Lesmana E, Rao S, Keehn A, Edwinson AL, Makol A, et al.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association •
Alpha-gal syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with Lone Star tick bites in the United States. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. A retrospective chart review of patients who underwent serological testing for suspected AGS between 2014 and 2023 at Mayo Clinic was performed. Patients with positive serology were age and sex matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. Of 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative control subjects. AGS patients reported a higher frequency of tick bites (odds ratio [OR], 26.0; 95% confidence interval [CI], 9.8-68.3), reported a higher prevalence of urticaria (56% vs 37%; P = .0008), and were less likely to have asthma (OR, 0.4; 95% CI, 0.3-0.7). They had a lower prevalence of heartburn (6% vs 12%; P = .03) and bloating (6% vs 13%; P = .03). A total of 47% had GI symptoms, and a higher proportion were female than those without GI symptoms (69% vs 35%; P = .002). During a mean follow-up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. A diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] •
To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. Two-year OS was 71% in arm A (95% CI: 55-87%) vs. 53% in arm B (95% CI: 36-71%); H was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30-1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25-1.04) for progression, 0.43 (0.13-1.40) for locoregional failure, and 0.43 (0.17-1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.
The journal of allergy and clinical immunology. In practice •
The true global scale of anaphylaxis remains elusive, because many episodes occur in the community without presentation to health care facilities, and most regions have not yet developed reliable systems with which to monitor severe allergic events. The most robust data sets currently available are based largely on hospital admissions, which are limited by inherent issues of misdiagnosis, misclassification, and generalizability. Despite this, there is convincing evidence of a global increase in rates of all-cause anaphylaxis, driven largely by medication- and food-related anaphylaxis. There is no evidence of parallel increases in global all-cause anaphylaxis mortality, with surprisingly similar estimates for case-fatality rates at approximately 0.5% to 1% of fatal outcomes for hospitalizations due to anaphylaxis across several regions. Studying regional patterns of anaphylaxis to certain triggers have provided valuable insights into susceptibility and sensitizing events: for example, the link between the mAb cetuximab and allergy to mammalian meat. Likewise, data from published fatality registers can identify potentially modifiable risk factors that can be used to inform clinical practice, such as prevention of delayed epinephrine administration, correct posturing during anaphylaxis, special attention to populations at risk (such as the elderly on multiple medications), and use of venom immunotherapy in individuals at risk of insect-related anaphylaxis.