Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma.

Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the accumulation of intratumoral T cells and tumor growth delay, and, in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation.

Extreme Lateral Interbody Fusion (XLIF) with Lateral Modular Plate Fixation: Preliminary Report on Clinical and Radiological Outcomes.

The lateral transpsoas approach (extreme lateral interbody fusion, or XLIF) allows surgeons to use various lordotic cage sizes to help restore intervertebral disk height, correct sagittal alignment, and improve fusion rates. The use of standalone devices has consistently raised doubts due to the high risk of complications and inadequate functional recovery that a circumferential arthrodesis can support. The recent introduction of a novel XLIF cage with adapted lateral plate fixation (XLPF) may further enhance the structural rigidity, consolidating the cage and plate into a singular modular entity. Nine patients from our surgical centers underwent a procedure of 1-level XLIF with XLPF in selected cases. We observed that XLPF does not extend the intraoperative footprint and provides immediate rigidity to the anterior column without any additional risk of complications and with minimal increased time compared to the traditional cage implant procedure. Although it has been shown that the use of interbody fusion cages with supplemental posterior fixation improves stabilization in all directions, the technique of standalone lateral cages may also have a place in spine surgery in that the stability may be sufficient in selected cases, such as junctional syndrome and in some forms of degenerative scoliosis.

Regenerative Medicine Solutions for Rotator Cuff Injuries in Athletes: Indications and Outcomes.

Rotator cuff (RC) injuries include a wide range of pathologic states. Athletes are perhaps the most susceptible to RC injuries ranging from tendinopathy to partial or full-thickness tears, due to functional overload and repetitive movements, causing abstention from sports for long periods. Regenerative medicine keeps giving us multiple choices to fight the disability caused by these pathologies. A literature search was performed, and findings related to the structure-function of rotator cuff units, pathophysiology of injuries, regenerative medicine treatments, and future strategies were outlined. Platelet-rich plasma (PRP) has a greater number of articles and clinical trials, accompanied by stem cells progenitor, prolotherapy, and new approaches such as microfragmented adipose tissue and exosomes. RC injuries in athletes can cause pain, functional impotence, and the risk of recurrence, and can lead them to stop playing sports. Regenerative medicine offers a range of treatments, but some of them need further studies to underline their actual validity.

Comparison of blood volume biofeedback hemodialysis and conventional hemodialysis on cardiovascular stability and blood pressure control in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Despite the improvements in hemodialysis (HD) technology, 20-30% of sessions are still complicated by hypotension or hypotension-related symptoms. Biofeedback systems have proven to reduce the occurrence of such events, but no conclusive findings can lead to wider adoption of these systems. We conducted this systematic review and meta-analysis of randomized clinical trials to establish whether the use of blood volume tracking systems compared to conventional hemodialysis (C-HD) reduces the occurrence of intradialytic hypotension. METHODS: The PRISMA guidelines were used to carry out this systematic review. Randomized clinical trials that evaluated the incidence of intradialytic hypotension during C-HD and blood volume tracking-HD were searched in the current literature. PROSPERO registration number: CRD42023426328. RESULTS: Ninety-seven randomized clinical trials were retrieved. Nine studies, including 347 participants and 13,274 HD treatments were considered eligible for this systematic review. The results showed that the use of biofeedback systems reduces the risk of intradialytic hypotension (log odds ratio = 0.63, p = 0.03) in hypotension-prone patients (log odds ratio = 0.54, p = 0.04). When analysis was limited to fluid overloaded or hypertensive patients, it did not show the same effect (log odds ratio = 0.79, p = 0.38). No correlation was found in systolic blood pressure drop during dialysis and in post-dialysis blood pressure. CONCLUSIONS: The use of blood volume tracking systems may be effective in reducing the incidence of intradialytic hypotension and allowing for easier attainment of the patients' ideal dry body weight. New studies to examine the long-term effects of the use of blood volume tracking systems on real hard endpoints are needed.

Combined Anterior Odontoid Screw Fixation and C1-C2 Jefferson Fracture Anterior Fixation: A Step-by-Step Technical Note.

BACKGROUND: Combined triple atlas (C1)-axis (C2) fixation has been described in previous literature as a safe, effective, and minimally invasive procedure for complex atlas and odontoid fractures that allows for a greater range of motion compared with posterior approaches and atlanto-occipital fusion. However, it is rarely performed due to the occipital-cervical diastasis resulting from often-fractured C1 joint masses. No evidence-based consensus has been reached regarding the treatment of complex atlantoaxial fractures, and the choice of surgical strategy is based only on clinical experience. METHODS: We report the combined triple C1-C2 fixation technique with manual reduction of the joint masses during patient positioning on the operating table, which allowed for effective stabilization during a single surgical session. We describe our experience in the management of a 75-year-old patient presenting with an acute complex type II fracture of C1, which also involved 1 lateral mass, combined with a type II odontoid fracture and occipital-cervical diastasis. RESULTS: We provide a step-by-step guide for combined triple C1-C2 anterior fixation with manual fracture reduction and describe the clinical case of an acute complex type II fracture of C1, which also involved 1 lateral mass, combined with a type II odontoid fracture and occipital-cervical diastasis. CONCLUSIONS: Combined triple C1-C2 fixation represents a safe and efficient minimally invasive anterior approach for complex type II fractures of C1 with type II odontoid fractures. Manual reduction of the joint masses during patient positioning allows for effective stabilization in a single surgical session.

Impact of pruritus in patients undergoing hemodialysis in Italy: a patient-based survey.

BACKGROUND: Itching is an annoying symptom which afflicts patients with chronic renal failure. We aimed to assess the impact and patient's perception and experience of itching in the dialysis population in Italy. METHODS: A questionnaire was developed by the National Hemodialysis and Dialysis Association of Italy (ANED) and administered to 996 hemodialysis recipients across 153 Italian dialysis centers. The main outcomes investigated by the questionnaire were patients' satisfaction on answers regarding the nature of itching; continuing to talk about itching with the nephrologist; beliefs about resolution of itching. RESULTS: A total of 1903 patients from 153 centers responded to the questionnaire. Patients who responded had a mean age of 67.9 ± 13.8 years (63.9% male) and were stratified by itch discomfort graded as mild (35.9%), moderate (29.6%), and severe (34.4%). Severe itching disrupted patients' daily lives, strained their relationships, caused anxiety, and diminished their quality of life. Patients with severe itch were more likely to talk about it with dialysis staff and to undertake dermatological visits. However, only 18.0% of patients reporting severe itching found the clinicians' responses satisfactory, compared to 49.1% of mild itch patients. Those who continued talking to nephrologists about itching received more satisfactory response. However, 40.8% believed itching could not be alleviated and were less likely to discuss it with nephrologists. CONCLUSIONS: There is an intricate relationship between the severity of itching, patient perceptions, and healthcare communication among hemodialysis patients. A substantial proportion of patients experiencing severe itching expressed feelings of resignation, highlighting the pressing need for enhanced clinician-patient communication.

Clinical, Radiologic, and Surgical Features of Brain Metastases in Colorectal Cancer. A Strong Correlation Between Surgical Patterns and Outcome.

BACKGROUND: Brain metastases (BMs) from colorectal cancer (CRC) are a small percentage of metastatic patients and surgery is considered the best choice to improve survival. While most research has focused on the risk of CRC spreading to the brain, no studies have examined the characteristics of BMs in relation to surgery and outcome. In this study, we evaluate the clinical and radiologic features of BMs from CRC patients who underwent surgery and analyze their outcomes. METHODS: The study is a retrospective observational analysis that included a cohort of 31 patients affected by CRC surgically-treated for their related BMs. For all patients, clinical and surgical data (number, site, side, tumor and edema volume, and morphology) were recorded. RESULTS: Analysis found that synchronous diagnosis and lesion morphology, particularly cystic versus solid, had the most significant impact on survival (6 vs. 22 months, P = 0.04). To compare BMs with cystic morphology to those with solid morphology, a multivariate analysis was conducted. No significant differences were observed between the 2 groups in terms of age, sex, clinical onset, or performance status. The analysis revealed no significant differences in localization with regard to site, tumor and edema volume, biology, or complications rate. CONCLUSIONS: BMs derived from CRC have a significantly different prognosis depending on whether they present as a solid or cystic pattern. Although solid pattern is more common, cystic BMs in this tumor type are less frequent and are associated with a poorer prognosis, regardless of molecular expression, location, size, and adjuvant treatment.

3-Dimensional Printed Model of the Temporal Bone for Neurosurgical Training.

