Dietary Pterostilbene for MTA1-Targeted Interception in High-Risk Premalignant Prostate Cancer.

Prostate cancer remains one of the most prevalent cancers in aging men. Active surveillance subpopulation of patients with prostate cancer includes men with varying cancer risk categories of precancerous disease due to prostatic intraepithelial neoplasia (PIN) heterogeneity. Identifying molecular alterations associated with PIN can provide preventable measures through finding novel pharmacologic targets for cancer interception. Targeted nutritional interception may prove to be the most appropriate chemoprevention for intermediate- and high-risk active surveillance patients. Here, we have generated two prostate-specific transgenic mouse models, one overexpressing MTA1 (R26MTA1 ) and the other overexpressing MTA1 on the background of Pten heterozygosity (R26MTA1 ; Pten+/f ), in which we examined the potential chemopreventive efficacy of dietary pterostilbene. We show that MTA1 promotes neoplastic transformation of prostate epithelial cells by activating cell proliferation and survival, leading to PIN development. Moreover, MTA1 cooperates with PTEN deficiency to accelerate PIN development by increasing cell proliferation and MTA1-associated signaling. Further, we show that mice fed with a pterostilbene-supplemented diet exhibited more favorable histopathology with decreased severity and number of PIN foci accompanied by reduced proliferation, angiogenesis, and inflammation concomitant to reduction in MTA1 and MTA1-associated CyclinD1, Notch2, and oncogenic miR-34a and miR-22 levels. PREVENTION RELEVANCE: Developing novel interceptive strategies for prostate cancer chemoprevention is a paramount goal in clinical oncology. We offer preclinical evidence for the potential of pterostilbene as a promising natural agent for MTA1-targeted interceptive strategy in future cancer prevention trials towards protecting select patients with prostate cancer under active surveillance from developing cancer.

Sporadic Burkitt Lymphoma Presenting with Middle Cranial Fossa Masses with Sphenoid Bony Invasion and Acute Pancreatitis in a Child.

Acute pancreatitis in children is usually due to infection, trauma, or anatomical abnormalities and is rarely due to obstruction from malignancy. Sporadic Burkitt lymphoma (BL) is an aggressive non-Hodgkin B-cell lymphoma that usually involves the bowel or pelvis, with isolated cases presenting as acute pancreatitis. We report a case of BL in a 12-year-old male presenting as acute pancreatitis with obstructive jaundice and a right middle cranial fossa mass invading the sphenoid bone. The common bile duct in this case was dilated to 21 mm in diameter on abdominal ultrasound and to 26 mm on magnetic resonance cholangiopancreatography (MRCP), significantly greater than any value reported in the literature for BL. Given the rapidly progressing nature of BL, we emphasize the importance of recognizing heterogeneous presentations of this disease to improve patient survival. We also conclude that it is important to consider malignancy in a child with acute pancreatitis, particularly in the presence of obstructive jaundice or multisystem involvement. Other Presentations. This case report has no prior publications apart from the abstract being accepted to the 2020 SIOP (International Society of Pediatric Oncology) meeting and 2020 ASPHO conference (canceled due to the COVID-19 pandemic) and subsequently published as an abstract only in Pediatric Blood and Cancer. We have also presented the abstract as a poster presentation at our institution's (NYU Langone Hospital-Long Island, previously known as NYU Winthrop) annual research day conference in 2020.

Broad ligament Extraintestinal Gastrointestinal Stromal Tumor (EGIST): Case report and brief overview of EGIST.

•Highly suspicious pelvic mass may require preoperative biopsy for diagnosis.•Neoadjuvant imatinib lowers EGIST tumor burden in extensive disease preoperatively.•EGIST resection aims at complete surgical resection and negative margins.•This case was managed with complete surgical resection and adjuvant imatinib.•Prognostic factors in EGIST are size, mitosis, location and genetic mutations.

Grape Powder Supplementation Attenuates Prostate Neoplasia Associated with Pten Haploinsufficiency in Mice Fed High-Fat Diet.

SCOPE: Previous studies have identified potent anticancer activities of polyphenols in preventing prostate cancer. The aim of the current study is to evaluate the chemopreventive potential of grape powder (GP) supplemented diets in genetically predisposed and obesity-provoked prostate cancer. METHODS AND RESULTS: Prostate-specific Pten heterozygous (Pten+/f ) transgenic mice are fed low- and high-fat diet (LFD and HFD, respectively) supplemented with 10% GP for 33 weeks, ad libitum. Prostate tissues are characterized using immunohistochemistry and western blots, and sera are analyzed by ELISA and qRT-PCR. Pten+/f mice fed LFD and HFD supplemented with 10% GP show favorable histopathology, significant reduction of the proliferative rate of prostate epithelial cells (Ki67), and rescue of PTEN expression. The most potent protective effect of GP supplementation is detected against HFD-induced increase in inflammation (IL-1ß; TGF-ß1), activation of cell survival pathways (Akt, AR), and angiogenesis (CD31) in Pten+/f mice. Moreover, GP supplementation reduces circulating levels of oncogenic microRNAs (miR-34a; miR-22) in Pten+/f mice. There are no significant changes in body weight and food intake in GP supplemented diet groups. CONCLUSIONS: GP diet supplementation can be a beneficial chemopreventive strategy for obesity-related inflammation and prostate cancer progression. Monitoring serum miRNAs can facilitate the non-invasive evaluation of chemoprevention efficacy.

Necrotizing Myositis: A Rare Necrotizing Soft Tissue Infection Involving Muscle.

INTRODUCTION: Necrotizing myositis (NM) is an extremely rare necrotizing soft tissue infection involving muscle. Unlike similar infections (eg, necrotizing fasciitis, clostridial myonecrosis) that can be more readily diagnosed, NM can have a benign presentation then rapidly progress into a life-threatening condition with a mortality rate of 100% without surgical intervention. CASE REPORT: A 74-year-old man with a history of prostate cancer with radiation therapy, seed implants, and 2 transurethral resection procedures presented to the emergency department after a fall. He was initially diagnosed and treated for urosepsis. Sixteen hours after presentation, he complained of pain and swelling of his right groin. Computed tomography of the abdomen and pelvis showed gas findings suspicious for necrotizing infection of the bilateral thighs. Surgical exploration revealed NM. Separate cultures from the left thigh and bladder grew Streptococcus intermedius, Clostridium clostridioforme, and Peptostreptococcus, suggesting a possible common source of infection from the prostate gland or the osteomyelitic pubic symphysis, which subsequently spread to the bilateral thighs. CONCLUSIONS: To the best of the authors' knowledge, this is the first reported case of S intermedius and C clostridioforme causing NM. A high index of suspicion is required for extremely rare conditions like NM, because early diagnosis and surgical intervention significantly reduce mortality.

An unusual presentation of Merkel cell carcinoma: a case report.

Merkel cell carcinoma (MCC) is a rare, aggressive carcinoma that usually arises in sun-exposed regions. MCC is a primary neuroendocrine tumor that arises in the skin. This report describes an unusual case of MCC on the buttocks that was treated with excision, radiation and chemotherapy. Physicians should consider MCC as a differential diagnosis when encountering a rapidly growing, painless lesion. Early diagnosis and treatment may improve patient survival rates.

Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology.

BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

Wound Care Center of Excellence: A Process for Continuous Monitoring and Improvement of Wound Care Quality.

GENERAL PURPOSE: To provide information about a study using a new process for continuous monitoring to improve chronic wound care quality.This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.After completing this continuing education activity, you should be better able to:1. Recognize problems associated with chronic wound care.2. Identify methods used in this project to improve care.3. Illustrate the findings from this and similar projects and implications for providing improved wound care.Patients with chronic wounds require complex care because of comorbidities that can affect healing. Therefore, the goal of this project was to develop a system of reviewing all hospitalized patients seen by the study authors' wound care service on a weekly basis to decrease readmissions, morbidity, and mortality. Weekly multidisciplinary conferences were conducted to evaluate patient data and systematically assess for adherence to wound care protocols, as well as to create and modify patient care plans. This review of pathology and the performance of root-cause analyses often led to improved patient care.

Up-regulation of Wnt/ß-catenin expression is accompanied with vascular repair after traumatic brain injury.

Recent data suggest that repairing the cerebral vasculature after traumatic brain injury (TBI) may help to improve functional recovery. The Wnt/ß-catenin signaling pathway promotes blood vessel formation during vascular development, but its role in vascular repair after TBI remains elusive. In this study, we examined how the cerebral vasculature responds to TBI and the role of Wnt/ß-catenin signaling in vascular repair. We induced a moderate controlled cortical impact in adult mice and performed vessel painting to visualize the vascular alterations in the brain. Brain tissue around the injury site was assessed for ß-catenin and vascular markers. A Wnt transgenic mouse line was utilized to evaluate Wnt gene expression. We report that TBI results in vascular loss followed by increases in vascular structure at seven days post injury (dpi). Immature, non-perfusing vessels were evident in the tissue around the injury site. ß-catenin protein expression was significantly reduced in the injury site at 7 dpi. However, there was an increase in ß-catenin expression in perilesional vessels at 1 and 7 dpi. Similarly, we found increased number of Wnt-GFP-positive vessels after TBI. Our findings suggest that Wnt/ß-catenin expression contributes to the vascular repair process after TBI.

Major Histopathologic Diagnoses of Chronic Wounds.

PURPOSE: To clarify the histopathology of acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Describe the parameters and significance of this study.2. Identify chronic wound diagnosis and treatment.3. Differentiate the histopathology of osteomyelitis and vasculitis. OBJECTIVE: The presence of a chronic wound can result in significant morbidity/mortality. Understanding the pathological alterations of wound tissue that are refractory to standard wound therapy is essential for effective wound management and healing. The authors describe 4 wound etiologies, specifically, acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. SETTING: A tertiary care hospital. DESIGN: A retrospective review of 1392 wound operations performed during a 24-month period at a tertiary care hospital was conducted. Tissue specimens reviewed included soft tissue infections of the lower extremity, sacrum, hip/pelvis, trunk, perineum, and buttocks. MAIN RESULTS: Acute osteomyelitis is defined as bone tissue with a predominance of polymorphonuclear leukocytes, evidence of osteoclast bone resorption with scalloping of the cortical bone edges, and bone detritus. Chronic osteomyelitis is defined as bone tissue with a significant amount of fibrosis surrounding devitalized tissue and heavy infiltration of lymphocytes and plasma cells. Primary-type vasculitis is defined primarily as inflammation and necrosis of blood vessel walls. In cutaneous lesions of granulomatosis with polyangiitis, ulceration with numerous inflammatory granulomas is seen in the papillary dermis. Secondary vasculitis is defined by vessel wall infiltration by inflammatory cells and fibrinoid necrosis of the small vessel wall. CONCLUSIONS: Pathologies of these 4 types of wounds can complicate standard algorithms designed for diagnosis and treatment, and accurate diagnosis through histopathologic analysis can help tailor targeted treatment.

Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), the foremost cause of morbidity and mortality in persons under 45 years of age worldwide, leads to about 200,000 victims requiring hospitalization and approximately 52,000 deaths per year in the United States. TBI is characterized by cerebral edema leading to raised intracranial pressure, brain herniation, and subsequent death. Current therapies for TBI treatment are often ineffective, thus novel therapies are needed. Recent studies have shown that an osmotic transport device (OTD) is capable of reducing brain water content and improving survival in mice with severe cerebral edema. Here we compare the effects of a craniectomy and an OTD plus craniectomy on neurological function in mice after TBI. Animals treated with a craniectomy plus an OTD had significantly better neurological function 2 days after TBI compared with those treated with craniectomy only. This study suggests that an OTD for severe brain swelling may improve patient functional outcome. Future studies include a more comprehensive neurological examination, including long-term memory tests.

Primary CNS T-cell lymphoma of the spinal cord: case report and literature review.

Primary central nervous system lymphoma (PCNSL) accounts for 1% of all lymphoma diagnoses and as many as 6% of all central nervous system (CNS) tumors. Most cases of PCNSL are of B-cell type; few are of T-cell lineage. PCNSL mainly occurs intracranially; primary spinal-cord lymphoma only occurs rarely. Moreover, intramedullary presentation without intracranial lesions is virtually unknown. Herein, we present a case of primary T-cell CNS lymphoma limited to the intramedullary spinal cord in an 82-year-old white man, along with a review of the literature on this condition and similar conditions.

Repeated mild traumatic brain injury results in long-term white-matter disruption.

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

Visual and Contextual Modeling for the Detection of Repeated Mild Traumatic Brain Injury.

Currently, there is a lack of computational methods for the evaluation of mild traumatic brain injury (mTBI) from magnetic resonance imaging (MRI). Further, the development of automated analyses has been hindered by the subtle nature of mTBI abnormalities, which appear as low contrast MR regions. This paper proposes an approach that is able to detect mTBI lesions by combining both the high-level context and low-level visual information. The contextual model estimates the progression of the disease using subject information, such as the time since injury and the knowledge about the location of mTBI. The visual model utilizes texture features in MRI along with a probabilistic support vector machine to maximize the discrimination in unimodal MR images. These two models are fused to obtain a final estimate of the locations of the mTBI lesion. The models are tested using a novel rodent model of repeated mTBI dataset. The experimental results demonstrate that the fusion of both contextual and visual textural features outperforms other state-of-the-art approaches. Clinically, our approach has the potential to benefit both clinicians by speeding diagnosis and patients by improving clinical care.

Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat.

Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for active sports and military personnel. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the time course of brain vulnerability to rmTBI in a rat model of mild cortical controlled impact. An initial mild injury was followed by a second injury unilaterally at an interval of 1, 3, or 7 days. RmTBI animals were compared to single mTBI and sham treated animals. Neuropathology was assessed using multi-modal magnetic resonance imaging (MRI), followed by ex vivo tissue immunohistochemistry. Neurological and behavioral outcomes were evaluated in a subset of animals receiving rmTBI 3 days apart and shams. RmTBI 1 or 3 days apart but not 7 days apart revealed significantly exacerbated MRI-definable lesion volumes compared to single mTBI and shams. Increases in cortical tissue damage, extravascular iron and glial activation assessed by histology/immunohistochemistry correlated with in vivo MRI findings where shorter intervals (1 or 3 days apart) resulted in greater tissue pathology. There were no neurological deficits associated with rmTBI 3 day animals. At 1 mo post-injury, animals with rmTBI 3 days apart showed reduced exploratory behaviors and subtle spatial learning memory impairments were observed. Collectively, our findings suggest that the mildly-impacted brain is more vulnerable to repetitive injury when delivered within 3 days following initial mTBI.

Endometriosis of abdominal and pelvic wall scars: multimodality imaging findings, pathologic correlation, and radiologic mimics.

Implantation of an endometriotic lesion within a pelvic or abdominal wall scar is an uncommon but well-described condition that may be the underlying cause of acute or chronic recurrent abdominal or pelvic pain, especially after cesarean section. Radiologists may not consider scar endometriosis when it is encountered at cross-sectional imaging. Cesarean section scars are the most common site of extraovarian or extrauterine endometriosis. The condition also has been identified in other uterine surgery-related scars and in the skin, subcutaneous tissues, and abdominal and pelvic wall musculature adjacent to these scars. The most plausible cause of scar endometriosis is implantation of endometrial stem cells at the surgical site at the time of uterine surgery. Patients with scar endometriosis may be asymptomatic or present with cyclical pain corresponding to the menstrual cycle. Cross-sectional imaging findings vary from the nonspecific to those suggestive of the diagnosis when combined with clinical history. In particular, the presence of blood products in an anterior abdominal wall mass at magnetic resonance (MR) imaging with no other explanation is strongly suggestive of scar endometriosis. Ultrasonography, computed tomography, and MR imaging may be used to depict an endometriotic lesion, exclude endometriosis, or provide evidence for an alternative diagnosis.

Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury.

Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression.

Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase.

Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent finding in ALK+, but not ALK-negative ALCL (ALK- ALCL), and the c-myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c-myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c-myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c-myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL.

Radiology-Pathology Conference: carcinosarcoma of the colon.

Carcinosarcomas are very uncommon tumors, which are comprised of both malignant epithelial and mesenchymal elements. They occur most commonly in the head and neck, respiratory tract, and female reproductive organs. In the gastrointestinal tract, they are most often found in the oropharynx, esophagus, and, to a lesser extent, in the stomach. Carcinosarcomas rarely originate from the colon, but when they do, they are extremely aggressive malignancies. We report the radiologic and pathologic findings of a patient with a carcinosarcoma believed to have arisen from the colon and which involved the adjacent mesentery and omentum.