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Despite the significant clinical consequences and socioeconomic costs of gun-shot wounds to the head (GSWH), studies examining pre-hospital risk factors, geo-spatial patterns, and economic cost are lacking.A retrospective analysis was performed for GSWH patients (single or multiple injuries) presenting to the level one Ryder Trauma Center (hospital patients) as well as the Miami Dade County Medical Examiner (ME) Department, from October 2013 to October 2015. Additionally, ME data was queried from the previous decade (2008-2017) to analyze longitudinal trends.402 consecutive cases met inclusion criteria: 297 (74%) presented to the ME and 105 (26%) presented to the hospital. GSWH in our cohort had a case fatality rate of 89%, predominantly afflicting males, Caucasians, and victims of suicide, with a mean age of 41.9 ± 20.6 years. Hospital patients were more likely to be Black males from low socioeconomic (SES) regions involved in assault. Older, Caucasian males were overrepresented in patients attempting and completing suicide, thus comprised a higher percentage of ME cases. Geo-spatial analysis of hospital patient injury zip-codes illustrates GSWH are significantly clustered in low-income urban centers with greater poverty rates. In Miami-Dade County, the economic burden of GSWH, as measured by total healthcare costs and lifetime productivity losses, was estimated to be $11,867,415 and $246,179,498 respectively.In the first analysis of GSWH with the inclusion of both hospital and ME data in a representative urban setting, our findings demonstrate pre-hospital risk factors and the unequal distribution of the significant economic costs of GSWH.

Rationale and Objectives Peer learning is a case-based group-learning model intended to improve performance. In this descriptive paper, we describe multi-institutional, multi-subspecialty, web-based radiology case conferences and summarize the participants’ experiences. Materials and Methods A semi-structured, 27-question survey was administered to radiologists participating in abdominal, cardiothoracic, and musculoskeletal case conferences. Survey questions included demographics, perceived educational value and challenges experienced. Survey question formats were continuous, binary, five-point Likert scale or text-based. The measures of central tendencies, proportions of responses and patterns were tabulated. Results From 57 responders, 12/57 (21.1%) were abdominal, 16/57 (28.1%) were cardiothoracic, and 29/57 (50.8%) were musculoskeletal conference participants; 50/56 (89.3%) represented academic practice. Median age was 45 years (range 35–74); 43/57 (75.4%) were male. Geographically, 16/52 (30.8%) of participants were from the East Coast, 16/52 (30.8%) Midwest, 18/52 (34.6%) West Coast, and 2/52 (3.8%) International. The median reported educational value was 5/5 (interquartile range 5–5). Benefits of the case conference included education (50/95, 52.6%) and networking (39/95, 41.1%). Participants reported presenting the following cases: “great call" 32/48 (66.7%), learning opportunity 32/48 (66.7%), new knowledge 41/49 (83.7%), “zebras” 46/49 (93.9%), and procedural-based 16/46 (34.8%). All 51/51 (100%) of responders reportedly gained new knowledge, 49/51 (96.1%) became more open to group discussion, 34/51 (66.7%) changed search patterns, and 50/51 (98%) would continue to participate. Reported challenges included time zone differences and support from departments for a protected time to participate. Conclusion Peer learning through multi-institutional case conferences provides educational and networking opportunities. Current challenges and desires include having department-supported protected time and ability to receive continuing medical education credit.

Highlights • Inflammatory pseudotumor are non-neoplastic tumors of the abdomen. • They may be large and invasive. • They may cause significant morbidity and mortality. • There is limited information in the literature about management., Introduction There is a wide differential diagnosis for intraabdominal tumors. Surgical resection and microscopic analysis of tissue structure can identify tumor origin in most cases. Most rapidly growing invasive tumors are neoplastic. Inflammatory pseudotumors are a subcategory of intraabdominal tumors that are non-neoplastic and can be rapidly growing. Urachal cysts originate from the dome of the bladder; however they are typically not invasive. There is limited literature on the appropriate management of these tumors. Presentation A 37-year-old female presenting with symptoms of abdominal pain was found to have a large intraabdominal mass invading multiple organs. Core biopsies demonstrated inflammation. The mass grew significantly over the course of a year and patient's abdominal pain worsened. The patient was taken to the operating room for resection. Final pathology revealed reactive fibrous tissue with acute and chronic inflammation invading bladder, urethra, abdominal wall, appendix, and ovary. Intraoperative frozen section demonstrated low grade spindle cells with concern for inflammatory pseudotumor but final pathology demonstrated inflammation. Discussion Although benign, these tumors cause significant morbidity due to their size and level of organ invasion. Management should involve surgical resection as well as potential post-operative chemotherapy or NSAIDs based off clinical picture. We demonstrate the importance of close follow up for residual disease or recurrence of patients with inflammatory pseudotumors of the abdomen. Conclusion This case highlights difficulties in diagnosis of a tumor that has potential to cause significant morbidity. There is need for further research to discover the best management after surgical resection of these tumors.

Highlights • Coat’s plus syndrome is a rare genetic condition. • Manifestations of this syndrome include ophthalmologic symptoms along with systemic manifestations such as gastrointestinal bleeding. • This case report demonstrates significant morbidity and ultimately mortality associated with this condition. • Further research is needed in this area to treat patients with GI bleeding in Coat’s plus syndrome., Introduction Coat’s plus syndrome is an extremely rare genetic syndrome that leads to a variety of symptoms. We are reporting a case of Coat's plus syndrome that had persistent GI bleeding and review of current literature. Presentation of case The patient is a female in her 40 s with a history of coat's disease and end stage renal failure on dialysis. The etiology of renal failure was not discovered, and the patient was being worked up for a kidney transplant. The patient required admission after deterioration of nutritional status with a BMI of 14.3. During admission the patient initially had intermittent GI bleeding requiring weekly blood transfusions. On work up of the GI bleed, no etiology was identified either. As a result persistent negative GI bleed work up, we pursued alternative diagnoses. The history of Coat’s disease prompted us to work up the patient for Coat's plus syndrome. A genetic test confirmed the presence of CTC-1 gene mutation, which results in Coat's plus syndrome. With no treatment available as of yet, the patient continued to deteriorate into multi-organ failure. Discussion We present an example of GI bleeding in Coat's plus syndrome, only identified thru genetic testing, that is very rare and complex in nature. Despite numerous workups, no specific etiology was identified for the GI bleeding. Conclusion Previous reports have not investigated cause of GI bleeding, since it is extremely rare in the literature. Further investigation is warranted to understand cause and effects of GI bleeding in this rare genetic disease.

OBJECTIVEDiscitis and osteomyelitis are seen in end-stage renal disease (ESRD) patients due to repeated vascular access for hemodialysis and urinary tract infections leading to recurrent bacteremia. Discitis and osteomyelitis are underdiagnosed due to the nonspecific initial presentation of back pain. In this article, we review the literature for better understanding of the problem and the importance of early diagnosis by primary care physicians and nephrologists. In addition, we discuss the decision-making, follow-up, management, and neurological outcomes.METHODSA detailed PubMed search was performed using the following terms: “end stage renal disease (ESRD)” and “chronic renal failure (CRF),” combined with “spine infections,” “spondylodiscitis,” “discitis,” and “osteomyelitis.” Search results were limited to articles written in English, case reports, and case series from 1973 to 2012. Editorials, reviews, and commentaries were excluded. Only studies involving human patients were included. The authors also included 4 patients from their own patient population.RESULTSA total of 30 articles met the inclusion criteria. Including the 4 patients from the authors’ patient population, 212 patients with spine infections and maintenance dialysis were identified. The patients’ ages ranged from 38 to 78 years. The duration of dialysis ranged from a few days to 16 years. The time from onset of back pain to diagnosis ranged from 3 days to 6 months. The most common causative organism was Staphylococcus aureus, followed by Staphylococcus epidermidis and gram-negative bacteria. Most of the patients were treated with antibiotics alone (76.8%), although surgery was indicated when patients presented with neurological deficits (p < 0.011). Approximately one-quarter of the patients developed neurological deficits, with devastating consequences. Fever and neurological deficits at presentation, culture positive for methicillin-resistant S. aureus, and age > 65 years were highly correlated with mortality in our analysis.CONCLUSIONSSeveral risk factors lead to failure of antibiotics and progression of disease in patients with ESRD. Challenges to diagnosis include vague presenting symptoms, co-existing destructive spondyloarthropathy, poor immune response, chronic elevations of inflammatory markers, and recurrent bacteremia. Infectious processes are more likely to cause permanent neurological deficits than transient deficits. The authors recommend close observation and serial imaging of these patients for early signs of neurological deficits. Any signs of disease progression will require aggressive surgical debridement.

