Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary.

Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels.Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC.Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC.

Determining the role and responsibilities of the community epilepsy nurse in the management of epilepsy.

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.

Circulating levels of PCSK9, ANGPTL3 and Lp(a) in stage III breast cancers.

BACKGROUND / SYNOPSIS: Cholesterol and lipids play an important role in sustaining tumor growth and metastasis in a large variety of cancers. ANGPTL3 and PCSK9 modify circulating cholesterol levels, thus availability of lipids to peripheral cells. Little is known on the role, if any, of circulating lipid-related factors such as PCSK9, ANGPTL3 and lipoprotein (a) in cancers. OBJECTIVE/PURPOSE: To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. METHODS: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n = 9) or benign (n = 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. RESULTS: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 ± 27.1 ng/mL vs. 78.5 ± 19.3 ng/mL, p < 0.05, n = 14). Moreover, PCSK9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho = 0.34, p < 0.05, n = 46). In contrast, ANGPTL3 and Lp(a) plasma levels did not display any association with breast disease status and lipids did not correlate with disease severity. CONCLUSION: In this small cohort of 46 women, PCSK9 levels tended to increase with the severity of the breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia, and a potential role in tumor evasion, present results warrant further investigation into a possible association between PCSK9 levels and breast cancer severity in larger cohorts of women.

Janus Particle Preparation through UV-Induced Partial Photodegradation of Spin-Coated Particle Films.

Janus particles contain two or more chemical properties typically on opposing faces. With various property combinations possible, there are several potential applications, such as surfactants and drug delivery. However, scaling up the particle production process at reasonable cost is a limiting factor, and the method reported here aims to circumvent this issue. The process is based on a top-down destructive strategy that consists of two steps. Photocatalytic titanium dioxide particles prefunctionalized with a surface coating were assembled as particle films via spin-coating on a substrate. The particle films were placed directly under an ultraviolet light source, which induced the photodegradation of the surface coating only on the particle surfaces exposed to the light. The generated Janus particles were amphiphobic-amphiphilic in character. The Janus particles had a theoretical Janus balance close to ideal and remained attached at a hexane/water interface after disruption. They were able to make Pickering emulsions of water in silicone oil with a low energy input. The reported method may be easily scaled up to facilitate the production of gram-scale yields. The use of UV is clean and efficient and can be applied to semiconductor particles with surface coatings that are susceptible to photodegradation, making this method highly versatile.

Identification and referral of patients with refractory epilepsy from the primary to the tertiary care interface in New South Wales, Australia.

OBJECTIVES: This mixed-method feasibility study conducted in New South Wales (NSW), Australia, aimed to explore clinical practices around the identification of patients with refractory epilepsy and referral from primary care to Tertiary Epilepsy Centers. The perceptions of general practitioners, neurologists, and adults living with refractory epilepsy were considered. METHODS: Fifty-two data collection events were achieved through 22 semi-structured interviews with six neurologists and 12 adults who currently have, or have had refractory epilepsy, and four family members, 10 clinical observations of patient consultations and 20 surveys with general practitioners. A thematic analysis was conducted on the qualitative data alongside assessment of observational fieldnotes and survey data. FINDINGS: Two main themes emerged: 1) Patient healthcare pathways and care experiences highlighted the complex and deeply contextualized experiences of both patients and healthcare professionals, from first identification of people's seizures, in primary and community care settings, to referral to Tertiary Epilepsy Centers, shedding light on a fragmented, nonstandardized referral process, influenced by both individual and shared-care practices. 2) Factors impacting referrals and patient pathways indicated that onward referral to a Tertiary Epilepsy Center is affected by the knowledge, or the lack thereof, of healthcare professionals regarding treatment options. Barriers include limited person-centered care, shared decision-making, and refractory epilepsy education for healthcare professionals, which can delay patients' disease identification and can hinder speedy referral pathways and processes, in Australia for up to 17 years. In addition, person-centered communication around care pathways is affected by relationships between clinicians, patients, and family members. CONCLUSION: This study has identified a noticeable lack of standardized care across epilepsy-related healthcare sectors, which recognizes a need for developing and implementing clearer epilepsy-related guidelines and Continuing Professional Development in the primary and community care settings. This, however, requires greater collaboration and commitment in the primary, community, and tertiary care sectors to address the ongoing misconceptions around professional roles and responsibilities to optimize shared-care practices. Ultimately, prioritizing person-centered care on both patients' and professionals' agendas, in order to improve satisfaction with care experiences of people living with complex epilepsy.

