Treatment of Gastrointestinal Bleeding in the Biliopancreatic Limb with Embolization in a Patient with Duodenal Switch Anatomy.

Introduction: Biliopancreatic diversion with duodenal switch (BPD/DS) is an uncommon type of bariatric surgery that can rarely lead to bleeding in the biliopancreatic limb. The altered anatomy poses significant diagnostic and therapeutic challenges. Case Presentation: We present an unusual case of a woman status post-BPD/DS nearly a decade ago who presented with gastrointestinal bleeding in the duodenum of the biliopancreatic limb, a rare phenomenon given the unique surgery. Conclusion: We illustrate a promising minimally invasive option of successfully treating the bleeding by interventional radiology (IR) embolization as an alternative to more invasive and challenging options of balloon-assisted enteroscopy, lumen-apposing metal stent placement and surgical intraoperative enteroscopy.

Identification of sentinel lymph nodes in esophageal cancer patients using contrast-enhanced EUS with peritumoral injections.

Objectives: The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer. Methods: Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration was performed on LNs considered suspicious by EUS alone, as well as LNs enhanced on CE-EUS. Performance of each modality was compared using FNA cytology as reference standard. Results: A total of 132 LNs were detected with EUS, of which 59 showed enhancement on CE-EUS. Fifty-three LNs underwent FNA, and 22 LNs were determined to be malignant. Among the latter, 10 were considered suspicious by EUS, whereas the other 12 LNs underwent FNA only because of CE-EUS enhancement. Contrast-enhanced EUS showed enhancement in 19 of the 22 malignant LNs. The rate of metastatic node identification from EUS was 45% (10/22), and it was 86% (19/22; P = 0.008) for CE-EUS. Eight subjects (8/30 [27% of study total]) had nodal status upgraded by the addition of CE-EUS, which influenced LN staging and clinical management. Conclusions: Fine-needle aspiration of LNs identified by CE-EUS may increase metastasis positive rate by ruling out LNs not associated with the tumor drainage pattern. In addition, CE-EUS seems to identify more metastatic LNs that would not be biopsied under the standard EUS criteria.

Recurrent bleeding duodenal and colonic ulcers due to post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation as the result of immunosuppressant medications. Epstein-Barr virus (EBV) has been implicated in most of these cases, specifically with B-cell predominant lymphoma. This case report describes a 24-year-old female who presented with recurrent GI bleed within 6 months post-orthostatic heart transplant. Endoscopic evaluations including video capsule study, push enteroscopy, and colonoscopy revealed multiple ulcerated lesions in duodenum, jejunum, and colon secondary to Epstein-Barr Virus-associated monomorphic PTLD. Despite continuation of rituximab after discharge, she returned to the hospital for recurrent GI bleed requiring additional endoscopic intervention. PTLD is a devastating disease of the post-transplant population. Due to a high risk of recurrent GI bleeding, patients with PTLD may benefit from careful monitoring by gastroenterology as an outpatient with a low threshold for repeat endoscopic evaluation despite being on immunotherapy or chemotherapy.

Estimating brain effective connectivity from EEG signals of patients with autism disorder and healthy individuals by reducing volume conduction effect.

Studying brain connectivity has shed light on understanding brain functions. Electroencephalogram signals recorded from the scalp surface comprise inter-dependent multi-channel signals each of which is a linear combination of simultaneously active brain sources as well as adjacent non-brain sources whose activity is widely volume conducted to the scalp through overlapping patterns. Evaluation of brain connectivity based on multivariate autoregressive (MVAR) model identification from neurological time series can be a proper tool for brain signal analysis. However, the MVAR model only considers the lagged influences between time series while ignoring the instantaneous effects (zero-lagged interactions) among simultaneously recorded neurological signals. Hence predicting instant interactions may result in fake connectivity, which may lead to misinterpreting in results. In this study, we aim to find instantaneous effects from coefficients of the MVAR model acquired using an ADALINE neural network and investigate the efficiency of the proposed algorithm by applying it to a simulated signal. We show that our coefficients are estimated accurately from channels of the simulated signal. Moreover, we apply the proposed method on a dataset of a group of 18 healthy children and 10 children with autism by comparing their effective connectivity estimated by direct directed transfer function method using new and old coefficients. Finally, to show the efficiency of the algorithm we exploit the support vector machine method for classifying the dataset. We show that there is a significant improvement in the results obtained from the proposed method.

Cholestatic Liver Injury in a Patient with Tertiary Syphilis.

Syphilis is a common infection that has variable presentations. We report a rare case of a 64-year-old male with 3 weeks of abdominal pain, back pain, and neurologic deficits including memory impairment who was found to have neurosyphilis causing a cholestatic liver injury. Workup included a positive rapid plasma reagin (RPR) and enzyme immunoassay (EIA), a positive cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL), and a liver biopsy, which was compatible with a diagnosis of syphilitic hepatitis. Completion of a 14-day course of penicillin and 1 month of physical therapy resulted in near full-functional and biochemical recovery.

Effective brain connectivity estimation between active brain regions in autism using the dual Kalman-based method.

Brain connectivity estimation is a useful method to study brain functions and diagnose neuroscience disorders. Effective connectivity is a subdivision of brain connectivity which discusses the causal relationship between different parts of the brain. In this study, a dual Kalman-based method is used for effective connectivity estimation. Because of connectivity changes in autism, the method is applied to autistic signals for effective connectivity estimation. For method validation, the dual Kalman based method is compared with other connectivity estimation methods by estimation error and the dual Kalman-based method gives acceptable results with less estimation errors. Then, connectivities between active brain regions of autistic and normal children in the resting state are estimated and compared. In this simulation, the brain is divided into eight regions and the connectivity between regions and within them is calculated. It can be concluded from the results that in the resting state condition the effective connectivity of active regions is decreased between regions and is increased within each region in autistic children. In another result, by averaging the connectivity between the extracted active sources of each region, the connectivity between the left and right of the central part is more than that in other regions and the connectivity in the occipital part is less than that in others.

Acute Gastrointestinal Hemorrhage due to Epstein-Barr Virus Colitis.

Epstein-Barr virus (EBV) is a member of the herpesvirus family that is associated with various disease manifestations, including EBV-associated colitis. There are few case reports describing hemorrhage associated with EBV colitis. We report a 61-year-old woman with acute gastrointestinal bleeding due to EBV colitis after initiation of methylprednisolone and enoxaparin for spinal cord infarction. To our knowledge, there are only a few case reports of hemorrhagic EBV colitis. Perhaps we need to have a higher suspicion for EBV in cases of colitis associated with hemorrhage even in relatively immunocompetent patients.

nCREANN: Nonlinear Causal Relationship Estimation by Artificial Neural Network; Applied for Autism Connectivity Study.

Quantifying causal (effective) interactions between different brain regions are very important in neuroscience research. Many conventional methods estimate effective connectivity based on linear models. However, using linear connectivity models may oversimplify the functions and dynamics of the brain. In this paper, we propose a causal relationship estimator called nonlinear Causal Relationship Estimation by Artificial Neural Network (nCREANN) that identifies both linear and nonlinear components of effective connectivity in the brain. Furthermore, it can distinguish between these two types of connectivity components by calculating the linear and nonlinear parts of the network input-output mapping. The nCREANN performance has been verified using synthesized data and then it has been applied on EEG data collected during rest in children with autism spectrum disorder (ASD) and typically developing (TD) children. The results show that overall linear connectivity in TD subjects is higher, while the nonlinear connectivity component is more dominant in ASDs. We suggest that our findings may represent different underlying neural activation dynamics in ASD and TD subjects. The results of nCREANN may provide new insight into the connectivity between the interactive brain regions.

Esophageal adenocarcinoma in a first-degree relative increases risk for esophageal adenocarcinoma in patients with Barrett's esophagus.

Background: The significance of a family history of esophageal adenocarcinoma in the progression to esophageal adenocarcinoma in patients with Barrett's esophagus has not been thoroughly evaluated. The purpose of this study is to evaluate the presence of esophageal adenocarcinoma in a first-degree relative in patients with Barrett's esophagus. Methods: A retrospective cohort study was conducted of patients with Barrett's esophagus at a tertiary care center undergoing radiofrequency ablation. Family history, demographics, and pathology and endoscopy reports were assessed in all patients. Findings: Three hundred and one patients with Barrett's esophagus were assessed. Nineteen patients who had a diagnosis of esophageal adenocarcinoma on index endoscopy were excluded. Nineteen (6.7%) patients had a first-degree relative with esophageal adenocarcinoma. Four (21.1%) of these patients progressed to esophageal adenocarcinoma. Of patients without first-degree relative with esophageal adenocarcinoma 22/263 (8.7%) progressed to esophageal adenocarcinoma. In a logistic regression model adjusted for sex and the number of radiofrequency ablation treatments, we found that family history of esophageal adenocarcinoma was a significant independent predictor of progression to esophageal adenocarcinoma (odds ratio = 5.55, 95% confidence interval: 1.47-20.0). Conclusion: Our study indicates that Barrett's esophagus patients with a first-degree family member with esophageal adenocarcinoma are at 5.5-fold higher risk for disease progression to esophageal adenocarcinoma. Family history of esophageal adenocarcinoma in Barrett's esophagus patients should be considered in patient surveillance and radiofrequency ablation treatment, beyond recommended guidelines.

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

19 Channel Z-Score and LORETA Neurofeedback: Does the Evidence Support the Hype?

Neurofeedback is a well-investigated treatment for ADHD and epilepsy, especially when restricted to standard protocols such as theta/beta, slow cortical potentials and sensori-motor rhythm neurofeedback. Advances in any field are welcome and other techniques are being pursued. Manufacturers and clinicians are marketing 'superior' neurofeedback approaches including 19 channel Z-score neurofeedback (ZNFB) and 3-D LORETA neurofeedback (with or without Z-scores; LNFB). We conducted a review of the empirical literature to determine if such claims were warranted. This review included the above search terms in Pubmed, Google scholar and any references that met our criteria from the ZNFB publication list and was restricted to group based studies examining improvement in a clinical population that underwent peer review (book chapters, magazine articles or conference presentations are not included since these are not peer reviewed). Fifteen relevant studies emerged with only six meeting our criterion. Based on review of these studies it was concluded that empirical validation of these approaches is sorely lacking. There is no empirical data that supports the notion that 19-channel z-score neurofeedback is effective or superior. The quality of studies for LNFB was better compared to ZNFB and some suggestion for efficacy was demonstrated for ADHD and Tinnitus distress. However, these findings need to be replicated, extended to other populations and have yet to show any "superiority." Our conclusions continue to emphasize the pervasive lack of evidence supporting these approaches to neurofeedback and the implications of this are discussed.

Four Channel Multivariate Coherence Training: Development and Evidence in Support of a New Form of Neurofeedback.

As the field of neurofeedback and neuromodulation grows, trends toward using neurofeedback to treat problems of brain dysfunction have emerged. While the use of connectivity based fMRI guided neurofeedback has shown itself to be efficacious, the expense related to the treatment calls for a more practical solution. The use of QEEG guided neurofeedback in the treatment has shown promise as an emerging treatment. To date, EEG based neurofeedback approaches have used technology with limited sophistication. We designed a new form of neurofeedback that uses four channels of EEG with a multivariate calculation of coherence metrics. Following a mathematical presentation of this model, we present findings of a multi-site study with clinical subjects with various diagnoses. We compared this form of multivariate coherence neurofeedback to the more standard two channel coherence training. Findings showed that there was a significant difference between the groups with four channel multivariate coherence neurofeedback leading to greater changes in EEG metrics. Compared to two channel coherence training, four channel multivariate coherence neurofeedback led to a greater than 50% change in power and 400% in coherence values per session. The significance of these findings is discussed in relation to complex calculations of effective connectivity and how this might lead to even greater enhancements in neurofeedback efficacy.

Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure.

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4⁻5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages.

Neural Connectivity in Epilepsy as Measured by Granger Causality.

