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Clostridioides difficile infection (CDI) is the leading cause of health care–associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment. Small intestinal bacterial overgrowth (SIBO) has been associated with functional gastrointestinal disorders. Here, the authors show that SIBO may be a result of dietary preferences, and patient symptoms correlate with changes in small intestinal microbial composition but not with SIBO.

Alpelisib selectively inhibits the p110α catalytic subunit of PI3Kα and is approved for treatment of breast cancers harboring canonical PIK3CA mutations. In head and neck squamous cell carcinoma (HNSCC), 63% of PIK3CA mutations occur at canonical hotspots. The oncogenic role of the remaining 37% of PIK3CA noncanonical mutations is incompletely understood. We report a patient with HNSCC with a noncanonical PIK3CA mutation (Q75E) who exhibited a durable (12 months) response to alpelisib in a phase II clinical trial. Characterization of all 32 noncanonical PIK3CA mutations found in HNSCC using several functional and phenotypic assays revealed that the majority (69%) were activating, including Q75E. The oncogenic impact of these mutations was validated in 4 cellular models, demonstrating that their activity was lineage independent. Further, alpelisib exhibited antitumor effects in a xenograft derived from a patient with HNSCC containing an activating noncanonical PIK3CA mutation. Structural analyses revealed plausible mechanisms for the functional phenotypes of the majority of the noncanonical PIK3CA mutations. Collectively, these findings highlight the importance of characterizing the function of noncanonical PIK3CA mutations and suggest that patients with HNSCC whose tumors harbor activating noncanonical PIK3CA mutations may benefit from treatment with PI3Kα inhibitors.

According to the International Association of Pancreatology and the American Pancreatic Association, two of three criteria must be met for diagnosing acute pancreatitis: upper abdominal pain; lipase more than 3 times upper limit of normal; and imaging criteria with either computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound.1 She already does not meet two of the above criteria and thus pancreatitis is unlikely to be contributing to her symptoms. [...]she may have gallstones but with lack of pain and nausea/vomiting, it is unlikely she has symptomatic gallstone disease. CT of her abdomen and pelvis was pursued but no diagnostic abnormalities were reported that could explain her anorexia. Because of her continued inability to tolerate oral intake, EGD was performed, which revealed antral deformity with contraction, scarring, and pinhole opening. Total parenteral nutrition could be pursued if nasogastric or nasojejunal feeding were not possible before other management options. Because of the nature of her pin-holesized pyloric channel and malnourishment, fluoroscopy-assisted balloon dilation was used.

INTRODUCTION:Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown.METHODS:We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied.RESULTS:Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery.DISCUSSION:Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor, representing only about 1-3% of all exocrine pancreatic neoplasms. SPNs typically occur in young women in their second to fourth decade of life. SPNs are usually benign neoplasms; however has up to 20% malignancy potential. A 30-year-old woman, with no significant past medical history presented to the emergency department with shortness of breath, dizziness, and palpitations.. Laboratory evaluation was only significant for an elevated D-dimer of 1001 ng/ml and thus a CT angiogram of her chest as well as CT of her abdomen was pursued. Pulmonary embolism was ruled out. Her symptoms resolved spontaneously but CT of her abdomen revealed an 8 cm heterogeneously attenuating mass near her descending abdomen. MRI of her abdomen again showed a complex mass arising in the periampullary region/pancreaticoduodenal groove. EGD and endoscopic ultrasound confirmed a partially cystic periduodenal mass and needle biopsies were consistent with solid pseudopapillary tumor of the pancreas. The patient underwent a pylorus-resecting Whipple resection with removal of the pylorus, duodenum, and a portion of the proximal jejunum, head of pancreas, common bile duct, gallbladder, and regional lymph nodes. Lymph nodes were negative for tumor. Her post-operative course was initially uncomplicated but at follow-up she developed diarrhea related to fat malabsorption and treated with pancreatic enzyme supplementation. This case demonstrates a rare tumor, namely solid pseudopapillary neoplasm of the pancreas in an otherwise healthy young woman. The pathogenesis of these tumors remains unclear. Typical presentation of SPN is nonspecific and may include abdominal pain. In our patient, this neoplasm was incidentally found on cross-sectional imaging with no initial abdominal symptoms. SPNs typically are large tumors and occur anywhere within the pancreas. They typically start as solid tumors and due to significant degeneration, they will often appear cystic on imaging. Management is typically surgical resection, which is often curative. SPNs are usually limited to the pancreas in over 95% of cases and local recurrence rate is less than 10% within 4 years. Overall prognosis of SPNs is good even if there is local recurrence or metastasis.

Introduction: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain related to defecation, change in stool frequency, or change in stool form. Borderline personality disorder (BPD) is a psychiatric disorder characterized by instability in relationships, behavior, self-image, and mood, which can result in functional impairments. Somatic complaints are common in patients with BPD. Poor outcomes in IBS have been linked to anxiety and depression, but its relationship to BPD is less well defined. Methods: Patients living in Olmsted County who were seen at Mayo Clinic in Rochester, MN from 1985 to November 2017 were identified. The study was limited to Olmsted County to limit bias from the referral nature of the Mayo Clinic practice. ICD9 and ICD10 codes for borderline personality disorder and irritable bowel syndrome were used for database query. Prevalence rates for each disorder were calculated. Results: From January 1985 to November 2017, 1641 patients from Olmsted County, MN were diagnosed with borderline personality disorder. The median age at BPD diagnosis was 30 years (interquartile range [IQR] of 22 to 40 years). 78% of patients with BPD were female. 135 patients were excluded from analysis due to lack of research consent. Of the patients diagnosed with BPD, 205 patients also had a concurrent diagnosis of irritable bowel syndrome (12.5%). In total, 6686 unique patients had the diagnosis of irritable bowel syndrome from 1985 to November 2017. The median age at IBS diagnosis was 45 years (IQR of 32 to 63 years). 74% of patients with IBS were female. 509 patients were excluded from analysis due to lack of research consent. Of the 6686 patients with IBS, 205 patients had a concurrent diagnosis of BPD (3.1%). Conclusion: The prevalence of IBS in North America is common with most prevalence estimates ranging from 10% to 15%. The fact that IBS is similarly common (12.5%) in the BPD patient population is consistent with the limited literature on the topic and suggests that clinicians treating BPD should be aware of IBS symptoms and be able to use them in making a diagnosis. Somewhat surprisingly to us, the prevalence of BPD in the IBS population is at or only very slightly above the population prevalence of the disorder (variably 2-3%). This suggests that while attention to psychiatric symptoms in IBS remains important and appropriate, the vast majority of IBS patients do not have comorbid borderline personality disorder.