Given the association between functional disability and suicidal ideation (SI) in late life , this study examined associations between functional disability and SI among older adults receiving problem solving therapy (PST) for depression. PST is a promising intervention for SI  and has been shown to be effective in reducing functional disability among older adults with depression . Regression analyses with adults age 65-91 (n=65) found that level of SI  at baseline was not significantly associated with change in SI from pre- to post-treatment. However, lower baseline disability  and greater reduction in disability  were significantly associated with greater reduction in SI after controlling for age and baseline SI. These results suggest that treatments that decrease disability may be particularly advantageous for reducing SI in older depressed adults.


The textilome or still called gossybipoma is a very rare but well known and not insignificant post-operative grave lesion in the abdominal and gynecological surgery. It is a foreign body compound of gauze or surgical drape omitted in the operation site. The difficulties of diagnosis delay generally the discovery of abdominal textilome. The clinicals symptoms are: chronic disorders of the transit in sub-occlusive or occlusive syndromes. Erect Abdominal X-ray has little contributory in the diagnosis, but the ultrasound remains more reliable. Abdominal CT Scan allows a precise topographic diagnosis; certain teams propose explorations by MRI. We report a case of intra-colic textilome (sigmoïde), presenting acute abdomen in forme of an occlusive syndrome in patient who was operated 3 years ago for uterine fibroid.


The specific aim of this case study was to describe how monitoring ballistocardiogram (BCG) waveforms can detect early heart failure (HF) changes. HF significantly impairs quality of life and is the principal cause for hospital readmissions in older adults. HF prevalence in American adults aged 65 years and older is expected to increase over 70% by 2030. Detecting worsening HF is challenging. Invasive arterial waveforms display blood pressure changes with each heartbeat; BCG waveforms display repetitive body motions resulting from ejection of blood into the great vessels. BCG waveforms change as cardiac function changes. Currently, BCG signals can be captured non-invasively using sensors placed under a bed mattress and provide heart and respiratory rates. We have developed a new way to analyze the BCG waveform using an innovative closed-loop physiological model of the cardiovascular system. The subject, a 94-year old female with hypertension, presented to her physician with symptoms associated with a new diagnosis of acute mixed congestive HF. Mean heart and respiratory rate trends obtained from her bed sensor in the prior two months did not indicate HF. We simulated cardiac cycles using normal cardiac function data, mildly impaired diastolic function data, and the subject’s echocardiography data. The results demonstrated BCG waveform changes that correlated with decreasing cardiac output related to worsening diastolic function. New methods for clinically interpreting BCG waveforms present a significant opportunity for improving early HF detection and improving outcomes. Working on a clinical problem from an engineering perspective merges two disciplines, creating a new methodology.


A 74-year-old female with a history of diabetes mellitus, hypertension, atrial fibrillation  presented with chest and back pain. A 12-lead electrocardiogram (ECG) was ordered at triage demonstrating possible aberrant pacemaker activity .Upon evaluation, the treatment team determined that the patient had no history of pacemaker placement. Physical examination revealed that the patient had an over-the-counter transcutaneous electrical nerve stimulation (TENS) unit adhered to her back to treat her back pain. Once the TENS device was removed, a repeat ECG demonstrated rate-controlled atrial fibrillation without any other electrical discharges .TENS units are external electrostimulators that produce electrical current with variable frequency, amplitude and duration, delivered through skin electrodes.3Artifactual ECG changes inconsistent with a patient’s presentation, particularly in patients with back pain, should prompt consideration by the emergency physician of the presence of a TENS unit causing artifacts.What do we already know about this clinical entity?Electrocardiogram (ECG) artifacts are well described phenomena attributable to various sources. While traditional Transcutaneous Electrical Nerve Stimulation (TENS) units have been known to cause ECG changes, ECG abnormalities due to over the counter TENS units in the emergency department (ED) setting have not been previously reported.What is the major impact of the image(s)?TENS devices are a known pain treatment modality that are now increasingly available over the counter. These devices may induce artifactual changes on ECGsHow might this improve emergency medicine practice?Careful and thorough history and physical exam in the emergency department may prompt the emergency physician to the presence of a TENS device as the cause of electrocardiographic artifact.


China has about 20% of the world’s total dementia population. Since most elders with dementia are living at home with care by family members, communities are fundamental support resources for families as well as patients. Dementia-friendly community initiatives aim to empower families with dementia and increase their social inclusion. Within the Chinese political context, the community level governmental organization called Ju-wei-hui has played a key role in community engagement. Within this context, a Community Based Participatory Action Research (CBPAR) process is utilized to increase public awareness on dementia and caring strategies. Our team collaborated with 15 Ju-wei-hui offices across Beijing to design a series of courses and teaching modules together. Five hundred community residents participated and positively evaluated the project. A major finding is that CBPAR could be an effective strategy to develop dementia-friendly communities across China.


Remote measurements of thermal radiation are very important for analyzing the solar effect in various environments. This paper presents a novel real-time remote temperature estimation method by applying a deep learning-based regression method to midwave infrared hyperspectral images. A conventional remote temperature estimation using only one channel or multiple channels cannot provide a reliable temperature in dynamic weather environments because of the unknown atmospheric transmissivities. This paper solves the issue  with the proposed surface temperature-deep convolutional neural network (ST-DCNN) and a hyperspectral thermal camera (TELOPS HYPER-CAM MWE). The 27-layer ST-DCNN regressor can learn and predict the underlying temperatures from 75 spectral channels. Midwave infrared hyperspectral image data of a remote object were acquired three times a day  for 7 months to consider the dynamic weather variations. The experimental results validate the feasibility of the novel remote temperature estimation method in real-world dynamic environments. In addition, the thermal stealth properties of two types of paint were demonstrated by the proposed ST-DCNN as a real-world application. The relationships between solar radiance and emitted thermal radiative energy are important for infrared stealth technology. Radiated solar energy (6000 K) heats an object, which then radiates thermal energy according to Planck’s law . One of The surface temperature of an object is independent of the wavelength, and can be estimated from even a single spectral band with a known atmospheric transmissivity and surface emissivity. In addition, the atmospheric conditions are crucial for surface temperature estimation . The atmConventional approaches usually require an atmospheric correction to remotely estimate the temperature . A previA two-channel-based method such as a split window algorithm can estimate the surface temperature as a linear function of two brightness temperatures . AlthougA four channel-based surface temperature estimation method was proposed in Reference . They reA multi-channel method was proposed using longwave hyperspectral thermal infrared for high-emissivity surfaces . They usAn accurate remote surface temperature estimation is difficult under dynamically varying weather conditions. The above-mentioned approaches  have their own advantages and disadvantages. These methods work if the specific conditions are satisfied, such as the known atmospheric transmissivity, known water vapor contents, and known surface emissivity. On the other hand, they cannot guarantee the temperature accuracy if the required atmospheric information is unavailable online or the weather conditions change abruptly.In this paper, the problem of a remote surface temperature estimation in a dynamic weather environment is solved by focusing on the sensor, database (DB), and deep learning scheme. A new hyperspectral thermal infrared camera  was adopted to analyze both the solar radiance and thermal radiation in the 1.5–5.5 The remainder of this paper is organized as follows. The remote surface temperature estimation was based on the brightness temperature as shown in An open path Michelson interferometer can be prepared using an active or passive approach for outdoor applications . The forA Michelson interferometer receives an input beam of radiation, divides the beam into two paths, and then recombines the two beams after a path difference . A beam p and wavenumber The intensity as a function of the path difference in the interferometer This is a Fourier cosine transformation. The inverse transform can extract the desired spectrum . If two BBs with known temperatures M(ν˜)Equation :(5)LBB(νquations  and 7)..(4)M(ν˜)Equation .(6)G(ν˜If an unknown scene spectrum is measured (Equation :(8)LS can be estimated from the spectral radiance L is adopted to extract the spectral information. The midwave thermal hyperspectral images usually show lower sensitivity than longwave thermal hyperspectral images on the surface emissivity in a remote temperature estimation . The surThe proposed ST-DCNN consisted of 27 layers, as shown in The TELOPS HYPER-CAM MWE model was used in this study, as shown in The object surface was painted with a gray color and was located in a coastal area with a 78 m distance to the FTIR sensor system. The object surface data were acquired from 1 December–30 June, three times a day  with 75 spectral bands   and meanOne of many applications of remote temperature estimation is to check the thermal stealth effect of different types of paint on ships, buildings, etc. by solar radiation. This paper proposed a novel remote surface temperature estimation method using a surface temperature-deep convolutional neural network (ST-DCNN) from midwave hyperspectral thermal images. Estimating the surface temperature remotely in a dynamically varying weather environment is a very challenging problem. The key idea was to apply the specially designed 27-layer deep convolutional neural network to a huge database consisting of spectral radiance–surface temperature sensor pairs. The spectral radiance data were extracted successfully by applying the FFT to the interferogram followed by wavenumber calibration and two blackbody-based radiometric calibrations. The inverse of Planck’s law to the spectral radiance produced the spectral brightness temperature containing both the surface emissivity and atmospheric transmissivity implicitly. The proposed ST-DCNN learned the weight parameters successfully using the 65,920 training samples. According to the experimental results, the proposed ST-DCNN showed an RMSE of


Kaposi's Sarcoma is a general angiosarcoma induced by viral growth factors, including interleukin 6 of Human Herpes Virus Type 8 ( HHV-8 ). It is preferably localized at limbs extremeties. The eyelid localization is very rare. This is an old patient of 68 years, which has since 3 years superior eyelid swelling of the right eye (A). Biopsy histopathological examination shows an aspect of Kaposi 's sarcoma. HIV serology was negative. The treatment then is surgical excision without safety margins with reconstruction in a the same operative time: external canthotomy and upper eyelid sliding flap sutured end-to-end. The outcome was favorable with a good cosmetic result without local recurrence after 6 months follow up (B).


Parkin ablation. The quantitative proteomic data was obtained using SWATH-MS methodology and mitochondrial function was assessed through measurement of oxygen consumption rate using the Seahorse XF Analyzer. This data facilitates comparisons with previous proteomic and functional data obtained using the exact same methods. A complete set of proteomic data is contained in In this paper, we provide proteomic and functional data for synaptic mitochondria from the striatum of rats with  Specifications TableValue of the data•These data sets provide a useful resource to identify different synaptic mitochondrial processes that are affected due to loss of Parkin.•This data will aid in comparisons of synaptic mitochondrial changes in Parkin KO rats with other PD animal models.1e96 Extracellular Flux Analyzer is provided. No significant alteration of either the respiratory state . All protocols were conducted within NIH-approved guidelines for the Care and Use of Laboratory Animals with the approval and oversight of the University of Nebraska Medical Center Institutional Animal Care and Use Committee.Male Long Evans Hooded (LEH) (RRID:RGD_2308852) control and Parkin KO rats 2.2Brains were rapidly isolated from the animals, and the striatum , protein concentration was determined using a Pierce 660 nm Protein Assay , and the filter aided sample preparation method 2.4RRID:SCR_015786) using our published reference spectral library http://cybert.ics.uci.edu/) q-values < 0.05.Striatal synaptic mitochondrial peptides were analyzed using SWATH data-independent analysis (DIA) mode on a TripleTOF 5600 (SCIEX) followed by targeted data extraction as described previously Michael J Fox Foundation (Grant #9524).Funding support was provided by a grant from the


Cystic lesion around knee usually presents as painless swelling and diagnosed incidentally by imaging for any internal derangement of the knee. Few cases presented with pain. Intra-tendinous patellar ganglion is very rare in location for the disease. Ganglionic cyst usually treated by aspiration followed by steroid and surgical excision in some cases. We reported a case with anterior knee pain due to patellar intra-tendinous ganglion cyst which treated conservatively with no recurrence even after one year. A ganglion is a benign cystic mass containing clear high-viscosity mucinous fluid with a dense fibrous connective tissue capsule lined by flat spindle-shaped cells that is rich in hyaluronic acid and other mucopolysaccharides , 2. GangA 39-year-old boy presented to us with complaints of dull anterior knee pain for three months. He had visited several general practitioners for which he was given symptomatic analgesics. On examination, there was minimal swelling in form of the fullness of paratendon area and slight extensor lag with quadriceps muscle wasting 1 cm) without any instability with active range of motion 150-1200  confirmed a moving well-defined echogenic lesion within the patellar tendon with approximate 1.2 ml volume. The radiological diagnosis was an intratendinous patellar ganglion (ITPG) cyst. The patient was explained regarding treatment option like aspiration and anti-inflammatory injections/surgery if conservative therapy fails, but he chooses to observe and follow up. Even after one-year follow-up the patient is doing well with no recurrence of symptom.Ganglia arise from the mucoid degeneration and occurs in tendon sheath though they can occur in bones, joints and even other soft tissues . HistoloThe intra-tendinous patellar ganglion is a rare location for the disease but should be kept as one of the differential diagnosis for anterior knee pain. Imaging study is key to diagnosis in an unusual location.


As the number of indicated malignancies for which immune checkpoint inhibitor therapy such as pembrolizumab grows the descriptions of associated immune-related adverse events (irAEs) increases as well. On rare occasions immunotherapy can lead to development of Hemophagocytic Lymphohistiocytosis (HLH) which is a potentially lethal inflammatory disorder characterized by histiocyte activation and cytokine storm. At this time no cases of HLH developing in head and neck squamous cell carcinoma (HNSCC) patients receiving pembrolizumab have been reported.Here we describe the first documented case of pembrolizumab-induced HLH in a 61 year-old male with metastatic HNSCC after having received multiple prior cycles of pembrolizumab without event. Following cycle 14 the patient developed fever associated with new pancytopenia and transaminitis prompting hospital admission. Infectious workup was negative, his metastatic lesions were found to be stable, and there was no evidence of new malignancy. Further workup demonstrated hyperferritinemia and bone marrow biopsy demonstrated hemophagocytosis concerning for pembrolizumab-induced HLH. Etoposide and dexamethasone therapy was initiated leading to clinical improvement and safe discharge.Immunotherapy is a groundbreaking therapeutic intervention for patients with malignancy, however by nature of their mechanism carry a risk of inflammatory side effects. In rare circumstances these inflammatory reactions include potentially deadly syndromes such as HLH. As immunotherapeutics such as pembrolizumab become more widely utilized increased awareness of complications such as HLH is clinically relevant. Checkpoint inhibitors such as pembrolizumab are an innovative therapeutic intervention for patients with an ever-expanding number of malignancies and have led to profound clinical responses. However, this same class of drugs carries a significant risk for inflammatory side effects known as immune-related adverse events (irAEs). As an unintended consequence of their mechanism wherein they are thought to enhance cytotoxic T-cell activity against cancer cells they may also promote the pathologic hyperinflammatory state known as Hemophagocytic Lymphohistiocytosis (HLH). Here we present the first documented case of HLH arising secondary to pembrolizumab therapy in a patient with metastatic head and neck squamous cell carcinoma (HNSCC) who responded well to classical HLH therapy including dexamethasone and etoposide. By presenting this case we aim to increase awareness of potentially lethal complications of immunotherapy given the increasing number of indications for checkpoint inhibitors such as pembrolizumab.A 61 year-old gentleman with a history of p16+ squamous cell carcinoma of the oropharynx with metastatic spread to bilateral lungs initially received cisplatin and radiotherapy with subsequent transition to clinical trial involving 6 weeks of anti-platelet therapy (aspirin/clopidogrel) with concurrent pembrolizumab followed by pembrolizumab monotherapy after completion of the trial. He demonstrated stable disease while on treatment with excellent tolerance to immunotherapy over his first nine months of treatment with no significant irAEs.Four days following cycle 14 of pembrolizumab the patient developed fever > 39.5 °C and malaise prompting a visit to his primary care provider who prescribed a course of oral antibiotics without symptomatic improvement. He subsequently presented to his Oncology clinic, was found to have a new pancytopenia and transaminitis as well as tender hepatomegaly on exam concerning for autoimmune hepatitis, and was admitted to the hospital for methylprednisolone therapy. Admission bloodwork compared to most recent values from 3 weeks prior is presented in Table 2 and etoposide 150 mg/m2 per published guidelines for HLH [Infectious workup including acute hepatitis panel was negative while haptoglobin was within normal limits. Peripheral smear demonstrated pancytopenia with rare schistocytes. Abdominal CT demonstrated periportal edema and gallbladder wall thickening consistent with acute hepatitis as well as new splenomegaly. Due to progressive pancytopenia despite methylprednisolone bone marrow biopsy was performed demonstrating widespread hemophagocytosis Fig.  while adThe patient’s hospital course was complicated by neutropenia with eventual count improvement allowing for safe discharge on dexamethasone taper and outpatient etoposide infusions. Ferritin was trended as a marker of treatment response as demonstrated in Fig. The patient’s outpatient course was notable for an ESBL soft-tissue abscess requiring hospital admission for incision/drainage and antibiotics, which delayed his 4th week of etoposide. In addition, his 7th week dose of etoposide was held due to transient neutropenia and thrombocytopenia. He otherwise completed a standard HLH regimen and by the time of restaging scans 3 months after HLH diagnosis he had returned to his woodworking business, regained all lost weight (~ 11.5 kg), and demonstrated normalization of his liver function testing as well as improvement in his WBC and platelet counts. Initial restaging scans demonstrated stable pulmonary metastatic disease and no new visceral metastases. The patient was monitored off immunotherapy for 8 months without disease progression before developing progressive mediastinal lymphadenopathy and a painful ischial metastatic lesion. He otherwise exhibited unchanged pulmonary disease. The patient underwent radiation to the osseous lesion with clinical improvement and pembrolizumab was restarted. To date the patient has received 5 cycles pembrolizumab since immunotherapy re-initiation with interval reduction in lymph node size, stable pulmonary metastases, no new or progressive bony disease, and no clinical evidence of recurrent HLH.HLH is an uncommon yet life-threatening hematologic disorder characterized by aberrant immune-cell activation, pro-inflammatory cytokine release, and multi-organ dysfunction. HLH is diagnosed based on meeting at least 5 of 8 criteria set forth by the Histiocyte Society representing common pathologic findings in patients with HLH . These cImmunotherapy represents a revolutionary cancer treatment modality that via a wide array of mechanisms increases immune cell activity against tumor cells. Two programmed cell death-1 (PD-1) receptor inhibitors, nivolumab and pembrolizumab, are approved for the treatment of recurrent/metastatic HNSCC. PD-1 is expressed by immune cells and helps regulate self-tolerance by downregulating the immune response. Binding of PD-1 by PD-1 ligand (PD-L1) in the tumor microenvironment compromises normal T-cell function and may promote conversion of cytotoxic T-cells into T-regulatory cells . InterfeHematologic side effects of immunotherapy are less commonly described however reviews of immunotherapeutic complications report the most common hematologic aberrations are hemolytic anemia and immune thrombocytopenic purpura . On veryOn literature review, the case reports discussing immunotherapy-induced HLH have described a wide range of underlying malignancies including Squamous Cell Carcinoma of the Lung, Urothelial Carcinoma, Thymic Carcinoma, Merkel Cell Carcinoma, Breast Cancer, and Melanoma however to our knowledge this is the first report of immunotherapy-induced HLH in a HNSCC patient –11. The The optimal management of irAEs continues to evolve with organizations like the Society for Immunotherapy of Cancer (SITC), National Comprehensive Cancer Network (NCCN), and American Society for Clinical Oncology (ASCO) recently publishing management guidelines , 13. GenThe treatment armamentarium for irAEs such as HLH is rapidly expanding with increasing observational evidence and numbers of clinical trials evaluating cytokine and immune modulation with targeted agents. Daclizumab  has been described as having successfully treated secondary HLH with the proposed mechanism being depletion of pathologically-activated T-cells that demonstrate increased CD25 expression , 17. OthIn addition to studies evaluating novel therapeutics for irAEs there is increasing interest in understanding the safety and efficacy of rechallenging patients with immunotherapy following irAE resolution. To this end, a recent cohort study of patients with lung cancer who developed irAEs evaluated restarting immunotherapy once the initial event had resolved; retreated patients who did not have a tumor response prior to the irAE demonstrated increased overall survival compared to those that were not retreated while retreated patients who exhibited tumor response prior to the irAE demonstrated similar overall survival to those that were not retreated . As prevTo our knowledge, this is the first described case of pembrolizumab-induced HLH in HNSCC. The patient’s HLH was treated successfully with dexamethasone and etoposide. Due to disease progression while on observation pembrolizumab was restarted without complication to date. As the applications of immunotherapy continue to expand there will be more patients who suffer very rare side effects such as immunotherapy-induced HLH. Given the increasing numbers of case reports of immunotherapy-induced HLH as well as the lack of data regarding optimal treatment for HLH increased awareness of the potential development of HLH in patients receiving immunotherapy is clinically relevant and warrants further research.


Aedes triseriatus) (La Crosse virus (LACV) is the most common cause of pediatric arthropod-borne viral  encephalitis in the United States  was notified of a suspected LACV encephalitis case in a boy aged 2 years from western North Carolina. The following day, NCDPH was notified that the patient’s brother, aged 11 years, was also ill with symptoms consistent with viral meningoencephalitis. Laboratory testing confirmed that both siblings had evidence of recent LACV infection .Aedes mosquito larvae  were found on the premises, multiple windows and doors lacked effective screens, and the yard was within close proximity (<50 m) to a mixed hardwood forest. Additional mosquito samples (adult mosquitoes collected by large-bore aspirator and mosquitoes reared from eggs collected by ovitraps) were obtained; mosquitoes from egg collections were tested for LACV infection by real-time reverse transcription–polymerase chain reaction (RT-PCR) (An interagency environmental assessment team who visited the siblings’ residence identified multiple risk factors associated with increased risk for LACV transmission (To identify additional LACV patients among two or more persons residing at the same location, 331 confirmed or probable LACV case reports meeting the case definitionhttps://www.cdc.gov/lac/index.html.These identified cases indicate that LACV disease risk can occur coincidently or noncoincidentally in time in persons at the same physical residence and further support surveillance data indicating that the disease is highly focal, occurring in a limited geographic area (


Nature leads this week with a story about a modern potato famine - this time in Russia. Science explores the continuing skirmishes over drug-patent profits.


The paper presents spatio-temporal dataset of building occupants captured using 200 Bluetooth Low Energy (BLE) beacons installed on different locations in two buildings. It contains 8426 data points of 11 building occupants collected with a sampling rate of 5 seconds during different times in a 12 days' interval. Each spatio-temporal data point comprises location and time components correspond to a building location which can be visualized using an OpenStreetMap (OSM) file of a building. As thThe different values of step length and turning angle exists in a user trajectory which spans over 1000 spatio-temporal points are shown in The provided spatio-temporal dataset collected for developing the applications lack the building information context and require semantic enrichment processes . ConventThe presented dataset is primarily used for developing the applications of safety management in dynamic environments. Analyzing the pre-processed spatio-temporal trajectories can lead to important insights about user movements in facilities. The data article presents a very basic data processing of spatio-temporal trajectories. For advanced trajectory-based applications to understand occupant behaviors, processed trajectories need to be transformed into matrixes, tensors, and graphs for performing additional computations to extract knowledge . Eventua


Bioscience Reports (2018)https://doi.org/10.1042/BSR20180231KD analysis of FP binding data as shown in Table 2 in the Accepted Manuscript. Further investigation using non-reducing SDS–PAGE found previously undetected PDZ–PDZ dimerization triggered by extended incubation with the small-molecule compounds under stringent labeling conditions. This dimerization is not accounted for by our mixed-KD model. The final Version of Record instead reports apparent KD values determined from FP titrations with PDZ domains treated to minimize PDZ–PDZ dimerization while preserving high levels of small-molecule adduct formation, together with associated changes in text.After acceptance and the publication of the Accepted 3, follow-up experiments revealed unexpected variability in the binding constants obtained by the mixed-Bioscience Reports.This has been approved by the Editorial Board of


OBJECTIVES/SPECIFIC AIMS: Bladder cancer patients being considered for immune checkpoint blockade are often judged on immunohistochemical staining for the checkpoint target protein PD-L1 in the original surgery or biopsy sample. However, sampling error or the clinical evolution of most patients’ cancer can render the original PD-L1 assessment no longer accurate. In contrast, circulating tumor cells (CTCs) allow serial noninvasive sampling of the current tumor status throughout a patient’s clinical course including those with the highest metastatic potential. We therefore sought to develop a method for quantifying PD-L1 expression in CTCs towards addressing inherent limitations of current UC management. METHODS/STUDY POPULATION: This work utilizes both cancer cell lines as well as patient samples. Positive and negative control cancer cell lines were assessed via “industry standard” antibodies for PD-L1 expression via Western blots and immunofluorescence, and a threshold-based method was developed for reliable quantification. PDL-1 expression was additionally verified via interferon-mediated up-regulation. CTCs isolated from bladder cancer patient samples via a density centrifugation method were then assessed for PD-L1 via the same antibodies. RESULTS/ANTICIPATED RESULTS: We will show preliminary preclinical and clinical data that validates the sensitivity and specificity of our assay. A case study will be presented that illustrate the potential useful of the novel approach we describe and which should be complementary to current clinical practices. In a patient with metastatic bladder cancer, this method effectively detected the PD-L1 expression in CTCs taken at a time coincident to when the patient derived an excellent response to the PD-L1 checkpoint inhibitor Pembrolizumab. DISCUSSION/SIGNIFICANCE OF IMPACT: This work highlights the potential utility of CTCs in the management of bladder cancer. It may be the case that this assay in conjunction with current methods of patient selection for immunotherapy may allow for better response prediction than either method alone.


OBJECTIVES/SPECIFIC AIMS: We aim to show that amyloid accumulation in an animal model of Alzheimer’s disease leads to a preferential disruption of inhibitory parvalbumin-expressing interneurons, and the peri-neuronal nets that surround them, resulting in downstream network alterations to potentially explain early mechanisms of memory impairment in the disease. METHODS/STUDY POPULATION: We employ the 5xFAD mouse model of familial Alzheimer’s disease crossed with transgenic mouse lines which fluoresce red or green in specific neuronal populations. We conducted immunostaining and immunoblotting in amyloid accumulating animals compared with healthy littermate control. Future experiments will be performed in human postmortem tissue to translate these results from mouse model to the human population. Electrophysiological recordings from acute mouse brain slices were conducted as a functional assay. RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that PNNs are disrupted and that activity-associated levels of PV are reduced. Both inhibitory PV and excitatory pyramidal cell populations exhibit altered spiking and synaptic activity during sharp wave ripple events. DISCUSSION/SIGNIFICANCE OF IMPACT: By elucidating the specific neuronal sub-type that is responsible for hippocampal network disruption, future studies could attempt a targeted optogenetic or pharmacological intervention to restore network activity important for memory consolidation.


The patient was operated via the pterional approach but resection had been halted due to severe haemorrhage and only tumour biopsy could be obtained. The diagnosis of cavernous sinus haemangioma was established by histopathology and confirmed by subsequent digital subtraction angiography. The patient refused second surgery or adjuvant radiosurgery and the treatment strategy was observation and follow-up. Retrospectively, we included the key radiographic features of cavernous sinus haemangioma which would facilitate pre-operative diagnosis and avoid unforeseen operative complications. Diagnostic radiographic features include a well-defined mass in the cavernous sinus which shows isodense to slightly hyperdense attenuation on non-contrast CT scan with possible adjacent pressure bone remodelling. On MRI, it shows remarkable high T2 signal; intense homogenous enhancement or characteristic progressive contrast enhancement on sequential enhanced images. On digital subtraction angiography, it may demonstrate a vascular blush.Cavernous haemangioma of the cavernous sinus is a rare vascular malformation. It's often confused with other parasellar masses. Here, we report a case of a female with a left parasellar mass which was misdiagnosed as schwannoma  A 48-year-old female presented with a history of progressive headache and blurring of vision of 1 year duration. Her physical and neurological examinations were unremarkable. Routine laboratory investigations and pituitary hormonal profile were all normal.Non-contrast CT scan of the brain revealed a large extra axial mass at the sellar and left parasellar regions. It appears homogeneous and shows isodense to slightly hyperdense attenuation relative to the adjacent brain parenchyma. No internal calcifications or necrosis. The lesion effaces the prepontine cistern. Examination of the bone window showed smooth bone remodelling and erosion of the medial part of the sphenoid wing. No evidence of bone hyperostosis. T1 weighted images and remarkable high signal on T2 weighted images  vascular spaces lined by flat endothelial lining. Some vascular spaces were empty but most spaces were filled with blood cells ; a pictuFollowing surgery, digital subtraction angiography was performed and showed a tumour blush at the lateral projection during the late arterial and venous phases supplied from small meningeal branches of the internal carotid artery . It alsoPost-operative neurological examination revealed paralysis of the left third cranial nerve with ptosis in the left eye and loss of light reflex; however, it gradually improved. The patient refused second surgery for total excision of the lesion or adjuvant radiosurgery and preferred the strategy of follow up and observation.1,2 Cavernous haemangioma is one of the four most common types of cerebral vascular malformations.2 They commonly occur intra axially within cerebral parenchyma1,3 ; however, they can also occur within extra axial spaces and when they occur extra axially they have the propensity to develop at the cavernous sinus.4 Extra axial haemangiomas have the same histologic features as intra axial lesions but have a different clinical picture, radiologic findings, and management.3Cavernous haemangiomas, also known as cavernous angiomas or cavernomas, are defined as vascular malformations formed of abnormal dilated vascular spaces with no intervening neural tissue.5 as in our case. Cavernous sinus haemangioma has not been reported before in the Egyptian population; however, several cases were documented in Japan.1,4,6,7 The clinical presentation is insidious and patients usually suffer from headache and dysfunction of the cranial nerves passing through the cavernous sinus, presenting by ptosis, diplopia or facial neuralgia. Optic chiasm may be compressed in large masses and patients may thus present with decreased visual acuity.5Cavernous sinus haemangioma has a predilection to middle-aged females7,8Cavernous sinus haemangiomas are divided pathologically into three types. Type A is a sponge-like lesion with intact pseudocapsule which consists of thin-walled vascular sinusoids with scanty intervening connective tissue; this type usually demonstrates homogeneous contrast enhancement on MRI. Type B is a mulberry-like lesion with absent or incomplete pseudocapsule which contains ample solid parenchyma with well-formed vasculature and connective tissue, and Type C which has both Type A and Type B compositions. Types B and C usually demonstrate heterogeneous contrast enhancement on contrast enhanced MRI studies.7,8 Jinhu and colleagues retrospectively reported MRI features of 21 surgically confirmed cavernous haemangiomas of the cavernous sinus. Most of the cases presented with a well-demarcated dumbbell-shaped appearance at the parasellar region extending to the middle cranial fossa laterally and sellar regions medially. Similar to our case, the cavernous haemangioma usually encircles the cavernous segment of the internal carotid artery without occluding it.7 Non-contrast CT shows a well-demarcated lesion of similar density or slightly higher density to the brain parenchyma . It also shows intense homogeneous post-contrast enhancement. Calcifications are not common in haemangiomas however adjacent bony remodeling and erosion may happen.2 MRI reveals mass which elicits isointense or hypointense signal on T1 weighted images and remarkably hyperintense (CSF like) signal on T2 weighted images with homogeneous post-contrast enhancement.1 Some studies observed heterogeneous enhancement on the first contrast-enhanced series and subsequent homogeneous contrast enhancement or progressive “filling in” enhancement on subsequent contrast-enhanced series especially in histopathological types B and C.7 Unlike intra-axial cavernous angiomas, cavernous sinus haemangioma does not demonstrate T2 hypointense margin or blooming effect on gradient-echo sequences secondary to scanty hemosiderin deposition.9 Angiographically, haemangiomas exhibit a high degree of vascularity and a vascular blush has been reported5 ; however, they may be angiographically subtle.2 Tc-99m tagged red blood cell (RBC) imaging was recently recommended for the diagnosis of cavernous sinus haemangioma in the setting of nondiagnostic surgical biopsy.8,9Radiological imaging is essential for the prediction of cavernous sinus haemangioma and differentiation of haemangioma from similar intracavernous sinus masses. CT, MRI and digital subtraction angiography are helpful for diagnosis of cavernous sinus haemangioma.2 Our case was similar to meningiomas as it elicited homogeneous signal on T1 and T2 weighted images and was similar to trigeminal schwannomas as it elicited high T2 signal and caused widening of the ipsilateral foramen ovale; however, unlike meningiomas and schwannomas; the mass elicited characteristic remarkably high (CSF like) signal on T2 weighted images. Cartilaginous masses such as chondrosarcomas or chordomas are also hard to differentiate from cavernous sinus haemangiomas because they elicit high signal on T2 weighted images and demonstrate intense contrast enhancement; however, they are usually associated with calcifications and adjacent bone destruction.10 A characteristic MR feature of the lesion in our case was its dynamic enhancement pattern. Following contrast administration, the lesion showed early heterogeneous contrast enhancement on the initial axial images that changed to homogeneous enhancement on the subsequent coronal and sagittal post-contrast images. This progression of contrast enhancement took only the acquisition time for obtaining the contrast enhanced T1 weighted sequences (about 2 min per sequence); this can be explained by the pathological nature of the lesion being composed of thick-walled vascular sinusoids which caused this short delay to achieve homogeneous contrast enhancement. This rapid increase in the degree of contrast enhancement is characteristic for cavernous sinus hemangioma as it is not seen in other lesions7 ; angioblastic meningiomas, neurilemomas, and chondrosarcomas may display heterogeneous enhancement however they usually lack progressive “filling in” enhancement pattern or delayed homogeneous enhancement on subsequent sequences.7The differential diagnosis includes similar cavernous sinus masses.11 However, the reported perioperative mortality rate was high due to uncontrollable severe bleeding.12 Therefore the pre-operative diagnosis is important because it requires the surgeon to be ready to tackle such pathology with low surface bipolar coagulation with no attempt to debulk the lesion without complete coagulation and shrinkage. Thus, the surgeon mindset should be delivered to that pathology.1,2 Also, piecemeal removal can be performed after the main feeding arteries are interrupted.4 Stereotactic radiosurgery or radiation therapy has been proposed as primary therapy for patients with inoperable lesions, for those that undergo limited subtotal resection as adjuvant therapy or as a pre-treatment for direct surgical excision as it suppresses tumour growth and decreases vascularity of the mass.13,14Treatment of choice is surgical excision.Cavernous sinus cavernous haemangioma is a rare vascular malformation and an uncommon cause of cavernous sinus masses.Differentiation of cavernous sinus haemangioma from similar intracavernous sinus masses like meningiomas and schwannomas is often challenging.Preoperative diagnosis is crucial as it requires a different surgical technique to avoid intraoperative profuse bleeding.MRI, CT and angiography studies can help to predict the diagnosis and to differentiate cavernous sinus haemangioma from similar cavernous sinus masses.Cavernous sinus haemangioma on non-contrast CT scan appears as a mass in the cavernous sinus which shows isodense to slightly hyperdense attenuation with intense homogeneous contrast enhancement and possible adjacent smooth bone remodeling and erosion.T2 signal; intense homogenous enhancement or characteristic progressive contrast enhancement on sequential enhanced images.Cavernous sinus haemangioma has characteristic MRI features of remarkably high Angiographically, cavernous haemangiomas may show vascular blush as they exhibit a high degree of vascularity but sometimes they might be angiographically subtle.


Background and Aims: Postpolypectomy bleeding and incomplete polyp removal are important complication and quality concerns of colonoscopy for colon cancer prevention. We investigated if endoscopic mucosal stripping (EMS) as a technical modification of traditional cold snare polypectomy to avoid submucosal injury during removal of non-pedunculated colon polyps could prevent postpolypectomy bleeding and facilitate complete polyp removal.Methods: This is an Internal Review Board exemption-granted retrospective analysis of 5,142 colonoscopies with snare polypectomy performed by one of the authors (ZJC) at Minnesota Gastroenterology ambulatory endoscopy centers during a 12-year period divided into pre-EMS era  and EMS era  with systemic adoption of EMS starting 2013. Change in postpolypectomy bleeding rate before and after EMS adoption and EMS polypectomy completeness were evaluated.Results: Zero postpolypectomy bleeding case was found during EMS era (rate 0%) compared with 10 bleeding cases during pre-EMS era (rate 0.336%). This difference was statistically significant (P = 0.0055) and remained so after excluding 2 bleeding cases of pedunculated polyps (P = 0.012). All bleeding cases involved hot snare polypectomy. Histological examination of the involved polyps showed substantial submucosal vascular damage in contrast to a remarkable paucity of submucosa in comparable advanced polyps removed using EMS. Both biopsy and follow-up colonoscopy examination of the polypectomy sites confirmed that EMS more completely removed non-pedunculated advanced polyps.Conclusions: EMS polypectomy was effective in preventing postpolypectomy bleeding and facilitated complete polyp removal. Colonoscopy for colon cancer screening is effective at both mortality reduction through early detection and prevention through removal of precancerous polyps –8. TheseAside from EMR and ESD, little attention has been given to polypectomy technique as a risk factor for postpolypectomy bleeding. Indeed, the generally accepted and widely used traditional snare polypectomy technique to guillotine the ensnared polyp with or without heat coagulation has not changed much for nearly 5 decades –37. To pThis was a retrospective investigation of data incorporating electronic medical record and pathology slides at Minnesota Gastroenterology, PA (MNGI). An Internal Review Board exemption was granted for the investigation. The patients were those who had colonoscopy with snare polypectomy under Current Procedural Terminology (CPT) code 45385 by ZJC at MNGI ambulatory endoscopy centers during a 12-year period divided into pre-EMS era (2005–2012) and EMS era (2013–2016). A database search was performed for postpolypectomy bleeding cases requiring hospitalization and advanced polyps defined as polyps with villous features, high-grade dysplasia, sessile serrated adenoma with cytological dysplasia (SSACD) as well as any adenomatous polyps 10 mm or larger. Because MNGI had extensive local practice coverage and a 24-h staffed complication telephone line, it had an almost complete catch rate for complications which were peer-reviewed and fed-back to the involved endoscopists for quality improvement.Endoscopic mucosal stripping (EMS) is the endoscopic removal of polyp-containing mucosa by mechanical stripping using a cold snare. It is a modification of TCSP in that EMS strips the mucosa off the ensnared submucosa at the potential space between them Figure  rather tFor small polyps (≤ 5 mm), TCSP generally works well. To ensure complete resection, we prefer snare over biopsy forceps except for diminutive polyps 2 mm or smaller  and routWhile submucosal entrapment can be avoided for smaller polyps by optimally placing the snare and gently lifting the polyp, this may become inevitable with larger polyp removal. Although the above described technique still applies, the entrapped submucosa often prevents separation of snare from polypectomy site even after the polyp-containing mucosa has already been stripped off. Under such circumstances, there is no need to further pull the snare by brute force. Instead, opening the snare slightly and sliding it over the entrapped submucosa will release the snare and any stripped off yet still seemingly attached polyp-containing mucosa from the polypectomy site. The entrapped submucosa from these larger polyps frequently forms a thicker pseudostalk but submucosal injury remains minimal.For even larger polyps that cannot be removed in one piece, EMS piecemeal polypectomy can be performed. Because EMS' lack of submucosal injury creates a less bloody or deformed polypectomy site in comparison with traditional cold or hot snare polypectomy, any residual polyp tissue is better visualized facilitating complete polyp removal Figure .Hospitalization-requiring postpolypectomy bleeding rates of all and non-pedunculated colon polyps before and after EMS adoption.Completeness of EMS polyp removal determined by polypectomy site biopsy and examination during follow-up colonoscopy at intervals recommended by national society guidelines , 14.Colonoscopies were performed using variable stiffness colonoscopes  for most cases and FUSE full spectrum colonoscopes  for a few cases as part of a trial. Polypectomies were performed using mostly oval snares  and, in a few cases, spiral snare  and Exacto snare .As part of MNGI quality measurement, the following annual colonoscopy statistics were reported for ZJC for 2014 and 2016: cecum reach rate 99.5–100%, screening colonoscopy adenomatous polyp detection rates 50.3–60.1% for males and 42.1–54.0% for females.Statistical analysis was performed using Fisher's exact test.n = 2973) and EMS era  (Table P = 0.0055) and remained so after excluding the 2 pedunculated polyp cases (P = 0.012).A total of 5,142 colonoscopies with snare polypectomy performed by ZJC at MNGI ambulatory endoscopy centers during 12 years were divided into pre-EMS era  that were removed using a cold snare, all were removed using a hot snare. These included ten 8–40 mm TAs , one 25 mm tubulovillous adenoma (TVA), four 6–10 mm sessile serrated adenomas (SSA) and one 5 mm lipoma. Except for one case which only had partial retrieval of the resected polyp and had no submucosa microscopically, all remaining nine cases showed evidence of cauterized submucosa often with visible blood vessels near cauterized edge as illustrated in Figure For comparison, we also microscopically examined 20 consecutive cases of advanced colon polyps removed using EMS. These polyps contained only variable amount of muscularis mucosae and scanty, if any, submucosa with no blood vessels Table . These fExtensive biopsies were performed on the edge x4) and pseudostalk (x1) of 10 randomly selected advanced polyp sites after endoscopically complete removal by EMS. No polyp residue was found in any samples. Ninety-seven neoplastic EMS polypectomy sites were followed from 6 months to 4 years, including 38 polypectomy sites in 23 patients after removal of advanced polyps. None of the 59 non-advanced neoplastic polyp (< 10 mm and without advanced features) sites had any residual or recurrent polyps on follow-up colonoscopy. The vast majority  advanced polyp sites also had no polyps on follow-up colonoscopy  and was carried out in accordance with the approved protocol of Clinical and Histopathological Review of Mucosal Stripping as a Colonoscopy Polypectomy Technical Innovation and the recommendations of Minnesota Gastroenterology Quality Committee. All subjects gave written informed consent to the colonoscopy procedures and treatment in accordance with the Declaration of Helsinki.This retrospective study was granted Exemption from IRB Review Determination on May 12, 2016 (IRB ID: 5502) by Sterling IRB (ZC initiated the investigation concept and design, acquisition, analysis and interpretation of data, drafting and revising of the manuscript. KB participated in the acquisition, analysis and interpretation of data as well as critical revision of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Inhibitory control, a key modulatory component of cognition guiding strategy and behaviour, can be affected by diverse contingencies. We explore here the effect of expectation of reward over behavioural adjustment in a Stop Signal Task modulated by reward. We hypothesize that cognitive control is modulated by different expectation of the reward.N = 21) were informed of the different monetary feedbacks they would receive after each successful inhibition. Unexpected Reward participants (N = 24) were only told that they would receive monetary reward after correct inhibitory trials, but not the amounts or differences.Participants were allocated to two groups differing in their degree of knowledge in what to expect from rewards. Expected Specific Reward participants -, compared to the Unexpected Reward group.Knowledge of reward magnitudes seems to play a role in cognitive control irrespective of feedback magnitude. The manipulation of reward expectation appears to trigger different strategies for cognitive control, inducing a bottom-up effect of external cues, or a top-down effect given by the anticipation of incoming rewards. This is an early exploration to unearth possible higher order modulators - expectation and motivation- of cognitive control. This approach aims to gain insight into diverse psychopathological conditions related to impulsivity and altered reward systems such as Attention Deficit Hyperactive Disorder (ADHD), personality disorders, substance abuse, pathological gambling and cognitive aspects of Parkinson Disease.The online version of this article (10.1186/s40359-019-0332-x) contains supplementary material, which is available to authorized users. The concept of inhibitory control in human cognition can be approached from its basic motor and reflexive aspects to elaborate control processes such as planned actions and strategies , it can reactive control process  group analyzes. Between conditions [Increasing Vs Decreasing]. GLM Univariate between blocks [effect of order] Group analysis for block comparison between groups [ESRG Vs URG]. Table S6. Reward Stop Signal Task (RSST). Group analysis for block comparison between groups [ESRG Vs URG] and between conditions [Increasing Vs Decreasing]. GLM Univariate between blocks [effect of order]. Table S7. Group analysis for reward magnitude comparison between groups [ESRG Vs URG] and between conditions [Increasing Vs Decreasing]. GLM Univariate between rewards [effect of reward magnitudes] Figure S1. Time performances for Expected (ESRG) and Unexpected (URG) reward groups. (PDF 445 kb)


A 57-year-old woman with a 15-year history of a slowly growing fibrous dysplastic maxillary bony tumor underwent total left maxillectomy with subsequent maxillary reconstruction with anterolateral thigh single perforator free flap and orbital floor reconstruction with a titanium mesh implant. A 57-year-old woman presented with a 15-year history of a slowly growing left maxillary bony tumor causing significant proptosis and distortion of her left orbit with associated loss of vision . The patWhat are the material options for reconstruction of the orbital floor after orbital-content sparing total maxillectomy?What are the options for soft tissue reconstruction after total maxillectomy?What is fibrous dysplasia?What are the treatment options for fibrous dysplasia tumors?Numerous materials, both alloplastic and autogenous, are available for reconstructing damaged or resected orbital walls to restore orbital structure and volume. Autogenous calvarial bone graft has traditionally been the standard material used and shown to have a slight advantage in donor site morbidity over the use of rib and ilium.The use of local, regional, or distant free flaps for soft tissue reconstruction after total maxillectomy can result in good function and aesthetics. Free flaps are commonly used; however, a temporalis muscle flap may be used for small- to medium-sized palate defects.GNAS1) gene, which encodes the alpha subunit of the stimulatory G protein.10Fibrous dysplasia is a noninherited developmental anomaly of bone where bone marrow in the medullary cavity is replaced by fibrous connective tissue and poorly formed trabecular bone.Incidentally discovered, asymptomatic, radiographically characteristic fibrous dysplasia lesions do not require further assessment, and follow-up radiographs every 6 months to look for new progression are recommended.A 57-year-old woman with a 15-year history of a slowly growing fibrous dysplastic maxillary bony tumor underwent total left maxillectomy with subsequent maxillary reconstruction with anterolateral thigh single perforator free flap and orbital floor reconstruction with a titanium mesh implant.


The remainder of laboratory studies were normal. Computed tomography (CT) images were obtained  with periumbilical and left upper quadrant abdominal pain. The pain began abruptly 12 hours prior to presentation and was worsening. Her pain increased with supine position and was associated with nausea and vomiting. Her past medical history was significant for hypertension, gastroesophageal reflux disease and obesity. Prior to presentation in our ED, she underwent a laparoscopic Roux-en-Y procedure for weight loss 10 years prior at an outside hospital. On arrival, pertinent vitals included a heart rate of 115 beats per minute, 20 breaths per minute and blood pressure of 190/100 mmHg. Laboratory studies in the ED were significant for a leukocytosis  imaging showing a characteristic “swirl sign.”What is the major impact of the images?While the surgically altered abdomen may seem intimidating anatomically, there are tell-tale abnormalities that can be easily recognized on CT by the informed physician.How might this improve emergency medicine practice?We can be better advocates for bariatric surgery patients by knowing their potential post-operative complications and associated findings on imaging.


We present a 31-year-old male who sustained an isolated stellate corneal laceration associated with an open globe injury. The patient presented with mild, right eye pain one hour after glass was sustained to the face during a motor vehicle collision. Visual acuity was 20/100 (baseline 20/20), but no obvious facial or ocular trauma was noted. Extraocular movements were intact. Slit lamp examination revealed a central stellate corneal laceration, peaked 4mm non-reactive pupil, flat anterior chamber, and a falsely negative Seidel sign . IntraocOcular trauma accounts for roughly 3% of emergency department visits and is a major cause of unilateral visual impairment and permanent visual loss in young individuals.Documented patient informed consent and/or Institutional Review Board approval has been obtained and filed for publication of this case report.What do we already know about this clinical entity?Open globe rupture is an ophthalmologic emergency. Speedy recognition by the emergency department provider and ophthalmologic intervention are essential to restoring functional outcome.What is the major impact of the image(s)?A globe rupture with false negative Seidel sign is a rare but known occurrence when ocular contents “plug” the opening, as seen in this patient image.How might this improve emergency medicine practice?The case highlights the importance of good clinical exam after ocular trauma. Providers should consider further workup with computed tomography imaging with any injury involving high-velocity metal or glass.


Metastases to the orbit occur rarely in midgut neuroendocrine tumor (NET) patients with only 20 cases reported to date. Patients typically present with bilateral involvement of the recti muscles and experience symptoms such as diplopia, proptosis, and decreased vision. Although orbital MRI remains the gold standard for imaging orbital disease, many orbital lesions are now detected on somatostatin-receptor (SSTR) based imaging such as 68Ga-DOTATATE PET-CT.Patient 1 is a 72 year-old female with a well-differentiated G3 ileal NET who was incidentally diagnosed with orbital metastases during a hospitalization for pre-septal cellulitis in 2018. Her disease has been controlled with capecitabine rather than local therapy.Patient 2 is a 68 year-old male with a G2 ileal NET who was diagnosed with orbital involvement after developing left peri-orbital swelling in 2017. He was found to have bilateral rectus muscle involvement and was treated with image-guided radiation therapy (IGRT) to both orbits and achieved disease control.Patient 3 is a 63 year-old female with a well-differentiated G3 ileal NET who was incidentally diagnosed with bilateral orbital masses in her recti after undergoing a 68Ga-DOTATATE PET-CT in 2015. She was asymptomatic initially however has now developed diplopia. She will be starting 177Lu-DOTATATE peptide radionuclide receptor therapy (PRRT) shortly.Patient 4 is a 72 year-old male with a grade 2 ileal NET who was incidentally diagnosed with a left lateral rectus metastasis in 2007. This was monitored via surveillance MRI until it began to grow and became symptomatic in 2015. The patient received stereotactic radiation to the site and has been asymptomatic since.Patient 5 is a 61 year-old female with a grade 2 ileal NET who developed progressive diplopia in 2016. Bilateral orbital metastases were noted on orbital MRI and she completed IGRT to the sites shortly thereafter. In the setting of continued growth of the masses she was switched to chemotherapy with capecitabine which has controlled her orbital disease.NETs can metastasize to the orbits. Orbital disease now often is detected on SSTR-based imaging rather than orbital MRI; when found, it changes treatment approach and surveillance for patients. Orbital metastases represent an exceedingly rare metastatic manifestation of neuroendocrine tumors (NETs) and occur through hematogenous dissemination via the carotid and ophthalmic artery . OrbitalThe most common symptoms at presentation for patients with metastatic orbital involvement include diplopia, proptosis, and decreased vision. Other common symptoms include eyelid swelling, chemosis and redness. Unilateral rather than bilateral involvement is more frequent, and the rectus muscles are often involved , 8. The Patients with orbital involvement from NETs typically carry an excellent prognosis with 10-year survival rates of close to 40%, which is in stark contrast to the poor systemic prognosis seen in other malignancies when orbital involvement is detected . This maPatient 1 is a 72-year-old female who was initially diagnosed in 1997 with a well differentiated G3 (Ki-67 20%) metastatic jejunal NET. Her primary tumor was resected after diagnosis and a liver transplant was performed in 1998 for bulky symptomatic liver metastases. She has received a series of therapies including octreotide, lanreotide, and everolimus for her carcinoid syndrome (CS) and disease control. In May 2017, a 68Ga-DOTATATE PET-CT revealed somatostatin receptor (SSTR) avidity in bilateral orbits although she was asymptomatic from a visual symptom standpoint  metastatic ileal NET in 2012. Post-resection of his primary, the patient began treatment with octreotide. Eventually, he enrolled on a clinical trial with 177Lu-DOTATATE PRRT. During a hospitalization in November 2017, while admitted for abdominal pain, he developed left peri-orbital swelling. This prompted an orbital MRI which demonstrated bilateral extraocular masses in his recti muscles  disease on later biopsies. She had stable disease controlled on octreotide until 2014 when she had disease progression which required everolimus, multiple hepatic artery embolizations and debulking of bulky adenopathy in her right paratracheal region. She underwent her first 68Ga-DOTATATE PET-CT in April 2015 which revealed bilateral extraocular masses in her right medial and left infraorbital rectus muscles. She was asymptomatic initially from these lesions; however, during her initial visit at VUMC in June 2018 for consideration of 177Lu-DOTATATE PRRT, due to persistent CS, she mentioned worsening diplopia and visual acuity. A pre-treatment 68Ga-DOTATATE PET-CT was repeated which revealed increased SSTR avidity in the recti at the site of the previously known lesions  metastatic small intestine (not otherwise specified) NET in February 2010. She remained symptom free until April 2014 when she was started on monthly octreotide. In the setting of progressive disease, she subsequently received sunitinib and everolimus. She began to develop progressive diplopia and right ocular pain in August 2016. This prompted an orbital MRI which revealed bilateral recti masses in the right lateral and superior left medial muscles. She was evaluated by radiation oncology shortly thereafter and was treated with IGRT to 52Gy, which completed in October 2016. Although her right ocular pain improved, she had persistent diplopia. Her post-treatment orbital MRI in January 2017 revealed a mild increase in size of her right lateral rectus mass (Fig. We have described here five cases of midgut NET patients who presented with orbital metastases at various stages of their disease presentation. Of the five patients, three were initially asymptomatic from their orbital involvement. Four out of the five patients presented with bilateral involvement, which is different from the unilateral predominant pattern described in the literature. This discrepancy may be due to the increased sensitivity of current imaging modalities which capture lesions missed by prior imaging techniques. All the patients had rectus muscle involvement which is the most common orbital structure involved from existing case descriptions Table . OrbitalThree of the five patients were treated with external beam radiation; two of these patients received IGRT and one received five fractions of stereotactic radiosurgery. Two of the three patients who received radiation achieved improved visual symptoms and disease control locally. One patient progressed through IGRT, but eventually achieved disease control with capecitabine. Of the two patients who did not receive radiation therapy, one achieved intra-orbital disease control with capecitabine plus temozolomide. We are hopeful the other patient will also achieve orbital disease control with PRRT. None of the patients in our series had any attempt at surgical resection.Prior to the 1980s, orbital exenteration was considered the recommended treatment for orbital metastases . With imOne of the therapeutic areas of great promise in midgut NET is PRRT. 177Lu-DOTATATE PRRT was FDA approved in January 2018 and represents another cytoreductive treatment option available for patients. In Europe, PRRT approaches with other radionuclides such as 90Y have been utilized successfully. 177Lu-DOTATATE PRRT involves targeted radiation where lutetium 177, a beta emitting radionuclide, is conjugated to a SSTR analog and is internalized by neuroendocrine cells expressing SSTR2 . ReportsOrbital metastases are rare, occurring in 2–3% of all malignancies . Of the


Intracranial lipomas represent approximately 1% of intracranial lesions generally felt to represent the abnormal persistence of the meninx primitiva and are commonly accompanied by various developmental brain abnormalities. We report a case of midline intracranial lipoma and evolving frontal lobe fluid-attenuated inversion recovery (FLAIR) abnormality concerning for glial neoplasm in a patient with intractable epilepsy. Our case shows evolving magnetic resonance imaging (MRI) features over two decades raising suspicion for low-grade neoplasm which was ultimately found to represent cortical dysplasia. Intracranial lipomas are rare lesions generally felt to represent the abnormal persistence of the meninx primitiva. They represent approximately 1% of intracranial lesion and are commonly accompanied by various developmental brain abnormalities. Most lipomas reported are located near the midline and are pericallosal in nature with agenesis of the corpus callosum commonly observed ,3. We reOur patient is a 43-year-old ambidextrous male with a 20-year history of intractable seizures. His seizure semiology typically included a hot flash and other sensory auras with evolution into focal motor activity predominately on the right. Workup for seizure etiology included magnetic resonance imaging (MRI) revealing the large midline lipoma, partial callosal agenesis, and an adjacent lesion in the left frontal lobe presumed to represent a glial neoplasm based on the radiographic appearance. The left anterior medial frontal lobe lesion consisted of nodular calcification with peripheral enhancement and extensive FLAIR signal changes involving bilateral cingulate gyri and the left frontal lobe Figure .Medical management efforts had failed to control his seizures and he was referred for surgical treatment options. The enhancing lesion was noted to progress with additional imaging and the extent of edema also expanded. The concern for progressive glial neoplasia and poor seizure control prompted a recommendation for surgical resection. The decision was made to proceed with neuronavigation-guided resection of the left frontal enhancing mass and partial frontal lobectomy utilizing intraoperative electroencephalogram (EEG), cortical mapping, and somatosensory evoked potentials (SSEP) monitoring.Intraoperative samples sent for frozen pathology were found to have Rosenthal fibers and focal calcification and felt to likely represent glial neoplasm. Permanent pathologic evaluation revealed a lipoma and focal cortical dysplasia, Palmini Type IA, in the adjacent brain. The mild cortical architectural abnormalities and associated white matter gliosis can be seen on hematoxylin and eosin (H&E) and glial fibrillary acidic protein (GFAP) stains and neurofilament protein (NFP) staining in the areas of gliosis shows no evidence of dysmorphic neurons, giant neurons or balloon cells Figure .Post-operative imaging Figure  shows a Post-resection recovery included a moderate supplementary motor area syndrome including hemiparesis, delayed speech, and changes in effect. These changes gradually resolved and the patient was found to be neurologically intact at outpatient follow-up. Seizure control occurred immediately after resection. Antiepileptic agents were continued and gradually removed over subsequent months without recurrence. The patient remained seizure-free three years post resection. 18-month follow-up imaging found stable T2/FLAIR changes with small unchanged areas of perilesional enhancement Figure .Intracranial lipomas are commonly accompanied by other abnormalities of development which are likely a result of a defect in differentiation of the meninx primitiva during neural tube flexion. Although various cortical abnormalities have been described in association with intracranial lipomas, the underlying pathology remains poorly understood ,5. A fewWhile concurrent abnormalities are often related to a common underlying developmental pathology, this is simply unknown. In the setting of lipomas, cortical dysplasias may change over time.


Atrioventricular groove hematomas during mitral valve surgery range from simple hematomas to complex atrioventricular disruptions that cause frank rupture with massive bleeding and subsequent mortality. A small or moderate-sized hematoma is reported to be present in the left atrioventricular groove in 10 to 30% of all patients immediately after mitral valve replacement. Despite the fact that atrioventricular groove hematomas are inherently unstable and unpredictable, conservative strategies are recommended due to the high mortality associated with additional surgical repair. Such conservative strategies, however, would not resolve the potential risk of rupture, and there also appears to be a certain degree of uncertainty to be overcome using the current advances in cardiac surgery.We present a case of atrioventricular hematoma during double valve replacement which was treated with conservative management. A left ventricular pseudoaneurysm developed after surgery, but spontaneously resolved completely within six months. After reflecting on our case, we developed a check sheet, including the anesthesiologist’s transesophageal echocardiography findings, for reasonable intraoperative decision-making regarding conservative management vs. additional surgical repair. Our check sheet helps organize the pathophysiological understanding of the injury and integrates partial findings from complementary viewpoints, and can be used to accurately assess intense situations and develop a common understanding among surgical team members.Our case involved an atrioventricular groove hematoma that occurred during mitral valve surgery and caused a left ventricular pseudoaneurysm. Conservative strategies yielded positive results. We hope our experience and original check sheet will be of value to surgical teams facing similar situations. Atrioventricular groove (AVG) hematomas during mitral valve surgery range from simple hematomas to complex AVG disruptions that cause frank rupture with massive bleeding and subsequent mortality . KirklinA 64-year-old man, with severe multi-valvular disease detected during preoperative evaluation for colon diverticulitis, was referred for heart valve surgery. He had suffered recurrent life-threatening diverticular bleeding and accompanying heart failure. Transthoracic echocardiography (TTE) showed severe aortic regurgitation classified as type II (cusp prolapse) according to the functional classification developed by El Khoury et al., and severe mitral regurgitation caused by degenerative bi-leaflet prolapse with multiple eccentric regurgitant jets, exacerbated by secondary factors, including mitral annular and left ventricular (LV) dilation. Secure mitral repair with a shorter cardiopulmonary bypass (CPB) time would have been difficult due to the complex lesion; double valve replacement (DVR) was a safer and simpler procedure.The anterior leaflet of the mitral valve was excised and its chordae cut at their insertion into the papillary muscles. The posterior leaflet and its subvalvular apparatus were preserved. A 29-mm bovine pericardial bioprosthesis was implanted in the intra-annular position and a 25-mm bovine pericardial bioprosthesis replaced the prolapsed aortic valve .After DVR completion, extensive hematoma occurred surrounding the posterior atrioventricular groove during weaning from CPB. We suspected that deeply placed sutures around the posterior mitral annulus might have cut through the left ventricular wall. Full CPB support, aimed at a prompt reduction of the intraventricular pressure, was re-instituted immediately, and inotropic agents were tapered off to weaken the force of muscular contractions with the hope of suppressing the exacerbation of the injury. Routine intraoperative transesophageal echocardiography (TEE) monitoring was not utilized in this case; stable left ventricular contractility without bleeding was confirmed only by direct inspection before choosing conservative management. The re-weaning process was performed without any hemodynamic instability. The sternum was closed under stable conditions after administration of protamine sulfate.The patient was taken into intensive care and extubated 12 h postoperatively. Postoperative routine TTE was unremarkable, whereas contrast-enhanced, electrocardiography (ECG)-gated, multi-detector computed tomography (CT) imaging on postoperative day 18 revealed a pseudoaneurysm (20 × 12 mm) arising from the posterior wall of the left ventricle just below the implanted mitral valve (Fig. Six months postoperatively, the pseudoaneurysm had completely disappeared on CT imaging Fig. . Three yRupture of the posterior wall of the left ventricle following mitral valve surgery is a rare but potentially fatal complication . This coAVG hematoma is usually detected at the termination of CPB when the heart starts beating again on its own , 6–8. WhWith intraoperative TEE , 7, 8, tAVG hematoma occasionally causes LV pseudoaneurysms in the chronic phase , 5. AlthWe presented a case of AVG hematoma that occurred during mitral valve surgery and caused left ventricular pseudoaneurysm. Conservative strategies yielded positive results in our case. We hope our experience and original check sheet designed for reasonable intraoperative decision-making are valuable for surgical team members facing similar situations.