Farshad Nassiri

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Treatment of posthemorrhagic ventricular dilation in preterm infants: a systematic review and meta-analysis of outcomes and complications

OBJECT The optimal clinical management of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD)/posthemorrhagic hydrocephalus (PHH) in premature infants remains unclear. A common approach involves temporary treatment of hydrocephalus in these patients with a ventriculosubgaleal shunt (VSGS), ventricular access device (VAD), or external ventricular drain (EVD) until it becomes evident that the patient needs and can tolerate permanent CSF diversion (i.e., ventriculoperitoneal shunt). The present systematic review and meta-analysis aimed to provide a robust and comprehensive summary of the published literature regarding the clinical outcomes and complications of these 3 techniques as temporizing measures in the management of prematurity-related PHVD/PHH. METHODS The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library for studies published through December 2013 on the use of VSGSs, VADs, and/or EVDs as temporizing devices for the treatment of hydrocephalus following IVH in the premature neonate. Data pertaining to patient demographic data, study methods, interventions, and outcomes were extracted from eligible articles. For each of the 3 types of temporizing device, the authors performed meta-analyses examining 6 outcomes of interest, which were rates of 1) obstruction; 2) infection; 3) arrest of hydrocephalus (i.e., permanent shunt independence); 4) mortality; 5) good neurodevelopmental outcome; and 6) revision. RESULTS Thirty-nine studies, representing 1502 patients, met eligibility criteria. All of the included articles were observational studies; 36 were retrospective and 3 were prospective designs. Nine studies (n = 295) examined VSGSs, 24 (n = 962) VADs, and 9 (n = 245) EVDs. Pooled rates of outcome for VSGS, VAD, and EVD, respectively, were 9.6%, 7.3%, and 6.8% for obstruction; 9.2%, 9.5%, and 6.7% for infection; 12.2%, 10.8%, and 47.3% for revision; 13.9%, 17.5%, and 31.8% for arrest of hydrocephalus; 12.1%, 15.3%, and 19.1% for death; and 58.7%, 50.1%, and 56.1% for good neurodevelopmental outcome. CONCLUSIONS This study provides robust estimates of outcomes for the most common temporizing treatments for IVH in premature infants. With few exceptions, the range of outcomes was similar for VSGS, VAD, and EVD.

Cervical Spine Clearance in Obtunded Patients After Blunt Traumatic Injury: A Systematic Review

Cervical spine trauma is a major public health problem and a common reason for admission to trauma wards and intensive care units. The cervical spine is injured in 2.3% to 4.3% (14) of blunt traumas. Resultant neurologic impairment is encountered in 33% to 54% (57) of patients with cervical spine trauma. In fact, more than 50% of all acute spinal cord injuries affect the cervical spine (8, 9). Unfortunately, these injuries have poor functional outcomes. Mortality after traumatic cervical spinal cord injury may exceed 20% (1013), and survivors often face lifelong physical disability, along with the associated emotional, psychological, and social burdens (6, 8, 14, 15). The economic costs of spinal cord injury are enormous. In the United States, the total annual direct cost of spinal cord injuries approaches

Neural precursor cell transplantation enhances functional recovery and reduces astrogliosis in bilateral compressive/contusive cervical spinal cord injury.