BACKGROUND AND OBJECTIVES: The development of neurosurgical skills stands out as a paramount objective for neurosurgery residents during their formative years. Mastery of intricate and complex procedures is a time-intensive process marked by a gradually ascending learning curve. Consequently, the study and simulation on surgical models assume significant importance. One of the most intricate neuroanatomical regions includes the petrous and mastoid portions of the temporal bone. These regions host critical, highly functional, and vital neurovascular structures, including the facial nerve, cochlea, semicircular canals, internal carotid artery, and middle ear. This fully open-source 3-dimensional (3D) model of the temporal bone, created for educational purposes, should be easily and economically reproducible using a 3D printer, offering all residents the opportunity to understand the spatial location, three-dimensional anatomical structures, and fundamental intricacies of mastoidectomy. METHODS: A 3D model of the temporal bone was fabricated using a computed tomography (CT) scan derived from an actual human body. The CT scan of the model was meticulously juxtaposed with the reference sample CT scan. Neurosurgical residents were recruited as participants for this study. Each participant was tasked with executing a mastoidectomy on 2 separate occasions, with a 2-week interval between attempts. Throughout these sessions, various parameters, including the time taken for task completion, the volume of bone removal, and any potential complications, were systematically registered. RESULTS: The mean volume of bone removed increased by 34.5%, and the mean task time and the mean number of complications decreased by 10.3% and 25%, respectively, during the training. CONCLUSION: Engaging in training with cost-effective anatomical models constitutes a valuable tool for refining technical skills during residency. We posit that this type of model training should be incorporated as part of the trainee's curriculum during the residency program because of the myriad advantages evidenced by the findings of this study.

The Impact of the COVID-19 Pandemic and Lockdown on the Outcome of Glioblastoma.

BACKGROUND: Rapid spread of the SARS-CoV-2 pandemic in 2020 led to an indirect effect on non-COVID patients. Since neuro-oncology cases are unique and brain tumors need a specific therapeutic protocol at proper doses and at the right times, the effects of the pandemic on health care services for patients with glioblastomas (GBs) and their impact on overall survival (OS) and quality of life are not yet known. METHODS: We conducted a retrospective study of 142 GB patients who underwent surgery, radiation, and chemotherapy before and after the lockdown period, aiming to determine the differences in access to care, treatment modality, and adjuvant therapies, and how the lockdown changed the prognosis. RESULTS: The number of procedures performed for GB during the pandemic was comparable to that of the prepandemic period, and patients received standard care. There was a significant difference in the volume of lesions measured at diagnosis with a decreased number of "accidental" diagnoses and expression of a reduced use by the patient for a checkup or follow-up examinations. Patients expressed a significantly lower performance index in the lockdown period with longer progression-free survival (PFS) in the face of a comparable mean time to OS. CONCLUSION: Patients treated surgically for GB during the pandemic period had a more pronounced and earlier reduction in performance status than patients treated during the same period the year before. This appears to be primarily due to lower levels of care in the rehabilitation centers and more frequent discontinuation of adjuvant care.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Histological, molecular, clinical and outcomes characteristics of Multiple Lesion Glioblastoma. A retrospective monocentric study and review of literature / Características histológicas, moleculares, clínicas y de resultados de lesiones múltiples del glioblastoma. Un estudio monocéntrico retrospectivo y revisión de literatura

Background Multiple lesion glioblastoma (M-GBM) represent a group of GBM patients in which there exist multiple foci of tumor enhancement. The prognosis is poorer than that of single-lesion GBM patients, but this actually is a controversial data. Is unknown whether multifocality has a genetic and molecular basis. Our specific aim is to identify the molecular characteristics of M-GBM by performing a comprehensive multidimensional analysis. Methods The surgical, radiological and clinical outcomes of patients that underwent surgery for GBM at our institution for 2 years have been retrospectively reviewed. We compared the overall survival (OS), progression free survival and extent of resection (EOR) between M-GBM tumors (type I) and S-GBM (single contrast-enhancing lesion, type II). Results A total of 177 patients were included in the final cohort, 12 patients had M-GBM and 165 patients had S-GBM. Although patients with M-GBM had higher tumor volumes and midline location, the EOR was not different between both type of lesions. Higher percentage of tumors with EGFR overexpression was detected in M-GBM. PFS and OS was significantly shorter in M-GBM. Conclusions Considering no differences in EOR, patients with M-GBM showed shorter PFS and OS in comparison with S-GBM. Evidences about the M-GBM origin as a multifocal lesion because its molecular profile are suggested (AU)