Evaluation of liver parenchyma stiffness in patients with liver tumours: optimal strategy for shear wave elastography.

OBJECTIVES: To determine the methodology of non-invasive test for evaluation of liver stiffness (LS) with tumours using two-dimensional (2D) shear wave elastography (SWE). METHODS: One hundred and twenty-seven patients with liver tumours underwent 2D-SWE before surgery to measure liver and spleen stiffness (SS). Two-dimensional SWE values were obtained in the liver at 0-1 cm, 1-2 cm and >2 cm from the tumour edge (PLS-1, PLS-2 and RLS, respectively). The influence of tumour-associated factors was evaluated. The area under the receiver operating characteristic curve (AUC) for each value was analysed to diagnose cirrhosis. RESULTS: PLS-1 was higher than PLS-2, which was even higher than RLS (p < 0.001). The AUCs of PLS-1, PLS-2, RLS and SS for diagnosing cirrhosis were 0.760, 0.833, 0.940 and 0.676, with the specificity of 75.7%, 67.6%, 90.3% and 77.4%, respectively. Tumour sizes, locations or types showed no apparent influence on 2D-SWE values except for RLS, which was higher in patients with primary hepatic carcinomas (p < 0.05). CONCLUSIONS: LS with tumours is best measured at >2 cm away from the tumour edge. SS measurement could be used as an alternative to LS measurement in the event of no available liver for detection. KEY POINTS: • Tumour-associated factors impact background liver stiffness assessment. • Background liver stiffness is best measured at >2 cm from tumour edge. • Spleen stiffness can be an alternative to assess background liver stiffness.

Assessing the readability, quality and accuracy of online health information for patients with low anterior resection syndrome following surgery for rectal cancer.

AIM: Management of low anterior resection syndrome (LARS) requires a high degree of patient engagement. This process may be facilitated by online health-related information and education. The aim of this study was to systematically review current online health information on LARS. METHOD: An online search of Google, Yahoo and Bing was performed using the search terms 'low anterior/anterior resection syndrome' and 'bowel function/movements after rectal cancer surgery'. Websites were assessed for readability (eight standardized tests), suitability (using the Suitability Assessment of Materials instrument), quality (the DISCERN instrument), accuracy and content (using a LARS-specific content checklist). Websites were categorized as academic, governmental, nonprofit or private. RESULTS: Of 117 unique websites, 25 met the inclusion criteria. The median readability level was 10.4 (9.2-11.7) and 11 (44.0%) websites were highly suitable. Using the DISCERN instrument, seven (28.0%) websites had clear aims, two (8.0%) divulged the sources used and four (16.0%) had high overall quality. Only eight (32.0%) websites defined LARS and ten (40.0%) listed all five major symptoms associated with the LARS score. There was variation in the number of websites that discussed dietary modifications (80.0%), self-help strategies (72.0%), medication (68.0%), pelvic floor rehabilitation (60.0%) and neuromodulation (8.0%). The median accuracy of websites was 93.8% (88.2-96.7%). Governmental websites scored highest for overall suitability (P = 0.0079) and quality (P < 0.001). CONCLUSIONS: Current online information on LARS is suboptimal. Websites are highly variable, important content is often lacking and material is too complex for patients.

Comparison between conventional colectomy and complete mesocolic excision for colon cancer: a systematic review and pooled analysis : A review of CME versus conventional colectomies.

BACKGROUND: Complete mesocolic excision (CME) is advocated based on oncologic superiority, but not commonly performed in North America. Many data are case series with few comparative studies. Our aim was to perform a systematic review comparing outcomes between CME and non-CME colectomy. METHODS: A systematic review was performed according to PRISMA guidelines of MEDLINE, EMBASE, HealthStar, Web of Science, and Cochrane Library. Studies were included if they compared conventional resection (non-CME) to CME for colon cancer. Quality was assessed using methodological index for non-randomized studies (MINORS). The main outcome measures were short-term morbidity and oncologic outcomes. Weighted pooled means and proportions with 95% CI were calculated using a random-effects model when appropriate. RESULTS: Out of 825 unique citations, 23 studies underwent full-text reviews and 14 met inclusion criteria. Mean MINORS score was 13.3 (range 11-15). The mean sample size in CME group was 1166 (range 45-3756) and 945 (range 40-3425) in non-CME. Four papers reported plane of dissection, with CME plane achieved in 85.8% (95% CI 79.8-91.7). Mean OR time in CME group was 167 min (163-171) and 138 min (135-142) in conventional group. Perioperative morbidity was reported in six studies, with pooled overall complications of 22.5% (95% CI 18.4-26.6) for CME and 19.6 (95% CI 13.6-25.5) for non-CME. Anastomotic leak occurred in 6.0% (95% CI 2.2-9.7) of CME resections versus 6.0% (95% CI 4.1-7.9) in non-CME. CME had more lymph nodes, longer distance to high tie, and specimen length in all studies. Nine studies compared long-term oncologic outcomes and only three reported statistically significant higher disease-free or overall survival in favor of CME. Local recurrence was lower after CME in two of four studies. CONCLUSIONS: The quality of evidence is limited and does not consistently support the superiority of CME. Better data are needed before CME can be recommended as the standard of care for colon cancer resections.

Minimally invasive surgery for stage III colon adenocarcinoma is associated with less delay to initiation of adjuvant systemic therapy and improved survival.

BACKGROUND: Minimally invasive surgery (MIS) may improve surgical recovery and reduce time to adjuvant systemic therapy after colon cancer resection. The objective of this study was to determine the effect of MIS on the initiation of adjuvant systemic therapy and survival in patients with stage III colon cancer. METHODS: The 2010-2014 National Cancer Database was queried for patients with resected stage III colon adenocarcinoma, and divided into MIS, which included laparoscopic and robotic approaches, and open surgery. Propensity-score matching was used to balanced open and MIS groups. The main outcome measures were delayed initiation of adjuvant systemic therapy (defined as > 8 weeks after surgery) and 5-year overall survival (OS). Multiple Cox regression was performed to identify independent predictors for 5-year OS, including an interaction between delayed systemic therapy and MIS, and adjusted for clustering at the hospital level. RESULTS: There were 86,680 patients that were included in this study. Overall, 45% (38,713) underwent MIS colectomy, of which 93% underwent laparoscopic and 7% robotic surgery. After matching, 33,183 open patients were balanced to 33,183 MIS patients. Patient, tumor, and facility characteristics were similar in the matched cohort. More patients in the MIS group received adjuvant therapy within 8 weeks of surgery (49% vs. 42%, p < 0.001), and fewer MIS patients did not receive any systemic therapy (30% vs. 35%, p < 0.001). Delayed initiation of systemic therapy > 8 weeks was associated with worse 5-year OS (HR 1.27, 95%CI 1.19-1.36). MIS was independently associated with improved survival (HR 0.92, 95%CI 0.86-0.97). This relationship remained even if 90-day mortality was excluded. CONCLUSIONS: MIS approaches are associated with less delay to the initiation of adjuvant systemic therapy and improved survival in patients with stage III colon adenocarcinoma. Surgeons should favor MIS approaches for the treatment of stage III colon adenocarcinoma whenever possible.

18F-FDG PET and high-resolution MRI co-registration for pre-surgical evaluation of patients with conventional MRI-negative refractory extra-temporal lobe epilepsy.

