Age is the most important independent risk factor for stroke; however aging animals are rarely used in stroke studies. Previous work demonstrated that young male mice had more edema formation after an induced stroke than aging animals. An important contributor to cerebral edema formation is the Na-K-Cl cotransporter (NKCC). We examined the expression of NKCC in young (10-12 week) and aging (15-16 months) C57BL6 male mice after middle cerebral artery occlusion (MCAO) and investigated the effect of pharmacological inhibition of NKCC with Bumetanide on cerebral edema formation. Both immunofluorescent staining and Western blotting analysis showed that NKCC expression was significantly higher in the ischemic penumbra of young compared to aging mice after stroke. Edema formation was significantly more robust in young mice and was reduced with Bumetanide. Bumetanide had no effect on cerebral edema in aging mice after MCAO. This suggests that NKCC expression and edema formation are age dependent after ischemic stroke.
IntroductionLung cancer is one of the most common cancers in the world and it is the leading cause of cancer-related deaths, among men and women, in the United States. In advanced non-small cell lung cancers, immune checkpoint inhibitors such as programmed cell death protein-1 inhibitors (PD-1 inhibitors) have become second-line therapy and have revolutionized the management in selective cases conferring better overall response rates and progression free survival.MethodsWe present a case series and review of literature emphasizing this immune-related adverse events (irAEs) in patients with metastatic non-small cell lung cancer and esophageal cancer who were treated with Nivolumab as a second line therapeutic option.ResultsPD-1 inhibitors such as, Nivolumab and Pembrolizumab, have shown a stable regression of various malignancies, such as metastatic melanoma, renal cell carcinoma and metastatic non-small cell lung cancer. We describe 2 cases of such immune related adverse effects associated with immune check point inhibitors with recovery in one of the patients. Steroid therapy has been the cornerstone for treatment for such immune related adverse effects. Importance has also been laid on the typical radiographic patterns of pneumonitis and interstitial lung disease associated with immunotherapy.ConclusionsWe attempt to raise awareness, discuss early management strategies and hypothesize an association between the incidence and development of these adverse events in cancer patients treated with anti-PD-1 immunotherapeutic agents.
Since the inception of critical care medicine and artificial ventilation, literature and research on weaning has transformed daily patient care in intensive care units (ICU). As our knowledge of mechanical ventilation (MV) improved, so did the need to study patient-ventilator interactions and weaning predictors. Randomized trials have evaluated the use of protocol-based weaning (vs. usual care) to study the duration of MV in ICUs, different techniques to conduct spontaneous breathing trials (SBT), and strategies to eventually extubate a patient whose initial SBT failed. Despite considerable milestones in the management of multiple diseases contributing to reversible respiratory failure, in the application of early rehabilitative interventions to preserve muscle integrity, and in ventilator technology that mitigates against ventilator injury and dyssynchrony, major barriers to successful liberation from MV persist. This review provides a broad encompassing view of weaning classification, causes of weaning failure, and evidence behind weaning predictors and weaning modes.
Brentuximab vedotin is used for relapsed classical Hodgkin’s lymphoma and mature T-cell lymphomas. We present a unique case of severe hypertriglyceridemia after one dose of single-agent brentuximab therapy. A Middle-Eastern male with a history of primary progressive cutaneous gamma/delta T-cell lymphoma was started on single-agent brentuximab vedotin therapy. Two weeks after single dose brentuximab therapy, he complained of severe epigastric pain, nausea, vomiting and was admitted to the intensive care unit with acute pancreatitis. Physical examination revealed an acutely ill patient with abdominal tenderness and laboratory data showed triglyceride levels of 3175 mg/dL, glycated hemoglobin (HbA1C) 9%, lipase 145 U/L and glucose 594 mg/dL. Computed tomography scan of the abdomen and pelvis confirmed acute interstitial pancreatitis. With medical management patient triglyceride levels decreased and the patient improved. This is the first case report in literature depicting, brentuximab induced hypertriglyceridemia leading to acute pancreatitis. It is a serious complication and can be lethal. Therefore, it is critical to maintain a high index of suspicion for hypertriglyceridemia induced pancreatitis after single dose brentuximab therapy.
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