8 billion (16). These factors make diligent and efficient cervical spine clearance protocols a critical priority. The exclusion of cervical spine injury in obtunded patients with trauma poses a significant challenge given the lack of a reliable clinical examination. Common practices at many trauma centers include routine acquisition of cervical spine magnetic resonance imaging (MRI), dynamic radiography (flexion and extension), or continued cervical immobilization until patients are awake and asymptomatic after a negative computed tomography (CT) scan (17, 18). These protocols may increase health care costs unduly, place critically ill patients at risk for deterioration during transportation, and prolong cervical collar immobilization and its associated illnesses. On the other hand, the consequences of missing an injury can be devastating and may include loss of functional ability, independence, and possibly life (1921). The primary aim of this study was to elucidate the role for further routine imaging or prolonged cervical immobilization in excluding significant cervical spine injury after negative CT results in obtunded patients who had blunt traumatic injury. Methods This systematic review was done according to a predefined protocol (Supplement) in accordance with MOOSE (Meta-analysis Of Observational Studies in Epidemiology) guidelines (22) and the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) Statement (23). Supplement. Study Protocol Search Strategy We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL, Google Scholar, and the Cochrane Library from January 2000 through November 2014 for studies on the role of CT followed by a validating test in evaluating the cervical spine of obtunded trauma patients. We used, in various combinations, keywords and Medical Subject Headings terms pertinent to the patient population (altered, comatose, intensive care, intubated, mental status, obtunded, unconscious, unevaluable, unexaminable, unreliable, or unresponsive), medical condition (fracture, injury, instability, or trauma), anatomical site of interest (cervical-spine or cervical), and relevant radiological imaging methods (clearance, computed tomography, CT, dynamic, extension, flexion, fluoroscopy, imaging, magnetic resonance, MDCT, MR, MRI, plain film, radiograph, or X-ray). We also manually searched the references of relevant studies to identify additional studies for consideration. Selection Criteria Three investigators independently evaluated the studies for eligibility. Selection criteria included a study of any design (randomized, controlled trial; prospective cohort study; or retrospective cohort study). Studies were eligible if the diagnostic protocol of interest included a negative finding on a helical CT scan of the entire cervical spine followed by a confirmatory test. We included only the population of obtunded patients with blunt trauma (Glasgow Coma Scale [GCS] score 14, unreliable clinical examination, or intubation). Only English-language studies documenting the outcome measures of missed cervical spine injury or intervention after a negative CT result and additional findings of a validating test were included. We excluded studies with a sample size of fewer than 10 patients and studies in which partial cervical spine CT scans were used. For studies reporting data on overlapping cohorts from the same institution, we included only the study with the most inclusive cohort to prevent duplication. Studies evaluating only the pediatric population were excluded. Studies that examined awake and obtunded patients were included only if the outcomes of unreliable patients were analyzed separately. Abstracts from meeting proceedings were excluded if the data were not published in full-text articles in a peer-reviewed journal. Disagreements among the 3 reviewers about the decision to include or exclude a study were resolved by consensus and, if necessary, consultation with a fourth reviewer. Data Extraction and Quality Assessment Data from eligible studies were independently extracted by the 3 primary reviewers and verified for accuracy by the fourth reviewer. Discrepancies were resolved by discussion and consensus. We used data collection forms that included the following fields: title, author, year and country of publication, study design, sample size, patient demographic characteristics, Injury Severity Score, GCS score, definition of obtunded, mechanism of injury, CT specifications, further imaging or follow-up of patients with negative CT scans, image interpreter, missed acute cervical spine injuries, and changes in management. The 3 primary reviewers performed quality assessment independently. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool (24) and examined patient selection, the index test and reference standard used, and flow and timing to determine whether the risk of bias and concerns about applicability to the review question were low, unclear, or high among eligible studies. Definition of Variables Our primary outcome of interest was clinically significant cervical spine injury missed by CT and detected by the confirmatory test. A clinically significant injury was defined as one resulting in mechanical instability or requiring intervention or change in management. We excluded soft tissue signal changes that did not affect spine stability. The definition of cervical spine instability varied among included studies and was assessed by using many classification systems. Most eligible studies defined instability in accordance with the work of White and Panjabi (25) on biomechanics of the spine. Previous studies defined unstable and purely ligamentous injuries as those involving all 3 columns (26). We adopted and documented cervical spine instability outcomes as reported by the authors of included studies, regardless of the classification used. Changes in management after negative CT results and positive findings on a validating test included prolonged external immobilization or operative stabilization. An obtunded patient was defined as someone who was not fully awake and had an altered level of consciousness (GCS 14). These patients lacked a reliable neurologic examination that could aid in the diagnosis of spinal injury. High-quality CT scans were defined as those protocolled with narrow slice width (1 to 3 mm) and reconstruction in multiple planes. A well-interpreted CT study was defined as an image read by a health professional with special training and expertise in reading such images (that is, a consultant radiologist) rather than an on-call physician or radiology resident. Data Synthesis and Analysis Studies were grouped on the basis of how further evaluation of obtunded trauma patients with negative results from cervical spine CT was handled. The first group included studies that routinely performed MRI after a CT scan that was interpreted as normal. The second group comprised studies in which patients were routinely evaluated with dynamic radiography after negative CT results. The third group included studies in which patients were followed with serial physical examination after a normal CT result, with further imaging obtained as guided by clinical indications (for example, neurologic deficit). For each group, we examined mechanical cervical spine instability, need for operative stabilization, and collar use after negative CT results and additional findings on the confirmatory test. We examined high-quality studies separately. These reports fulfilled 4 criteria: prospective study design, low risk of bias and low concerns about applicability in all domains on the QUADAS-2 tool, well-interpreted CT images, and use of high-quality CT specifications. Given the small number of events (if any), formal meta-analysis was not possible. Data from individual studies are displayed in forest plots with 95% CIs. Exact binominal 1-sided 95% CIs were calculated for each proportion obtained from eligible studies (27). We used R, version 3.1.2 (R Foundation for Statistical Computing), to generate all forest plots. Role of the Funding Source This study received no funding. Results Characteristics of Included Studies Our search yielded 2112 results, of which 1959 were excluded after title and abstract screening. Another 125 were excluded after full-text review (Appendix Figure). The remaining 28 studies (2855) were included, and they reported on a total of 3627 obtunded blunt trauma patients with negative results from cervical spine CT and a validating test. Twenty studies (28, 29, 32, 34, 35, 37, 4044, 46, 4855) were retrospective cohort studies, and 8 (30, 31, 33, 36, 38, 39, 45, 47) were prospective cohort studies. Descriptions of eligible studies are provided in Appendix Tables 1 and 2. Details of methodological assessment of included studies with the QUADAS-2 tool are presented in Appendix Table 3. Appendix Figure. Summary of evidence search and selection. CT = computed tomography. Appendix Table 1. Characteristics of Included Studies Appendix Table 2. Outcomes of Eligible Studies Appendix Table 3. Quality Assessment of Eligible Studies Wit

