Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions.

Bruton's Tyrosine Kinase (BTK) is considered crucial in the activation and survival of both physiological and malignant B-cells. In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic. However, ibrutinib's feasibility might not end there. Several other kinases with established involvement with solid malignancies (i.e., EGFR, HER2) have been found to be inhibited by this agent. Recent discoveries indicate that BTK is a potential anti-solid tumor therapy target. Consequently, ibrutinib, a BTK-inhibitor, has been studied as a therapeutic option in solid malignancies. While most preclinical studies indicate ibrutinib to be an effective therapeutic option in some specific indications, such as NSCLC and breast cancer, clinical trials contradict these observations. Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer. This review aims to describe the milestones in translating BTK inhibitors to solid tumors in order to understand the future potential of this agent better.

Acute psychomotor agitation - challenges for psychiatrists and neurologists: a case study.

Purpose: Bilateral thalamic ischemia can, paradoxically, manifest itself with various non-sensory clinical symptoms, thereby complicating diagnosis. Case description: A 59-year-old woman was admitted to an Emergency Department about and hour and a half after she was found with altered mental status. Her initial symptoms were psychomotor agitation and slight confusion. No evident focal neurological deficit was observed at that time and computed tomography was negative. After acute drug intoxication was excluded, a transfer to a psychiatric unit was considered. Simultaneously, short stenosis of the left posterior cerebral artery was diagnosed with the use of computed tomography angiography. Magnetic resonance imaging revealed bilateral acute ischemia of the medial parts of the thalamus, and immediate thrombolysis and thrombectomy treatment was initiated. Both procedures were successful and the patient was discharged in good general condition. Comment: Psychomotor agitation may be an atypical manifestation of a bilateral thalamic ischemia. This may lead to misdiagnosis and reduce the likelihood of proper treatment.