Hyperprolactinemia-induced acute ischemic stroke.

Strokes are the fifth leading cause of death in the United States with almost 800,000 patients seeking emergency care each year-most of whom are seen for ischemic strokes. Acute ischemic strokes (AIS) can be caused by emboli in diseases such as atrial fibrillation as well as thrombus formation in the form of platelet deposition in patients with atherosclerotic disease. Platelet activation by immunomodulators including thromboxane A2 (TXA2), serotonin, and thrombin have been extensively delineated; however, the activation by hormones such as prolactin has only recently been revealed. We present a case of a 25-year-old male with a history of pituitary microadenoma and hyperprolactinemia who presented with an acute ischemic stroke in the setting of medication non-compliance. To our knowledge, this is the first known case of AIS in a patient with known hyperprolactinemia who presented with a stroke due to be medication non-compliance.

Stat3 and CCAAT enhancer-binding protein ß (C/ebpß) activate Fanconi C gene transcription during emergency granulopoiesis.

Interferon consensus sequence-binding protein (Icsbp) is required for terminating emergency granulopoiesis, an episodic event responsible for granulocyte production in response to infections and a key component of the innate immune response. Icsbp inhibits the expression of Stat3 and C/ebpß, transcription factors essential for initiating and sustaining granulopoiesis, and activates transcription of Fanconi C (FANCC), a DNA repair protein. In prior studies, we noted accelerated bone marrow failure in Fancc-/- mice undergoing multiple episodes of emergency granulopoiesis, associated with apoptosis of bone marrow cells with unrepaired DNA damage. Additionally, we found increased expression of Fanconi C and F proteins during emergency granulopoiesis. These findings suggest that Icsbp protects the bone marrow from DNA damage by increasing activity of the Fanconi DNA repair pathway, but the mechanisms for FANCC activation during initiation of emergency granulopoiesis are unclear. In this study, we observed that Stat3 and C/ebpß activate FANCC transcription and contribute to DNA repair. Our findings indicate that FancC expression is increased during Stat3- and C/ebpß-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp. Our work reveals that Stat3- and C/ebpß-mediated FancC expression is a critical component for initiating and sustaining key innate immune responses.

Canadian Association of Radiologists Annual Scientific Meetings: How Many Abstracts Go on to Publication?

PURPOSE: To determine the percentage of abstracts presented at the Canadian Association of Radiologists (CAR) annual scientific meetings that go on to publication. METHODS: Records of previous CAR meetings from the years 2005-2011 were obtained. An Internet search was performed to determine which abstracts went on to publication. Abstracts were assessed according to exhibit category (Resident Award Papers), educational institution, publishing journal, and time to publication. RESULTS: Of the 402 abstracts presented, 112 (28%) were published. Overall, an average of 37% of Radiologists-In-Training Presentations, 34% of Scientific Exhibits, and 20% of Educational Exhibits went on to publication. The University of British Columbia and University of Ottawa published the largest number of abstracts (66 and 62, respectively) from the years 2005-2011. The University of Montreal had the largest percentage of abstracts published (42%). The range of publishing journals was wide, but the top publisher was the Canadian Association of Radiologists Journal (27%). Eighty-three percent of abstracts were published within 3 years of being presented. CONCLUSION: In total, 28% of all the abstracts presented at the CAR conferences between 2005 and 2011 were published. Further exploration into the reasons and barriers for abstracts not being published may be a next step in future research.

Role of immunotherapy in chondrosarcoma: A case report and review of the literature.

