Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Management of Open Pediatric Fractures: Proposal of a New Multidisciplinary Algorithm.

BACKGROUND: An algorithm for managing open fractures in children is still being debated; the present study suggests an evidence-based way to manage these patients in the emergency department. METHODS: The literature on "Open fractures in children" was carefully analyzed using keywords. The primary sources were The Cochrane Library, PubMed, and Researchgate. CONCLUSION: We proposed an evidence-based algorithm for managing open fractures in children to standardize clinical practice and improve the care of these patients.

Long-term outcome after brace treatment of Scheuermann's kyphosis: an observational controlled cohort study.

BACKGROUND: In the literature, there are several papers on Scheuermann's kyphosis. It is a structural deformity of the spine that is characterized by anterior wedging of 5° or more of 3 adjacent thoracic vertebral bodies with kyphosis measuring greater than 45° between T5 and T12. Bracing treatment is able to obtain, during skeletal growth, remodeling of the deformed vertebrae. AIM: The aim of this study was to evaluate the effectiveness of conservative treatment in Scheuermann's kyphosis at a minimum follow-up of 10 years. DESIGN: This is an observational controlled cohort study nested in a prospective clinical on-going database in patients with Scheuermann kyphosis. SETTING: Inpatients and outpatients in Rome. METHODS: From a consecutive series of patients included in a prospective database, we selected 158 patients with thoracic Scheuermann's kyphosis who were treated using an anti-gravity brace: 93 males and 65 females. The mean age at the beginning of the treatment was 14 years. The time bracing prescribed was a max of 20 hours daily and a min of 16 hours daily. Weaning was started when a full recovery of vertebral geometry was seen on a lateral radiograph view or when growing was ended. Radiographical measurements were performed on radiographs from a lateral projection at baseline (t1), at the end of the treatment (t2) and at 10 years of minimum follow-up (t3). To avoid the great variance in the range of curve angles in thoracic kyphosis (TK) that rely on the radiological position, X-rays were performed observing the following position: standing with head straight, arms bent at 45° and hands lightly placed on a support. The anterior wedging angle (Alpha) of the apex vertebra and the degrees of the curve (Cobb methods) were analyzed using statistical analysis. RESULTS: The results from our study showed that in 158 patients with TK curves, the mean Cobb angle was 57.6±6.3 SD at baseline, 43.3±7.8 SD at the end of treatment and 44.49±7.4 SD at ten years of follow-up. The alpha angle was 14.43±2.535 SD at baseline and 8.571±3.589 SD at the end of treatment, and after ten years of follow-up, it was 8.654±3.57 SD. The mean duration of treatment was 28.42±12.07 months, and the mean follow-up was 128.3±11.07 months. The difference between baseline and end of treatment, tested with the one-way ANOVA comparisons test, was significant (P<0.0001) for both Cobb angle and alpha; instead, the difference between the end of treatment and follow-up was not significant (P=0.3277). CONCLUSIONS: The results confirm that conservative treatment in Scheuermann's kyphosis during skeletal growth is effective. Bracing treatment can remodel the deformed vertebrae. CLINICAL REHABILITATION IMPACT: At the 10-year follow-up after bracing, kyphosis curve correction was stable over time.

Anterolateral congenital tibial bowing: case report.

Background: The treatment of congenital curvatures (bowing) of the tibia still represents a challenging problem for all pediatric orthopedic surgeons because of its unpredictable course, especially if pseudoarthrosis occurs after a pathologic fracture of the tibia. Case presentation: We describe the case of a child affected by an isolated curvature of his left leg. The congenital malformation was discovered at birth and no other pathological clinical finding was present. The first x-ray showed the presence of a congenital curvature of the tibia of the antero-lateral type. He was born in another country (Romania) and when he first came to our clinical observation at the Orthopedic and Traumatology Department, Pediatric Hospital "Bambino Gesu'", Rome, the child was 14 months of age and had already started walking. Only a leg discrepancy of about 2 cm was present with consequent pelvis obliquity. At the beginning, we prescribed external lower limb orthoses and a simple shoe rise to prevent a tibial pathologic fracture and reduce pelvic obliquity. At periodical clinical follow-up visits and despite the external lower limb orthoses prescribed, a progressive worsening of the severe congenital tibial curvature was observed together with signs and symptoms, such as pain and limping, that suggested an objective "pre-fracture stage" of the tibial curvature; we decided to perform surgery. At the time of surgery, the child was three and a half years old. Surgery consisted of a double osteotomy, both of the fibula and of the tibia. Subtraction of the distal meta-diaphyseal portion of the fibula and tibial osteotomy in Correspondence: of the major anterolateral curvature. The tibial osteotomy was then stabilized by an internal Rush rod inserted proximally to the tibia under the cartilage growth plate and made it end inside the distal tibial epiphysis, crossing the distal tibial cartilage growth plate, preserving the ankle joint. Results: The patient had an immediately excellent outcome. The tibial osteotomy site healed perfectly. At periodical orthopedic follow-up visits, the child was found to be always better. No clinical significative evidence of growth disturbances, due to the Rush rod that crossed the distal tibial cartilage growth plate, were noted. X-rays showed that the Rush rod progressively migrated with tibial growth together with the tibial bone growth, always getting further away from the distal tibial cartilage growth plate. Moreover, even the leg-length discrepancy and the pelvic obliquity improved. After an eight-year follow up, the patient, now a young boy of 11 and a half years, has an excellent outcome. Conclusions: Our case report undoubtedly provides further important information for the treatment of these rare congenital disorders. In particular, it highlights the management of the "pre-fracture stage" in a severe congenital tibial antero-lateral curvature in a very young child and describes the surgical technique performed.

A Non-Linear Body Machine Interface for Controlling Assistive Robotic Arms.

OBJECTIVE: Body machine interfaces (BoMIs) enable individuals with paralysis to achieve a greater measure of independence in daily activities by assisting the control of devices such as robotic manipulators. The first BoMIs relied on Principal Component Analysis (PCA) to extract a lower dimensional control space from information in voluntary movement signals. Despite its widespread use, PCA might not be suited for controlling devices with a large number of degrees of freedom, as because of PCs' orthonormality the variance explained by successive components drops sharply after the first. METHODS: Here, we propose an alternative BoMI based on non-linear autoencoder (AE) networks that mapped arm kinematic signals into joint angles of a 4D virtual robotic manipulator. First, we performed a validation procedure that aimed at selecting an AE structure that would allow to distribute the input variance uniformly across the dimensions of the control space. Then, we assessed the users' proficiency practicing a 3D reaching task by operating the robot with the validated AE. RESULTS: All participants managed to acquire an adequate level of skill when operating the 4D robot. Moreover, they retained the performance across two non-consecutive days of training. CONCLUSION: While providing users with a fully continuous control of the robot, the entirely unsupervised nature of our approach makes it ideal for applications in a clinical context since it can be tailored to each user's residual movements. SIGNIFICANCE: We consider these findings as supporting a future implementation of our interface as an assistive tool for people with motor impairments.

An Overview on Carbon Quantum Dots Optical and Chemical Features.

Carbon quantum dots are the materials of a new era with astonishing properties such as high photoluminescence, chemical tuneability and high biocompatibility. Since their discovery, carbon quantum dots have been described as nanometric high-fluorescent carbon nanoparticles, but this definition has become weaker year after year. Nowadays, the classification and the physical explanation of carbon quantum dots optical properties and their chemical structure remain matter of debate. In this review, we provide a clear discussion on these points, providing a starting point for the rationalization of their classification and a comprehensive view on the optical and chemical features of carbon quantum dots.

Is Surface Topography Useful in the Diagnosis of Scoliosis? Validation of the Biometrical Holistic of Human Body (BHOHB).

BACKGROUND: The concern around repeated exposure to X-rays has been motivating doctors involved in scoliosis to seek alternative solutions. Surface topography (ST) analysis is a modern system that has been shown to have good results. The purpose of the study is to validate the new BHOHB hardware for the investigation of scoliosis in adolescents by comparing it to X-ray examinations and to assess the reliability of intraoperator and interoperator tests. METHODS: Ninety-five patients were enrolled in our study. All the patients were analyzed via the BHOHB method 2 times by 2 independent physicians (t0) and for a second time 2 or 3 months later (t1). The Pearson correlation coefficient was used to evaluate the relationship between the measurements obtained by BHOHB and the gold standard. The intraclass correlation coefficient (ICC) was used to assess intra- and interoperator reliability. Statistical analysis was performed with the GraphPad Prism 8 software. RESULTS: The correlations between the first and second operators in the measurements and between the BHOHB method and X-ray showed a very good to excellent r for both. A very good correlation was also confirmed for prominence measured by operators and by the BHOHB machine. Intra- and interoperator reliability was found to be very positive for both the first and the second physicians. CONCLUSIONS: We can state that ST can be useful for diagnosing and treating scoliosis. The recommendation is to use it primarily to evaluate the evolution of the curve, as in this mode, you can reduce the patient's exposure to X-rays. The results indicate that BHOHB measures are comparable to radiographs and not influenced by the operator.

An unusual case of extra-nodal interdigitating dendritic cell neoplasm: sarcoma or not?

INTRODUCTION: Interdigitating dendritic cell sarcoma (IDCS) represents an extremely rare neoplasm frequently originating from T-cell- associated dendritic antigen-presenting cells normally populating the paracortex of lymph nodes. Diagnosis is challenging due to the rarity of this neoplasm and the overlapping features with the other primary and metastatic spindle cell neoplasm, even more, when localized in an extra-nodal site. PATIENTS AND METHODS: Herein we report a case of 48 Years old woman with a six-month history of centimetric, quiet painful mass of the philtrum without other significant comorbidity. RESULTS: Histological report showed a proliferation of quiet bland spindle to plump cell, scattered multinucleated giant cell in a subtle background of lymphocytes. IHC study displays only positivity for S-100 and fine, granular scattered cytoplasmatic stain for CD68; all dendritic IHC markers were negative. Morphological and immunohistochemical analyses were consistent with extra-nodal Interdigitating Dendritic Cell Neoplasm. CONCLUSION: Interdigitating Dendritic Cell Sarcoma is a rare and challenging entity with a variable prognosis. We present a case of extra-nodal IDCS whit low worrisome histological features, emphasizing the need for further efforts to better definitely this rare neoplasm ad its potential for malignancy.

Intradural extramedullary cervical metastasis from Merkel cell carcinoma: a case report and literature review.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare aggressive primary skin carcinoma with an incidence of 44 cases per 100,000. The natural course of MCC often results in rapid growth and early metastasis. On the other hand, the spinal cord is rarely affected and frequently features the end stage of the disease. The aim of this paper was to clarify the management of patients with spine metastasis from a skin lesion and showed a case-based update. CASE PRESENTATION: A 73-year-old female was admitted to the Neurosurgical Department in December 2021 for a sudden right hemiparesis with bladder dysfunction and a history of cutaneous Merkel cell carcinoma. A magnetic resonance imaging (MRI) of the central nervous system (CNS) showed an intradural-extramedullary right-sided C6-C7 tumor with mass effect and edema of the cervical cord. The patient underwent a C6-C7 laminectomy with microsurgical total resection of the intradural extramedullary lesion. The neuropathological examination identified a metastasis from Merkel cell carcinoma. Nowadays, evidence for spinal metastasis from malignities skin cancer is generally lacking, probably because they are extremely rare. The exact time of life expectancy is controversial, and some clinicians use a cutoff of 3 months to determine whether surgical intervention should be offered, while others advocate at least 6 months of life expectancy. CONCLUSIONS: To the best of our knowledge, we showed the first case of solitary intradural extramedullary cervical spine metastasis from MCC. We recommend to consider metastasis of MCC in the differential diagnosis of spinal metastasis.

The conservative treatment of congenital scoliosis with hemivertebra: Report of three cases.

Introduction: Scoliosis is the most common type of congenital vertebral disease. This spinal disorder may be due to a failure of formation, segmentation, or a combination thereof. Complete failure of formation causes hemivertebra which can lead to unbalanced growth and deformation. Statistically, 25% of congenital curves do not evolve, 25% progress slightly, while the remaining 50% develop quickly and require treatment. Hemivertebrae can be divided into three types: non-segmented, semi-segmented, and fully-segmented. The fully-segmented types are most likely to progress. Hemivertebra in the thoracolumbar region shows higher rates of progression compared with those in the lumbar area. The treatment may be either conservative or surgical. In general, bracing is not recommended in short and rigid curves, although it may help process secondary curves. Objective: To assess the effectiveness of bracing in congenital scoliosis due to hemivertebra. Cases presentation: Searching in our database, we found three cases of patients with congenital scoliosis due to fully-segmented hemivertebra. The first of them was 6 years old at the time of diagnosis with a fully-segmented hemivertebra in L5, determining an L1-L5 (S1) lumbar curve. The second one was 10 years old at the time of diagnosis with a fully-segmented hemivertebra in L2 and a T11-L4 (L5 sacralized) thoracolumbar curve. The last one was 3 years old at the time of diagnosis with a fully-segmented hemivertebra in L3 (in six lumbar bodies), determining a thoracolumbar curve T12-L4. Results: We utilized a Milwaukee brace for the first patient, a Boston brace for the second patient, and a Progressive Action Short Brace (PASB) for the third patient. At the beginning of the treatment, the Cobb angles measured 23°, 53°, and 25°, respectively. During treatment, the Cobb angles measured 22°, 35°, and 15°, respectively. At the end of treatment, the Cobb angles measured 18°, 45°, and 12°, respectively. At long-term follow-up, the curves measured 20°, 45°, and 12° Cobb angles, respectively. Conclusions: Comparing our cases with those found in the literature we can confirm the ability of conservative treatment to change the natural history of congenital lumbar scoliosis due to failure of formation. From our experience, in all cases of CS with hemivertebra, before considering a surgical approach, conservative treatment should be implemented as early as possible without waiting for the progressive deformation of the adjacent normal vertebrae.

Survey, Analysis and Comparison of Radar Technologies for Embedded Vital Sign Monitoring.

Contactless vital sign monitoring systems are becoming increasing in demand for a wide range of biomedical applications. Millimetre-wave radars and embedded signal processing are the most promising technologies to enable non-contact vital signs monitoring. In this work, the challenging task of heart rate estimation from radar data has been addressed. Three different radar systems from Infineon, Texas Instruments and Acconeer, and four algorithms, FFT, Median-FFT, STFT and Median-STFT, have been analysed and compared against a reference sensor. Accuracy, as well as power figures, have been reported for all the radar systems. A dataset of 16 volunteers has been acquired, yielding a total of 400 minutes of radar-recorded vital sign data. The accuracy of the four investigated algorithms has been reported on average and per subject for every radar. The algorithm exploiting the Short Time Fourier Transform (STFT) is able to achieve an error as low as 0.02% on a single person and of 6.4% in heart rate estimation on average across the whole dataset.

Extended surgical resection for nonfunctioning duodenal neuroendocrine tumor.

Duodenal neuroendocrine tumors (NETs) account for <3% of all gastrointestinal NET. Most lesions are small-sized and are located in the first or second duodenal part. Tumoral grading, evaluated by Ki67 index, strongly influences patient's outcome. Endoscopic resection is recommended for lesions measuring <2 cm, while pancreaticoduodenectomy should be the treatment of choice for large duodenal NET; Whipple procedure should be preferred in case of duodenal origin and contiguity with gastric antrum. Involvement of surrounding structures, as well as the presence of resectable liver metastases, does not contraindicate surgical resection. Herein we report a case of a 68-year-old male, presenting with an extensive mass of the descending pre-ampullary duodenal part, with involvement of the right colon and the presence of a pericholecystic single liver metastasis. In spite of such advanced disease, surgery on the patient was successful, with an uneventful postoperative outcome.

Initial In-Brace Correction: Can the Evaluation of Cobb Angle Be the Only Parameter Predictive of the Outcome of Brace Treatment in Patients with Adolescent Idiopathic Scoliosis?

Background: Patients with a better initial in-brace correction could show a higher probability of a successful outcome. However, no one has investigated whether parameters can affect the outcomes. The aim of this retrospective study was to evaluate if the initial correction rate (ICR) could be predictive of the bracing outcome and to determine the role of some mechanical and biological parameters in ICR. Methods: The study population comprised 449 patients who met the inclusion criteria. Curve correction > 10° Cobb defines brace treatment success. Success and failure groups were compared in terms of the Risser sign, initial Cobb angle, initial Perdriolle value and ICR. Results: ICR significantly correlates with initial Perdriolle. The success group had a significantly lower value of Pedriolle and initial Cobb angles, Risser sign and ICR than the failure group. The ICR and lower Risser were significantly associated with the brace treatment outcome. This seems particularly suitable for positivity prediction (Predicting value VP+: 87%). Conclusions: This study confirms that immediate in-brace correction can foretell the brace treatment outcome. Patients with a low Risser sign and a high rate of in-brace correction showed a bracing success of 87%. A correlation between rotation and in-brace correction confirms that rotation is among the parameters that influence the deformed spine reaction to corrective actions the most.

L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling.

BACKGROUND: Cancer stem cells (CSC) have been implicated in tumor progression. In ovarian carcinoma (OC), CSC drive tumor formation, dissemination and recurrence, as well as drug resistance, thus contributing to the high death-to-incidence ratio of this disease. However, the molecular basis of such a pathogenic role of ovarian CSC (OCSC) has been elucidated only to a limited extent. In this context, the functional contribution of the L1 cell adhesion molecule (L1CAM) to OC stemness remains elusive. METHODS: The expression of L1CAM was investigated in patient-derived OCSC. The genetic manipulation of L1CAM in OC cells provided gain and loss-of-function models that were then employed in cell biological assays as well as in vivo tumorigenesis experiments to assess the role of L1CAM in OC cell stemness and in OCSC-driven tumor initiation. We applied antibody-mediated neutralization to investigate L1CAM druggability. Biochemical approaches were then combined with functional in vitro assays to study the molecular mechanisms underlying the functional role of L1CAM in OCSC. RESULTS: We report that L1CAM is upregulated in patient-derived OCSC. Functional studies showed that L1CAM promotes several stemness-related properties in OC cells, including sphere formation, tumor initiation and chemoresistance. These activities were repressed by an L1CAM-neutralizing antibody, pointing to L1CAM as a druggable target. Mechanistically, L1CAM interacted with and activated fibroblast growth factor receptor-1 (FGFR1), which in turn induced the SRC-mediated activation of STAT3. The inhibition of STAT3 prevented L1CAM-dependent OC stemness and tumor initiation. CONCLUSIONS: Our study implicate L1CAM in the tumorigenic function of OCSC and point to the L1CAM/FGFR1/SRC/STAT3 signaling pathway as a novel driver of OC stemness. We also provide evidence that targeting this pathway can contribute to OC eradication.

A New Proximal Femur Reconstruction Technique after Bone Tumor Resection in a Very Small Patient: An Exemplificative Case.

For patients too young to be fitted with an expandable prosthesis, limb salvage surgery requires other strategies. The main problems are related to the impossibility of implanting an expandable prosthesis to the residual bone growth that is much too big in relation to the bone size, with the precocious implant loosening and/or the residual absence of bone growth, as well as the problem of limb length and shape difference. In this paper, we report a possible reconstruction solution using a composite prosthesis for an Ewing's sarcoma of the proximal femur in an infant patient. After resection, a femoral stem was cemented into the distal third of a homoplastic humerus; a carbon fiber plate was used to stabilize the bone/homograft interface. At the one-year follow-up, the patient was free of disease and able to walk with only a slight limp. This case report describes a possible solution for very small patients. An adult humerus is of the right size to replace a child's lower limb segments, and the distal humerus can be shaped, maintaining a cortex stiff enough to support a prosthesis. Very young patients might obtain a faster osteointegration of the graft than adults, due to their higher biological activity and, in this case, the diapasonal shape of the allograft might also have contributed to accelerated fusion. Moreover, the use of a graft to fit the prosthesis avoids loosening issues due to canal widening, hypothetically providing more growing time before system failure and revision surgery. However, although this technique is promising, further studies are necessary to confirm our findings and to verify if this procedure allows easier future prosthesis implantation.

Treatment of CSF leakage and infections of dural substitute in decompressive craniectomy using fascia lata implants and related anatomopathological findings.

PURPOSE: Decompressive craniectomy (DC) is widely used to treat raised intracranial pressure (ICP) in cranial trauma and stroke. It is accompanied by numerous complications. The aim of our study is to assess the surgical treatment of infections related to the use of a dural substitute with concurrent CSF leakage performed at our institution. MATERIAL AND METHODS: A retrospective analysis of a series of 72 patients who underwent DC between 2011 and 2017 was performed. Seven cases (9%) showed infection related to the use of xenograft (bovine pericardium) and coexisting CSF leakage. Epidural/subdural empyemas were observed in seven cases; three in conjunction with an intracerebral abscess. For reconstruction, free anterolateral thigh fascia lata flaps were used, based on the size of the defect. RESULTS: After removal of the dural substitute and the implant of free fascia lata, infection and CSF leaks resolved in all. An anatomopathological examination of the implant at the later time of cranioplasty (CP) showed the tissue had become vascularized exhibiting integration with the native dura. No complications related to the harvesting of the fascia lata were observed. CONCLUSIONS: Fascia lata is a validated source of autologous grafts; it is cost-free and would appear to be the biological material most similar to the dura mater. The implanted material appears to maintain a lasting vitality when covered over with a well-vascularized scalp, even after a period of months, achieving a successful suppression of infection. Subsequent skull reconstruction is performed safely and easily using artificial bone.

Long-term results after brace treatment with Progressive Action Short Brace in adolescent idiopathic scoliosis.

BACKGROUND: In the literature, there are few papers on long-term results after brace treatment and there is no consensus on whether scoliotic curves stop progressing at skeletal maturity. To date the factors that could influence curve behaviour following bracing have not been fully determined. AIM: The aim of this study was to evaluate the results and the loss of the scoliotic curve correction in a cohort of patients treated with Progressive Action Short Brace (PASB) brace during adolescence and to compare patient outcomes of under and over 30 Cobb degrees 10 years after brace removal. DESIGN: This is an observational controlled cohort study nested in a prospective clinical on-going database including 1536 patients with idiopathic scoliosis. SETTING: Inpatients and outpatients in Rome. POPULATION: The study enrolled 163 patients with idiopathic adolescent scoliosis who had been treated with the PASB brace at a 10 years minimum long-term follow-up examination. METHODS: One hundred sixty-three (female) patients with adolescent idiopathic scoliosis (AIS) treated with the Progressive Action Short Brace (PASB) at a mean age of 13.4 years (range 10-34) had accepted to undergo long-term follow-up examination. All patients had clinical and radiological examinations, but only 62 replied to some simple questions (including work status, pregnancy and pain) the population was divided into two groups based on Cobb degrees (< 30° and ≥ 30°). Statistical analysis was applied to test the efficacy of our hypothesis. RESULTS: The patients underwent a long-term follow-up after brace removal at a mean age of 13.46 years (±3.4). The prebrace mean curve was 28.98° (±7.918); after treatment, the mean was 13.88° and increased to a minimum of 15.35° in the 10 years following brace removal. However, there was no significant difference between the mean Cobb angle at the end of weaning and the mean Cobb angle at long-term follow-up. The curve angle at baseline of patients who were treated with a brace was reduced by 15° during the treatment, but at follow-up the curve size was found to have lost 2°. The over 30° group showed a prebrace scoliotic mean curve of 37.26°; at the end of weaning, the mean curve angle was 22.98° which increased to a mean of 25.07° at follow-up. The <30° group showed a prebrace scoliotic mean curve of 24.40° which, at the end of weaning, had reduced to a mean of 8.69°, increasing to 9.98° at follow-up. There was no significant difference in the mean progression of curve magnitude between the ˂ 30° and ≥ 30° groups at the long-term follow-up. Work status was 62% full-time and 11% part-time. 24% had given birth. Three percent presented back pain related to instability of the spine. No patients underwent surgery after maturity but one patient had indication to surgical treatment. CONCLUSIONS: The PASB brace is effective for the treatment of lumbar and thoracolumbar scoliosis and is characterized by positive long-term outcomes, including in patients demonstrating moderate curves. In both groups, at 10-years minimum follow-up after bracing, scoliotic curves did not deteriorate beyond their original curve size after bracing in both groups at the 10-years minimum follow-ups. CLINICAL REHABILITATION IMPACT: At 10 years follow-up after bracing, scoliotic curves had not deteriorated beyond their original curve size.

Long-Term Outcomes of Once-Daily Accelerated Partial-Breast Irradiation With Tomotherapy: Results of a Phase 2 Trial.

PURPOSE: We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery. METHODS AND MATERIALS: From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings. RESULTS: The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up. CONCLUSIONS: This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR.

Full-Length TrkB Variant in NSCLC Is Associated with Brain Metastasis.

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK.

Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells.

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.