The effects of uninvolved side epiphysiodesis for limb length equalization in children with unilateral cerebral palsy: clinical evaluation with the Edinburgh visual gait score.

PURPOSE: Hemiplegic cerebral palsy patient may present a shorten leg on the hemiplegic side that afflicts negatively the kinematic of the uninvolved limb. Thus, the aim of this study was to investigate the modification of gait kinematic after epiphysiodesis for limb equalization and secondary to verify the prediction of correction. METHODS: Skeletally immature hemiplegic patients with a minimum limb leg discrepancy (LLD) of 2.5 cm were treated with epiphysiodesis of the unaffected knee and clinically evaluated with Edinburgh visual gait score (EVGS). Green-Anderson curve was used to predict time decision for correction. RESULTS: Ten LLD patients were evaluated with the Edinburgh visual gait score (EVGS) before and after surgery. Mean age was 12.7 years, mean follow-up was 6.7 years, and mean LLD was 3.4 cm before surgery and 1.2 cm at final follow-up. After lower limb equalization surgery, improvement in gait kinematics was observed on both the uninvolved and hemiplegic limb of hemiplegic cerebral palsy patients (p < 0.001). Final correction did not reach expected correction (2.3 vs. 2.8 cm). However, the difference was not statistically significant (p = 0.058). CONCLUSION: This is the first study to report improvement on both the uninvolved and hemiplegic limb gait kinematics after limb equalization surgery. Due to the impaired dorsiflexion of the hemiplegic foot, LLD target at the end of growth should range between 0.5 and 1.5 cm.

Diverticulitis, surgery, evidence-based medicine, and the Steve Jobs' dots: a narrative review.

PURPOSE: Emergency treatment of acute diverticulitis remains a hazy field. Despite a number of clinical studies, randomized controlled trials (RCTs), guidelines and surgical societies recommendations, the most critical hot topics have yet to be addressed. METHODS: Literature research from 1963 until today was performed. Data regarding the principal RCTs and observational studies were summarized in descriptive tables. In particular we aimed to focus on the following topics: the role of laparoscopy, the acute care setting, the RCTs, guidelines, observational studies and classifications proposed by literature, the problem in case of a pandemic, and the importance of adapting treatment /place/surgeon conditions. RESULTS: In the evaluation of these points we did not try to find any prospective evolution of the concepts achievements. On the contrary we simply report the individuals strands of research from a retrospective point of view, similarly to what Steve Jobes said: "you can't connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future". We have finally obtained what can be defined "a narrative review of the literature on diverticulitis". CONCLUSIONS: Not only evidence-based medicine but also the contextualization, as also the role of 'competent' surgeons, should guide to novel approach in acute diverticulitis management.

Successful bridging treatment and healing of enteric fistulae by vacuum-assisted closure (VAC) therapy and targeted drainage in patients with open abdomen.

PURPOSE: The object of this study was to investigate the bridging treatment of enteric fistulae by vacuum-assisted closure (VAC) therapy in patients with open abdomen. METHODS: We retrospectively analyzed patients who have been treated between 1 January 2007 and 31 December 2008 at the intensive care unit of the Department of General Surgery, Medical University Vienna. Control of the fistula was established by VAC therapy to bridge the patients to the time of the fistula resection. RESULTS: In the period of investigation, we treated nine (six men/three women) patients suffering from enteric fistulae with VAC therapy. The median age of the patients was 48 (range, 37-67) years. The median duration of VAC therapy was 76 (range, 53-128) days. The median length of stay in the intensive care unit was 44 (range, 25-127) days. The median APACHE II score was 23 (range, 18-25). The predicted mortality was 40%; the actual mortality was 11% (one patient). Primary fascial closure was achieved after median 91 (range, 89-92) days in three patients (33%) and secondary fascial closure after median 292 (range, 252-546) days in another three patients (33%). Fistulae were cured with VAC (five patients, 56%) and surgical resection (three patients, 33%). None of the patients developed a refistulation at the time of follow-up. CONCLUSIONS: Control of enteric fistulae by VAC therapy can lead to spontaneous fistula closure and is associated with a low mortality.

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance.

INTRODUCTION: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA. METHODS: Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. RESULTS: A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). CONCLUSION: This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Recommendations for the management of MPS VI: systematic evidence- and consensus-based guidance.

INTRODUCTION: Mucopolysaccharidosis (MPS) VI or Maroteaux-Lamy syndrome (253200) is an autosomal recessive lysosomal storage disorder caused by deficiency in N-acetylgalactosamine-4-sulfatase (arylsulfatase B). The heterogeneity and progressive nature of MPS VI necessitates a multidisciplinary team approach and there is a need for robust guidance to achieve optimal management. This programme was convened to develop evidence-based, expert-agreed recommendations for the general principles of management, routine monitoring requirements and the use of medical and surgical interventions in patients with MPS VI. METHODS: 26 international healthcare professionals from various disciplines, all with expertise in managing MPS VI, and three patient advocates formed the Steering Committee group (SC) and contributed to the development of this guidance. Members from six Patient Advocacy Groups (PAGs) acted as advisors and attended interviews to ensure representation of the patient perspective. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with expertise and experience managing patients with MPS VI and the manuscript has been evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. RESULTS: A total of 93 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions. Consensus was reached on all statements after two rounds of voting. The greatest challenges faced by patients as relayed by consultation with PAGs were deficits in endurance, dexterity, hearing, vision and respiratory function. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). CONCLUSION: This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS VI and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Orthopaedic challenges for mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are a group of diseases characterized by abnormal accumulation of glycosaminoglycans (GAGs). Although there are differences among the various disease types, the osteoarticular system is always involved. The aim of the present study was to establish a framework for MPS-related orthopaedic manifestations and for their treatment. The authors, affiliated to three different Italian Orthopaedic Centres, report data taken from the literature reviewed in light of their accumulated professional experience. Bone alterations make up what is known as dysostosis multiplex, involving the trunk and limbs and with typical radiological findings. Joints are affected by pathological tissue infiltrations. The cervical spinal cord is involved, with stenosis and cervical and occipitocervical instability. In MPS there is a much higher incidence of scoliosis compared with healthy subjects without any particular distinctive feature. Kyphosis of the spine is more frequent and also more severe because of its possible neurological complications, and it is localized at the thoracolumbar level with a malformed vertebra at the top of the deformity. Evolving forms, and those associated with neurological damage, require anteroposterior spine fusion. The hip is invariably involved, with dysplasia affecting the femoral neck (coxa valga), the femoral epiphysis (loss of sphericity, osteonecrosis), and the femoral acetabulum which is flared. All these features explain the tendency to progressive hip migration. Genu valgum is often found (a deviation of the physiological axis with an obtuse angle opening laterally). This deformity is often localized at the proximal tibial metaphysis; it causes functional limitations and leads to an irregular erosion of the articular cartilage. In young patients who still have the growth plate, it is possible to execute a medial hemiepiphysiodesis, a temporary inhibition of cartilage growth, with progressive axis correction. In this paper, the characterisation of clinical features and the review of treatments are divided into separate sections based on the part of the body involved. The conclusions of each section are presented as a summary. One section discusses the high risk of anaesthesia-related complications requiring the collaboration of specifically trained personnel.

Unique medical issues in adult patients with mucopolysaccharidoses.

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.

Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 years.

BACKGROUND: Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (<12 years). METHODS: In this study, we evaluated: urinary GAG content, hepato/splenomegaly, heart valvulopathies, otorinolaryngological symptoms, joint range of motion, growth, distance covered in the 6-minute walk test, neurological involvement. For data analysis, the 27 patients were divided into three groups according to the age at start of ERT: ≤5 years, >5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a "severe" phenotype were compared with "attenuated" ones. RESULTS: Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. CONCLUSIONS: Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons.

Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure.

BACKGROUND: Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder characterized by progressive multi-organ disease. The standard of care for patients with the severe phenotype (Hurler syndrome, MPS I-H) is early hematopoietic stem cell transplantation (HSCT). However, skeletal disease, including hip dysplasia, is almost invariably present in MPS I-H, and appears to be particularly unresponsive to HSCT. Hip dysplasia may lead to pain and loss of ambulation, at least in a subset of patients, if left untreated. However, there is a lack of evidence to guide the development of clinical guidelines for the follow-up and treatment of hip dysplasia in patients with MPS I-H. Therefore, an international Delphi consensus procedure was initiated to construct consensus-based clinical practice guidelines in the absence of available evidence. METHODS: A literature review was conducted, and publications were graded according to their level of evidence. For the development of consensus guidelines, eight metabolic pediatricians and nine orthopedic surgeons with experience in the care of MPS I patients were invited to participate. Eleven case histories were assessed in two written rounds. For each case, the experts were asked if they would perform surgery, and they were asked to provide information on the aspects deemed essential or complicating in the decision-making process. In a subsequent face-to-face meeting, the results were presented and discussed. Draft consensus statements were discussed and adjusted until consensus was reached. RESULTS: Consensus was reached on seven statements. The panel concluded that early corrective surgery for MPS I-H patients with hip dysplasia should be considered. However, there was no full consensus as to whether such a procedure should be offered to all patients with hip dysplasia to prevent complications or whether a more conservative approach with surgical intervention only in those patients who develop clinically relevant symptoms due to the hip dysplasia is warranted. CONCLUSIONS: This international consensus procedure led to the construction of clinical practice guidelines for hip dysplasia in transplanted MPS I-H patients. Early corrective surgery should be considered, but further research is needed to establish its efficacy and role in the treatment of hip dysplasia as seen in MPS I.

Mesh fixation in laparoscopic incisional hernia repair: glue fixation provides attachment strength similar to absorbable tacks but differs substantially in different meshes.

BACKGROUND: Laparoscopic ventral hernia repair has gained popularity among minimally invasive surgeons. However, mesh fixation remains a matter of discussion. This study was designed to compare noninvasive fibrin-glue attachment with tack fixation of meshes developed primarily for intra-abdominal use. It was hypothesized that particular mesh structures would substantially influence detachment force. STUDY DESIGN: For initial evaluation, specimens of laminated polypropylene/polydioxanone meshes were anchored to porcine abdominal walls by either helical titanium tacks or absorbable tacks in vitro. A universal tensile-testing machine was used to measure tangential detachment forces (TF). For subsequent experiments of glue fixation, polypropylene/polydioxanone mesh and 4 additional meshes with diverse particular mesh structure, ie, polyvinylidene fluoride/polypropylene mesh, a titanium-coated polypropylene mesh, a polyester mesh bonded with a resorbable collagen, and a macroporous condensed PTFE mesh were evaluated. RESULTS: TF tests revealed that fibrin-glue attachment was not substantially different from that achieved with absorbable tacks (median TF 7.8 Newton [N], range 1.3 to 15.8 N), but only when certain open porous meshes (polyvinylidene fluoride/polypropylene mesh: median 6.2 N, range 3.4 to 10.3 N; titanium-coated polypropylene mesh: median 5.2 N, range 2.1 to 11.7 N) were used. Meshes coated by an anti-adhesive barrier (polypropylene/polydioxanone mesh: median 3.1 N, range 1.7 to 5.8 N; polyester mesh bonded with a resorbable collagen: median 1.3 N, range 0.5 to 1.9 N), or the condensed PTFE mesh (median 3.1 N, range 2.1 to 7.0 N) provided a significantly lower TF (p < 0.01). CONCLUSIONS: Fibrin glue appears to be an appealing noninvasive option for mesh fixation in laparoscopic ventral hernia repair, but only if appropriate meshes are used. Glue can also serve as an adjunct to mechanical fixation to reduce the number of invasive tacks.

Septic physeal separation of proximal femur in a newborn.

In newborns physeal separations and septic osteomyelitis or arthritis are unusual, representing a problem in diagnosis and treatment. Therapy needs to be carried out soon in order to prevent anatomical and functional consequences. Association between septic event and physeal separation is rare. We report a 28-day-old female, admitted for elevated temperature, who underwent three nonorthopaedic surgical procedures before, and orthopaedic evaluation 8 days after admission. After an X-ray and an ultrasonography a septic arthritis with consequent hip dislocation was supposed. Only at the time of surgery a separation between the epiphysio-trochanteric nuclei complex and the femoral shaft was observed, with clear hip joint. The interest in this case consists in the difficulty of the differential diagnosis at the first evaluation, the orthopaedic misdiagnosis based on the lack of complete preoperative imaging, and finally the long-term excellent result after a prompt surgical treatment.

Adjuvant bisphosphonates in endocrine-responsive breast cancer: what is their place in therapy?

Recent advances in the treatment of early breast cancer have improved clinical outcomes and prolonged survival, especially in women with endocrine-responsive disease. However, cancer therapies including cytotoxic chemotherapy, ovarian suppression, and aromatase inhibitors can drastically reduce circulating estrogen, increasing bone loss and fracture risk. Because most women with early breast cancer will live for many years, it is important to protect bone health during cancer therapy. Several recent clinical trials combining adjuvant endocrine therapy with bisphosphonates have demonstrated efficacy for preventing cancer treatment-induced bone loss in pre- and postmenopausal women with early breast cancer. The largest body of evidence supporting the use of adjuvant bisphosphonates comes from studies with zoledronic acid; however, studies with risedronate, ibandronate, and denosumab (a biologic agent) have also demonstrated efficacy for preventing bone loss. Adding zoledronic acid to endocrine therapy prevents bone loss and improves bone mineral density (BMD). In addition, preclinical studies suggest that bisphosphonates have direct and indirect antitumor activity, such as inducing tumor cell apoptosis, reducing tumor cell adhesion and invasion, reducing angiogenesis, activating immune responses, and synergy with chemotherapy agents, among others. Clinical trials have demonstrated significantly improved disease-free survival in patients receiving adjuvant endocrine therapy plus zoledronic acid compared with endocrine therapy alone. Ongoing studies will further define the role of adjuvant bisphosphonates in maintaining bone health and improving clinical outcomes. The available evidence suggests that pre- and postmenopausal patients may receive clinical benefit from including bisphosphonates as part of their adjuvant treatment regimen for endocrine-responsive early breast cancer.

Is Endocrine Therapy Really Pleasant? Considerations about the Long-Term Use of Antihormonal Therapy and Its Benefit/Side Effect Ratio.

Endocrine therapy has become a key part in the adjuvant treatment of hormone responsive breast cancer. The positive effect on relapse risk reduction is well defined, but therapy is not free from bothersome side effects for which estrogen deprivation accounts to a great extent. Since endocrine therapy is usually prescribed for 5 years or longer to optimally display its protective effect, and because physical strain is missing, good tolerability and safety properties are important, particularly in low-risk patients. While tamoxifen has been the standard adjuvant endocrine treatment with well documented efficiency, it is increasingly replaced by third generation aromatase inhibitors due to their better effectiveness and tolerability. Because tamoxifen holds a risk for life-threatening adverse events such as endometrial cancer, pulmonary embolism, and stroke, its recommended duration of therapy is limited to 5 years, also because extension beyond that time did not produce a measurable advantage. While some side effects are present both with tamoxifen and aromatase inhibitors, differences in side effect profiles are well established. Although side effects of aromatase inhibitor-related therapy usually are mild and common to symptoms of menopause, misconception of the symptoms and their mechanism of action, as well as lack of knowledge about how to handle them, can easily lead to dangerous discontinuation of therapy.

Pulled elbow in infancy: Diagnostic role of imaging.

PURPOSE: Pulled elbow is a common injury in infancy. Typically the child, after a sudden pull, refuses to use the arm. The history and clinical findings are sufficient to make the diagnosis, and radiography or ultrasonography are not necessary. When imaging procedures are performed, a few small signs are useful to confirm the diagnosis of pulled elbow. MATERIALS AND METHODS: The authors reviewed the radiographic and ultrasonographic signs reported to be suggestive of pulled elbow (increased radio-condylar distance, increased radio-coronoid distance, proximal radio-ulnar diastasis, deviation of the radio-condylar line) and attempted to confirm their presence in children affected by this trauma. RESULTS: Increased radio-condylar and radio-coronoid distance were present in 8 of 8 cases; proximal radio-ulnar diastasis and deviation of the radio-condylar line were inconsistently present. Ultrasonography gave contradictory results: CONCLUSIONS: In typical cases of pulled elbow, radiography or ultrasonography are not necessary for diagnosis and treatment. Imaging procedures are recommended only in the case of non typical history, in the presence of deformity or traumatic skin lesions and in children over six years of age. Increased radio-coronoid distance on the affected side is the most frequent and visible sign, which can confirm the diagnosis of pulled elbow. Increased radio-condylar distance is also present, but it is not easy to visualize. Proximal radio-ulnar diastasis and deviation of the radio-condylar line are inconstant. Ultrasonography is difficult to standardize.