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Jason K Panchamia, Carmelina Gurrieri, Adam W Amundson Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Jason K PanchamiaDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USATel +1 507-284-9698Fax + 1 507-284-0120Email Panchamia.Jason@mayo.eduBackground: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease primarily affecting the upper and lower motor neurons. Patients present with a variety of clinical manifestations inevitably resulting in death secondary to respiratory insufficiency from muscle weakness and consequential pulmonary complications. Despite the lack of universal consensus on the ideal anesthetic approach to amyotrophic lateral sclerosis patients undergoing lower extremity total joint surgery, there are few noteworthy anesthetic considerations in this cohort.Case Report: A 75-year-old male with multiple medical comorbidities, including a recent diagnosis of amyotrophic lateral sclerosis, presented to a large academic medical center for a right total hip arthroplasty revision. The patient’s preoperative neurologic examination demonstrated brisk deep tendon reflexes, visible fasciculations of lower extremities, and motor weakness of upper and lower extremities. Serology demonstrated an elevated creatine kinase, and an electromyography study showed active denervation in the cervical, thoracic, and lumbosacral regions. After a careful risk-benefit analysis was performed, involving a multidisciplinary team approach, the patient successfully underwent the surgical procedure with a spinal anesthetic and minimal sedation. Perioperative course was unremarkable, and there were no neurologic complications in the first 6 months after surgery.Conclusion: Patients with amyotrophic lateral sclerosis present unique challenges for anesthesia providers. General anesthesia may potentially worsen respiratory function; therefore, alternative methods to avoiding airway manipulation should be considered. Conversely, regional techniques may carry the risk of exacerbating pre-existing neurologic symptoms. Currently, no definite guidelines exist on the perioperative anesthetic management of amyotrophic lateral sclerosis patients; ultimately, the decision to perform regional anesthesia should be based on analyzing a patient’s risk against the potential benefits.Keywords: arthroplasty, replacement, anesthesia, spinal, neurodegenerative diseases, risk assessment

Abstract: Hemorrhoidal disease is a frequent cause of morbidity among the general population with a reported incidence of 4.4%, but little is known about its incidence and clinical features in kidney transplant recipients. Among 116 patients who had undergone kidney transplantation and were evaluated for hemorrhoidal disease, 82 had no hemorrhoids (70.6%), 28 (24%) had grade I hemorrhoids, and 6 (5.4%) had grade II hemorrhoids at the pretransplantation evaluation. Twenty-seven out of 116 recipients (22.4%) developed grade III or IV hemorrhoids after transplantation and underwent surgery. Hemorrhoidal disease was more frequent in patients with a pretransplantation history of hemorrhoids, with a rapid weight increase in the posttransplantation period, or who were aged between 30 and 50 years. Immunosuppressive therapy may play an important role in the worsening of hemorrhoidal disease among kidney transplant recipients. A prompt diagnosis and surgical treatment, whenever necessary, is mandatory for patients with clinical signs of worsening of hemorrhoids. [Copyright &y& Elsevier]

Abstract Background Glycogen Synthase Kinase-3 (GSK-3) α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM). Methods GSK-3 α and β expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis. Results GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. Conclusions These data suggest that in MM cells GSK-3α and β i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors.