Focused Expertise of IOTox GI Service Can Improve Quality of Clinical Care and Outcome of Immune Mediated Diarrhea/Colitis Among Inpatients: A Retrospective Review and Quality Improvement Project

Alice Saji pictured. Gastroenterology, Hepatology, Nutrition Saji A, Jacob J, Issac A, Kuang A, Wang Y, Thomas AS. S132 Focused Expertise of IOTox GI Service Can Improve Quality of Clinical Care and Outcome of Immune Mediated Diarrhea/Colitis Among Inpatients: A Retrospective Review and Quality Improvement Project. The American journal of gastroenterology. 2021;116(1):S57-S58. doi: 10.14309/01.ajg.0000773000.80092.4chttps://openworks.mdanderson.org/aprn-week-22/1001/thumbnail.jp

Factor XII and Upar Upregulate Neutrophil Functions to Influence Wound Healing

Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12–/–) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor–mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474). Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface expression of αMβ2 integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in F12–/– mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into F12–/– hosts was sufficient to correct the neutrophil migration defect in F12–/– mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated

Paraneoplastic Dermatosis in a Patient with Anaplastic Large-Cell Lymphoma: Case Report and Literature Review

Background/Aims: Paraneoplastic dermatoses are skin disorders that are associated with malignancy. Anaplastic large T-cell lymphoma (ALTCL) has rarely been associated with paraneoplastic skin manifestations such as gangrenous foot ulcers and erythroderma. Methods: We describe a case of ALTCL presenting as a large annular skin rash. The clinical picture, course, and treatment will be discussed along with current hypotheses on the mechanism of paraneoplastic syndromes. Results: Skin manifestations in ALTCL most commonly arise in two distinct ways; either as primary cutaneous lymphoma manifestation or as systemic disease with secondary metastasis. Less commonly, systemic disease causes skin manifestations secondary to a paraneoplastic process without infiltration of malignant cells. This is thought to be mediated by an immunologic reaction to tumor antigen or the result of cytokines and other inflammatory markers produced by the tumor itself. Conclusion: Paraneoplastic dermatoses could be the initial presentations of systemic lymphoma. Knowledge about their association with anaplastic large-cell lymphoma may help with timely diagnosis. In a patient with unexplained dermatosis associated with B symptoms who is unresponsive to topic treatment, an investigation for systemic lymphoma workup is warranted

Pilot study: Comparing efficacy of 14-day triple therapy Clarithromycin versus levofloxacin on eradication of Helicobacter Pylori infection in Syrian population single-center experience

Context: Goals: To compare the efficacy of standard triple therapy with clarithromycin versus triple therapy with levofloxacin for treatment of Helicobacter pylori-positive infection in a referral hospital in Damascus, Syria. Design: pilot prospective open-label randomized controlled trial. Subjects and Methods: Eighty treatment-naive patients who tested positive for H. pylori gastric infection were randomly assigned to one of two treatment groups with randomization ratio of 50/50. Group (A) was treated with clarithromycin (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg), each twice/day for 14 days, while Group (B) was treated with levofloxacin (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg), each twice/day for 14 days.[1] After 6 weeks of treatment, all patients underwent endoscopy and biopsy to evaluate H. pylori infection eradication. Results: Forty patients were allocated in each group; 37 patients completed the follow-up in each group. Thirteen patients in Group (A) were cured, with an eradication rate of 35.1% according to per-protocol analysis (PPA) and 32.5% according to intention-to-treat analysis (ITT), while in Group (B), 11 patients were cured, with an eradication rate of 29.7% according to PPA and 27.5% according to ITT with P = 0.80. No serious adverse events reported in both the groups. Conclusions: Clarithromycin is slightly better than levofloxacin in treatment of H. pylori gastric infection, but both regimens show low effectiveness with suboptimal eradication rates in our selected population

Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions

Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas. In particular, it has been reported that UTUC harbored a higher level of FGFR3 alterations associated with a T-cell depleted immune microenvironment. The therapeutic landscape in urothelial carcinoma is rapidly evolving, with immune checkpoint inhibitors forming part of the standard of care. A greater understanding of the molecular alterations and immune microenvironment leads to the development of new treatment combinations and targeted therapy. This review summarizes the available evidence concerning the use of immune checkpoint inhibitors and the biological rationale underlying their use in high-grade UTUC

Health-Seeking Behaviors and Misconceptions about Osteoarthritis in Patients and the General Population in Saudi Arabia

Osteoarthritis (OA) is a public health disease that causes decreased mobility and leads to poor quality of life. A person’s health-seeking behavior can influence their understanding of a disease, which in turn can alter its course. The objectives of this study were to measure the misconceptions about osteoarthritis and to identify the associated health-seeking behaviors. An online, self-administered, questionnaire-based study was conducted with 872 Arabic-speaking participants divided into three strata, group 1 comprising of patients with OA, group 2 participants with joint pain (without OA) and group 3 comprised of general population. Multivariate logistic regression analysis found that seeking care from general practitioners [3.29 (1.19, 9.16)], taking advice from friends [2.83 (1.08, 7.42)], seeking care from chiropractors [3.67 (1.02, 13.60)] and podiatrist [4.64 (1.31, 16.51)] were significantly associated with misconceptions, whereas, the odds were lower for those using social media [0.16 (0.06, 0.46)] and expert websites [0.63 (0.40, 0.99)]. The findings of this study imply that the level of misconceptions is high amongst all three strata.. Expert websites and social media have a positive effect on the management of osteoarthritis. However, general practitioners and allied health workers should regularly update their knowledge using refresher courses

Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies

Abstract Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. NCT03430882 enrolled patients with mTOR pathway aberrant tumors to receive sapanisertib, carboplatin and paclitaxel. Primary objective was safety and secondary objectives were clinical response and survival. One patient had a dose-limiting toxicity at dose level 4. There were no unanticipated toxicities. Grade 3–4 treatment-related adverse events included anemia (21%), neutropenia (21%), thrombocytopenia (10.5%), and transaminitis (5%). Of 17 patients evaluable for response, 2 and 11 patients achieved partial response and stable disease, respectively. Responders included a patient with unclassified renal cell carcinoma harboring EWSR1-POU5F1 fusion and a patient with castrate resistant prostate cancer harboring PTEN loss. Median progression free survival was 3.84 months. Sapanisertib in combination with carboplatin plus paclitaxel demonstrated a manageable safety profile, with preliminary antitumor activity observed in advanced malignancies harboring mTOR pathway alterations