Imaging of Pulsatile Tinnitus.

Tinnitus is a common complaint that approximately three-fourths of adults will experience at some point in their life. While for many it is a mild nuisance, for some it can be debilitating, affecting cognition and quality of life, increasing stress, and leading to anxiety, depression, and in severe circumstances even suicide. Pulsatile tinnitus refers to the perception of a heartbeat-like sound without external stimulus. Although less common than nonpulsatile tinnitus, pulsatile tinnitus raises concern for underlying disease that can have a high risk of causing the patient harm if undiagnosed, and most of these patients will have positive findings at imaging. While these findings are often subtle, identifying them can have a meaningful impact on the patient's quality of life. The literature on pulsatile tinnitus is changing rapidly with improved imaging techniques and novel minimally invasive treatment options. A careful history and physical examination together with appropriate imaging are therefore critical in identifying the underlying cause. With emerging surgical, endovascular, and supportive technologies, the vast majority of patients with bothersome pulsatile tinnitus can be cured or have their symptoms ameliorated. The objective of this narrative review is to present a comprehensive analysis of the currently available literature on pulsatile tinnitus, with a focus on understanding its pathophysiologic mechanisms, diagnostic pathways, imaging findings, and the spectrum of available management strategies and ultimately to propose a structured framework that aids radiologists as well as clinicians in identifying an underlying diagnosis and guiding management of these patients. ©RSNA, 2024 Supplemental material is available for this article.

Vessel Wall Imaging in Angiogram-Negative Diffuse Subarachnoid Hemorrhage Reveals a Ruptured Lenticulostriate Aneurysm.

A patient presented with acute onset headache and subsequent unconsciousness. The neurologic exam showed left-sided myoclonic jerking and right flaccid hemiparalysis. Noncontrast computed tomography revealed diffuse subarachnoid hemorrhage (SAH) with acute hydrocephalus. Initial digital subtraction angiography (DSA) showed no culprit source for SAH. Repeat DSA on day 7 after initial presentation raised suspicion for left internal carotid artery ophthalmic segment and left lateral lenticulostriate artery (LSA) aneurysms. A magnetic resonance vessel wall imaging (VWI) exam was performed given the presence of multiple potential culprit aneurysms. Vessel wall enhancement around the dome of the left LSA aneurysm suggested rupture, which then facilitated treatment with surgical clipping. LSA aneurysms are exceedingly rare and challenging to treat. Given the associated high degree of morbidity, expedient diagnosis is critical to direct management. VWI could be a valuable tool for detecting ruptured aneurysms in the setting of angiogram-negative SAH.

Gastrobronchial fistula after sleeve gastrectomy: clinical and radiographic findings.

We describe a patient who developed an intractable leak from the gastric sleeve after laparoscopic sleeve gastrectomy, resulting in the development of a gastrobronchial fistula. Affected individuals typically have a persistent leak from the gastric sleeve with recurrent subphrenic abscesses, and when a gastrobronchial fistula develops, these patients may present with paroxysms of coughing immediately after ingestion of solids or liquids. In the appropriate clinical setting, a barium study not only may show the leak, but also directly visualize the gastrobronchial fistula. If aggressive endoscopic dilation procedures and/or endoscopic placement of stents or clips fail to facilitate healing of the leak and fistula, these patients may require surgical intervention, with conversion of the sleeve to a Roux-en-Y gastric bypass or even a partial or total gastrectomy. The development of a gastrobronchial fistula after sleeve gastrectomy therefore can be extremely challenging to manage.

BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands.

Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth. We discovered that BPTF occupies heparanase (Hpse) regulatory elements, activating its expression. Increased heparanase activity results in reduced cell surface abundance of the NCR co-ligands: heparan sulfate proteoglycans (HSPGs). Using gain and loss of function approaches we show that elevated heparanase levels suppress NK cell cytolytic activity to tumor cells in culture. These results suggest that BPTF activates heparanase expression, which in turn reduces cell surface HSPGs and NCR co-ligands, inhibiting NK cell activity. Furthermore, gene expression data from human breast cancer tumors shows that elevated BPTF expression correlates with reduced antitumor immune cell signatures, supporting conserved roles for BPTF in suppressing antitumor immunity. Conditional BPTF depletion in established mouse breast tumors enhances antitumor immunity, suggesting that inhibiting BPTF could provide a novel immunotherapy.