PURPOSE: Epilepsy that originates outside of the temporal lobe can present some of the most challenging problems for surgical therapy, especially for patients with conventional magnetic resonance imaging (MRI)-negative refractory extra-temporal lobe epilepsy (ETLE). This study aimed to evaluate the clinical value of pre-surgical 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) and high-resolution MRI (HR-MRI) co-registration in patients with conventional MRI-negative refractory ETLE, and compare their surgical outcomes. METHODS: Sixty-seven patients with conventional MRI-negative refractory ETLE were prospectively included for pre-surgical 18F-FDG PET and HR-MRI examinations. Under the guidance of 18F-FDG PET and HR-MRI co-registration, HR-MRI images were re-read. Based on the image result changes from first reading to re-reading, patients were divided into three groups: Change-1 (lesions of subtle abnormality could be identified in re-read), Change-2 (non-specific abnormalities reported in the first reading were considered as lesions on HR-MRI re-read) and No-change. Post-surgical follow-ups were conducted for up to 59 months. RESULTS: Visual analysis of 18F-FDG PET showed focal or regional abnormality in 46 patients (68.6%), while the abnormal rate increased to 94.0% (P < 0.05) by co-registration. Of the 67 patients, 46.3% of them were identified as Change-1, and 11.9% as Change-2 after co-registration and HR-MRI re-read. Patients with Change-1 and -2 were more likely to be recommended to receive surgical resection (P < 0.001). In the 17 post-surgical patients, 88% had good outcomes, whereas 11.7% had poor outcomes during our study period. CONCLUSION: Pre-surgical evaluation by co-registration of 18F-FDG PET and HR-MRI could improve the identification of the epileptogenic onset zone (EOZ), and may further guide the surgical decision-making and improve the outcome of the refractory ETLE with normal conventional MRI; therefore, it should be recommended as a standard procedure for pre-surgical evaluation of these patients.

Impact of Tumor Deposits on Oncologic Outcomes in Stage III Colon Cancer.

BACKGROUND: The prognosis of tumor deposits in stage III colon adenocarcinoma is poorly described. OBJECTIVE: The purpose of this study was to determine the impact of tumor deposits on oncologic outcomes in patients with stage III colon cancer. DESIGN: This was a multicenter retrospective cohort study. SETTINGS: The 2010 to 2014 National Cancer Database was queried for patients with resected stage III colon adenocarcinoma on final pathology. PATIENTS: Patients were divided into 3 groups: lymph nodes+tumor deposits-, lymph nodes+tumor deposits+, and lymph nodes-tumor deposits+. MAIN OUTCOME MEASURES: The main outcome was 5-year overall survival. RESULTS: Of 74,577 patients, there were 55,800 patients with lymph nodes+tumor deposits-, 13,740 patients with lymph nodes+tumor deposits+, and 5037 patients with lymph nodes-tumor deposits+. The groups had similar patient and facility characteristics, but patients with lymph nodes+tumor deposits+ had more advanced tumor characteristics. Patients with lymph nodes-tumor deposits+ were less likely to receive adjuvant systemic therapy (52% vs 74% lymph nodes+tumor deposits- and 75% lymph nodes+tumor deposits+, p < 0.001) and had a longer delay to initiation of adjuvant treatment (>8 weeks; 43% vs 33% lymph nodes+tumor deposits- and 33% lymph nodes+tumor deposits+, p < 0.001). Patients with lymph nodes+tumor deposits+ had the lowest 5-year overall survival (46.0% vs 63.4% lymph nodes+tumor deposits- vs 61.9% lymph nodes-tumor deposits+, p < 0.001). On multivariate analysis, patients with lymph nodes-tumor deposits+ had similar 5-year overall survival compared with patients with lymph nodes+tumor deposits- with ≤3 positive lymph nodes (HR, 0.93; 95% CI, 0.87-1.01). Patients with lymph nodes+tumor deposits+ had worse prognosis regardless of the number of involved lymph nodes (≤3 +lymph nodes: HR, 1.37; 95% CI, 1.28-1.47 and ≥4 +lymph nodes: HR, 1.30; 95% CI, 1.22-1.38). Of those not receiving adjuvant treatment, patients with lymph nodes-tumor deposits+ were younger and had more adverse tumor features than lymph node+ disease. Lymph nodes-tumor deposits+ was independently associated with less delivery of adjuvant systemic therapy (OR, 0.81; 95% CI, 0.80-0.82). LIMITATIONS: This study was limited by its retrospective analysis of a prospective database. CONCLUSIONS: The prognosis of patients with N1c disease is similar to nodal involvement without tumor deposits, yet these patients were less likely to receive adjuvant systemic therapy. Improvement in the delivery of appropriate care in these patients may increase survival and should be a target of future quality initiatives. See Video Abstract at http://links.lww.com/DCR/A666.

Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report.

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

Diversity of Total Bacterial Communities and Chemoautotrophic Populations in Sulfur-Rich Sediments of Shallow-Water Hydrothermal Vents off Kueishan Island, Taiwan.

Shallow-water hydrothermal vents (HTVs) are an ecologically important habitat with a geographic origin similar to that of deep-sea HTVs. Studies on shallow-water HTVs have not only facilitated understanding of the influences of vents on local ecosystems but also helped to extend the knowledge on deep-sea vents. In this study, the diversity of bacterial communities in the sediments of shallow-water HTVs off Kueishan Island, Taiwan, was investigated by examining the 16S ribosomal RNA gene as well as key functional genes involved in chemoautotrophic carbon fixation (aclB, cbbL and cbbM). In the vent area, Sulfurovum and Sulfurimonas of Epsilonproteobacteria appeared to dominate the benthic bacterial community. Results of aclB gene analysis also suggested involvement of these bacteria in carbon fixation using the reductive tricarboxylic acid (rTCA) cycle. Analysis of the cbbM gene showed that Alphaproteobacterial members such as the purple non-sulfur bacteria were the major chemoautotrophic bacteria involving in carbon fixation via the Calvin-Benson-Bassham (CBB) cycle. However, they only accounted for <2% of the total bacterial community in the vent area. These findings suggest that the rTCA cycle is the major chemoautotrophic carbon fixation pathway in sediments of the shallow-water HTVs off Kueishan Island.

Ileal pouch-anal anastomosis for ulcerative colitis: a Canadian institution's experience.

BACKGROUND: We aimed to summarize the outcomes of ulcerative colitis (UC) patients receiving an ileal pouch-anal anastamosis (IPAA) over an 11-year period at a high-volume Canadian inflammatory bowel disease (IBD) center. METHODS: A retrospective chart review was performed for subjects with UC who underwent IPAA between 2002 and 2013. Patient charts were reviewed for demographic data, clinical characteristics, preoperative medical treatment, and surgical outcomes. Univariate and multivariate logistic regression modeling were used to determine significant factors in postoperative outcomes. RESULTS: Seven hundred fifty-eight were included from the IBD database. The median age at the time of surgery was 37.1 (±12.1). Mean preoperative disease duration was 8.1 years (±8.7). Three hundred sixty-nine patients (48.7 %) had systemic corticosteroids (>15 mg/day) within 30 days prior to surgery. Of these, 286 patients had high dose (>30 mg/day) corticosteroids within 7 days of their first surgery. One hundred nine (14.0 %) IPAA procedures were performed laparoscopically. Pelvic pouches were created in traditional 2 (n = 460) and 3 (n = 285) stages; the remainder (n = 13) was performed in non-traditional staged operations. Early complications, defined as occurring within the same stay in hospital, consisted of pelvic abscess (n = 135, 17.8 %), small bowel obstruction (n = 134, 17.7 %), wound infection (n = 108, 14.3 %), and deep vein thrombosis (n = 33, 4.4 %). The overall pouch leak rate was 92 (12.1 %). There was one death in our study. The median length of stay was 10.3 days (SD6.0). Late complications, defined as occurring after discharge from hospital, consisted of anal stricture (n = 55, 7.3 %), pouch fistula (n = 26, 3.4 %), and functional pouch failure (n = 7, 0.9 %). CONCLUSIONS: IPAA has been found to be a safe and effective method of surgical management of UC patients in a high-volume IBD center.

Voxel-based morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative epilepsies.

