Dysphagia in elderly men with myasthenia gravis Kluin, Karen J.; Bromberg, Mark B.; Feldman, Eva L. ...
Journal of the neurological sciences,
06/1996, Letnik:
138, Številka:
1
Journal Article
Recenzirano
Eight elderly men whose primary symptoms of myasthenia gravis were decreased speech and swallowing ability were seen for speech pathology evaluations and videofluoroscopic swallow studies. All ...patients had fatigable flaccid dysarthria and greater than expected pharyngeal phase dysphagia on videofluoroscopy; eight had decreased pharyngeal motility as demonstrated by residual material in the valleculae and pyriform sinuses bilaterally; seven had episodes of laryngeal penetration secondary to overflow of residual material; and five experienced silent aspiration despite gag reflexes and the ability to cough to command. Five patients required feeding tubes because their dysphagia responded poorly to treatment. Videofluoroscopic swallow studies revealed a common swallowing profile with pharyngeal phase dysphagia greater than expected from patient symptoms. Dysphagia did not improve at the same rate as other manifestations of myasthenia gravis.
Abstract
Background
Trastuzumab stimulates HER2-specific T cell responses and increases tumour PD-L1 expression, and anti-PD-1 antibody can help enhance T cell-specific immunity of trastuzumab. We ...conducted a phase II trial of pembrolizumab with chemotherapy/trastuzumab.
Methods
Patients (pts) with previously untreated HER2 IHC 3+ or FISH+ tumours irrespective of PD-L1 status received intravenous P 200 mg flat dose, T 6 mg/kg (after 8 mg/kg load), O 130 mg/m2 every 3 weeks and oral C 850 mg/m2 2 weeks on/1 week off. 22 pts received 1 cycle of induction P/T prior to initiation of chemotherapy. The primary endpoint was 6-months PFS; with target accrual of 37 pts. Secondary endpoints included safety, OS, ORR, and biomarker analysis.
Results
Accrual completed and 100% of the 37 evaluable pts had tumour regression (ranging from -4% to -100%). The RECIST 1.1 ORR was 81% (27 PR, 3 CRs), and 12 (52%) of pts that received induction P/T x 1 cycle showed reduction in target lesions. Median PFS was 14.2 months (mo), with 70% 6 mo PFS. Median follow up was only 8 mo. In pts with available material, 14/36 (40%) had PD-L1 CPS >1 and median TMB was 4.4 mut/Mb (0-10.6). There was no correlation between PD-L1 status and PFS or OS. ERBB2 amplification was evident by tissue-NGS in 17/30 (63%) and ctDNA-NGS in 17/30 (58%) pre-treatment, while the remaining pts were ERBB2- by NGS likely due to tumour heterogeneity or low tumour content. CtDNA decreased in 16/24 tested pts after 1 cycle of induction T/P alone. irAEs included interstitial nephritis Gr4 (3%), transaminitis Gr3 (11%), Gr4 (3%), colitis Gr3 (3%).
Conclusions
40% remain on therapy, and so the primary endpoint should be reached by 9/19. Updated survival, correlative studies and will be presented. These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial (NCT03615326).
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center.
Funding
Merck.
Disclosure
Y.Y. Janjigian: Advisory / Consultancy, Research grant / Funding (self): Bristol-Meyers; Advisory / Consultancy, Research grant / Funding (self): Eli Lily; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Merck; Research grant / Funding (self): Amgen; Advisory / Consultancy, Research grant / Funding (self): Bayer; Research grant / Funding (self): Boehringer Ingelhiem; Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Imugene. S. Maron: Non-remunerated activity/ies, Research Collaboration Only: Guardant Health; Shareholder / Stockholder / Stock options: Calithera; Travel / Accommodation / Expenses: Merck; Licensing / Royalties, Non-remunerated activity/ies, Research Collaboration Only: Genentech. G.Y. Ku: Advisory / Consultancy, Research Support: Arog; Advisory / Consultancy, Research Support: Bristol-Myers Squibb; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Research Support: Merck; Advisory / Consultancy, Research Support: Pieris; Advisory / Consultancy, Research Support: Zymeworks. D.H. Ilson: Advisory / Consultancy: Merck; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pieris; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Britsol Myers Squibb; Advisory / Consultancy, Contracted Research: Taiho. D. Solit: Advisory / Consultancy: Pfizer; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Loxo Oncology; Advisory / Consultancy: Illumina; Advisory / Consultancy: Vivideon Therapeutics; Honoraria (institution), Speaker Bureau / Expert testimony: Lilly Oncology. J.F. Hechtman: Research grant / Funding (institution): Bayer; Honoraria (institution): Medscape; Advisory / Consultancy: Axiom Healthcare Strategies; Advisory / Consultancy: Cor2Ed. M. Lamendola-Essel: Advisory / Consultancy: Rockefeller University. All other authors have declared no conflicts of interest.
Comparison between cranial CT and magnetic resonance (MR) imaging in 10 patients with recent pontine infarction indicates a distinct superiority for MR. However, MR changes often failed to correlate ...with the degree of neurological dysfunction. Regions of abnormal signal intensity appeared to involve areas with normal neurologic function.
Patients with primary amyloidosis may develop peripheral neuropathy as an early feature. Sural nerve biopsy is reported to be a sensitive method for diagnosing amyloidosis in such patients. We ...identified nine patients, ultimately diagnosed as having amyloidosis, who were referred for peripheral neuropathy of undetermined etiology. In six, a sural nerve biopsy demonstrated no amyloid. Subsequent examination of other tissue or of the contralateral sural nerve eventually resulted in the correct diagnosis. We conclude that sural nerve biopsy may be less sensitive than previously believed for the diagnosis of amyloidosis in patients with peripheral neuropathy secondary to amyloid. When the clinical suspicion of amyloidosis is high, a nondiagnostic sural nerve biopsy should not discourage the performance of further investigative studies.
The genetic basis for myotonic dystrophy (DM) is a CTG trinucleotide repeat expansion. The number of CTG repeats commonly increases in affected individuals of successive generations, in association ...with anticipation. We identified a large DM family in which multiple members had minimal CTG repeat expansions, and in which the number of CTG repeats remained in the minimally expanded range through at least three, and possibly four, generations. This relative stability of minimal CTG repeat expansions may help to maintain the DM mutation in the population.
Although polyneuropathies associated with IgM and IgG monoclonal gammopathies have been well described, polyneuropathy with IgA monoclonal gammopathy of undetermined significance (MGUS) is less ...commonly seen and has not been well studied. We reviewed the clinical and electrodiagnostic features of 5 such patients, and the sural nerve biopsy findings in 4 of them. One patient was diabetic, while 4 were free of other diagnoses commonly associated with neuropathy. Clinical presentations were varied. Electrodiagnostic and histological studies ranged from primary demyelination to primary axon loss to a mixed axonal/demyelinating picture. Three patients who were treated appeared to respond to prednisone or intravenous gamma globulin, despite clear clinical, electrodiagnostic, and histological differences. We conclude that the polyneuropathy associated with IgA MGUS is heterogeneous, similar to that in IgM and IgG MGUS. A trial of immunomodulating therapy appears to be warranted in such patients if the neuropathy is sufficiently severe.
On magnetic resonance imaging (MRI) studies, wedge-shaped areas of signal abnormality noted in association with liver lesions have been attributed to secondary phenomena and are said to be ...substantially larger than the actual tumor. We describe the MRI and pathological appearance of a wedge-shaped cholangiocarcinoma. In cases where therapy might be affected, biopsy of wedge-shaped MRI abnormalities associated with hepatic malignancy should be considered for accurate tumor staging.
Intramural perforation of the colon proximal to the rectosigmoid is a rare complication of the barium enema examination. We present a case in which air and barium entered the wall of the transverse ...colon, and then dissected through the transverse mesocolon during double-contrast barium enema in an asymptomatic patient with no known underlying colonic disease.
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