Immune checkpoint blockade toxicity among patients with cancer presenting to the emergency department.

OBJECTIVES: We sought to estimate the prevalence of patients with cancer presenting to the emergency department (ED) who are undergoing treatment with immune checkpoint blockade (ICB) therapy; report their chief complaints; describe and estimate the prevalence of immune-related adverse events (IRAEs). METHODS: Four abstractors reviewed the medical records of patients with cancer treated with ICB who presented to an ED in Paris, France between January 2012 and June 2017. Chief complaints, underlying malignancy and ICB characteristics, and the final diagnoses according to the emergency physician were recorded. Abstractors noted if an emergency physician identified that a patient was receiving an ICB and if the emergency physician considered the possibility of an IRAE. The gold standard as to whether an IRAE was the cause was the patients' referring oncologist's opinion that the ED symptoms were attributed to ICB and IRAE according to post-ED medical records. Descriptive statistics were reported. RESULTS: Among the 409 patients treated with ICB at our institution, 139 presented to the ED. Chief complaints were fatigue (25.2%), fever (23%), vomiting (13.7%), diarrhoea (13.7%), dyspnoea (12.2%), abdominal pain (11.5%), confusion (8.6%) and headache (7.9%). Symptoms were due to IRAEs in 20 (14.4%) cases. The most frequent IRAEs were colitis (40%), endocrine toxicity (30%), hepatitis (25%) and pulmonary toxicity (5%). Patients with IRAEs compared with those without them more frequently had melanoma; had received more distinct courses of ICB treatment, an increased number of ICB medications and ICB cycles; and had a shorter time course since the last infusion of ICB. Emergency physicians considered the possibility of an IRAE in 24 (17.3%) of cases and diagnosed IRAE in 10 (50%) of those with later confirmed IRAE. IRAE was more likely to be missed when the referring oncologist was not contacted or when the patient had respiratory symptoms, fatigue or fever. CONCLUSIONS: ICB exposes patients to potentially severe IRAEs. Emergency physicians must identify patients treated with ICB and consider their toxicity when patients present to the ED with symptoms compatible with IRAEs.

Monitoring Personalized Learning Curves for Emergency Ultrasound With Risk-adjusted Learning-curve Cumulative Summation Method.

BACKGROUND: Ultrasound (US) has been a regular practice in emergency departments for several decades. Thus, train our students to US is of prime interest. Because US image acquisition ability can be very different from a patient to another (depending on image quality), it seems relevant to adapt US learning curves (LCs) to patient image quality using tools based on cumulative summation (CUSUM) as the risk-adjusted LC CUSUM (RLC). OBJECTIVES: The aim of this study was to monitor LC of medical students for the acquisition of abdominal emergency US views and to adapt these curves to patient image quality using RLC. METHODS: We asked medical students to perform abdominal US examinations with the acquisition of 11 views of interest on emergency patients after a learning session. Emergency physicians reviewed the student examinations for validation. LCs were plotted and the student was said proficient for a specific view if his LC reached a predetermined limit fixed by simulation. RESULTS: Seven students with no previous experience in US were enrolled. They performed 19 to 50 examinations of 11 views each. They achieve proficiency for a median of 9 (6-10) views. Aorta and right pleura views were validated by seven students; inferior vena cava, right kidney, and bladder by six; gallbladder and left kidney by five; portal veins and portal hilum by four; and subxyphoid and left pleura by three. The number of US examinations required to reach proficiency ranged from five to 41 depending on the student and on the type of view. LC showed that students reached proficiency with different learning speeds. CONCLUSIONS: This study suggests that, when monitoring LCs for abdominal emergency US, there is some heterogeneity in the learning process depending on the student skills and the type of view. Therefore, rules based on a predetermined number of examinations to reach proficiency are not satisfactory.

Alterations in Diets of Patients With Nonceliac Gluten Sensitivity Compared With Healthy Individuals.

BACKGROUND & AIMS: There is evidence that food components beyond gluten cause symptoms in patients with gluten sensitivity without celiac disease (nonceliac gluten sensitivity [NCGS]). We investigated the diets and nutritional characteristics of patients with NCGS. METHODS: We performed a prospective observational study of 29 patients with NCGS seen at the outpatient clinic for celiac disease and other food intolerances of the University of Salerno in Italy from September 2015 through April 2016. Our study also included 37 control subjects. An experienced dietitian administered a validated food frequency questionnaire (from the European Prospective Investigation into Cancer and Nutrition) to collect information on amounts of common foods consumed. Patients and control subjects also completed the Eating Attitudes Test for diet-related disorders. Patients with NCGS completed the Minnesota Multiphasic Personality Inventory 2-I questionnaire. Differences in frequencies between patients and control subjects were calculated using chi-square test, whereas differences between continuous variables were calculated using Student t test. All tests were 2-tailed with significance level set at P < .05. RESULTS: Comparing the mean value of food daily eaten, we found that patients with NCGS ate smaller amounts of bread, rice, pasta, and cheese than control subjects. The patients ingested lower mean amounts of carbohydrates (P < .001), proteins (P = .001), fiber (P = .002), and polyunsaturated fatty acids (P = .01). More patients with NCGS than control subjects reported avoiding fruit, vegetables, milk, and dairy products, as well as snacks and mixed spices that are traditionally considered unsafe for people with gastrointestinal symptoms. Seven patients and 3 control subjects with scores ≥20 on the Eating Attitudes Test were invited for a psychological consultation; it did not confirm the presence of altered eating behaviors. Patients with NCGS had scores >65 from the Minnesota Multiphasic Personality Inventory, indicating a high level of concern for their health. CONCLUSIONS: In an observational study, we found that patients with NCGS eat different foods than healthy individuals; patients consume lower levels of proteins, carbohydrates, fiber, and polyunsaturated fatty acids. Their diets should be routinely analyzed and possibly corrected to avoid nutritional deficiencies.

Life events and the onset of celiac disease from a patient's perspective.

Stressful events have been investigated in various immune-mediated diseases but not in celiac disease. Our aim was to examine the relationship of stressful events assessed by the standardized interview of Paykel with the diagnosis of celiac disease in comparison to patients, with a diagnosis of gastroesophageal reflux disease used as the control group. Adults with celiac disease (n = 186) reported more frequent and more severe life events in the years prior to the diagnosis than control patients (n = 96) (67.2% vs. 37.5%, p < 0.001, mean Paykel score 11.5 vs. 13.4, p = 0.001, respectively). Findings were not significantly different between celiac disease and control patients for the time lapse between the event and the diagnosis (mean 5.5 vs. 5.7 months). Pregnancy was defined as a negative event by 20.3% of celiac women, but never by control women. Findings were confirmed when analyses were repeated in the subgroup of patients of both groups with diagnosis made within one year of onset of symptoms. Data indicate that, before diagnosis, the number of stressful events in celiac disease was more frequent although less severe than in the control group suggesting that life events may favor the clinical appearance of celiac disease or accelerate its diagnosis.

Anisakis, just think about it in an emergency!

A few years ago, Anisakis infection was almost unknown. Since the first observation in the Netherlands in 1960, several cases of gastrointestinal infections due to a zoonosis sustained by this nematode have been described in countries in which the consumption of raw or uncooked fish (e.g., marinated or salted) is common. Japan alone accounts for 90% of all cases of anisakiasis described in the literature because of the widespread use of raw fish in traditional Japanese cuisine, with sushi and sashimi. Nonetheless, other cases have been reported in Europe, North and South America, and Asia. In Italy, this zoonosis is rare and mostly transmitted by the ingestion of marinated anchovies in coastal areas, or fashion foods (sushi, sashimi, etc.) in inland areas. Once eaten, this parasite can cause an acute form of disease characterized by severe abdominal pain, and for this reason many patients receive the final diagnosis only on obtaining the surgical specimen. Since conservative medical treatment for acute anisakiasis relies on endoscopic removal of the nematode from the gastrointestinal wall if performed within 12h from the ingestion of contaminated fish, it should be compulsory to consider this parasitosis in the accident and emergency department. Here we describe two cases of infection by Anisakis simplex due to ingestion of marinated anchovies in a coastal area of the Tyrrhenian Sea and discuss the types and varieties of Anisakis infection in humans.

Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

BACKGROUND & AIMS: Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin. METHODS: Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45. RESULTS: Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients. CONCLUSIONS: Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not be used to diagnose NCGS.