OBJECTIVE: In the presurgical workup of magnetic resonance imaging (MRI)-negative (MRI(-) or "nonlesional") pharmacoresistant focal epilepsy (PFE) patients, discovering a previously undetected lesion can drastically change the evaluation and likely improve surgical outcome. Our study utilizes a voxel-based MRI postprocessing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle abnormalities in a consecutive cohort of MRI(-) surgical candidates. METHODS: Included in this retrospective study was a consecutive cohort of 150 MRI(-) surgical patients. MAP was performed on T1-weighted MRI, with comparison to a scanner-specific normal database. Review and analysis of MAP were performed blinded to patients' clinical information. The pertinence of MAP(+) areas was confirmed by surgical outcome and pathology. RESULTS: MAP showed a 43% positive rate, sensitivity of 0.9, and specificity of 0.67. Overall, patients with the MAP(+) region completely resected had the best seizure outcomes, followed by the MAP(-) patients, and patients who had no/partial resection of the MAP(+) region had the worst outcome (p < 0.001). Subgroup analysis revealed that visually identified subtle findings are more likely correct if also MAP(+) . False-positive rate in 52 normal controls was 2%. Surgical pathology of the resected MAP(+) areas contained mainly non-balloon-cell focal cortical dysplasia (FCD). Multiple MAP(+) regions were present in 7% of patients. INTERPRETATION: MAP can be a practical and valuable tool to: (1) guide the search for subtle MRI abnormalities and (2) confirm visually identified questionable abnormalities in patients with PFE due to suspected FCD. A MAP(+) region, when concordant with the patient's electroclinical presentation, should provide a legitimate target for surgical exploration.

Reduced complications from intracranial grid insertion by using a small grid size and a precise protocol during monitoring.

BACKGROUND: A study of the risk factors associated with complications during intracranial EEG monitoring led to a change in protocol for monitoring and implantation at our centres. We conducted a study to identify any reduction in complications following the changed protocols involving the use of smaller subdural electrode arrays, continuous ICP monitoring, use of a central line, and intake of prophylactic antibiotics and dexamethasone. METHODS: We prospectively collected data on patient outcomes between 2005 and 2012 (group B) compared with patients between 1988 and 2004 (group A) before the protocol changes. RESULTS: Seventy-one patients in group A and 58 patients in group B underwent intracranial electrode implantation. Complications directly related to grids occurred in 25 % of group A vs. 8.6 % in group B (p < 0.05) and those indirectly related to grids were 11.2 % in group A vs. none in group B. The rate of transient complications requiring no treatment was 12.5 % in group A versus 1.7 % in group B. The rate of transient complications requiring treatment was 10 % in group A and 6.9 % in group B. There were two deaths in group A. The infection rate was higher in group B than group A (5.2 % vs. 2.8 %; p = 0.90). Since 2008 there have been no infective complications. Complications directly related to intracranial EEG monitoring were significantly reduced using the revised protocol (p < 0.05). Regression analysis identifying only the size of the grids (≤4 × 8 grid arrays) implanted was an independent predictor of more complications in group A (P < 0.05). CONCLUSIONS: Complication rates following intracranial implantation decreased following the use of a small grid size and adherence to a stringent protocol.

Linking MRI postprocessing with magnetic source imaging in MRI-negative epilepsy.

OBJECTIVE: MRI-negative (MRI-) pharmacoresistant focal epilepsy (PFE) patients are most challenging for epilepsy surgical management. This study utilizes a voxel-based MRI postprocessing technique, implemented using a morphometric analysis program (MAP), aiming to facilitate detection of subtle focal cortical dysplasia (FCD) in MRI- patients. Furthermore, the study examines the concordance between MAP-identified regions and localization from magnetic source imaging (MSI). METHODS: Included in this retrospective study were 25 MRI- surgical patients. MAP was performed on T1-weighted MRI, with comparison to a normal database. The pertinence of MAP+ areas was confirmed by MSI, surgical outcome and pathology. Analyses of MAP and MSI were performed blindly from patients' clinical information and independently from each other. RESULTS: The detection rate of subtle changes by MAP was 48% (12/25). Once MAP+ areas were resected, patients were more likely to be seizure-free (p=0.02). There were no false positives in the 25 age-matched normal controls. Seven patients had a concordant MSI correlate. Patients in whom a concordant area was identified by both MAP and MSI had a significantly higher chance of achieving a seizure-free outcome following complete resection of this area (p=0.008). In the 9 resected MAP+ areas, pathology revealed FCD type IA in 7 and type IIB in 2. INTERPRETATION: MAP shows promise in identifying subtle FCD abnormalities and increasing the diagnostic yield of conventional MRI visual analysis in presurgical evaluation of PFE. Concordant MRI postprocessing and MSI analyses may lead to the noninvasive identification of a structurally and electrically abnormal subtle lesion that can be surgically targeted.

