Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin

We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoinsulinemia. Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. We recommend reserving SGLT2 inhibitor therapy to type 2 diabetics, discontinuing medication and treating patients presenting with ketoacidosis due to SGLT-2 inhibitors with higher concentrations of dextrose with appropriate doses of insulin to help resolve acidosis

Frequency of silent carotid artery stenosis in diabetics and its associated factors: An analysis in tertiary care hospital

Objective: To estimate frequency of silent carotid artery stenosis and its associated factors in diabetic patients attending a tertiary care hospital.Methods: This cross-sectional study was conducted in tertiary care Civil Hospital, Karachi from March 2019 to September 2019,. A total of 166 patients with Diabetes Mellitus were included in this study. Brief history was taken for the duration of DM, treatment, and smoking habits. Carotid artery stenosis (CAS) wafrs measured by Doppler ultrasound of right and left common, internal, and external carotid arteries.Results: Frequency of silent carotid artery stenosis (CAS) in diabetic patients was observed in 28.92% (48/166) cases. The mean age ±SD of the patients was 54.8 ±7.96 years. 27 (22.29%) patients were smoker and all were male. Out of 166 diabetic patients, 59 (35.54%) were treated with insulin and 107 (64.46%) were treated with oral hypoglycemic.Conclusion: Substantial number of diabetic patients with increasing age, increased duration of diabetes and smoking habits have significant silent Silent Carotid Artery Stenosis (CAS)

Factors Associated with the Maintenance of Colonic Insufflation During Colonoscopy

Colonoscopy is a diagnostic and therapeutic procedure performed for several indications including colorectal cancer (CRC) screening, adenoma surveillance, and investigation of gastrointestinal symptoms. Insufflation of the colon with gas allows for adequate visualization of the mucosal tissue and advancement of the endoscope; however, it can cause pain and discomfort. Thus, the majority of colonoscopies are performed with sedation in order to mitigate discomfort and enhance the colonoscopy experience for both the patient and the endoscopist. We hypothesized that deeper levels of sedation would lead to more difficulty in maintaining insufflation. We aimed to evaluate factors associated with difficulty maintaining insufflation. Methods: We performed a prospective study of all patients who underwent outpatient colonoscopies at the Veteran Affairs Medical Center in Oklahoma City between November 2019 and March 2020. Colonoscopies were performed by gastroenterology fellows and attending gastroenterologists. Indications for colonoscopies were CRC screening, positive fecal immunochemical test, symptomatic, and adenoma surveillance. Procedures were done under Monitored Anesthesia Care (MAC) with propofol or moderate sedation with fentanyl, midazolam, and diphenhydramine. Insufflation was done with carbon dioxide. Data collection involved two parts. Firstly, baseline demographic information was obtained from the electronic medical record (EMR) along with colonoscopy details including type and doses of sedatives; total number of polyps, size of polyps, and specific location in colon; and total procedure times including insertion and withdrawal. Secondly, a post-procedure questionnaire was completed by the endoscopists and recorded the bubble score, endoscopic maneuvers, and difficulty maintaining insufflation. Results: A total of 542 participants underwent colonoscopies during this period. Twelve participants were excluded from the study and 37 participants did not have completed questionnaires. We found that difficulty maintaining insufflation was reported in 129 (26%) participants compared to 364 participants where no difficulty was reported. Multivariate analysis showed that patients who had difficulty maintaining insufflation were more likely to be of an older age (P=0.003), had undergone MAC sedation (P=<0.0001), were more likely to have longer procedure times (P=.0025) and fellow involvement (P=0.0002) with the procedure. Discussion: We observed that difficulty in maintaining insufflation during colonoscopy was reported in over one-quarter of the colonoscopies done. We found four factors associated with difficulty maintaining insufflation: use of propofol sedation, older age, fellow involvement, and longer procedural times. We could not find literature that explored maintenance of insufflation. Further investigation into these factors and their relationship with maintaining insufflation is warranted as this may improve the colonoscopy experience

Name the Syndrome: Cytokine Release Syndrome or Toxic Shock Syndrome in a Patient on Avelumab for Ependymal Tumor

Introduction: The use of immune checkpoint inhibitors (ICIs) has dramatically changed the outlook of cancer therapy. As a result, their use is becoming prevalent and a more diverse range of clinicians will encounter patients on immunotherapy and their immune-related adverse events (irAEs). Our objective is to describe a case of suspected cytokine release storm in a patient enrolled in a phase I trial on combination therapy with PDL1 inhibitor Avelumab and oral DNA PK inhibitor who was initially treated as toxic shock syndrome. Case: A 38 year-old-woman with an ependymal tumor on a phase I trial with PDL1 Inhibitor Avelumab and oral DNA PK inhibitor presented with fever and rash a few hours after receiving Avelumab infusion. On exam, vitals were Temperature 39.2 C, HR 148, BP 87/45, RR 30, Pulse Ox 98% on ambient air. Examination was significant for an alert and conversant woman with macular erythema which involved the face, upper extremities, chest, and thighs. Indwelling lines were noted: a peritoneal catheter and a PICC line. There were scattered areas of desquamation on her chest and upper extremities. She was treated with broad-spectrum antimicrobials including clindamycin but her clinical status remained unchanged after 12 hours. It was decided to start methylprednisone for a possible adverse reaction to Avelumab. Given the concern for cytokine release syndrome, she was also given a single dose of Tocilizumab 800mg. Her condition improved dramatically in the next 24 hours; she was transferred out of the ICU on Day 3 of hospitalization and discharged home on Day 7 with a prednisone taper. On a follow-up appointment, her therapy was changed to an alkylating agent. Discussion: We present a case of CRS induced by Avelumab which resulted in rapid improvement of the rash and hemodynamic status of the patient after Tociluzimab. Our differential diagnosis included septic shock, including toxic shock syndrome. These circumstances are likely to be encountered by clinicians who are not primarily practicing in oncology.CRS is a systemic inflammatory disease characterized by a massive release of cytokines. By increasing the activity of the immune system against cancer cells and subsequently the host’s non-cancer cells, ICIs can lead to cytokine-mediated toxicity among which IL-6 plays a key role. CRS has now also been recognized to occur with ICIs, especially PD1 and PDL1 inhibitors. To our best knowledge, seven case reports have described CRS after pembrolizumab and nivolumab; however, none have specifically described this reaction to Avelumab. Rash was described in two case reports. Notably, our case is the only one that an ICI was used for an ependymal tumor. Two of the case reports described using tocilizumab and two used Mycophenolate. Corticosteroids were used in all cases and all patients recovered. Due to the increasing use of ICIs, more clinicians need to be aware that they can trigger CRS

Role of multifunctional Chemerin in obesity and preclinical diabetes

Background: Chemerin is a multifuntional peptide involved in lipid and glucose metabolism. Elevated levels of this peptide have been associated with insulin resistance and systemic inflammation. This study aims to identify whether Chemerin along with other inflammatory markers (TNFalpha and hsCRP) can discriminate subjects with subclinical diabetes.METHODOLOGY/FINDINGS: Fifty-two asymptomatic healthy volunteers and 22 chronic diabetics (T2DM) were enrolled in a cross sectional study design. They were subjected to a 75 g oral glucose tolerance test [OGTT (2-h glucose\u3e200 mg/dL)] and were then classified as either newly diagnosed diabetics (NDM) (n=23) or healthy controls (n=29). Our results showed a higher Chemerin level in NDM (p\u3c0.01; MWU) compared to controls and previously diagnosed DM. Using ROC analysis, Chemerin level in NDM and T2DM had AUC of 0.963 and 0.764 respectively, compared to healthy controls. We suggest that the cut off of 13.7 ng/ml of Chemerin can discriminate 73% of NDM subjects with impaired glucose level with 91% and 96% of sensitivity and specificity respectively. Elevated serum Chemerin in NDM group is a surrogate of impairment in glucose metabolism in obese individual.CONCLUSIONS: Chemerin along with other inflammatory biomarkers suggest an ongoing inflammatory process in a high risk obese group that indicates a pre-diabetic state

Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial

Background and aims: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV.Approach and results: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation.Conclusions: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing