Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field

Power-assisted pedicle screws placement: Is it as safe and as effective as manual technique? Narrative review of the literature and our technique

Pedicle screws are the gold standard in spine surgery, allowing a solid tricolumnar fixation which is unmatched by hooks and wires. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. The aim of this review is to summarize and expose potential risks and advantages of power pedicle screws placing. The literature showed that the use of power tools offers an acceptable safety profile, comparable to manual technique. With an adequate training, the power technique may speed up the screw placing, reduce the fluoroscopy time and the physical stress to the spine surgeon. Regarding differences in pull-out strength between power and manual techniques, the literature is still uncertain and inconsistent, both in clinical and preclinical studies. The choice between the use of power and manual freehand pedicle screws placing is still based on the surgeon’s own preference

Thyroid autoimmune disorders and cancer

In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant, even if the exact mechanisms at the basis of this association are still not clear. Growing incidence of TC coincides with increased registration of autoimmune thyroid disorders (AITD) suggesting an association between those pathologies. Elevated TSH levels and thyroid autoimmunity were defined as independent risk factors for TC. However a lot of evidence suggests that autoimmunity and inflammation, per se, are risk factors for TC. The link between inflammation and TC involves multiple components of the immune system, extracellular matrix, stroma, and adipose tissue, with pro-tumoral activity of inflammation being opposed to anti-inflammatory effects, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells, belonging both to innate (macrophages) and adaptive (lymphocytes) immune responses, are interconnected with fibroblasts, endothelial cells, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines. Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment. Future studies will be necessary to understand the connections between thyroid autoimmunity and cancer, also in order to design a tailored therapy for TC patients with AITD

Molecular testing in the diagnosis of differentiated thyroid carcinomas

Different genetic mutations and other molecular alterations in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) can be detected in fine-needle aspiration (FNA) of thyroid nodules, and can be used successfully to ameliorate cancer diagnosis and management of patients with thyroid nodules. The greatest experience has been obtained with the diagnostic use of BRAF mutation that is strongly specific for malignancy when detected using well-validated techniques. The strongest diagnostic result can be obtained testing FNA samples for a panel of mutations that typically involve TERT, BRAF, PAX8/PPARγ, RAS, and RET/PTC. Finding any of these mutations in a thyroid nodule provides strong indication for malignancy and helps to refine clinical management for a significant proportion of patients with indeterminate cytology. The use of molecular markers, as TERT, BRAF, PAX8/PPARγ, RAS, and RET/PTC, may be considered for patients with indeterminate FNA cytology (FNAC) to help guide management. In patients with indeterminate TIR3 FNA, the combination of precise molecular marker expression analysis with molecular mutations evaluations could ameliorate significantly the accuracy of cancer diagnosis. However other prospective studies are needed to identify more accurate molecular markers. Finally, the knowledge of these molecular pathways has permitted the development of new targeted therapies for aggressive TC

Freehand power-assisted pedicle screw placement in scoliotic patients: results on 5522 consecutive pedicle screws

Pedicle screws is the current gold standard in spine surgery, achieving a solid tricolumnar fixation which is unreachable by wires and hooks. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. However, placing a pedicle screw remains a technically demanding procedure with significant risk of complications. The aim of this article is to retrospectively evaluate safety and accuracy of free-hand power-assisted pedicle screw placement in a cohort of patients who underwent correction and fusion surgery for scoliosis (both idiopathic and non-idiopathic) in our department. A retrospective review of all patients with scoliosis who underwent surgery and received a postoperative CT scan in our department in a 9-year period was undertaken. Screw density, number and location of pedicle screws were measured using pre and postoperative full-length standing and lateral supine side-bending radiographs. Then, postoperative CT scan was used to assess the accuracy of screw placement according to Gertzbein-Robbins scale. Malpositioned screws were divided according to their displacement direction. Finally, intra and postoperative neurological complications and the need for revision of misplaced screws were recorded. A total of 205 patients were included, with a follow-up of 64.9 ± 38.67 months. All constructs were high density (average density 1.97 ± 0.04), and the average number of fusion levels was 13.72 ± 1.97. A total of 5522 screws were placed: 5308 (96.12%) were grade A, 141 (2.5%) grade B, 73 (1.32%) grade C. Neither grade D nor grade E trajectories were found. The absolute accuracy (grade A) rate was 96.12% (5308/5522) and the effective accuracy (within the safe zone, grade A + B) was 98.6% (5449/5522). Of the 73 misplaced screws (grade C), 59 were lateral (80.80%), 8 anterior (10.95%) and 6 medial (8.22%); 58 were in convexity, while 15 were in concavity (the difference was not statistically significant, p = 0.33). Intraoperatively, neither neurological nor vascular complications were recorded. Postoperatively, 4 screws needed revision (0.072% of the total): Power-assisted pedicle screw placing may be a safe an accurate technique in the scoliosis surgery, both of idiopathic and non-idiopathic etiology. Further, and higher quality, research is necessary in order to better assess the results of this relatively emerging technique

Correction to: High-grade dysplastic spondylolisthesis: surgical technique and case series

