Efficacy of antimicrobial medicated ventricular catheters: a network meta-analysis with trial sequential analysis.

There is paucity of evidence regarding relative performance of antibiotic-medicated (AM), silver-medicated (SM) and non-medicated (NM) ventricular catheters in controlling infection rate. We aim to quantitatively synthesize the current evidence after addition of the three-armed British Antibiotic and Silver Impregnated Catheters for ventriculoperitoneal Shunts (BASICS) trial, understand the need for further evidence using trial sequential analysis (TSA) and incorporate the indirect evidence using network meta-analysis (NMA). Randomized controlled trials (RCTs) comparing AM, SM and NM ventriculoperitoneal shunt (VPS) or external ventricular drain (EVD) were included. Antibiotic-medicated VPS show a significantly lower infection rate as compared to non-medicated VPS (RR 0.44; 95% CI: 0.27-0.73; p = 0.001), however, TSA reveals need for further evidence. SM including both EVD as well as VPS were found to be inferior to AM while no significant difference was found in comparison to the NM catheters. In NMA for VPS, the AM were found to be significantly better than SM (RR 0.41, 95% CI: 0.22-0.75) as well as NM (RR 0.42; 95% CI: 0.25-0.71) with a SUCRA of 99.8% and a mean rank of 1. However, antibiotic medicated shunts did not show a statistically significant association with reoperation rate (RR 0.99; 95% CI:0.81-1.20; p = 0.9) with no further need for evidence as per TSA.

Allyl sulfide promotes osteoblast differentiation and bone density via reducing mitochondrial DNA release mediated Kdm6b/H3K27me3 epigenetic mechanism.

Age-associated bone loss or osteoporosis is a common clinical manifestation during aging (AG). The mechanism underlying age-associated osteoblast dysfunction induced by oxidative damage in the mitochondria and loss of bone density remains elusive. Here, we demonstrated the effect of allyl sulfide (AS), a natural organosulfur compound, on mitochondrial (mt) function in bone marrow-derived mesenchymal stem cells (BMMSCs) and bone density in AG mice. The data demonstrate that AS treatment in AG mice promotes BMMSCs differentiation and mineralization via inhibition of mitochondrial oxidative damage. The data also indicate that AG related mito-damage was associated with reduced mitochondrial biogenesis and oxidative phosphorylation, and release of a greater concentration of mtDNA. Furthermore, the data showed that mtDNA caused histone H3K27 demethylase inhibition, KDM6B, and subsequent inflammation by unbalancing mitochondrial redox homeostasis. KDM6B overexpression in AG BMMSCs or AS administration in AG mice restores osteogenesis and bone density in vitro and in vivo. Mechanistically, AS or the mitochondrial-specific antioxidant Mito-TEMPO increased KDM6B expression and upregulated the expression of Runx2 in BMMSCs, probably via epigenetic inhibition of H3K27me3 methylation at the promoter. These data uncover the previously undefined role of AS mediated prevention of mtDNA release, promoting osteogenesis and bone density via an epigenetic mechanism. Therefore, AS could be a potential drug target for the treatment of aging-associated osteoporosis.

Cerebellar mutism after posterior fossa tumor resection in children: a multicenter international retrospective study to determine possible modifiable factors.

PURPOSE: A preliminary survey of pediatric neurosurgeons working at different centers around the world suggested differences in clinical practice resulting in variation in the risk of pediatric cerebellar mutism (CM) and cerebellar mutism syndrome (CMS) after posterior fossa (PF) tumor resection. The purposes of this study were (1) to determine the incidence and severity of CM and CMS after midline PF tumor resection in children treated at these centers and (2) to identify potentially modifiable factors related to surgical management (rather than tumor biology) that correlate with the incidence of CM/CMS. METHODS: Attending pediatric neurosurgeons at British Columbia's Children's Hospital (BCCH) and neurosurgeons who completed a pediatric neurosurgery fellowship at BCCH were invited to provide data from the center where they currently practiced. Children aged from birth to less than 18 years who underwent initial midline PF tumor resection within a contemporary, center-selected 2-year period were included. Data was obtained by retrospective chart and imaging review. Modifiable surgical factors that were assessed included pre-resection surgical hydrocephalus treatment, surgical positioning, ultrasonic aspirator use, intraoperative external ventricular drain (EVD) use, surgical access route to the tumor, and extent of resection. CM was defined as decreased or absent speech output postoperatively and CMS as CM plus new or worsened irritability. RESULTS: There were 263 patients from 11 centers in 6 countries (Canada, Germany, the Netherlands, India, Indonesia, and the USA). Median age at surgery was 6 years (range < 1 to 17 years). The overall incidence of postoperative CM was 23.5% (range 14.7-47.6% for centers with data on ≥ 20 patients). The overall incidence of CMS was 6.5% (range 0-10.3% for centers contributing data on ≥ 20 patients). A multivariate logistic regression on the full data set showed no significant association between pre-resection surgical hydrocephalus treatment, prone position, ultrasonic aspirator use, EVD use, telovelar approach, complete or near total resection, or treating center and either postoperative CM or CMS. CONCLUSIONS: While there was variation in surgical management of midline PF tumors among centers participating in this study, the factors in management that were examined did not predict postoperative CM or CMS.

Tuberous Sclerosis Complex as a Social Determinant of Health, Alongside Its Psychiatric Comorbidities: A Case Report.

Tuberous sclerosis complex (TSC) is a neurocutaneous disease that manifests across multiple body systems. While there are substantial guidelines and protocols for managing the physical presentation of the disease, managing the psychosocial factors and the adverse effects as a social determinant of health is complex and unclear. This study discusses a patient with TSC who was hospitalized for pneumonia and how both her psychiatric and somatic symptoms were managed. Here we present the case of a 38-year-old Caucasian female with shortness of breath and generalized weakness. She had a past medical history of TSC and pneumothorax. This patient presented to the emergency department agitated and initially combative with her care team. Ultimately, she was administered dexmedetomidine to reduce her agitation. Here we suggest that this patient's agitation and other psychiatric symptoms are intimately related to her diagnosis of TSC. Because of the heavy burden of TSC on the patient's life, the patient's aggressive nature could be an act of displacement of feelings from her medical complications onto her interactions with others. The patient understood that her complications hindered her ability to function as a healthy 38-year-old and perform activities of daily living without severe exhaustion. Just as her condition and its secondary complications hindered her body, feelings of anger and despair hindered her ability to appropriately interact and socialize with others. TSC is a debilitating condition that targets the body and mind. While much research has gone into treating each somatic system it may affect, there is a disconnect between the psychiatric aftermath and the toll that such a condition's psychiatric comorbidities may take on its patients.

Beta-Thalassemia in Adulthood Previously Suspected as Treatment-Resistant Iron Deficiency Anemia: A Case Report.

Beta-thalassemia (ß-thalassemia) is a hematologic genetic condition that causes microcytic anemia due to defective synthesis of the hemoglobin beta chain. As a hypochromic microcytic anemia that is commonly associated with symptoms such as fatigue and pallor when identified in adulthood, ß-thalassemia may be commonly underdiagnosed or misdiagnosed as iron deficiency anemia. This study presents a case of a patient with ß-thalassemia who was initially misdiagnosed with treatment-resistant iron deficiency anemia. Here, we present the case of a 66-year-old male of Mediterranean descent with a history of military service who presented with persistent fatigue. He had a past medical history of hypertension, diabetes mellitus type 2, sleep apnea, and iron deficiency anemia. Despite undergoing unnecessarily prolonged iron supplementation for suspected iron deficiency anemia, the patient's complete blood count and peripheral blood smear continued to identify hypochromic microcytic anemia. Ultimately, hemoglobin electrophoresis was performed, and mutations were identified in the hemoglobin beta chain consistent with ß-thalassemia minor. Due to its rarity and wide variation in presentation, ß-thalassemia may be frequently misdiagnosed. ß-thalassemia is a spectrum of disorders ranging from ß-thalassemia minor, which may be asymptomatic and incidentally discovered in adulthood, to ß-thalassemia major, which may include bone marrow deformities from extramedullary hematopoiesis and require frequent blood transfusions to sustain life. Therefore, patients who present with symptoms of ß-thalassemia minor may not be identified until later in life after undergoing decades of ineffective treatment. ß-thalassemia is a multifactorial disease with a variety of clinical presentations that can easily be misdiagnosed as other types of anemia. This case highlights the importance of performing thorough laboratory testing and casting a wide net of differential diagnoses when evaluating patients with treatment-resistant anemia. This case calls for further research on the genetic contributions to ß-thalassemia as well as improved ways to identify this disorder, particularly in patients who may not have a severe form that is easily diagnosed in early childhood.

Pretemporal Transcavernous Approach to Basilar Tip Aneurysms: Operative Technique and Surgical Nuances: 3-Dimensional Operative Video.