Chondrosarcomas (CSs) consist of a heterogenous group of primary bone cancers arising from malignant cells which produce cartilaginous matrix. As the second most common primary bone cancer, CS are often resistant to systemic chemotherapy due to poor vascularization, slow proliferation, and expression of multidrug-resistant pumps. Immune checkpoint inhibitors have transformed the field of oncology and are now designated as frontline therapy for many solid tumor cancers. Several studies have demonstrated increased expression of programed cell death 1 (PD-1) and PD-L1 in CS tissue in vitro, which has led to the development of multiple clinical trials for immunotherapy in patients with aggressive CS. In this review, we highlight the ongoing investigation into the role for immunotherapy in CS. We also report the case of a 44-year-old female with a history of stage IV primary CS of the right shoulder who underwent radical resection with recurrence and demonstrated a spectacular sustained response to pembrolizumab at our center. Our review highlights the need for further studies investigating the role of immunotherapy in the treatment of aggressive bone sarcomas that are resistant to standard surgical resection, chemotherapy, and radiation treatment.

Chondrosarcoma is a cancer of the cells that make cartilage and is often removed surgically. However, when the cancer spreads to other organs such as the lungs or are in areas unreachable by surgeons, there are not many effective treatments. While targeted treatments are in development, many of them have unclear effectiveness. A new and rapidly growing area of cancer treatment is known as immunotherapy, which uses the body's own immune system to kill cancer cells. In this review, we discuss trials in using immunotherapy against aggressive forms of chondrosarcoma. We also present the case of a patient where an immunotherapy agent called pembrolizumab was highly effective in preventing disease progression.

The Prognostic and Therapeutic Potential of DNA Damage Repair Pathway Alterations and Homologous Recombination Deficiency in Lung Cancer.

Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as targeted therapy and immunotherapy, have significantly improved outcomes. However, many patients with lung cancer do not benefit from existing therapies or develop progressive disease, leading to increased morbidity and mortality despite initial responses to treatment. Alterations in DNA-damage repair (DDR) genes represent a cancer hallmark that impairs a cell's ability to prevent deleterious mutation accumulation and repair. These alterations have recently emerged as a therapeutic target in breast, ovarian, prostate, and pancreatic cancers. The role of DDR alterations remains largely unknown in lung cancer. Nevertheless, recent research efforts have highlighted a potential role of some DDR alterations as predictive biomarkers of response to treatment. Despite the failure of PARP inhibitors (main class of DDR targeting agents) to improve outcomes in lung cancer patients, there is some evidence suggesting a role of PARP inhibitors and other DDR targeting agents in benefiting a distinct subset of lung cancer patients. In this review, we will discuss the existing literature on DDR alterations and homologous recombination deficiency (HRD) state as predictive biomarkers and therapeutic targets in both non-small cell lung and small cell lung cancer.

Bone-cartilage mismatch in the medial tibial plateau: A MRI study.

BACKGROUND: Bone-cartilage mismatch is a variation in which the surface curvature of the articular cartilage is incongruent with the curvature of the underlying subchondral bone. The purpose of this study is to investigate the prevalence of this variant in the medial tibial plateau (MTP) and examine potential association with clinical findings and intra-articular derangements using MRI. METHODS: A quantitative and qualitative retrospective analysis of 98 knee MRI studies was performed. Bone and cartilage depths of the MTP were measured to assess bone-cartilage morphology and classified into congruent (concave bone-concave cartilage) and incongruent (concave bone-convex cartilage) patterns. Associations between bone-cartilage mismatch and clinical findings and other MRI changes were assessed using Fisher's exact test. RESULTS: By quantitative assessment, four individuals (4%) had MTP incongruent morphology (bone-cartilage mismatch). The mean bone depth ± standard deviation (SD) was 2.3 ± 0.6 mm concave in the congruent group, and 1.4 ± 0.6 mm concave in the incongruent group. The mean cartilage depth ± SD was 0.7 ± 0.7 mm concave in the congruent group, and 0.9 ± 0.5 mm convex in the incongruent group. By qualitative assessment, three individuals (3%) had incongruent morphology. Although not statistically significant, a higher proportion of individuals (3 of 4; 75%) with incongruent cartilage demonstrated chondromalacia patellae compared to those with congruent cartilage (38 of 94; 40%). CONCLUSION: Bone-cartilage mismatch was present in 3-4% of the knees. Individuals with incongruent cartilage demonstrated a trend of a higher proportion of chondromalacia patellae. Larger studies are needed to evaluate this further.