Chilaiditi Syndrome: A Case Report, Literature Review, and Proposition of a Novel Management Staging System.

Chilaiditi's sign refers to colonic interposition between the liver and the diaphragm in the right subphrenic space secondary to the relaxation of the suspensory ligaments of the right colic flexure. The diagnosis of Chilaiditi's sign is based on radiological findings with the following three criteria: 1) The right hemidiaphragm must be adequately elevated above the liver by the intestine, 2) the bowel must be distended by air to illustrate pseudo-pneumoperitoneum, and 3) the superior margin of the liver must be depressed below the level of the left hemidiaphragm. In this report, we present the case of a 49-year-old female presenting with signs and symptoms suggestive of Chilaiditi syndrome managed with laparoscopic surgery. We also present a literature review with a summary of previous studies and propose a novel management staging system for this syndrome.

Inducible TgfbR1 and Pten deletion in a model of tongue carcinogenesis and chemoprevention.

Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem, with a need for novel approaches to chemoprevention and treatment. Preclinical models that recapitulate molecular alterations that occur in clinical HNSCC patients are needed to better understand molecular and immune mechanisms of HNSCC carcinogenesis, chemoprevention, and efficacy of treatment. We optimized a mouse model of tongue carcinogenesis with discrete quantifiable tumors via conditional deletion of Tgfßr1 and Pten by intralingual injection of tamoxifen. We characterized the localized immune tumor microenvironment, metastasis, systemic immune responses, associated with tongue tumor development. We further determined the efficacy of tongue cancer chemoprevention using dietary administration of black raspberries (BRB). Three Intralingual injections of 500 µg tamoxifen to transgenic K14 Cre, floxed Tgfbr1, Pten (2cKO) knockout mice resulted in tongue tumors with histological and molecular profiles, and lymph node metastasis similar to clinical HNSCC tumors. Bcl2, Bcl-xl, Egfr, Ki-67, and Mmp9, were significantly upregulated in tongue tumors compared to surrounding epithelial tissue. CD4+ and CD8 + T cells in tumor-draining lymph nodes and tumors displayed increased surface CTLA-4 expression, suggestive of impaired T-cell activation and enhanced regulatory T-cell activity. BRB administration resulted in reduced tumor growth, enhanced T-cell infiltration to the tongue tumor microenvironment and robust antitumoral CD8+ cytotoxic T-cell activity characterized by greater granzyme B and perforin expression. Our results demonstrate that intralingual injection of tamoxifen in Tgfßr1/Pten 2cKO mice results in discrete quantifiable tumors suitable for chemoprevention and therapy of experimental HNSCC.

Should We Perform Incidental Appendectomy in Trauma Patients Undergoing Laparotomy?

Incidental appendectomy (IA) is sometimes performed in patients undergoing abdominal operations to prevent subsequent development of appendicitis. Patients who undergo laparotomy for major abdominal trauma are at high risk of developing dense adhesions, increasing the risk of future operations. Therefore, there is a potential benefit to IA for patients undergoing trauma laparotomy. We performed a retrospective review of patients who underwent IA during laparotomy for abdominal trauma at a Level 1 trauma center between January 2010, and June 2020. Twenty-three patients underwent IA; they tended to be young (33.7 ± 18.9 years) and male (87%) with 12 penetrating and 11 blunt injuries. Regarding indications, 13 had no documented intra-operative abnormalities of the appendix, 6 patients had a fecalith, and 3 had trauma to the appendix. One patient's appendix was adhered to the peritoneum and one patient had unusual anatomic location. Only one patient developed an appendiceal stump leak after IA.

Black raspberry extract inhibits regulatory T-cell activity in a murine model of head and neck squamous cell carcinoma chemoprevention.

Head and neck squamous cell carcinomas (HNSCC) are one of the most diagnosed malignancies globally, with a 5-year survival rate of approximately 40% to 50%. Current therapies are limited to highly invasive surgery, aggressive radiation, and chemotherapies. Recent reports have demonstrated the potential phytochemical properties of black raspberries in inhibiting the progression of various cancers including HNSCCs. However, the effects of black raspberry extracts on immune cells of the tumor microenvironment, specifically regulatory T cells during HNSCC, have not been investigated. We used a mouse model of 4-nitroquinoline-1-oxide (4NQO) chemically induced HNSCC carcinogenesis to determine these effects. C57BL/6 mice were exposed to 4NQO for 16 weeks and regular water for 8 weeks. 4NQO-exposed mice were fed the AIN-76A control mouse diet or the AIN76 diet supplemented with black raspberry extract. At terminal sacrifice, tumor burdens and immune cell recruitment and activity were analyzed in the tumor microenvironment, draining lymph nodes, and spleens. Mice fed the BRB extract-supplemented diet displayed decreased tumor burden compared to mice provided the AIN-76A control diet. Black raspberry extract administration did not affect overall T-cell populations as well as Th1, Th2, or Th17 differentiation in spleens and tumor draining lymph nodes. However, dietary black raspberry extract administration inhibited regulatory T-cell recruitment to HNSCC tumor sites. This was associated with an increased cytotoxic immune response in the tumor microenvironment characterized by increased CD8+ T cells and enhanced Granzyme B production during BRB extract-mediated HNSCC chemoprevention. Interestingly, this enhanced CD8+ T-cell antitumoral response was localized at the tumor sites but not at spleens and draining lymph nodes. Furthermore, we found decreased levels of PD-L1 expression by myeloid populations in draining lymph nodes of black raspberry-administered carcinogen-induced mice. Taken together, our findings demonstrate that black raspberry extract inhibits regulatory T-cell recruitment and promotes cytotoxic CD8 T-cell activity at tumor sites during HNSCC chemoprevention. These results demonstrate the immunomodulatory potential of black raspberry extracts and support the use of black raspberry-derived phytochemicals as a complementary approach to HNSCC chemoprevention and treatment.

Giant Proximal Right Colon Submucosal Hematoma Leading to a Large Bowel Obstruction.

A 41-year-old female with a previous history of chronic obstructive pulmonary disease (COPD) and polycythemia presented to the emergency department with worsening shortness of breath and cough which progressed to respiratory distress requiring mechanical ventilation. During her hospital stay, she developed abdominal distention followed by a fever and a four-point decrease in hemoglobin. A non-contrasted abdominopelvic CT scan was ordered which showed a very large retroperitoneal hematoma adjacent to the right colon with subtle active bleeding. Selective angioembolization of a distal segment of the right colic artery was performed by Interventional Radiology (IR) to achieve hemostasis and hemodynamic stability. Due to the persistent and worsening abdominal distention, a CT scan with contrast was ordered which clearly showed a submucosal hematoma in the region of the right colon extending from the hepatic flexure to the cecum. The hematoma was completely obstructing the proximal and mid ascending colon leading to a large bowel obstruction. Exploration of the abdomen showed severe bowel dilation, and frank ischemia of the hepatic flexure of the colon. Right hemicolectomy with primary ileocolonic anastomosis to evacuate the right retroperitoneal hematoma was subsequently performed. The patient was discharged on post-operative day 16 with no major complications.

STAT1 is regulated by TRIM24 and promotes immunosuppression in head and neck squamous carcinoma cells, but enhances T cell antitumour immunity in the tumour microenvironment.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a significant problem and is frequently resistant to current treatments. STAT1 is important in anti-tumour immune responses against HNSCC. However, the role of STAT1 expression by tumour cells and its regulation during HNSCC is unclear. METHODS: We determined the effects of STAT1 inhibition on tumour development and immunity in CAL27 and UMSCC22A HNSCC cell lines in vitro and in a HNSCC carcinogen-induced model in vivo. RESULTS: STAT1 siRNA knockdown in human HNSCC cells impaired their proliferation and expression of the immunosuppressive marker PD-L1. Stat1-deficient mice displayed increased oral lesion incidence and multiplicity during tumour carcinogenesis in vivo. Immunosuppressive markers PD-1 in CD8+ T cells and PD-L1 in monocytic MDSCs and macrophages were reduced in oral tumours and draining lymph nodes of tumour-bearing Stat1-deficient mice. However, STAT1 was required for anti-tumour functions of T cells during HNSCC in vivo. Finally, we identified TRIM24 to be a negative regulator of STAT1 that plays a similar tumorigenic function to STAT1 in vitro and thus may be a potential target when treating HNSCC. CONCLUSION: Our findings indicate that STAT1 activity plays an important role in tumorigenicity and immunosuppression during HNSCC development.

Patient Satisfaction in Outpatient Radiology: Effects of Modality and Patient Demographic Characteristics.

Objective: To characterize predictors of patient satisfaction in outpatient radiology, we examined whether patient satisfaction differs across radiology modalities and demographic groups. Methods: A random sampling of Press-Ganey outpatient services surveys for radiology and non-radiology visits from September 2008 to September 2017 were retrospectively analyzed. Composite scores averaged across all Likert items were analyzed as both a continuous variable and a dichotomous variable of dissatisfaction (defined as ≤3 on the 5-point scale). Results: Among 9983 radiology surveys, mammography had higher composite scores than MRI, CT, radiography, US, and NM/PET (p < 0.001) and lower dissatisfaction (3.9%) than CT (6.7%), MRI (7.3%), and radiography (8.2%). Low-scoring responses were most common in the Facilities domain (7.8%) and least common in Overall Assessment (3.8%). Satisfaction metrics were lowest for ages 20-29 and highest for ages 70-79. Lower dissatisfaction rates were seen among Hispanics (3%) and whites (6%), compared to blacks (10%) and Asians (18%). Conclusion: Significant differences in patient satisfaction were found across imaging modalities and demographic variables. Further investigations to identify contributing factors may help improve patient experiences.

Inhibition of PI3K Isoform p110γ Increases Both Anti-Tumor and Immunosuppressive Responses to Aggressive Murine Head and Neck Squamous Cell Carcinoma with Low Immunogenicity.

HNSCC is the sixth most common cancer, with around 650,000 new cases yearly. Gain of function mutations in the PI3K pathway are common in HNSCC, and inhibition of the PI3K p110γ subunit has shown promise in HNSCC treatment. However, given that PI3K p110γ plays an important role in myeloid and lymphoid immune cell function, it is essential to understand how PI3K p110γ inhibition affects the anti-tumor immune response independent of tumor cells. To elucidate PI3K p110γ function in HNSCC, we employed an orthotopic mouse model using poorly immunogenic and aggressive cell line MOC2 on Pik3cg-/- mice. We observed that wild-type and Pik3cg-/- mice displayed similar rates of HNSCC tumor growth and metastasis after 20 days following tumor injection. T-cell infiltration and intrinsic T-cell responses to MOC2 oral tumors were comparable between wild-type and Pik3cg-/- mice. Interestingly, the immune response of tumor-bearing Pik3cg-/- mice was marked by increased anti-tumor cytotoxic molecules (IFN-γ, IL-17)) by T-cells and immune checkpoint marker (PD-L1, PD-1) expression by myeloid cells and T-cells compared to tumor-bearing wild-type mice. Taken together, our findings demonstrate that inhibition of PI3K p110γ modulates tumor-associated immune cells, which likely potentiates HNSCC treatment when used in combination with selective checkpoint inhibitors.

Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses.

Contact hypersensitivity (CHS) is the most common occupational dermatological disease. Dendritic cells (DCs) mediate the sensitization stage of CHS, while T-cells facilitate the effector mechanisms that drive CHS. Black raspberry (Rubus occidentalis, BRB) and BRB phytochemicals possess immunomodulatory properties, but their dietary effects on CHS are unknown. We examined the effects of diets containing BRB and protocatechuic acid (PCA, a constituent of BRB and an anthocyanin metabolite produced largely by gut microbes), on CHS, using a model induced by 2,4-dinitrofluorobenze (DNFB). Mice were fed control diet or diets supplemented with BRB or PCA. In vitro bone-marrow derived DCs and RAW264.7 macrophages were treated with BRB extract and PCA. Mice fed BRB or PCA supplemented diets displayed decreased DNFB-induced ear swelling, marked by decreased splenic DC accumulation. BRB extract diminished DC maturation associated with reduced Cd80 expression and Interleukin (IL)-12 secretion, and PCA reduced IL-12. Dietary supplementation with BRB and PCA induced differential decreases in IL-12-driven CHS mediators, including Interferon (IFN)-γ and IL-17 production by T-cells. BRB extracts and PCA directly attenuated CHS-promoting macrophage activity mediated by nitric oxide and IL-12. Our results demonstrate that BRB and PCA mitigate CHS pathology, providing a rationale for CHS alleviation via dietary supplementation with BRB or BRB derived anthocyanins.