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.

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.

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.

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.

Preventing Ventricular Catheter Displacement and Infection with the "Catheter-Locking Device-Assisted" Technique: A Retrospective Study of 231 Patients.

BACKGROUND: Inserting cerebrospinal fluid diversion devices such as external ventricular drains (EVDs) and ventriculoperitoneal shunts (VPSs) is a critical procedure. Unfortunately, complications such as catheter misplacement, dislocation, or infection can occur. Various surgical strategies aim to reduce these risks. One recent innovation is the "catheter-locking device-assisted" technique for EVD surgery. In this study, we examined its application in a larger group of cases encompassing both EVDs and VPSs over a 30-month period, with a focus on these complications. METHODS: All adult patients who underwent a shunt procedure for noninfectious hydrocephalus at our institution from January 2021 to June 2023 were reviewed. We compared complications between those treated with the "standard" technique (subgroup A) and those managed with the "catheter-locking device-assisted" approach (subgroup B). RESULTS: In the EVD surgical group (initial procedures, n = 161), 6 patients (3.7%) required reoperation owing to the catheter misplacement caused by inadvertent migration of the ventricular catheter within the operating room ("early" migration), while 11 patients (6.8%) experienced unintentional postoperative dislodgement ("delayed" migration). Seven patients (4.3%) developed an EVD-related infection after an average duration of 7.4 days. None of these complications were observed in subgroup B patients (P < 0.05). Among VPS patients (n = 137), 4 (2.9%), all in subgroup A, required reoperation due to intraoperative migration of the catheter (P = 0.121); no other complications were identified. CONCLUSIONS: The "catheter-locking device-assisted" technique may significantly decrease the occurrence of the most common EVD complications and can also prove beneficial in VPS surgery. However, further investigation is necessary.

Report and Abstracts of the 15th Congress of the Mediterranean Forum of Physical and Rehabilitation Medicine: Rome, July 6-8, 2023.

The 15th Mediterranean Forum of Physical and Rehabilitation Medicine (MFPRM) Congress, held in Rome from 6 to 8 July 2023, brought together over 600 PRM specialists and residents from 51 countries and 5 continents to share knowledge, perspectives, and research findings. The Congress focused on the theme "Beyond COVID," highlighting the resilience and adaptability of PRM in the face of the pandemic. Presentations showcased the latest advancements in PRM across various subspecialties, including orthopedics and sports re-education, neurological disorders, pharmacotherapy and pain, pediatrics disorders, musculoskeletal disease, ergonomics and robotics, spasticity management, ICF and evaluation scales, spinal cord injury, musculoskeletal ultrasounds, rehabilitation of patients with cancers disease, post COVID-19 re-education, cardio-respiratory and urogynecological disorders, and traumatic brain injury. The congress successfully served as a platform for knowledge exchange, collaboration, and innovation in PRM, highlighting the importance of international cooperation and the resilience of PRM in adapting to emerging challenges.

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.

Mononuclear or Coordination Polymer Complexes? Both Are Possible for 3,6,9-Trioxaundecanedioic Acid.

Investigating the driving forces leading to the formation of a specific supramolecular architecture among a wide spectrum of all the possibly obtainable structures is not an easy task. The contemporary literature provides several models for correctly predicting the thermodynamically accessible structures that can originate from a library of building blocks. Definitions are rigid by their very nature, so their application may sometimes require a shift in perspective. In the study presented herein, we describe the crystal structures of three metallo-supramolecular architectures assembled from deprotonated derivatives of 3,6,9-trioxaundecanedioic acid and Mn(II), Co(II) and Zn(II). In the Mn(II) case, the complexation resulted in a complex of a discrete/heptacoordinated nature, whereas the other two structures appeared as helical polymers. To explain such an anomaly, in this work, we describe how the interplay between the flexibility of the ligand spacer and the number of coordinating atoms involved determines the divergent or convergent organisation of the final coordination architecture.

Correction to "Highly Efficient Supramolecular Photocatalyst for CO2 Reduction with Eight Carbon-Carbon Bonds between Ru(II) Photosensitizer and Re(I) Catalyst Unit".

[This corrects the article DOI: 10.1021/acscatal.3c01407.].

3-Dimensionally Printed Affordable Nose Model: A Reliable Start in Endoscopic Training for Young Neurosurgeons.

BACKGROUND: Training neurosurgical skills is one of the most important tasks of a residency program. Techniques' complexity and pathology rarity define a long learning curve for mastering different surgical skills for which simulation on anatomic samples is extremely important. For this purpose, cadaver laboratory training is the most reliable tool. However, since access to cadaveric specimens is limited, due to costs and availability, surgical skills could be developed using inanimate models. This work aimed to develop a printable 3-dimensional model of the nasal cavity and sellar floor using an open-source downloadable file, to give residents the opportunity to improve their endoscopic surgical skills in a low-risk atmosphere with little cost. METHODS: The 3D model was realized taking as a sample a real-case CT scan imaging from which the sellar floor was removed. A quail egg was placed underneath the printed model covering the sellar floor opening. Under endoscopic visualization, the "sellar floor" was drilled by each participant with the goal of sparing the egg's inner membrane. Once the task was achieved, surgeons were asked to participate in a satisfaction survey. RESULTS: The total cost for printing was 6.31€ (6,72$). A satisfaction survey showed technical improvement (90%), increased confidence (80%), and bringing learned skills into the operating room (70%), leading to a 100% agreement in introducing this project into residency programs. CONCLUSIONS: Training on affordable anatomic models represents a useful tool in technical skills improvement. We believe this model could help residents bring their technical capabilities to more sophisticated levels.

Adult IDH Wild-Type Glioblastoma Ultrastructural Investigation Suggests a Possible Correlation between Morphological Biomarkers and Ki-67 Index.

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma.

Photocatalyzed CO2 reduction to CO by supramolecular photocatalysts made of Ru(II) photosensitizers and Re(I) catalytic subunits containing preformed CO2TEOA adducts.

Two new supramolecular photocatalysts containing Ru(II) polypyridine units as light-harvesting photosensitizers and Re(I) polypyridine subunits as catalytic centers have been prepared. The new species, RuRe2A and Ru2ReA, contain catalytic Re(I) subunits coordinated by the preformed CO2TEOA adduct (known to be the effective catalytic subunits; TEOA is triethanolamine) and exhibit quite efficient and selective photoreduction of CO2 to CO, with outstanding TONs of 2368 and 2695 and a selectivity of 99.9% and 98.9%, respectively. Such photocatalytic properties are significantly improved with respect to those of previously studied RuRe2 and Ru2Re parent compounds, containing chloride ligands instead of the CO2TEOA adduct. Comparison between photocatalytic performance of the new species and their parent compounds allows to investigate the effect of the CO2TEOA insertion process as well as the eventual effect of the presence of chloride ions in solution on the photocatalytic processes. The improved photocatalytic properties of RuRe2A and Ru2ReA compared with their parent species are attributed to a combined effect of different distribution of the one-electron reduced form of the supramolecular photocatalysts on the Ru-subunit(s) (leading to decreased CO formation due to a poisoning ligand loss process) and on the Re-subunit(s) and to the presence of chloride ions in solution for RuRe2 and Ru2Re, which could interfere with the CO2TEOA adduct formation, a needed requisite for CO forming catalysis. These results strongly indicate the utility of preparing supramolecular photocatalysts containing preformed adducts.

Can Post-Operative Posterior Reversible Encephalopathy Syndrome (PRES) Be Considered an Insidious Rare Surgical Complication?

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by neurological symptoms and distinctive neuroimaging findings. There are a few cases reported in the literature in which PRES can occur after surgery, and there is no clear direct relationship between a procedure and its debut. Methods: We performed a review of the literature by analyzing all reported cases of PRES syndrome which debuted after a surgical procedure with the aim of identifying the clinical features, the timing of the symptoms' onset and the therapy of patients suffering from this unusual surgical complication. Results: The total number of patients collected was 47, with a mean age of 40.9 years. Postoperative PRES can occur in either pediatric or adult patients (ages 4-82 years). The most frequent form of comorbidity reported was cardiovascular disease (fourteen patients, 29.78%). Sixteen patients (36%) had no relevant risk factors or comorbidities at the time of the surgical procedure. The types of surgery most correlated were cranial neuro and maxillofacial surgery (twenty-one patients, 44.68%) followed by transplant surgery (eight patients, 17%). The time of onset of PRES after surgery occurred within the first 3 weeks (mean time of onset 4.7 days), and when rapidly treated with antihypertensive and antiepileptic drugs appeared to have a reversible and benign course. Conclusion: PRES syndrome can be considered a rare complication of procedures and can occur following a wide range of surgeries, especially cranial and transplant surgery. Being able to recognize it in time and treat it ensures a full reversibility of symptoms in most cases.

EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases.

Background: Brain metastases (BMs) is one of the most frequent metastatic sites for non-small-cell lung cancer (NSCLC). It is a matter of debate whether EGFR mutation in the primary tumor may be a marker for the disease course, prognosis, and diagnostic imaging of BMs, comparable to that described for primary brain tumors, such as glioblastoma (GB). This issue was investigated in the present research manuscript. Methods: We performed a retrospective study to identify the relevance of EGFR mutations and prognostic factors for diagnostic imaging, survival, and disease course within a cohort of patients affected by NSCLC-BMs. Imaging was carried out using MRI at various time intervals. The disease course was assessed using a neurological exam carried out at three-month intervals. The survival was expressed from surgical intervention. Results: The patient cohort consisted of 81 patients. The overall survival of the cohort was 15 ± 1.7 months. EGFR mutation and ALK expression did not differ significantly for age, gender, and gross morphology of the BM. Contrariwise, the EGFR mutation was significantly associated with MRI concerning the occurrence of greater tumor (22.38 ± 21.35 cm3 versus 7.68 ± 6.44 cm3, p = 0.046) and edema volume (72.44 ± 60.71 cm3 versus 31.92 cm3, p = 0.028). In turn, the occurrence of MRI abnormalities was related to neurological symptoms assessed using the Karnofsky performance status and mostly depended on tumor-related edema (p = 0.048). However, the highest significant correlation was observed between EGFR mutation and the occurrence of seizures as the clinical onset of the neoplasm (p = 0.004). Conclusions: The presence of EGFR mutations significantly correlates with greater edema and mostly a higher seizure incidence of BMs from NSCLC. In contrast, EGFR mutations do not affect the patient's survival, the disease course, and focal neurological symptoms but seizures. This contrasts with the significance of EGFR in the course and prognosis of the primary tumor (NSCLC).

Role of 1p/19q Codeletion in Diffuse Low-grade Glioma Tumour Prognosis.

BACKGROUND/AIM: In the latest 2021 WHO classification of central nervous system tumours (CNS), gliomas that present isocitrate dehydrogenase (IDH) mutations are defined as diffuse low-grade gliomas (DLGGs). IDH mutations are commonly observed in this tumour type. The Extent of Resection (EOR) positively influence survival; however, it is still debated whether the predictive value of EOR is independent of the 1p/19q co-deletion. We carried out a retrospective analysis on patients operated on for DLGG at the Sant'Andrea University Hospital Sapienza University of Rome, correlating the outcome with the presence of 1p/19q co-deletion and EOR. PATIENTS AND METHODS: The study examined 66 patients with DLGG who had undergone surgery for tumour resection between 2008 and 2018. Patients with DLGG were divided into two groups; diffuse astrocytoma (DA) in which 1p/19q codeletion is absent and oligodendroglioma (OG) in which 1p/19q codeletion is present. According to EOR, both groups were divided into two subgroups: subtotal resection (STR) and gross total resection (GTR). Three end-point variables were considered: overall survival (OS), progression-free survival (PFS) and time to malignant transformation (TMT). RESULTS: In the DA group, the GTR subgroup had an average OS of 81.6 months, an average PFS of 45.9 months and an average TMT of 63.6 months. After surgery, these patients had an average Karnofsky Performance Score (KPS) of 83.4. The STR subgroup had an average OS of 60.4 months, PFS was 38.7 months, and TMT was 46.4 months, post-operative KPS was 83.4. In contrast, in the OG group, the GTR averagely had 101.7 months of OS, 64.9 months of PFS, 80.3 months of TMT and an average post-operative KPS of 84.2, and the STR subgroup had an average of OS of 73.3 months, PFS of 48.2 months, TMT of 57.3 and an average postoperative KPS of 96.2. CONCLUSION: In patients affected by DLGGs, 1p/19q codeletion is significantly associated with prolonged survival and longer time-to-malignant transformation (TMT) compared to the absence of 1p/19q codeletion. Also, the extent of surgical resection (EOR) in DLGG patients has been confirmed as one of the main prognostic factors. However, its predictive value is substantially influenced by the presence of the 1p/19q codeletion.

Clinical Efficacy of Adjuvant Radiotherapy for World Health Organization Grade II Intracranial Meningioma.

BACKGROUND: Maximal surgical resection remains the treatment of choice for grade II meningiomas, and for some authors it is sufficient to guarantee a long indolent course even without postsurgical radiotherapy (RT), but there is no consensus on the use of RT in this patient population. METHODS: We retrospectively compared clinical and radiologic outcomes between World Health Organization grade I (group A) and grade II (group B) surgically treated meningiomas, focusing on the role of adjuvant RT. We registered clinical, surgical, and radiologic data to detect differences in survival and functional outcome between the 2 groups. RESULTS: The final cohort consisted of 284 patients for group A and 94 patients for group B. Group B showed a higher risk of developing recurrence independently of the extent of resection (7.75% for Group A vs. 27.7% for Group B, P = 0.01). Patients who did not undergo adjuvant RT documented recurrence in 50% of cases, compared with 19% of patients who underwent RT (P = 0.024). There is a weak difference in the risk of developing postoperative seizures in the group submitted to radiotherapy (P = 0.08). Performance status remained stable for both groups, but for Group B it tended to decrease significantly after 1 year with regard to extent of resection and RT. CONCLUSIONS: Recurrence is more frequent for grade II meningiomas, even though there are no significant differences in terms of complications and functional outcome. Radiotherapy in grade II meningiomas does indeed lead to better control of recurrence but leads to an increased risk of seizures and reduced performance status.

Bromodomain and Extraterminal Domain (BET) Protein Inhibition Hinders Glioblastoma Progression by Inducing Autophagy-Dependent Differentiation.

Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant primary brain tumor, and it is characterized by a high recurrence incidence and poor prognosis due to the presence of a highly heterogeneous mass of stem cells with self-renewal capacity and stemness maintenance ability. In recent years, the epigenetic landscape of GBM has been explored and many epigenetic alterations have been investigated. Among the investigated epigenetic abnormalities, the bromodomain and extra-terminal domain (BET) chromatin readers have been found to be significantly overexpressed in GBM. In this work, we investigated the effects of BET protein inhibition on GBM cell reprogramming. We found that the pan-BET pharmacological inhibitor JQ1 was able to promote a differentiation program in GBM cells, thus impairing cell proliferation and enhancing the toxicity of the drug Temozolomide (TMZ). Notably, the pro-differentiation capability of JQ1 was prevented in autophagy-defective models, suggesting that autophagy activation is necessary for BET protein activity in regulating glioma cell fate. Given the growing interest in epigenetic therapy, our results further support the possibility of introducing a BET-based approach in GBM clinical management.