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Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

Glioblastoma is the most common primary malignant brain tumour. Despite decades of intensive research in the disease, its prognosis remains poor, with an average survival of only 14 months after diagnosis. The remarkable level of intra‐ and interpatient heterogeneity is certainly contributing to the lack of progress in tackling this tumour. Epigenetic dysregulation plays an important role in glioblastoma biology and significantly contributes to intratumour heterogeneity. However, it is becoming increasingly clear that it also contributes to intertumour heterogeneity, which historically had mainly been linked to diverse genetic events occurring in different patients. In this review, we explore how DNA methylation, chromatin remodelling, microRNA (miRNA) dysregulation, and long noncoding RNA (lncRNA) alterations contribute to intertumour heterogeneity in glioblastoma, including its implications for advanced tumour stratification, which is the essential first step for developing more effective patient‐specific therapeutic approaches. Glioblastoma is a malignant brain tumour characterised by prominent heterogeneity at both the intra‐ and interpatient level. Despite advances in the genetic and transcriptional stratification of patients, clinical outcomes have not improved. Here we review epigenetic dysregulation in glioblastoma, focusing on its contribution to interpatient heterogeneity with an emphasis on classification refinement and novel therapeutic approaches.

Background Glioblastoma is the most common and aggressive malignant brain tumour in the adult population and its prognosis is dismal. The heterogeneous nature of the tumour, to which epigenetic dysregulation significantly contributes, is among the main therapeutic challenges of the disease. Results We have leveraged SYNGN, an experimental pipeline enabling the syngeneic comparison of glioblastoma stem cells and expanded potential stem cell (EPSC)-derived neural stem cells to identify regulatory features driven by chromatin remodelling specifically in glioblastoma stem cells. Conclusions We show epigenetic regulation of the expression of genes and related signalling pathways contributing to glioblastoma development. We also identify novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2.

Glioblastoma (GBM) is the most common primary brain cancer. It causes death mainly by local invasion via several routes, including infiltration of white matter tracts and penetration of perivascular spaces. However, the pathways that mediate these invasion routes are only partly known. Here, we conduct an integrative study to identify cell states and central drivers of route-specific invasion in GBM. Combining single-cell profiling and spatial protein detection in patient-derived xenograft models and clinical tumor samples, we demonstrate a close association between the differentiation state of GBM cells and their choice of invasion route. Computational modeling identifies ANXA1 as a driver of perivascular involvement in GBM cells with mesenchymal differentiation and the transcription factors RFX4 and HOPX as orchestrators of growth and differentiation in diffusely invading GBM cells. Ablation of these targets in tumor cells alters their invasion route, redistributes the cell states, and extends survival in xenografted mice. Our results define a close association between GBM cell differentiation states and invasion routes, identify functional biomarkers of route-specific invasion, and point toward targeted modulation of specific invasive cell states as a therapeutic strategy in GBM. Glioblastoma (GBM) is a common brain cancer characterized by local invasion. Here, authors identify regulators of GBM cell differentiation states and invasion routes, demonstrating that targeting these regulators alters invasion patterns and extends survival in mouse models.

Background The purpose of the study is to evaluate clinical and radiological outcomes in those patients with femoral head fracture, treated with open reduction and internal fixation through Gibson approach and Ganz flip trochanter osteotomy. The treatment of Pipkin fractures is very challenging, especially for small trauma centers, because of the unusual fracture patterns and high-level surgical skills required. Case presentation Between 2017 and 2020, nine cases of Pipkin fractures came to the Emergency Department at the Trauma Center of our Hospital in Rome. Inclusion criteria were the diagnosis of femoral head fracture, the open reduction and internal fixation as surgical choice and at least 24 months follow-up. Patients older than 65 years and those treated through total hip replacement or combined hip procedure (CHP) were excluded. Thus, five patients were included in our case series. The clinical outcome was evaluated according to Western Ontario and McMaster Universities Arthritis Index, Vail Hip score, modified Harris Hip score and Merle D’Aubignè Postel score. Radiographic assessment was scored according to Epstein-Thompson classification and heterotopic ossification was assessed through Brooker classification. The mean follow-up was 24 months (range 12-24). Average modified Harris Hip score was 92.1 points (range 75.9–100), and the average Vail score was 81.8 (range 55-95). WOMAC score was assessed in three different subscales, pain (A), stiffness (B) and physical condition (C), with the following results: 1.4 A (range 0-7), 1.2 B (range 0-6) and 6.4 C (range 0-22). Merle d’Aubignè Postel score resulted excellent for four patients and good for one patient. According to Epstein-Thompson score of the radiological outcome, four patients showed a good result and one a fair result. No mechanical or infective complications occurred in the five patients. Conclusions Gibson’s approach and surgical hip dislocation through Ganz trochanteric flip osteotomy allow a good exposure of the femoral head and acetabulum, giving us the possibility to perform an anatomical reduction of the fracture. In our case series, satisfactory clinical and radiological short-term results were obtained without significant complications.

Background The purpose of the study is to evaluate the use of the suprapectineal quadrilateral surface (QLS) plates associated with the anterior intrapelvic approach (AIP) to the acetabulum in the surgical treatment of acetabular fractures with anterior involvement. Methods We did a retrospective study of patients surgically treated with QLS plates and AIP for acetabular fractures with the involvement of the anterior column, between February 2018 and February 2020, in our Hospital. The following data were recorded: mechanism of injury, the pattern of fracture, presence of other associated injuries, the time before performing the surgery, surgical approach, position on operating table, time of surgery, intraoperative bleeding, hospitalization time, intraoperative and postoperative complications. Follow-ups were performed at 1, 3, 6, 12 months, then annually. The clinical-functional outcome was assessed with the Merle d’Aubigne Postel score (MAP) modified by Matta; while the radiological outcome with the Matta Radiological Scoring System (MRSS). A Chi-square test was utilized to examine associations between parametric variables. Results We included 34 patients, mean age 62.1, with an average follow-up of 20.7 months. The most frequent traumatic mechanism was road trauma. There were 15 isolated anterior columns and 19 associated patterns. There were 5 cases of associated visceral injuries, and 10 cases of other associated skeletal fractures. All patients were in the supine position. The surgical approach used was the AIP in all cases, with the addition of the first window of the ilioinguinal approach in 16 cases and of the Kocher-Langenbeck approach in 2 cases. The average time before performing the surgery was 8.5 days. The mean time of the surgery and the mean length of stay after surgery were 227.9 min and 8.2 days, respectively. There weren’t cases of intra-operative complications, while there were postoperative complications in 5 patients. The MRSS was judged anatomical in 26 cases, imperfect in 7 cases and poor in 1 case. The average MAP value was 15.2. We observed a significant relationship between the radiological outcome and the clinical outcome ( p  < 0.05). Conclusions The QLS plates in association with the AIP approach represent an effective treatment strategy for the treatment of acetabular fractures with anterior involvement.

Cerebrovascular malformations include a wide range of blood vessel disorders affecting brain vasculature. Neuroimaging differential diagnosis can result unspecific due to similar phenotypes of lesions and their deep localization. Next-generation sequencing (NGS) platforms simultaneously analyze several hundreds of genes and can be applied for molecular distinction of different phenotypes within the same disorder’s macro-area. We discuss about the main criticisms regarding molecular bases of cerebral cavernous malformations (CCM) and brain arteriovenous malformations (AVM), highlighting both common pathogenic aspects and genetic differences leading to lesion development. Many recent studies performed on human CCM and AVM tissues aim to detect genetic markers to better understand molecular bases and pathogenic mechanism, particularly for sporadic cases. Several genes involved in angiogenesis show different expression patterns between CCM and AVM, and these could represent a valid starting point to project a NGS panel to apply for differential cerebrovascular malformation diagnosis.