The Association between t-PA Administration and In-Hospital Mortality following Acute Ischemic Stroke in Puerto Rican Patients.

OBJECTIVE: Despite being the standard of care, thrombolytic therapy with tissue plasminogen activator (t-PA) is currently administered to only 5% of acute ischemic stroke (AIS) patients in the United States. Published scientific information regarding both the use of t-PA for AIS in Hispanic patients and its impact on short-term mortality is scarce. The objectives of this study are to investigate, among Puerto Rican patients hospitalized with AIS, the rate of t-PA administration, and the risk of in-hospital mortality in patients who received t-PA vs. those patients who did not receive t-PA. METHODS: We performed a secondary analysis of data from patients with AIS admitted to acute care facilities throughout Puerto Rico in study years 2007, 2009, and 2011who were participating in the Puerto Rico Cardiovascular Disease Surveillance System. Multivariate logistic regression was used to determine the independent association between treatment with t-PA within 4.5 hours of symptom onset and in-hospital mortality. RESULTS: Of the 1968 study patients hospitalized with AIS, 104 (5%) received t-PA treatment. After adjustments for demographic and clinical confounders, patients receiving t-PA had similar odds of in-hospital mortality as patients not receiving t-PA did (OR = 2.49, 95% CI = 0.81-7.66). The receipt of concomitant anticoagulation medication was independently associated with relatively lower odds of in-hospital mortality (OR = 0.42, 95% CI = 0.20-0.88). Being over 80 years of age (OR = 2.03, 95% CI = 1.13-3.68), being obese (OR = 1.88, 95% CI = 1.01-3.49), and arriving in an ambulance (OR = 3.61, 95% CI = 1.95-6.68) were all independently associated with relatively higher odds of in-hospital mortality. CONCLUSION: Among patients hospitalized in Puerto Rico with acute ischemic stroke, t-PA treatment was not significantly associated with in-hospital mortality.

BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.

Genetic studies in fruit flies have implicated the chromatin remodeling complex nucleosome remodeling factor (NURF) in immunity, but it has yet to be studied in mammals. Here we show that its targeting in mice enhances antitumor immunity in two syngeneic models of cancer. NURF was disabled by silencing of bromodomain PHD-finger containing transcription factor (BPTF), the largest and essential subunit of NURF. We found that both CD8+ and CD4+ T cells were necessary for enhanced antitumor activity, with elevated numbers of activated CD8+ T cells observed in BPTF-deficient tumors. Enhanced cytolytic activity was observed for CD8+ T cells cocultured with BPTF-silenced cells. Similar effects were not produced with T-cell receptor transgenic CD8+ T cells, implicating the involvement of novel antigens. Accordingly, enhanced activity was observed for individual CD8+ T-cell clones from mice bearing BPTF-silenced tumors. Mechanistic investigations revealed that NURF directly regulated the expression of genes encoding immunoproteasome subunits Psmb8 and Psmb9 and the antigen transporter genes Tap1 and Tap2 The PSMB8 inhibitor ONX-0914 reversed the effects of BPTF ablation, consistent with a critical role for the immunoproteasome in improving tumor immunogenicity. Thus, NURF normally suppresses tumor antigenicity and its depletion improves antigen processing, CD8 T-cell cytotoxicity, and antitumor immunity, identifying NURF as a candidate therapeutic target to enhance antitumor immunity. Cancer Res; 76(21); 6183-92. ©2016 AACR.

The nucleosome remodeling factor.

An essential component of the chromatin remodeling machinery is NURF (Nucleosome Remodeling Factor), the founding member of the ISWI family of chromatin remodeling complexes. In vertebrates and invertebrates alike, NURF has many important functions in chromatin biology including regulating transcription, establishing boundary elements, and promoting higher order chromatin structure. Since NURF is essential to many aspects of chromatin biology, knowledge of its function is required to fully understand how the genome is regulated. This review will summarize what is currently known of its biological functions, conservation in the most prominent model organisms, biochemical functions as a nucleosome remodeling enzyme, and its possible relevance to human cancer.