Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic's Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients' charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [

Background Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced malignancies. However, they are associated with the development of multiple gastrointestinal immune-related adverse events (GI-irAEs). We aimed to evaluate the types and severity of GI-irAEs associated with ICI therapy, to identify potential risk factors for developing GI-irAEs and to determine the relationship of GI-irAEs development to tumor responsiveness and overall survival. Methods All patients who received ICIs for advanced malignancies at our center were included. Medical records were reviewed, and data extraction included: baseline demographic characteristics, immunotherapy regimens, development of GI-irAEs, response to treatment, and overall survival. Overall survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method. Results Five hundred sixty-seven patients received ICI therapy for stage IV malignancies. Forty-one (7%) patients experienced at least one GI-irAE. Among those experiencing GI-irAEs, 23 (56%) developed hepatitis, 17 (42%) developed colitis, four (10%) developed pancreatitis, and two (5%) developed gastritis. Patients who developed GI-irAEs experienced a better response to ICI therapy compared to patients who did not develop GI-irAEs (41% vs. 27%, P = 0.003). The 2-year overall survival rate of stage IV cancer patients who developed GI-irAEs was 62% (95% confidence interval (CI): 49 - 79) and 36% for those who did not develop GI-irAEs (95% CI: 32 - 41) (P = 0.002). The median follow-up time of surviving patients was 28 months. Twelve (29%) of the patients receiving dual ICI therapy developed GI-irAEs. Conclusion Hepatitis, colitis, and pancreatitis were the most commonly encountered GI-irAEs with ICI therapy. Development of these GI-irAEs was associated with superior tumor responsiveness and better overall survival.

INTRODUCTION: Immune checkpoint inhibitors (iCPI) have recently gained an essential role in treating cancer at advanced stages. However, it has been associated with the development of gastrointestinal immune-related adverse events (GI-IrAEs). We aimed in our study to assess the incidence and nature of GI-IrAEs as well as to investigate the effects of developing GI-IrAEs on cancer response to iCPI and overall survival. METHODS: We retrospectively identified adult patients diagnosed with end-stage malignancy who were treated with any iCPI at our tertiary center between 8/2014 and 8/2017. Charts were reviewed for baseline characteristics, immunotherapy regimens, response to treatment, development of GI-IrAEs, and patient’s overall 1-year survival. Patients in whom the etiology of GI-IrAEs was unclear were excluded. The overall 1-year survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method. RESULTS: We included 492 patients with end-stage cancer receiving iCPI. The majority of patients were white 451(92%) with a median age of 64.5 years. (Table 1) GI-IrAEs were in the form of autoimmune hepatitis 18(48.5%), autoimmune colitis 16(43.5%), autoimmune pancreatitis 4 (11%), and a combination of autoimmune colitis and hepatitis in 1 patient. (Figure 1) Brain cancer was associated with the highest risk of GI-IrAEs 16 (44.4%) followed by renal cell carcinoma 7 (19.4%). Nivulomab was associated with the highest risk for GI-IrAEs (55.6%) followed by Pembrulizumab 14 (38.9%). Forty-one percent of Patients who developed GI-IrAEs had an adequate cancer response to immunotherapy compared to 25.7% in patients without GI-IrAEs (P-value = 0.022). Eighty- three percent of patients whose cancer responded to iCPI survived at 1 year compared to 36 % among non-responders (P < 0.0001). Seventy-eight percent of patients who developed GI-IrAEs survived at 1 year compared to 53% in patients without GI-IrAEs (P < 0.005). CONCLUSION: The incidence of gastrointestinal toxicity associated with iCPI is second only in frequency to dermatological toxicity. In our study, among the white population with end-stage cancer receiving iCPI, autoimmune hepatitis, colitis, and pancreatitis were fairly common and associated with better cancer response to immunotherapy and overall survival at 1 year. GI-IrAEs might be an indicator of immune system activation, thus may be a reason to continue, rather than discontinue, immunotherapy agents as tolerated.

Background: Insulin pumps are increasingly being used as a method of insulin delivery in patients with type 1 diabetes mellitus (T1DM). Diabetic ketoacidosis (DKA) is a serious complication of T1DM. This study aims to identify causes of DKA in T1DM patients on insulin pump, and to compare these with patients with T1DM on multiple daily insulin injections (MDII). Methods: This was a prospective observational pilot study assessing DKA between 2 groups of patients with T1DM: (1) on insulin pump and (2) on MDII. Demographic and clinical data were obtained from chart review. Patients’ knowledge on insulin and diabetes care was assessed with a questionnaire we devised. Results: We enrolled 17 adult patients - 12 on insulin pump (7 Medtronic, 3 Tandem, 2 Animas) and 5 on MDII - who were admitted to the ICU for DKA management. Eleven (65%) were females, all were Caucasian, with median age in pump users 27.0 years (IQR 22.5,39.5) vs. MDII 38.0 (IQR 32.0,51.0)(p=0.045). The rest of the demographic data were comparable. Majority of the patients on insulin pump had a pump &gt;5 years and had the current pump &lt;5 years. Six were given pump training in the physician’s office and 6 by the insulin pump company. In patients on insulin pump, 41% of DKA cases were pump- and tubing- related, 41% were due to non-adherence and 18% were due to an infection. In contrast, all the MDII patients had DKA due to non-adherence. Insulin pump patients had significantly higher adherence (p= 0.014) and better knowledge of managing hyperglycemia on sick days (p = 0.029) than MDII patients. Conclusion: A significant proportion of DKA in pump users was due to pump issues. Non-adherence was common in both pump users and MDII. Continued education on pump use may reduce the rate of DKA in pump users. Disclosure M. Amir: None. S. Al Ashi: None. M. Lansang: None. M. Al-Jaghbeer: None.