Key Points An international panel established the first ever diagnostic criteria for iMCD based on review of 244 clinical cases and 88 tissue samples. The criteria require multicentric lymphadenopathy with defined histopathology, ≥2 clinical/laboratory changes, and exclusion of iMCD mimics.

Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells. Here we report for the first time that SLs induce DNA damage in the form of DNA double-strand breaks (DSBs) and activate the DNA damage response signaling by inducing phosphorylation of ATM, ATR and DNA-PKcs and co-localization of the DNA damage signaling protein, 53BP1, with γH2AX nuclear foci. We further report that in addition to DSBs induction, SLs simultaneously impair DSBs repair, mostly homology-directed repair (HDR) and to a lesser extent non-homologous end joining (NHEJ). In response to SLs, RAD51, the homologous DSB repair protein, is ubiquitinated and targeted for proteasomal degradation and it fails to co-localize with γH2AX foci. Interestingly, SLs synergize with DNA damaging agents-based therapeutics. The combination of PARP inhibitors and SLs showed an especially potent synergy, but only in BRCA1-proficient cells. No synergy was observed between SLs and PARP inhibitors in BRCA1-deficient cells, supporting a role for SLs in HDR impairment. Together, our data suggest that SLs increase genome instability and cell death by a unique mechanism of inducing DNA damage and inhibiting DNA repair.

Background and study aims Cirrhosis has historically been considered a relative, if not absolute, contraindication to cholecystectomy. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been developed for use in non-operative candidates with cholecystitis; however, little data exist for use of the procedure in patients with cirrhosis. Patients and methods This was a retrospective series involving two large tertiary referral centers performing EUS-GBD. Patients with cirrhosis who underwent EUS-GBD for cholecystitis between August 2014 and December 2018 were identified. The primary endpoint was the rate of technical success, defined as EUS-guided placement of a lumen-apposing metal stent (LAMS) from duodenum to gallbladder. Patient demographics, procedural details, adverse events (AEs), post-procedural symptoms, and clinical success were recorded. Results Fifteen patients (9 females, 6 males) with cirrhosis underwent EUS-GBD during the study period. Mean patient age was 61 ± 17.1yrs, mean MELD-Na 15 ± 7. Etiology of cirrhosis was HCV (n = 2), alcohol (n = 4), non-alcoholic fatty liver disease (n = 8), and autoimmune hepatitis (n = 1).The technical success rate was 93.3 % and mean procedure time was 64 ± 59 minutes. Initial puncture site was duodenum (n = 11), stomach (n = 3) and jejunum (n = 1) and portion of gallbladder used for drainage was neck (n = 4) and body (n = 11). Fourteen patients went on to clinical success and two AEs occurred in this cohort. One decompensation event occurred in a patient with Child-Pugh class C disease 3 weeks post-procedure. Mean length of follow-up was 373 ± 367.3 days; one death occurred due to underlying malignancy. Conclusion EUS-GBD is safe and efficacious in managing cholecystitis in patients with Child-Pugh A and B cirrhosis who are non-operative candidates. Further studies are needed to determine optimal patient selection and procedural technique.

A lpha-gal allergy is characterized by a reaction to beef, pork, and other mammalian meat and derived products, typically hours after ingestion, and is diagnosed by the presence of elevated serum alpha-gal IgE antibodies. [1][2][3] The allergy appears to develop after the bite of a hard tick and has been described in the United States (particularly the southeastern United States; Supplementary Figure 1), Europe, Africa, Australia, Central and South America, and Asia. [4][5][6] Symptoms can include pruritus, rash, diarrhea, abdominal cramping, shock, and anaphylaxis, the latter of which is defined by the involvement of 2 or more systems (skin, gastrointestinal [GI], cardiac, pulmonary). GI symptoms are caused by IgE-mediated degranulation of mast cells and histamine receptors in the GI tract.Management of the allergy includes counseling on the avoidance of mammalian meat and sometimes dairy and other mammalian-derived products. 7 In case of exposure, short-and long-acting oral antihistamines such as diphenhydramine and fexofenadine may be used to ameliorate both GI and allergic symptoms.Allergy and oncology journals have primarily published research on alpha-gal allergy, and it has not been described previously in the GI literature. We describe patients with the allergy who presented with isolated GI symptoms.

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