INDICATIONS CORRIDORS AND LIMITS OF EXPOSURE: This approach provides a 360° view of the anterior upper third of posterior fossa which can tackle any kind of complex basilar aneurysm. It combines the benefits of both pterional/orbitozygomatic and subtemporal approaches. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: Computed tomography angiography revealed a low-lying basilar apex, so a full transcavernous approach was used. Electroencephalogram, somatosensory evoked potentials, and brainstem auditory evoked response are essential modalities to monitor during temporary clipping. ESSENTIAL STEPS OF THE PROCEDURE: Anterior clinoidectomy, dissection of cavernous sinus, and posterior clinoidectomy to expose the perforator-free zone of basilar artery proximal to the superior cerebellar artery are essential steps described in detail in the video. Analyzing the perforator anatomy around the aneurysm before putting a clip is utmost essential. PITFALLS/AVOIDANCE OF COMPLICATIONS: Clipping a basilar aneurysm using this approach requires a neurosurgeon to have a sound knowledge of the neuroanatomy as well as a skilled handset for performing clinoidectomy and cavernous sinus dissection to avoid neurovascular injury. VARIANTS AND INDICATIONS FOR THEIR USE: Pterional/orbitozygomatic (for high riding bifurcation), subtemporal (low riding bifurcation), and endovascular therapy (small aneurysm with narrow neck) are other options used for these aneurysms.

Exploring the Impact of Auditory Hallucinations on Sudden Sensorineural Hearing Loss in Adulthood: A Case Report.

Auditory hallucinations are sounds that patients perceive as coming from outside of their body. Though the mechanism causing auditory hallucinations is not entirely understood, there is a significant amount of evidence suggesting that auditory hallucinations leave lasting impacts on the brain in the same regions that are involved in auditory processing. Sudden sensorineural hearing loss (SSNHL) is a poorly understood condition in which patients lose their hearing typically in the fifth decade of life. Here we present a case of a 42-year-old female with a history of schizophrenia with auditory hallucinations who experienced SSNHL at age 40. As the patient had no known risk factors for SSNHL, we propose that this patient's SSNHL is linked to her history of auditory hallucinations. Through the presentation of this case, we hope to explore the pathogenesis of auditory hallucinations and investigate a potentially bidirectional association between auditory hallucinations and SSNHL. This study calls for further investigation into the impacts of auditory hallucinations on the brain, possible etiologies of SSNHL, and the possibility that auditory hallucinations serve as a risk factor for SSNHL.

Navigating Community-Based Psychiatry Care of Pediatric Patients in Low-Resource Settings: A Case Report.

This case report examines the experience of a nine-year-old male with autism spectrum disorder (ASD) who was admitted to his rural community emergency department (ED) for the treatment of aggressive behaviors, agitation, and violence. Despite a high prevalence of such behaviors within the autistic pediatric population, multiple inpatient facilities that offer pediatric psychiatric services refused to transfer his care. Many other commonly used resources and treatment modalities were also not available, resulting in a nine-day ED boarding experience with minimal symptomatic improvement. Pharmacotherapy was utilized, but nationally recommended guidelines were not appropriately followed. Although this case is one of many pediatric patients who received inadequate psychiatric care from their local ED, it is significant in identifying specific areas of improvement within Northeast Louisiana psychiatric healthcare. This case report of a nine-year-old male with autism underlines the hardships faced by patients and their families due to the gaps in our current healthcare infrastructure and emphasizes the importance of protocols and resources for patient populations with higher-than-average wellness needs.

Early Gamma Knife Therapy (Without EBRT) in Operated Patients of Glioblastoma Multiforme.

Background: The standard therapy for glioblastoma (GBM) has been external beam radiotherapy (EBRT) with concomitant temozolomide (TMZ) given for six cycles, after maximum possible surgical resection although recurrences after chemoradiation are mostly in-field. Objective: To compare the effects of early GKT (without EBRT) along with TMZ to those receiving standard chemoradiotherapy (EBRT + TMZ) after surgery. Methods: This was a retro-prospective study on histologically proven GBMs operated at our center between January 2016 and November 2018. The EBRT group consisted of 24 patients who received EBRT + TMZ for six cycles. The GKT arm consisted of 13 consecutive patients who received Gamma Knife within 4 weeks of surgery along with lifelong temozolomide. Patients were followed up every 3 months with CEMRI brain and PET-CT. The primary endpoint was overall survival (OS) with progression-free survival (PFS) being the secondary endpoint. Results: At a mean follow-up of 13.7 months, the median overall survivals in GKT and EBRT groups were 11.07 and 13.03 months, respectively (HR = 0.59; P value = 0.19; 95% CI: 0.27-1.29). The median PFS for GKT group was 7.03 months (95% CI: 4.17-17.3) as compared to 11.07 months (95% CI: 5.33-14.03) for the EBRT group. There was no statistical difference in the PFS or OS between the GKT and EBRT groups. Conclusion: Our study shows that Gamma Knife therapy (without EBRT) to residual tumor/tumor bed after primary surgery with concurrent temozolomide has similar progression-free (PFS) and overall survival (OS) rates when compared to conventional treatment (EBRT).

