Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7.

FBXW7 is an E3 ubiquitin ligase that targets proteins for proteasome-mediated degradation and is mutated in various cancer types. Here, we use CRISPR base editors to introduce different FBXW7 hotspot mutations in human colon organoids. Functionally, FBXW7 mutation reduces EGF dependency of organoid growth by ~10,000-fold. Combined transcriptomic and proteomic analyses revealed increased EGFR protein stability in FBXW7 mutants. Two distinct phosphodegron motifs reside in the cytoplasmic tail of EGFR. Mutations in these phosphodegron motifs occur in human cancer. CRISPR-mediated disruption of the phosphodegron motif at T693 reduced EGFR degradation and EGF growth factor dependency. FBXW7 mutant organoids showed reduced sensitivity to EGFR-MAPK inhibitors. These observations were further strengthened in CRC-derived organoid lines and validated in a cohort of patients treated with panitumumab. Our data imply that FBXW7 mutations reduce EGF dependency by disabling EGFR turnover.

Reliability of a Novel Classification System for Thoracic Disc Herniations.

STUDY DESIGN: This is a cross-sectional survey. OBJECTIVE: The aim was to assess the reliability of a proposed novel classification system for thoracic disc herniations (TDHs). SUMMARY OF BACKGROUND DATA: TDHs are complex entities varying substantially in many factors, including size, location, and calcification. To date, no comprehensive system exists to categorize these lesions. METHODS: Our proposed system classifies 5 types of TDHs using anatomic and clinical characteristics, with subtypes for calcification. Type 0 herniations are small (≤40% of spinal canal) TDHs without significant spinal cord or nerve root effacement; type 1 are small and paracentral; type 2 are small and central; type 3 are giant (>40% of spinal canal) and paracentral; and type 4 are giant and central. Patients with types 1 to 4 TDHs have correlative clinical and radiographic evidence of spinal cord compression. Twenty-one US spine surgeons with substantial TDH experience rated 10 illustrative cases to determine the system's reliability. Interobserver and intraobserver reliability were determined using the Fleiss kappa coefficient. Surgeons were also surveyed to obtain consensus on surgical approaches for the various TDH types. RESULTS: High agreement was found for the classification system, with 80% (range 62% to 95%) overall agreement and high interrater and intrarater reliability (kappa 0.604 [moderate to substantial agreement] and kappa 0.630 [substantial agreement], respectively). All surgeons reported nonoperative management of type 0 TDHs. For type 1 TDHs, most respondents (71%) preferred posterior approaches. For type 2 TDHs, responses were roughly equivalent for anterolateral and posterior options. For types 3 and 4 TDHs, most respondents (72% and 68%, respectively) preferred anterolateral approaches. CONCLUSIONS: This novel classification system can be used to reliably categorize TDHs, standardize description, and potentially guide the selection of surgical approach. Validation of this system with regard to treatment and clinical outcomes represents a line of future study.

One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids.

Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show efficacy of cytosine and adenine base editors in modeling CTNNB1 hot-spot mutations in hepatocyte organoids. Next, we use C > T base editors to insert nonsense mutations in PTEN in endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug sensitivity assays on organoids harboring either PTEN or PTEN and PIK3CA mutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C > T and A > G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes.

Technique for Validation of Intraoperative Navigation in Minimally Invasive Spine Surgery.

BACKGROUND: Intraoperative 3-dimensional navigation is an enabling technology that has quickly become a commonplace in minimally invasive spine surgery (MISS). It provides a useful adjunct for percutaneous pedicle screw fixation. Although navigation is associated with many benefits, including improvement in overall screw accuracy, navigation errors can lead to misplaced instrumentation and potential complications or revision surgery. It is difficult to confirm navigation accuracy without a distant reference point. OBJECTIVE: To describe a simple technique for validating navigation accuracy in the operating room during MISS. METHODS: The operating room is set up in a standard fashion for MISS with intraoperative cross-sectional imaging available. A 16-gauge needle is placed within the bone of the spinous process before intraoperative cross-sectional imaging. The entry level is chosen such that the space between the reference array and the needle encompasses the surgical construct. Before placing each pedicle screw, accuracy is verified by placing the navigation probe over the needle. RESULTS: This technique has identified navigation inaccuracy and led to repeat cross-sectional imaging. No screws have been misplaced in the senior author's cases since adopting this technique, and there have been no complications attributable to the technique. CONCLUSION: Navigation inaccuracy is an inherent risk in MISS, but the described technique may mitigate this risk by providing a stable reference point.