The effectiveness of interventions to reduce neurological injuries in rugby union: a systematic review

Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion‐compression spinal cord injury. Bilateral C6‐level clip contusion‐compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain‐derived NPCs, vehicle, or sham operation. Long‐term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft‐derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP‐positive and chondroitin sulfate proteoglycan‐positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell‐treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation.

Pituitary stem cells: candidates and implications

BACKGROUND:Rugby is characterized by high-speed collisions among the players that predispose them to injuries, particularly to the head, neck, and spine. OBJECTIVE:To evaluate the effectiveness of current neurological injury prevention strategies in rugby union. METHODS:Systematic review in May 2010. We assessed the quality and content of studies that evaluated injury prevention strategies for rugby players and reported on neurological outcomes. We searched OVID Medline, OVID HealthStar, CINAHL, Sport Discus, PubMed, Scholars Portal Physical Education Index, Web of Science, and the Cochrane Controlled Clinical Trials Register (CENTRAL) and conducted a manual search of the cited literature lists of each included study. RESULTS:Ten articles are included in the review, with 2 of these assessing both headgear and mouthguards. Four studies reported insignificant reductions in neurological injury with the use of headgear. The results of 4 studies on the effectiveness of mouthguards in preventing neurological injury were inconclusive. Four studies reported significant reductions in neurological injury after the implementation of nationwide multifaceted injury prevention strategies with a focus on education CONCLUSION:There is limited evidence to support the effectiveness of mouthguards and headgear in reducing neurological injuries; however, system-wide, mandatory interventions are useful in reducing neurological injuries in rugby.

