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BackgroundSkeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.MethodsA longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release).ResultsSecond line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038).ConclusionsOur data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients’ prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

This article explores how recent utopian studies have conceptualized hope as a shapeless “horizon” characterized by its collective, positive and revolutionary core, and compares it to recent discussions on hope in the fields of feminist theory and affect studies that problematize affirmative conceptualizations of hope, happiness and optimism in calling for a more complex vision on the topic. Such reflections will be applied to the increasingly realistic contemporary feminist dystopias of recent years, which demonstrate a decisive change concerning where and how dystopian worlds are set and represented. Finally, an analysis of the novel The Book of X (2019) by Sarah Rose Etter, with its stunning lack of any utopian horizon traditionally intended, will try to break open Baccolini and Moylan’s definition of “critical dystopia”, detaching the presence of a critical angle from the presence of a properly intended utopian opening.

Glioblastoma (GBM) is a primary CNS tumor that is highly lethal in adults and has limited treatment options. Despite advancements in understanding the GBM biology, the standard treatment for GBM has remained unchanged for more than a decade. Only 6.8% of patients survive beyond five years. Telomerase, particularly the hTERT promoter mutations present in up to 80% of GBM cases, represents a promising therapeutic target due to its role in sustaining telomere length and cancer cell proliferation. This review examines the biology of telomerase in GBM and explores potential telomerase-targeted therapies. We conducted a systematic review following the PRISMA-P guidelines in the MEDLINE/PubMed and Scopus databases, from January 1995 to April 2024. We searched for suitable articles by utilizing the terms “GBM”, “high-grade gliomas”, “hTERT” and “telomerase”. We incorporated studies addressing telomerase-targeted therapies into GBM studies, excluding non-English articles, reviews, and meta-analyses. We evaluated a total of 777 records and 46 full texts, including 36 studies in the final review. Several compounds aimed at inhibiting hTERT transcription demonstrated promising preclinical outcomes; however, they were unsuccessful in clinical trials owing to intricate regulatory pathways and inadequate pharmacokinetics. Direct hTERT inhibitors encountered numerous obstacles, including a prolonged latency for telomere shortening and the activation of the alternative lengthening of telomeres (ALT). The G-quadruplex DNA stabilizers appeared to be potential indirect inhibitors, but further clinical studies are required. Imetelstat, the only telomerase inhibitor that has undergone clinical trials, has demonstrated efficacy in various cancers, but its efficacy in GBM has been limited. Telomerase-targeted therapies in GBM is challenging due to complex hTERT regulation and inadequate inhibitor pharmacokinetics. Our study demonstrates that, despite promising preclinical results, no Telomerase inhibitors have been approved for GBM, and clinical trials have been largely unsuccessful. Future strategies may include Telomerase-based vaccines and multi-target inhibitors, which may provide more effective treatments when combined with a better understanding of telomere dynamics and tumor biology. These treatments have the potential to be integrated with existing ones and to improve the outcomes for patients with GBM.

Background: The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods: We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results: All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions: Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes.

Introduction: Neurosurgery is considered a technically demanding specialty; nonetheless, it also requires non-technical skills (NTSs) to reach mastery. Research question: This study seeks to understand how important NTSs are perceived by neurosurgeons across diverse roles and socio-economic backgrounds. The objective is to identify key NTSs and explore their role in surgical precision, teamwork, and collaboration. Material and method: An international survey involving 372 neurosurgeons from various socio-economic and cultural contexts was conducted. The extensive sample and inclusive methodology provide a comprehensive perspective on the perceived importance of NTSs in neurosurgery. Results: The survey results highlight the universal significance of NTSs among neurosurgeons. Attention to detail, humility, and self-awareness are considered essential for surgical precision, effective teamwork, and collaboration. The findings underscore the necessity for integrated training programs that combine NTSs with technical skills. Discussion and conclusion: The study emphasizes the importance of effective training methods such as simulations, mentorship, and role-playing in equipping neurosurgeons to navigate the complexities of their profession. Future research should focus on optimizing teaching methods for NTSs, comparing traditional courses, online modules, and hybrid training programs. Addressing the global disparity in neurosurgical care, particularly in low- and middle-income countries, is crucial for improving patient outcomes worldwide.

Abstract Negative thermal expansion (NTE) alloys possess great practical merit as thermal offsets for positive thermal expansion due to its metallic properties. However, achieving a large NTE with a wide temperature range remains a great challenge. Herein, a metallic framework-like material FeZr2 is found to exhibit a giant uniaxial (1D) NTE with a wide temperature range (93-1078 K, $${\bar{\alpha }}_{l}=-34.01\times {10}^{-6}\,{{{{{{\rm{K}}}}}}}^{-1}$$ α ¯ l = − 34.01 × 10 − 6 K − 1 ). Such uniaxial NTE is the strongest in all metal-based NTE materials. The direct experimental evidence and DFT calculations reveal that the origin of giant NTE is the couple with phonons, flexible framework-like structure, and soft bonds. Interestingly, the present metallic FeZr2 excites giant 1D NTE mainly driven by high-frequency optical branches. It is unlike the NTE in traditional framework materials, which are generally dominated by low energy acoustic branches. In the present study, a giant uniaxial NTE alloy is reported, and the complex mechanism has been revealed. It is of great significance for understanding the nature of thermal expansion and guiding the regulation of thermal expansion.

Background/Objectives: Lumbar disc herniation, a complex challenge in spinal health, significantly impacts individuals across diverse age groups. This article delves into the intricacies of this condition, emphasising the pivotal role of anatomical considerations in its understanding and management. Additionally, lumbar discectomy might be considered an “easy” surgery; nevertheless, it carries significant risks. The aim of the study was to present a groundbreaking “three-step approach” with some anatomical insight derived from our comprehensive clinical experiences, designed to systematise the surgical approach and optimise the outcomes, especially for young spine surgeons. We highlighted the purpose of the study and introduced our research question(s) and the context surrounding them. Methods: This retrospective study involved patients treated for lumbar disc herniation at a single institution. The patient demographics, surgical details, and postoperative assessments were meticulously recorded. All surgeries were performed by a consistent surgical team. Results: A total of 847 patients of the 998 patients initially included completed the follow-up period. A three-step approach was performed for every patient. The recurrence rate was 1.89%. Furthermore, the incidence of lumbar instability and the need for reoperation were carefully examined, presenting a holistic view of the outcomes. Conclusions: The three-step approach emerged as a robust and effective strategy for addressing lumbar disc herniation. This structured approach ensures a safe and educational experience for young spinal surgeons.

Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.

Background: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. Methods: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. Results: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black–reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. Case presentation: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black–tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. Conclusions: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.

Study design: Prospective study. Objective: To evaluate the influence of preoperatively assessed psychosomatic traits on postoperative pain, disability, and quality of life outcomes. Summary of background data: Anterior cervical discectomy and fusion (ACDF) is a widely employed surgical procedure for treating cervical spondylosis. Despite its effectiveness, various studies have reported non-success rates in terms of alleviating disability and pain. Psychological factors have become increasingly recognized as critical determinants of surgical outcomes in various medical disciplines. The full extent of their impact within the context of ACDF remains insufficiently explored. This case series aims to assess the influence of preoperative psychological profiling on long-term pain, disability and quality of life outcomes. Methods: We conducted a prospective cohort study of prospectively collected data from 76 consecutive patients who underwent ACDF with PEEK inter-fixed cages from July 2019 to November 2021. The preoperative psychological traits were assessed using the Symptom Checklist 90 (SCL-90) questionnaire. The Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), Neck Disability index (NDI), EuroQol-5D (EQ-5D), and Short Form-36 (SF-36) were collected preoperatively, one month postoperatively, and at least one year after the surgical procedure. Results: The correlation analyses revealed associations between psychosomatic traits and multiple preoperative and postoperative outcome measures. The univariate analyses and linear regression analyses demonstrated the influence of the Global Severity Index (GSI) over the final follow-up scores for the ODI, VAS, NDI, EQ-5D, and SF-36. The GSI consistently exhibited a stronger correlation with the final follow-up pain, disability, and quality of life outcomes with respect to the correspondent preoperative values. Conclusion: This study highlights the importance of psychosomatic traits as predictive factors for ACDF outcomes and emphasizes their relevance in preoperative assessment for informing patients about realistic expectations. The findings underscore the need to consider psychological profiles in the preoperative workup, opening avenues for research into medications and psychological therapies. Recognizing the influence of psychosocial elements informs treatment strategies, fostering tailored surgical approaches and patient care.