Personality dimensions, depression, and eating behavior in individuals seeking bariatric surgery: a cluster analysis.

Introduction: Psychiatric comorbidity is frequent in bariatric surgery candidates. This study aimed to classify bariatric surgery patients according to patterns of preoperative measures of the severity of the eating disorder (ED), depression, and personality traits. Methods: In the present cross-sectional study, 115 adult candidates for bariatric surgery (75 females, 65.22% of sample; mean age 37) were considered for analysis. Patients' sociodemographic and psychopathological variables were collected. K-Means clustering analysis was adopted to classify bariatric surgery candidates according to their preoperative Eating Disorder Inventory-2 (EDI-2) scores. In addition, we assessed depression and personality traits using the Beck Depression Inventory-2 (BDI-2) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: Cluster analysis based on EDI-2 revealed two preoperative patterns: higher severity (n = 39), and low severity (n = 76). The more severe EDI-2 group had higher scores on the BDI-2 and presented higher scores on several MMPI-2 dimensions, particularly those related to anxiety (Psychasthenia, Anxiety, Fears, Obsessiveness), depression (Depression, including both content and clinical MMPI-2 subscales), externalizing symptoms (Anger, Cynicism, Type A Behavior), and social functioning (Social Introversion, Family Problems, Work Interference). Discussion: Eating disorders symptoms in candidates for bariatric surgery are closely related to depression and different psychological conditions assessed with MMPI-2. These psychological variables should be evaluated preoperatively and targeted with more specific psychological interventions.

Safety of An Enhanced Recovery After Surgery Protocol After Head and Neck Free Tissue Transfer.

OBJECTIVES: Implementing enhanced recovery after surgery (ERAS) protocols and decreasing length of stay (LOS) have become a priority for major surgeries, including microvascular free tissue transfer (MVFTT) reconstruction of the head and neck. We describe an ERAS protocol with the goal to further reduce length of stay beyond national medians. METHODS: Retrospective chart review between August 2016 and February 2023, including all patients who underwent MVFTT after oral cavity, skull base, salivary gland, and cutaneous ablative surgery. An ERAS protocol was implemented in March 2020. RESULTS: A total of 383 patients were included. Approximately 59.8% underwent oral cavity MVFTT, 34.5% cutaneous and lateral skull base, and 5.8% maxillary and anterior skull base. A total of 209 (54.7%) patients had surgery prior to implementation of the ERAS protocol and 174 (45.3%) after. Median LOS decreased from 9 days (interquartile interval [IQR] 8-11) to 6 (IQR 5-7.5, p < 0.0001) following oral cavity MVFTT. For cutaneous and lateral skull base reconstruction, median LOS decreased from 6 days (IQR 5-8) to 3 (IQR 3-7, p < 0.0001). For anterior skull base and sinonasal MVFTT, median LOS decreased from 8 (IQR 7-9) to 5 days (IQR 4.5-7, p = 0.0005). Rate of discharge to skilled nursing or subacute rehabilitation facilities decreased (24% before ERAS, 9.2% after, p < 0.0001). Thirty-day readmission rate was similar before and after implementation (10.5% vs. 10.3, p = 0.954). Discharge to facility was associated with readmission (OR 2.34, 95% CI 1.12-4.89, p = 0.024). CONCLUSION AND RELEVANCE: Implementation of the ERAS protocol was associated with decreased LOS. There was no increase in rate of readmission. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Table Correction: Effectiveness of eHealth Smoking Cessation Interventions: Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/45111.].

Perforator-based chimeric ulnar forearm microvascular free tissue transfer reconstruction of post-radiated tracheoesophageal puncture fistulae.

