve root herniation), repair techniques (suturing, clipping, fibrin glue, polyethylene glycol (PEG) hydrogel, and polyglycolic acid sheet), and postoperative management (drainage duration). Postoperative complications were evaluated in terms of dural leak, prolonged bed rest, headache, nausea/vomiting, delayed wound healing, postoperative neurological deficit, surgical site infection (SSI), and reoperation for DT. We performed multivariable regression analyses to evaluate the predictors of postoperative complications associated with DT.


The Bone & Joint Journal
Vol. 99-B, Issue 10 | Pages 1366 - 1372
1 Oct 2017
Rickert M Fleege C Tarhan T Schreiner S Makowski MR Rauschmann M Arabmotlagh M

Aims

We compared the clinical and radiological outcomes of using a polyetheretherketone cage with (TiPEEK) and without a titanium coating (PEEK) for instrumented transforaminal lumbar interbody fusion (TLIF).

Materials and Methods

We conducted a randomised clinical pilot trial of 40 patients who were scheduled to undergo a TLIF procedure at one or two levels between L2 and L5. The Oswestry disability index (ODI), EuroQoL-5D, and back and leg pain were determined pre-operatively, and at three, six, and 12 months post-operatively. Fusion rates were assessed by thin slice CT at three months and by functional radiography at 12 months.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 229 - 237
1 Feb 2016
Roberts SB Dryden R Tsirikos AI

Aims

Clinical and radiological data were reviewed for all patients with mucopolysaccharidoses (MPS) with thoracolumbar kyphosis managed non-operatively or operatively in our institution.

Methods

In all 16 patients were included (eight female: eight male; 50% male), of whom nine had Hurler, five Morquio and two Hunter syndrome. Six patients were treated non-operatively (mean age at presentation of 6.3 years; 0.4 to 12.9); mean kyphotic progression +1.5o/year; mean follow-up of 3.1 years (1 to 5.1) and ten patients operatively (mean age at presentation of 4.7 years; 0.9 to 14.4); mean kyphotic progression 10.8o/year; mean follow-up of 8.2 years; 4.8 to 11.8) by circumferential arthrodesis with posterior instrumentation in patients with flexible deformities (n = 6).


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 555 - 559
1 Apr 2010
Deguchi M Shinjo R Yoshioka Y Seki H

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13.

In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six.

We concluded that SAA is better than CRP as a post-operative inflammatory marker.


We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration.

There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

Cite this article: Bone Joint J 2013;95-B:1239–43.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1244 - 1249
1 Sep 2013
Jeon C Park J Chung N Son K Lee Y Kim J

We investigated the spinopelvic morphology and global sagittal balance of patients with a degenerative retrolisthesis or anterolisthesis. A total of 269 consecutive patients with a degenerative spondylolisthesis were included in this study. There were 95 men and 174 women with a mean age of 64.3 years (sd 10.5; 40 to 88). A total of 106 patients had a pure retrolisthesis (R group), 130 had a pure anterolisthesis (A group), and 33 had both (R+A group).

A backward slip was found in the upper lumbar levels (mostly L2 or L3) with an almost equal gender distribution in both the R and R+A groups. The pelvic incidence and sacral slope of the R group were significantly lower than those of the A (both p < 0.001) and R+A groups (both p < 0.001). The lumbar lordosis of the R+A group was significantly greater than that of the R (p = 0.025) and A groups (p = 0.014). The C7 plumb line of the R group was located more posteriorly than that of the A group (p = 0.023), but was no different from than that of the R+A group (p = 0.422). The location of C7 plumb line did not differ between the three groups (p = 0.068). The spinosacral angle of the R group was significantly smaller than that of the A group (p < 0.001) and R+A group (p < 0.001).

Our findings imply that there are two types of degenerative retrolisthesis: one occurs primarily as a result of degeneration in patients with low pelvic incidence, and the other occurs secondarily as a compensatory mechanism in patients with an anterolisthesis and high pelvic incidence.

Cite this article: Bone Joint J 2013;95-B:1244–9.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 73 - 77
1 Jan 2011
Altaf F Osei NA Garrido E Al-Mukhtar M Natali C Sivaraman A Noordeen HH

We describe the results of a prospective case series of patients with spondylolysis, evaluating a technique of direct stabilisation of the pars interarticularis with a construct that consists of a pair of pedicle screws connected by a U-shaped modular link passing beneath the spinous process. Tightening the link to the screws compresses bone graft in the defect in the pars, providing rigid intrasegmental fixation. We have carried out this procedure on 20 patients aged between nine and 21 years with a defect of the pars at L5, confirmed on CT. The mean age of the patients was 13.9 years (9 to 21). They had a grade I or less spondylolisthesis and no evidence of intervertebral degeneration on MRI. The mean follow-up was four years (2.3 to 7.3). The patients were assessed by the Oswestry Disability Index (ODI) and a visual analogue scale (VAS). At the latest follow-up, 18 patients had an excellent clinical outcome, with a significant (p < 0.001) improvement in their ODI and VAS scores. The mean ODI score at final follow-up was 8%. Assessment of the defect by CT showed a rate of union of 80%. There were no complications involving the internal fixation.

The strength of the construct removes the need for post-operative immobilisation.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1478 - 1481
1 Nov 2007
Aono H Ohwada T Kaneko N Fuji T Iwasaki M

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth.

We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion.

The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection.