Importance of PET/CT in Initial Workup of Head and Neck Squamous Cell Carcinoma.

Objective: Assess the impact of positron emission tomography/computed tomography (PET/CT) on disease staging at presentation in patients with head and neck squamous cell carcinoma. Study Design: Retrospective cross-sectional review. Setting: Academic multicenter single institution (Geisinger Health System). Methods: All patients who had PET/CT imaging during workup for head and neck squamous cell carcinoma were included in the study. Pre- and post-PET/CT clinical staging were recorded. Statistical analyses were performed for patients with a change in clinical staging or detection of second primary malignancies on PET/CT. Results: A total of 292 patients were included in the study, 238 of whom underwent PET/CT imaging as part of their initial workup. Twenty-eight (11.9%) patients were clinically upstaged on PET/CT with 7 patients having treatment alterations based on imaging. Eighteen (7.6%) patients were found to have second primary malignancies on PET/CT. Conclusion: The current study further illustrates the importance of PET/CT in the workup of head and neck squamous cell carcinoma. Without the inclusion of PET/CT imaging, 19.3% of patients would have either been staged inappropriately or had second primary malignancies missed, again confirming the necessity of comprehensive functional imaging during the initial pretreatment workup.

Defining Duplex Ultrasound Criteria for In-Stent Restenosis of the Carotid Artery Using Computed Tomographic Angiography.

Introduction Duplex ultrasound (DUS) velocity measurement is the preferred method for evaluating carotid artery stenosis. However, velocity criteria based upon native carotid arteries may not apply to internal carotid artery stents. Previously, catheter-based angiography was used to determine DUS velocity criteria for in-stent restenosis (ISR), but conventional angiography is invasive and can be limited. This study sought to define duplex ultrasound velocity criteria for predicting internal carotid artery in-stent restenosis by correlating in-stent velocities with computed tomographic angiography (CTA) measurements of percent stenosis. Methods A retrospective chart review was conducted on all patients who underwent internal carotid artery (ICA) stenting within our health system between January 2013 and February 2020. Thirty-eight surveillance DUS studies from 32 patients were found to have CTA performed within 30 days. Centerline reconstructions of internal carotid artery stents were created using Aquarius iNtuition software (TeraRecon, Durham, NC, USA). Two independent observers measured percent stenosis by three built-in methods. Stenotic areas were matched to DUS-measured peak systolic velocities (PSV) and end-diastolic velocities (EDV). Internal carotid artery PSV (stent) to common carotid artery (CCA) PSV ratios (ICA/CCA) were calculated, and receiver operating characteristic (ROC) curves were generated. The optimal DUS velocity criteria in the stented ICA were determined by maximizing Youden's index. Results Mean vessel diameter measurement of percent stenosis resulted in the most accurate model for all DUS velocity parameters (PSV, EDV, and ICA/CCA ratio) and was used for threshold determinations (area under the receiver operating characteristics (AUROC): 0.99, 0.96, and 0.96, respectively). A PSV cutoff of 240 cm/s for ≥60% ISR resulted in the highest Youden's index (97%) with 100% sensitivity and 97% specificity. Secondary DUS parameters included an EDV ≥50 cm/s (Youden's index 84%) and an ICA/CCA ratio ≥ 2.2 (Youden's index 91%). Conclusions Velocity criteria to predict internal carotid artery ISR is needed to inform decisions for possible reintervention. Using CTA, we found that a PSV ≥240 cm/s on carotid DUS can predict ≥60% ISR with high sensitivity and specificity. This value can be used as an alternative to current velocity criteria based on native carotid arteries. However, the optimal thresholds for EDV and ICA/CCA ratio were similar to native carotid arteries.

Changes to the Simian Immunodeficiency Virus (SIV) Reservoir and Enhanced SIV-Specific Responses in a Rhesus Macaque Model of Functional Cure after Serial Rounds of Romidepsin Administrations.