Tracheoesophageal puncture (TEP) performed during total laryngectomy in the primary treatment of laryngeal cancer is the standard method for voice restoration. Following adjuvant radiotherapy, the TEP site can experience complications resulting in a tracheoesophageal fistula (TEF) with chronic leakage making oral alimentation unsafe due to aspiration. Here, we describe a technique using chimeric ulnar artery perforator forearm free flaps (UAPFF) in the reconstruction of these complex deformities. Four patients underwent chimeric UAPFF reconstruction of TEP site TEFs following primary TL with TEP and adjuvant radiotherapy. No flap failures or surgical complications occurred. Average time from end of radiotherapy to persistent TEF was 66 months (range 4-190 months). All patients had resolution in their TEF with average time to total oral diet achievement of 22 days (14-42 days). Chimeric UAPFF reconstruction is a safe and effective method to reconstruct recalcitrant TEP site TEFs.

Outcomes of Head and Neck Microvascular Free Tissue Transfer for Advanced Cutaneous Squamous Cell Carcinoma: A Comparison of Solid Organ Transplant Recipients to Nontransplant Patients.

BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.

Neighborhood socioeconomic status and race are associated with incidence disparities in oral cavity cancers.

OBJECTIVES: To determine the association between neighborhood socioeconomic status (nSES), race and incidence rate trends of oral cavity cancer (OCC). MATERIALS AND METHODS: We used data from the SEER (Surveillance, Epidemiology, and End Results) 18 Census Tract-level SES and Rurality Database (2006-2018) database of the National Cancer Institute to create cohorts of OCC patients between 2006 and 2018. Annual incidence rates were calculated and trends in rates were estimated using joinpoints regression. RESULTS: The incidence of OCC is the highest among low nSES White Americans (2.86 per 100 000 persons) and the lowest among high nSES Black Americans (1.17 per 100 000 persons). Incidence has significantly increased among Asian Americans (annual percent change [APC]: low nSES-2.4, high nSES-2.6) and White Americans (APC: low nSES-1.4, high nSES-1.6). Significant increases in the incidence of oral tongue cancer in these groups primarily drive this increase. Other increases were noted in alveolar ridge cancer among White Americans and hard palate cancer among Asian Americans. OCC incidence decreased significantly in Hispanic Americans of high nSES (APC: -2.5) and Black Americans of low nSES (APC: -2.7). Floor of mouth cancer incidence decreased among most groups. CONCLUSION: Despite the overall decreasing incidence of OCC, these trends are inconsistent among all OCC subsites. Differences are seen by race, nSES, and subsite, indicating intersectional barriers that extend beyond nSES and race and ethnicity alone. Further research on risk factors and developing interventions targeting vulnerable groups is needed.

Effectiveness of eHealth Smoking Cessation Interventions: Systematic Review and Meta-Analysis.

BACKGROUND: Rapid advancements in eHealth and mobile health (mHealth) technologies have driven researchers to design and evaluate numerous technology-based interventions to promote smoking cessation. The evolving nature of cessation interventions emphasizes a strong need for knowledge synthesis. OBJECTIVE: This systematic review and meta-analysis aimed to summarize recent evidence from randomized controlled trials regarding the effectiveness of eHealth-based smoking cessation interventions in promoting abstinence and assess nonabstinence outcome indicators, such as cigarette consumption and user satisfaction, via narrative synthesis. METHODS: We searched for studies published in English between 2017 and June 30, 2022, in 4 databases: PubMed (including MEDLINE), PsycINFO, Embase, and Cochrane Library. Two independent reviewers performed study screening, data extraction, and quality assessment based on the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. We pooled comparable studies based on the population, follow-up time, intervention, and control characteristics. Two researchers performed an independent meta-analysis on smoking abstinence using the Sidik-Jonkman random-effects model and log risk ratio (RR) as the effect measurement. For studies not included in the meta-analysis, the outcomes were narratively synthesized. RESULTS: A total of 464 studies were identified through an initial database search after removing duplicates. Following screening and full-text assessments, we deemed 39 studies (n=37,341 participants) eligible for this review. Of these, 28 studies were shortlisted for meta-analysis. According to the meta-analysis, SMS or app text messaging can significantly increase both short-term (3 months) abstinence (log RR=0.50, 95% CI 0.25-0.75; I2=0.72%) and long-term (6 months) abstinence (log RR=0.77, 95% CI 0.49-1.04; I2=8.65%), relative to minimal cessation support. The frequency of texting did not significantly influence treatment outcomes. mHealth apps may significantly increase abstinence in the short term (log RR=0.76, 95% CI 0.09-1.42; I2=88.02%) but not in the long term (log RR=0.15, 95% CI -0.18 to 0.48; I2=80.06%), in contrast to less intensive cessation support. In addition, personalized or interactive interventions showed a moderate increase in cessation for both the short term (log RR=0.62, 95% CI 0.30-0.94; I2=66.50%) and long term (log RR=0.28, 95% CI 0.04-0.53; I2=73.42%). In contrast, studies without any personalized or interactive features had no significant impact. Finally, the treatment effect was similar between trials that used biochemically verified or self-reported abstinence. Among studies reporting outcomes besides abstinence (n=20), a total of 11 studies reported significantly improved nonabstinence outcomes in cigarette consumption (3/14, 21%) or user satisfaction (8/19, 42%). CONCLUSIONS: Our review of 39 randomized controlled trials found that recent eHealth interventions might promote smoking cessation, with mHealth being the dominant approach. Despite their success, the effectiveness of such interventions may diminish with time. The design of more personalized interventions could potentially benefit future studies. TRIAL REGISTRATION: PROSPERO CRD42022347104; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=347104.

Incidence of Post-denosumab Rebound Hypercalcaemia in Bony-Metastatic Breast Cancer.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation.

Safety of microvascular free tissue transfer reconstruction of the head and neck in the setting of chronic pharmacologic immunosuppression.

BACKGROUND: Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population. METHODS: Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020. RESULTS: Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%. CONCLUSIONS: MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression.

Pitfalls and progress in adrenocortical carcinoma diagnosis: the utility of a multidisciplinary approach, immunohistochemistry and genomics.

SUMMARY: Adrenocortical carcinoma is a rare disease with poor prognosis whose clinical heterogeneity can at times present a challenge to accurate and timely diagnosis. We present the case of a patient who presented with extensive pulmonary lesions, mediastinal and hilar lymphadenopathy and an adrenal mass in whom the oncological diagnosis was initially uncertain. Through the use of immunohistochemistry, biochemistry and genomic testing, an accurate diagnosis of adrenocortical carcinoma was ultimately made which resulted in more directed treatment being administered. The use of multidisciplinary input and genomics to aid in diagnosis and prognosis of adrenocortical carcinoma is discussed. LEARNING POINTS: Adrenocortical carcinomas can present a diagnostic challenge to clinicians given it is a rare malignancy with significant clinical heterogeneity. Specialist multidisciplinary team input is vital in the diagnosis and management of adrenocortical carcinomas. Hormonal testing is recommended in the diagnostic workup of adrenal masses, even in the absence of overt clinical signs/symptoms of hormone excess. Immunostaining for the highly sensitive and specific steroidogenic factor-1 is vital for accurate diagnosis. Genomics can provide prognostic utility in management of adrenocortical carcinoma.

End-of-Life Care Requires Caution with Use of Continuous Glucose Monitoring.

Use of medical device technologies for diabetes mellitus, including continuous glucose monitoring devices, is becoming more frequently encountered in end-of-life care. Good communication is paramount to determine patient and carer preferences for if, when, and how blood glucose monitoring should occur in the end-of-life setting. We present two differing cases of how continuous glucose monitoring in an Australian setting impacted end-of-life care for the patients and their carers.

Pediatric Tracheal Lobular Capillary Hemangioma: A Case Report and Review of the Literature.

Chronic cough is a common complaint in the pediatric population and can have many different etiologies. We present a rare case of a tracheal lobular capillary hemangioma (LCH), also known as pyogenic granuloma, causing chronic cough in a child. In this case, the tracheal LCH was managed successfully with laser ablation. A review of the literature reveals only 2 other reported pediatric cases of tracheal LCH. Laryngoscope, 131:1729-1731, 2021.

Effects of repetitive hyperbaric oxygen therapy on neuroprotection in middle cerebral artery occlusion rats.

Hyperbaric oxygen (HBO) has been suggested as a possible therapy for brain injury. However, the effects of HBO after transient brain ischemia are inconsistent and the underlying mechanisms are not fully known. The present study aimed to investigate the effects of repetitive HBO intervention in a transient middle cerebral artery occlusion (MCAO) animal model. Seventy-two Sprague-Dawley rats received MCAO and were randomly assigned to normal air control or HBO intervention groups. Each group was divided into 3 subgroups according to the intervention time period (7, 14, and 21 days). HBO was started 24 h post-MCAO for 1 h/day at 3.0 ATA with no-air breaks. After the final intervention, half of the rats in each subgroup were sacrificed and the right motor cortex was removed to examine levels of Akt phosphorylation and glutathione (GSH), as well as glutathione peroxidase (GPx) and reductase (GR) activity. The other half of the rats were used to examine infarct volume. At 24 h post-MCAO and the end of the final intervention, rats underwent tests to examine motor performance. We noted that 14- and 21-day HBO interventions significantly reduced infarct volume and increased Akt phosphorylation and GSH levels and GPx and GR activity. Motor performance was also significantly improved after 14- and 21-day interventions. No significant differences were observed between the controls and 7-day intervention groups. Repetitive HBO intervention starting 24 h post-MCAO and applied for at least 14 days, provided neuroprotective effects through modulating the cell survival pathway and antioxidative defense system.

Arrhythmogenic Right Ventricular Cardiomyopathy: A Review of Living and Deceased Probands.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially life-threatening genetic cardiomyopathy with a spectrum of clinical presentations including sudden cardiac death (SCD). METHODS: Clinical and genetic data of 44 probands referred to a cardiac genetics clinic (2007-2017) who met 2010 Task Force Criteria (TFC) for ARVC diagnosis were included. RESULTS: Thirty-three (33) (75%) male, 20 (45%) were referred by the Victorian Institute of Forensic Medicine. Presentation that lead to diagnosis included ARVC-related SCD (n=19), SCD due to alternate cause of death (n=1), aborted cardiac arrest (n=6), stable symptomatic ventricular tachycardia (n=14), palpitations (n=3) and presyncope (n=1). Left ventricular involvement (50%) was more common in the SCD subgroup (84% vs 21%, p<0.001). Genetic testing (n=39) revealed a pathogenic mutation in 16 (commonest: plakophillin-2 (n=9)), a variant of uncertain significance (VUS) in 15, with no abnormality in eight. In the SCD subgroup, median age at death was 44.7 years and 74% were male. Genetic testing (n=16) in this subgroup revealed a pathogenic mutation in six patients (commonest: desmoplakin (n=4)). Comparison of the two commonest mutations (PKP2 and desmoplakin [DSP]) showed DSP mutation was more frequently associated with SCD (p<0.01) and LV involvement (p<0.001). Screening of 117 relatives has lead to ARVC diagnosis in 29 patients. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy has a heterogeneous and often severe clinical presentation. Sudden cardiac death and aborted cardiac arrest (ACA) are common, demonstrating electrical abnormalities appear early in the ARVC phenotype. Left ventricular involvement was common and may reflect a worse prognosis. Genetic testing is essential in family screening and may be helpful in risk assessment. Desmoplakin mutation is associated with LV involvement and may be indicative of worse prognosis and increased risk of SCD. Genetic screening of proband family members in a specialised multidisciplinary clinic is essential in early diagnosis of affected family members.

Understanding sociodemographic factors related to health outcomes in pediatric obstructive sleep apnea.

