Differential Regulation of the STING Pathway in Human Papillomavirus-Positive and -Negative Head and Neck Cancers.

Squamous cell carcinomas, which arise from the cells that line the mucosal surfaces of the head and neck, represent the most common type of head and neck cancers (HNSCC). Human papillomavirus (HPV) infection has been strongly associated with the development of oropharyngeal cancers, which are cancers that occur in the back of the throat, including the tonsils and base of the tongue. HNSCCs with and without HPV infection have distinct pathology, with HPV-positive patients having higher levels of immune infiltration, activation in the tumor microenvironment and better response to radiation and chemotherapy. It is, however, unclear whether HPV infection in HNSCCs has the potential to activate innate-immune sensing pathways and if these cancers possess intrinsic immunogenicity associated with HPV infection. Here we investigate the innate immune stimulator of interferon genes (STING) pathway and immune responses to STING activation in HNSCCs and uncover fundamental differences in the regulation of this pathway in cell lines versus primary human clinical specimens. We show that while STING is differentially expressed in HPV-positive and -negative HNSCC cell lines, they exhibit a gross functional defect in signaling through this pathway. However, STING activation in immune cell populations generated immune signatures predicted to elicit useful tumoricidal mechanisms. In contrast, IHC analysis of human tissue microarrays revealed enhanced STING expression in HPV-related tumors and high intratumoral expression of STING correlated with increased survival. SIGNIFICANCE: STING is an important innate immune sensor of cytosolic DNA, inducing essential antiviral and antitumoral responses. This research shows that STING expression is enhanced in HPV-positive HNSCC patient tissue, with high intratumoral STING expression correlating with increased survival. In addition, STING activation in immune cell populations augmented antitumoral effects against HNSCCs, suggesting patients may benefit from the use of STING agonists in combination with traditional therapies.

Seizure following general anesthesia for cystoscopy and urethral dilatation: A case report.

Seizure and anesthesia is a topic necessitating more studies to understand its mechanism. Some anesthetic agents triggers seizures, while others can control it. We are here reporting a case of apparently healthy young adult patient who underwent diagnostic cystoscopy and urethral dilatation under general anesthesia and who developed seizure immediately after admission to the postanaesthetic care unit.

Vesical tumor within an inguinal bladder hernia: A case report.

Bladder herniation through the inguinal canal is a rare condition, accounting for only 1-4% of all inguinal hernias. Most patients are asymptomatic or have atypical symptoms. 65-year-old male who presented with gross hematuria, right inguinal swelling. Diagnosed preoperatively by CT scan to have bladder neoplasm within a right inguinal vesical hernia. Patient. Underwent TURBT and hernia repair. Inguinal bladder hernia is rare and occurs more commonly in obese male patients above 50 years of age. CT scan is the radiological modality choice to confirm the diagnosis prior intervention to avoid intraoperative complications such as bladder injury.

Old Dog, New Trick: Type I IFN-Based Treatment for Acute Myeloid Leukemia.

Despite strong biological rationale for the use of type-I IFNs for the treatment of acute myeloid leukemia (AML), their usage is limited to few hematologic malignancies. Here, we propose that innate immune sensing machinery, particularly the stimulator of IFN genes pathway, may be exploited to deliver antileukemic effects in AML.

Neural Network Analysis of Crystalluria Content to Predict Urinary Stone Type.

PURPOSE: To investigate the relationship between urinary stone type and the type of crystals in the urine. PATIENTS AND METHODS: This retrospective study involved 485 patients with urinary stones treated at King Saud University Medical City from May 2015 to June 2017. Clinical data were obtained from medical records. Different statistical analysis methods were applied, including basic contingency analysis, analysis of variance, logistic regression, discriminant analysis, partition modeling, and neural network evaluations. RESULTS: Of 485 patients, 47 had crystals detected by urinalysis. The most common type of crystal was calcium oxalate (n = 31), which had the highest association with calcium oxalate stones. Uric acid crystals (n = 8) were associated with uric acid stones. The neural network model used for determining the sensitivity and specificity showed an R-square value of 0.88, with an area under the curve of 0.94 for calcium oxalate, 0.94 for carbonate apatite, and 1.0 for uric acid. CONCLUSION: The predictive algorithm developed in the present study may be used with a patient's clinical parameters to predict the stone type. This approach predicts the stone types associated with certain patient characteristics with a high sensitivity and specificity, indicating that the models may be a valuable clinical tool in the diagnosis, management, and monitoring of stone diseases.

Exposure of Urology Residents to the Management of Urethral Strictures in Saudi Arabia: Should the Program for Postgraduates Be Customized?

PURPOSE: This study aimed to assess the exposure and knowledge of urology residents in the management of urethral stricture (US) and to determine if they would be able to perform urethroplasty after graduation and whether urethroplasty should be included as a competency in the training program. PATIENTS AND METHODS: An online survey was sent to all residents enrolled in any urology training program in Saudi Arabia. Fifty-eight (approximately 50%) of the 114 residents who were sent the survey provided responses. RESULTS: Most of the residents (45 residents, 77.6%) who responded were exposed to fewer than ten cases of US during their last year of training. Fifty-six residents (96.6%) attended five or fewer urethroplasty procedures in their last year of training. Twenty-three (40%) residents did not attend any urethroplasty procedure in the last year. The most common procedures attended by the residents were minimally invasive treatments (89% cystoscopy with dilatation and 79% direct visual internal urethrotomy (DVIU)). Most residents responded that they would manage newly diagnosed 1 cm US with either cystoscopy and dilatation or with DVIU 53 (91%). For the first recurrence of US, 46 (79%) residents responded that they would still prefer dilatation or DVIU. For the second, third, and chronic recurrences of US, 20 (34.5%), 6 (10.3%), and 5 (8.6%) residents, respectively, responded that they would perform dilatation or DVIU. Residents had low expectations for the success rate of urethroplasty; only 32 (55.2%) residents thought it had a high success rate. CONCLUSION: Urethroplasty is a specialized urological procedure, one that residents have variable exposure to. Privilege to perform such a procedure after graduating should be modified to ensure the best outcome for patients.