Paul D. Sponseller

Bio: Paul D. Sponseller is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Scoliosis & Medicine. The author has an hindex of 63, co-authored 487 publications receiving 15186 citations. Previous affiliations of Paul D. Sponseller include University of Wisconsin-Madison & Johns Hopkins University School of Medicine.

The revised Ghent nosology for the Marfan syndrome

Abstract: The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counselling. These Ghent criteria, comprising a set of major and minor manifestations in different body systems, have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, are not applicable in children or necessitate expensive and specialised investigations. The recognition of variable clinical expression and the recently extended differential diagnosis further confound accurate diagnostic decision making. Moreover, the diagnosis of MFS—whether or not established correctly—can be stigmatising, hamper career aspirations, restrict life insurance opportunities, and cause psychosocial burden. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are the cardinal clinical features. In the absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of either of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a new scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines.

Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

Abstract: Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.

Complications of growing-rod treatment for early-onset scoliosis: analysis of one hundred and forty patients

Abstract: Background: Previous reports have indicated high complication rates associated with non-fusion surgery in patients with early-onset scoliosis. This study was performed to evaluate the clinical and radiographic complications associated with growing-rod treatment. Methods: Data from the multicenter Growing Spine Study Group database were evaluated. Inclusion criteria were growing-rod treatment for early-onset scoliosis and a minimum of two years of follow-up. Patients were divided into treatment groups according to rod type (single or dual) and rod location (subcutaneous or submuscular). Complications were categorized as wound, implant, alignment, and general (surgical or medical). Surgical procedures were classified as planned and unplanned. Results: Between 1987 and 2005, 140 patients met the inclusion criteria and underwent a total of 897 growing-rod procedures. The mean age at the initial surgery was six years, and the mean duration of follow-up was five years. Eighty-one (58%) of the 140 patients had a minimum of one complication. Nineteen (27%) of the seventy-one patients with a single rod had unplanned procedures because of implant complications, compared with seven (10%) of the sixty-nine patients with dual rods (p ≤ 0.05). Thirteen (26%) of the fifty-one patients with subcutaneous rod placement had wound complications compared with nine of the eighty-eight patients (10%) with submuscular rod placement (p ≤ 0.05). The patients with subcutaneous dual rods had more wound complications, more prominent implants, and more unplanned surgical procedures than did those with submuscular dual rods (p ≤ 0.05). The risk of complications occurring during the treatment period decreased by 13% for each year of increased patient age at the initiation of treatment. The complication risk increased by 24% for each additional surgical procedure performed. Conclusions: Regardless of treatment modality, the management of early-onset scoliosis is prolonged; therefore, complications are frequent and should be expected. Complications can be reduced by delaying initial implantation of the growing rods if possible, using dual rods, and limiting the number of lengthening procedures. Submuscular placement reduces wound and implant-prominence complications and reduces the number of unplanned operations. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

Deep wound infections after neuromuscular scoliosis surgery: a multicenter study of risk factors and treatment outcomes.

Abstract: Study Design. A retrospective case-control study evaluating risk factors for infection, causative organisms, and results of treatment in patients with cerebral palsy or myelomeningocele who underwent fusion for scoliosis was performed. Objectives. To identify risk factors for infection, and to characterize the infections in terms of infecting organisms and response to treatment. Summary of Background Data. No previous studies have analyzed risk factors or causative organisms, nor have they indicated results of treatment for infections in this group of patients. Methods. After a 10-year retrospective review of 210 surgically treated patients, deep wound infections developed in 16 patients with myelomeningocele and 9 patients with cerebral palsy. These patients were studied extensively for possible risk factors, along with 50 uninfected patients matched for age, diagnosis, and year of surgery. Statistical testing was performed to identify risk factors. The courses of the infections were characterized in terms of organisms isolated and response to treatment. Treatment was performed in a stepwise fashion and classified in terms of the most successful step: debridement and closure, granulation over rods, or instrumentation removal. Results. Of the 10 risk factors tested, 2 were found to be significant: degree of cognitive impairment and use of allograft. Findings showed that 52% of the infections were polymicrobial. Gram-negative organisms were isolated as commonly as gram-positive organisms. The most common organisms were coaguiase-negative Staphylococcus, Enterobacter, Enterococcus, and Escherichia coli. Debridement and closure were successful in 11 of 25 patients with deep wound infection. Of the 14 patients with infection not resolved by serial debridements and closure, 2 were managed successfully by allowing the wound to granulate over rods, and 7 required rod removal for persistent wound drainage. There were three symptomatic pseudarthroses, infections resulting from gram-positive organisms were most often managed successfully with debridement and closure (P = 0.012). Conclusions. Patients with cerebral palsy or myeiomeningocele who have severe cognitive impairment, and those who received allograft may be at increased risk for infection. Infections are more often polymicrobial and caused by gram-negative organisms than is typical for elective orthopedic procedures. This suggests an enteric source. Treatment with debridement and closure was not always successful. Patients in whom infection develops are then at increased risk for pseudarthrosis.

Vitamin D deficiency.

Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

ESC Guidelines for the management of grown-up congenital heart disease (new version 2010).

Abstract: Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks, and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC Web Site (http://www.escardio.org/guidelines/rules). Members of this Task Force were selected by the ESC to represent all physicians involved with the medical care of patients in this pathology. In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing and reviewing panels have provided disclosure statements of all relationships they may have which …

Mechanisms of Estrogen Action

Abstract: Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ERα and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen r...