Transcallosal Suprachoroidal Approach for a Small Third Ventricular Colloid Cyst.

Background and Introduction: The interhemispheric transcallosal approach provides an elegant pathway to access the lesions of the third ventricle. However, every step of this approach is fraught with hazards which must be negotiated delicately. A comprehensive knowledge of surgical anatomy coupled with technical skill is necessary for optimum surgical results. Objective: This video aims to address the surgical nuances of the suprachoroidal transcallosal approach while accessing the lesions around the foramen of Monro in the anterior and middle part of the third ventricle. Surgical Technique: A 16-year-old boy presented with worsening headaches with episodes of speech arrest and blank stare for 6 years, which had become more frequent over the past 4-5 months. Radiology showed a subcentimeteric colloid cyst at the foramen of monro. A transcallosal corridor was used to reach the foramen of monro, and the suprachoroidal access was adopted to uncover the colloid cyst and excise it completely preserving the deep veins. Results: The patient had uneventful recovery and radiology showed complete excision of the cyst. Conclusion: Transcallosal approach, being minimally invasive, exploits the natural extra-axial corridor (interhemispheric) obviating the need for a cortical incision. The suprachoroidal approach mitigates the risks of thalamostriate vein injury, basal ganglia stroke, and hemiparesis.

Surgical Track and Scalp Implantation Following Intraventricular Meningiomas Excision: A Report with Review of Literature.

Meningiomas are benign intracranial neoplasms arising from arachnoid cap cells. High grade meningiomas are uncommon and metastasis from these is an extremely rare event. Commonest sites of metastasis from high grade meningiomas include lung, liver, lymph nodes and bone. It is unusual for meningiomas to recur in the surgical track following excision. More so, it is even the rarest phenomenon for a meningioma to implant in subgaleal location. Various mechanisms have been proposed for the scalp implantation vis-à-vis CSF dissemination, direct surgical implantation etc., It may apply to all histological grades of meningiomas. Even the benign tumors have been shown to seed at postoperative scar. This seems to have provoked our interest to review the literature regarding this scalp implantation. We have reviewed all the cases where surgical excision of intracranial meningiomas has led to seeding of surgical track as well as scalp. We have discussed the various genetic aberrations that can guide us regarding the progression of the tumor and prognosis. We also report a case of surgical track and scalp implantation of an atypical intraventricular meningioma following excision.

Molecular Characterization of IDH Wild-type Diffuse Astrocytomas: The Potential of cIMPACT-NOW Guidelines.

IDH wild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles. cIMPACT-NOW recommendations incorporated in the new 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors urge minimal molecular criteria to identify a subset that has an aggressive clinical course similar to IDH -wt glioblastomas (GBMs). This paper describes the use of a panel of molecular markers to reclassify IDH -wt grade 2/3 diffuse astrocytic gliomas (DAGs) and study median overall survival concerning for to IDH -wt GBMs in the Indian cohort. IDH -wt astrocytic gliomas (grades 2, 3, and 4) confirmed by IDHR132H immunohistochemistry and IDH1/2 gene sequencing, 1p/19q non-codeleted with no H3F3A mutations were included. TERT promoter mutation by Sanger sequencing, epidermal growth factor receptor amplification, and whole chromosome 7 gain and chromosome 10 loss by fluorescence in situ hybridization was assessed and findings correlated with clinical and demographic profiles. The molecular profile of 53 IDH -wt DAGs (grade 2: 31, grade 3: 22) was analyzed. Eleven cases (grade 2: 8, grade 3: 3) (20.75%) were reclassified as IDH -wt GBMs, WHO grade 4 ( TERT promoter mutation in 17%, epidermal growth factor receptor amplification in 5.5%, and whole chromosome 7 gain and chromosome 10 loss in 2%). Molecular GBMs were predominantly frontal (54.5%) with a mean age of 36 years and median overall survival equivalent to IDH -wt GBMs (18 vs. 19 mo; P =0.235). Among grade 2/3 DAGs not harboring these alterations, significantly better survival was observed for grade 2 versus grade 3 DAGs (25 vs. 16 mo; P =0.002). Through the incorporation of a panel of molecular markers, a subset of IDH -wt grade 2 DAGs can be stratified into molecular grade 4 tumors with prognostic and therapeutic implications. However, IDH -wt grade 3 DAGs behave like GBMs irrespective of molecular profile.