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Background: Deep brain stimulation (DBS) is a promising neuromodulation therapy for patients with medically refractory epilepsy not suitable for surgical resection. The Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial has demonstrated a reduction in seizures which is sustained in the long-term [1, 2]. Methods: Eight patients (7 female, 1 male; age range 21-41 years) underwent bilateral DBS insertion from July 2012 until January 2014. Target selection was the anterior nucleus of the thalamus in 6 patients and centromedian nucleus of the thalamus in 2 patients. Preoperative evaluation consisted of electroencephalogram (EEG), video EEG, magnetic resonance imaging (MRI), neuropsychological evaluation, Liverpool seizure severity scale and Quality of Life in Epilepsy (QOLIE). Mean follow up period was 36 months. Results: Seven patients had complex partial seizures with secondary generalization and one patient had juvenile myoclonic epilepsy Two patients had previous vagal nerve stimulator (VNS) insertion, 1 patient had a left temporal lobectomy and one further patient had previous limited left temporal lobe resection for dysembyonic neuroepithelial tumour (DNET) and VNS insertion. At follow up, 3 patients (37.5%) had more than 50% reduction in seizure frequency, 2 patients (25%) had around 50% reduction in seizure frequency, in 2 patients (25%) seizure frequency was unchanged and one patients' seizure pattern changed to drop attacks only. One patient had the DBS system removed at 27 months due to lack of efficacy. Postoperative neuropsychological outcomes were performed in 5 patients and this demonstrates improvement in mood and QOLIE in 3 patients (37.5%) and no significant change from baseline in 2 patients (25%). There were no postoperative complications or adverse device effects in the follow up period. Conclusion: This small series replicates the results of SANTE trial providing further data in support of DBS stimulation being an efficacious and safe treatment for patients with medically refractory partial and secondarily generalized epilepsy. [ABSTRACT FROM AUTHOR]

The article offers information on the International Society for Cellular Therapy's (ISCT) Annual Meeting to be held in Las Vegas, Nevada as of May 2015 featuring topics including cellular immunotherapy, tissue engineering and role of nonprofit organizations in advancing cellular therapies.

The poor grade subarachnoid haemorrhage patients represent a unique cohort with lack of clear treatment protocol. Most neurosurgical units in the UK will manage them at local hospital until they make a significant recovery, this period can put them at higher risk of rebleed while with aggressive treatment a significant subset can achieve a favourable outcome. Identification of this subset is difficult and decision to treat them is associated with significant commitment of neurosurgical and ITU resources. Recent paper by Szklener has come up with a scale for prognostication in this subgroup of patients. We wanted to check the validity of this scale in our patient population and see if this scale can be used to guide early patient transfer and aggressive management at the Neurosurgical unit. We retrospectively reviewed our referral database for all poor grade subarachnoid patients referred over 2 years. Demographic information, Fisher and WFNS scores, admitting leucocyte count and outcome information as per MRS were obtained. These were scored as per the scale suggested by Szklener. A total of 115 poor grade subarachnoid patients were referred over the study time frame. 47 of them were accepted for admission. 18/47 patients achieved a favourable outcome (GOS4-5). Only 1 patient managed in peripheral hospital had a good outcome. There was a significant association between Szklener's score and achieving a favourable outcome p = 0.002. A selective admission policy could work specially with current economic climate, achieving outcomes comparable to admit-all. However, to optimise outcomes for all patients an aggressive standardised management at peripheral hospitals and a uniform admission policy assisted by Szklener score may be adopted. Szklener's model predicts the outcome better than WFNS and age but more validation is needed. [ABSTRACT FROM AUTHOR]

Objectives: Deep brain stimulation (DBS) is a recommended option for the treatment of movement disorders in well-selected patients. Both rechargeable and non-rechargeable devices are available; one of the advantages of a rechargeable DBS device may lie in the avoidance of costs for battery replacements and associated risks and hospitalisations. The objective of this study was to evaluate the economic impact of using a rechargeable DBS device over a non-rechargeable device in patients treated for either Parkinson's Disease (PD) or Dystonia. Methods: An economic model (Markov Model) was built to follow a group of dystonia and PD DBS patients over time comparing two scenarios, one assuming a rechargeable and one assuming a non-rechargeable device, for first implant and replacements. The model captures patients' replacement surgeries, hospitalisations, adverse events and deaths. Data for the model were sourced from the Medtronic product surveillance registry (PSR; patient characteristics, adverse events and consequences associated with implant and replacement surgeries) and non-rechargeable device longevity data from Medtronic performance registry based modelling analyses. For the rechargeable device longevity, current longevity (9 years) and a hypothetical longevity scenario (15 years) were tested. Clinical expert advice was used to inform model assumptions. Costs were estimated from a UK health care perspective. Sensitivity analyses were undertaken to test for parameter uncertainty, including time horizon. Results: Results of the base case analysis (16 year time horizon) show:For PD,an average of 3.68 battery replacements in the non-rechargeable vs 0.62 in the rechargeable group; for Dystonia, 5.08 and 0.74 replacements in the non-rechargeable vs the rechargeable group(15-year hypothetical device longevity). Over 16 years,the model suggests cost savings of £15,564 (PD) and £27,954 (Dystonia) using the 9 year device longevity, and £20,418 and £32,060, respectively, for a 15-year hypothetical device longevity. Sensitivity analyses showed that over a patient's life time, cost savings were £28,450(PD) and £65,413(dystonia)(15- year hypothetical device longevity). Conclusion: The use of a rechargeable DBS device in this model is cost saving in the long-term compared to a nonrechargeable device. Prolonging rechargeable device life to 15 years is predicted to reduce DBS treatment costs and would thus improve DBS therapy cost-effectiveness, for both PD and dystonia. This analysis was funded by Medtronic. Simon Eggington, Katherine Stromberg, Silke Walleser Autiero and Todd Weaver are employees of Medtronic. Professor Paul Eldridge received compensation for his work providing clinical advice and review on this project. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness and safety of the use of DBS to reduce motor complications of PD patients has been substantiated by several randomized controlled trials (Schuepbach et al., 2013). Motor improvement following DBS is sustained for up to 10 years as reported by Deuschl et al. 2013. An in-depth evaluation of real world outcomes following DBS will add to the existing database of knowledge and be a useful tool for physicians. As part of an on-going, large scale registry study, we investigated the effectiveness and safety-related real-world outcomes of a multiple independent current source control (MICC) Deep Brain Stimulation (DBS) System for use in the management of motor symptoms of levodopa-responsive Parkinson's disease (PD). Methods: This is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. Patients were implanted with a CE-marked, MICC-based DBS system (Vercise, Boston Scientific). Subjects will be followed up at 6 and 12 months and up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms will be evaluated. Clinical endpoints will be evaluated at baseline and during study follow up that include Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. Adverse events are also collected. Results: Preliminary data suggests an overall improvement in Quality of life at 6 months post implant as compared with Baseline as measured by a 17.6% (n = 89) improvement in PDQ-39 Summary Index. Over 90% of patients, caregivers and clinicians reported improvement as compared with Baseline. This report will provide the safety and effectiveness outcomes of the first cohort of subjects analyzed at 6 (N=150) and 12 months (N=100) post-implantation as compared with baseline. Conclusion: Deep Brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment option for patients with advanced Parkinson's disease (PD). A device that enables fractionalization of current using a multiple source mode of delivery (MICC) can permit the application of a well-defined, shaped electrical field. This registry represents the first comprehensive, large scale collection of real-world outcomes and includes evaluation of the safety and effectiveness of the Vercise DBS System up to 12 months post lead placement. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the epileptogenic zone in patients with medically refractory epilepsy referred to the epilepsy surgery programme with invasive intracranial monitoring and report our experience and subsequent surgical outcomes. Design: Retrospective Review. ubjects: 72 consecutive patients (29 male, 43 female; age range 14-60 years) who underwent invasive monitoring procedures (depth electrodes, subdural grids and strips) from March 2008 to March 2015. Methods: Patients were identified from a prospective database. Epileptogenic zone identification, seizure semiology, subsequent surgery performed, complications and postoperative Engel scores were analysed. Results: Over 116 months, 72 patients underwent 74 invasive monitoring procedures. Epilepsy syndromes included 51 patients with temporal lobe epilepsy, 20 patients with frontal lobe epilepsy and 3 patients with parietal lobe epilepsy. The epileptogenic zone was identified in 54 (73%) recordings (39 temporal onset, 12 frontal onset and 3 parietal onset). 14 patients had bilateral seizure onset, 4 had multifocal onset and 2 patients had no seizures recorded. Complications were two intracranial haematomas (2.7%), one retained metal lead contact (1.4%) and one localised temporal lobe oedema (1.4%). 51 patients (71%) were then deemed to be suitable for surgical resections. Of these, 36 patients underwent surgery (24 temporal, 10 frontal and 2 parietal resections), 7 are awating surgery, 5 declined and 3 were not suitable due to medical co-morbidites. Awake resections were performed in 6 left temporal and 3 left frontal resections. The most common surgical pathology was cortical dysplasia (52%). Median postoperative period was 35 months. Postoperative Engel scores of class 1 and 2 were 33% in the temporal resection group and 60% in the frontal resection group (overall 40%). Complications included 3 patients with mood changes (12%) and 1 patient each (4%) with thromboembolism, contralateral haemorrhage, transient nominal dysphasis and Stven Johnson syndrome from a subdural empyema. Conclusion: Invasive monitoring performed as part of epilepsy surgery workup is safe and effective in localising the epileptogenic zone in patients with medically refractory epilepsy. In carefully selected patients, subsuquent surgical resections can result in satisfactory postoperative seizure control. [ABSTRACT FROM AUTHOR]

Background: Dorsal root entry zone lesioning (DREZ) lesioning as a treatment of intractable neuropathic pain after brachial pleexus avulsion injury has proven to have long lasting pain relief (1). However, the safety and success of this method depends on accurate localisation of the DREZ. Difficulties in accurately localising the DREZ due to the lack of normal anatomy motivated the development of a neurophysiological techinique to identify the DREZ. Methods: A multimodal approach was developed over a consecutive series of 22 patients. The method comprised spinal cord somatosensory evoked potentials with peripheral nerve stimulation and spinal cord motor evoked potentials. In addition, the integrity of the ascending and descending pathways was monitord during thermocoagulation radiofrequency lesioning with transcranial motor evoked potentials and somatosensory evoked potentials. Results: The corticospinal tract and dorsal columns were located reliably using these methods thereby allowing identification of the lesion site lying between these two functional columns. Postoperatively, 90% of patients reported complete pain relief. 10% (2 patients) had partial pain relied and both were at the start of the series whilst the technique was being developed. One has been reoperated and is now pain free. The median follow up period after surgery was 18 months. There were no long term complications but there were transient lower limb clumsiness and numbness reflecting mild dorsal column loss. Conclusion: A multimodal neurophysiological approach improves the accuracy of localising the DREZ for thermocoagulation lesioning in the treatment of neuropathic deafferentiation pain after brachial plexus avulsion injuries. The results were excellent and long lasting with minor side effects. This continous monitoring provides the additional safety needed to create adequate leaiosn reflected by these good results. [ABSTRACT FROM AUTHOR]

Introduction: The effectiveness and safety of the use of Deep Brain Stimulation (DBS) to reduce motor complications of subjects with Parkinson's disease (PD) has been substantiated by several randomized controlled trials (Deuschl et al., 2006, Weaver et al., 2009, Okun et al., 2012, Scheupbach et al., 2013). Motor improvement following DBS is sustained for up to 10 years as reported by Castrioto et al. An in-depth evaluation of real-world outcomes following DBS will add to the existing database of knowledge and prove to be a useful tool for physicians. We present the outcomes of a large scale clinical registry that compiles the effectiveness and safety-related real-world outcomes of a multiplesource, constant-current DBS System in the treatment of levodoparesponsive PD. Methods: The Vercise DBS Registry is a prospective, onlabel, multi-center, international registry sponsored by Boston Scientific Corporation. The Vercise DBS system (Boston Scientific) is a CE-marked, multiple-source, constant-current system with a rechargeable battery. Subjects will be followed up at 3, 6.12 months and up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms will be evaluated. Clinical endpoints will be evaluated at baseline and during study follow up that include Unified Parkinson's Disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. The registry also utilizes the newly developed MDS UPDRS for the evaluation of motor symptoms and includes the evaluation of non-motor symptoms of PD (Non-Motor Symptom Assessment Scale) following DBS. Adverse events are also collected. Results: This report will provide the safety and effectiveness outcomes of the first cohort of subjects implanted with the Vercise DBS System analyzed at 6 months post-implantation as compared with baseline. Discussion: The Vercise DBS registry study represents the first comprehensive, large scale collection of real-world outcomes and evaluation of the safety and effectiveness of the Vercise DBS System. This report will provide such data from the first cohort of subjects analyzed at 6 months post-implantation as compared with baseline. [ABSTRACT FROM AUTHOR]

The article offers information related to the "British Journal of Neurosurgery" and informs that clinical pain management course for pain professionals and trainees will be held during July 4-6, 2013, in Liverpool, England.

