Prothrombin Time and Coagulation Factor IX as Hemostatic Risk Markers for Legg- Calvé-Perthes Disease.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. METHODS: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. RESULTS: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. CONCLUSIONS: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis.

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I = 92%, odds ratio = 2.51; USA group I = 5%, odds ratio = 3.26; and Asian group I = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1-10 per day; odds ratio = 2.73, for 10-20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1-9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.

Legg-Calvé-Perthes disease.

Current knowledge of the causes and risk factors of Legg-Calvé-Perthesdisease (LCPD) does not allow effective preventive strategies. The outcome in adulthood is usually good. Hip osteoarthritis rarely develops before 50 years of age. The risk of osteoarthrosis depends chiefly on the final degree of joint incongruence. Age at onset and the lateral pillar classification are the two main outcome predictors and serve to guide the surgical indications based on the studies by Herring's group. Non-operative treatment is not effective. In contrast, femoral varus osteotomy and Salter's innominate osteotomy provide good outcomes. In severe forms, however, combining these two techniques or performing a triple pelvic osteotomy seem preferable. Surgery is now performed considerably less often than in the past, as it is effective only in patients with lateral pillar group B or B/C disease with onset after eight years of age. In other situations, therapeutic abstention is recommended.

A case control study to determine the association between Perthes' disease and the recalled use of tobacco during pregnancy, and biological markers of current tobacco smoke exposure.

AIMS: It is well established that there is a strong association between Perthes' disease and worsening socioeconomic deprivation. It has been suggested that the primary determinant driving this association is exposure to tobacco smoke. This study aimed to examine this hypothesis. PATIENTS AND METHODS: A hospital case-control study (n = 149/146) examined the association between tobacco smoke exposure and Perthes' disease, adjusting for area-level socioeconomic deprivation. Tobacco smoke exposure was assessed by parental questionnaire of smoking habits during pregnancy, and by quantitative assay of current exposure using the urinary cotinine-creatinine ratio, which is a widely used and validated measure of tobacco smoke exposure. RESULTS: The odds of Perthes' disease significantly increased with reported in utero exposure after adjustment for socioeconomic deprivation (maternal smoking odds ratio (OR) 2.06, 95% confidence interval (CI) 1.17 to 3.63; paternal smoking OR 2.09, 95% CI 1.26 to 3.46). The cotinine-creatinine ratio was significantly greater in cases, OR 1.63 (95% CI 1.09 to 2.43), suggesting a greater 'dose' of current tobacco exposure. CONCLUSION: An association exists between tobacco smoke exposure and Perthes' disease but we remain unable to disentangle the association with socioeconomic deprivation. Cite this article: Bone Joint J 2017;99-B:1102-8.

The Pathogenesis and Treatment of Legg-Calvé-Perthes Disease.

Legg-Calvé-Perthes disease is a childhood hip condition in which the blood supply to the capital femoral epiphysis is interrupted, causing osteonecrosis and chondronecrosis that lead to progressive deformity of the femoral head and secondary degenerative osteoarthritis in later life. The etiology of Legg-Calvé-Perthes disease remains unclear, with both biological and mechanical factors playing important roles in the pathogenesis of the condition. The treatment of Legg-Calvé-Perthes disease remains controversial but is dependent on several salient factors, including the age at clinical onset, the extent of epiphyseal involvement, the stage of the disease, and the degree of femoral head deformity. The literature supports operative containment treatment in the early stage of disease. Such treatment has led to improved femoral head sphericity with better patient outcomes in multicenter prospective cohort studies. The number of hips that need to be treated operatively in order to achieve a modest treatment effect remains high. Multicenter prospective cohort studies have shown that 6 to 7 patients need to be managed to create 1 spherical femoral head that would not have otherwise occurred.

Skeletal immaturity, rostral sparing, and disparate hip morphologies as biomechanical causes for Legg-Calvé-Perthes' disease.

Legg-Calvé-Perthes' (Perthes') disease is a developmental disease of the hip joint that may result in numerous short and long term problems. The etiology of the disease remains largely unknown, but the mechanism is believed to be vascular and/or biomechanical in nature. There are several anatomical characteristics that tend to be prevalent in children with Perthes' disease, namely: skeletal immaturity, reduced height, and rostral sparing. We present an overview of the literature, summarizing the current understanding of the pathogenesis, particularly related to how the formation of the vasculature to the femoral epiphysis places children aged 5-8 at a higher risk for Perthes' disease, how skeletal immaturity and rostral sparing could increase the probability of developing Perthes' disease, and how animal models have aided our understanding of the disease. In doing so, we also explore why Perthes' disease is correlated to latitude, with populations at higher latitudes having higher incidence rates than populations closer to the Equator. Finally, we present five hypotheses detailing how Perthes' disease could have a biomechanical cause. Clin. Anat. 29:759-772, 2016. © 2016 Wiley Periodicals, Inc.

