Andrew Kim

Identification of Retinol Binding Protein 1 Promoter Hypermethylation in Isocitrate Dehydrogenase 1 and 2 Mutant Gliomas

BACKGROUND Mutations in isocitrate dehydrogenase 1 (IDH1) and associated CpG island hypermethylation represent early events in the development of low-grade gliomas and secondary glioblastomas. To identify candidate tumor suppressor genes whose promoter methylation may contribute to gliomagenesis, we compared methylation profiles of IDH1 mutant (MUT) and IDH1 wild-type (WT) tumors using massively parallel reduced representation bisulfite sequencing. METHODS Reduced representation bisulfite sequencing was performed on ten pathologically matched WT and MUT glioma samples and compared with data from a methylation-sensitive restriction enzyme technique and data from The Cancer Genome Atlas (TCGA). Methylation in the gene retinol-binding protein 1 (RBP1) was identified in IDH1 mutant tumors and further analyzed with primer-based bisulfite sequencing. Correlation between IDH1/IDH2 mutation status and RBP1 methylation was evaluated with Spearman correlation. Survival data were collected retrospectively and analyzed with Kaplan-Meier and Cox proportional hazards analysis. All statistical tests were two-sided. RESULTS Methylome analysis identified coordinated CpG island hypermethylation in IDH1 MUT gliomas, consistent with previous reports. RBP1, important in retinoic acid metabolism, was found to be hypermethylated in 76 of 79 IDH1 MUT, 3 of 3 IDH2 MUT, and 0 of 116 IDH1/IDH2 WT tumors. IDH1/IDH2 mutation was highly correlated with RBP1 hypermethylation (n = 198; Spearman R = 0.94, 95% confidence interval = 0.92 to 0.95, P < .001). The Cancer Genome Atlas showed IDH1 MUT tumors (n = 23) to be RBP1-hypermethylated with decreased RBP1 expression compared with WT tumors (n = 124). Among patients with primary glioblastoma, patients with RBP1-unmethylated tumors (n = 102) had decreased median overall survival compared with patients with RBP1-methylated tumors (n = 22) (20.3 months vs 36.8 months, respectively; hazard ratio of death = 2.48, 95% confidence interval = 1.30 to 4.75, P = .006). CONCLUSION RBP1 promoter hypermethylation is found in nearly all IDH1 and IDH2 mutant gliomas and is associated with improved patient survival. Because RBP1 is involved in retinoic acid synthesis, our results suggest that dysregulation of retinoic acid metabolism may contribute to glioma formation along the IDH1/IDH2-mutant pathway.

Simultaneous sinus lift and implant installation: prospective study of consecutive two hundred seventeen sinus lift and four hundred sixty-two implants.

PURPOSE If less than 4 mm of residual bone is remained in posterior maxilla, two-stage operation is recommended for implant installation. However, if primary stability could be obtained using tapered designed implants, one-stage surgery could be performed with reliable success rate in severely resorbed maxilla. The purpose of this prospective study was to evaluate survival and success rates of the implants simultaneously placed into grafted sinus using rough-surfaced implant. MATERIALS AND METHODS A total of two hundred seventeen consecutive sinus lifting through lateral approach and four hundred sixty-two simultaneous implants were installed from November 2003 for 5.5 years. Xenogenic bone was used solely for bone graft materials. Second surgery was performed around 6 months after operation and porcelain fused metal or gold crown was used for definitive restorations. Cumulative survival and success rates were evaluated according to residual alveolar bone height (RABH), smoking status, and Schneiderian membrane perforation. RESULTS The mean follow-up was 57.1 ± 15.6 (36-98) months. Of the four hundred sixty-two implants, two hundred sixty-two implants (56.7%: group 1) were installed in posterior maxilla less than 4-mm RABH and two hundred implants (43.3%: group 2) were placed in over 5-mm RABH. The cumulative survival and success rates were 98.91% and 96.54%. There was no statistically significant difference in success rate between group 1 and group 2 (p = .3135). Perforation of the membrane was not related to success (p = .7162), but smoking status is significantly related with implant failure (p = .0003). CONCLUSIONS Sinus lifting with simultaneous implant placement could be used to treat atrophic maxilla in patients with minimal RABH when initial stability could be obtained by using taper designed implants with surgical techniques. Smoking is a possible factor for implant failure. Membrane perforation did not have an adverse effect on implant success if the membrane was repaired with absorbable membrane and fibrin glue.

Abruptly attenuated terminal ictal pattern in pediatrics.

Purpose: We examined the ictal discharges at the end of pediatric seizures and categorized the various patterns. One particular pattern, termed “abruptly attenuated termination” was studied in detail. Methods: Ictal segments captured on video-EEG monitoring during a 26-month interval were analyzed for a variety of ictal termination patterns, including one that we rigorously defined as abruptly attenuated termination pattern (AAT). We studied the associations between AAT and the other ictal EEG and clinical features. Results: AAT was noted in 16 of 200 (8%) pediatric seizures. All 16 were immediately preceded by repetitive spikes or spike-waves. The presence of AAT also correlated with ictal spread pattern, initial ictal pattern, laterality of onset, seizure duration, age, and epilepsy etiology. AAT is more often noted in children older than 6 months and in children with idiopathic or cryptogenic forms of epilepsy. Conclusions: The minority of pediatric seizures recorded in a tertiary epilepsy monitoring unit end with diffuse, synchronized abrupt attenuation. AAT probably is the result of an active process that is developmentally related. It appears to require some degree of mature and intact neurophysiology and may involve the thalamocortical circuit.

Immediate free iliac bone graft after nonsegmental mandibular resection and delayed implant placement: a case series.

Background:Resection of mandibular tumors without proper reconstruction may lead to unfavorable esthetic and function results. The purpose of this case series was to describe clinical results and a technique to prevent tissue loss using nonvascular iliac grafts immediately following tumor resection and long-term stability of the implants. Materials and Methods:Three female patients presented with oral neoplasms (2 ameloblastoma and 1 ossifying fibroma). The mandibular reconstruction was performed with nonvascularized iliac grafts simultaneous with tumor removal. Subsequently, 10 dental implants were placed 6 to 9 months after reconstruction and restored. Survival and success of the implants were evaluated. Results:Marginal mandibulectomy in 1 patient and buccal bone resection in 2 patients was performed; the resection sites were reconstructed with an immediate nonvascularized iliac graft. All implants survived and were successful during follow-up periods between 44 and 105 months. Mean marginal bone loss of 10 implants was 0.09 mm. Conclusions:Immediate reconstruction with nonvascularized iliac grafts following tumor resection may be a viable treatment option for nonsegmental inlay osseous defects. In these case series, the resorption of the iliac bone was minimal after 6 to 9 months consolidation periods.

Subapical osteotomy to correct dental implant malpositioning and vertical ridge deficiency: A clinical report

This clinical report describes a subapical osteotomy to correct vertical ridge deficiency and malpositioned maxillary anterior implants. A 37-year-old woman with a noncontributory medical history presented with the chief complaint of an unesthetic implant-supported prosthesis. The maxillary left central and lateral incisors were restored with metal ceramic restorations. Gingiva-colored porcelain was fabricated to compensate for severe vertical and horizontal soft tissue deficiency. The patient was dissatisfied with the esthetics associated with the restorations and soft tissues since she presented with a high smile line and gingival display. Under general anesthesia, a subapical osteotomy was performed. The implant and ridge segment was coronally repositioned to correct the ridge deficiency. The surgical procedure and postoperative healing were uneventful. The surgical outcome was stable for a follow-up period of 3 years. The subapical osteotomy provided a satisfactory clinical outcome in managing a severely deficient residual ridge and malpositioned maxillary anterior implants as an alternative treatment to other surgical approaches.

[Not Quite] The Ketogenic Diet in a Pill

Researchers at Okayama University, Japan showed lactate dehydrogenase (LDH) inhibition suppresses neuronal excitation in vitro, reduces EEG discharges and seizures in rodent models, and may provide a novel mechanism for anticonvulsant medications in human patients.

