Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. METHODS: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. RESULTS: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. CONCLUSIONS: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. TRIAL REGISTRATION: NCT04539964; August 31, 2020.

Outcomes of laparoscopic and open ventriculoperitoneal shunt placement.

OBJECTIVE: Ventriculoperitoneal (VP) shunt placement requires a concurrent abdominal procedure. For peritoneal access laparoscopic or open approach may be utilized. Our aim was to compare patient/procedure characteristics and outcomes by peritoneal approach for VP shunts in children. METHODS: NSQIP-Pediatric procedure targeted cerebral spinal fluid shunt Participant Use Data Files from 2016 to 2020 were queried. Patients were grouped into laparoscopic vs open abdominal approach. Patient demographics, procedure characteristics and 30-day outcomes were compared. RESULTS: 7742 NSQIP-Pediatric patients underwent VP shunt placement. Patients undergoing laparoscopic approach were older and required less preoperative support. Mean operative time was longer with laparoscopy (mean(SD): 74.2(48.1) vs. 64.6(39) minutes, p â€‹< â€‹0.0001) but had shorter hospital LOS. There was no difference in SSI, readmissions, or reoperation rates. CONCLUSION: Patients undergoing laparoscopy for distal VP shunts are older with less support needs preoperatively. While laparoscopic approach had a shorter hospital LOS, there was no demonstratable difference in SSI, readmissions or reoperations between approaches. Further studies are needed to assess long-term outcomes.

Surgical treatment for chronic subdural hematoma in the elderly: A retrospective analysis.

Background: Chronic subdural hematoma (CSDH) is primarily a disease of the elderly. Less invasive interventions are often offered for elderly (> 80 years) patients due to concerns for elevated surgical risk, although data suggesting a clear outcome benefit is lacking. Methods: All patients aged 65 years or older who underwent surgical treatment for CSDH at a single institution over a 4-year period were evaluated in this retrospective analysis. Surgical options included twist drill craniostomy (TDC), burr hole craniotomy (BHC), or standard craniotomy (SC). Outcomes, demographics, and clinical data were collected. Practice patterns and outcomes for patients older than 80 years old were compared to the age 65-80 cohort. Results: 110 patients received TDC, 35 received BHC, and 54 received SC. There was no significant difference in post-operative complications, outcomes, or late recurrence (30-90 days). Recurrence at 30 days was significantly higher for TDC (37.3% vs. 2.9% vs 16.7%, p 80 group, SC had higher risk of stroke and increased length of stay. Conclusion: Twist drill craniostomy, burr hole craniostomy, and standard craniotomy have similar neurologic outcomes in elderly patients. Presence of thick membranes is a relative contra-indication for TDC due to high 30-day recurrence. Patients > 80 have higher risk of stroke and increased length of stay with SC.

Laparoscopic Co-surgeon Ventriculoperitoneal Shunt Placement Versus Single Surgeon Mini Laparotomy.

INTRODUCTION: Ventriculoperitoneal (VP) shunt placement is one of the most common treatments for pediatric hydrocephalus. However, device failures often occur, requiring operative revision of either the intraventricular or intraperitoneal shunt catheters. Historically, shunt placement was performed via laparotomy, but there has been a trend towards laparoscopic-assisted placement of the intraperitoneal portion of the shunt. We examined the outcomes of laparoscopic-assisted versus open VP shunt placement utilizing a local institutional retrospective review. METHODS: Single institution 2012-2017 retrospective review of all cases was performed. Patients were divided into two groups - laparoscopic and open. Thirty-day outcomes, patient age, surgery performed, surgical control time (SCT), length of stay (LOS), and readmission were analyzed.  Results: Cohort analysis inclusion criteria included 188 patients. The cohort analysis showed both decreased laparoscopic-assisted SCT (56.4 vs 32.1 min, p<0.0001) and postop complications (16.7% vs 7.1%, p<0.07). There was no significant difference in surgical site infection or readmission rates.  Conclusion: Local analysis show advantages for laparoscopic-assisted VP shunt placement over open single surgeon techniques with decreased SCT, LOS, and unplanned interventions.

Endoscopic Third Ventriculostomy and Endoscopic Intracranial Cyst Fenestration in an Outpatient Ambulatory Surgery Center Yields Reduced Cost But Equal Efficacy and Safety Compared with Surgery in the Hospital.

BACKGROUND: A transition is underway in neurosurgery to perform relatively safe surgeries outpatient, often at ambulatory surgery centers (ASC). We sought to evaluate whether simple intracranial endoscopic procedures such as third ventriculostomy and cyst fenestration can be safely and effectively performed at an ASC, while comparing costs with the hospital. METHODS: A retrospective chart review was performed for patients who underwent elective intracranial neuroendoscopic (NE) intervention at either a quaternary hospital or an affiliated ASC between August 2014 and September 2017. Groups were compared on length of stay, perioperative and 30-day morbidity, as well as clinical outcome at last follow-up. The total cost for these procedures were compared in relative units between all ASC cases and a small subset of hospital cases. RESULTS: In total, 16 NE operations performed at the ASC (mean patient age 29.8 years) and 37 at the hospital (mean age 15.4 years) with average length of stay of 3.5 hours and 23.1 hours respectively (P < 0.05). There were no acute complications in either cohort or morbid events requiring hospitalization within 30 days. Surgical success was noted for 75% of the ASC patients and 73% of the hospital cohort. The mean cost of 5 randomly selected hospital operations with same-day discharge and 5 with overnight stay was 3.4 and 4.1 times that of the ASC cohort, respectively (P < 0.05). CONCLUSIONS: Elective endoscopic third ventriculostomy and other simple NE procedures can be safely and effectively performed at an ASC for appropriate patients with significantly reduced cost compared with the hospital.

