Cervical kyphosis correction in Marfan syndrome: our experience and literature review.

BACKGROUND: Spinal deformities are common in Marfan syndrome (MFS). They usually involve the thoraco-lumbar spine but rarely involves the cervical spine. Kyphosis is the common spine deformity of the cervical spine and mandates surgical correction as they are at risk of neurological deterioration since they are refractory to conservative management. Few studies of surgical correction of spine deformity included cervical deformity. OBJECTIVES: To analyze the challenges faced during surgery, clinical and radiological outcome, and complications following surgical correction for cervical kyphosis in Marfan syndrome. METHODS: We identified that 5 patients with a diagnosis of MFS with cervical kyphosis who underwent fusion surgery between the years 2010 and 2022 were reviewed, retrospectively. We analyzed the demographic details, radiological parameters, operative variables (blood loss and nuances), perioperative complications, length of stay, clinical and radiological outcome, and complications following fusion surgery for cervical kyphosis in MFS. RESULTS: The mean age of patients was 16.6 ± 4.72 years (range, 12-23 years). The average kyphotic vertebra involved is 3 ± 0.7 bodies (range 2-4) with 2 patients with thoracic deformity. All patients underwent surgical deformity correction. All patients improved clinically with Nurick grade (pre vs. post: 3.4 vs. 2.2) and mJOA (pre vs. post: 8.2 vs. 12.6). There was significant deformity correction from 37.48° to 9.1°. Mean blood loss encountered was 900 ± 173.2 ml. Perioperative complications: wound complication with CSF leak (1). Late complications: ventilator dependence (1) and junctional kyphosis (1). Mean length of hospital stay was 103 ± 178.9 days. All patients were doing symptomatically better after mean follow-up of 58 ± 28.32 months. One patient is bedridden and hospitalized. CONCLUSION: Cervical kyphosis is a rare spine deformity in patients with MFS, and they usually present with neurological deterioration mandating surgical correction. Multidisciplinary approach (pediatrics, genetics and cardiology) is required for systematic evaluation of these patients. They should be evaluated with necessary imaging to rule out associated spinal deformity (atlanto-axial subluxation, scoliosis, and intraspinal pathology like ductal ectasia). Our results suggest better surgical outcome in terms of low operative complications with neurologic improvement in MFS patients. These patients require regular follow-up to identify late complications (instrument failure, non-union, and pseudarthrosis).

Epilepsy Smart Schools: Educational intervention improves knowledge, attitude, and practices regarding epilepsy among school teachers.

INTRODUCTION: Discrimination and stigma associated with epilepsy in schools impact the academic and mental aptitude of children with epilepsy. Teachers pre-sensitized to seizures exhibit a positive attitude along with better knowledge about epilepsy. The aim was to assess the impact of an interactive one-day educational workshop regarding epilepsy on the prevalent knowledge, attitude, and practices toward epilepsy among school teachers. METHODS: Conducted in December 2021 in a tertiary care teaching hospital of rural background in Northern India, this cross-sectional study included school teachers from government schools of Faridkot district of Punjab. The intervention consisted of a one-day interactive workshop on epilepsy and school health consisting of 100 minutes of lectures (4 lectures each of 25 minutes), 60 minutes of role plays, and 20 minutes of active discussion with participants (5 minutes after each session). The lectures were prepared using World Health Organization's Mental Health Gap (WHO's mhGAP) guidelines and elucidated knowledge regarding epilepsy and skills to provide first aid to seizures. School teachers were assessed on a pre and post-test structured questionnaire to assess their knowledge of, attitude, and practices regarding epilepsy before and immediately after the intervention. RESULTS: Two hundred and thirty teachers participated and the majority were from government primary schools, mean age was 43 ± 7 years and females (n = 121,53%) outnumbered males. Commonly reported sources of information regarding epilepsy by school teachers were family and friends (n = 91,40%) followed by social (n = 82, 36%) and public media (n = 81,35%), and the least common were doctors (n = 56,24%) and healthcare workers (n = 29, 13%). Fifty-six percent (n = 129) had witnessed seizures in either a stranger(n = 84,37%), family, or friend (n = 31,13%) and student of their class(n = 14,6%). Post-educational intervention, significant improvement was seen in the knowledge of and attitude regarding epilepsy including recognizing subtle features of epilepsy like blank stare (pre/post = 5/34) and transient change in behavior (pre/post = 16/32), non-contagiousness of epilepsy (pre/post = 158/187)and belief that children with epilepsy have normal intelligence (pre/post = 161/191) and a significant decrease in a number of teachers who thought that they need more time and attention in class (pre/post = 181/131). Post-educational sessions, significantly more number of teachers would allow children with epilepsy in their classroom (pre/post = 203/227), follow correct ways to provide first aid for seizures, and would allow their participation in all extracurricular activities even in high-risk outdoor games like swimming (pre/post = 4/36) and deep sea diving (pre/post = 7/18). CONCLUSION: The educational intervention had a positive impact on the knowledge, practices, and attitude regarding epilepsy but had a few, unexpected reverse effects as well. A single workshop may not be aptly adequate to provide accurate information regarding epilepsy. Sustained efforts in this direction are needed at the national and global level to develop the concept of "Epilepsy Smart Schools".

Complex congenital atlantoaxial dislocation in an infant: case report.

The authors report the case of congenital atlantoaxial dislocation in a 9-month-old female infant, who presented with progressive quadriparesis and respiratory failure. The problems in management due to such an early age of presentation, including atypical clinical presentation, unique radiological findings, limited management options, and variable clinical outcomes discussed. This is the youngest case of non-syndromic congenital atlantoaxial dislocation, reported to date, and is a unique combination of lateral, rotatory, and antero-posterior atlantoaxial dislocation.

Spontaneous Ventriculostomy into the Subdural Space in a Neonate with Congenital Hydrocephalus.

We report a case of spontaneous temporary resolution of congenital hydrocephalus due to drainage into the subdural space, which is not a physiological space for cerebrospinal fluid (CSF). This is the first report of spontaneous drainage of CSF into the subdural space, and we term it "ventriculosubdurostomy." We highlight the fact that spontaneous resolution of hydrocephalus due to drainage into a nonphysiological CSF space is temporary.

Cavernous malformations of central nervous system in pediatric patients: our single-centered experience in 50 patients and review of literature.

PURPOSE: Cavernous malformations (CMs) are rare developmental cerebrovascular malformations of the central nervous system with a childhood prevalence of 0.3 to 0.53%. Our purpose was to assess the clinical features and microsurgical outcome in pediatric central nervous system (CNS) CMs. MATERIAL AND METHODS: We retrospectively enrolled all the CM patients admitted to our institute from 1 January 2001 to 31 December 2014. Data was analyzed for their clinical features and surgical outcome. RESULTS: A total of 50 patients with CMs (30 supratentorial, 14 infratentorial, and 6 spinal) with a mean age of 14 years (3-18 years, SD ±4.64) were enrolled into the study. Most of these patients (78%) were male. Size varied from 1.2 to 6 cm. Three patients had multiple CMs. Symptoms of CMs were site specific. Seizure was the most common symptom (63.3%) of CMs at supratentorial location followed by headache (46%) and neurodeficiency (26%), while all brainstem and spinal CMs presented with neurodeficiencies. History of clinically significant acute hemorrhage was present in 19.2% of supratentorial (ST) superficial CMs, 50% of ST deep CMs, 25% of cerebellar CMs, 44.4% of brainstem CMs, and 50% of spinal CMs. Forty-five CMs in 44 patients were surgically excised. Their follow-up ranged from 6 to 162 months (mean 47.2 months, SD ±53). All supratentorial CM patients showed improvement in their symptoms. Patients with preoperative seizure showed good seizure control with Engel scale I in 16 (94.1%) and Engel scale II in 1 (5.9%). In infratentorial (IT) and spinal CM patients, 92.3 and 66.7% had improvement in their neurodeficiencies, respectively. There was no mortality in our series. CONCLUSION: Microsurgical excision of CNS CM results in excellent neurological outcome in pediatric patients. Early intervention is necessary in spinal CMs for better outcome.

