Expansile duraplasty and obex exploration compared with bone-only decompression for Chiari malformation type I in children: retrospective review of outcomes and complications.

OBJECTIVE: While a select population of pediatric patients with Chiari malformation type I (CM-I) remain asymptomatic, some patients present with tussive headaches, neurological deficits, progressive scoliosis, and other debilitating symptoms that necessitate surgical intervention. Surgery entails a variety of strategies to restore normal CSF flow, including increasing the posterior fossa volume via bone decompression only, or bone decompression with duraplasty, with or without obex exploration. The indications for duraplasty and obex exploration following bone decompression remain controversial. The objective of this study was to describe an institutional series of pediatric patients undergoing surgery for CM-I, performed by a single neurosurgeon. For patients presenting with a syrinx, the authors compared outcomes following bone-only decompression with duraplasty only and with duraplasty including obex exploration. Clinical outcomes evaluated included resolution of syrinx, scoliosis, presenting symptoms, and surgical complications. METHODS: A retrospective review was conducted of the medical records of 276 consecutive pediatric patients with CM-I operated on at a single institution between 2001 and 2015 by the senior author. Imaging findings of tonsillar descent, associated syrinx (syringomyelia or syringobulbia), basilar invagination, and clinical assessment of CM-I-attributable symptoms and scoliosis were recorded. In patients presenting with a syrinx, clinical outcomes, including syrinx resolution, symptom resolution, and impact on scoliosis progression, were compared for three surgical groups: bone-only/posterior fossa decompression (PFD), PFD with duraplasty (PFDwD), and PFD with duraplasty and obex exploration (PFDwDO). RESULTS: PFD was performed in 25% of patients (69/276), PFDwD in 18% of patients (50/276), and PFDwDO in 57% of patients (157/276). The mean follow-up was 35 ± 35 months. Nearly half of the patients (132/276, 48%) had a syrinx. In patients presenting with a syrinx, PFDwDO was associated with a significantly higher likelihood of syrinx resolution relative to PFD only (HR 2.65, p = 0.028) and a significant difference in time to symptom resolution (HR 2.68, p = 0.033). Scoliosis outcomes did not differ among treatment groups (p = 0.275). Complications were not significantly higher when any duraplasty (PFDwD or PFDwDO) was performed following bone decompression (p > 0.99). CONCLUSIONS: In this series of pediatric patients with CM-I, patients presenting with a syrinx who underwent expansile duraplasty with obex exploration had a significantly greater likelihood of syrinx and symptom resolution, without increased risk of CSF-related complications, compared to those who underwent bone-only decompression.

Teaching the Emergency Neurologic Life Support Course at Two Major Hospitals in Phnom Penh, Cambodia.

OBJECTIVE: To determine the effect of offering a subset of the Emergency Neurological Life Support (ENLS) course modules on provider knowledge and self-reported confidence in acute management of neurocritically ill patients in a low-middle income country (LMIC). METHODS: Eight ENLS modules were provided by in-person lecture using English to Khmer translated slides and a medical translator to physicians and nurses of 2 hospitals in Phnom Penh, Cambodia in May 2019. Providers included emergency, neurology, neurologic surgery, and general intensive care. Demographics, pre- and postcourse knowledge of ENLS content areas, and pre- and postcourse confidence in managing neurocritically ill patients were assessed. Data were pooled across both hospitals for analysis. RESULTS: A total of 57 health care providers were approached for participation: 52 (25 physicians, 27 nurses) participated; 45 completed all study instruments. Pre- and postcourse knowledge scores showed no significant differences between providers. Postcourse, 37/45 (82.2%) participants reported that the content had prepared them for acute management of neurocritically ill patients. Satisfaction with module content ranged from 77.8%-80.0% per module. For the 8 modules, a majority of participants agreed that course material had provided them with knowledge and skills to provide acute care for patients' neurologic emergencies (68.4%-88.6%). CONCLUSIONS: Provision of ENLS course module content increased LMIC provider self-reported knowledge and confidence in acute management of neurocritically ill patients immediately postcourse. Tailoring ENLS course presentation to a particular LMIC setting warrants additional investigation, as does the effect of ENLS course training on neurocritically ill patient outcomes in the LMIC setting.

Tobacco use, immunosuppressive, chronic pain, and psychiatric conditions are prevalent in women with symptomatic mesh complications undergoing mesh removal surgery.

Purpose: To identify demographic and clinical characteristics of patients with symptomatic pelvic floor mesh complications who underwent mesh removal at our academic medical center. The secondary goal was to determine patient-reported outcomes after mesh removal. Materials and Methods: We conducted a retrospective review of consecutive patients from 2011-2016 undergoing removal of mesh graft for treatment of symptomatic mesh-related complications. Patient demographics, comorbidities, symptoms, and mesh factors were evaluated. Outcomes after explant were determined by the Patient Global Impression of Improvement and a Likert satisfaction scale. Results: One hundred fifty-six symptomatic patients underwent complete or partial pelvic floor mesh removal during the study period. Mid-urethral slings comprised 86% of explanted mesh grafts. Mesh exposure or erosion was identified in 72% of patients. Eighty-one percent of patients presented with pain, and 35% reported pain in the absence of exposure or erosion. Pre-operative comorbidities included psychiatric disease (54.5%), chronic pain (34.0%), irritable bowel syndrome (20.5%) and fibromyalgia (9.6%). Forty-three percent of patients reported current or past tobacco use. At mean follow-up of 14 months, 68% of responding patients reported improvement on the Patient Global Impression of Improvement after surgery. Conclusions: This research identified tobacco use, and psychiatric, immunosuppressive, and chronic pain conditions as prevalent in this cohort of patients undergoing mesh removal. Surgical removal can improve presenting symptoms, including for patients with pain in the absence of other indications.

Anti-PD-L1 antibody direct activation of macrophages contributes to a radiation-induced abscopal response in glioblastoma.

BACKGROUND: Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an "abscopal effect," whereby unirradiated neoplastic cells outside treatment sites are recognized and attacked by the immune system. Radiation combined with anti-programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma clinical trials, but the mechanism and relevance of the abscopal effect during this response remain unknown. METHODS: We modified an immune-competent, genetically driven mouse glioma model (forced platelet derived growth factor [PDGF] expression + phosphatase and tensin homolog loss) where a portion of the tumor burden is irradiated (PDGF) and another unirradiated luciferase-expressing tumor (PDGF + luciferase) is used as a readout of the abscopal effect following systemic anti-PD-L1 immunotherapy. We assessed relevance of tumor neoepitope during the abscopal response by inducing expression of epidermal growth factor receptor variant III (EGFRvIII) (PDGF + EGFRvIII). Statistical tests were two-sided. RESULTS: Following radiation of one lesion, anti-PD-L1 immunotherapy enhanced the abscopal response to the unirradiated lesion. In PDGF-driven gliomas without tumor neoepitope (PDGF + luciferase, n = 8), the abscopal response occurred via anti-PD-L1 driven, extracellular signal-regulated kinase-mediated, bone marrow-derived macrophage phagocytosis of adjacent unirradiated tumor cells, with modest survival implications (median survival 41 days vs radiation alone 37.5 days, P = 0.03). In PDGF-driven gliomas with tumor neoepitope (PDGF + EGFRvIII, n = 8), anti-PD-L1 enhanced abscopal response was associated with macrophage and T-cell infiltration and increased survival benefit (median survival 36 days vs radiation alone 28 days, P = 0.001). CONCLUSION: Our results indicate that anti-PD-L1 immunotherapy enhances a radiation- induced abscopal response via canonical T-cell activation and direct macrophage activation in glioblastoma.