Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

Background: Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Patients and methods: Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Results: Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Conclusion: Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

Neurochemical changes after morphine, dizocilpine or riluzole in the ventral posterolateral thalamic nuclei of rats with hyperalgesia.

A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA receptors in animal models of inflammation. Most studies analyze glutamate effects at the spinal cord level. In this work, the effects of morphine, dizocilpine and riluzole on the hyperalgesia induced by carrageenan administration in the rat paw model were investigated. The effects of morphine and riluzole on the release of glutamate and aspartate and on the concentrations of citrulline and arginine in dialysates of the ventral posterolateral nucleus of the thalamus were also examined. All three drugs decreased hyperalgesia when administered prior to carrageenan injection. Morphine decreased the glutamate concentration in dialysates of the ventral posterolateral nucleus but did not affect the concentrations of the other amino acids. The effect of morphine was observed in the absence of painful stimulation and when pressure applied to the rat paw induced a nociceptive reaction. Riluzole decreased the concentrations of glutamate and aspartate and those of citrulline and arginine in the presence or absence of painful stimulation. These experiments suggest that morphine and riluzole attenuate the hyperalgesia induced by injection of carrageenan in the rat hind paw, at least partly, by decreasing glutamate release in the ventral posterolateral thalamic nucleus.

Effect of precipitated withdrawal on extracellular glutamate and aspartate in the nucleus accumbens of chronically morphine-treated rats: an in vivo microdialysis study.

Excitatory amino acids release during morphine or naloxone administration was studied in rats. Microdialysis in freely moving animals and capillary electrophoresis with laser-induced fluorescence detection were used to measure several amino acids including glutamate and aspartate in the extracellular fluid at the nucleus accumbens. Perfusion with a calcium-free Ringer's solution decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its baseline levels, suggesting partial synaptic origin of these amino acids. The first morphine injection decreased glutamate and aspartate to 50% of its baseline level. After repeated morphine injections this effect disappeared, suggesting tolerance. Naloxone injections to morphine-dependent rats increased 300% glutamate and aspartate release; these experiments suggest that excitatory amino acid release in the nucleus accumbens might play a role in morphine withdrawal.

Glutamate measured by 6-s resolution brain microdialysis: capillary electrophoretic and laser-induced fluorescence detection application.

In the present experiment the combination of brain microdialysis and CZE-LIFD permitted the measurement of glutamate in 100 nl microdialysis samples collected every 5 or 6 s. Samples were collected every 6 s, in rats anesthetized with two different anesthetic agents (ketamine and sodium thiopental). A microdialysis probe was inserted in the cortex of an anesthetized rat in the territory irrigated by the middle cerebral artery. The artery was clamped for 30 s and then released. The samples were derivatized with fluorescein isothiocyanate I (FITC) by means of a continuous-flow reactor, collected and injected into a home-made CZE-LIFD instrument. Glutamate decreased immediately after clamping the artery in ketamine anesthetized rats and increased 1 min after the onset of the ischemia in sodium thiopental anesthetized rats. In another experiment a 60 mM KCl solution was injected through a microdialysis probe inserted in the hippocampus of an anesthetized rat. In the first 5 s after the KCl solution reached the tissue, glutamate increased but gamma-aminobutytic acid and glutamine did not. The experiments show that time resolution of brain microdialysis can be reduced to a few seconds if the analytical technique is the proper one.

Involvement of calcium in the cardiac depressant actions of a garlic dialysate.

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.

Health information privacy reform.

Statutory protection for personal health information privacy is in clear need of reform. With few exceptions, current legal safeguards provide uneven coverage and limited protection. Absence of a uniform federal code of fair health information practices leaves individual rights in health information compromised, exposes data users, and poses a potential threat to the integrity of the data. Current legislative proposals for national health care reform seek to standardize privacy protection while simultaneously facilitating usage of personal health information in an electronic data network. Reform provisions for confidentiality of health data will establish explicit duties for "health information trustees" and should strengthen privacy safeguards in the workplace.

In vitro biologic responses to native and surface-modified asbestos.