Bariatric Bypass Surgery to Resolve Complicated Childhood Morbid Obesity: Case Report Study.

Children obesity has become one of the most important public health problems in many countries worldwide. Although the awareness of childhood obesity as a modifiable health risk is high, but many societies do not prioritize this issue as a health care problem, which may lead to comorbidities and even premature death. Despite the rising interest in bariatric surgery for children, only laparoscopic sleeve gastrectomy (LSG) is being considered in resolving childhood obesity who failed other dietary or drug therapies; however many of LSG procedures failed to reduce the weight in children or resulted in complications postsurgery.Here, we present a novel bariatric procedure to clue out a female child 13 years old presented with Legg-Calvé-Perthes disease-associated morbid obesity. The surgical bariatric technique applied both fundal resection and surgical bypass in pediatric obesity using the Elbanna novel bariatric technique.Bariatric surgical bypass may be considered in complicated-childhood cases who failed all other options.

[Perthes disease]. / Morbus Perthes.

Morbus Perthes today still poses a challenge for the orthopaedic surgeon because of the unclear aetiology as well as the controversial discussion about the role and kind of multiple treatment principles. The prognosis depends upon clinical (e.g. age at onset, reduction of range of motion, gender) and radiological (extent of necrosis, containment) parameters. Of these, only the reduced range of motion and a loss of containment can be adressed therapeutically, be it in a conservative and/or operative concept. Pelvic osteotomies have the advantage of a high potential of correction without the biomechanic disadvantages which are associated with intertrochanteric varus osteotomies. Nowadays, the use of orthoses is considered to be obsolete. Non-containment is targeted mainly on the symptomatic treatment and the correction of residual deformities. Based on the outcome after the final stage there is a risk of premature osteoarthritis with the need of early total hip replacement.

Current perspectives on the pediatric hip: selected topics in hip dysplasia, Perthes disease, and chondrolysis: synopsis of the hip subspecialty session at the POSNA Annual Meeting, May 1, 2013, Toronto.

The following are proceedings from the Hip Breakout Session held at the 2013 annual meeting of the Pediatric Orthopaedic Society of North America in Toronto, Canada. The organizer's goal of the meeting was to gather experts with years of clinical experience to discuss topics based upon both experience and current clinical evidence. The topics that were selected represented the most commonly encountered pathology where there are wide variations of clinical practice. The invited speakers were asked to summarize both their clinical experience and the current scientific evidence and to summarize areas that require further scientific investigation.

Female patients with late-onset legg-calvé-perthes disease are frequently gymnasts: is there a mechanical etiology for this subset of patients?

BACKGROUND: The cause of Legg-Calvé-Perthes disease (LCPD) is unknown. We have observed a relatively high prevalence of female gymnasts presenting with LCPD. The purpose of this study was to determine: (1) the percentage of LCPD patients exposed to high-level gymnastics training, (2) the demographics of this subset of patients, and (3) their clinical outcomes. METHODS: Several adolescent female gymnasts presented to our clinic with recent-onset LCPD. We reviewed our cases to discern the prevalence and treatment of the disorder in this patient cohort. From 1999 to 2010, 572 patients were evaluated for a diagnosis of LCPD at our tertiary referral center. Clinical records were retrospectively reviewed. Of those, 13 patients had a history of gymnastics participation with 8 patients (all females) having competitive participation. RESULTS: For females aged 10 years and older presenting with LCPD, 7 of 9 patients (78%) were involved in high-level competitive gymnastics. These patients had disease onset between 10 and 12 years of age (mean, 11 y). Competitive gymnasts represented 6.6% (8 of 120) of females with LCPD and 1.4% (8 of 572) of all patients evaluated with LCPD during the study period. Only 1 of 111 females below 10 years with LCPD participated in competitive gymnastics (χ, P<0.0001).Patients underwent a variety of treatments. Two patients underwent nonoperative treatment, and the remainder underwent surgical management. All 7 gymnasts had a Stulberg IV result. In the nongymnast group of females 10 years and older, there were 1 Stulberg III result and 1 Stulberg IV result. CONCLUSIONS: At our center, competitive gymnasts comprise >75% of the female patients over the age of 10 who presented with late-onset LCPD. Results in general were poor. Further studies are needed to explore the association between the physical demands of advanced gymnastic training and the development of LCPD in this subset of patients. LEVEL OF EVIDENCE: IV, case series.

