Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis

Background: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. Methods: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. Results: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p 4 cm: 21%, 40%, 51%, p <.001) and resection rate (17%, 4%, 7%, p <.001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10–1.23), tail versus head 1.35 (95%CI 1.29–1.41)). Conclusions: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail

Periodicities in the Daily Proton Fluxes from 2011 to 2019 Measured by the Alpha Magnetic Spectrometer on the International Space Station from 1 to 100 GV

We present the precision measurement of the daily proton fluxes in cosmic rays from May 20, 2011 to October 29, 2019 (a total of 2824 days or 114 Bartels rotations) in the rigidity interval from 1 to 100 GV based on 5.5×109 protons collected with the Alpha Magnetic Spectrometer aboard the International Space Station. The proton fluxes exhibit variations on multiple timescales. From 2014 to 2018, we observed recurrent flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. The rigidity dependence of the 27-day periodicity is different from the rigidity dependences of 9-day and 13.5-day periods. Unexpectedly, the strength of 9-day and 13.5-day periodicities increases with increasing rigidities up to ∼10 GV and ∼20 GV, respectively. Then the strength of the periodicities decreases with increasing rigidity up to 100 GV.</p

Needle electromyographic findings in 98 patients with myositis.

Item does not contain fulltextBACKGROUND/AIMS: Little is known about the distribution of electromyographic (EMG) abnormalities in myositis even though this is relevant in daily practice. METHODS: A retrospective semiquantitative analysis of needle EMG findings was performed in a group of 98 patients with myositis. The frequency, type, and distribution of abnormalities were studied. The influence of the use of corticosteroids and the stage of the disease were evaluated. RESULTS: In most patients, a myopathic pattern with spontaneous activity was found, although several clinically relevant exceptions were noted. Long-duration motor unit potentials were found in all three diagnostic groups and were not associated with disease duration. In the lower extremity a distal to proximal gradient was present, adding to the diagnostic confusion with neurogenic diseases, and spontaneous activity was absent in a relatively large group although none of the patients in the acute stage of the disease had a normal EMG. The use of corticosteroids reduced the number of abnormal findings in dermatomyositis and polymyositis, but not in inclusion body myositis. CONCLUSION: A myopathic pattern with spontaneous activity was most frequently found, although several clinically relevant exceptions were noted. These results illustrate the spectrum of EMG findings in myositis, and may aid the clinician in the interpretation of the EMG in these patients

Calpain inhibition prevents amyloid-β-induced neurodegeneration and associated behavioral dysfunction in rats

Amyloid-β (Aβ) is toxic to neurons and such toxicity is - at least in part - mediated via the NMDA receptor. Calpain, a calcium dependent cystein protease, is part of the NMDA receptor-induced neurodegeneration pathway, and we previously reported that inhibition of calpain prevents excitotoxic lesions of the cholinergic nucleus basalis magnocellularis of Meynert. The present study reveals that inhibition of calpain is also neuroprotective in an in vivo model of Aβ oligomer-induced neurodegeneration in rats. Aβ-induced lesions of the nucleus basalis induced a significant decrease in the number of cholinergic neurons and their projecting fibers, as determined by analysis of choline-acetyltransferase in the nucleus basalis magnocellularis and cortical mantle of the lesioned animals. Treatment with the calpain inhibitor A-705253 significantly attenuated cholinergic neurodegeneration in a dose-dependent manner. Calpain inhibition also significantly diminished the accompanying neuroinflammatory response, as determined by immunohistochemical analysis of microglia activation. Administration of β-amyloid markedly impaired performance in the novel object recognition test. Treatment with the calpain inhibitor, A-705253, dose-dependently prevented this behavioral deficit. In order to determine whether pre-treatment with the calpain inhibitor is necessary to exhibit its full protective effect on neurons we induced Aβ toxicity in primary neuronal cultures and administered A-705253 at various time points before and after Aβ oligomer application. Although the protective effect was higher when A-705253 was applied before induction of Aβ toxicity, calpain inhibition was still beneficial when applied up to 1 h post-treatment. We conclude that inhibition of calpains may represent a valuable strategy for the prevention of Aβ oligomer-induced neuronal decline and associated cognitive deterioration.