A comparative study was made of in vitro biologic responses to native chrysotile, amosite, and crocidolite and corresponding asbestos fibers whose surfaces were modified by metal oxides. Interferon induction by influenza virus was depressed by approximately 50% by all native asbestos whereas corresponding surface modified asbestos minimally affected this nonspecific cellular defense mechanism. The release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), and lysosomal enzymes, beta-N-acetylglucosaminidase (beta-NAG) and beta-glucuronidase (beta-Gluc), by rat alveolar macrophages after exposure to either native or surface-modified asbestos (which is indicative of membrane damage) was monitored. Although both native and surface-modified asbestos induced significant leakage of LDH, generally, lesser amounts of the enzyme were released as a result of exposure to the latter than to native asbestos. Whereas all forms of native asbestos caused significant release of beta-NAG and beta-Gluc, leakage of these enzymes from macrophages exposed to surface-modified asbestos was minimal. In contrast to native asbestos which induced irritation of cell membranes, as indicated by hemolysis of sheep erythrocytes, surface-modified asbestos exhibited minimal hemolytic activity. The findings indicate that surface modification of different asbestos by metal oxides generally lessened the adverse effect of the native mineral on the aforementioned biologic entities.

Respiratory morbidity in wollastonite workers.

Medical and environmental surveys were conducted at a wollastonite mine and mill in 1976 and in 1982. Health testing included chest radiography, spirometry, and a questionnaire. Workers at a nearby electronics plant were also examined in 1982 for a comparison of lung function and respiratory symptoms. Both wollastonite and control workers showed significant smoking effects for chronic respiratory symptoms, but differences between the groups were not detected. Pneumoconiosis was found in 3% (3/108) of the wollastonite workers in 1982, but none showed a significant progression from their 1976 radiographs. The lung function tests of the 108 wollastonite workers examined in 1982 showed dust related changes in FEV1, FEV1/FVC ratio, and peak flow rate which were independent of age, height, and smoking habit (p less than 0.01). For non-smokers alone, only the FEV1/FVC ratio declined significantly with dust-years of exposure (p less than 0.01). The comparison of lung function in 1982 between a high dust exposed subgroup of wollastonite workers and the control population showed a significantly lower FEV1/FVC ratio and peak flow rate in the study group (p less than 0.05). Analysis of 1976-82 changes in pulmonary function showed that wollastonite workers with higher dust exposure had a significantly greater decline in peak flow over the period than workers with lower exposures (p less than 0.01). These data suggest that long term cumulative exposure to wollastonite may impair ventilatory capacity as reflected by changes in the FEV1/FVC ratio and peak flow rate.

Cotton induced bronchoconstriction detected by a forced random noise oscillator.

Lung function responses to inhaled cotton dust were evaluated in a group of 58 healthy subjects by spirometry (MEFV curves) and forced random noise impedance parameters. Twenty-one of these subjects were also examined by body plethysmography to assess changes in airway resistance (Raw). For the study group as a whole, alterations in lung mechanical function after exposure to cotton dust were detected by maximal expiratory volumes and flows (p less than 0.001) and impedance parameters (p less than 0.01) but not by Raw. Subjects showing responses in MEFV curves also showed increases in Thevenin or effective resistance at low frequencies (R1, R5-9, R5-9/R20-24), suggesting that the limitation of flow occurred predominantly in the peripheral airways. By contrast, non-responders on MEFV measurements were found to have significant increases in effective resistance both at low and at high frequencies (R1, R5-9, R20-24), suggesting a central airways effect. MEFV curve non-responders also exhibited a significantly lower baseline effective resistance profile than MEFV curve responders. The data indicate that under the conditions of the experiment measures of the Thevenin resistance (real part of impedence) by the forced random noise method are reliable indicators of cotton induced bronchoconstriction. Measurement variability, however, suggests that, at present, these are more appropriate for group studies and should remain adjuncts to standard tests of lung function such as spirometry.

Acute lung function response to cotton dust in atopic and non-atopic individuals.

Acute spirometric responses to inhaled cotton dust were examined in a population of 226 healthy, non-asthmatic adults whose atopic status had been evaluated by skin prick tests to 10 common environmental allergens. Exposure to cotton dust occurred in model cardrooms where elutriated dust levels were carefully controlled (1.02 mg/m3). Atopy, defined as positive prick tests to at least two allergens, was observed in 26% of subjects. Significant forced expiratory volume in one second (FEV1) decrements occurred after exposure to cotton dust independent of atopic status (p less than 0.001). The mean FEV1 decline in atopic subjects, however, was significantly greater than in non-atopic subjects (p less than 0.05). Degree of atopy, as measured by number of positive skin tests, also exhibited a significant association with cotton induced decrements in FEV1 (p less than 0.05). These data suggest that atopy may be an important determinant of the magnitude of the acute pulmonary response to cotton dust. This may reflect the non-specific airways hyperresponsiveness that has been described in non-asthmatic, atopic individuals.

Effects of lignite fly ash particulates and soluble components on the interferon system.

Induction of interferon by influenza virus was depressed by approximately 50% when mammalian (LLC-MK2) cell monolayers were pretreated with lignite fly ash. The presence of fly ash, however, did not impair the ability of exogenous interferon to confer antiviral cellular resistance. Influenza virus multiplication in cell monolayers pretreated with fly ash attained a twofold higher level of growth than that noted in normal cell monolayers. This was related to suppression of viral interferon induction by fly ash. Whereas aqueous extracts of fly ash had no adverse effect on interferon induction, extractions of fly ash by either polar or nonpolar solvents, by horse serum with or without EDTA (a metal chelator), and fractionation of serum extracts yielded corresponding compounds, most likely organic and inorganic, that were antagonistic to viral interferon induction. Residual fly ash particulates after extraction by horse serum with EDTA were still capable of inhibiting viral induction of interferon. These findings indicate that several soluble components inherent to lignite fly ash and the particulate matrix per se may modify, independently or in concert, cellular defense behavior. Neither polar, nonpolar, nor horse serum extracts of lignite fly ash, however, showed mutagenic activity as determined by the Salmonella histidine reversion assay. Removal of cell-membrane-bound sialic acid (N-acetylneuraminic acid) by neuraminidase or pretreatment of lignite fly ash with sialic acid abolished the adverse activity of fly ash on viral interferon induction. This suggests that the interaction of cell-membrane-bound sialic acid residue with fly ash particulates may be involved in the altered state of cellular behavior described in response to viral induction of interferon.

Pneumoconiosis and lung function in a group of kaolin workers.

In June 1981, 65 current and former workers at a kaolin mine and mill were examined by chest radiography, spirometry, and a questionnaire. Five (13%) of 39 current workers and 3 (19%) of 16 former workers with 5 yr or more of exposure had radiographic evidence of pneumoconiosis. Among the 8 workers with pneumoconiosis, conglomerate upper lobe lesions were present in one half. No pneumoconiosis was observed among 8 current workers with less than 5 yr of exposure. Lung function testing showed significant reductions (p less than 0.05) in FVC, FEV1, and peak flow rate in kaolin workers compared with that in a control group. Environmental sampling during the testing period showed airborne dust to be composed of kaolinite (96%) and titanium dioxide (4%). Additional controlled epidemiologic studies among kaolin workers are needed to generate reliable prevalence data for pneumoconiosis and to assess the impact of dust exposure on pulmonary function.

Roentgenographic evidence of asbestos exposure in a select population of railroad workers.

A volunteer population of 266 current and former railroad workers was examined with posteroanterior and oblique chest roentgenograms, and a comprehensive occupational smoking history. Seventy-five percent of participants were over the age of 60, and 80% had fewer than 10 years of railroad-related asbestos exposure. Roentgenographic evidence of asbestosis was found in only six workers (2%), whereas 20% had one or more pleural changes. Radiological abnormalities were related to latency period, age, and occupation, but not to smoking habit. While selection factors qualify the results of this study, the findings support the exposure and suggest a past and future history of asbestos mortality and morbidity among steam era railway workers.