Does Advanced Imaging Aid in the Preoperative Evaluation of Patients With Moyamoya Disease?

Background Moyamoya disease is characterized by progressive nonatherosclerotic stenosis and eventual occlusion of the supraclinoid cerebral arteries with the associated development of abnormal collateral vessels. Treatment of moyamoya disease revolves around restoring cerebral blood flow (CBF) distal to the steno-occlusive disease. Numerous modalities can be used to assess hemodynamic parameters. We sought to determine the impact of preoperative imaging on surgical decision-making. Methods A retrospective review was performed of all patients seen with the diagnosis of moyamoya. Patients were grouped on presentation based on CT/MRI findings of infarction, hemorrhage, or normal. Patients who did not have all of the preoperative tests were excluded. Preoperative radiological results were dichotomized as either normal or abnormal. Results During a five-year period, 34 patients with moyamoya met the inclusion criteria. All patients had an abnormal magnetic resonance angiography (MRA) Non-invasive Optimal Vessel Analysis (NOVA; VasSol, Inc, River Forest, IL). Three patients had normal initial MRI. All symptomatic patients had abnormal preoperative workup and underwent revascularization, as all were found to have abnormal single photon emission computed tomography (SPECT). The only occasion where the decision for surgery or type of surgery was influenced by imaging findings was in patients with nonclassical or minimal symptoms. Conclusion Although hemodynamic imaging studies can aid in establishing a preoperative baseline of CBF and cerebral vascular reserve (CVR) for follow-up studies, the true implication of these tests in the preoperative evaluation of clearly symptomatic moyamoya patients is debatable. In asymptomatic/mildly symptomatic patients, hemodynamic studies are necessary to determine the need for treatment. For symptomatic patients, surgery can be performed without an exhaustive and costly preoperative hemodynamic evaluation.

Influence of Spinal Deformity Construct Design on Adjacent-Segment Biomechanics.

BACKGROUND: Adjacent level degeneration is a precursor to construct failure in adult spinal deformity surgery, but whether construct design affects adjacent level degeneration risk remains unclear. Here we present a biomechanical profile of common deformity correction constructs and assess adjacent level biomechanics. METHODS: Standard nondestructive flexibility tests (7.5 Nm) were performed on 21 cadaveric specimens: 14 pedicle subtraction osteotomies (PSOs) and 7 anterior column realignment (ACR) constructs. The ranges of motion (ROM) at the adjacent free level in flexion, extension, axial rotation, and lateral bending were measured and analyzed. RESULTS: ACR constructs had a lower ROM change on flexion at the proximal adjacent free level than constructs with PSO (1.02 vs. 1.32, normalized to the intact specimen, P < 0.01). Lateral lumbar interbody fusion adjacent to PSO and 4 rods limits ROM at the free level more effectively than transforaminal interbody fusion and 2 rods in correction constructs with PSO. Use of 2 screws to anchor the ACR interbody further decreased ROM at the proximal adjacent free level on flexion, but adding 4 rods in this setting added no further limitation to adjacent segment motion. CONCLUSIONS: ACR constructs have less ROM change at the adjacent level compared to PSO constructs. Among constructs with ACR, anchoring the ACR interbody with 2 screws reduces motion at the proximal adjacent free level. When PSOs are used, lateral lumbar interbody fusion adjacent to the PSO level has a greater reduction in adjacent-segment motion than transforaminal interbody fusion, suggesting that deformity construct configuration influences proximal adjacent-segment biomechanics.

Surgical anatomy of minimally invasive lateral approaches to the thoracolumbar junction.

OBJECTIVE: The thoracolumbar (TL) junction spanning T11 to L2 is difficult to access because of the convergence of multiple anatomical structures and tissue planes. Earlier studies have described different approaches and anatomical structures relevant to the TL junction. This anatomical study aims to build a conceptual framework for selecting and executing a minimally invasive lateral approach to the spine for interbody fusion at any level of the TL junction with appropriate adjustments for local anatomical variations. METHODS: The authors reviewed anatomical dissections from 9 fresh-frozen cadaveric specimens as well as clinical case examples to denote key anatomical relationships and considerations for approach selection. RESULTS: The retroperitoneal and retropleural spaces reside within the same extracoelomic cavity and are separated from each other by the lateral attachments of the diaphragm to the rib and the L1 transverse process. If the lateral diaphragmatic attachments are dissected and the diaphragm is retracted anteriorly, the retroperitoneal and retropleural spaces will be in direct continuity, allowing full access to the TL junction. The T12-L2 disc spaces can be reached by a conventional lateral retroperitoneal exposure with the rostral displacement of the 11th and 12th ribs. With caudally displaced ribs, or to expose T12-L1 disc spaces, the diaphragm can be freed from its lateral attachments to perform a retrodiaphragmatic approach. The T11-12 disc space can be accessed purely through a retropleural approach without significant mobilization of the diaphragm. CONCLUSIONS: The entirety of the TL junction can be accessed through a minimally invasive extracoelomic approach, with or without manipulation of the diaphragm. Approach selection is determined by the region of interest, degree of diaphragmatic mobilization required, and rib anatomy.

Single-Position Prone Lateral Interbody Fusion Improves Segmental Lordosis in Lumbar Spondylolisthesis.

OBJECTIVE: Single-position surgery in prone position is a novel technique for lateral interbody fusion with pedicle screw fixation. We performed a radiographic comparison of patients treated for spondylolisthesis using the prone lateral (PL) transpsoas approach versus the traditional dual position (DP) approach (lateral decubitus then prone). METHODS: Thirty consecutive patients with spondylolisthesis were treated using the PL approach (n = 15) versus the dual position approach (n = 15). Radiographic factors in the groups were retrospectively compared. RESULTS: The groups were similar for age, sex, body mass index, and implant size, but there were more 15° (vs. 10°) cages inserted in the dual position group. Radiographically the groups had similar baseline spinopelvic parameters, lumbar lordosis (LL), segmental lordosis, anterolisthesis, and disc height (P > 0.05). Postoperatively the PL group demonstrated a larger improvement in segmental lordosis (5.1° vs. 2.5°, P = 0.02), but not overall LL (6.3° vs. 3.1°, P = 0.14). Both groups had similar improvements in pelvic tilt, disc height, and spondylolisthesis reduction (P > 0.05). The mean relative distance of the implant from the posterior edge of the vertebral body was greater in the PL group (26% vs. 17%, P < 0.001) indicating a tendency for more anterior cage placement. However, there was no significant correlation between the relative cage position and the increase in segmental lordosis (P = 0.35), so this result alone did not explain the relative increase in lordosis seen. CONCLUSIONS: This is the first study to our knowledge to demonstrate an improvement in segmental lordosis for patients with single-level spondylolisthesis using the PL approach.

Risk Factors for Proximal Junctional Kyphosis Following Surgical Deformity Correction in Pediatric Neuromuscular Scoliosis.