Epilepsy is a chronic neurological disorder characterized by repeated seizures or excessive electrical discharges in a group of brain cells. Prevalence rates include about 50 million people worldwide and 10% of all people have at least one seizure at one time in their lives. Connectivity models of epilepsy serve to provide a deeper understanding of the processes that control and regulate seizure activity. These models have received initial support and have included measures of EEG, MEG, and MRI connectivity. Preliminary findings have shown regions of increased connectivity in the immediate regions surrounding the seizure foci and associated low connectivity in nearby regions and pathways. There is also early evidence to suggest that these patterns change during ictal events and that these changes may even by related to the occurrence or triggering of seizure events. We present data showing how Granger causality can be used with EEG data to measure connectivity across brain regions involved in ictal events and their resolution. We have provided two case examples as a demonstration of how to obtain and interpret such data. EEG data of ictal events are processed, converted to independent components and their dipole localizations, and these are used to measure causality and connectivity between these locations. Both examples have shown hypercoupling near the seizure foci and low causality across nearby and associated neuronal pathways. This technique also allows us to track how these measures change over time and during the ictal and post-ictal periods. Areas for further research into this technique, its application to epilepsy, and the formation of more effective therapeutic interventions are recommended.

Retroperitoneal nodular fasciitis: a benign etiology on the differential diagnosis of malignant gastric outlet obstruction.

Nodular fasciitis is a relatively rare, benign and proliferative lesion that is not typically found in the retroperitoneal (RP) space and has not been previously reported as a cause of gastric outlet obstruction (GOO). GOOs are frequently associated with malignancies, however, benign etiologies should be considered as well. We report the first case of GOO secondary to nodular fasciitis in the form of a spontaneously regressing RP mass that was initially concerning for malignancy.

EEG biofeedback for autism spectrum disorder: a commentary on Kouijzer et al. (2013).

Research conducted by Kouijzer et al. (Appl Psychophysiol Biofeedback 38(1):17-28, 2013) compared the effects of skin conductance biofeedback and EEG-biofeedback on patients with autistic spectrum disorders to determine their relative efficacy. While they found a difference between treatment and control groups, there was no significant difference on many variables between the two treatment groups. From this, the increase in symptom alleviation from autistic spectrum disorder was attributed to non-specific factors surrounding the study. We now offer alternative explanations for their findings and propose different options for future studies. We hypothesize that the location and type of neurofeedback used adversely impacted the findings. We speculate that had they used a form of EEG-biofeedback that can combat deficiencies in connectivity and also trained the areas of the brain most affected by autism, there may have then been a significant difference between the effectiveness of EEG-biofeedback versus skin conductance biofeedback.

Using quantitative and analytic EEG methods in the understanding of connectivity in autism spectrum disorders: a theory of mixed over- and under-connectivity.

Neuroimaging technologies and research has shown that autism is largely a disorder of neuronal connectivity. While advanced work is being done with fMRI, MRI-DTI, SPECT and other forms of structural and functional connectivity analyses, the use of EEG for these purposes is of additional great utility. Cantor et al. (1986) were the first to examine the utility of pairwise coherence measures for depicting connectivity impairments in autism. Since that time research has shown a combination of mixed over and under-connectivity that is at the heart of the primary symptoms of this multifaceted disorder. Nevertheless, there is reason to believe that these simplistic pairwise measurements under represent the true and quite complicated picture of connectivity anomalies in these persons. We have presented three different forms of multivariate connectivity analysis with increasing levels of sophistication (including one based on principle components analysis, sLORETA source coherence, and Granger causality) to present a hypothesis that more advanced statistical approaches to EEG coherence analysis may provide more detailed and accurate information than pairwise measurements. A single case study is examined with findings from MR-DTI, pairwise and coherence and these three forms of multivariate coherence analysis. In this case pairwise coherences did not resemble structural connectivity, whereas multivariate measures did. The possible advantages and disadvantages of different techniques are discussed. Future work in this area will be important to determine the validity and utility of these techniques.

A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation.

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46-66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20-73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha-fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3-36 months) while that of the treated was 80 months (15-152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥ 151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV-associated HCC.

A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel.

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.