Deep brain stimulation for Parkinson’s disease: meta-analysis of results of randomized trials at varying lengths of follow-up

The pituitary is the master endocrine gland of the body. It undergoes many changes after birth, and these changes may be mediated by the differentiation of pituitary stem cells. Stem cells in any tissue source must display (1) pluripotent capacity, (2) capacity for indefinite self-renewal, and (3) a lack of specialization. Unlike neural stem cells identified in the hippocampus and subventricular zone, pituitary stem cells are not associated with one specific cell type. There are many major candidates that are thought to be potential pituitary stem cell sources. This article reviews the evidence for each of the major cell types and discuss the implications of identifying a definitive pituitary stem cell type.

Neuroendocrine tumor of unknown origin metastasizing to a growth hormone-secreting pituitary adenoma.

OBJECTIVE Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinsons disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up. METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups. RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99-4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar. CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.

Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis

BACKGROUND Metastasis of a neuroendocrine tumor to the anterior pituitary is extremely rare. METHODS A 55-year-old woman presented with features suggestive of acromegaly and bone and joint pain. A bone scan suggested metastatic disease. A biopsy of the lumbar spinal lesions revealed a neuroendocrine tumor. Magnetic resonance imaging of the sella demonstrated a lesion with parasellar and suprasellar extensions. Given the need for tissue diagnosis and optic compression, the sellar lesion was removed via transsphenoidal hypophysectomy. RESULTS Histology of the biopsy indicated two different tumors in close association. One showed histological features of a pituitary adenoma, whereas the other was a neuroendocrine carcinoma. The pituitary adenoma was immunopositive for growth hormone (GH), whereas the neuroendocrine carcinoma was immunopositive for serotonin and bombesin and immunonegative for GH. CONCLUSIONS This is the first report of a serotonin and bombesin immunopositive neuroendocrine tumor of unknown primary origin metastatic to a GH-secreting pituitary adenoma, resulting in acromegaly.

Exploring the expectation-actuality discrepancy: a systematic review of the impact of preoperative expectations on satisfaction and patient reported outcomes in spinal surgery.

BACKGROUND Atraumatic needles have been proposed to lower complication rates after lumbar puncture. However, several surveys indicate that clinical adoption of these needles remains poor. We did a systematic review and meta-analysis to compare patient outcomes after lumbar puncture with atraumatic needles and conventional needles. METHODS In this systematic review and meta-analysis, we independently searched 13 databases with no language restrictions from inception to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic needles and conventional needles for any lumbar puncture indication. Randomised trials comparing atraumatic and conventional needles in which no dural puncture was done (epidural injections) or without a conventional needle control group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of postdural-puncture headache incidence and additional safety and efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS We identified 20 241 reports; after exclusions, 110 trials done between 1989 and 2017 from 29 countries, including a total of 31 412 participants, were eligible for analysis. The incidence of postdural-puncture headache was significantly reduced from 11·0% (95% CI 9·1-13·3) in the conventional needle group to 4·2% (3·3-5·2) in the atraumatic group (relative risk 0·40, 95% CI 0·34-0·47, p<0·0001; I2=45·4%). Atraumatic needles were also associated with significant reductions in the need for intravenous fluid or controlled analgesia (0·44, 95% CI 0·29-0·64; p<0·0001), need for epidural blood patch (0·50, 0·33-0·75; p=0·001), any headache (0·50, 0·43-0·57; p<0·0001), mild headache (0·52, 0·38-0·70; p<0·0001), severe headache (0·41, 0·28-0·59; p<0·0001), nerve root irritation (0·71, 0·54-0·92; p=0·011), and hearing disturbance (0·25, 0·11-0·60; p=0·002). Success of lumbar puncture on first attempt, failure rate, mean number of attempts, and the incidence of traumatic tap and backache did not differ significantly between the two needle groups. Prespecified subgroup analyses of postdural-puncture headache revealed no interactions between needle type and patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient position, indication for lumbar puncture, bed rest after puncture, or clinician specialty. These results were rated high-quality evidence as examined using the grading of recommendations assessment, development, and evaluation. INTERPRETATION Among patients who had lumbar puncture, atraumatic needles were associated with a decrease in the incidence of postdural-puncture headache and in the need for patients to return to hospital for additional therapy, and had similar efficacy to conventional needles. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture. FUNDING None.