STUDY DESIGN: Single-center retrospective cohort analysis. OBJECTIVE: The aim of this study was to evaluate risk factors associated with the development of proximal junctional kyphosis (PJK) in pediatric neuromuscular scoliosis (NMS). SUMMARY OF BACKGROUND DATA: PJK is a common cause of reoperation in adult deformity but has been less well reported in pediatric NMS. METHODS: Sixty consecutive pediatric patients underwent spinal fusion for NMS with a minimum 2-year follow-up. PJK was defined as >10° increase between the inferior end plate of the upper instrumented vertebra (UIV) and the superior end plate of the vertebra two segments above. Regression analyses as well as binary correlational models and Student t tests were employed for further statistical analysis assessing variables of primary and compensatory curve magnitudes, thoracic kyphosis, proximal kyphosis, lumbar lordosis, pelvic obliquity, shoulder imbalance, Risser classification, and sagittal profile. RESULTS: The present cohort consisted of 29 boys and 31 girls with a mean age at surgery of 14 ±â€Š2.7 years. The most prevalent diagnoses were spinal cord injury (23%) and cerebral palsy (20%). Analysis reflected an overall radiographic PJK rate of 27% (n = 16) and a proximal junctional failure rate of 7% (n = 4). No significant association was identified with previously suggested risk factors such as extent of rostral fixation (P = 0.750), rod metal type (P = 0.776), laminar hooks (P = 0.654), implant density (P = 0.386), nonambulatory functional status (P = 0.254), or pelvic fixation (P = 0.746). Significant risk factors for development of PJK included perioperative use of halo gravity traction (38%, P = 0.029), greater postoperative C2 sagittal translation (P = 0.030), decreased proximal kyphosis preoperatively (P = 0.002), and loss of correction of primary curve magnitude at follow-up (P = 0.047). Increase in lumbar lordosis from post-op to last follow-up trended toward significance (P = 0.055). CONCLUSION: Twenty-seven percent of patients with NMS developed PJK, and 7% had revision surgery. Those treated with halo gravity traction or with greater postoperative C2 sagittal translation, loss of primary curve correction, and smaller preoperative proximal kyphosis had the greatest risk of developing PJK.Level of Evidence: 4.

Reprogramming Axial Level Identity to Rescue Neural-Crest-Related Congenital Heart Defects.

The cardiac neural crest arises in the hindbrain, then migrates to the heart and contributes to critical structures, including the outflow tract septum. Chick cardiac crest ablation results in failure of this septation, phenocopying the human heart defect persistent truncus arteriosus (PTA), which trunk neural crest fails to rescue. Here, we probe the molecular mechanisms underlying the cardiac crest's unique potential. Transcriptional profiling identified cardiac-crest-specific transcription factors, with single-cell RNA sequencing revealing surprising heterogeneity, including an ectomesenchymal subpopulation within the early migrating population. Loss-of-function analyses uncovered a transcriptional subcircuit, comprised of Tgif1, Ets1, and Sox8, critical for cardiac neural crest and heart development. Importantly, ectopic expression of this subcircuit was sufficient to imbue trunk crest with the ability to rescue PTA after cardiac crest ablation. Together, our results reveal a transcriptional program sufficient to confer cardiac potential onto trunk neural crest cells, thus implicating new genes in cardiovascular birth defects.

Internal Maxillary to Middle Cerebral Artery Bypass Using an Anterior Tibial Artery Graft, Performed Using a 3-Dimensional Exoscope: 2-Dimensional Operative Video.

Fusiform aneurysms remain challenging entities to treat, as maintenance of flow and prevention of branch occlusion are concerns. Use of endovascular stents may risk nearby branch occlusion. We present a 31-yr-old male with a prior subarachnoid hemorrhage from a left middle cerebral artery (MCA) M1 aneurysm. Informed consent for use of the operative video and information was obtained from the patient. Initially, open clipping was performed with noted residual because of risk of nearby branches. On angiography, a growing fusiform segment distal to the initial aneurysm was noted. The patient was referred to our institution for this finding, and a multidisciplinary team reviewed the case. Endovascular treatment was felt to be risky, as stenting could jail nearby MCA branches. Clipping would also risk occlusion because of scaring from previous hemorrhage. Sufficient flow would be needed, and because the ipsilateral superficial temporal artery was sacrificed in the initial craniotomy, the internal maxillary artery (IMAX) was chosen as the bypass source. A cerebrovascular neurosurgeon, skull base otolaryngologist, and vascular surgeon worked together to perform a left-side IMAX to MCA bypass using an anterior tibial artery graft under 3-dimensional exoscopic visualization. Specifically, a 9-0 nylon suture on a BV-130 needle along with straight and tying forceps were used along with heparinized saline. The bypass was noted to be of robust flow, and the patient did very well on postoperative follow-up. The utilization of an anterior tibial artery graft, IMAX exposure, and corresponding bypass provides educational value, as there are only a limited number of videos on this topic.

