Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence.

It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10(-82)), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.

Pedobarographic analysis following Ponseti treatment for congenital clubfoot.

UNLABELLED: Current methods of treating congenital clubfeet provide high rates of functional outcomes. Despite the clinical outcomes, radiographic assessment suggests residual equinus deformity of the hindfoot. It is unclear whether these deformities result in abnormal foot-floor pressures and whether they correlate with clinical outcome. We evaluated 28 feet in 20 patients following Ponseti treatment for clubfoot by clinical and pedobarographic examination a mean of 33 months after removal of the last cast. The data were compared to age- and weight-matched normal subjects and to the unaffected foot in the unilaterally affected patients. Despite ankle range of motion of 30 degrees and a physiologic hindfoot valgus alignment in 19 cases, pedobarography suggested differences in maximum force, impulse, contact area, and peak pressure compared to normal subjects. Compared to the unaffected foot the only difference was reduced peak pressure over the medial hindfoot and forefoot with increased pressure over the lateral midfoot. Similar to radiographic abnormalities in studies on treated clubfeet with good functional outcome, pedobarographic analyses show differences compared to a control group. The value of pedobarographic analysis for predicting successful treatment of congenital clubfoot is questionable since it does not correlate with the clinical outcome in patients treated with the Ponseti method. LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Heterotopic ossification around the elbow following burns in children: results after excision.

BACKGROUND: Major burn injuries close to joints alter the function of the musculoskeletal system through tissue loss and limitation of joint motion. In children with involvement of the hand, wrist, and forearm, restriction of elbow motion secondary to heterotopic ossification following a burn injury severely limits the function of the upper extremity. The purpose of this study was to review elbow function following excision of heterotopic ossification around the elbow in children. METHODS: Eight children (ten elbows) from a population of 3245 consecutive patients who were admitted to our pediatric burn center were found to have severe heterotopic ossification of the elbow, leading to an inability to reach the mouth for feeding and the head and the perineum for self-care. Excision of the heterotopic ossification was undertaken if the patient had this limitation of function and if movement was restricted to a total arc of motion of <50 degrees. Pain was not an indication for the operation. The procedure was performed at an average of 17.3 months following the injury. RESULTS: Seven children (nine elbows) were available for follow-up at an average of fifty-six months after surgery. All nine elbows had an improved arc of motion (an average increase of 57 degrees ). Following excision, heterotopic ossification did not recur. All children were able to reach the face and the perineum following the operation. CONCLUSIONS: Excision of heterotopic ossification around the elbow following a burn injury in children can improve the arc of motion and improve the function of the extremity. A relatively simple operative and postoperative regimen can achieve satisfactory results.

Early results of the Ponseti method for the treatment of clubfoot in distal arthrogryposis.

BACKGROUND: Clubfoot occurs in approximately one in 1000 live births and is one of the most common congenital birth defects. Although there have been several reports of successful treatment of idiopathic clubfoot with the Ponseti method, the use of this method for the treatment of other forms of clubfoot has not been reported. The purpose of the present study was to evaluate the early results of the Ponseti method when used for the treatment of clubfoot associated with distal arthrogryposis. METHODS: Twelve consecutive infants (twenty-four feet) with clubfoot deformity associated with distal arthrogryposis were managed with the Ponseti method and were retrospectively reviewed at a minimum of two years. The severity of the foot deformity was classified according to the grading system of Diméglio et al. The number of casts required to achieve correction was compared with published data for the treatment of idiopathic clubfoot. Recurrent clubfoot deformities or complications during treatment were recorded. RESULTS: Twenty-two clubfeet in eleven patients were classified as Diméglio grade IV, and two clubfeet in one patient were classified as Diméglio grade II. Initial correction was achieved in all clubfeet with a mean of 6.9 +/- 2.1 casts (95% confidence interval, 5.6 to 8.3 casts), which was significantly greater than the mean of 4.5 +/- 1.2 casts (95% confidence interval, 4.3 to 4.7 casts) needed in a cohort of 219 idiopathic clubfeet that were treated during the same time period by the senior author with use of the Ponseti method (p = 0.002). Six feet in three patients had a relapse after initial successful treatment. All relapses were related to noncompliance with prescribed brace wear. Four relapsed clubfeet in two patients were successfully treated with repeat casting and/or tenotomy; the remaining two relapsed clubfeet in one patient were treated with extensive soft-tissue-release operations. CONCLUSIONS: Our early-term results support the use of the Ponseti method for the initial treatment of distal arthrogrypotic clubfoot deformity. Longer follow-up will be necessary to assess the risk of recurrence and the potential need for corrective clubfoot surgery in this patient population, which historically has been difficult to treat nonoperatively.

Foot abduction brace in the Ponseti method for idiopathic clubfoot deformity: torsional deformities and compliance.

The Ponseti method has shown to be effective in treating idiopathic clubfoot deformity. Application of a foot abduction brace is crucial to long term outcome. Compliance and possible effect on femoral anteversion and tibial torsion were assessed in 20 children with an average bracing period of 33 months. Nineteen patients were compliant with the bracing protocol and highly satisfied with the treatment protocol. Ultrasound measurement of femoral anteversion (40.5 degrees) and tibial external torsion (38.4 degrees) of the affected side were within the normal range. Range of motion of the ankle joint in all clubfeet resulted in an average dorsiflexion of 27.5 degrees. Among our patient group, the method proved to be highly accepted by almost all families, with excellent functional results. Application of the foot abduction brace did not result in pathological changes of femoral anteversion or tibial torsion.

Treatment of the complex idiopathic clubfoot.

Treatment with the Ponseti method corrects congenital idiopathic clubfeet in the majority of patients. However, some feet do not respond to the standard treatment protocol. We describe the characteristics and treatment results of these complex idiopathic clubfeet. We identified 50 patients (75 clubfeet) from 762 consecutive patients treated at five institutions. Clinically, complex clubfeet were defined as having rigid equinus, severe plantar flexion of all metatarsals, a deep crease above the heel, a transverse crease in the sole of the foot, and a short and hyperextended first toe. The Achilles' tendon was exceptionally tight and fibrotic up to the middle of the calf. Correction was achieved in all patients by modifying the Ponseti manipulation and casting technique. Correction required an average of five casts (range, 1-10 casts). Two patients (4%) not initially recognized as having complex clubfeet had a posterior release with tendo Achillis lengthening. There were seven relapses that responded to casting. Three patients had a second tenotomy. Modifying the treatment protocol for complex clubfeet successfully corrected the deformity without the need for extensive corrective surgery.