Unravelling the enigma of Perthes disease.

Perthes disease is an idiopathic avascular necrosis of a juvenile hip. Although 2010 marked a century since it was first described, the aetiology remains unknown. It is suggested that adverse socioeconomic circumstances may be a key precipitant. This work describes recent studies that explore the disease epidemiology. Descriptive studies include a case register from Merseyside, hospital discharge data from Scotland, analysis of the world's largest community disease register (General Practice Research Database [GPRD]) and a systematic review of incidence. Analytical studies include a nested case-controlled study in the GPRD and a hospital case-controlled study. The studies demonstrated a striking north-south divide in the UK incidence of Perthes disease, similar to that seen in many adult diseases. There was a sustained fall in disease frequency in all studies, with a narrowing of the north-south divide. There was a strong association with area deprivation, independent of living in an urban environment. Internationally, equatorial regions were unaffected by disease and northern Europe had the highest incidence, which was primarily a function of race although latitude was an independent predictor. Individual characteristics associated with the disease were congenital anomalies of the genitourinary tract and a structural abnormality of arterial calibre. Despite a falling incidence, Perthes disease remains an important cause of child morbidity and exemplifies socioeconomic inequalities. A deprivation-related exposure, acting early in development, appears critical. The aetiological factor in Perthes disease remains elusive but it is likely that unravelling this enigma may unlock additional secrets pertaining to the developmental origins of this and other diseases.

Comorbidities in Perthes' disease: a case control study using the General Practice Research database.

Perthes' disease is an osteonecrosis of the juvenile hip, the aetiology of which is unknown. A number of comorbid associations have been suggested that may offer insights into aetiology, yet the strength and validity of these are unclear. This study explored such associations through a case control study using the United Kingdom General Practice Research database. Associations investigated were those previously suggested within the literature. A total of 619 cases of Perthes' disease were included, as were 2544 controls. The risk of Perthes' disease was significantly increased with the presence of congenital anomalies of the genitourinary and inguinal region, such as hypospadias (odds ratio (OR) 4.04 (95% confidence interval (CI) 1.41 to 11.58)), undescended testis (OR 1.83 (95% CI 1.12 to 3.00)) and inguinal herniae (OR 1.79 (95% CI 1.02 to 3.16)). Attention deficit hyperactivity disorder was not associated with Perthes' disease (OR 1.01 (95% CI 0.48 to 2.12)), although a generalised behavioural disorder was (OR 1.55 (95% CI 1.10 to 2.17)). Asthma significantly increased the risk of Perthes' disease (OR 1.44 (95% CI 1.17 to 1.76)), which remained after adjusting for oral/parenteral steroid use. Perthes' disease has a significant association with congenital genitourinary and inguinal anomalies, suggesting that intra-uterine factors may be critical to causation. Other comorbid associations may offer insight to support or refute theories of pathogenesis.

Legg-Calvé-Perthes disease in the UK: geographic and temporal trends in incidence reflecting differences in degree of deprivation in childhood.

OBJECTIVE: Little is known about Legg-Calvé-Perthes disease, a common childhood precursor to osteoarthritis of the hip. This study was undertaken to analyze the incidence of Legg-Calvé-Perthes disease in the UK, with respect to geographic and temporal trends over a 19-year period. METHODS: The General Practice Research database was analyzed to identify incident cases between 1990 and 2008 in children ages 0-14 years. Incidence rates were calculated by year and by region (National Health Service Strategic Health Authority regions in England, and Scotland, Wales, and Northern Ireland), and the association with regional markers of deprivation examined. RESULTS: Over the 19-year period there was a dramatic decline in Legg-Calvé-Perthes disease incidence, with annual rates among children 0-14 years old declining from 12.2 per 100,000 to 5.7 per 100,000 (P < 0.001). There was also marked geographic variation, with incidence rates in Scotland more than twice those in London (10.39 [95% confidence interval 8.05-13.2] versus 4.6 [95% confidence interval 3.4-6.1] per 100,000 0-14-year-olds). A more rapid decline in incidence was apparent in the Northern regions compared to Southern regions. The quintile with the highest degree of deprivation had the highest disease incidence (rate ratio 1.49 [95% confidence interval 1.10-2.04]) and, with the exception of London, regional incidence showed a strong linear relationship with regional deprivation score (P < 0.01). CONCLUSION: The incidence of Legg-Calvé-Perthes disease in the UK has a strong North-South divide, with a greater disease incidence within the Northern regions of the UK. There was a marked decline in incidence over the study period, which was more marked in Northern areas. The declining incidence, along with the geographic variation, suggests that a major etiologic determinant in Legg-Calvé-Perthes disease is environmental and closely linked to childhood deprivation.

The time of the insult/triggering event in Legg-Calvé-Perthes' disease determined by incubation period modeling and the age distribution of children with Perthes'.

The time when the insult/triggering event occurs in Legg-Calvé-Perthes' (LCPD) is unknown. the purpose of this study was to determine, using the mathematical tool of incubation period modeling, the time of such event and the incubation period for LCPD. We reviewed 2,911 children with LCPD from 10 different centers around the world. They were divided into two groups: those from India (505 children, mean age 8.1 ± 2.3 years) and those from other than India (2,406 children, mean age 5.8 ± 2.2 years). A simple distribution with an excellent fit to the data was ln(y) = a + bx + cxln(x), where y is the proportion of children with LCPD at age of diagnosis x (r(2) = 0.994 for non-Indian and 0.959 for Indian children). The age of the triggering event was 1.32 years for non-Indian and 2.77 years for Indian children; the median incubation period was 4.30 years non-Indian and 5.33 years for Indian patients. Knowing the incubation period and age of triggering event narrows the number of potential etiologies in LCPD. this study does not support a prenatal triggering event as postulated in the past. similar incubation periods with different ages at diagnosis supports a common insult which occurs at different ages in different populations dependent upon local factors such as geographic location and ethnicity.

Environmental tobacco and wood smoke increase the risk of Legg-Calvé-Perthes disease.

BACKGROUND: The etiology of Legg-Calvé-Perthes disease (LCPD) remains unknown. A few studies have suggested passive smoke inhalation may be a risk factor, although the association is not confirmed and a causal relationship has not been established. QUESTIONS/PURPOSES: We therefore undertook this study to confirm an association between environmental tobacco smoke, firewood smoke, and socioeconomic status and the risk of LCPD. METHODS: We prospectively recruited 128 children with LCPD and 384 children attending the hospital for other orthopaedic complaints. The control subjects were frequency-matched with the cases by age and gender. Conditional logistic regression was used to assess the association between the exposures and risk of LCPD. RESULTS: The main risk factors for LCPD were indoor use of a wood stove (adjusted odds ratio [OR], 2.56) and having a family member who smoked indoors (adjusted OR, 2.07). Children from the middle socioeconomic group appeared to be at a greater risk of developing LCPD (adjusted OR, 3.60). CONCLUSIONS: This study provides further evidence that environmental tobacco smoke is associated with an increased risk of LCPD. Exposure to wood smoke also appears to be a risk factor. However, it remains unclear why there are profound differences in the incidence of the disease between regions when the prevalence of smoking is comparable and why bilateral involvement and familial disease are infrequent.

Perthes' disease: deprivation and decline.

INTRODUCTION: Perthes' disease is a childhood hip disorder which frequently precipitates premature osteoarthritis necessitating joint replacement in young adults. The highest incidence reported worldwide is in Merseyside, UK, where a unique disease register is maintained. OBJECTIVE: To describe the temporal trends in disease incidence in a geographically defined area of Merseyside, and to examine the relationship to area deprivation. DESIGN: Descriptive observational study utilising a regional disease register in Merseyside, UK, 1976-2009. PATIENTS: 1082 children with Perthes' disease (682 from a geographically defined area). OUTCOME: Disease incidence by region, year and deprivation quintile (measured by the Index of Multiple Deprivation 2007, and the Child Well-Being Index 2009). RESULTS: There was a dramatic decline in incidence over the study period in Liverpool, with rates falling from 14.2 to 7.7 cases/10,000 0-14-year-olds (p<0.001). Incidence rates halved in nearby Knowsley (p=0.01) but remained largely static in the more affluent region of Sefton, where the annual incidence remained at around 7.2 cases/10,000 0-14-year-olds (p=0.73). The association with area deprivation is striking, with the most deprived quintiles having over three times the incidence of the most affluent quintiles (11.5 vs 3.8 cases/10,000 0-14-year-olds; p<0.001). Incidence by electoral ward was strongly correlated to ward deprivation score (p<0.001). CONCLUSION: There was a marked decline in disease incidence over the study period, particularly in more deprived areas. The magnitude of the association with deprivation, and the changing incidence, strongly suggest that environmental factor(s) are a major aetiological determinant in Perthes' disease.