Oncovascular Surgery for Soft-Tissue Sarcomas of the Lower Limbs with Vascular Contact: Comparison of Arterial Reconstruction and Arterial Subadventitial Dissection.

BACKGROUND: Soft-tissue sarcomas represent approximately 1% of adult malignancies. When they involve the lower limbs (LLs) and come into contact with blood vessels, the therapeutic choice was historically a primary amputation. Today, radical surgical resection with wide margins of safety is the primary therapeutic option for multidisciplinary limb-salvage surgery. The aim was to compare the morbidity and mortality results of an oncologic resection of LL soft-tissue sarcomas with arterial replacement (AR) to that obtained with arterial subadventitial dissection (ASD). METHODS: All consecutive patients with arterial close contact soft-tissue sarcomas of LL were included. Two groups were formed: an AR group where AR was performed following surgical resection and an ASD group in which the artery in contact with the tumor was preserved by ASD. Fisher's exact test was used. RESULTS: Eighteen patients with a median age of 61.50 (interquartile range [IQR] 54.25-69.75) years underwent oncovascular surgery with orthopedic and vascular surgeons between August 2013 and May 2022. Sarcomas were all located in the thigh. Nine patients were enrolled in each of the 2 groups. The 6-month survival rate was 77.78% in the AR group and 100% in the ASD group (P = 0.4). In the AR group, 2 patients presented local recurrence, with a median recurrence-free time of 24.48 (IQR 14.08-34.87) months, and 2 patients presented distant metastases, with metastasis-free time of 13.45 (IQR 8.12-35.11) months. In the ASD group, no local recurrence was observed, and 2 patients presented metastases with a median metastasis-free time of 3.90 (IQR 3.18-4.61) months. Six patients in the AR group and 7 in the ASD group required surgical revision (P = 0.017). No major amputation was necessary. CONCLUSIONS: Oncovascular surgery for LL sarcomas with ASD is certainly more locally morbid perioperatively than that with AR but provides patients with better medium-term survival.

Metastatic Kaposi sarcoma in a non-HIV patient leading to metacarpal lysis then upper-limb amputation: a case report.

We report the case of a HIV-seronegative 57 year-old man, with known classic Kaposi's disease and in whom a secondary localization in the upper left limb led to carpal and metacarpal lysis in the left hand. This unfavorable local evolution led to left transhumeral amputation.

Severe asthma guidelines in children and adolescents: A practical document for physicians.

Asthma is a common disease in childhood with a minority of affected children suffering from severe asthma. Patients with severe asthma require high dose inhaled glucocorticoids plus a second controller and/or systemic corticosteroids to be well-controlled or remain uncontrolled despite such treatment. Although only a small subset of children and adolescents falls in this category, the management of affected patients represents a major concern for pediatricians. Guidelines and recommendations have been designed to guide the management of this group of patients. Though the terms "recommendations" and "guidelines" are often used interchangeably, it should be noted that the first one should be used more narrowly to identify specific actions and the second one to broadly refer to the umbrella under which multiple recommendations for a specific condition are provided. Moreover, the availability of several and sometimes-conflicting documents on severe asthma management both in adult and pediatric age could generate confusion among health care professionals. The manuscript analyses seven papers addressing severe asthma, comparing any key aspects and differences. Finally, we tried to create a more practical document for physicians to simplify the interpretation of the several available documents on severe asthma management focusing the pediatric age.

Superficial acral fibromyxoma: a case of missed diagnosis.

Superficial acral fibromyxoma (SAFM) is a rare, benign, slow-growing fibroblastic tumour of the soft tissue that is part of the group of myxoid soft-tissue neoplasms. It is a rare entity and usually occurs in the acral regions. We report the case of a 64-year-old man who presented to the emergency room for a lesion expected to have occurred as a result of an ingrown toenail. Because this patient had a history of repeated recurrences despite multiple surgical wedge excisions, we performed a complete surgical excision, and the pathological analysis confirmed the suspected diagnosis of SAFM. There was no recurrence at the 6-month follow-up. This case highlights the fact that this tumour is still misunderstood and underrecognized by surgeons and this often leads to delayed diagnosis. Although it is a rare entity, clinicians should be aware of this tumour in cases of recurring ingrown toenails.

Overall survival in patients with re-excision of positive microscopic margins of limb and trunk wall soft tissue sarcoma operated outside of a reference center: a nationwide cohort analysis.

BACKGROUND: This French nationwide NETSARC exhaustive prospective cohort aims to explore the impact of systematic re-excision (RE) as adjuvant care on overall survival (OS), local recurrence free survival (LRFS), and local and distant control (RFS) in patients with soft tissue sarcoma (STS) with positive microscopic margins (R1) after initial resection performed outside of a reference center. METHODS: Eligible patients had experienced STS surgery outside a reference center from 2010 to 2017, and had R1 margins after initial surgery. Characteristics and treatment comparisons used chi-square for categorical variables and Kruskall-Wallis test for continuous data. Survival distributions were compared in patients reexcised (RE) or not (No-RE) using a log-rank test. A Cox proportional hazard model was used for subgroup analysis. RESULTS: A total of 1,284 patients had experienced initial STS surgery outside NETSARC with R1 margins, including 1,029 patients with second operation documented. Among the latter, 698 patients experienced re-excision, and 331 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, tumor size, tumor depth, and histotype in the population of patients re-excised (RE) or not (No-RE). The study identified RE as an independent favorable factor for OS (HR 0.36, 95%CI 0.23-0.56, p<0.0001), for LRFS (HR 0.45, 95%CI 0.36-0.56, p<0.0001), and for RFS (HR 0.35, 95%CI 0.26-0.46, p<0.0001). CONCLUSION: This large nationwide series shows that RE improved overall survival in patients with STS of extremities and trunk wall, with prior R1 resection performed outside of a reference center. RE as part of adjuvant care should be systematically considered.

Engineering Novel 3D Models to Recreate High-Grade Osteosarcoma and its Immune and Extracellular Matrix Microenvironment.

Osteosarcoma (OS) is the most common primary bone cancer, where the overall 5-year surviving rate is below 20% in resistant forms. Accelerating cures for those poor outcome patients remains a challenge. Nevertheless, several studies of agents targeting abnormal cancerous pathways have yielded disappointing results when translated into clinic because of the lack of accurate OS preclinical modeling. So, any effort to design preclinical drug testing may consider all inter-, intra-, and extra-tumoral heterogeneities throughout models mimicking extracellular and immune microenvironment. Therefore, the bioengineering of patient-derived models reproducing the OS heterogeneity, the interaction with tumor-associated macrophages (TAMs), and the modulation of oxygen concentrations additionally to recreation of bone scaffold is proposed here. Eight 2D preclinical models mimicking several OS clinical situations and their TAMs in hypoxic conditions are developed first and, subsequently, the paired 3D models faithfully preserving histological and biological characteristics are generated. It is possible to shape reproducibly M2-like macrophages cultured with all OS patient-derived cell lines in both dimensions. The final 3D models pooling all heterogeneity features are providing accurate proliferation and migration data to understand the mechanisms involved in OS and immune cells/biomatrix interactions and sustained such that engineered 3D preclinical systems will improve personalized medicine.

Biological Treatments and Target Therapies for Pediatric Respiratory Medicine: Not Only Asthma.

We present a description of pediatric pneumology biological medications and other target therapies. The article aims at introducing the importance of a molecular approach to improve treatments. The first item treated was T2-High asthma and its current biological treatment and prescribing indications to propose a flow-chart to guide the clinical choice. Molecular rationales of such treatments are used to introduce a more general description of the biological and molecular approach to target therapies application. We introduce a general interpretation approach to neutrophilic asthma using the molecular plausibility one in order to propose possible future treatments mainly targeting interleukin-1 (IL-1), IL-17, IL-12, and IL-23. Indeed, cytokines can be excellent targets for several biological treatments. Downregulation of specific cytokines can be crucial in treating autoinflammatory and rheumatological diseases with a pulmonary involvement. Such conditions, although rare, should be early recognized as they can involve significant improvement with a properly targeted therapy. We face these conditions in a cherry-picking fashion picturing SAVI (STING-associated vasculopathy with onset in infancy), CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), and COPA (coat proteins alpha syndrome) syndrome pulmonary involvement. Such examples are functional to introduce molecular-based approach for patients with rare conditions. Molecular plausibility can be highly valuable in treating patients with not-approved but possibly highly effective therapies. Due to the rarity of these conditions, we stress the concept of basket trials using the example of cytokinin-directed immunosuppressive treatment. Lastly, we provide an example of augmentative therapy using the alpha1 antitrypsin deficiency as a model. In summary, the article presents a collection of the most recent achievements and some possible future developments of target therapies for pediatric pulmonary conditions.

Difficult and Severe Asthma in Children.

Asthma is the most frequent chronic inflammatory disease of the lower airways affecting children, and it can still be considered a challenge for pediatricians. Although most asthmatic patients are symptom-free with standard treatments, a small percentage of them suffer from uncontrolled persistent asthma. In these children, a multidisciplinary systematic assessment, including comorbidities, treatment-related issues, environmental exposures, and psychosocial factors is needed. The identification of modifiable factors is important to differentiate children with difficult asthma from those with true severe therapy-resistant asthma. Early intervention on modifiable factors for children with difficult asthma allows for better control of asthma without the need for invasive investigation and further escalation of treatment. Otherwise, addressing a correct diagnosis of true severe therapy-resistant asthma avoids diagnostic and therapeutic delays, allowing patients to benefit from using new and advanced biological therapies.

A Novel, Portable MESH Nebulizer-An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers.

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device. Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'-IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone. Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability. Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.

Relationship between quality of life and behavioural disorders in children with persistent asthma: a Multiple Indicators Multiple Causes (MIMIC) model.

Knowledge on multiple interdependences between quality of life (QoL) and behavioural problems in relation to asthma severity and control is undetermined. The aims of the study were: (i) to assess the relationship of QoL and behavioural problems with asthma severity and control (ii) to predict children's "abnormal/borderline" status with variation in QoL. For these purposes a multicenter case-control study on 47 Severe Asthma (SA) and 94 Moderate Asthma (MA) children was performed. The MIMIC approach was applied to investigate the effect of SA and non-controlled asthma (NC) on QoL and behavioural disorders. Logistic regression was used to estimate probabilities of having an "abnormal/borderline" status with variation in QoL. The MIMIC model showed that the magnitude of the effect of SA and NC was larger on QoL (ß = -0.37 and ß = -0.30, respectively) than on behavioural problems (ß = 0.27). With regards to the probability of having a borderline status, in MA a QoL of 1 returned a probability of 0.81, whereas in SA a QoL of 1 returned a probability of 0.89. In conclusion, SA children are highly affected by impaired QoL and behavioural problems. The MIMIC model allowed us to obtain a comprehensive assessment of QoL and behavioural problems with asthma severity and control.

Percutaneous Image-Guided Cryoablation of Osteoblastoma.

OBJECTIVE. The aim of this observational study was to assess safety and clinical outcomes of percutaneous image-guided cryoablation (CA) to treat osteoblastomas (OBs) at various osseous sites. MATERIALS AND METHODS. A retrospective search was performed to identify patients presenting with painful OBs who underwent CA at the University Hospitals of Strasbourg between March 2007 and December 2018. Ten patients (seven men, three women; median age, 21 years old) were identified and included. Medical records were reviewed to assess complications and clinical outcomes. RESULTS. Median OB diameter was 16.5 mm (range, 16-28 mm). OBs were located in the spine (n = 7), calcaneus (n = 1), fibula (n = 1), and third metacarpal bone (n = 1). In 90% of cases (n = 9), one or more critical structures were within 1 cm of the OB (median distance, 5 mm; range, 2-8 mm), thus requiring extensive protective measures. Technical success was achieved in all cases. Two (20%) immediate neural complications were noted. One major complication was consistent with a permanent sensory deficit of the arm. One minor complication was consistent with a transient right Horner syndrome, which completely resolved after 48 hours with high-dose steroids. Median clinical follow-up was 12 months. Primary clinical success was 100% and 78% at 1 and 12 months of follow-up, respectively, with two patients presenting with recurring pain. CONCLUSION. Percutaneous image-guided CA represents an effective therapeutic option for patients affected by painful OBs; the safety profile of the procedure is acceptable as long as comprehensive protective measures are deployed in light of the frequent close proximity of critical structures.

Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France.

BACKGROUND: Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. MATERIALS AND METHODS: Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. RESULTS: A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. CONCLUSION: Initial diagnostic management requires improvement, especially outside of specialized centers. IMPLICATIONS FOR PRACTICE: This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives.

Asthma: Differential Diagnosis and Comorbidities.

Childhood asthma remains a multifactorial disease with heterogeneous clinical phenotype and complex genetic inheritance. The primary aim of asthma management is to achieve control of symptoms, in order to reduce the risk of future exacerbations and progressive loss of lung function, which results especially challenging in patients with difficult asthma. When asthma does not respond to maintenance treatment, firstly, the correct diagnosis needs to be confirmed and other diagnosis, such as cystic fibrosis, primary ciliary dyskinesia, immunodeficiency conditions or airway and vascular malformations need to be excluded. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Moreover, all possible risk factors or comorbidities (gastroesophageal reflux, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea and obesity) should be investigated. At the same time, the possible reasons for poor symptom control need to be find in all modifiable factors which need to be carefully assessed. Non-adherence to medication or inadequate inhalation technique, persistent environmental exposures and psychosocial factors are, currently, recognized as the more common modifiable factors. Based on these premises, investigation and management of asthma require specialist multidisciplinary expertise and a systematic approach to characterizing patients' asthma phenotypes and delivering individualized care. Moreover, since early wheezers are at higher risk of developing asthma, we speculate that precocious interventions aimed at early diagnosis and prevention of modifiable factors might affect the age at onset of wheezing, reduce the prevalence of persistent later asthma and determine long term benefits for lung health.

Exercise-Induced Bronchospasm and Allergy.

Sport is an essential part of childhood, with precious and acknowledged positive health effects but the impact of exercise-induced bronchoconstriction (EIB) significantly reduces participation in physical activity. It is important to recognize EIB, differentiating EIB with or without asthma if the transient narrowing of the airways after exercise is associated with asthmatic symptoms or not, in the way to select the most appropriate treatment among the many treatment options available today. Therapy is prescribed based on symptoms severity but diagnosis of EIB is established by changes in lung function provoked by exercise evaluating by direct and indirect tests. Sometimes, in younger children it is difficult to obtain the registration of difference between the preexercise forced expiratory volume in the first second (FEV1) value and the lowest FEV1 value recorded within 30 min after exercise, defined as the gold standard, but interrupter resistance, in association with spirometry, has been showed to be a valid alternative in preschool age. Atopy is the main risk factor, as demonstrated by epidemiologic data showing that among the estimated pediatric population with EIB up to 40% of them have allergic rhinitis and 30% of these patients may develop adult asthma, according with atopic march. Adopting the right treatment and prevention, selecting sports with no marked hyperventilation and excessive cooling of the airways, children with EIB can be able to take part in physical activity like all others.

Omalizumab in patient with aspirin exacerbated respiratory disease and chronic idiopathic urticaria.

Aspirin hypersensitivity associated with chronic rhinosinusitis-with or without nasal polyposis-and asthma resistant to conventional therapy defines the aspirin-exacerbated respiratory disease (AERD). We describe the case of a 15-year-old female patient with adverse reaction to aspirin, chronic rhinosinusitis, and severe asthma. She also experienced chronic idiopathic urticaria worsened by non-steroidal anti-inflammatory drug administration. AERD was diagnosed based on clinical history and symptoms. Given the poor responsiveness to standard therapy for respiratory and cutaneous symptoms, omalizumab was administered for 24 weeks with control of respiratory symptoms and short term improvement of cutaneous symptoms. Pediatr Pulmonol. 2017;52:E26-E28. © 2016 Wiley Periodicals, Inc.

Minimally invasive surgery with locking plate for periprosthetic femoral fractures: technical note.

PURPOSE: Periprosthetic fractures of the femur are increasing due to the increase of arthroplasties and the aging population. They concern a population that is often elderly and with important comorbidities that complicate managing this already complex pathology. Usual complications of classic osteosynthesis are numerous, including infections and nonunions and the need for delayed weight bearing after surgery. METHODS-RESULTS: The development of locking plates has allowed complication avoidance. When used in minimally invasive surgery, they combine the biological advantages of closed-wound surgery to the mechanical advantages of locking plates, which have better stability in fragile bones. We propose a technical update on handling such fractures by using locking plates under minimally invasive surgery. DISCUSSION-CONCLUSION: In our experience, under certain guidelines, this allows for immediate post-operative full weight bearing, which is beneficial to these often elderly patients.

Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone.

BACKGROUND: Giant cell tumours (GCT) of bone are benign neoplasms associated with a high rate of local recurrence after extensive intra-lesional curettage. Recently, understanding of the biological molecular availability of strong anti-osteoclastic drugs has suggested their potential value in reducing local recurrences after curettage. Through a phase II clinical trial, we investigated the effect of a short treatment with zoledronic acid (ZOL) after intra-lesional curettage of GCT, as well as local recurrence and tolerance of the treatment. METHODS AND PATIENTS: Twenty-four patients were enrolled in a multicentre, phase 2 study. The patients were treated with extensive intra-lesional curettage followed by five courses of ZOL (4 mg IV every 3 weeks). The clinical and biological tolerance of each patient was assessed. Patients were reviewed clinically and by X-ray every 6 months until the end of the study (36 months). RESULTS: Eighteen out of 20 patients reported side-effects with ZOL, mainly grade 1 and 2 effects. The local recurrence rate was 15%; three patients had a recurrence, one at 4 months (huge GCT of the sacrum), one at 24 months (patient who discontinued the treatment after the first course of ZOL), and one after the observational period, at 58 months. Finally, local relapse-free survival was 82 ± 9% at 60 months. CONCLUSION: Short adjuvant treatments with ZOL after extensive intra-lesional curettage of GCT were associated with a low rate of recurrence but did not prevent local recurrence in this study. No serious general adverse effects were observed. More studies are needed to evaluate the potential benefit of medical bisphosphonate injections combined with intra-lesional curettage in the treatment of GCTB.

Leukotriene synthesis during respiratory syncytial virus bronchiolitis: influence of age and atopy.

Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis in infants and an important risk factor for the development of recurrent wheezing and asthma. Cysteinyl leukotrienes were implicated in the pathophysiology of these diseases, and are being targeted for their diagnosis and therapy. We measured urinary leukotriene E4 (LTE4) in infants with RSV bronchiolitis in comparison with controls without respiratory infection, and investigated whether medical and family history, age, and passive exposure to tobacco smoke are related to urinary leukotriene excretion. We studied 33 infants with bronchiolitis and 25 controls, 1-12 months of age. Demographic and historical data were obtained from informed-consent forms and questionnaires completed by the parents. RSV was detected in nasal secretions by enzyme-linked immunoassay. Urine samples were collected on day of admission and were analyzed for LTE4 with an enzyme-linked immunoassay. Urinary LTE4 was 8-fold higher in infants with bronchiolitis than in controls. Leukotriene excretion was significantly higher in infected infants <6 months of age with a medical history of eczema or dry cough and/or family history of asthma. Multivariate analysis revealed that eczema and dry cough are independently associated with high LTE4 excretion during bronchiolitis. Exposure to tobacco smoke did not affect urinary LTE4. Our study shows that leukotriene synthesis during bronchiolitis is particularly elevated in younger infants with an atopic/asthmatic background. Urinary LTE4 may become a valuable, noninvasive marker for the identification of patients who will benefit most from therapy with leukotriene modifiers for management of bronchiolitis.