Natural History and Predictors for Hemorrhage in Supratentorial Brain Arteriovenous Malformations.

Background/Objectives: Approximately half of the patients harboring supratentorial brain arterio-venous malformations (stAVMs) present with hemorrhage, and another considerable proportion suffer from epileptic seizures. An important milestone in the management of this vascular pathology is acknowledging their natural history, especially across long periods of time. The aim of this study was to assess the predictive factors for hemorrhage and for epileptic seizures as presenting symptoms in stAVMs. Methods: We retrospectively analyzed patients with stAVMs admitted to our institution between 2012 and 2022 and evaluated predictive factors for hemorrhage and the risk factors associated with epileptic seizures. Results: The cohort included 169 patients, 78 of them (46.2%) presenting with intracerebral hemorrhage (ICH). Seventy-seven (45.5%) patients suffered from epileptic seizures. The annual hemorrhagic rate was 1.28%/year. Unruptured lesions (p = 0.001, OR 3.1, 95% CI 1.6-6.2), superficial venous drainage (p = 0.007, OR 2.7, 95% CI 1.3-5.7) and large nidus size (p = 0.025, OR 4, 95% CI 1.2-13.5) were independently associated with seizures. Among unruptured lesions, superficial venous drainage (OR 2.6, p = 0.036, 95% CI 1.06-6.3) and frontal/temporal/parietal location (OR 2.7, p = 0.040, 95 CI% 1.04-6.9) significantly increased the risk of seizures as a presenting symptom in multivariate analysis. Patients younger than 18 (p = 0.003, OR 4.5, 95% CI 1.6-12.2), those with AVMs < 3 cm (p = 0.03, OR 2, 95% CI 1.07-3.9) or those with deep located AVMs (p = 0.035, OR 2.3, 95% CI 1.06-5.1) presented statistically more often with ICH in multivariate regression. Small size (HR 1.8, 95% CI 1.09-3, p = 0.022) and exclusively deep venous drainage (HR 2.2, 95% CI 1.2-4, p = 0.009) were independent predictors for ICH, in time-dependent birth-to-diagnosis analysis. After shifting the birth-to-diagnosis curve by 10 years, unique arterial feeder demonstrated a positive correlation with ICH presentation as well. Conclusions: Small AVMs, those with exclusively deep venous drainage, unique arterial feeder or deep location may pose higher hemorrhagic risks for the patient, and therapeutic strategies should be tailored accordingly. When managing unruptured brain AVMs, it is important to consider the risk of developing seizures, in addition to the lifelong risk of hemorrhage, in determining the optimal treatment approach for each patient.

Grading of glioma tumors using digital holographic microscopy.

Gliomas are the most common type of cerebral tumors; they occur with increasing incidence in the last decade and have a high rate of mortality. For efficient treatment, fast accurate diagnostic and grading of tumors are imperative. Presently, the grading of tumors is established by histopathological evaluation, which is a time-consuming procedure and relies on the pathologists' experience. Here we propose a supervised machine learning procedure for tumor grading which uses quantitative phase images of unstained tissue samples acquired by digital holographic microscopy. The algorithm is using an extensive set of statistical and texture parameters computed from these images. The procedure has been able to classify six classes of images (normal tissue and five glioma subtypes) and to distinguish between gliomas types from grades II to IV (with the highest sensitivity and specificity for grade II astrocytoma and grade III oligodendroglioma and very good scores in recognizing grade III anaplastic astrocytoma and grade IV glioblastoma). The procedure bolsters clinical diagnostic accuracy, offering a swift and reliable means of tumor characterization and grading, ultimately the enhancing treatment decision-making process.

Clinical outcomes of posterior fossa arteriovenous malformations: a single center experience.

BACKGROUND: Posterior fossa arterio-venous malformations (pfAVMs) are challenging lesions due to the anatomical particularities of the posterior fossa, and the high incidence of hemorrhagic presentation. The two most important goals when treating AVMs are preserving neurological function and preventing rupture, or a second hemorrhage. The aim of this study was to analyze the clinical and imaging features of pfAVMs to identify the factors that influence the prognosis of these patients. METHODS: We conducted a single-center retrospective observational study that included patients treated at our institution with pfAVMs between January 1997 and December 2021. RESULTS: A total of 48 patients were included. A good modified Rankin score (mRS) was observed in 33 cases (69%) at presentation. Thirty-four patients (71%) presented with a ruptured AVM. Out of these, 19 patients (40%) had intraventricular hemorrhage. Microsurgical resection was performed in 33 cases (69%), while in the other cases, the patients opted for conservative management (7 cases, 15%), stereotactic radiosurgery (SRS) (6 cases, 12%), or endovascular treatment (2 cases, 4%). Patients ≤ 30 years old were more prone to hemorrhagic presentation (OR: 5.23; 95% CI: 1.42-17.19; p = 0.024) and this remained an independent risk factor for rupture after multivariate analysis as well (OR: 4.81; 95% CI: 1.07-21.53; p = 0.040). Following multivariate analysis, the only factor independently associated with poor prognosis in the surgically treated subgroup was a poor clinical status (mRS 3-5) at admission (OR: 96.14; 95% CI: 5.15-1793.9; p = 0.002). CONCLUSIONS: Management of posterior fossa AVMs is challenging, and patients who present with ruptured AVMs often have a poor clinical status at admission leading to a poor prognosis. Therefore, proper and timely management of these patients is essential.

Healthcare Professionals' Specialists' Perception of Telemedicine in Romania-A Quantitative Study of Beliefs, Practices, and Expectations.

BACKGROUND: Telemedicine is the service of delivering medical care from a distance through the means of modern technology. It has many advantages, including improved access, decreased costs for both patients and clinics, more flexibility and availability, as well as more precise and individualized therapies. However, it is equally important to take into consideration all the challenges associated with this innovative way of providing care. This virtual technology has had an exponential growth, especially since the beginning of the COVID-19 pandemic, because it delivers great outcomes and suggests exciting future promises. METHODS: The study involved the collection of responses from an online questionnaire comprising 26 questions that was distributed to healthcare professionals in Romania. RESULTS: The questionnaire was completed by a number of 1017 healthcare professionals. We investigated and analyzed whether telehealth is seen as an important constituent of the healthcare system, if it is perceived as necessary, safe, well-managed by lawmakers, and easy to use, what advantages it has, what common practices specialists already employ and, additionally, the openness toward becoming more digitally educated for the purpose of streamlining the use of telemedicine. CONCLUSIONS: This paper reports on the perception of telemedicine among healthcare professionals in Romania, as constructive feedback represents an essential piece of the puzzle in assuring the smooth transition toward this facet of modern healthcare.

Clinical Applications of Artificial Intelligence-An Updated Overview.

Artificial intelligence has the potential to revolutionize modern society in all its aspects. Encouraged by the variety and vast amount of data that can be gathered from patients (e.g., medical images, text, and electronic health records), researchers have recently increased their interest in developing AI solutions for clinical care. Moreover, a diverse repertoire of methods can be chosen towards creating performant models for use in medical applications, ranging from disease prediction, diagnosis, and prognosis to opting for the most appropriate treatment for an individual patient. In this respect, the present paper aims to review the advancements reported at the convergence of AI and clinical care. Thus, this work presents AI clinical applications in a comprehensive manner, discussing the recent literature studies classified according to medical specialties. In addition, the challenges and limitations hindering AI integration in the clinical setting are further pointed out.

GFAPδ: A Promising Biomarker and Therapeutic Target in Glioblastoma.

GFAPδ, the delta isoform of the glial fibrillary acidic protein, is mainly expressed in the subventricular zone of the brain, together with other neural stem cell markers like nestin. The authors of this paper were among the first that described in detail the expression of GFAPδ and its correlation with malignancy and invasiveness in cerebral astrocytoma. Later, several papers confirmed these findings, showing that the alternative splice variant GFAPδ is overexpressed in glioblastoma (CNS WHO grade 4) compared with lower grade gliomas. Other studies suggested that a high GFAPδ/α ratio is associated with a more malignant and invasive behavior of glioma cells. Moreover, the changing of GFAPδ/α ratio affects the expression of high-malignant genes. It is now suggested that discriminating between predominant GFAP isoforms, GFAPδ or GFAPα, is useful for assessing the malignancy state of astrocytoma, and may even contribute to the classification of gliomas. Therefore, the purpose of this paper is to review the literature with emphasize on the role of GFAPδ as a potential biomarker, and as a possible therapeutic target in glioblastoma.

Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance.

Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered "non-functional" ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer is it possible to translate the knowledge about ncRNAs and their modifications into clinical practice.

Microsurgical approach for symptomatic brain AVMs - single center experience.

Objectives: Brain arteriovenous malformations (AVMs) represent high-flow vascular lesions made up of a complex network of feeding arteries and draining veins interposed by a nidus and without a capillary bed. The management of the AVMs represents a challenge, and the optimal treatment should be considered based on the particularities of each AVM. This paper aims to provide outcome data for the cohort of patients with AVMs that underwent surgical treatment. Methods: A retrospective review of patients who presented with AVMs between 2001 and 2019 was conducted. Patients were included if they underwent surgery, preoperative and postoperative angiographic studies were available. Results: 91 patients were included. The SM grade was 1 in 16 cases (17,6%), 2 in 27 patients (29.7%), 3 in 29 patients (31,9%), 4 in 12 cases (13.2%) and grade 5 in 7 cases (7.7%). In 58 (63.7%) cases the AVMs were ruptured. Complete microsurgical resection was achieved in 82 cases (90.1%). Unruptured AVM (87.9% vs. 63.8% for ruptured AVMs; p = 0.015), low-grade AVM (86% vs. 60.4% for grade III-V AVMs; p = 0.006) and cortical location (79.5% vs. 30.8% for deep AVM; p < 0.0001) were the factors associated with a good outcome on mRS scale. Conclusions: Microsurgical resection is the curative treatment for AVMs and offers a good functional outcome if selection criteria are met.

Fighting Cancer Stem Cell Fate by Targeting LIS1 a WD40 Repeat Protein.

Cancer is one of the most frequent and devastating diseases. Previous reports have shown that radio and chemo-resistant cancer stem cell (CSC) population is primarily responsible for cancer recurrences after radiotherapy and chemotherapy. Other studies demonstrated that Lissencephaly-1 (LIS1) protein, also known as platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1), a dynein-binding protein involved in neural stem cell division, plays a crucial role in maintaining CSC population in hematological malignancies. Moreover, one recent report demonstrated that LIS1 gene is preferentially expressed in CD133+ glioblastoma cells and may have also an important role in regulating CD133+ CSC in glioblastoma. The hypothesis of this paper is that LIS1 plays a key role in maintaining CD133+ CSC population in various solid cancers by orientating the cell division plane through an interaction with dynein and therefore controlling the stem cell fate regulatory mechanism. As CD133+ CSC population is responsible for radio- and chemo-resistance, which finally determines the cancer recurrences and metastases, identifying the molecular mechanisms which regulate the CD133+ CSC population represents a major target for cancer research. Given the structure of LIS1, which contains WD40 repeat domain, small peptide inhibitors could be used to alter its function. Therefore, the impact of confirming this hypothesis is significant because LIS1 may become an important molecular target for future adjuvant anticancer therapies directed against radio- and chemo-resistant CSC population.

Central pancreatectomy: a comprehensive, up-to-date meta-analysis.

BACKGROUND: Central pancreatectomy (CP) is the alternative to distal pancreatectomy (DP) for specific pathologies of the mid-pancreas. However, the benefits of CP over DP remain controversial. This study aims to compare the two procedures by conducting a meta-analysis of all published papers. METHODS: A systematic search of original studies comparing CP vs. DP was performed using PubMed, Scopus, and Cochrane Library databases up to June 2018. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist was followed. RESULTS: Twenty-one studies were included (596 patients with CP and 1070 patients with DP). Compared to DP, CP was associated with significantly higher rates of overall and severe morbidity (p < 0.0001), overall and clinically relevant pancreatic fistula (p < 0.0001), postoperative hemorrhage (p = 0.02), but with significantly lower incidences of new-onset (p < 0.0001) and worsening diabetes mellitus (p = 0.004). Furthermore, significantly longer length of hospital stay (p < 0.0001) was observed for CP patients. CONCLUSIONS: CP is superior to DP regarding the preservation of pancreatic functions, but at the expense of significantly higher complication rates and longer hospital stay. Proper selection of patients is of utmost importance to maximize the benefits and mitigate the risks of CP.

MicroRNA based theranostics for brain cancer: basic principles.