Purpose: The aim of the present study is to evaluate the results of our all posterior-one stage surgical technique for the reduction and fusion of high-grade high-dysplastic spondylolisthesis. Methods: Patients over 11 years old with high-grade spondylolisthesis treated by reduction and circumferential fusion with a posterior-only approach were reviewed. Data about operative time, blood loss, length of stay, intra- and postoperative complications were collected. Meyerding grade (M), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), lumbosacral angle (LSA), slip angle (SLIP), lumbar index (LI) and severity index were measured on preoperative and last follow-up. Sagittal vertical axis (SVA) was used to assess sagittal balance. Results: Of the 14 included patients, L5-S1 arthrodesis was performed in 12 cases, and L4-S1 was performed in 2 cases. Average surgical time was 275 ± 65 min; average blood loss was 635 ± 375 mL. Average length of stay of was 3.9 ± 1.5 days. The SLIP angle improves from 33.8° ± 7.3° to 6.4° ± 2.5°, (p = 0.002); the lumbosacral angle improves from 68.8° ± 18.6° to 100.7° ± 13.2°, (p = 0.01); and the SVA decreased from 49.4 ± 22.1 mm to 34.4 ± 8.6 mm (p = 0.02). No significant changes were observed in PI, PT and SS. Thoracic kyphosis (TK) and lumbar lordosis (LL) did not change significantly. At last follow-up, no patient had surgical site infection or mechanical complications; no pseudoarthrosis was observed. No revision surgery was performed. Conclusion: Although technically demanding, reduction and fusion with one stage all posterior approach prove to be a safe and effective

Chemokines in hyperthyroidism

The term “hyperthyroidism” indicates a condition due to an exaggerate production of thyroid hormone; the most frequent cause is Graves’ disease (GD). We review cytokines and chemokines in hyperthyroidism, with a special focus in GD. In GD, recruited Th1 lymphocytes are responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates Th1 chemokines release from thyrocytes, initiating and perpetuating the autoimmune process. Circulating levels of these chemokines are associated with the active phase of GD. Additional studies are necessary to investigate whether Th1 chemokines could be a novel therapeutic target in this disease

Relationship of Demoralization With Anxiety, Depression, and Quality of Life: a Southern European Study of Italian and Portuguese Cancer Patients

Background: Demoralization syndrome is a significant condition that has not been greatly studied in Southern European countries. Aims: To extend the knowledge of demoralization in Southern Europe by examining its prevalence according to different methods of assessment, its relationship with anxiety and depression, and its impact on quality of life (QoL) among cancer patients. Methods: A convenience sample of 195 cancer outpatients from two oncology centers (102 from Lisbon, Portugal, and 93 from Ferrara, Italy) participated in an observational, cross-sectional study using the Diagnostic Criteria of Psychosomatic Research-Demoralization interview (DCPR/D) and psychometric tools (Demoralization scale-DS; Patient Health Questionnaire-9/PHQ-9; Hospital Anxiety Depression Scale-HADS; and European Quality of Life-5-EQ-5D). Results: A 25.1% prevalence (CI 95%, 0.19-0.31) of clinically relevant demoralization was reported on the DCPR/D interview. A total demoralization score cutoff score ≥ 25 maximized sensitivity (81.6%), and specificity (72.6%) in identifying DCPR/D demoralized patients. The DCPR/D and DS were associated with poorer levels of QoL. About half of the patients who were demoralized were not clinically depressed (PHQ-9). Self-reported suicidal ideation (PHQ-9 item 9) was found in a minority of patients (8.2%), most of whom (77%) were cases of depression (PHQ-9), but one-quarter (23%) were not depressed, yet moderately/severely demoralized (DCPR/D and DS). Conclusions: This Southern European study confirms the importance of demoralization in cancer patients as a different condition with respect to depression and its relationship with poor QoL and suicidal ideation.info:eu-repo/semantics/publishedVersio

Total knee replacements using rotating hinge implants in polio patients: clinical and functional outcomes

Little evidences are available in the literature concerning the outcomes of total knee replacement (TKR) in poliomyelitis patients with severe knee deformities or degeneration. Encouraging results have been reported concerning the use of constrained implants, i.e., rotating hinge knee prosthesis (RHK), compared to less constrained ones. The purpose of this paper is to report our experience with rotating hinge total knee replacement, using only RHK prosthesis, to determine functional results, complications, and survival of TKR in poliomyelitis patients. We performed a retrospective chart review of 14 patients with a history of knee osteoarthritis following poliomyelitis that underwent primary TKR, for a total of 15 surgical procedure (one bilateral case). Preoperative and postoperative clinical measurements have been conducted for all patients using the Knee Society Score (KSS). Hip-knee angle, recurvatum knee angle, and Insall-Salvati index were evaluated with full weight-bearing panoramic view X-ray preoperatively and postoperatively. The 2-year postoperative clinical KSS significantly improved from the preoperative scores. The average clinical KSS improved from 32,9 (range 3-48) preoperatively to 77,4 (range 60-88) postoperatively (P value < 0.005). The average functional KSS improved from 32,5 (range 10-60) preoperatively to 59,4 (range 30-95) postoperatively (P value < 0.005). TKR is a successful treatment in improving knee function and patient's quality of life. Using constrained implants, especially rotating hinge implants in polio patients with a quadriceps muscle weakness, could be a good alternative to maintain a physiological kinematics and reducing the revision rate due to knee instability

Immune and inflammatory cells in thyroid cancer microenvironment

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer