Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The causes of ALS are poorly understood, although the protein TDP-43 has been suggested to play a critical role in disease pathogenesis. Here we show that Ataxin-2, a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2 (SCA2), is a potent modifier of TDP-43 toxicity in animal and cellular models. The proteins associate in a complex that depends on RNA. Ataxin-2 is abnormally localized in spinal cord neurons of ALS patients. Likewise, TDP-43 shows mislocalization in SCA2. To assess a role in ALS, we analyzed the Ataxin-2 gene (ATXN2) in 915 ALS patients. We found intermediate-length polyQ expansions (27–33 Qs) in ATXN2 significantly associated with ALS. These data establish ATXN2 as a relatively common ALS disease susceptibility gene. Further, these findings indicate that the TDP-43/Ataxin-2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.

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were complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1, 2, 3, 4 years. Secondary endpoints were adverse events, disease progression, recurrence rate, time to recurrence, treatment success after recurrence. Patients who achieved CE-IM were included for the durability analysis. Kaplan-Meir analysis was performed to assess durability where any recurrence was considered a failure. Results: 70 patients (mean age 67.6 years, 88.6% male, mean BE Prague C 2.5+/-4.3 cm, Prague M 4.3 +/-4.6 cm), HGDZ64%, LGD 36%) were studied. 65.7% of the patients were treatment naïve, the rest had prior EMR (nZ6), RFA (nZ13) or both (nZ5). Median follow-up was 27.4 months (IQR 16.1-43.4). CE-D and CE-IM at 1 year were 96.7% and 73.8%, respectively. The median number of CB sessions to achieve CE-IM at 1 year was 3 (IQR 2-3.5). Table 1 shows the rates of CE-D and CE-IM for years 1-4, allowing for retreatment with CB or "touch-up" APC. The rate of CE-IM was above 90% at 2, 3 and 4 years, with no difference between treatment-naïve and previously-ablated The durability (rates of CE-D and CE-IM) of CB response in 45 patients who achieved CE-D or CE-IM at 1 year followed until last follow-up or recurrence of dysplasia or IM are presented in Figure 1. One patient had an LGD recurrence at 21.7 months and 3(4.3%) patients had a recurrence of IM; all were successfully retreated with CB ablation. The median time to recurrence was 18.6 months (Figure 1). No patient progressed beyond their baseline dysplasia grade or developed cancer. The incidence of stricture requiring dilation was 7.1%. 1 patient (1.4 %) developed self-limited bleeding. Conclusion: Recurrence rate of IM after initial CB eradication is low. CB ablation has high efficacy, safety, and durability for eradicating dysplasia and intestinal metaplasia in dysplastic BE as a primary or rescue therapy.

INTRODUCTION: Primary gastric lymphoma is a rare entity of which the specific variant, mucosa-associated lymphoid tissue (MALT) lymphomas may be the best recognized given its association with Helicobacter pylori (H. pylori) infection. It has been thought that repetitive immune stimulation from underlying infection is influential in the pathogenesis of this tumor. However up to 10% of gastric MALT lymphomas are diagnosed without a concomitant H. pylori infection. The pathogenesis and management of H. pylori-negative gastric MALT lymphomas remains uncertain. CASE DESCRIPTION/METHODS: 65 year old woman with Celiac disease and GERD presented with worsening severe reflux and epigastric pain. She underwent EGD which revealed multiple superficial ulcers in the cardia with notable nodularity, ulceration, and friability. Cold forceps biopsies of the abnormal mucosa demonstrated diffuse atypical small B-Cell lymphoid infiltrate with features compatible with low grade MALT lymphoma. Of note, immunostain for H. Pylori was negative. Subsequent H. pylori stool antigen assay as well H. pylori IgG, IgM, and IgA were all negative. Given her negative antibodies indicating she truly had no exposure to H. Pylori, the patient has been referred to oncology for multidisciplinary management. DISCUSSION: This case of early stage gastric MALT lymphoma without evidence of active H. pylori infection elucidates that there is limited literature for the management for these patients. Studies have suggested that H. pylori eradication therapy can be efficacious for a proportion of H. pylori-negative gastric MALT lymphomas, possibly due to a false negative detection by biopsy. Local radiation therapy with curative intent and single agent rituximab therapy rather than H. pylori eradication have also been explored as alternate options. The data stems from retrospective studies and single agent prospective trials. Thus, there may be a role for future research directly comparing treatment strategies for optimal management of this clinical entity.

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