Parkinson’s disease is a neurodegenerative disorder characterized by different motor, vegetative, behavioral, and cognitive impairments, with worsening quality of life. Virtual reality devices have given promising results in neurorehabilitation as they can provide multisensory stimulation in a realistic environment. This study aims to test the efficacy of virtual reality training by using Computer Assisted Rehabilitation Environment in cognitive impairment in a sample of PD. 31 patients affected by PD were enrolled. All PD patients underwent 24 sessions of Computer Assisted Rehabilitation Environment training. The participants were assessed at baseline (T0) and after two months (T1). Our results suggested that Computer Assisted Rehabilitation Environment training may be effective in the cognitive and emotional domains, particularly by improving executive function, anxiety, and depressive symptoms. These changes have helped to improve self-efficacy and coping strategies. These results indicate greater cognitive and physical effort to overcome stressors. Our results show that Computer Assisted Rehabilitation Environment training was beneficial in improving cognitive functions. Longer duration training may be especially beneficial for patients with mild cognitive impairment. Our findings open the door to tailored personalized treatments based on the patient's motor and cognitive profiles.

To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB 1 ) and 2 (CB 2 ) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] − 24.83, 95% confidence interval [ 95% CI] − 34.89, − 14.76, p  < 0.00001) or the synthetic cannabinoid (CB) agonists ACPA, WIN55,212-2, CP55,940 (CB 1/2 -non-selective) and AM1241 (CB 2 -selective) (MD − 28.73, 95% CI − 45.43, − 12.02, p  = 0.0008) are associated with significant reduction in paw withdrawal frequency. Consistently, the synthetic agonists AM1241 and JWH015 (CB 2 -selective) increased paw withdrawal threshold (MD 0.89, 95% CI 0.79, 0.99, p  < 0.00001), and ACEA (CB 1 -selective), AM1241 and JWH015 (CB 2 -selective) reduced spontaneous flinches (MD − 4.85, 95% CI − 6.74, − 2.96, p  < 0. 00001) in osteolysis-bearing male mice. In rats, significant increase in paw withdrawal threshold is associated with the administration of ACEA and WIN55,212-2 (CB 1/2 -non-selective), JWH015 and AM1241 (CB 2 -selective) in osteolysis-bearing females (MD 8.18, 95% CI 6.14, 10.21, p  < 0.00001), and treatment with AM1241 (CB 2 -selective) increased paw withdrawal thermal latency in males (mean difference [MD]: 3.94, 95% CI 2.13, 5.75, p  < 0.0001), confirming the analgesic capabilities of CB 1/2 ligands in rodents. In human, treatment of cancer patients with medical cannabis (standardized MD − 0.19, 95% CI − 0.35, − 0.02, p  = 0.03) and the plant-derived delta-9-THC (20 mg) (MD 3.29, CI 2.24, 4.33, p  < 0.00001) or its synthetic derivative NIB (4 mg) (MD 2.55, 95% CI 1.58, 3.51, p  < 0.00001) are associated with reduction in pain intensity. Bioinformatics validation of KEGG, GO and MPO pathway, function and process enrichment analysis of mouse, rat and human data revealed that CB 1 and CB 2 receptors are enriched in a cocktail of nociceptive and sensory perception, inflammatory, immune-modulatory, and cancer pathways. Thus, we cautiously conclude that pharmacological modulators of CB 1/2 receptors show promise in the treatment of cancer-induced bone pain, however further assessment of their effects on bone pain in genetically engineered animal models and cancer patients is warranted.

Primary brain tumours are rare but carry a significant morbidity and mortality burden. Malignant gliomas are the most common subtype and their incidence is increasing within our ageing population. The diagnosis and treatment of gliomas involves substantial interplay between multiple specialties, including general medical physicians, radiologists, pathologists, surgeons, oncologists and allied health professionals. At any point along this pathway, patients can present to acute medicine with complications of their cancer or anti-cancer therapy. Increasing the awareness of malignant gliomas among general physicians is paramount to delivering prompt radiological and histopathological diagnoses, facilitating access to earlier and individualised treatment options and allows for effective recognition and management of anticipated complications. This article discusses evidence-based real-world practice for malignant gliomas, encompassing patient presentation, diagnostic pathways, treatments and their complications, and prognosis to guide management outside of specialist centres.