Perioperative benefit and outcome of thoracic epidural in esophageal surgery: a clinical review.

Surgery for esophageal cancer is a highly stressful and painful procedure, and a significant amount of analgesics may be required to eliminate perioperative pain and blunt the stress response to surgery. Proper management of postoperative pain has invariably been shown to reduce the incidence of postoperative complications and accelerate recovery. Neuraxial analgesic techniques after major thoracic and upper abdominal surgery have long been established to reduce respiratory, cardiovascular, metabolic, inflammatory, and neurohormonal complications.The aim of this review is to evaluate and discuss the relevant clinical benefits and outcome, as well as the possibilities and limits of thoracic epidural anesthesia/analgesia (TEA) in the setting of esophageal resections. A comprehensive search of original articles was conducted investigating relevant literature on MEDLINE, Cochrane reviews, Google Scholar, PubMed, and EMBASE from 1985 to July2017. The relationship between TEA and important endpoints such as the quality of postoperative pain control, postoperative respiratory complications, surgical stress-induced immunosuppression, the overall postoperative morbidity, length of hospital stay, and major outcomes has been explored and reported. TEA has proven to enable patients to mobilize faster, cooperate comfortably with respiratory physiotherapists and achieve satisfactory postoperative lung functions more rapidly. The superior analgesia provided by thoracic epidurals compared to that from parenteral opioids may decrease the incidence of ineffective cough, atelectasis and pulmonary infections, while the associated sympathetic block has been shown to enhance bowel blood flow, prevent reductions in gastric conduit perfusion, and reduce the duration of ileus. Epidural anesthesia/analgesia is still commonly used for major 'open' esophageal surgery, and the recognized advantages in this setting are soundly established, in particular as regards the early recovery from anesthesia, the quality of postoperative pain control, and the significantly shorter duration of postoperative mechanical ventilation. However, this technique requires specific technical skills for an optimal conduction and is not devoid of risks, complications, and failures.

Posterior reversible encephalopathy syndrome in the Intensive Care Unit after liver transplant: a comparison of our experience with the existing literature.

Posterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by altered mental status, seizures, headache, vomiting and visual disturbances, most often described after transplantation and immunosuppressive therapy. PRES is commonly first diagnosed by the neuroradiologist, rather than the clinician, as it is characterized by very typical magnetic resonance imaging (MRI) features, i.e., hyperintense lesions in the territories of the posterior cerebral artery. Here we report our experience in the Intensive Care Unit (ICU) with a case of tacrolimus-related PRES after liver transplant, presenting with sudden neurological deterioration and diffuse and massive hyperintensities upon brain MRI. Discontinuation of tacrolimus, as prompted by the established literature, permitted the patient to eliminate tacrolimus-associated toxicity, whereas its substitution with everolimus and mycofenolic acid allowed the maintenance of immunosuppression while avoiding acute organ rejection and reducing the dosage of corticosteroids. The lowering of blood pressure with drugs reported in the literature for use in PRES proved to be effective but challenging, requiring the use of multiple drugs and only slowly leading to proper control of hypertensive peaks. Nonetheless, hypertension management and supportive therapy allowed for a complete neurological restitutio ad integrum of the patient. In conclusion, tacrolimus-related brain adverse events need to be promptly recognized, especially during the first months after transplantation. When tacrolimus-related PRES occurs, immunosuppressive therapy may be safely and efficiently switched to everolimus and mycofenolic acid. This strategy may help not only to avoid acute organ rejection but also to reduce the dosage of corticosteroids, which might interfere with proper control of hypertension.

Progress in elucidating the structural and dynamic character of G Protein-Coupled Receptor oligomers for use in drug discovery.

G Protein-Coupled Receptors (GPCRs) are the most targeted group of proteins for the development of therapeutic drugs. Until the last decade, structural information about this family of membrane proteins was relatively scarce, and their mechanisms of ligand binding and signal transduction were modeled on the assumption that GPCRs existed and functioned as monomeric entities. New crystal structures of native and engineered GPCRs, together with important biochemical and biophysical data that reveal structural details of the activation mechanism(s) of this receptor family, provide a valuable framework to improve dynamic molecular models of GPCRs with the ultimate goal of elucidating their allostery and functional selectivity. Since the dynamic movements of single GPCR protomers are likely to be affected by the presence of neighboring interacting subunits, oligomeric arrangements should be taken into account to improve the predictive ability of computer-assisted structural models of GPCRs for effective use in drug design.

Helicopter rescue and prehospital care for drowning children: two summer season case studies.

BACKGROUND: Drowning is the second leading cause of unintentional injury-related death in children <14 years of age and is one of the most important causes of accidental injury between the ages of 1 and 4 years. In this study, the characteristics of non-fatal unintentional drownings in a small series of pediatric victims were examined. METHODS: We retrospectively analyzed data collected by the rescue team from May to October in two consecutive years (2006, 2007). RESULTS: Nine accidents occurred in public waters, while 5 occurred in lakes and rivers. The submersion time reported ranged from approximately 5 to 15 min. The ground emergency service with basic life support rescue experts intervened within a mean of 12 min. Advanced cardiac life support maneuvers were implemented by the helicopter medical crew for all victims. Ten of the 14 children remained in cardiocirculatory arrest despite cardiopulmonary resuscitation (CPR). The Glasgow Coma Scale (GCS) was <8 in all cases. Field resuscitation ultimately proved successful for every child. Thus, none was transported by the helicopter with ongoing CPR. All submersion-injured children survived. No postanoxic cerebral injury or major neurological complications were detected. CONCLUSION: Assuring safe tracheal ventilation, achieving intravenous access, and stabilizing both respiratory and hemodynamic disturbances on the ground before transferring the patient are the keys to out-of-hospital management. Our 100% survival rate likely results from adequate primary out of-hospital care. Promptly dispatching a helicopter with a specialized medical crew is very expensive, but is worth the cost because it offers a better chance of survival.

Activated recombinant protein C in septic shock early after liver transplantation: a case report.

Severe infectious diseases after liver transplant are associated with high risk of multiorgan failure and mortality. Septic shock is difficult to manage in this setting since it is often unresponsive to conventional aggressive therapy. Adjuvant therapies have been proposed in association with full combination treatment to sustain the failing organs and improve outcomes in severe sepsis. Recombinant human activated protein C drotrecogin alfa, Xigris) has been occasionally administered to treat posttransplant sepsis to modulate and downregulate the complex network of inflammatory and coagulopathic processes. Herein we have reported on a patient who was given drotrecogin alfa 15 days following liver transplant for acute septic shock originating from a nosocomially acquired pneumonia. Recombinant activated drotrecogin alfa, associated with conventional aggressive treatment, was efficacious to revert the life-threatening "slippery slope" of vasoplegia and uncontrolled diffuse inflammation.

In silico binding free energy predictability by using the linear interaction energy (LIE) method: bromobenzimidazole CK2 inhibitors as a case study.

Protein kinase CK2 is essential for cell viability, and its control regards a broad series of cellular events such as gene expression, RNA, and protein synthesis. Evidence of its involvement in tumor development and viral replication indicates CK2 as a potential target of antineoplastic and antiviral drugs. In this study the Linear Interaction Energy (LIE) Method with the Surface Generalized Born (SGB) continuum solvation model was used to study several bromobenzimidazole CK2 inhibitors. This methodology, developed by Aqvist, finds a plausible compromise between accuracy and computational speed in evaluating binding free energy (DeltaGbind) values. In this study, two different free binding energy models, named "CK2scoreA" and "CK2scoreB", were developed using 22 inhibitors as the training set in a stepwise approach useful to appropriately select both the tautomeric form and the starting binding position of each inhibitor. Both models are statistically acceptable. Indeed, the better one is characterized by a correlation coefficient (r2) of 0.81, and the predictive accuracy was 0.65 kcal/mol. The corresponding validation, using an external test set of 16 analogs, showed a correlation coefficient (q2) of 0.68 and a prediction root-mean-square error of 0.78 kcal/mol. In this case, the LIE approach has been proved to be an efficient methodology to rationalize the difference of activity, the key interactions, and the different possible binding modes of this specific class of potent CK2 inhibitors.