BACKGROUND: Because of the complexity of the blood-brain barrier (BBB), brain tumors, especially the most common and aggressive primary malignant tumor type arising from the central nervous system (CNS), glioblastoma, remain an essential challenge regarding diagnostic and treatment. There are no approved circulating diagnostic or prognostic biomarkers, nor novel therapies like immune checkpoint inhibitors for glioblastoma, and chemotherapy brings only minimal survival benefits. The development of molecular biology led to the discovery of new potential diagnostic tools and therapeutic targets, offering the premise to detect patients at earlier stages and overcome the current poor prognosis. MAIN BODY: One potential diagnostic and therapeutic breakthrough might come from microRNAs (miRNAs). It is well-known that miRNAs play a role in the initiation and development of various types of cancer, including glioblastoma. The review aims to answer the following questions concerning the role of RNA theranostics for brain tumors: (1) which miRNAs are the best candidates to become early diagnostic and prognostic circulating biomarkers?; (2) how to deliver the therapeutic agents in the CNS to overcome the BBB?; (3) which are the best methods to restore/inhibit miRNAs? CONCLUSIONS: Because of the proven roles played by miRNAs in gliomagenesis and of their capacity to pass from the CNS tissue into the blood or cerebrospinal fluid (CSF), we propose miRNAs as ideal diagnostic and prognostic biomarkers. Moreover, recent advances in direct miRNA restoration (miRNA mimics) and miRNA inhibition therapy (antisense oligonucleotides, antagomirs, locked nucleic acid anti-miRNA, small molecule miRNA inhibitors) make miRNAs perfect candidates for entering clinical trials for glioblastoma treatment.

Multiple myeloma: recognition and management.

Multiple myeloma is the malignant proliferation of plasma cells involving more than 10 percent of the bone marrow. The multiple myeloma cell produces monoclonal immunoglobulins that may be identified on serum or urine protein electrophoresis. Bone pain related to multiple lytic lesions is the most common clinical presentation. However, up to 30 percent of patients are diagnosed incidentally while being evaluated for unrelated problems, and one third of patients are diagnosed after a pathologic fracture, commonly of the axial skeleton. Multiple myeloma must be differentiated from other causes of monoclonal gammopathy, including monoclonal gammopathy of undetermined significance, heavy chain disease, plasmacytoma and Waldenstrom macroglobulinemia. Chemotherapy with melphalan-prednisone is the standard treatment for multiple myeloma. Other treatment modalities include polychemotherapy and bone marrow transplantation. Only 50 to 60 percent of patients respond to therapy. The aggregate median survival for all stages of multiple myeloma is three years.

Military penetrating craniocerebral injuries. Applications to civilian triage and management.

Although facilities at many civilian centers far exceed those historically available to military neurosurgeons in the field, the principles derived from combat injuries continue to apply. It is hoped that there may be differences in salvageability at the margin owing to the availability of more sophisticated imaging and critical care monitoring techniques, neuroanesthesia, and the advent of possible pharmacologic neural salvage agents.

Acute subdural hematoma after aneurysmal rupture; evacuation with aneurysmal clipping after emergent infusion computed tomography: case report.

A 74-year-old woman sought treatment after an initial subarachnoid hemorrhage verified on computed tomographic scan with no focal neurological deficit. Shortly after admission, she sustained a second subarachnoid hemorrhage with acute neurological decompensation. A repeat computed tomographic scan revealed increased blood along the right medial temporal region, as well as in the interhemispheric fissure and bilateral sylvian cisterns. Also evident was a right hemispheric acute subdural hematoma. The patient's rapidly deteriorating neurological status precluded a cerebral angiogram; therefore, a double-dose infusion computed tomographic scan was performed. This revealed a cerebral artery aneurysm adjacent to the right medial temporal hematoma. She was taken to the operating room on the basis of this study. After evacuation of the right hemispheric subdural hematoma and clipping of the right posterior communicating artery aneurysm, the patient made a rapid, full neurological recovery.

Subarachnoid hemorrhage due to intracranial aneurysm: current management.

Intracranial aneurysms cause in excess of 28,000 subarachnoid hemorrhages per year in North America. The combined mortality and morbidity from aneurysmal subarachnoid hemorrhage exceeds 40%, and therefore yields a remarkably high toll of human and economic loss. As a lesion that is treatable, even curable at particular stages, management decisions are critical. In spite of significant advances in surgical technique, the mortality rate remains high. Erroneous diagnosis in good-grade patients significantly contributes to the lack of improvement in current statistics. Diagnosis and subsequent contemporary management is discussed.

The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment.

The authors have updated a series of 166 prospectively followed unoperated symptomatic patients with arteriovenous malformations (AVM's) of the brain. Follow-up data were obtained for 160 (96%) of the original population, with a mean follow-up period of 23.7 years. The rate of major rebleeding was 4.0% per year, and the mortality rate was 1.0% per year. At follow-up review, 23% of the series were dead from AVM hemorrhage. The combined rate of major morbidity and mortality was 2.7% per year. These annual rates remained essentially constant over the entire period of the study. There was no difference in the incidence of rebleeding or death regardless of presentation with or without evidence of hemorrhage. The mean interval between initial presentation and subsequent hemorrhage was 7.7 years.

Penetrating craniocerebral injuries in the Israeli involvement in the Lebanese conflict, 1982-1985. Analysis of a less aggressive surgical approach.

From June, 1982, through June, 1985, 113 patients were evacuated to Rambam Maimonides Medical Center with penetrating craniocerebral injuries sustained in ongoing military hostilities in Lebanon. Two factors distinguished this group of patients from those presenting in earlier conflicts: 1) this was the first large series in which computerized tomography (CT) was routinely used to initially evaluate combat head injuries; and 2) in an effort to preserve maximum cerebral tissue, intracranial debridement was significantly less vigorous than that advocated during the Korean or Vietnam conflicts. No efforts were made to locate or remove in-driven bone or metal fragments visualized on CT unless they readily presented themselves on gentle irrigation. In fact, it was elected to treat a number of patients without intracranial hematomas nonoperatively. The acute outcome was quite similar to that reported in Vietnam series in respect to both complications and mortality. Of the 83 survivors, 46 were Israeli citizens and thus were available for follow-up review. These 46 patients were reevaluated in late 1988, a mean follow-up period of 5.9 years. None had died in the interim; 10 had developed chronic seizure disorders, and there was one case of delayed meningitis in a patient with no retained fragments. Repeat CT scans were performed on 43 patients; 22 (51%) were found to have retained intracranial bone fragments. No relationship existed between the presence of retained fragments and the development of either a seizure disorder or an infection of the central nervous system. These findings suggest that not only is it unnecessary to reoperate for retained bone fragments, but it may also be possible to temper the initial debridement in an effort to preserve additional cerebral tissue.

Heterogeneity of cerebral cavernous hemangiomas diagnosed by MR imaging.

The cavernous hemangioma (cavernoma) is increasingly recognized as a vascular malformation of the brain that may present with seizures, hemorrhage, or progressive neurological deficit. Since 1985 we have identified 13 cases of presumed cavernoma of the brain based on the findings on CT, selective angiography, and magnetic resonance (MR) imaging. In each case CT showed a high density lesion that was "occult" or "cryptic" on angiography. However, within all lesions MR revealed a complex internal structure consisting of reticulated patches of high and low intensity signal surrounded by a hypointense rim on T1- and T2-weighted pulse sequences. Of the nine operated cases, five resected specimens were compatible with pure arteriovenous malformations (AVMs), and the other four were mixtures of cavernoma with either AVM or venous angioma. Our experience strongly suggests that the above complex of radiographic findings is not at all specific for the cavernoma. We propose that the major common factor shared by such "cavernomatoid" malformations is low blood flow. We believe low flow lesions follow a relatively benign clinical course, and they readily lend themselves to surgical resection.

Surgical excision of a cavernous hemangioma of the rostral brain stem: case report.

A 23-year-old pregnant woman presented with sudden diplopia, ataxia, hemiparesis, and headache secondary to a brain stem hemorrhage. Magnetic resonance imaging (MRI) revealed a hematoma associated with a probable cavernous hemangioma of the rostral brain stem. In this report, we discuss the MRI findings leading to the preoperative diagnosis, as well as the surgical techniques involved in the successful resection.

Treatment of a central arteriovenous malformation of the mandible with cyanoacrylate: a 4-year follow-up.

Large arteriovenous malformations of the jaws are relatively rare, potentially life-threatening lesions. When the lesion is not suspected, extraction of teeth can be fatal. The occurrence and treatment of arteriovenous vascular communications in the head and neck region have traditionally presented most perplexing problems. Traditional treatment has usually involved the obtaining of proximal and distal vascular control and surgical removal of the lesions, when feasible. This article presents a case that is of particular interest because it illustrates the successful use of cyanoacrylate as the only treatment for a large arteriovenous malformation of the left side of the mandible. A 4-year follow-up shows no evidence of the lesion and demonstrates complete regeneration of bone in the same area.