A practical, simple, and useful method of categorizing interictal EEG features in children

We introduce a simple scheme of categorizing interictal EEG in patients with pediatric epilepsy. Five patterns of EEG can be determined by using 2 interictal EEG domains: organization of the background activity and a morphology/topography of epileptiform discharges. These patterns relate to commonly recognized categories of pediatric epilepsy: familial epilepsies, genetic generalized epilepsies, self-limited epilepsies, epilepsies with encephalopathy, and focal structural epilepsies. Each group has distinguishable clinical presentations, inheritance patterns, and outcomes. This categorization may be a useful educational tool; it may also guide decisions about further testing and management.

Endoscopic removal of an aspirated healing abutment and screwdriver under conscious sedation.

Purpose:Aspiration of foreign bodies during dental treatment is a medical emergency that requires prompt removal. In this study, aspiration of screwdriver and healing abutment is reported with literature review. Materials and Methods:A 26-year-old male patient was referred from a local dental clinic with the suspicion of ingestion of a screwdriver and healing abutment during the second-stage surgery. The patient reported symptoms including dyspnea, cough, and foreign body sensation. On the chest radiograph, a radiopaque foreign body resembling the screwdriver and healing abutment was observed at the right mid lung. Results:Bronchoscopic examination using flexible cable was performed under conscious sedation, and microforceps were used to remove the instruments. Aspirated screwdriver and healing abutment were removed safely under intravenous sedation. The patient did not have any symptoms associated with lung aspiration after removal of the foreign body during follow-up periods. Conclusion:Bronchoscopic removal is the most recommended procedure for removal of the aspirated foreign body. This can be performed under conscious sedation. Precautions, such as tethering the screwdriver, are recommended during implant procedures.

Extending high-frequency oscillation analysis to pediatric electrocorticography: Ripple effect

Pediatric epilepsy surgery often can be performed successfully without invasive monitoring to define the epileptic zone. For example, candidates for certain procedures like hemispherectomy or corpus callosotomy usually do not require investigations with invasive electrodes or intraoperative electrocorticography (ECoG); similarly, children with mesial temporal sclerosis may not need invasive monitoring, particularly if there is no sign of cortical dysplasia.1 Children with other forms of focal lesions present different challenges. Pediatric surgical series show that the most common pathology is focal cortical dysplasia2 and the exact extent of the lesion is not always apparent on imaging. Some centers, including our own, prefer single-stage resections with ECoG guidance to prolonged recordings using intracranial electrodes, particularly in those patients with congruent noninvasive findings implicating a discrete focus. The seizure focus can be noninvasively localized from multiple sources including ictal EEG, interictal EEG, seizure semiology, MRI, SPECT, PET, and magnetoencephalography. …

Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma: Imaging characteristics and clinical outcomes

No guidelines exist for the management of pulmonary nodules in patients with hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation. The 172 patients with HCC who were listed for liver transplant at our institution received both pretransplant chest computed tomography (CT) and follow‐up CT. Pulmonary nodules on CT were characterized and followed on subsequent scans by a blinded radiologist, with a consensus review with a second radiologist being performed for equivocal cases. Nodule characteristics and outcomes were examined with chi‐square tests, and the posttransplant survival of patients with different nodule outcomes was compared. Cumulative probabilities of waiting‐list removal for nontransplant patients and cumulative probabilities of undergoing transplantation for all patients were also compared between patients with and without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules represented HCC metastases, 1.0% represented other bronchopulmonary malignancies, and 2.7% represented infections. None of the malignant nodules exhibited a triangular/lentiform shape or calcifications. There were no statistically significant differences in pulmonary nodule outcomes between patients who underwent transplantation and those who did not undergo transplantation. No significant differences in posttransplant survival were found between patients with different nodule outcomes. There was also no significant difference between patients with and without nodules in the cumulative probabilities of waiting‐list removal. However, the cumulative probability of undergoing liver transplantation was borderline significantly higher in patients without pulmonary nodules. In conclusion, despite the low prevalence of malignant nodules, all pulmonary nodules besides triangular/lentiform‐shaped or calcified nodules should be followed with serial CT while the patient is on the transplant list, with biopsy performed for new and/or enlarged nodules. Both malignancy and active infection must be excluded when one is confronted with enlarged pulmonary nodules. Clinicians should also be aware of the possibility of reactivation of a granulomatous infection after transplantation. Liver Transpl 21:1169–1178, 2015.