Objective An international panel of pain specialists (anesthesiology, neurology, neurosurgery, and psychology) and research methodologists developed a screening tool to identify patients who may be suitable for spinal cord stimulation ( SCS)-the Refractory Chronic Pain Screening Tool ( RCPST) prototype. We describe a feasibility study to explore practicality and validity of this prototype. Design Consecutive outpatients were screened in two centers ( United Kingdom and United States). Sixty chronic pain adults without satisfactory pain relief despite treatment were assessed using RCPST (by pain specialist without expertise in neurostimulation) and then evaluated by two pain specialists experienced in SCS implantation and management to determine whether the patient should be referred for SCS. To maintain blinding, the participating physicians did not inform each other or the patient of assessment outcome. Sensitivity and specificity of the RCPST prototype were calculated using implanters' judgment as 'gold standard.' Results The average age of patients was 47.7 years; 53% were female. Fifty-seven patients completed the study (one withdrew consent, two lost to follow-up). The pain specialists agreed the prototype was easy to use and took <10 minutes to complete. Implanter agreement was moderate ( Kappa: 0.63, 95% confidence interval: 0.35-0.91). The prototype had low sensitivity (40%, 19-61%) and moderate specificity (78%, 65-92%). Using the same questionnaire with a modified decision algorithm, new prototypes were generated with range of high sensitivity (80-100%) and specificity (89-97%) values. Conclusions The RCPST aims to identify patients that should be referred for consideration for neurostimulation. The final implant decision requires appropriate neurological diagnostic workup, psychological assessment, and trial stimulation. RCPST was considered practical for routine clinical practice and contained appropriate questions. Sensitivity needs to be improved. A future study should select and validate the ideal RCPST prototype. [ABSTRACT FROM AUTHOR]

Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. In this study, we report the development of a novel strategy to specifically activate and expand human CD56+ (NCAM1) natural killer (NK) immune cells from normal donors and patients with neuroblastoma. Enriched CD56+ cells from peripheral blood were mixed with CD56- fraction at 1:1 ratio and cultured in the presence of OKT3, interleukin (IL)-2, and -15 for five days and then without OKT3 for 16 more days. The final products contained more than 90% CD56+ cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B. Successful clinical scale-up in a good manufacturing practices (GMP)-compliant bioreactor yielded effector cells that in a neuroblastoma xenograft model slowed tumor growth and extended survival without GVHD. Investigation of CD56+ cells from patients with neuroblastoma revealed a similar postactivation phenotype and lytic activity. Our findings establish a novel and clinically expedient strategy to generate allogeneic or autologous CD56+ cells that are highly cytotoxic against neuroblastoma with minimal risk of GVHD. [ABSTRACT FROM AUTHOR]

Abstract: CD34+-selection of hematopoietic grafts for patients undergoing autologous hematopoietic stem cell transplantation (HSCT) is frequently used to obtain a tumor-free graft. The majority of published experience is with peripheral blood stem cell (PBSC) products; only scant information has been published on bone marrow (BM) grafts. We reviewed our experience using CD34+ selection of BM grafts in children undergoing autologous BM transplantation. After obtaining institutional approval, we performed a retrospective review of the medical records of patients who underwent autologous stem cell collection at St. Jude. From January 1, 1999, to December 31, 2003, 373 patients underwent autologous HSCT; 131 received marrow grafts, 237 received PBSC grafts, and 5 received a combination. Seventeen patients underwent BM harvests for CD34+ selection of their stem cell grafts. Sixteen patients received 19 CD34 purified grafts processed on the Isolex 300i Magnetic Cell Selection System® device. Four patients were not included in the engraftment analysis as 1 did not receive the collected product, 1 received a tandem product, and 2 received products that were composed of 2 or 3 combined purified products. Following selection, marrow grafts contained a median of 1.4 × 106 CD34+ cells/kg (range: 0.09-8.3 × 106/kg) and a median of 0.014 ×108 total nucleated cell cells/kg (range: 0.001-0.09 × 108/kg). The median CD34% recovery was 30.9% (range: 9.3%-57.1%), with the median CD34 purity being 95.5% (range: 62.2%-98.8%). All patients engrafted. The median time to absolute neutrophil count ≥500/mm3 was 19 days (range: 12-35 days), and to platelet recovery was 28 days (range 18-37 days). No patient died from transplant-related complications. Our study demonstrates that CD34+-selection of marrow grafts is feasible, and these grafts are able to successfully reconstitute hematopoiesis in patients undergoing autologous BMT. [Copyright &y& Elsevier]

Abstract: CD4+ CD25+ regulatory T cells have been the subject of intense investigation and have been shown to modulate immune responses in the settings of autoimmunity, cancer and transplantation. The assessment and optimization of purification schemes for specific cellular subtypes such as CD4+ CD25+ regulatory T cells is a critical consideration in developing cell-based therapies in the clinical setting. In the following studies, different strategies for magnetic isolation are compared and the parameters which affect the overall potency of purified human CD4+ CD25+ regulatory T cells are discussed. The data demonstrate that large-scale magnetic isolation can be used to efficiently and reproducibly purify human CD4+ CD25+ regulatory T cells capable of modulating alloreactive T cell responses. The ability to rapidly purify the desired cells from peripheral blood suggests that magnetic isolation may be a suitable alternative to cell sorting for clinical settings, where large numbers of CD4+ CD25+ regulatory T cells may be necessary. [Copyright &y& Elsevier]

Background aims. Methods for processing products used for hematopoietic progenitor cell (HPC) transplantation must ensure their safety and efficacy. Personnel training and ongoing competency assessment is critical to this goal. Here we present results from a global survey of methods used by a diverse array of cell processing facilities for the initial training and ongoing competency assessment of key personnel. Methods. The Alliance for Harmonisation of Cellular Therapy Accreditation (AHCTA) created a survey to identify facility type, location, activity, personnel, and methods used for training and competency. A survey link was disseminated through organizations represented in AHCTA to processing facilities worldwide. Responses were tabulated and analyzed as a percentage of total responses and as a percentage of response by region group. Results. Most facilities were based at academic medical centers or hospitals. Facilities with a broad range of activity, product sources and processing procedures were represented. Facilities reported using a combination of training and competency methods. However, some methods predominated. Cellular sources for training differed for training versus competency and also differed based on frequency of procedures performed. Most facilities had responsibilities for procedures in addition to processing for which training and competency methods differed. Although regional variation was observed, training and competency requirements were generally consistent. Conclusions. Survey data showed the use of a variety of training and competency methods but some methods predominated, suggesting their utility. These results could help new and established facilities in making decisions for their own training and competency programs. [ABSTRACT FROM AUTHOR]

Background: The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles. This study evaluated whether the extent of surgery and receiving adjuvant radiotherapy after an initial operation along with other patient characteristics influenced the recurrence and survival rates of atypical meningiomas. Methods: The clinical and surgical notes of the 79 patients with grade II atypical meningioma treated at our center over 13 years were retrospectively evaluated. The histology grading was consistent with WHO 2007 classification. The Simpson grading system was used to assess the extent of surgical resection. Kaplan Meier analysis, Cox multivariate regression analysis, and the Log-rank test were conducted using STATA® statistical package. Results: The average age at the time of initial operation was 58 years, and 54 % were males. The mean follow-up period was 50 months. In Cox multivariate analysis, only Simpson grading was predictive of recurrence (hazard ratio = 2.22 / 1 increase in Simpson grade. p = 0.003). Simpson grade I patients had a relapse-free survival rate of 97 and 74 % at one and five years, respectively, compared with 88 and 32 % in the subtotal resection group (Simpson grades II to IV). There was no statistically significant correlation between recurrence and subjecting patients to postoperative radiotherapy. Apart from Simpson grade I patients, there was a general trend for worse outcome in irradiated patients. Conclusions: The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Meta-analysis for the existing literature is needed. [ABSTRACT FROM AUTHOR]

Background: Tremor is an important cause of disability and poor quality of life amongst multiple sclerosis (MS) patients. We assessed the outcomes of ventral intermediate (VIM) nucleus deep brain stimulation for the treatment of multiple sclerosis (MS)–associated tremor at a single centre in a prospective fashion. Methods: Sixteen patients (9 female, 7 male) with a mean age of 41.7 years (range 24–59) underwent surgery. The median duration of MS prior to surgery was 6.5 years and median duration of tremor prior to surgery was 4 years. Case selection was by multidisciplinary assessment with carers, therapists, neurosurgeons and movement disorder neurologists. Tremor was scored pre-operatively and at 6 to 12 months post operatively using Bain and/or Fahn–Tolosa–Marin systems. The Euro-Qol 5D tool was used to assess quality of life before and after surgery. Results: The mean tremor reduction was 39 % with a range between 0 and 87 %. Five of 16 patients achieved at least 50 % tremor reduction and 11 of 16 achieved at least 30 % tremor reduction at last follow up, mean 11.6 months (range 3–80). Tremor was significantly reduced as rated by Bain scores (Wilcoxon matched pairs, Z = 3.07, p = .002) and tended to significance as rated by Fahn scores (Wilcoxon matched pairs, Z = 1.85, p = 0.06). Sub-analysis of activities of daily living measures from the Fahn system showed post operative improvement in feeding (statistically significant), hygiene, dressing, writing and working. Mean visual analogue scores (0–100) of patient reported well-being increased from 54.6 to 57.4 post operatively with a trend to significance (Student’s t -test, t = 1.26, p = 0.2). Euro-Qol 5D utility values increased following surgery with a trend to significance which was greater in the group with at least 50 % tremor reduction than in those with none or at least 30 % tremor reduction. Conclusions: VIM DBS may reduce severe, disabling tremor in patients with MS. This tremor reduction tends to be associated with improved quality of life and function in those who respond. Patient reported outcome measures may not correlate with physician rated clinical outcome such as tremor scoring systems and more subtle assessment of these patients is required. [ABSTRACT FROM AUTHOR]

Background aims. Retroviral transduction of anti-CD19 chimeric antigen receptors significantly enhances the cytotoxicity of natural killer (NK) cells against B-cell malignancies. We aimed to validate a more practical, affordable and safe method for this purpose. Methods. We tested the expression of a receptor containing CD3ζ and 4-1BB signaling molecules (anti-CD19-BB-ζ) in human NK cells after electroporation with the corresponding mRNA using a clinical-grade electroporator. The cytotoxic capacity of the transfected NK cells was tested in vitro and in a mouse model of leukemia. Results. Median anti-CD19-BB-ζ expression 24 h after electroporation was 40.3% in freshly purified ( n =18) and 61.3% in expanded ( n = 31) NK cells; median cell viability was 90%. NK cells expressing anti-CD19-BB-ζ secreted interferon (IFN)-γ in response to CD19-positive target cells and had increased cytotoxicity. Receptor expression was detectable 6 h after electroporation, reaching maximum levels at 24-48 h; specific anti-CD19 cytotoxicity was observed at 96 h. Levels of expression and cytotoxicities were comparable with those achieved by retroviral transduction. A large-scale protocol was developed and applied to expanded NK cells (median NK cell number 2.5 × 108, n = 12). Median receptor expression after 24 h was 82.0%; NK cells transfected under these conditions exerted considerable cytotoxicity in xenograft models of B-cell leukemia. Conclusions. The method described here represents a practical way to augment the cytotoxicity of NK cells against B-cell malignancies. It has the potential to be extended to other targets beyond CD19 and should facilitate the clinical use of redirected NK cells for cancer therapy. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To perform a quantitative MRI and retrospective electrophysiological study to investigate whether persistent post-surgical seizures may be due to brain structural and functional abnormalities in temporal lobe cortex beyond the margins of resection and/or bilateral abnormalities in patients with temporal lobe epilepsy (TLE). Methods: In 22 patients with left TLE and histopathological evidence of hippocampal sclerosis, we compared pre-surgical brain morphology between patients surgically remedied (Engel''s I) and patients with persistent post-surgical seizures (PPS, Engel''s II–IV) using voxel-based morphometry (VBM). Routine pre-surgical EEG and invasive and non-invasive telemetry investigations were additionally compared between patient groups. Results: Results indicated widespread structural and functional abnormalities in patients with PPS relative to surgically remedied patients. In particular, patients with PPS had significantly reduced volume of the ipsilateral posterior medial temporal lobe and contralateral medial temporal lobe relative to surgically remedied patients. Furthermore, successful surgery was associated with clear anterior (89%) and unilateral (100%) temporal lobe EEG abnormalities, whilst PPS were associated with widespread ipsilateral (91%) and bilateral (82%) temporal lobe abnormalities. Discussion: We suggest that these preliminary data support the hypothesis that PPS after temporal lobe surgery are due to functionally connected epileptogenic cortex remaining in the ipsilateral posterior temporal lobe and/or in temporal lobe contralateral to resection. [Copyright &y& Elsevier]

Determines the variation in coverage by ethnic group of neonatal (Guthie) screening programme in south London, Great Britain. Descriptive coverage study and variations by morbidity, district residence and ethnic group; Subjects of the study; Lists of public health implications.

Introduction Treatment with chimeric antigen receptor modified T cells targeting CD30 (CD30.CAR-Ts) without lymphodepletion was found to be safe with preliminary efficacy in patients (pts) with relapsed/refractory (r/r) CD30+ lymphomas (Ramos et al., JCI 2017). We report the results of a phase 1b/2 trial of CD30.CAR-Ts infused after lymphodepletion in pts with r/r CD30+ Hodgkin (HL) and Non-Hodgkin lymphoma (NHL). Objectives The primary objective of the phase Ib portion of the study was to determine the phase 2 dose of CD30.CAR-Ts using a standard 3+3 design. Methods Pts ≥ 18 years with r/r CD30+ HL or NHL having failed ≥2 prior therapies were eligible. Two dose levels were tested: 1 × 108 CAR-Ts/m2 (DL1) and 2 × 108 CAR-Ts/m2 (DL2). The first 8 pts (including the 3 pts on DL1) received bendamustine (benda) 90 mg/m2 × 2 days and the remaining 16 pts received benda 70 mg/m2 and fludarabine (flu) 30 mg/m2 × 3 days. Results At the time of data cut off (10/1/2018), 24 pts had been treated and undergone response assessment. The median age was 35.5 years (range: 23-70). 22 pts had HL, 1 had enteropathy associated T cell lymphoma and 1 had Sezary syndrome. Pts had undergone a median of 7.5 prior lines of therapy (range: 3-17). 23 pts had received prior brentuximab vedotin. 15 pts had prior autologous stem cell transplant (SCT) and 7 had prior allogeneic SCT. As there were no dose limiting toxicities, DL2 was administered as the phase 2 dose. 3 pts developed grade 1 cytokine release syndrome (CRS) and 1 pt had grade 2 CRS which responded to tocilizumab. 19 out of 24 pts had evidence of disease prior to lymphodepletion and were included in efficacy analysis. 10 pts had a CR at the 6 week assessment (53%, all in benda/flu cohort), 2 had partial response (11%), 2 had stable disease (11%), and 5 had progressive disease (26%, including all 3 pts treated at DL1). At median follow up of 180 days, the median PFS was 164 days. The median PFS for the 14 evaluable pts who received benda/flu at DL2 was 389 days. Using peripheral blood PCR, CD30.CAR-Ts peaked at wk 2 post infusion, with increasing CAR-Ts in pts receiving a higher dose or more robust lymphodepletion (3.4 × 103 ± 2.9 × 103 copies/ug of DNA for DL1-beda vs. 61 × 103 ± 41 × 103 for DL2-benda vs. 49 × 103 ± 16 × 103 for benda/flu). These differences were confirmed by flow cytometry (CD3+CAR+ cells = 13%±9% for DL1-benda vs 21%±10% for DL2-benda vs 35%±8% for benda/flu). There was also improved persistence at wk4 for higher dose and with addition of flu to lymphodepletion (0.06 × 103 ± 0.01 × 103 vs. 0.44 × 103 ± 0.41 × 103 vs. 25 × 103 ± 11 × 103/ug of DNA at wk 4 for DL1-benda, DL2-benda, and benda/flu, respectively). Conclusion CD30.CAR-Ts administered with lymphodepletion with benda/flu are safe and have promising anti-tumor activity for pts with r/r CD30+ lymphomas. A higher dose of CD30.CAR-Ts and the addition of flu to lymphodepletion increased T cell expansion and persistence and translated to improved efficacy. [ABSTRACT FROM AUTHOR]

Background Trigeminal neuralgia (TGN) is a debilitating disorder, and in patients for whom medical management is not sufficient, there are several therapeutic options. Microvascular decompression (MVD) for TGN has been shown to be highly effective; however, pain does recur after MVD in some patients. Therapeutic options for recurrent TGN are the same as those for primary TGN, including re-exploration of MVD (re-MVD). In this study we review our practice of re-MVD, comparing it with alternative options and assessing its safety and efficacy. Methods Retrospective analysis of prospectively collected data of patients undergoing re-MVD between 2007 and 2016. Results Thirty-two patients underwent re-MVD, all with a Barrow Neurosurgical Institute Pain Index (BNPI) of IV or V. Postoperatively, 87% of patients reported an improvement in their BNPI to III or better, with 50% being BNPI 1 or 2. Eleven patients without distortion or vascular conflict at the time of re-exploration underwent intraoperative neurolysis, and 90% reported improvement in their BNPI. Kaplan-Meier analysis showed a median pain-free period of 36 months after re-MVD. There were no significant complications. Conclusions Re-MVD is a safe and effective method of treating recurrent TGN. Intraoperative neurolysis is an important tool in re-exploration and should be considered when there is no ongoing compression or distortion of the trigeminal nerve. [ABSTRACT FROM AUTHOR]