Outcomes in the radiosurgical management of metastatic spine disease.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes. METHODS AND MATERIALS: A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response. RESULTS: Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT. CONCLUSIONS: Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.

Multiplex clonal analysis in the chick embryo using retrovirally-mediated combinatorial labeling.

Lineage analysis plays a central role in exploring the developmental potential of stem and progenitor cell populations. In higher vertebrates, a variety of techniques have been used to label individual cells or cell populations, including interspecies grafting, intracellular microinjection, and Cre-mediated recombination. However, these approaches often suffer from difficulties in progenitor cell targeting, low cellular resolution and/or ectopic labeling. To circumvent these issues, here we utilize replication incompetent avian (RIA) retroviruses to deliver combinations of fluorescent proteins into distinct cellular compartments in chick embryos. In particular, RIA-mediated lineage tracing is optimal for long term mapping of dispersing cell populations like the neural crest. Using this tool, we confirm that trunk neural crest cells are multipotent. Furthermore, our RIA vector is engineered to be fully adaptable for other purposes such as cell fate analysis, gene perturbation studies and time-lapse imaging. Taken together, we present a novel approach of multiplex lineage analysis that can be applied to normal and perturbed development of diverse cell populations in avian embryos.

Development of Proximal Junctional Kyphosis After Minimally Invasive Lateral Anterior Column Realignment for Adult Spinal Deformity.

BACKGROUND: Development of proximal junctional kyphosis (PJK) after correction of adult spinal deformity (ASD) undermines sagittal alignment. Minimally invasive anterior column realignment (ACR) is a powerful tool for correction of ASD; however, long-term PJK rates are unknown. OBJECTIVE: To characterize PJK after utilization of ACR in ASD correction. METHODS: A retrospective multi-institution cohort analysis per STROBE criteria was conducted of all patients who underwent lateral lumbar interbody fusion (LLIF) or ACR for ASD from 2010 to 2015. All patients obtained preoperative and follow-up upright radiographs, assessing spinal alignment and development of PJK. Patients without proper imaging or minimum 1-yr follow-up were excluded. RESULTS: A total of 73 of 112 patients who underwent either LLIF or ACR for ASD met inclusion criteria. Mean follow-up was 22.8 mo. There was significant improvement of all spinopelvic parameters. Overall, PJK and proximal junctional failure (PJF) rates were 20.5% and 11%, respectively. The incidence of PJK increased with greater corrective surgery (0% LLIF, 30% ACR, 42.9% ACR + posterior column osteotomy (PCO); P < .001). PJF rates increased (0% LLIF, 11% ACR, 40% ACR + PCO; P = .005). Risk factors included location of the upper-instrumented vertebra at T10-L1 vs L2-L4 (P = .007), age (P = .029), severity of ASD, and overcorrection of sagittal imbalance. CONCLUSION: The incidence of PJK after minimally invasive ACR is slightly lower than reported after open surgery but greater than in LLIF only and increases with PCO utilization. The PJK rate increases when crossing the TL junction, sagittal imbalance severity, and overcorrection. Elderly patients are at an increased risk, suggesting need for age appropriate correction goals.

Incisional Hernia After Minimally Invasive Lateral Retroperitoneal Surgery: Case Series and Review of the Literature.