Preoperative Acetazolamide Challenge in Pediatric Chiari I Malformation.

PURPOSE: In patients who present with headaches and Chiari 1 malformation without cranial nerve or brainstem dysfunction or syrinx formation, the decision to decompress can be difficult to make. We present a case series examining the use of acetazolamide as a diagnostic aid to determine candidacy for decompression. METHODS: A single pediatric neurosurgeon's (M.M.H.) experience from 2003 to 2018 was retrospectively reviewed. All cases evaluated in the clinic for CPT code of Chiari 1 malformation were analyzed. Inclusion criteria were patients with diagnosis of Chiari 1 malformation and headache-predominant symptoms who underwent an acetazolamide challenge test. Exclusion criteria included age over 18, syrinx, or significant clinical evidence of brainstem compression or cranial nerve dysfunction. Data were recorded with respect to response to acetazolamide. Surgical outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) pain category and the improve/same/worse (IWS) scale. Overall satisfaction from surgery was also recorded. RESULTS: Forty-five patients met inclusion criteria and underwent acetazolamide challenge. Thirty-three (73.3%) patients showed improvement of their symptoms with acetazolamide challenge (responders). Of the 33 responders, 25 (75.8%) underwent Chiari decompression. The remaining 8 (24.2%) responders experienced persistent improvement of their symptoms after the acetazolamide trial and did not require intervention. Twelve (26.7%) patients did not improve with acetazolamide (nonresponders) of which 11 (91.7% of nonreponders) never required intervention. One nonresponder eventually underwent Chiari decompression due to progressively worsening and debilitating headaches. All twenty-five (100%) responders improved after surgery and 24 (96%) were satisfied with the outcome of surgery. The average responder CCOS pain score was 3.52 out of 4. The nonresponder who did not improve with acetazolamide had persistent severe headaches after decompression. The CCOS pain score for this nonresponder was 2 out of 4. CONCLUSION: Pediatric headache-predominant Chiari 1 malformation presents a difficult diagnostic dilemma. The authors describe a trial of acetazolamide as a preoperative diagnostic tool to aid the decision to decompress. Further studies will need to be performed to determine the effectiveness of preoperative acetazolamide in identifying which patients may benefit from surgical decompression.

Converting Pediatric Patients and Young Adults From a Shunt to a Third Ventriculostomy: A Multicenter Evaluation.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is an effective primary treatment for certain forms of hydrocephalus. However, its use in children with an existing shunt is less well known. OBJECTIVE: To report a multicenter experience in attempting to convert patients from shunt dependence to a third ventriculostomy and to determine predictors of success. METHODS: Three participating centers provided retrospectively collected information on patients with an attempted conversion from a shunt to an ETV between December 1, 2008, and April 1, 2018. Demographic, clinical, and radiological data were recorded. Success was defined as shunt independence at the last follow-up. RESULTS: Eighty patients with an existing ventricular shunt underwent an ETV. The median age at the time of the index ETV was 9.9 yr, and 44 (55%) patients were male. The overall success rate was 64% (51/80), with a median duration of follow-up of 2.0 yr (range, 0.1-9.4 yr). Four patients required a successful repeat ETV at a median of 1.7 yr (range, 0.1-5.7 yr) following the index ETV. Only age was predictive of ETV failure on multivariate analysis (odds ratio 0.86 [95% CI 0.78-0.94], P = .005). No patient less than 6 mo of age underwent an ETV, and of the 5 patients between 6 and 12 mo of age, 4 failed. CONCLUSION: Although not every shunted patient will be a candidate for an ETV, nor will they be successfully converted, an ETV should at least be considered in every child who presents with a shunt malfunction or who has an externalized shunt.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with hydrocephalus: a systematic review and meta-analysis.

OBJECT: The objective of this systematic review and meta-analysis was twofold: to answer the question "What is the evidence for the effectiveness of prophylactic intravenous antibiotics for infection prevention in shunt surgery?" and to make treatment recommendations based on the available evidence. METHODS: The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to prophylactic antibiotic use in children undergoing a shunt operation. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). A meta-analysis was conducted using a random-effects model to calculate a cumulative estimate of treatment effect using risk ratio (RR). Heterogeneity was assessed using chi-square and I(2) statistics. A sensitivity analysis was also conducted. Based on the quality of the literature and the result of the meta-analysis, a recommendation was rendered (Level I, II, or III). RESULTS: Nine studies (4 Class I, 3 Class II, and 2 Class III) met our inclusion criteria. Of 7 randomized controlled trials (RCTs), 3 were downgraded from Class I to Class II because of significant quality issues, and all RCTs were potentially underpowered. In only 2 Class in retrospective cohort studies were preoperative antibiotic agents found to be protective against shunt infection. When data from the individual studies were pooled together, the infection rate in the prophylactic antibiotics group was 5.9% compared with 10.7% in the control group. Using a random-effects model, the cumulative RR was 0.55 (95% CI 0.38-0.81), indicating a protective benefit of prophylactic preoperative intravenous antibiotics. A sensitivity analysis of RCTs only (n = 7) also demonstrated a statistical benefit, but an analysis of higher-quality RCTs only (n = 4) did not. Conclusions Within the limits of this systematic review and meta-analysis, administration of preoperative antibiotic agents for shunt surgery in children was found to lower the infection risk (quality of evidence: Class II; strength of recommendation, Level II). RECOMMENDATION: The use of preoperative antibiotic agents can be recommended to prevent shunt infection in patients with hydrocephalus. It was only by combining the results of the various underpowered studies (meta-analysis) that the use of preoperative antibiotics for shunt surgery in children was shown to lower the risk of shunt infection. STRENGTH OF RECOMMENDATION: Level II, moderate degree of clinical certainty.

Passive language mapping with magnetoencephalography in pediatric patients with epilepsy.

OBJECT: Functional mapping is important for determining surgical candidacy and also in epilepsy surgery planning. However, in young children and uncooperative patients, language mapping has been particularly challenging despite the advances in performing noninvasive functional studies. In this study the authors review a series of children with epilepsy who underwent language mapping with magnetoencephalography (MEG) while sedated or sleeping, to determine receptive language localization for presurgical evaluation. METHODS: The authors undertook a retrospective review of patients who underwent MEG between December 2007 and July 2009, and identified 15 individuals who underwent passive language testing as part of their presurgical evaluation because they were unable to participate in traditional language testing, such as Wada or functional MRI. Factors necessitating passive language testing included age and neurocognitive development. RESULTS: Three of the 15 patients were deemed candidates for epilepsy surgery based on the results from standard preoperative testing, including video electroencephalography, MRI, and passive receptive language testing using MEG technology. The MEG studies were used successfully to localize language in all 3 patients, creating opportunities for seizure freedom through surgery that would not otherwise have been available. All 3 patients then underwent resective epilepsy surgery without experiencing postoperative language deficits. CONCLUSIONS: This case series is the first to look at language mapping during sleep (passive language mapping) in which MEG was used and is the first to evaluate passive language testing in a patient population with intracranial pathological entities. This case series demonstrates that MEG can provide an alternative method for receptive language localization in patients with barriers to more traditional language testing, and in these 3 cases surgery was performed safely based on the results.

Resection of infantile brain tumors after neoadjuvant chemotherapy: the St. Jude experience.

OBJECT: Brain tumors in infants are often large, high grade, and vascular, making complete resection difficult and placing children at risk for neurological complications and excessive blood loss. Neoadjuvant chemotherapy may reduce tumor vascularity and volume, which can facilitate resection. The authors evaluated how an ongoing institutional prospective chemotherapy trial would affect patients who did not have a gross-total resection (GTR) immediately and who therefore required further surgical intervention to achieve definitive tumor resection. METHODS: Thirteen infants (4 girls and 9 boys) who were enrolled in an institutional protocol in which they were treated with multiagent chemotherapy (methotrexate, vincristine, cisplatin, and cyclophosphamide with vinblastine for high-risk patients) subsequently underwent second-look surgery. The primary outcome was extent of resection achieved in postchemotherapy surgery. Secondary outcomes included intraoperative blood loss, radiographic response to the chemotherapy, complications during chemotherapy, and survival. RESULTS: Three infants underwent biopsy, 9 underwent subtotal resection, and 1 patient did not undergo surgery prior to chemotherapy. On subsequent second-look surgery, 11 of 13 patients had a GTR, 1 had a near-total resection, and 1 had a subtotal resection. In each case, a marked reduction in tumor vascularity was observed intraoperatively. The average blood loss was 19% of estimated blood volume, and 6 (46%) of 13 patients required a blood transfusion. Radiographically, chemotherapy induced a reduction in tumor volume in 9 (69%) of 13 patients. Emergency surgery was required in 2 patients during chemotherapy, 1 for intratumoral hemorrhage and 1 for worsening peritumoral edema. The average follow-up period for this cohort was 16.5 months, and at last follow-up, 4 patients (31%) had died, 1 patient had progressive metastatic spinal disease, and the rest had either no evidence of disease or stable disease. CONCLUSIONS: A GTR of pediatric brain tumors is one of the most important predictors of outcome. The application of the authors' neoadjuvant induction chemotherapy protocol in a variety of tumor types resulted in devascularization of all tumors and volume regression in the majority, and subsequently facilitated resection, with acceptable intraoperative blood loss. Intracranial complications may occur during chemotherapy, ranging from incidental and asymptomatic to life threatening, necessitating close monitoring of these children.