Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer.

BACKGROUND: Brigatinib is a potent ROS1 inhibitor. The existing data on its clinical activity in ROS1-rearranged non-small cell lung cancer (NSCLC) are limited to four cases. METHODS: Six patients with ROS1-rearranged advanced NSCLC treated with brigatinib were identified through search of the internal databases of four participating cancer centers. Four additional patients were selected by PubMed and Google Scholar search. The objective response rate (ORR), progression-free survival (PFS) (RECIST v.1.1), duration of treatment (DOT), and safety were assessed. RESULTS: Of eight patients evaluable for response assessment (crizotinib naive-1, crizotinib resistant -7), three patients demonstrated a partial response (ORR-37%). One crizotinib-naive patient had an ongoing response at 21.6 months. Of seven crizotinib-resistant patients, two patients demonstrated a partial response (ORR-29%), and one patient (14%) had stable disease. PFS, available in four crizotinib-resistant patients, was 7.6 + , 2.9, 2.0, and 0.4 months. In crizotinib-resistant patients, DOT was 9.7 + , 7.7 + , 7.6 + , 4.0, 2.0, 1.1, 0.4 months, and was not reported in two patients. Genomic profiling in one responder revealed no ROS1 alteration, suggesting that the response was attributable to "off-target" brigatinib activity. In two patients with progressive disease, genomic profiling demonstrated a cMET exon 14 mutation + KRAS G12A mutation in one case, and a persisting ROS1-CD74 fusion + TP53 K139N, FGFR2 E250G, ATM G2695D, and NF1 R2258Q mutations in the other. No grade 3-5 toxicity was observed. CONCLUSION: Brigatinib demonstrated modest activity in crizotinib-resistant ROS1-rearranged NSCLC. Its intracranial and systemic activity should be assessed in correlation with the underlying molecular mechanism of crizotinib resistance.

Our series is the first to describe brigatinib activity in ROS1-altered NSCLC. In crizotinib-resistant patients, ORR with brigatinib was 29%. PFS with brigatinib was 7.6+, 2.9, 2.0, and 0.4 months. DOT with brigatinib was 9.7+, 7.7+, 7.6+, 4.0, 2.0, 1.1, 0.4 months. The correlation between response and molecular resistance needs further exploration.

Diagnosis of turkey meningoencephalitis virus infection in field cases by RT-PCR compared to virus isolation in embryonated eggs and suckling mice.

Turkey meningoencephalitis (TME) is a paralytic epornitic disease of turkeys caused by turkey meningoencephalitis virus (TMEV), an arthopod-borne flavivirus belonging to the Ntaya serogroup VI. A TMEV specific RT-PCR was compared with classical techniques for TMEV diagnosis, which include virus isolation in 8-day-old chicken embryonated eggs and suckling mice, on 17 TME flocks with neurological signs that occurred during the fall of 1997. In 11/17 flocks both the RT-PCR and the virus isolation methods detected virus, in 4/17 flocks a negative diagnosis was obtained by both methods, and two flocks were positive by RT-PCR only. In four flocks RT-PCR only detected virus after inoculation into embryonated eggs or suckling mice. There was a dose response effect in the yield of the RT-PCR product. Direct examination of turkey brains yielded bands of low to medium intensity. Use of RT-PCR after embryo and/or mouse inoculation resulted in products of far greater intensity. Thus, RT-PCR can be successfully used to amplify TMEV RNA in the brains of diseased turkeys but a negative result would require egg and mouse inoculation for enrichment of virus prior to RT-PCR.

Accumulation of Streptococcus mutans on light-cured composites and amalgam: an in vitro study.

The aim of the in vitro study was to examine the accumulation of Streptococcus mutans on light-cured composite materials and amalgam. Bacteria cultures were grown in a brain heart infusion medium, and their growth rate was determined through turbidity measurements. The data, so obtained, were evaluated statistically by analysis of variance (ANOVA) followed by Scheffe test. Experiments on amalgam showed better results compared to those on composite materials. There were no statistically significant differences in plaque accumulation on different composite materials after finishing and polishing procedures, compared to plaque accumulation on composite materials against a Mylar strip.

