Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report.

BACKGROUND: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.

Systemic arterial hypertension in head trauma.

The importance of maintaining adequate cerebral perfusion pressure to prevent cerebral ischemia is a well accepted concept in the management of patients with head injury. The potentially deleterious effects of too great a perfusion pressure, however, are generally less well appreciated. The occurrence of a hyperadrenergic state after head injury, and the effects of elevated blood pressure on the injured brain are reviewed, with emphasis placed on the pathophysiologic implications of a disturbance of the blood-brain barrier and of autoregulation in promoting brain swelling and formation of edema.

Severe head injury in children: experience of the Traumatic Coma Data Bank.

The outcome at discharge, 6 months, and 1 year after they had sustained severe head injuries was investigated in children (0-15 yr old at injury) who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank. Of 103 eligible children, the quality of recovery was assessed by the Glasgow Outcome Scale (GOS) at 6 months after injury in 92 patients (86% of series) and at 1 year in 82 patients (73% of series). The lowest post-resuscitation Glasgow Coma Scale score and pupillary reactivity were predictive of the 6-month GOS as were their interaction. Analysis of the first computed tomographic scan disclosed that bilateral swelling with/without midline shift was related to a poor outcome as was the presence of mass lesions. Comparison of age-defined subgroups of patients revealed that outcome was poorest in the 0- to 4-year-old patients, as reflected by their mortality, which increased to 62% by 1 year. Distinctive features of the injuries in the 0- to 4-year-olds included evacuated subdural hematomas (20% of patients) and hypotension (32% of patients). The most favorable outcome was attained by 5- to 10-year-olds (2/3 had a good recovery by 1 yr), whereas the GOS distribution of adolescents was intermediate between the children and adults. In summary, the GOS data reflect heterogeneity in the quality of outcome after severe head injury depending on age, neurological indices, and computed tomographic scan diagnostic category.

Drowning without aspiration: is this an appropriate diagnosis?

It has been reported that 10-15% of drowning victims do not aspirate water. We have revisited the original studies quoted to reach this conclusion and find it is without foundation. Sudden cardiac standstill is known to occur on land and, therefore, may also occur when the victim is in water. In the absence of the common finding of significant pulmonary edema in the victim's respiratory system, to conclude his or her death was caused by "drowning without aspiration" is unwise. All causes of sudden death that might occur in which respiration may not take place should receive serious consideration when examining bodies with such findings that are found in water.

Is it time to use evoked potentials to predict outcome in comatose children and adults?

OBJECTIVE: To determine the value of multimodality-evoked potential recordings in predicting outcome in comatose children. DESIGN: Prospective series and literature review. SETTING: Pediatric ICU in a university hospital. PATIENTS: Forty-one children with a Glasgow Coma Scale score of less than 8, who were admitted to the pediatric ICU between 1984 and 1989. INTERVENTIONS: Forty-one patients underwent brainstem auditory-evoked potential testing within 72 hrs of admission. Of these patients, 37 also had somatosensory-evoked potential testing at the same time. Four patients did not receive somatosensory-evoked potential testing for various nonmedical reasons. MEASUREMENTS AND MAIN RESULTS: Multimodality-evoked potential recordings were used to predict outcome in these comatose children. Outcomes were categorized as bad (death or chronic vegetative state) or good (all other outcomes). Survivor outcomes were determined at discharge and on subsequent follow-up visits from 1 to 3 yrs later. There were no false pessimistic predictions, and two false optimistic predictions in this series. A comprehensive literature review of coma outcome prediction, using multimodality-evoked potential recordings, revealed 20 series with 982 additional patients in whom the predictive errors of false optimism and false pessimism could be determined. Five cases of false pessimism and 99 cases of false optimism were identified in the 982 additional patients. If neonates are excluded, the false pessimism number is reduced to three. CONCLUSIONS: A bad outcome can be reliably predicted using multimodality-evoked potential recordings with little chance of a false pessimistic prediction. The acceptable error of false optimism occurs frequently, since patients often die of progressive neurologic and nonneurologic problems that may or may not be present at the time of the evoked potential recordings. Thus, in comatose children, multimodality-evoked potential recordings are a useful adjunct to clinical examination and other diagnostic aids in predicting outcome and in making decisions regarding the degree of intervention to offer.

Thrombotic and hemorrhagic complications in children with the lupus anticoagulant.

Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two.