Current pharmaceutical design
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Hyperglycemia is associated with increased mortality and morbidity in critically ill patients. Surgical patients commonly develop hyperglycemia related to the hypermetabolic stress response, which increases glucose production and causes insulin resistance. Although hyperglycemia is associated with worse outcomes, the treatment of hyperglycemia with insulin infusions has not provided consistent benefits. ⋯ Patients with diabetes mellitus experience chronic hyperglycemia and often require more intensive perioperative glucose management. When diabetic patients are evaluated before surgery, appropriate management of oral hypoglycemic agents is necessary as several of these agents warrant special consideration. Current recommendations for perioperative glucose management from national societies are varied, but, most suggest that tight glucose control may not be beneficial, while mild hyperglycemia appears to be well-tolerated.
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Pancreatic cancer is characterized by its intrinsic resistance to cytotoxic agents. But the underlying molecular mechanism is unclear. Studies demonstrate that angiogenesis, presence of highly resistant cancer stem cells (CSCs), dysregulation of cell cycle and apoptosis are main aspects of mechanisms of pancreatic cancer chemoresistance. ⋯ Conceivably, the dysregulation of Wnt/β-catenin signaling pathway is involved in pancreatic cancer chemoresistance. Though researchers have proven it in some other cancer types, however, there is no direct evidence for this reasoning in pancreatic cancer. Designing effective experiment setups to define the function and mechanism of Wnt/β-catenin signaling in pancreatic cancer chemoresistance and subsequently targeting the signaling to improve the sensitivity of chemotherapy in pancreatic cancer require a full understanding of the molecular mechanisms of Wnt/β-catenin signaling pathway in angiogenesis, maintaining of highly resistant CSCs, regulation of cell cycle and apoptosis in pancreatic cancer.
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Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. ⋯ Opioid treatment involved slightly opposite outcomes in the two patient groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher quality of evidence opioid induced deficits in cognitive functioning were associated with dose increase and the use of supplemental doses of opioids in cancer patients. Future perspectives should comprise the conduction of high quality randomized controlled trials (RCTs) involving relevant control groups and validated neuropsychological assessments tools before and after opioid treatment in order to further explore the complex interaction between pain, opioids and cognition.
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Lenalidomide is a second generation immunomodulatory agent (IMiD), which currently represents the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndrome (MDS) patients with deletion (5q). Lenalidomide has unique activity with a high transfusion independence rate observed in this subset of patients. ⋯ We highlight the mechanism of action and the recent advances in understanding the biology of del (5q) MDS. We also explore its potential use and the efforts to further improve its activity in non-del (5q) MDS.
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Bronchoscopic procedures are at times intricate and the patients often very ill. These factors and an airway shared with the pulmonologist present a clear challenge to anesthesiologists. The key to success lies in the understanding of both the underlying pathology and procedure being performed combined with frequent two-way communication between the anesthesiologist and the pulmonologist. ⋯ Topics discussed in this review include anesthesia for advanced diagnostic procedures as well as for interventional/ therapeutic procedures. The latter includes bronchoscopic tracheal balloon dilation, tracheobronchial stenting, endobronchial electrocautery, bronchoscopic cryotherapy and other techniques. Special situations, such as tracheoesophageal fistula and mediastinal masses, are also considered.