BACKGROUND: Minimally invasive lateral retroperitoneal (lateral-MIS) approaches to the spine involve traversing the lateral abdominal wall musculature and fascia. Incisional hernia is an uncommon approach-related complication. OBJECTIVE: To review the incidence, treatment, and preventative measures of incisional hernia after lateral-MIS approaches. METHODS: This is a retrospective review of cases performed by a single surgeon from 2011 to 2016. All patients who underwent lateral-MIS approaches at this institution were included. Patients with a postoperative diagnosis of lateral hernia on physical exam and corroborating advanced imaging findings were included in this study. Cases of flank bulge due to peripheral nerve injury were excluded. RESULTS: Three-hundred three patients underwent lateral-MIS approaches to the spine. Three (1%) patients with incisional hernia were identified. Two patients presented with a clinically symptomatic incisional hernia, while 1 patient was diagnosed incidentally after a routine abdominal magnetic resonance imaging for an unrelated reason. No patients suffered bowel entrapment or strangulation. CONCLUSION: Incisional hernia after lateral-MIS approaches is rare. Patients with incisional hernias may be susceptible to bowel incarceration and ischemia, though the incidence of this is probably low. Meticulous closure of the fascia is critical to avoiding this complication.

Minimally Invasive Lateral Transpsoas Interbody Fusion at the L4/5 Level: A Review of 61 Consecutive Cases.

BACKGROUND: Reported complication rates for minimally invasive lateral transpsoas interbody fusion (MIS-LIF) vary widely. The risk of lumbar plexus injury is particularly concerning at the L4-5 disc space. We report our experience with MIS-LIF at L4-5, and discuss the risk profile of transpsoas approaches at this level. OBJECTIVE: To evaluate safety of MIS-LIF at the L4/5 level. METHODS: This was a retrospective, IRB-approved cohort study performed at a single institution from 2011 to 2016. Patients who underwent MIS-LIF at L4-5 were included. Patients with multilevel fusions were excluded. We analyzed postoperative sensory and motor deficits, the date of resolution, health-related quality-of-life scores, and rate of fusion. RESULTS: Over a 5-yr period, 303 patients underwent MIS-LIF at our institution. Sixty-one patients had surgery only at the L4-5 level (20.1%). Twelve of these patients (19.6%) had postoperative neurological deficits including 2 motor deficits (2/61 = 3.2%) and 11/61 (18%) sensory deficits. At 12-mo follow-up, 3 of the deficits persisted for a long-term complication rate of 3/61 (4.9%), motor complication 2/61 (3.2%). Hospital stay and follow-up averaged 2.1 d and 15 mo. Average Oswestry Disability Index improved from 51.1 to 31.1 (P < .00001). Visual Analog Scale (VAS) improved from 7.4 to 3.9 (P < .016). There were no reoperations secondary to hardware failure or pseudoarthrosis. Fusion rate was 89% at 12 mo. CONCLUSION: MIS-LIF is a safe and effective approach for interbody fusion at L4-5 with low rate of lumbar plexus injury. Most immediate postoperative deficits will resolve over time.

Perioperative complications and risk factors in neuromuscular scoliosis surgery.

OBJECTIVE High rates of perioperative complications are associated with deformity correction in neuromuscular scoliosis. The current study aimed to evaluate complications associated with surgical correction of neuromuscular scoliosis and to characterize potential risk factors. METHODS Data were retrospectively collected from a single-center cohort of 102 consecutive patients who underwent spinal fusions for neuromuscular scoliosis between January 2008 and December 2016 and who had a minimum of 6 months of follow-up. A subgroup analysis was performed on data from patients who had at least 2 years of follow-up. Univariate and multivariate regression analyses, as well as binary correlational models and Student t-tests, were employed for further statistical analysis. RESULTS The present cohort had 53 boys and 49 girls with a mean age at surgery of 14.0 years (± 2.7 SD, range 7.5-19.5 years). The most prevalent diagnoses were cerebral palsy (26.5%), spinal cord injury (24.5%), and neurofibromatosis (10.8%). Analysis reflected an overall perioperative complication rate of 27% (37 complications in 27 patients), 81.1% of which constituted major complications (n = 30) compared to a rate of 18.9% for minor complications (n = 7). Complications were predicted by nonambulatory status (p = 0.037), increased intraoperative blood loss (p = 0.012), increased intraoperative time (p = 0.046), greater pelvic obliquity at follow-up (p = 0.028), and greater magnitude of sagittal profile at follow-up (p = 0.048). Pulmonary comorbidity (p = 0.001), previous operations (p = 0.013), history of seizures (p = 0.046), diagnosis of myelomeningocele (p = 0.046), increase in weight postoperatively (p < 0.005), and increased lumbar lordosis at follow-up (p = 0.015) were identified as risk factors for perioperative infection. CONCLUSIONS These results suggest that in neuromuscular scoliosis, patients with preexisting pulmonary compromise and greater intraoperative blood loss have the greatest risk of experiencing a major perioperative complication following surgical deformity correction.

Laser interstitial thermal therapy: A first line treatment for seizures due to hypothalamic hamartoma?

Successful treatment of hypothalamic hamartoma (HH) can result in the resolution of its sequelae including epilepsy and rage attacks. Risks and morbidity of open surgical management of this lesion have motivated the development of laser interstitial thermal therapy (LITT) as a less invasive treatment approach to the disease. Although overall morbidity and risk would appear to be lower, complications related to LITT therapy have been reported, and the longer-term follow-up that is now possible after initial experience helps address the question of whether LITT provides equivalent efficacy compared to other treatment options. We conducted a retrospective analysis of clinical outcomes in eight patients undergoing LITT for HH at our center using the Visualase/Medtronic device. Five patients had refractory epilepsy, one had rage attacks, and two had both. We also compared the published seizure-free outcomes over time and the complication rates for different interventional approaches to the treatment of epilepsy due to HH including open craniotomy, neuroendoscopic, radiosurgical, and radiofrequency approaches. With a mean follow-up of 19.1 months in our series of eight patients, six of seven epilepsy patients achieved seizure freedom, whereas the one patient with rage attacks only did not have improvement of his symptoms. A length of hospital stay of 2.6 days reflects low morbidity and rapid postoperative recuperation with LITT. Considering other reported series and case reports, the overall published seizure freedom rate of 21 of 25 patients is superior to published outcomes of HH cases treated by stereotactic radiosurgery (SRS), craniotomy, or neuroendoscopy, and comparable to radiofrequency ablation. The cumulative experience of our center with other published series supports relatively lower operative morbidity than more invasive approaches and efficacy that is as good or better than open craniotomy procedures and SRS. Although morbidity appears to be lower than other open approaches, complications related to LITT and their avoidance should be considered carefully.

Effects of hookah smoking on indoor air quality in homes.

INTRODUCTION: Hookahs (water pipes) are rapidly increasing in popularity worldwide. Evidence suggests that although perceived as safer than cigarette smoke, hookah smoke may be as, or even more, dangerous as cigarette smoke. METHODS: Air samples from 33 homes-11 where only hookah-smoking occurred, 12 with only cigarettes and 10 with no smoking-were collected to analyse concentrations of particulate matter (PM2.5), black carbon, elemental and organic carbon and carbon monoxide (CO). Air quality was assessed in rooms where smoking occurred and in an adjacent room. RESULTS: Hookah and cigarette smoking impaired home air quality. The rooms in which hookahs were smoked showed the highest concentrations for all pollutants. CO was significantly greater in the rooms where hookahs were smoked than in the cigarette-smoking rooms and the non-smoking households (p<0.05). In addition, CO levels in the rooms adjacent to where hookah was smoked were 2.5-fold to 4-fold greater than those in the smoking and non-smoking rooms of the cigarette homes (p<0.05). PM2.5 levels were also elevated in hookah homes compared to cigarette and non-smoking homes, although not significantly different. CONCLUSIONS: This study, the first of its kind, demonstrates potentially hazardous levels of home air pollution in rooms where hookahs are being smoked as well as in adjacent rooms. These levels were greater than those in cigarette smoking homes, raising concerns about potential negative health effects on all individuals living in homes where hookahs are smoked.

Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II.

BACKGROUND: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare. CASE DESCRIPTION: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. DESCRIPTION: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. CONCLUSION: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis.