A case report of an ischaemic stroke, caused by a primary cardiac intimal sarcoma.

BACKGROUND: Intimal sarcomas are an extremely rare type of primary cardiac malignancy. They most commonly present with symptoms of cardiac dysfunction. We present a case of intimal sarcoma identified without any cardiac signs or symptoms. Cardiac sarcomas historically carry a very poor prognosis. PRESENTATION: A 57-year-old man presented with a sudden onset of left limb weakness and disorientation. MRI brain identified an acute ischaemic stroke in the right anterior temporal lobe. Four months later, he presented again with transient left arm weakness. The patient had a normal cardiovascular examination and ECG. All other initial investigations for cryptogenic stroke were non-contributory. The patient did not initially get an echocardiogram. When this investigation was performed, after his second presentation, a large pedunculated mass was present in his left atrium. This was resected and identified histologically as a primary intimal sarcoma of his left atrium. The patient was treated with post-operative radiotherapy but declined chemotherapy. He recovered well post-operatively but subsequently passed away 14 months after diagnosis. CONCLUSIONS: It is possible for primary cardiac malignancies to present with only symptoms of systemic emboli. For this reason, echocardiography is a crucial investigation in cases of cryptogenic stroke. Some stroke guidelines do not definitively support routine echocardiography. Primary intimal cardiac sarcoma is a very rare condition with a poor prognosis. The literature is limited to case reports and optimal management is with surgical resection where possible. The role of post operative radiotherapy and chemotherapy is uncertain.

Characterization of an IDH1 R132H Rabbit Monoclonal Antibody, MRQ-67, and Its Applications in the Identification of Diffuse Gliomas.

The current diagnosis of diffuse glioma involves isocitrate dehydrogenase (IDH) mutation testing. Most IDH mutant gliomas carry a G-to-A mutation at IDH1 position 395, resulting in the R132H mutant. R132H immunohistochemistry (IHC), therefore, is used to screen for the IDH1 mutation. In this study, the performance of MRQ-67, a recently generated IDH1 R132H antibody, was characterized in comparison with H09, a frequently used clone. Selective binding was demonstrated by an enzyme-linked immunosorbent assay for MRQ-67 to the R132H mutant, with an affinity higher than that for H09. By Western and dot immunoassays, MRQ-67 was found to bind specifically to the IDH1 R1322H, with a higher capacity than H09. IHC testing with MRQ-67 demonstrated a positive signal in most diffuse astrocytomas (16/22), oligodendrogliomas (9/15), and secondary glioblastomas tested (3/3), but not in primary glioblastomas (0/24). While both clones demonstrated a positive signal with similar patterns and equivalent intensities, H09 exhibited a background stain more frequently. DNA sequencing on 18 samples showed the R132H mutation in all IHC positive cases (5/5), but not in negative cases (0/13). These results demonstrate that MRQ-67 is a high-affinity antibody suitable for specific detection of the IDH1 R132H mutant by IHC and with less background as compared with H09.

Considerations in assessing the abuse potential of psychedelics during drug development.

The recent increase in clinical research on the potential therapeutic uses of classic psychedelics has prompted the need to revisit the assessment of the abuse potential of these drugs. The term "classic psychedelic" is used in this manuscript to describe serotonergic 5-HT2A agonists that alter perception, cognition, and mood (i.e., psychedelic effects) and that are currently controlled in Schedule I of the Controlled Substances Act (CSA). Schedule I drugs are subject to the most restrictive controls under the CSA, as they are considered to have a high abuse potential and no currently accepted medical use in the United States (USA). However, these classic psychedelics were placed in Schedule I at the time the CSA was enacted in 1970, and their abuse potential has not been systematically assessed using modern methodology. This paper provides an overview of scientific evaluation of the abuse potential of classic psychedelics and delineates the data that will be needed in support of a recommendation for the rescheduling, if a drug product containing a classic psychedelic gains FDA approval. This article is part of the Special Issue on 'National Institutes of Health Psilocybin Research Speaker Series'.

Facilitators and Barriers to Clinical Pathway Uptake and Utilization Among Primary Care Providers in Saskatchewan - A Qualitative Study.

PURPOSE: Clinical Pathways (CPWs) are multidisciplinary, evidence-based, complex interventions designed to standardize patient care. In Saskatchewan, development, implementation and evaluation of the seven provincial CPWs (Hip & Knee, Spine, Pelvic Floor, Prostate Assessment, Fertility Care, Lower Extremity Wound Care and Acute Stroke) present significant challenges, leading to low utilization. This study aimed to identify facilitators and barriers to CPW utilization by Saskatchewan family physicians. METHODS: To identify the facilitators and barriers to CPWs, a qualitative interpretive approach consisted of eight one-on-one key informant interviews and five focus groups held with 30 family physicians in two larger urban and two smaller Saskatchewan cities. Inductive, thematic analysis of the interviews based on the Theoretical Domain Framework for behavioral changes was used to identify facilitators and barriers to CPW uptake and utilization. RESULTS: Fifty-one themes were mapped under 14 Theoretical Domain Framework domains. Major barriers included the following: system-level (knowledge and communication, social/professional identity, family physician engagement and education); objective clarification (goals, belief about consequences of implementing CPW); and technical and resource related (administrative, access to local specialists, enforcement and incentives). The most prominent barrier was lack of systematic CPW promotion and inconsistencies in communication between the following: organization-to-practitioner; organization-to-organization; and practitioner-to-practitioner. Facilitators who mitigated barriers were need for optimized and integrated information technology services (i.e., Electronic Medical Records) and optimism towards CPW usage and patient outcomes. CONCLUSIONS: This exploratory study identified specific improvements and recommendations required to promote uptake of CPWs based on perceived facilitators and barriers.

Single B Cell Cloning and Production of Rabbit Monoclonal Antibodies.

Monoclonal antibodies are among the most significant biological tools used in medicine and biology that have revolutionized the field of diagnostics, therapeutics, and targeted drug delivery systems for many diseases. Among them, rabbit monoclonal antibodies have attracted significant attention for having high affinity and specificity. During the past few decades, different techniques have been developed to produce monoclonal antibodies. Single B cell cloning technology offers many advantages compared to other methods and has been used to generate monoclonal antibodies from different species including rabbits. This review briefly describes some of these methods, with main focus on single B cell cloning and production of rabbit monoclonal antibodies.

Characterization of polyclonal antibodies to Herpes Simplex Virus types 1 and 2.

Infections with herpes simplex virus (HSV) types 1 and 2 have been linked to oral, facial, genital lesions, as well as some visceral organ changes in patients under immunosuppressed conditions. Immunohistochemistry (IHC) with HSV antibodies is used for identification of the viruses in tissue samples. In this study, two polyclonal antibodies, prepared separately with HSV-1 and HSV-2 immunogens, were characterized in comparison to a monoclonal antibody to HSV-1 (10A3). The polyclonal anti-HSV-1 and monoclonal antibody 10A3 were shown to be reactive to viral proteins of both HSV-1 and HSV-2 on Western blots, while the polyclonal anti-HSV-2 was reactive to HSV-2 proteins, but not to those of HSV-1. Cross-reactivity was not observed to proteins of six other frequently encountered herpes viruses. IHC characterization was performed on 29 cases of HSV-infected tissue samples, 61 samples infected with other herpes viruses and 35 samples without known infection. By IHC, the polyclonal anti-HSV-1 and a monoclonal antibody 10A3 exhibited a signal, mainly in a nuclear pattern, in all of the HSV-infected samples and not in other tissue types. A positive signal, mainly in the cytoplasm, was identified with the polyclonal anti-HSV-2 in 21 of the 29 HSV-infected samples. Genotyping analysis was successful in 14 of the HSV-infected samples, with IHC HSV-2 positivity correlative to the HSV-2 genotype. The results demonstrate that these antibodies are useful tools for identification of HSV-1 and HSV-2, and their combinatorial application may help to distinguish between these two types of infection.

Differences in Simulated Refractive Outcomes of Photorefractive Keratectomy (PRK) and Laser In-Situ Keratomileusis (LASIK) for Myopia in Same-Eye Virtual Trials.

The use of computational mechanics for assessing the structural and optical consequences of corneal refractive procedures is increasing. In practice, surgeons who elect to perform PRK rather than LASIK must often reduce the programmed refractive treatment magnitude to avoid overcorrection of myopia. Building on a recent clinical validation study of finite element analysis (FEA)-based predictions of LASIK outcomes, this study compares predicted responses in the validated LASIK cases to theoretical PRK treatments for the same refractive error. Simulations in 20 eyes demonstrated that PRK resulted in a mean overcorrection of 0.17 ± 0.10 D relative to LASIK and that the magnitude of overcorrection increased as a function of attempted correction. This difference in correction closely matched (within 0.06 ± 0.03 D) observed differences in PRK and LASIK from a historical nomogram incorporating thousands of cases. The surgically induced corneal strain was higher in LASIK than PRK and resulted in more forward displacement of the central stroma and, consequently, less relative flattening in LASIK. This FE model provides structural confirmation of a mechanism of action for the difference in refractive outcomes of these two keratorefractive techniques, and the results were in agreement with empirical clinical data.

Assessing the implementation processes of a large-scale, multi-year quality improvement initiative: survey of health care providers.

BACKGROUND: Beginning in 2012, Lean was introduced to improve health care quality and promote patient-centredness throughout the province of Saskatchewan, Canada with the aim of producing coordinated, system-wide change. Significant investments have been made in training and implementation, although limited evaluation of the outcomes have been reported. In order to better understand the complex influences that make innovations such as Lean "workable" in practice, Normalization Process Theory guided this study. The objectives of the study were to: a) evaluate the implementation processes associated with Lean implementation in the Saskatchewan health care system from the perspectives of health care professionals; and b) identify demographic, training and role variables associated with normalization of Lean. METHODS: Licensed health care professionals were invited through their professional associations to complete a cross-sectional, modified, online version of the NoMAD questionnaire in March, 2016. Analysis was based on 1032 completed surveys. Descriptive and univariate analyses were conducted. Multivariate multinomial regressions were used to quantify the associations between five NoMAD items representing the four Normalization Process Theory constructs (coherence, cognitive participation, collective action and reflexive monitoring). RESULTS: More than 75% of respondents indicated that neither sufficient training nor resources (collective action) had been made available to them for the implementation of Lean. Compared to other providers, nurses were more likely to report that Lean increased their workload. Significant differences in responses were evident between: leaders vs. direct care providers; nurses vs. other health professionals; and providers who reported increased workload as a result of Lean vs. those who did not. There were no associations between responses to normalization construct proxy items and: completion of introductory Lean training; participation in Lean activities; age group; years of professional experience; or employment status (full-time or part-time). Lean leader training was positively associated with proxy items reflecting coherence, cognitive participation and reflexive monitoring. CONCLUSIONS: From the perspectives of the cross-section of health care professionals responding to this survey, major gaps remain in embedding Lean into healthcare. Strategies that address the challenges faced by nurses and direct care providers, in particular, are needed if intended goals are to be achieved.

CD10 immunohistochemistry stains enteric mucosa, but negative staining is unreliable in the setting of active enteritis.

Ileal pouch-anal anastomosis is the definitive therapy for ulcerative colitis that is refractory to medical treatment or that has developed neoplasia. Patients with this procedure are routinely followed using directed endoscopic biopsies to monitor for dysplasia in the rectal cuff, residual/recurrent ulcerative colitis, and nonspecific acute inflammation of the ileal pouch (pouchitis), which have different clinical management and outcomes. Thus, accurate localization of mucosal biopsies is crucial to a definitive histological diagnosis, but is complicated by overlapping clinical presentations of pouchitis and ulcerative colitis, post-surgical and inflammatory changes to the mucosa, and altered endoscopic anatomy, resulting in difficulty determining whether a mucosal biopsy is ileal or rectal in origin for both the endoscopist and the pathologist. We explored the utility of CD10 immunohistochemistry to aid diagnosis in this clinical setting by highlighting the enteric mucosa, based on previous studies showing its utility in brush border staining and in the diagnosis of microvillous inclusion disease. We found uniformly positive CD10 immunostaining in normal enteric mucosa, but variable loss of expression in the setting of active enteritis. Specifically, CD10 staining was lost in up to 10% of the mucosa in 1/12 ileostomies and 4/13 enteric anastomoses, in 10-80% of the mucosa in 9/10 cases of Crohn's ileitis, in 10-60% of the mucosa in 7/16 ileal pouches, and in 20-90% of the mucosa in 6/8 cases of backwash ileitis, usually in the presence of active inflammation. There was no CD10 expression by normal or diseased colonic mucosa. Therefore, while CD10 immunostaining identifies normal enteric mucosa with 100% specificity, negative staining does not definitively exclude small intestinal mucosa in the setting of active enteritis, a common condition in ileal pouch mucosa.

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone.

BACKGROUND: Increased use of breast cancer screening has led to an increase in the number of diagnosed cases of ductal carcinoma in situ (DCIS). However, there is no definite way to predict progression or recurrence of DCIS. We analyzed the significance of biological markers and tumor characteristics in predicting recurrence in a large series of DCIS patients with long-term follow-up treated with breast conservation surgery (BCS) alone. METHODS: Clinical and pathological data were analyzed for 141 patients who underwent BCS for DCIS. All had negative surgical margins. Using local disease recurrence as an endpoint, we sought to determine the prognostic significance of several histopathological characteristics (tumor size, presence of necrosis, and subtype) and biological markers (estrogen receptor, progesterone receptor, and Her-2/neu.) RESULTS: At a median follow-up of 122 months (maximum follow-up, 294 months), 60 recurrences occurred, with a median time to recurrence of 191 months. On multivariate analysis, Her-2 positivity (3+) was found to be significantly associated with reduced time to tumor recurrence (P = .028). Tumor size and higher grade were marginally statistically significant (P = .099, P = .070). Neither necrosis nor tumor pathological characteristics were found to be significantly related to time to disease recurrence. CONCLUSIONS: Our results suggested that status of Her-2/neu, larger tumor size, and higher nuclear grade were significantly correlated with time to tumor recurrence in patients treated with BCS alone. Using logistical analyses, no significant correlation was found between tumor pathological characteristics and disease recurrence.

MicroRNA expression profiling of male breast cancer.

INTRODUCTION: MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers. METHODS: Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and five cases of male gynecomastia, and from 10 female ductal breast carcinomas. The RNA harvested was hybridized to miRNA microarrays (~1,100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicate). To further support the microarray data, an immunohistochemical analysis for two specific miRNA gene targets (HOXD10 and VEGF) was performed in a small series of male breast carcinoma and gynecomastia samples. RESULTS: We identified a male breast cancer miRNA signature composed of a large portion of underexpressed miRNAs. In particular, 17 miRNAs with increased expression and 26 miRNAs with decreased expression were identified in male breast cancer compared with gynecomastia. Among these miRNAs, some had well-characterized cancer development association and some showed a deregulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male with female breast cancer miRNA expression signatures, 17 significantly deregulated miRNAs were observed (four overexpressed and 13 underexpressed in male breast cancers). The HOXD10 and VEGF gene immunohistochemical expression significantly follows the corresponding miRNA deregulation. CONCLUSIONS: Our results suggest that specific miRNAs may be directly involved in male breast cancer development and that they may represent a novel diagnostic tool in the characterization of specific cancer gene targets.

Extra-gastrointestinal stromal tumor of the pancreas: case report and a review of the literature.

Gastrointestinal (GI) stromal tumors are mesenchymal tumors that arise from the GI tract. In rare cases, these tumors are found in intra-abdominal sites unrelated to the GI tract and are immunohistochemically similar to their GI tract counterparts. Primary pancreatic GI stromal tumors are very rare, with only 4 previous cases reported.