OBJECTIVES: (1) To examine relationships between socioeconomic status (SES) and successful treatment of pediatric obstructive sleep apnea (OSA) with adenotonsillectomy (T&A). (2) To explore sociodemographic factors and medical comorbidities that separate OSA and refractory OSA populations in children. METHODS: We retrospectively reviewed pediatric OSA patients (ages 0-18). Patients evaluated for OSA by pediatric otolaryngology between January 2014 and December 2015 were included. OSA was defined as requiring T&A. Refractory OSA (ROSA) was defined as recurring, polysomnography-proven, OSA after T&A, ultimately requiring another intervention, such as a multi-level airway operation. Clinical data were complemented with sociodemographic data. ZIP codes were used to approximate median household income. RESULTS: Our cohort included 105 ROSA and 53 OSA patients. These patients came from similar rates of single parent households and coverage by public insurance. Median household income for OSA patients was $47,086 (IQR $36,395-$60,196), compared to $45,696 (IQR $37,669-$56,203) for ROSA patients. Over 60% of all patients fell below the national household income average. Nearly half of the cohort resided in the three largest metro counties closest to our institution. These patients represented higher rates of single-parent households (p = 0.045) and public insurance (p = 0.002), and trends towards lower rates of ROSA (p = 0.138). CONCLUSION: Our results identified sociodemographic factors that may influence healthcare compliance and subsequently overall health outcomes. We identified no statistically significant difference in measures of SES between patients with refractory vs non-refractory OSA. Patients living closest to our medical center had lowest rates of ROSA, suggesting that access to care may affect outcomes of pediatric OSA.

Tumor Progression Following Petroclival Meningioma Subtotal Resection: A Volumetric Study.

BACKGROUND: One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. OBJECTIVE: To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. METHODS: Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as "tumor growth." RESULTS: Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm3/yr (range -0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. CONCLUSION: The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.

The Natural History of Petroclival Meningiomas: A Volumetric Study.

OBJECTIVES: This study characterizes primary petroclival meningioma growth rates, before intervention, using volumetric analysis. In addition, predictors of growth are analyzed. METHODS: Patients with previously untreated petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was used to perform volumetric analyses of tumor size and growth. Three-dimensional segmentation volumetric analyses were compared with volumes estimated utilizing three orthogonal dimensions. Tumor growth was defined as a 15% increase in volume. RESULTS: Thirty-four patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention were included. The mean age was 55.2 years, and 65.7% were women. The mean tumor volume at presentation was 5.6 cm (range, 0.1-25.8 cm) as determined from segmentation volumetric analysis. At a mean follow-up of 44.5 months (range, 3.7-125.1 mo), 88.2% of tumors grew. The mean annual volumetric growth rate was 2.38 cm/yr (-0.63 to 25.9 cm/yr). Tumor volume, T2 hyperintensity within the tumor, peritumoral edema, and ataxia and/or cerebellar symptoms at presentation were all significantly associated with greater rates of tumor growth. Ultimately, 10 (29.4%) patients underwent treatment during the follow-up period. CONCLUSION: Our experience demonstrates that the vast majority (88%) of untreated petroclival meningiomas grow; the mean volumetric growth rate was noted to be 2.38 cm/yr. We found a significant association between increased growth rate and larger tumor size at diagnosis, T2 hyperintensity within the tumor, peritumoral edema, and the presence of ataxia and/or cerebellar symptoms.

Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy.

Members of the AAA family of ATPases assemble into hexameric double rings and perform vital functions, yet their molecular mechanisms remain poorly understood. Here, we report structures of the Pex1/Pex6 complex; mutations in these proteins frequently cause peroxisomal diseases. The structures were determined in the presence of different nucleotides by cryo-electron microscopy. Models were generated using a computational approach that combines Monte Carlo placement of structurally homologous domains into density maps with energy minimization and refinement protocols. Pex1 and Pex6 alternate in an unprecedented hexameric double ring. Each protein has two N-terminal domains, N1 and N2, structurally related to the single N domains in p97 and N-ethylmaleimide sensitive factor (NSF); N1 of Pex1 is mobile, but the others are packed against the double ring. The N-terminal ATPase domains are inactive, forming a symmetric D1 ring, whereas the C-terminal domains are active, likely in different nucleotide states, and form an asymmetric D2 ring. These results suggest how subunit activity is coordinated and indicate striking similarities between Pex1/Pex6 and p97, supporting the hypothesis that the Pex1/Pex6 complex has a role in peroxisomal protein import analogous to p97 in ER-associated protein degradation.