Short-course antibiotic treatment of bone and joint infections in children: a retrospective study at Montpellier University Hospital from 2009 to 2013.

BACKGROUND: Acute haematogenous bone and joint infections (AHBJI) represent a diagnostic and therapeutic emergency in children, with significant potential sequelae in the case of delayed treatment. Although historically the recommendations for treatment have been based on surgery and prolonged antibiotic therapy, recent studies have demonstrated that short-course antibiotic therapy is also effective. OBJECTIVES: We evaluated a short-term antibiotic protocol for both osteomyelitis and septic arthritis in a 6 year retrospective study at the University Hospital of Montpellier. METHODS: This protocol was based on an initial intravenous treatment with a re-evaluation after 48 h and an early switch to oral therapy in the case of a favourable clinical course for a minimum total duration of 15 days. Antibiotics were selected based on local microbiological epidemiology and systematically adapted to bacteriological results. RESULTS: One hundred and seventy-six cases of AHBJI were included, comprising 56 patients with osteomyelitis, 95 with septic arthritis and 25 who had both of these. The aetiological agent was identified in 42% of the cases, with the main pathogens being Staphylococcus aureus (39%) and Kingella kingae (27%). The mean intravenous treatment duration was 4 days, while the total treatment duration was 15 days. There were no treatment failures, mild sequelae occurred in 1% of the cases and the secondary surgical revision rate was 7%. CONCLUSIONS: The results of this study are comparable to those reported for evaluations of prolonged antibiotic therapy protocols, thus indicating that a common short-term antimicrobial therapy for the management of both osteomyelitis and septic arthritis (minimum of 15 days) is a viable option for treating AHBJI in children. Further prospective studies to confirm these findings are hence warranted.

A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication.

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

An undetectable polymerase chain reaction signal in routine HIV plasma viral load monitoring is associated with better virological outcomes in patients receiving highly active antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess whether patients with undetectable viraemia [a negative polymerase chain reaction result (PCR(neg) )] and those with plasma viral load (PVL) < 40 HIV-1 RNA copies/mL but a detectable (positive) PCR signal (PCR(pos) ) had different outcomes in terms of the development of blips and virological failure (VF). METHODS: A multicentre observational database analysis was carried out. Data for patients whose highly active antiretroviral therapy (HAART) regime had been unchanged for ≥ 6 months by 1 January 2008, whose first two PVL measurements of 2008 were < 40 copies/mL and who had at least five PVL measurements between 1 January 2008 and 31 December 2010 were extracted from a multicentre observational database of 4928 patients receiving HAART. PVL assays used during this period had a detection threshold of 20 or 40 copies/mL. Undetectable PVL at baseline (BL PCR(neg) ) was defined as PCR(neg) at the first two PVL determinations of 2008. Multivariable Cox regression analysis was performed to investigate factors associated with the occurrence of blips and VF, defined as two consecutive PVL measurements > 40 copies/mL. RESULTS: Of the 1957 patients included in the study (mean age 47 years; median antiretroviral exposure 10.3 years), 1312 had BL PCR(neg) . Outcome events included 322 blips and 139 VFs, with incidence rates being significantly lower in patients with BL PCR(neg) than in those with BL PCR(pos) [13.0% vs. 23.4% (P < 0.0001) and 5.1% vs. 11.2% (P < 0.0001), respectively]. In multivariable analysis, BL PCR(neg) was associated with a reduced risk of blips [hazard ratio (HR) 0.58; 95% confidence interval (CI) 0.47-0.73; P < 0.0001] and VF (HR 0.44; 95% CI 0.31-0.62; P < 0.0001). CONCLUSIONS: Patients with PCR(neg) had better virological outcomes than those with PVL < 40 copies/mL but detectable viraemia. This suggests that the 'no-signal' information provided by currently commercially available HIV RNA quantification assays should be used routinely.

The suppression of immune activation during enfuvirtide-based salvage therapy is associated with reduced CCR5 expression and decreased concentrations of circulating interleukin-12 and IP-10 during 48 weeks of longitudinal follow-up.

BACKGROUND: It has been suggested that patients who initiate highly active antiretroviral therapy (HAART) late in their course of infection may have suboptimal CD4 T-cell gains, persistent alterations in T-cell subsets and residual inflammation. To address this issue, we carried out a comprehensive 48-week immunological study in HIV-infected patients who had experienced failures of prior therapies, had low CD4 cell counts, and were receiving enfuvirtide-based salvage therapy. METHODS: Immunological monitoring of peripheral lymphocytes from enfuvirtide-responder patients was performed over a 48-week period. A detailed assessment of immune cell subsets, their activation state [CD38 and human leucocyte antigen (HLA)-DR expression] and homeostasis [activation-induced cell death (AICD) and Ki67 expression], and the expression of co-receptors was performed by flow cytometry. Cytokine and chemokine signatures were assessed using multianalyte profiling technology. RESULTS: Enfuvirtide-based salvage therapy induced a progressive restoration of naïve and central memory CD4 T cells, associated with a decrease in their activation state, suppression of premature priming for AICD and increased expression of Ki67. In addition, a significant decrease in C-C chemokine receptor 5 (CCR5) expression was detected on CD4 T cells, which was strongly correlated with the suppression of immune activation. Changes in circulating proinflammatory molecules occurred; i.e. there were decreases in the concentrations of interleukin (IL)-12, macrophage inflammatory protein MIP-1α, MIP-1ß, monokine induced by IFNγ (MIG) and interferon-γ-inducible protein-10 (IP-10). The decline in circulating IL-12 and IP-10 was correlated with both the reduction in the viral load and CD4 T-cell restoration. CONCLUSIONS: This study shows that suppression of HIV-1 replication with enfuvirtide-based salvage therapy in patients with low CD4 cell counts may result in an immunological benefit, characterized by the restoration of CD4 T-cell subsets associated with decreased immune activation and suppression of inflammation.

Fingertip nail bed injuries in children: Comparison of suture repair versus glue (2-octylcyanoacrylate) with 1-year follow-up.

The main objective of this study was to compare the medium-term results of nail bed repair in children using glue (2-octylcyanoacrylate) versus absorbable sutures. The secondary objective was to compare the results of treatment in the emergency room versus the operating room. This retrospective review of 74 fingertip nail bed lacerations (68 children) evaluated the appearance and pain at the last follow-up visit (minimum of 1 year), and the operating time. Mean age was 3.3 years at time of injury (range 10 months-13 years), with a mean follow-up of 2.6 (1-7) years. Thirty-six nail beds were repaired with glue; 38 were sutured. The clinical outcomes in the two groups were similar. The rate of nail dystrophy was 14% (5% major) regardless of the technique. Nail bed repair time was significantly shorter in the glue group (10.2 vs. 20.3min, p<0.001). Forty-five repairs were performed in the operating room and 29 in the emergency room. The complication rate (early infections) was significantly higher in patients treated in the emergency room. Tissue adhesive (2-octylcyanoacrylate glue) is a reliable option for repairing nail bed lacerations, both in terms of outcomes and speed of repair. Treatment in the operating room is preferable.

Effects of marine noise pollution on Mediterranean fishes and invertebrates: A review.

Marine noise pollution (MNP) can cause a multitude of impacts on many organisms, but information is often scattered and general outcomes difficult to assess. We have reviewed the literature on MNP impacts on Mediterranean fish and invertebrates. Both chronic and acute MNP produced by various human activities - e.g. maritime traffic, pile driving, air guns - were found to cause detectable effects on intra-specific communication, vital processes, physiology, behavioral patterns, health status and survival. These effects on individuals can extend to inducing population- and ecosystem-wide alterations, especially when MNP impacts functionally important species, such as keystone predators and habitat forming species. Curbing the threats of MNP in the Mediterranean Sea is a challenging task, but a variety of measures could be adopted to mitigate MNP impacts. Successful measures will require more accurate information on impacts and that effective management of MNP really becomes a priority in the policy makers' agenda.

Bridging the gap between adult and paediatric outcomes in HIV-1 vertically infected children: a single-centre comparison with adult data.

UNLABELLED: Prognosis of HIV-1 infection dramatically improved during the last decade. Meanwhile, treatment-induced virological success has always been different in adult and children patients. AIM: To compare 10 years of follow up in HIV-1 vertically infected children and adult patients. METHODS: Monocentric retrospective longitudinal analysis of vertically HIV-1-infected children and adult patients followed in the Nice University Hospital between 1999 and 2008. Immunological, virological and antiretroviral treatment data were recorded. RESULTS: Forty children and 1752 adult patients were included. Between 1996 and 2008, the percentage of children receiving HAART increased from 3.2% to 91%. Mean CD4% in the paediatric group remained stable between 29 +/- 8.1% in 1998 and 30 +/- 9.4% in 2008. Mean adult CD4-cell count significantly increased from 410 in 1998 to 556 cells/mL in 2008. Logistic regression analysis showed that the children-to-adult difference for indetectability (HIV PCR-RNA below 400 copies/mL) was significant (p < 0.0001) with an odds ratio of 0.61 (CI(95th): 0.52-0.72). Year-to-patient interaction was also significant with a decreasing divergence over time (p: 0.038). CONCLUSION: Nowadays as in adult patients, the control of HIV-1 replication is achieved in nearly eight of 10 children and the percentage of patients with severe immunodeficiency dramatically decreased compared with the mid 1990s.

Median Nerve Entrapment after Supracondylar Humeral Fracture in a Young Child.

Median nerve entrapment after supracondylar humeral fracture in children is rare. We report a case of Gartland type III supracondylar humeral fracture complicated by an entrapment of the median nerve following closed reduction and percutaneous pinning in a 5-year-old child. The diagnosis of entrapment was made 14 months post injury following progressive motor and sensory palsy. Resection and end-to-end suture were performed, leading to complete sensory and motor recovery eight months later. This nerve complication is often unnoticed and should be suspected systematically before and after reduction of all displaced supracondylar humeral fracture in children. The indication of resection-suture or nerve graft depends on the entrapment and the delay of the palsy.

Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir.

BACKGROUND: We developed clinically relevant genotypic scores for resistance to fosamprenavir/ritonavir in HIV-1 protease inhibitor (PI)-experienced patients. METHODS: PI-experienced patients with virological failure receiving fosamprenavir/ritonavir as the sole PI for at least 3 months and with detectable fosamprenavir plasma levels were included. The impact of baseline protease mutations on virological response (VR, i.e. decrease in plasma HIV-1 RNA between baseline and month 3) was analysed using the Mann-Whitney test. Mutations with prevalence >10% and P value <0.10 were retained. The Jonckheere-Terpstra test was used to select the combination of mutations most strongly associated with VR. The association between score and VR was assessed by multivariate backward regression. RESULTS: In the 73 patients included, the median baseline HIV-1 RNA was 4.6 log(10) copies/mL (range: 2.7-6.9) and the mean decrease at month 3 was -1.07 +/- 1.40 log(10) copies/mL. Ninety per cent of the patients were infected by HIV-1 subtype B variants. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V - V77I - N88S + L90M) also took into account favourable mutations. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR. CONCLUSIONS: These clinically validated mutation scores should be of interest for the clinical management of PI-experienced patients. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V.

Monteggia injuries.

The Monteggia injury is defined as radial head dislocation with a fracture of the ulnar shaft. This combination should be sought routinely in patients with ulnar fractures, even when the displacement is small. The emergent management is simple, as reducing the ulnar fracture is usually sufficient to stabilise the radial head. Internal fixation of the ulna deserves to be widely used to fully stabilise the radial head. Irreducibility of the radial head at the acute stage may indicate an interposition, which requires open surgery on the joint. Radial head dislocation may occur even with minimal displacement of the ulnar fragment. Chronic Monteggia fractures are more challenging to treat and their outcomes are more variable. The radial head becomes irreducible after 2 to 3 weeks. When a simple surgical approach fails to ensure stable reduction, the most widely used method at present is open reduction of the radial head and proximal osteotomy of the ulnar shaft. Stability must be obtained intra-operatively. Without treatment, radial head dislocation may be well tolerated for several months or even years. In the long term, however, osteoarticular remodelling results in loss of joint congruence, pain and, eventually, osteoarthritis. Radiographs must therefore be obtained on an emergency basis and analysed with great care to avoid missing a Monteggia fracture.

Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant.

OBJECTIVES: There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. METHODS: The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. RESULTS: Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. CONCLUSION: Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.

[Aneurysmal bone cyst in 2006]. / Le kyste osseux anévrismal primitif: quoi de neuf en 2006?

The etiology of aneurysmal bone cyst is probably multifactorial. Recent progress in genetics and immunohistochemistry tends to prove that aneurysmal bone cyst is tumor and not a pseudo-tumor. Involvement of chromosomes 17p11-13 or 16q22 has been described. MRI is indispensable. Signs highly suggestive of aneurysmal bone cyst are: well-limited expansive bone lesion, low intensity T1 signal associated with high intensity T2 signal (liquid component), a low intensity peripheral line with enhancement after contrast injection, septal partitioning and fluid levels. Gadolinium injection is informative since it demonstrates the thick regular septal partitioning and the amorphous contents (lack of contrast uptake), a structure which is not seen in any other tumors, particularly malignant tumors. Plain x-ray and MRI contribute well to diagnosis but histological confirmation is always required. The debate on Ethibloc(R) remains open. For certain authors, this technique is an effective safe treatment which can be proposed as a first-line option. Ethibloc(R) should however be reserved for specialized teams because of the serious complications reported in the literature. A new treatment has also been reported to be promising, but further results will be required for confirmation. With this technique demineralized allogenic bone particles associated with autologous bone marrow are implanted in the cyst to achieve an osteogenic effect. This induces the cyst to pass from the destructive resorption phase to the repairing osteogenic phase. Curettage is not necessary. This method, which avoids extensive surgery and blood loss, is well adapted to difficult localizations such as the pelvis.

Acute ischemia and pink pulseless hand in 68 of 404 gartland type III supracondylar humeral fractures in children: Urgent management and therapeutic consensus.

UNLABELLED: No consensus exists regarding pulseless otherwise well-perfused hand in pediatric Gartland type III fractures. The purpose of this retrospective study was to describe our strategy and to determine the guidelines of therapeutic consensus. PATIENTS AND METHODS: 404 children were treated for a type III supracondylar humeral fracture. Extension fractures-induced acute vascular injuries were noticed in 68 patients and nerve injuries were associated in 32 of them. The radial pulse was absent in all patients with two clinical situations at the initial presentation: well-perfused hand with 'pink and warm' hand in 63 patients and ischemia with 'white and cold' hand in five. Urgent closed reduction of the fracture and stabilization were performed in 63 patients with pink pulseless hand, and immediate surgical exploration in the five patients with ischemia. RESULTS: 63 patients with vascular injury had posterolateral displacement and 5 had posteromedial displacement. Sixty-three of 68 patients had posterolateral displacement of whom 28 had concomitant median nerve injury and 4 had a deficit to both median and ulnar nerves. The palpable radial pulse was immediately restored in 42 patients and between few hours to eleven days later in eighteen. Three patients with ischemia after unsuccessful reduction required immediate surgical exploration revealing incarceration of the brachial artery at the fracture site. Release and decompression of the brachial artery restored a normal limb perfusion. The five patients with primary ischemia underwent immediate open exploration and vascular repair. One of them had a compartment syndrome and required anterior fasciotomy. The restoration of blood flow with palpable radial pulse was observed in all patients. Full spontaneous nerve recovery was observed in all patients. At an average follow-up of 8.4 years, all patients had normal circulatory status, including a palpable radial pulse. DISCUSSION: This study highlighted the reliability of non invasive strategy with good outcomes. We recommend urgent closed reduction of fracture. Close observation and monitoring is mandatory if pulseless hand remains warm and well-perfused. If the patients develop blood circulation disturbances or compartment syndrome following closed reduction, immediate vascular exploration is recommend.

[Exercise therapy in the treatment of idiopathic adolescent scoliosis: Is it useful?]. / La kinésithérapie dans le traitement de la scoliose idiopathique de l'adolescent : utile ou pas ?

Many practitioners, pediatricians, and general practitioners prescribe physical therapy when tracking scoliosis. However, has physical therapy alone proved its efficacy in the care of the scoliosis to slow down progression? Our purpose is to report the results of a literature review on the effectiveness of rehabilitation in idiopathic scoliosis. No current study presents sufficient scientific proof to validate the efficacy of isolated exercise therapy in scoliosis. Learned societies recognize, however, the efficacy of combining conservative therapy (brace+physiotherapy) in idiopathic scoliosis. Should we then still prescribe rehabilitation without brace treatment? Although physical therapy alone does not seem effective in treating scoliosis, it can limit potential painful phenomena and be beneficial for respiratory function. The physical therapist can also teach the teenager the classic principles of hygiene of the back. It may therefore be appropriate to prescribe physical therapy, but the principles and objectives must be explained to the patient and family in light of current evidence-based medicine.

Mosaicplasty for femoral osteochondritis dissecans.

The authors describe a surgical mosaicplasty technique, with an anterior surgical dislocation approach without trochanterotomy, for osteochondritis dissecans of the hip. A graft was taken from the lateral condyle of the knee. Two adolescents underwent this procedure with good results. No osteonecrosis was observed at the longest follow-up. Mosaicplasty is a useful treatment method for small osteochondritis dissecans (<2cm(2)).

[Spinal bone tumors in children]. / Les tumeurs osseuses rachidiennes chez l'enfant et l'adolescent.

The occurrence of back pain in children and adolescents varies from 30 to 51% in the literature. Bone tumors can be responsible for back pain. This paper presents the more common spinal bone tumors in children and adolescents, and specifies their etiology, their natural history, and their treatment as well.

[Mac Farland fractures: a retrospective study of 26 cases]. / Les fractures de Mac Farland: étude rétrospective d'une série de 26 cas.

PURPOSE OF THE STUDY: MacFarland fractures are known to have poor prognosis. There is a major risk of misalignment due to the formation of an epiphysiodesis bridge. The purpose of this study was to evaluate the functional and radiological outcome of these fractures in a retrospective series of patients. MATERIAL AND METHODS: We analyzed retrospectively the cases of 26 patients (14 boys and 12 girls), mean age 11 years 6 months (range 7-15) with MacFarland fractures. The Salter and Harris classification was Salter III (n = 17) and Salter IV (n = 9). Surgery was used for 21 patients and cast immobilization for five. Mean follow-up was 28.4 months (19-63 months). None of the children were lost to follow-up. Outcome was noted good (no stiffness, no pain, no limp, no misalignment, no surgical complication, no healing problem), fair (stiffness and/or pain and/or limp and/or healing problem without misalignment, no surgical complication), or poor (misalignment or surgical complication). RESULTS: The three-months postoperative assessment showed three patients with ankle pain, five with stiff ankles, one with a medial problem (snapping) and two with wound healing complications. The long-term outcome was considered good for 24 patients and fair in two (one wound adherence and one hypertrophic scar tissue). There were no poor outcomes. DISCUSSION: We used surgery more than is generally reported by other teams, opting for surgery when the displacement was 1 mm rather than the 2 mm used by others. Surgical treatment was arthrotomy in all cases to achieve anatomic reduction under direct view, followed by osteosynthesis. For some, this therapeutic scheme may be considered too surgical. In order to achieve anatomic reduction, we use an epiphyseal lag screw for cancellous bone to achieve better compression of the fracture line. A washer is also used to improve compression and maintain perfect reduction. Theoretically, the washer could raise the risk of perichondral virola and consequently an iatrogenic epiphysiodesis bridge, but we have not had any problems in our experience. Arthrotomy did not lead to ankle stiffness, which is feared by some, in any of our patients.