HIV persistence requires lifelong antiretroviral therapy (ART), calling for a cure. The histone deacetylase inhibitor, romidepsin, is used in the "shock and kill" approach with the goal of reactivating virus and subsequently clearing infected cells through cell-mediated immune responses. We tested serial and double infusions of romidepsin in a rhesus macaque (RM) model of SIV functional cure, which controls virus without ART. Off ART, romidepsin reactivated SIV in all RMs. Subsequent infusions resulted in diminished reactivation, and two RMs did not reactivate the virus after the second or third infusions. Therefore, those two RMs received CD8-depleting antibody to assess the replication competence of the residual reservoir. The remaining RMs received double infusions, i.e., two doses separated by 48-h. Double infusions were well tolerated, induced immune activation, and effectively reactivated SIV. Although reactivation was gradually diminished, cell-associated viral DNA was minimally changed, and viral outgrowth occurred in 4/5 RMs. In the RM which did not reactivate after CD8 depletion, viral outgrowth was not detected in peripheral blood mononuclear cells (PBMC)-derived CD4+ cells. The frequency of SIV-specific CD8+ T cells increased after romidepsin administration, and the increased SIV-specific immune responses were associated, although not statistically, with the diminished reactivation. Thus, our data showing sequential decreases in viral reactivation with repeated romidepsin administrations with all RMs and absence of viral reactivation after CD8+ T-cell depletion in one animal suggest that, in the context of healthy immune responses, romidepsin affected the inducible viral reservoir and gradually increased immune-mediated viral control. Given the disparities between the results of romidepsin administration to ART-suppressed SIVmac239-infected RMs and HIV-infected normal progressors compared to our immune-healthy model, our data suggest that improving immune function for greater SIV-specific responses should be the starting point of HIV cure strategies. IMPORTANCE HIV cure is sought after due to the prevalence of comorbidities that occur in persons with HIV. One of the most investigated HIV cure strategies is the "shock and kill" approach. Our study investigated the use of romidepsin, a histone deacetylase (HDAC) inhibitor, in our rhesus macaque model of functional cure, which allows for better resolution of viral reactivation due to the lack of antiretroviral therapy. We found that repeated rounds of romidepsin resulted in gradually diminished viral reactivation. One animal inevitably lacked replication-competent virus in the blood. With the accompanying enhancement of the SIV-specific immune response, our data suggest that there is a reduction of the viral reservoir in one animal by the cell-mediated immune response. With the differences observed between our model and persons living with HIV (PWH) treated with romidepsin, specifically in the context of a healthy immune system in our model, our data thereby indicate the importance of restoring the immune system for cure strategies.

Outcomes of transcaval endoleak embolization via laser fenestration of the inferior vena cava following endovascular abdominal aortic aneurysm repair.

This report describes a single center experience with laser fenestration of the inferior vena cava for the treatment of type 2 endoleak after endovascular abdominal aortic aneurysm repair. Our technique is reviewed, and clinical data after treatment are reported. Twelve patients underwent transcaval embolization via laser fenestration. Technical success was achieved in all cases (100%) with no postoperative complications. At a median follow-up of 12.9 months, no patient demonstrated a persistent endoleak and there were no cases of aortocaval fistula. Transcaval embolization, via laser fenestration, provides an additional strategy for the management of type 2 endoleak after endovascular abdominal aortic aneurysm repair.

High-fat diet exacerbates SIV pathogenesis and accelerates disease progression.

Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, indicating a potential reservoir expansion. The HFD induced prominent immune cell infiltration in the adipose tissue, an important SIV reservoir, and heightened systemic immune activation and inflammation, altering the intestinal immune environment and triggering gut damage and microbial translocation. Furthermore, HFD altered lipid metabolism and HDL oxidation and also induced liver steatosis and fibrosis. These metabolic disturbances triggered incipient atherosclerosis and heightened cardiovascular risk in the SIV-infected HFD-receiving nonhuman primates. Our study demonstrates that dietary intake has a discernable impact on the natural history of HIV/SIV infections and suggests that dietary changes can be used as adjuvant approaches for HIV-infected subjects, to reduce inflammation and the risk of non-AIDS comorbidities and possibly other infectious diseases.