The relationship between neuropsychological functioning and FDG-PET hypometabolism in intractable mesial temporal lobe epilepsy.

We examined the relationship between baseline neuropsychological functioning and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in intractable mesial temporal lobe epilepsy (MTLE). We hypothesized relationships between dominant temporal lobe hypometabolism and verbal memory and between nondominant temporal lobe hypometabolism and nonverbal memory in line with the lateralized material-specific model of memory deficits in MTLE. We also hypothesized an association between performance on frontal lobe neuropsychological tests and prefrontal hypometabolism. Thirty-two patients who had undergone temporal lobectomy for treatment of MTLE and who completed both presurgical FDG-PET and comprehensive neuropsychological investigations with widely used standardized measures were included. Age-adjusted composite measures were calculated for verbal memory, nonverbal memory, relative material-specific memory, IQ, executive function, attention/working memory, and psychomotor speed. Fluorodeoxyglucose positron emission tomography was analyzed with statistical parametric mapping (SPM) to identify hypometabolism relative to healthy controls. Pearson's correlation was used to determine the relationship between regions of hypometabolism and neuropsychological functioning. Dominant temporal lobe hypometabolism was associated with relatively inferior verbal memory, while nondominant temporal lobe hypometabolism was associated with inferior nonverbal memory. No relationship was found between performance on any frontal lobe measures and prefrontal hypometabolism. Statistical parametric mapping-quantified lateralized temporal lobe hypometabolism correlates with material-specific episodic memory impairment in MTLE. In contrast, prefrontal hypometabolism is not associated with performance on frontal lobe measures. We suggest that this is because frontal lobe neuropsychology tests may not be good measures of isolated frontal lobe functioning.

Regulation of pluripotent cell differentiation by a small molecule, staurosporine.

Research in the embryo and in culture has resulted in a sophisticated understanding of many regulators of pluripotent cell differentiation. As a consequence, protocols for the differentiation of pluripotent cells generally rely on a combination of exogenous growth factors and endogenous signalling. Little consideration has been given to manipulating other pathways to achieve pluripotent cell differentiation. The integrity of cell:cell contacts has been shown to influence lineage choice during pluripotent cell differentiation, with disruption of cell:cell contacts promoting mesendoderm formation and maintenance of cell:cell contacts resulting in the preferential formation of neurectoderm. Staurosporine is a broad spectrum inhibitor of serine/threonine kinases which has several effects on cell function, including interruption of cell:cell contacts, decreasing focal contact size, inducing epithelial to mesenchyme transition (EMT) and promoting cell differentiation. The possibility that staurosporine could influence lineage choice from pluripotent cells in culture was investigated. The addition of staurosporine to differentiating mouse EPL resulted in preferential formation of mesendoderm and mesoderm populations, and inhibited the formation of neurectoderm. Addition of staurosporine to human ES cells similarly induced primitive streak marker gene expression. These data demonstrate the ability of staurosporine to influence lineage choice during pluripotent cell differentiation and to mimic the effect of disrupting cell:cell contacts. Staurosporine induced mesendoderm in the absence of known inducers of formation, such as serum and BMP4. Staurosporine induced the expression of mesendoderm markers, including markers that were not induced by BMP4, suggesting it acted as a broad spectrum inducer of molecular gastrulation. This approach has identified a small molecule regulator of lineage choice with potential applications in the commercial development of ES cell derivatives, specifically as a method for forming mesendoderm progenitors or as a culture adjunct to prevent the formation of ectoderm progenitors during pluripotent cell differentiation.