Prediction of facial nerve position in large vestibular schwannomas using diffusion tensor imaging tractography and its intraoperative correlation.

OBJECTIVE: Resection of large Vestibular Schwannomas (VSs) can be associated with postoperative facial nerve injury. Diffusion-based tractography has emerged as a powerful tool for three-dimensional imaging and reconstruction of white matter fibers; however, tractography of the cranial nerves has not been well studied. In this prospective study, we aim to predict the position of facial nerve in large VSs (>3 cm) using Diffusion Tensor Imaging (DTI) tractography and correlate it with the intraoperative finding of the position of facial nerve. MATERIALS AND METHODS: Twenty patients with a large VS (>3 cm) undergoing surgery were subjected to preoperative DTI to predict the position of the facial nerve in relation to the tumor. The surgeon was blinded to the results of the preoperative DTI tractography. A comparative analysis was then made during operation. The location of the facial nerve in relation to the tumor was recorded during surgery using facial nerve stimulator. RESULTS: Of the 20 patients who underwent DTI tractography, it was not possible to preoperatively identify facial nerve in one patient. In another patient, although DTI tractography predicted the position of facial nerve, it was not identified intraoperatively. In the remaining 18 patients, DTI tractography accurately predicted the facial nerve position. The predicted position was in synchronization with the intraoperative facial nerve position in 16 patients (89% concordance). It was discordant in two patients (11%), but this was not found to be statistically significant (P = -0.3679). CONCLUSION: This study validates the reliability of facial nerve DTI-based fiber tracking for prediction of the facial nerve position in patients with large VSs. The reliable preoperative visualization of facial nerve location in relation to the VS will allow surgeons to plan tumor removal accordingly and may increase the safety of surgery.

Medial sphenoid wing meningiomas: Experience with microsurgical resection over 5 years and a review of literature.

BACKGROUND: Medial sphenoid wing meningiomas are medially located tumors on the sphenoid wing with attachment over the anterior clinoid process. They represent a distinct entity. These medial sphenoid wing meningiomas present a more difficult problem for the neurosurgeons because in a majority of cases, they involve the anterior visual pathways and arteries of the anterior circulation and may invade the cavernous sinus (CS). Higher morbidity, mortality and recurrence rates have been observed in these tumors compared with meningiomas in other locations. The rate of recurrence for medial sphenoid wing meningiomas is reported as being one of the highest amongst intracranial meningiomas. MATERIAL AND METHODS: The authors retrospectively analyzed 78 consecutive patients with the diagnosis of medial sphenoid wing meningioma who were operated in our department from January 2008 to December 2012. RESULTS: These patients, having a meningioma of the medial sphenoid ridge, were divided into two types depending on the involvement of CS. Diplopia, internal carotid artery encasement, and postoperative visual deterioration were more common in Type 2 tumors. Similarly, extent of resection and postoperative morbidity were greater in Type 2 patients. CONCLUSIONS: CS invasion confers an added risk to the surgical morbidity and outcomes. However, with proper surgical techniques, optimum outcomes can be achieved and overall surgical results at our center are found to be comparable to that of the current literature.

Bioefficacy and persistence of acephate in mungbean Vigna radiata (L.) Wilczek.