Antecedentes El glioblastoma multiforme multifocal (M-GBM) representa un grupo de pacientes con GBM en el que existen múltiples focos de mejora tumoral. El pronóstico es peor que el de los pacientes con GBM de lesión única, pero en realidad es un dato controvertido. Se desconoce si la multifocalidad tiene una base genética y molecular. Nuestro objetivo específico es identificar las características moleculares de M-GBM mediante la realización de un análisis multidimensional integral. Métodos Los resultados quirúrgicos, radiológicos y clínicos de los pacientes que se sometieron a cirugía para GBM en nuestra institución durante 2 años han sido revisados retrospectivamente. Comparamos la supervivencia general (SG), la supervivencia libre de progresión y el grado de resección (EOR) entre los tumores M-GBM (tipo I) y S-GBM (lesión única que mejora el contraste, tipo II). Resultados Un total de 177 pacientes fueron incluidos en la cohorte final, 12 pacientes tenían M-GBM y 165 pacientes tenían S-GBM. Aunque los pacientes con M-GBM tenían mayores volúmenes tumorales y ubicación en la línea media, el EOR no fue diferente entre ambos tipos de lesiones. Se detectó un mayor porcentaje de tumores con sobreexpresión de EGFR en M-GBM. PFS y OS fue significativamente más corto en M-GBM. Conclusiones Teniendo en cuenta que no hay diferencias en EOR, los pacientes con M-GBM mostraron PFS y OS más cortos en comparación con S-GBM. Se sugieren evidencias sobre el origen de M-GBM como una lesión multifocal porque se sugiere su perfil molecular (AU)

Preoperative 3D volume reconstruction of the posterior wall of the sphenoid sinus with Horos: A free, simple and reliable tool in endoscopic endonasal trans-sphenoidal surgery / Reconstrucción volumétrica 3D preoperatoria de la pared posterior del seno esfenoidal con Horos: una herramienta gratuita, sencilla y fiable en la cirugía endoscópica endonasal transesfenoidal

BackgroundThe purpose of the study was to create computer-aided design models of the sphenoid sinus with a free-source software in order to perform a preoperative planning during trans-sphenoidal endoscopic surgery (TES) and clarify the three-dimensional anatomical features of the sphenoid sinus and its surrounding structures.MethodsFor each patient a 3D volume rendering of the sphenoid sinus was obtained from a thin slice head and maxilla-facial CT scan using a free-source DICOM viewer. The 3D models obtained preoperatively were examined preoperatively by six neurosurgeons in order to identify the boundaries of the sella.ResultsFor the main anatomical landmark, all of the observers were able to recognize the anatomical structure at a rate ranging from 80 to 98%, 28 to 60% and 25 to 58% for expert (n=3), inexpert (n=3) and the entire group of observers (n=6), respectively. The analysis of the data shows that both observation groups presented a lower recognition rate of the following parameters: right and left medial and lateral optocarotid recesses and tumor prominence, however, the sellar prominence, clival recess, planum sphenoidalis, right and left ICA prominence, right and left optic prominences represent the main anatomical landmarks to be recognized during TES immediately before the opening of the sellar floor.ConclusionsThe use of a preoperative 3D imaging is not in itself a novelty in the literature, however the fact that a simple tool obtained with a free-source software like Horos can represent a considerable help in surgical practice without resorting to the use of more complex software and expensive represents the real utility of this work (AU)

AntecedentesEl objetivo del estudio es crear modelos de diseño asistido por ordenador del seno esfenoidal con software de código abierto para realizar la planificación preoperatoria durante la cirugía transesfenoidal endoscópica (TES) y dilucidar las características anatómicas tridimensionales del seno esfenoidal y las estructuras que lo rodean.MétodosPara cada paciente, se obtuvo una representación volumétrica en 3D del seno esfenoidal, a partir de una tomografía computarizada maxilofacial de corte fino utilizando un visor DICOM de fuente libre. Los modelos 3D obtenidos antes de la cirugía fueron revisados por seis neurocirujanos para identificar los límites de la silla turca.ResultadosPara el principal punto de referencia anatómico, todos los observadores fueron capaces de reconocer la estructura anatómica en un rango de 80 a 98%, 28 a 60% y 25 a 58% para los experimentados (n=3), los inexpertos (n=3) y todo el grupo de observadores (n=6), respectivamente. El análisis de los datos muestra que ambos grupos de observación presentaron una tasa de reconocimiento menor de los siguientes parámetros: recesos optocarotídeos medial y lateral izquierdo y prominencia tumoral, sin embargo, prominencia selar, receso clival, plano esfenoidal, prominencia ICA derecha e izquierda. Las prominencias ópticas derecha e izquierda representan los principales puntos de referencia anatómicos que deben reconocerse durante la TES inmediatamente antes de la apertura del suelo selar.ConclusionesEl uso de una imagen 3D preoperatoria no es en sí mismo una novedad en la literatura, sin embargo, el hecho de que una simple herramienta obtenida con un software de código abierto como Horos pueda representar una importante ayuda en la práctica quirúrgica, sin tener que recurrir al uso de un software más complejo y costoso, representa la verdadera utilidad de este trabajo (AU)