Objective To describe the indications and outcomes of upper cervical cord stimulation in trigeminal neuropathy. Methods A consecutive single-center series of patients was retrospectively reviewed. It included 12 patients with trigeminal neuropathy treated with upper cervical spinal cord stimulation. Clinical features, complications, and outcomes were reviewed. Results All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the level of the craniocervical junction. The mean follow-up period was 4.4 years (range, 0.3–21.1 years). The average coverage in the pain zone was 72% and the median baseline, trial, and postoperative numeric rating scale (NRS) was 7, 3, and 3, respectively. When compared with the baseline, the mean reduction achieved in the postoperative average numeric rating scale was 4 points, accounting for a 57.1% pain reduction. The long-term failure rate was 25%. Conclusions Despite there being enough evidence to consider upper cervical spinal cord stimulation as an effective treatment for patients with neuropathic trigeminal pain, a randomized controlled trial is needed to fully assess its indications and outcomes and compare it with other therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Brachial plexus avulsion (BPA) injuries can cause severe deafferentation pain. This has been successfully treated with dorsal root entry zone (DREZ) lesioning. Distortions in anatomy following a BPA injury can make identifying neural structures challenging. We describe a modification to the operative technique that improves the surgical view and the advanced intraoperative neuromonitoring (IONM) employed to identify DREZ. We have analysed the long-term outcomes for pain, quality of life, and complications in patients undergoing DREZ lesioning., Methods: This is a single-centre retrospective case series including patients who underwent DREZ lesioning with IONM for brachial plexus avulsion between 2012 and 2022. Analysed data included pre- and postoperative pain (VAS), quality of life score for chronic pain, and complications. The evolution of the surgical approach is discussed., Results: 44 consecutive patients underwent a DREZ lesioning procedure with intraoperative monitoring and mapping. In these patients the mean VAS score improved from 8.9 (7-10) to 1.87 (0-6) (p < 0.0001) at the time of discharge. 31 patients were followed-up for more than 12 months with a mean duration of follow-up of 41 months and their results were as follows: the mean VAS improved from 9.0 (7-10) to 4.1 (0-9) (p < 0.0001) at the last follow-up and the mean QOL values improved from 3.7 (2-6) to 7.4 (4-10) (p < 0.0001). The long-term outcomes were 'good' in 39%, 'fair' in 29% and 'poor' in 32% of patients. 55% of the patients were able to stop or reduce pain medications., Conclusions: Modifications of surgical technique provide better exposure of DREZ, and IONM aids in identifying DREZ in the presence of severe intra-dural changes. Long-term outcomes of DREZ lesioning indicate not only a reduction in pain but also a significant improvement in quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Hematopoietic stem cell transplantation (HSCT) represents an example of a highly complex and costly medical procedure with major applications in hematology and oncology. It is associated with life-threatening complications and, consequently, increased demands on healthcare resources. Although improving quality is an integral component of healthcare strategic planning, drivers of quality may be variable, and there is logical debate as to what drives quality in HSCT. Moreover, HSCT programs differ in structure and availability of resources, which drive the type of transplantations provided and determine what is affordable and/or economically feasible. The complexity of HSCT procedures with involvement of different stakeholders necessitates not only regulatory frameworks, but also robust quality systems to ensure consistent standards, demonstrate transparency for regulators, and define what quality means within the HSCT program. In an era of escalating healthcare complexity and heightened fiscal responsibility, transparency and accountability, accreditation contributes to ensuring that care meets the highest standards and can serve as a risk mitigation strategy. Quality management has become an indispensable tool for the management of a complex medical intervention such as HSCT. It allows the transplantation team to monitor its activities and identify areas for continuous improvement. The Worldwide Network for Blood and Marrow Transplantation invited a group of international experts in HSCT and quality management to work on providing a summary document about the key elements in quality and accreditation in HSCT and highlight the foremost challenges of implementing them, with a special focus on low- and middle-income economies., Competing Interests: Conflict of interest statement There are no conflicts of interest to report., (Copyright © 2022. Published by Elsevier Inc.)

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

The first meeting of the African Blood and Marrow Transplantation (AfBMT) was held in Casablanca from April 19, 2018 to April 21, 2018, with the aim of fostering hematopoietic stem cell transplantation (HSCT) activity in Africa. Out of the 54 African countries, HSCT is available only in six (Algeria, Egypt, Morocco, Nigeria, South Africa, and Tunisia). During this meeting, African teams and international experts from the Worldwide Network for Blood and Marrow Transplantation (WBMT) gathered to share their experience and discussed ways to help fill the gap. Nurses and patients held their meeting in parallel. International support and collaboration can help by providing expertise adapted to local resources and regional population needs. Local engagement including government and private participants are necessary to initiate and develop local HSCT capability., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to declare., (Copyright © 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Purpose: Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL)., Methods: We conducted 2 parallel phase I/II studies (ClinicalTrials.gov identifiers: NCT02690545 and NCT02917083) at 2 independent centers involving patients with relapsed or refractory HL and administered CD30.CAR-Ts after lymphodepletion with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. The primary end point was safety., Results: Forty-one patients received CD30.CAR-Ts. Treated patients had a median of 7 prior lines of therapy (range, 2-23), including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation. The most common toxicities were grade 3 or higher hematologic adverse events. Cytokine release syndrome was observed in 10 patients, all of which were grade 1. No neurologic toxicity was observed. The overall response rate in the 32 patients with active disease who received fludarabine-based lymphodepletion was 72%, including 19 patients (59%) with complete response. With a median follow-up of 533 days, the 1-year progression-free survival and overall survival for all evaluable patients were 36% (95% CI, 21% to 51%) and 94% (95% CI, 79% to 99%), respectively. CAR-T cell expansion in vivo was cell dose dependent., Conclusion: Heavily pretreated patients with relapsed or refractory HL who received fludarabine-based lymphodepletion followed by CD30.CAR-Ts had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR-T cell therapies beyond canonical B-cell malignancies.