Seventy percent of cancer patients will have metastatic bone disease, most commonly in the vertebra. Prognosis of metastatic lung cancer is poor and treatment is mostly palliative. To-date, there is no systematic review on the ideal treatment for lung cancer with spinal metastases in regards to mortality. Literature searches were performed based on PRISMA guidelines for systematic review. Thirty-nine studies comprising 1925 patients treated for spinal metastases of lung cancer met inclusion criteria. All analyses were performed using SAS and SPSS. Data were analyzed for meaningful comparisons of baseline patient characteristics, primary cancer type, metastatic lesion characteristics, treatment modality, and clinical and radiologic outcomes. Significantly greater mean survival length was seen in the non-surgical group (8.5 months, SD 6.6, SEM 0.17) compared to the surgical group (7.5 months, SD 4.5, SEM 0.25; p = 0.013). There was no statistically significant survival difference between different types of primary lung cancer: NSCLC (8.3 months, SD 13.8, SEM 0.91) and SCLC (7.0 months, SD 4.6, SEM 0.46; p = 0.36). Number of vertebral levels involved per lesion also did not exhibit significant difference: single lesion (11.3 months, SD 6.8, SEM 2.2) and multiple lesions (13.8 months, SD 15.7, SEM 3.6; p = 0.64). For patients with symptomatic spinal metastases from lung cancer, non-operative approaches experience significantly better survival outcomes (p = 0.013). Future clinical studies are needed to determine the best treatment algorithm to help maximize outcomes and minimize mortality in metastatic lung cancer.

Central neurocytomas are rare tumors, typically found in the third ventricle. We present the unusual case of a fourth ventricular central neurocytoma in a 70-year-old female presenting with imbalance and headaches, with an enhancing fourth ventricular mass on imaging. We examine the details of her clinical presentation, imaging characteristics, histopathologic analysis, and postoperative course. We performed a critical literature review of fourth ventricular central neurocytoma, identifying 6 previously reported cases. In contrast to our patient, the majority of these cases were in young males. The 2 females with fourth ventricular neurocytoma developed it at a much later age (mean 63.5 years) than their male counterparts (mean 22.8 years; P = 0.005). Despite being a rare cause for a fourth ventricular lesion, given the appropriate clinical context and radiographic findings, this should remain part of the differential diagnosis.

OBJECTIVE Carotid body tumors (CBTs), extraadrenal paragangliomas, are extremely rare neoplasms in children that often require multimodal surgical treatment, including preoperative anesthesia workup, embolization, and resection. With only a few cases reported in the pediatric literature, treatment paradigms and surgical morbidity are loosely defined, especially when carotid artery infiltration is noted. Here, the authors report two cases of pediatric CBT and provide the results of a systematic review of the literature. METHODS The study was divided into two sections. First, the authors conducted a retrospective review of our series of pediatric CBT patients and screened for patients with evidence of a CBT over the last 10 years (2007–2017) at a single tertiary referral pediatric hospital. Second, they conducted a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of all reported cases of pediatric CBTs to determine the characteristics (tumor size, vascularity, symptomatology), treatment paradigms, and complications. RESULTS In the systematic review (n = 21 patients [includes 19 cases found in the literature and 2 from the authors’ series]), the mean age at diagnosis was 11.8 years. The most common presenting symptoms were palpable neck mass (62%), cranial nerve palsies (33%), cough or dysphagia (14%), and neck pain (19%). Metastasis occurred only in 5% of patients, and 19% of cases were recurrent lesions. Only 10% of patients presented with elevated catecholamines and associated sympathetic involvement. Preoperative embolization was utilized in 24% of patients (external carotid artery in 4 and external carotid artery and vertebral artery in 1). Cranial nerve palsies (cranial nerve VII [n = 1], IX [n = 1], X [n = 4], XI [n = 1], and XII [n = 3]) were the most common cause of surgical morbidity (33% of cases). The patients in the authors’ illustrative cases underwent preoperative embolization and balloon test occlusion followed by resection, and both patients suffered from transient Horner’s syndrome after embolization. CONCLUSIONS Surgical management of CBTs requires an extensive preoperative workup, anesthesia, and multimodal surgical management. Due to a potentially high rate of surgical morbidity and vascularity, balloon test occlusion with embolization may be necessary in select patients prior to resection. Careful thorough preoperative counseling is vital to preparing families for the intensive management of these children. ABBREVIATIONS BTO = balloon test occlusion; CBT = carotid body tumor; CN = cranial nerve; ECA = external carotid artery; ICA = internal carotid artery; MIBG = iodine-123-meta-iodobenzylguanidine; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Background In recent years, there have been significant changes in the perception of valvular and vascular allograft transplants. Despite the constant evolution of the field of transplant and the involvement of multiple surgical specialties, there is not an official registry for administrative and clinical control. This study aims to design a registry of vascular and valvular allograft transplantation in Catalonia, Spain (ReVAC). Materials and Methods Three consecutive focal groups were designed. Focal groups established administrative, technical, and clinical requirements of ReVAC. ReVAC included patients with a transplanted cryopreserved vascular segment or cardiac valves that were distributed by Catalan tissue banks to public and private hospitals in Catalonia. Ten hospitals were involved in this study. Data were collected on 380 patients between January 1995 and November 2015. Results The project resulted in the completion of a growing platform available online. ReVAC was divided into the following 3 levels: patient-related, surgery-related, and transplant-related data. Online access is available through the website of applications of the "Generalitat de Catalunya." Conclusion ReVAC has been useful for administrative and clinical control of transplants in Catalonia. Currently, data related to outcomes of arterial allografts are available, reinforcing the current guideline-supported indications, as well as opening a window for further analysis and guideline creation.

Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), produces 5-fluorouracil (5-FU) within infected cancer cells, which in preclinical models has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. This combination treatment is under evaluation in a registrational Phase 3 trial in patients with recurrent high-grade glioma. Here, we investigated the feasibility of applying Toca 511 & Toca FC to medulloblastoma, the most common malignant tumor of the pediatric nervous system. Established (HDMB03, DAOY) and primary (PDX10) human medulloblastoma cells were transduced with RRVs encoding either Emerald green fluorescent protein reporter (RRV-EMD) or the CD enzyme (RRV-CD, i.e. Toca 511). RRV replication in vitro, examined by flow cytometry for EMD fluorescence, showed spread to >90% of cells in culture by day 10 post-inoculation. In contrast to non-transduced or RRV-EMD-transduced controls, RRV-CD-transduced medulloblastoma cells exhibited significant dose-dependent reduction of viability upon exposure to 5-FC, as measured by MTS assay. In vivo, stereotactic intracerebellar implantation of HDMB03 cells into nude mice without treatment resulted in cell dose-dependent median survival time and eventual 100% lethality at all cell doses tested, with median survival of 28 days after implantation of 1x10^5 tumor cells. In this orthotopic medulloblastoma model, mice with RRV-CD-transduced intracerebellar HDMB03 tumors exhibited long-term survival upon 5-FC treatment, as compared to mice treated with PBS or implanted with non-transduced cells (p=0.00007). No deaths occurred in these mice with RRV-CD-transduced HDMB03 tumors while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days). The results of this proof-of-concept study support further preclinical investigation of RRV-CD-mediated prodrug activator gene therapy for this pediatric malignancy.

Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV), encodes optimized yeast cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU) within infected cancer cells. In preclinical models of intracerebral glioblastoma, 5-FU generated locally by Toca 511 (RRV-CD) prodrug activator gene therapy has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. Early-phase clinical trials of Toca 511 in recurrent high-grade glioma showed highly promising evidence of therapeutic benefit, leading to a Phase III trial completed in late 2019 (n=400 patients, randomized 1:1 vs. standard chemotherapy), which appeared to show negative results overall. However, additional analysis showed possible efficacy in prespecified subgroups, and further clinical investigation is being pursued. In preclinical studies, we have also evaluated RRV for use in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Both established and primary human medulloblastoma cell lines supported efficient RRV replication in vitro, with spread to >90% of cells by day 10 post-inoculation, and RRV-CD-transduced medulloblastoma cells showed significant dose-dependent reduction of viability upon exposure to 5-FC, compared to controls. In an intracerebellar HDMB03 medulloblastoma model, RRV-CD-treated mice exhibited long-term survival while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days) as compared to controls (median survival 28 days, 100% lethality) (p=0.00007). These results support further evaluation of RRV-mediated prodrug activator gene therapy for pediatric brain tumors.

Toca 511, a clinical-stage retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), is designed to produce 5-FU which kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. This combination treatment is currently under evaluation in an international Phase 2/3 trial in patients with recurrent high-grade glioma. In the present study, we investigated the feasibility of further applying Toca 511 & Toca FC in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Aggressive chemotherapy regimens increase survival in children with this disease; however, systemic toxicity limits efficacy. Here we have initiated the first preclinical studies to evaluate RRV-mediated prodrug activator gene therapy in medulloblastoma. Human medulloblastoma cell lines (HDMB03, DAOY) or patient-derived primary medulloblastoma cells were transduced with RRVs encoding either Emerald green fluorescent reporter (RRV-EMD) or the CD enzyme (RRV-CD). RRV replication in vitro, examined by flow cytometry for EMD fluorescence, showed spread to >90% of cells in culture by day 10 post-inoculation. In contrast to non-transduced or RRV-EMD-transduced controls, RRV-CD-transduced medulloblastoma cells exhibited significant dose-dependent reduction of viability upon exposure to 5-FC, as measured by MTS assay. In vivo, stereotactic intracerebellar implantation of non-transduced HDMB03 cells into nude mice resulted in cell dose-dependent median survival time and eventual 100% lethality at all cell doses tested. In this orthotopic medulloblastoma model, mice with RRV-CD-transduced intracerebellar HDMB03 tumors demonstrated increased survival upon 5-FC treatment, as compared to mice treated with PBS or implanted with non-transduced cells. These results support further investigation of RRV-CD-mediated prodrug activator gene therapy for this pediatric malignancy.

This article outlines the antenatal screening tests available to women as part of NHS maternity care. The tests are part of managed screening programmes which are overseen by the UK National Screening Committee (NSC) and underpinned by standards, education and quality assurance.

This article reviews the development and organization of the Down's Syndrome Screening Policy by the National Screening Committee, outlining the implications for sonographer training and practice, and for antenatal ultrasound service provision.

Background. To assess whether the gestation at which abnormal uterine artery waveforms disappear is related to birthweight and complications of pregnancy. Methods. A prospective study of outcome of pregnancy after a uterine artery Doppler screening program set in an inner city teaching hospital. One thousand five hundred and twenty-four consecutive women attending the Obstetric Department for a routine anomaly scan at between 19 and 21 weeks gestation had maternal uterine arteries assessed using color wave Doppler. Those women in whom the flow was deemed abnormal were recalled for a further scan at 24-26 weeks gestation. The main outcome measures were birthweight, gestation at delivery and incidence of pre eclampsia. Results. The women in whom the uterine artery blood flow was normal at 20 weeks had babies with significantly higher mean birthweight than those who normalized between 20 and 24-26 weeks gestation ('late normalizers') after adjustment for confounding factors; gestational age, maternal height,...