A psychoanalytic study of migration: its normal and pathological aspects.

Without maintaining that it always follows the same steps, we could say that the migratory process passes through several phases. The feelings that prevail are those of intense sorrow for all that has been abandoned or lost, fear of the unknown, and the very profound experiences of loneliness, privation, and helplessness. Paranoid, confusional, and depressive anxieties occupy the scene in turn. This stage may be followed or replaced by a manic state in which the immigrant minimizes the transcendental significance of the change in his life or, on the contrary, magnifies the advantages of the change and overvalues everything in the new situation, disdaining what has been lost. After a variable period of time, nostalgia appears, and sorrow for the lost world. The immigrant begins to recognize feelings previously dissociated or denied and becomes capable of "suffering" his pain ("growing pains") while, at the same time, he becomes more accessible to the slow and progressive incorporation of elements of the new culture. The interaction between his internal and external world becomes more fluid. Recovery of the pleasure of thinking and desiring and of the capacity for making plans for the future, in which the past is regarded as such and not as a "lost paradise" where one constantly longs to return. In this period, it could be considered that mourning for the country of origin has been worked through to the maximum extent possible, facilitating integration of the previous culture into the new culture, without the need to renounce the old. All of this promotes an enrichment of the ego and the consolidation of a more evolved sense of identity.

Postoperative malignant hyperthermia episodes in patients who received "safe" anaesthetics.

Three cases of postoperative malignant hyperthermia (MH) episodes, after what was considered to be a "safe" anaesthetic, are described. In each case the temperature rose in a delayed fashion after an uneventful anaesthetic. Treatment included intravenous dantrolene, surface cooling and ventilation with 100 per cent oxygen. Stress in the postoperative period may have been the triggering factor responsible for these reactions. Patients should be monitored well into the postoperative period as MH episodes may occur long after surgery is completed. If stress represents a significant triggering mechanism then no anaesthetic technique can be considered entirely safe.

Life events, psychiatric screening, and psychosomatic illness.

The General Health Questionnaire (GHQ) and the Schedule of Recent Events (SRE) were administered to a consecutive series of referrals to a general hospital psychiatric consultation service. Control groups of psychiatric and medical inpatients matched for age and sex were also evaluated. Significantly greater life change was found in the consultation group as compared to the medical controls, providing further support for the cluster theory of illness. The General Health Questionnaire was found to be an effective screening instrument for nonpsychotic emotional illness in a general hospital inpatient setting. A significant positive correlation between the GHQ scores and the SRE scores suggests a relationship which merits further study in the epidemiology of psychosomatic illness. The implications of the significant correlation of physical and emotional illness to clinical medical practice is briefly discussed.

Inhibition of granulocyte erythrophagocytosis by HLA antisera.

The ability of HLA antisera to inhibit granulocyte erythrophagocytosis (EP) of opsonized red blood cells (RBC) was evaluated. Human granulocytes (PMN) were separated from heparinized whole blood by the Ficoll-Isopaque technique and suspended in McCoy's medium. EP occurred when the PMN were incubated with opsonized RBC. For six HLA antibody specificities evaluated, prior incubation of PMN with HLA antisera resulted in significant inhibition of EP without cytolysis when the PMN donor was positive for the specific HLA antigen, but not when the donor was negative for the antigen. The inhibition was time- and dose-dependent. Prior absorption of HLA antisera with HLA-specific platelets reduced or abolished the inhibition. An example of anti-NB1 also inhibited EP in 4 individuals. These data suggest that HLA antibody may adversely affect granulocyte phagocytic function. Inhibition of EP might be useful in evaluating compatibility prior to granulocyte transfusion.