Citations

239 Background: After trastuzumab (T) approval for advanced HER2-positive E/GEJ-AC, HER2 testing has increased in patients (pts) with resectable disease. Neoadjuvant carboplatin/paclitaxel chemoradiation (nCP-CRT) is a common therapy approach. We performed the largest evaluation, to our knowledge, of the prognostic impact of HER2 in E/GEJ-AC pts treated with nCP-CRT. Methods: We retrospectively reviewed medical records of all trimodality-eligible (T2+ or N+) pts with E/GEJ-AC who started nCP-CRT (usually 50.4 Gy) with planned surgery at Mayo Clinic (2014-2019). HER2 was tested using standard criteria for HER2 positivity (ie, immunohistochemistry 3+ or amplification by in situ hybridization). Clinicopathologic data and time to recurrence (TTR), disease free survival (DFS), overall survival (OS), survival after recurrence (SAR), and pathologic complete response (pCR – ie, no residual tumor in primary or nodes) were collected. Kaplan Meier and multivariate Cox analysis were used. Results: Of 161 consecutive eligible pts, HER2 status was available in 107 pts (HER2-positive n=26, HER2-negative n=81) of whom n=82 had surgery and n=19 had pCR. Most tumors were clinical T3 (80%) or N+ (81%), histologic grade 3 of 3 (62%). HER2 positivity was significantly associated with lower grade, but not with age, clinical T or N, or ECOG performance status (PS). A similar proportion of HER2-positive ( vs negative) pts had surgery. Among pts who had surgery, pCR rates were lower in HER2-positive ( vs negative) pts (11% [2/19] vs 27% [17/63]). After a median follow up of 23 mo, DFS and TTR were significantly shorter in HER2 positive ( vs negative) pts, independent of other pretreatment covariables (Table). Yet OS was comparable. Lung recurrence was enriched in HER2 positive ( vs negative) pts. Among pts with recurrence, SAR was longer in HER2-positive vs -negative pts. A total of 53% (10/19) of previously HER2-positive pts received T-based therapy after recurrence, and these pts were the drivers of favorable SAR (median 22 mo in n=10 HER2-positive pts who received T vs 11 mo in n=9 HER2-positive pts who did not receive T vs 11 mo in n=40 HER2-negative pts; P log-rank=.01). Conclusions: HER2 positivity ( vs negativity) is independently associated with shorter TTR and DFS, but more comparable OS. The adverse association of HER2 on tumor response and TTR may have been largely overcome through enhanced survival after recurrence, although OS data are maturing. These data may have implications for the design of endpoints in future curative-intent anti-HER2 trials. [Table: see text]

Abstract OBJECTIVE To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders ANIMALS 15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5). PROCEDURES All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated. RESULTS Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoanti-body does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.

The objectives of this article are to present a case of type II cryoglobulinemic vasculitis, explain why mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual cause of type II cryoglobulins and to discuss the aetiology, epidemiology, pathophysiology and treatment of cryoglobulinemic vasculitis. A 67-year-old woman presented with 4 months of weight loss, intermittent epistaxis and a purpuric skin rash. Prior to presentation, she was found to have an elevated rheumatoid factor. Further investigation revealed an acute kidney injury and elevated type II cryoglobulins suspicious for cryoglobulinemic vasculitis, which was confirmed by kidney biopsy. Additional workup for the weight loss included biopsy of newly found splenomegaly. Pathology revealed MALT lymphoma, a rare cause of type II cryoglobulinemic vasculitis. Successful medical therapy required treating the underlying malignancy with rituximab and high-dose steroids. After initial resolution of symptoms with this regimen, the patient’s vasculitis worsened, which was thought to be secondary to undertreatment of the lymphoma. Bendamustine was added to further treat the lymphoma, after which the patient recovered and was able to discharge without recurrence of symptoms at 6 months.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

Abstract Aims His–Purkinje conduction system pacing (HPCSP) utilizing His (HBP) or left bundle branch pacing (LBBP) in patients with atrial fibrillation (AF) and wide QRS duration has not been well studied. We assessed the benefit of left bundle branch block (LBBB) correction during HPCSP in AF patients undergoing atrioventricular junction (AVJ) ablation with LBBB, compared with those with narrow QRS duration. Methods and results This is an observational study in consecutive patients with typical LBBB or narrow QRS duration in whom we attempted HPCSP after AVJ ablation for refractory AF with a left ventricular ejection fraction (LVEF) ≤ 50%. Echocardiographic responses and clinical outcomes were assessed at baseline and during 1 year of follow-up. A total of 178 patients were enrolled, of which 170 achieved AVJ ablation + permanent HPCSP (age 69.3 ± 10.1 years; LVEF 34.3 ± 7.7%), 133 (78.2%) patients had a narrow QRS duration, and 37 (21.2%) had an LBBB. The QRS duration changed from a baseline of 159.7 ± 16.6 ms to a paced QRS duration of 110.4 ± 12.7 ms in the LBBB cohort and from 95.6 ± 10.4 to 100.8 ± 14.5 ms (both P < 0.001) in the narrow QRS cohort after AVJ ablation and pacing. Compared with the narrow QRS cohort, the LBBB cohort showed a greater absolute increase in LVEF (+22.3% vs. +14.2%, P < 0.001), higher super responder rate (71.4% vs. 49.2%, P = 0.011), and greater New York Heart Association (NYHA) class improvement (−1.9 vs. −1.4, P < 0.001) at 1 year. Conclusion Patients with LBBB have greater improvement in LVEF and NYHA class function than patients with narrow QRS from HPCSP after AVJ ablation.

Abstract Background Infection by hepatitis B and C viruses causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The WHO’s ambition to eliminate viral hepatitis by 2030 requires strategies specific to the dynamic disease profiles each nation faces. Large-scale human movement from high-prevalence nations to the United States and Canada have altered the disease landscape, likely warranting adjustments to present elimination approaches. However, the nature and magnitude of the new disease burden remains unknown. This study aims to generate a modeled estimate of recent HBV and HCV prevalence changes to the United States and Canada due to migration. Methods Total migrant populations from 2010-2019 were obtained from United Nations Migrant Stock database. Country-of-origin HBV and HCV prevalences were obtained for the select 40 country-of-origin nations from the Polaris Observatory and systematic reviews. A standard pivot table was used to evaluate the disease contribution from and to each nation. Disease progression estimates were generated using the American Association for the Study of the Liver guidelines and outcome data. Results Between 2010 and 2019, 7,676,937 documented migrants arrived in US and Canada from the selected high-volume nations. Primary migrant source regions were East Asia and Latin America. Combined, an estimated 878,995 migrants were HBV positive, and 226,428 HCV positive. The majority of both migrants (6,477,506) and new viral hepatitis cases (HBV=840,315 and HCV=215,359) were found in the United States. The largest source of HBV cases stemmed from the Philippines, and HCV cases from El Salvador. Conclusion Massive human movement has significantly changed HBV and HCV disease burdens in both the US and Canada over the past decade and the long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities and screening and treatment programs must be strategically adjusted in order to reduce morbidity, mortality, and healthcare expenses. Disclosures All Authors: No reported disclosures

This paper describes the diagnostic criteria for “Vestibular Migraine of Childhood”, “probable Vestibular Migraine of Childhood” and “Recurrent Vertigo of Childhood” as put forth by the Committee for the Classification of Vestibular Disorders of the Bárány Society (ICVD) and the Migraine Classification subgroup of the International Headache Society. Migraine plays an important role in some subgroups of children with recurrent vertigo. In this classification paper a spectrum of three disorders is described in which the migraine component varies from definite to possibly absent. These three disorders are: Vestibular Migraine of Childhood, probable Vestibular Migraine of Childhood and Recurrent Vertigo of Childhood. The criteria for Vestibular Migraine of Childhood (VMC) include (A) at least five episodes with vestibular symptoms of moderate or severe intensity, lasting between five minutes and 72 hours, (B) a current or past history of migraine with or without aura, and (C) at least half of episodes are associated with at least one migraine feature. Probable Vestibular Migraine of Childhood (probable VMC) is considered when at least three episodes with vestibular symptoms of moderate or severe intensity, lasting between five minutes and 72 hours, are accompanied by at least criterion B or C from the VMC criteria. Recurrent Vertigo of Childhood (RVC) is diagnosed in case of at least three episodes with vestibular symptoms of moderate or severe intensity, lasting between 1 minute and 72 hours, and none of the criteria B and C for VMC are applicable. For all disorders, the age of the individual needs to be below 18 years old. It is recommended that future research should particularly focus on RVC, in order to investigate and identify possible subtypes and its links or its absence thereof with migraine.