The bioefficacy, persistence and metabolism of foliar application of acephate 75 SP at the respective recommended and double doses of 1500 and 3000 g a.i. ha(-1) were studied on kharif mungbean crop. Acephate gave a very effective control of the pod borer, Helicoverpa armigera (Hubner) at the tested doses on mungbean crop throughout the cropping season, besides recording lower percent pod damage and higher grain yield. The recommended dose of acephate also recorded higher net returns and thus indicating its superiority. Persistence of acephate in mungbean leaves and soil was studied following applications of acephate @ 1500 and 3000 g a.i. ha(-1) at 30 days after sowing. Residues of acephate in mungbean leaves and soil were estimated using gas liquid chromatograph (GLC) and confirmed on gas chromatograph-mass spectrometry (GC-MS). Half-life periods for acephate in mungbean leaves were observed to be 2.98 and 3.27 days at single and double the application rates, respectively. Residues of acephate dissipated below its limit of quantification (LOQ) of 0.05 mg kg(-1) after 20 and 25 days at single and double the application dosage, respectively. Similarly, half-life periods for acephate in mungbean soil were observed to be 1.86 and 1.94 days at single and double the application rates, respectively. Residues of acephate dissipated below its LOQ of 0.05 mg kg(-1) after 10 and 15 days at single and double the application dosage, respectively.

Analytical method for determination of fipronil and its metabolites in vegetables using the QuEChERS method and gas chromatography/mass spectrometry.

An easy, simple, and efficient analytical method was validated for the determination of residues of fipronil and its metabolites in different vegetables comprising brinjal, cabbage, capsicum, cauliflower, okra, and tomato. The Quick, Easy, Cheap, Rugged and Safe method was used for the extraction and cleanup of fipronil and its metabolites on these vegetables. Final clear extracts of ethyl acetate were concentrated under vacuum and reconstituted into acetone, and residues were determined by GC/MS with an Rtx-5 capillary column. The retention times of desulfinyl, sulfide, fipronil, sulfone, and amide were 11.8, 15.8, 16.4, 19.7, and 24.1 min, respectively. The average recoveries obtained for fipronil and its metabolites at different spiking levels were determined to be above 85% in all samples. The repeatability and reproducibility in different matrixes ranged from 1.36 to 5.42 and 1.75 to 4.53%, respectively, for fipronil and its metabolites. The LOQ of this method was 0.01 mg/kg and LOD was 0.003 mg/kg.

Quadrigeminal cistern arachnoid cyst: A series of 18 patients and a review of literature.

BACKGROUND: Arachnoid cysts account for 1% of intracranial mass lesions. Quadrigeminal cistern arachnoid cysts are even rarer lesions. We report 18 cases of quadrigeminal cistern arachnoid cysts treated at our institute from 2002 to 2012. METHODS: We retrospectively analysed 18 patients with quadrigeminal cistern arachnoid cyst for clinical presentation, demographic profile, management and outcome. The age of the patients ranged from 29 days to 50 years (mean 17 years). The cysts were classified into 3 subtypes based on MRI findings. Surgical intervention was carried out in all the patients. RESULTS: Two patients had Type 1 cysts, 4 had Type 2 cysts and 12 had Type 3 cysts. Two patients (Type 1) underwent endoscopic third ventriculostomy (alone). Craniotomy and cyst wall excision along with ventriculocystostomy and cystocisternostomy were done in 4 patients with Type 2 cysts, and endoscopic fenestration of cysts to the sub-arachnoid space or the ventricles and endoscopic third ventriculostomy were done in 7 patients with Type 3 cysts. Two patients with Type 3 cysts underwent only endoscopic ventriculocystostomy and cystocisternostomy without endoscopic third ventriculostomy, while three patients underwent ventriculoperitoneal shunt. The follow- up period ranged from 6 months to 48 months (mean 23.7 ± 12.3 months). CONCLUSION: Quadrigeminal plate arachnoid cysts are generally symptomatic and require some form of surgical intervention. We believe that endoscopic fenestration of the cyst with cystocisternostomy or cystoventriculostomy, when combined with third ventriculostomy, is the procedure of choice for such patients. We do not recommend the placement of a ventriculoperitnoeal shunt alone. Operative re-exploration should be planned only after obtaining proper clinico-radiological correlation and not on the basis of imaging findings alone, as sometimes the cysts fail to regress but the symptoms improve.

Pediatric intracranial aneurysms--our experience and review of literature.

PURPOSE: Intracranial aneurysms in children are not as common as in adults and there are many differences in the etiology, demographic variables, aneurysm location, aneurysm morphological characteristics, clinical presentation, and outcome in pediatric and adult intracranial aneurysms. METHODS: All children (≤18 years) suffering from intracranial aneurysm managed at our center from July 2001 through June 2013 were included in the study, and the details of these patients were retrieved from the computerized database of our hospital. OBSERVATIONS: A total of 62 pediatric patients were treated for 74 aneurysms during the study period and constituted 2.3% of all intracranial aneurysms treated during the same period. The mean age at presentation was 13.5 years. Headache (82%) was the commonest presenting feature; other symptoms included seizures (21%), ictal loss of consciousness (27%), and motor/cranial nerve deficits (22.6%). Computed tomogram revealed subarachnoid hemorrhage in 58% of patients. Eighty-two percent of aneurysms were in anterior circulation. Sixty-seven percent of aneurysms were complex aneurysms. Fifty-eight percent of patients underwent surgical intervention while 30% underwent endovascular procedures. Twenty-one percent of the patients developed vasospasm. There was no postoperative mortality. Favorable outcome was seen in 72% of the patients. CONCLUSIONS: Pediatric intracranial aneurysms are uncommon as compared to in adult patients. Seizures and cranial nerve involvement are seen more often as the presenting features in children. Posterior circulation aneurysms are more common in children, as are the internal carotid artery bifurcation aneurysms. There is high incidence of giant, posttraumatic, and mycotic aneurysms in children.

Predictors of outcome in the non-operative management of thoracolumbar and lumbar burst fractures.

AIM: Burst fractures without neurological deficit are often treated successfully without surgery. A subgroup may fail non-operative treatment owing to pain, and opt for surgery. The following review was conducted to identify predictors of success or failure in the non-operative treatment of thoracolumbar burst fractures. METHODS: A cohort of 60 patients with T11-L4 thoracolumbar burst fractures were treated non-operatively, with bed rest and bracing until the pain abated sufficiently to allow mobilization. Patients were followed prospectively for a mean ± SD of 12 ± 14 months, and their data were reviewed retrospectively. RESULTS: Fifty-one patients successfully completed non-operative treatment. Owing to intractable pain in nine, surgery was undertaken. Ages in the non-operative and operative groups were 46 ± 18 and 68 ± 15 years respectively (p = 0.002). The residual canal and angulation at the site of the fracture were 63 ± 12% and 1.6 ± 8.4° in the non-operative group and 47 ± 15% and 6.6 ± 13.6° in the surgical group (p = 0.001 and 0.149 between groups, respectively). Regression analysis of age, gender, angulation, and residual canal showed that only age (OR, 1.099; 95% CI, 1.022-1.183; p = 0.011) and residual canal (OR, 0.795; 95% CI, 0.642-0.985; p = 0.035) were significant predictors of failure, ultimately undergoing surgery. CONCLUSION: Non-surgical treatment was more likely to prove sufficient in patients aged 46 ± 18 years, and residual canal of 63 ± 12%, than in older patients with ages of 68 ± 15, and canal of 47 ± 15%. The latter group was more likely to fail, undergoing surgery because of pain or instability.

Management of adult tethered cord syndrome: our experience and review of literature.

BACKGROUND: Tethered cord syndrome (TCS) is a complex clinicopathologic entity, mostly described in children with limited number of studies describing in adults. This unique and rare subgroup of patients presents with characteristic features of TCS, but unlike children, pain is a predominant clinical symptom. MATERIALS AND METHODS: Case records of 24 patients aged ≥16 years who had undergone surgery with a diagnosis of TCS between 2001 and 2011 were reviewed. Patients who have underwent surgery earlier for tethered cord or for diastematomyelia/spinal dysraphism and patients who had radiological evidence of tethering elements like lipoma of the cord on magnetic resonance imaging (MRI) were excluded from the study. RESULTS: Low backache was the most common presenting symptom. At the time of final follow-up, 15 (83.3%) patients had shown improvement in backache. Weakness improved by at least one grade in seven (77.8%) patients. Bladder symptoms improved in six (50%) patients. CONCLUSION: In case of symptomatic patient with low-lying cord, detethering is an advisable option.

Persistence of chlorantraniliprole granule formulation in sugarcane field soil.

Chlorantraniliprole, an anthranilic diamide insecticide with novel mode of action, is found effective against several lepidopteran as well as coleopteran, dipteran, and hemipteran pests. The present studies were carried out to study the persistence pattern of chlorantraniliprole on sugarcane field soil following application of granule formulation. The residues of chlorantraniliprole were estimated using high performance liquid chromatograph (HPLC) and confirmed by liquid chromatograph-mass spectrometry (LC-MS/MS). Following application of chlorantraniliprole (Ferterra 0.4G) at 100 and 200 g a.i. ha(-1), the average initial deposits of chlorantraniliprole were observed to be 0.88 and 1.59 mg kg(-1), respectively. These residues dissipated below the limit of quantification (LOQ) of 0.01 mg kg(-1) after 56 days of the application of insecticides at both the dosages. The half-life values (t 1/2) of chlorantraniliprole were worked out to be 8.36 and 8.25 days, at recommended and double the recommended dosages, respectively.

Renal Mucormycosis with Disseminated Lytic Bony Lesions.

Renal Mucormycosis is a lethal opportunistic infection with extensive tissue invasion leading to infarction. We report a diabetic lady with disseminated fungal pyelonephritis presenting with extensive lytic bony lesions mimicking malignancy. Prompt initiation of antifungal therapy and surgical debridement is the key to successful management. A clinician should have a high index of suspicion for Mucormycosis in a patient with non-resolving pyelonephritis and prolonged fever.

Incidence of Rebleed Following Cerebrospinal Fluid (CSF) Drainage in Poor Grade Subarachnoid Hemorrhage: An Institutional Experience.

BACKGROUND: The outcome of poor grade subarachnoid hemorrhage (SAH) is dismal. Some of these patients need cerebrospinal fluid (CSF) drainage procedure for the hydrocephalus and intraventricular hemorrhage (IVH) which may precipitate rebleeding. However, aneurysmal rebleed following CSF drainage procedure is controversial. OBJECTIVE: Our study aimed at analyzing the effect of CSF drainage procedure on aneurysmal rebleeding. MATERIAL AND METHODS: We retrospectively analyzed the records of all the consecutive patients diagnosed with poor grade aneurysmal SAH over three year period. Patients initially requiring either external ventricular drainage (EVD) or lumbar drain (LD) were included in the study group, and the rest (not requiring drainage) were included in the control group. Rebleeding was confirmed on computed tomography. The factors affecting rebleeding were analyzed. RESULTS: Overall 194 patients with poor grade SAH were enrolled in the study (91 males: 103 females; mean age: 50.6 years). The study group had 91 patients (83 EVD and 8 LD) while 103 patients were in the control group. Posterior circulation aneurysms, poor grade SAH, hydrocephalus, and IVH were more common in the study group P < 0.001. The rebleeding rate was 7.6% in the study group and 8.7% in the control group. On univariate analysis size >1 cm, multiplicity, multilobularity, vasospasm, and CSF drainage were significant risk factors for rebleeding (P < 0.001). On multivariate analysis aneurysm size >1 cm, CSF overdrainage >250 ml/day were significantly associated with risk of rebleeding. CONCLUSION: Ventricular drainage is essential to relieve acute hydrocephalus and drain IVH in SAH and we found no significant association between CSF drainage and rebleeding. However, rapid overdrainage of CSF can lead to aneurysm rupture, hence controlled controlled CSF drainage should be undertaken.

Correction of pediatric cervical kyphosis: our experience and systematic-literature review.

BACKGROUND: Pediatric cervical kyphosis is a distinct entity with diverse etiology (congenital, syndromic, traumatic, metabolic or neoplastic). Surgical correction in pediatric population is challenging due to their growing spine and low blood volume. PURPOSE: To analyse their presentation, surgical techniques and outcome of pediatric cervical kyphosis and systematically review the pertinent literature. DESIGN: Retrospective study. PATIENT SAMPLE: 16 patients aged ≤ 18 years who underwent correction for cervical kyphosis between 2009 and 2021. OUTCOME MEASURES: Nurick's grading, mJOA score and Global cobb's angle. METHODS: Clinical parameters (Nurick grading and mJOA score) were noted from database on admission and on follow-up at 6 months. Radiological parameters of assessment included Global Cobb's angle. The C2-C7 Cobb angle was the angle of C2 vertebra lower end plate and C7 vertebra lower end plate. For C1-2 kyphosis, anterior border of C1 and anterior border of C2 angle was taken. Radiographic parameters were studied on CT and radiographs of cervical spine to assess for stability, the degree of deformity correction and fusion status at 6 months follow-up. RESULTS: 16 patients with mean age of 14.2 ± 3 years (9 syndromic, 4 post-traumatic, 2 metabolic and 1 post-laminectomy). All underwent surgical correction, 6 underwent Antero-posterior spinal fusion, 6 underwent Posterior spinal fusion and 4 underwent Anterior spinal fusion. There was significant clinical improvement postoperatively with-Nurick grade (pre vs. post: 2.8 vs. 1.8, p = 0.004), mJOA score (pre vs. post: 11.3 vs. 14, p = 0.003). There was significant deformity correction of Cobb's angle from 40.7 ± 26.5° to 14.9 ± 10° (p = 0.001). Early complications included intraoperative hemodynamic instability (3) and wound complication (1). Mean follow-up was 76.9 ± 59.3 months. CONCLUSION: Pediatric cervical kyphosis is a debilitating condition which are managed surgically. Approach has to be individualized to the pathology and good results can be achieved. Patients should be screened for syndromic association and followed-up regularly.

Serum Vascular Endothelial Growth Factor and Endostatin as an Adjunct to Clinical Decision Making in Managing Radiation-induced Changes Post Gamma Knife Radiosurgery in Spetzler Martin Grade 3 Arteriovenous Malformations Patients: A Pilot Study.

BACKGROUND: Radiation induced changes (RIC) are the most common complications observed post Gamma Knife radiosurgery (GKRS) and may be observed within 6-18 months post procedure. It has been observed that almost one-third of RICs are symptomatic and half of them are persistent. There is no way to predict which patients will develop these changes and to what extent. METHODS: This was a prospective analytical pilot study with the aim of understanding the role of serum vascular endothelial growth factor (VEGF) and endostatin as predictive factors for clinically symptomatic RIC in intracranial arteriovenous malformations (AVMs) of Spetzler Martin (SM) grade 3 being managed with primary GKRS. RESULTS: A total of 15 patients were analyzed; 60% of them had a history of bleed. The median volume of AVM nidus was 4.36 mL. One-third of the patients had no imaging changes suggestive of RIC at 1 year follow-up and 2 of the patients had symptomatic RIC needing intervention. Before GKRS, the median values of serum concentration of endostatin and VEGF were 34.98 ng/mL and 168.37 pg/mL, respectively. The serum values of VEGF at 1 month post GKRS was much lower than the pre-GKRS values but not found to be predictive of RIC. No correlation could be observed with the levels of serum endostatin and RIC. CONCLUSIONS: Some patients may develop resistant edema and necrosis post GKRS for intracranial AVMs, which may warrant medical and surgical intervention. Serum biomarkers like VEGF and endostatin may vary in the post GKRS period and can be used to identify at-risk cases, however more studies are needed to decide on appropriate time of sampling and identify clinically relevant predictive factors.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Oleuropein activates autophagy to circumvent anti-plasmodial defense.

Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis." Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.