Do viral load and CD8 cell count at initiation of tritherapy influence the increase of CD4 T-cell count?

BACKGROUND: Tritherapies including protease inhibitors improve clinical status and usually increase CD4 T cell count. However, the dissociation between the marked decreases in viral load and the incomplete restoration of CD4 cell counts with a three-drug combination has been reported. We assessed this potential difference among our patients. METHODS: Patients were enrolled when a protease inhibitor was prescribed to them for the first time. Using a computerized medical record (ADDIS), we retrospectively assessed a potential relationship between the increase in CD4 T cells (deltaCD4) at M3, M6 and variables including sex, age, CDC staging, protease inhibitor, prior antiviral therapy, CD8 and viral load at baseline. We used Epi-Info 6.4 and BMDP software. RESULTS: Data were analyzed on 154 patients. The median CD4 T cell count was 157 at baseline, 215 at month 3 and 202 at month 6. The median viral load was 52000 copies at baseline, 530 at month 3 and 500 at month 6. In a univariate analysis, a significant relationship was found between deltaCD4 and CD8 at baseline. A statistically significant negative correlation appeared between the CD8 cell count at baseline and deltaCD4 at M6 (r=-0.28, Pearson). Moreover, we found that there also was a relationship between deltaCD4 and viral load at baseline. There was a correlation between deltaCD4 at M6 and the viral load at M0 (r=0.37, Pearson). In a multiple regression model, after CD8 count at baseline had been accounted for, we found a significant correlation between deltaCD4 and viral load at baseline (multiple r=0.33 at M3, and 0.40 at M6). CONCLUSIONS: Patients with a low viral load do not benefit from as great an increase in CD4 T cell count as others when they receive a tritherapy including protease inhibitors. These results suggest that another mechanism rather than direct viral pathogenicity leads to CD4 T cell destruction. This mechanism may not be efficiently stopped by antiviral therapy, especially protease inhibitors.

Prevalence of resistance mutations in antiretroviral-naive chronically HIV-infected patients in 1998: a French nationwide study.

OBJECTIVE: To estimate the prevalence of resistance-conferring mutations to antiretroviral drugs in previously untreated patients with chronic HIV-1 infection as a basis for French recommendations on viral genotyping before antiretroviral treatment initiation. DESIGN: Resistance mutations were sought in samples from 404 patients seen in 23 specialized centres throughout metropolitan France in 1998. METHODS: The protease and reverse transcriptase (RT) genes of plasma virions were sequenced. Primary and secondary protease and RT gene mutations were identified from the International AIDS Society resistance testing - USA panel. RESULTS: The prevalence of patients with primary and secondary mutations were 3.7% (95% CI 1.7-5.7) and 50.3% (95% CI 45.0-55.6), respectively. The prevalence of patients with mutations associated with resistance to nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors was 3.3% (95% CI 1.5-5.1) and 0.8% (95% CI 0.0-1.7), respectively. The prevalence of patients with NRTI primary mutations differed according to whether seropositivity had been diagnosed more or less than one year previously (0.2 versus 2.2% P = 0.023). Primary mutations associated with protease inhibitor resistance occurred at a prevalence of 1.9% (95% CI 0.5-3.4) with no difference according to the duration of known seropositivity. CONCLUSION: In France, in 1998, the prevalence of patients with primary mutations associated with resistance to antiretroviral drugs was low. Genotyping before the initiation of therapy was not recommended in chronically HIV-1-infected naive patients. A national sentinel survey of resistance in this clinical setting is performed regularly to update the recommendations for resistance testing.