Cortical thickness in childhood left focal epilepsy: Thinning beyond the seizure focus.

OBJECTIVE: Structural brain differences are found in adults and children with epilepsy, yet pediatric samples have been heterogeneous regarding seizure type, magnetic resonance imaging (MRI) findings, and hemisphere of seizure focus. This study examines whether cortical thickness and surface area differ between children with left-hemisphere focal epilepsy (LHE) and age-matched typically developing (TD) peers. We examined whether age differentially moderated cortical thickness between groups and if cortical thickness was associated with duration of epilepsy, seizure frequency, or neuropsychological functioning. METHODS: Thirty-five children with LHE and 35 TD children completed neuropsychological testing and 3T MR imaging. Neuropsychological measures included general intelligence and executive functioning. All MRIs were normal. Surface-based morphometric processing and analyses were conducted using FreeSurfer 6.0. Regression analyses compared age by cortical thickness differences between groups. Correlational analyses examined associations between cortical thickness in these areas with neuropsychological functioning or epilepsy characteristics. RESULTS: Left-hemisphere focal epilepsy displayed decreased cortical thickness bilaterally compared to TD controls across 6 brain regions but no differences in surface area. Moderation analyses revealed quadratic relationships between age and cortical thickness for left frontoparietal-cingulate and right superior frontal regions. Higher performance intelligence quotient (IQ) (PIQ) and verbal IQ (VIQ) and fewer parent reported executive function problems were associated with greater cortical thickness in TD children. SIGNIFICANCE: Children with LHE displayed thinner cortex extending beyond the hemisphere of seizure focus. The nonlinear pattern of cortical thickness across age occurring in TD children is not evident in the same manner in children with LHE. These differences in cortical thickness patterns were greatest in children 8-12 years old. Greater cortical thickness was associated with higher IQ and fewer executive control problems in daily activities in TD children. Thus, differences in cortical thickness in the absence of differences in surface area, suggest cortical thickness may be a sensitive proxy of subtle neuroanatomical changes that are related to neuropsychological functioning.

The utility of radiological upper gastrointestinal series and clinical indicators in detecting leaks after laparoscopic sleeve gastrectomy: a case-controlled study.

BACKGROUND: Leak after laparoscopic sleeve gastrectomy (LSG) often presents after hospital discharge, making timely diagnosis difficult. This study evaluates the utility of radiological upper gastrointestinal (UGI) series and clinical indicators in detecting leak after LSG. METHODS: A retrospective case-controlled study of 1762 patients who underwent LSG from 2006 to 2014 was performed. All patients with radiographically confirmed leaks were included. Controls consisted of patients who underwent LSG without leak, selected using a 10:1 case-match. Data included baseline patient characteristics, surgical characteristics, and UGI series results. Clinical indicators including vital signs, SIRS criteria, and pain score were compared between patients who developed leak and controls. RESULTS: Of 1762 LSG operations, 20 (1.1 %) patients developed leaks and were compared with 200 case-matched controls. Three patients developed leak during their index admission [mean = 1.3 days, range (1, 2)], while the majority (n = 17) were discharged and developed symptoms at a mean of 17.1 days [range (4, 63)] postoperatively. Patients diagnosed with leak were similar to controls in baseline and surgical characteristics. Contrast extravasation on routine postoperative UGI identified two patients with early leaks, but was negative in the remainder (89 %). Patients with both early and delayed leaks demonstrated significant clinical abnormalities at the time of leak presentation, prior to confirmatory radiographic study. In multiple regression analysis, independent clinical factors associated with leak included fever [OR 16.6, 95 % CI (4.04, 68.10), p < 0.0001], SIRS criteria [OR 7.0, 95 % CI (1.47, 33.26), p = 0.014], and pain score ≥9 [OR 19.1, 95 % CI (1.38, 263.87), p = 0.028]. CONCLUSIONS: Contrast extravasation on routine postoperative radiological UGI series may detect early leaks after LSG, but the vast majority of leaks demonstrate normal results and present 2-3 weeks after discharge. Therefore, clinical indicators (specifically fever, SIRS criteria, and pain score) are the most useful factors to raise concern for leaks prior to confirmatory radiographic study and may be used as criteria to selectively obtain UGI studies after LSG.

Intraoperative leak testing has no correlation with leak after laparoscopic sleeve gastrectomy.

BACKGROUND: Staple line leak is a serious complication of sleeve gastrectomy. Intraoperative methylene blue and air leak tests are routinely used to evaluate for leak; however, the utility of these tests is controversial. We hypothesize that the practice of routine intraoperative leak testing is unnecessary during sleeve gastrectomy. METHODS: A retrospective cohort study was designed using a prospectively collected database of seven bariatric surgeons from two institutions. All patients who underwent sleeve gastrectomy from March 2012 to November 2014 were included. The performance of intraoperative leak testing and the type of test (air or methylene blue) were based on surgeon preference. Data obtained included BMI, demographics, comorbidity, presence of intraoperative leak test, result of test, and type of test. The primary outcome was leak rate between the leak test (LT) and no leak test (NLT) groups. SAS version 9.4 was used for univariate and multivariate analyses. RESULTS: A total of 1550 sleeve gastrectomies were included; most were laparoscopic (99.8%), except for one converted and two open cases. Routine intraoperative leak tests were performed in 1329 (85.7%) cases, while 221 (14.3%) did not have LTs. Of the 1329 cases with LTs, there were no positive intraoperative results. Fifteen (1%) patients developed leaks, with no difference in leak rate between the LT and NLT groups (1 vs. 1%, p = 0.999). After adjusting for baseline differences between the groups with a propensity analysis, the observed lack of association between leak and intraoperative leak test remained. In this cohort, leaks presented at a mean of 17.3 days postoperatively (range 1-67 days). Two patients with staple line leaks underwent repeat intraoperative leak testing at leak presentation, and the tests remained negative. CONCLUSION: Intraoperative leak testing has no correlation with leak due to laparoscopic sleeve gastrectomy and is not predictive of the later development of staple line leak.

Routine extended (30 days) chemoprophylaxis for patients undergoing laparoscopic sleeve gastrectomy may reduce Portomesenteric vein thrombosis rates.

BACKGROUND: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days. OBJECTIVES: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis. SETTING: University Hospital. METHODS: Between 2012-2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018-2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed. RESULTS: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m2, respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively. CONCLUSIONS: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively.

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms.

In vivo quantification of myelin changes in the vertebrate nervous system.

Destruction or changes associated with myelin membranes in the CNS play a key role in the pathogenesis of multiple sclerosis and other related neurodegenerative disorders. A long-standing goal has been to detect and quantify myelin content in vivo. For this reason, we have developed a myelin-imaging technique based on positron emission tomography (PET). PET is a quantitative imaging modality that has been widely used in clinical settings for direct assessment of biological processes at the molecular level. However, lack of myelin-imaging probes has hampered the use of PET for imaging of myelination in the CNS. Here, we report a myelin-imaging agent, termed Case Imaging Compound (CIC) that readily penetrates the blood-brain barrier and preferentially localizes to myelinated regions of the brain. After radiolabeling with positron-emitting carbon-11, [(11)C]CIC-PET was conducted in longitudinal studies using a lysolethicin-induced rat model of focal demyelination and subsequent remyelination. Quantitative analysis showed that the retention of [(11)C]CIC correlates with the level of demyelination/remyelination. These studies indicate that, for the first time, [(11)C]CIC-PET can be used as an imaging marker of myelination, which has the potential to be translated into clinical studies in multiple sclerosis and other myelin-related diseases for early diagnosis, subtyping, and efficacy evaluation of therapeutic treatments aimed at myelin repair.

A novel PET marker for in vivo quantification of myelination.

C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type mouse brain, a pattern that was also consistently observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively labeled myelinated regions with high specificity. Biodistribution studies showed abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole brain at 5 min post injection and prolonged retention in the brain with 1.37% injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the radioactivity concentration to the level of myelination in the brain. These studies suggest that MeDAS is a sensitive myelin probe that provides a direct means to detect myelin changes in the brain. Thus, it can be used as a myelin-imaging marker to monitor myelin pathology in vivo.

Thrombophilia prevalence in patients seeking laparoscopic sleeve gastrectomy: extended chemoprophylaxis may decrease portal vein thrombosis rate.

BACKGROUND: Portomesenteric vein thrombosis (PMVT) may occur after laparoscopic sleeve gastrectomy (LSG). Previous studies have shown that PMVT patients may have undiagnosed thrombophilia. We recently changed our practice to check thrombophilia panel in every LSG patient preoperatively. OBJECTIVES: To estimate the thrombophilia prevalence in patients seeking LSG, and determine if extended chemoprophylaxis post LSG reduces PMVT. SETTINGS: University hospital. METHODS: Thrombophilia panels were drawn on every patient seeking LSG after July 2018 at 2 high-volume accredited bariatric surgery centers. A positive panel included factor VIII >150%; protein C <70%; protein S <55%; antithrombin III <83%; and activated protein C resistance <2.13. Patients with a positive panel were discharged on extended chemoprophylaxis. PMVT rates and bleeding occurrences were recorded for LSG patients from August 2018 to March 2019 and were compared with a historic cohort of LSG performed from January 2014 to July 2018. RESULTS: One thousand seventy-five patients seeking LSG had thrombophilia panel checked preoperatively. The cohort was 83% female; mean age and body mass index were 39.2 years and 43 kg/m2, respectively. Of the cohort, 52.4% (563/1075) had positive thrombophilia panel, including factor VIII elevation (91.5%), antithrombin III deficiency (6.0%), protein S deficiency (1.1%), protein C deficiency (.9%), and activated protein C resistance (.5%). Between January 2014 and July 2018, 13 PMVT were diagnosed among 4228 LSG (.3%) and there were 17 bleeding occurrences (.4%). After August 2018, one PMVT was diagnosed among 745 LSG (.1%) and there were 5 bleeding occurrences (.6%). CONCLUSIONS: The estimated thrombophilia prevalence in patients seeking LSG is 52.4%. The majority (91.5%) of these patients have factor VIII elevation. Extended prophylaxis may decrease PMVT postLSG.

Factor VIII elevation may contribute to portomesenteric vein thrombosis after laparoscopic sleeve gastrectomy: a multicenter review of 40 patients.

BACKGROUND: Portomesenteric vein thrombosis (PMVT) has been increasingly reported after laparoscopic sleeve gastrectomy (LSG). Factor VIII (FVIII) is a plasma sialoglycoprotein that plays an essential role in hemostasis. There is increasing evidence that FVIII elevation constitutes a clinically important risk factor for venous thrombosis. OBJECTIVES: To report the prevalence of FVIII elevation as well as other clinical characteristics in a multicenter series of patients who developed PMVT after LSG. SETTING: University hospitals. METHODS: A retrospective review was conducted of all patients that developed PMVT after laparoscopic bariatric surgery from 2006 to 2016 at 6 high-volume bariatric surgery centers. RESULTS: Forty patients who developed PMVT postoperatively, all after LSG, were identified. During this timeframe, 25,569 laparoscopic bariatric surgery cases were performed, including 9749 LSG (PMVT incidence after LSG = .4%). Mean age and body mass index were 40 years (18-65) and 43.4 kg/m2 (35-59.7), respectively. Abdominal pain was the most common (98%) presenting symptom. Of patients, 92% had a hematologic abnormality identified, and of these, FVIII elevation was the most common (76%). The vast majority (90%) was successfully managed with therapeutic anticoagulation alone. A smaller number of patients required small bowel resection (n = 2) and surgical thrombectomy (n = 1). There were no mortalities. CONCLUSIONS: A high index of clinical suspicion and prompt diagnosis/treatment of PMVT usually leads to favorable outcomes. FVIII elevation was the most common (76%) hematologic abnormality identified in this patient cohort. Further studies are needed to determine the prevalence of FVIII elevation in patients seeking bariatric surgery.

Thirty-Day Readmission After Laparoscopic Sleeve Gastrectomy­a Predictable Event?

BACKGROUND: Thirty-day readmission post-bariatric surgery is used as a metric for surgical quality and patient care. We sought to examine factors driving 30-day readmissions after laparoscopic sleeve gastrectomy (LSG). METHODS: We reviewed 1257 LSG performed between March 2012 and June 2014. Readmitted and nonreadmitted patients were compared in their demographics, medical histories, and index hospitalizations. Multivariable regression was used to identify risk factors for readmission. RESULTS: Forty-five (3.6 %) patients required 30-day readmissions. Forty-seven percent were readmitted with malaise (emesis, dehydration, abdominal pain) and 42 % with technical complications (leak, bleed, mesenteric vein thrombosis). Factors independently associated with 30-day readmission include index admission length of stay (LOS) ≥3 days (OR 2.54, CI = [1.19, 5.40]), intraoperative drain placement (OR 3.11, CI = [1.58, 6.13]), postoperative complications (OR 8.21, CI = [2.33, 28.97]), and pain at discharge (OR 8.49, CI = [2.37, 30.44]). Patients requiring 30-day readmissions were 72 times more likely to have additional readmissions by 6 months (OR 72.4, CI = [15.8, 330.5]). CONCLUSIONS: The 30-day readmission rate after LSG is 3.6 %, with near equal contributions from malaise and technical complications. LOS, postoperative complications, drain placement, and pain score can aid in identifying patients at increased risk for 30-day readmissions. Patients should be educated on postoperative hydration and pain management, so readmissions can be limited to technical complications requiring acute inpatient management.

Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair.

Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([(11)C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [(11)C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [(11)C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [(11)C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.