Nutraceuticals for Prevention of Chemotherapy-Induced Peripheral Neuropathy

A wide range of neurologic complications, including central neurotoxicity conditions and peripheral neurotoxicity, are associated with antineoplastic drug regimens. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and severe cancer treatment-related adverse effect, as well as the most diffuse type of neurotoxicity, because about one third of all patients who undergo chemotherapy may experience this side effect. CIPN can negatively impact the long-term quality of life of cancer survivors, and can lead to dose reduction of the chemotherapy agent, or possible cessation of treatment. Unfortunately, although several agents and protocols have been proposed, no prophylactic strategies have proven useful yet. Therefore, new alternative therapies have been considered for CIPN prevention. In this chapter, the authors analyze the potential applications of nutrients, dietary supplements and herbal products, such as single herbs, the Kampo medicine goshajinkigan and other herbal combinations, for CIPN prevention.

Application of the Athlete Biological Passport approach to the detection of growth hormone doping

Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective Test the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Design IGF-1 and P-III-NP distributions were obtained from 7 years of anti-doping data and applied as priors to analyse individual profiles from an hGH administration study in recreational athletes. Setting Academic and anti-doping laboratories. Elite (n=11,455) and recreational athletes (n=35). Intervention(s) An open-label, randomized, single site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Main Outcome Measure(s) Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. Results An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5-71.4 % across the hGH concentrations tested following 7 days of treatment, peaking at 57.1-100 % after 21 days of treatment, and was maintained between 37.5-71.4 % for the low and high dose groups one week after cessation of treatment. Conclusions These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Efficacy of the new Direct Acting Antiviral drugs in the treatment of Thalassemic HCV patients

Background and Objectives B-thalassemia major patients are susceptible to Hepatitis C Virus (HCV) infection owing to life-long dependency for blood-transfusion. Moreover, this patient population is at risk of progression of liver fibrosis or development of cirrhosis as a consequence of both iron overload and HCV infection. However, patients with haemoglobinopathies and CHC have been excluded from the major clinical trials that led to the approval of DAAs, Hence, at present, limited experience is available regarding the safety and efficacy of DAAs in this population which is traditionally considered difficult to treat. Hence, this study was carried out to evaluate efficacy and safety of the combination regimen of sofosbuvir and daclatasvir for HCV infection in B-thalassemia major patients. Methods This study was conducted on 200 subjects divided into two groups, first group contains150 HCVThalassemic patients while the second group contains 50 HCV only patients. Each group was classified into easy to treat or difficult to treat and received sofosbuvir 400mg + daclatasvir 60mg once/day for the duration of 12 or 24 weeks according to the NCCVH Hepatitis C treatment protocol 2015. Sustained virological response at post-treatment week-12 (SVR-12) was defined as negative HCV-RNA at week-12 post treatment. Results In group (I), successful SVR was achieved in all patients (100%) in subgroup (Ia) while in subgroup (Ib) 12 patients didn’t achieve SVR (15.38%), 4 patients stopped due to side effects(5.13%) and 62 patient achieved SVR (79.49) with overall successful SVR of 134 out of 150 HCV-Thalassemic patients in group (I) (89.33%). in group (II), 2 patients didn’t achieve SVR (5.71%)and 33 patients achieved SVR (94.29%) in subgroup (IIa) while in subgroup (IIb) 2 patients didn’t achieve SVR (13.33%) and 13 patients achieved SVR (86.67%) with overall successful SVR of 46out of 50 HCV only patients in group (II) (92%). few patients suffered from minor side effects that didn’t require cessation of treatment but 4 patients developed major side effects in group (Ib) that required cessation of treatment. There were marked improvement in liver enzymes, Fib4 score, hemoglobin level and transfusion requirements in HCVThalassemic group after treatment. Conclusion A combination of sofosbuvir and daclatasvir is an efficacious and tolerable treatment regimen with negligible side effects for patients with thalassemia major and HCV infection.

Nonsurgical Correction of Cryptotia in Newborn: A Case Report

Objective: To report on the result of nonsurgical correction of deformational auricular anomaly (cryptotia) using moulded silicone as a splint. Methods: Congenital auricular anomalies can be categorized as either malformed or deformational. Cryptotia as a deformational anomaly is defined as an ear having normal chondrocutaneous components with an abnormal architecture; therefore, it can be manipulated digitally into normal shape. Auricular deformation commonly affect the helix and antehelix. Since neonatal auricle is extremely pliable, we used early splinting to correct deformational ear anomalies. These splints are made from silicone, moulded into a small bar and held in place with the Steri-Strips™. The type of the auricular anomaly was documented both clinically and photographically before and two months after the cessation of treatment. Assessment of the result was made by comparing the pre- and post-treatment photograph. Result: In this case report, we applied this method to two newborn with cryptotia and the correction was achieved completely in two months after application of the silicone bar. The parents felt that auricular splinting is worthwhile. Conclusion: Deformational congenital auricular anomaly can be corrected nonsurgically using splinting therapy. The treatment is effective if initiated in the first three months of life. Patients and parents persistence is essential to reach satisfactory outcome. Adherence to treatmenr is crucial to negate the need for surgical treatment of congenital auricular anomalies.

Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature

Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients.Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms “HIV,” “AIDS,” “ritonavir,” “didanosine,” “maculopathy,” “retinopathy,” “visual loss,” and “toxicity” to retrieve the appropriate literature on the subject.Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treatment. Patient 2: A 55-year-old man complained of slowly progressive peripheral visual field constriction for the past 5 years. History disclosed didanosine therapy for 13 years, however, stopped 4 years before the onset of visual symptoms. No alteration of therapy was offered to patient 2 as didanosine therapy was interrupted 9 years previously. Since 2011, 11 cases of ritonavir maculopathy have been reported in the literature. Relentless worsening of vision was reported in 3/7 patients despite cessation of ritonavir therapy. Didonasine peripheral retinopathy was first described in 1992, and a total of 24 patients have been reported since. Relentlessly progressive peripheral retinopathy was diagnosed despite the previous cessation of therapy in 14 patients.Conclusion: Ritonavir causes a slowly progressive atrophic maculopathy, and didanosine toxicity results in a relentlessly progressing peripheral atrophic retinopathy. The relentless progression of both toxic retinopathies reflects permanent alterations of the retinal metabolism by these medications. Both ritonavir and didanosine toxic retinopathies are rare events, but their clinical presentation is highly specific.

The influence of monoclonal antibodies for cancer treatment on the endocrine system

Cancer is one of the main causes of mortality worldwide. Thanks to scientific research, new methods of cancer treatment, including molecularly targeted therapy, are being developed. Monoclonal antibodies are used to treat many diseases, including some types of cancer, and affect various systems of the human body. The presented article aims to present the adverse effects of molecularly targeted cancer therapy on the endocrine system based on the current literature data. Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 or its ligand PD-L1, can cause a variety of autoimmune adverse effects, among others, thyroid dysfunction, hypophysitis, and diabetes mellitus. The authors also paid attention to monitoring selected diagnostic parameters to prevent endocrine adverse effects during a therapy with monoclonal antibodies. The development of adverse effects may sometimes progress atypically and rapidly, and may be a life-threatening condition. Clinicians should choose individual schemes of treatment for particular patients. The patient’s condition should also be monitored before, during and after the therapy. The decision about the continuation of treatment with monoclonal antibodies should be based especially on a risk connected with the cessation of treatment. Clinical trials should be continued to improve knowledge about the side effects of monoclonal antibodies.

Radiotherapy and Its Impact on the Nervous System of Cancer Survivors

Radiotherapy is routinely used for the treatment of nearly all brain tumors, but it may lead to progressive and debilitating impairments of cognitive function. The growing evidence supports the fact that radiation exposure to CNS disrupts diverse cognitive functions including learning, memory, processing speed, attention and executive functions. The present review highlights the types of radiotherapy and the possible mechanisms of cognitive deficits and neurotoxicity following radiotherapy. The review summarizes the articles from Scopus, PubMed, and Web of science search engines. Radiation therapy uses high-powered x-rays, particles, or radioactive seeds to kill cancer cells, with minimal damage to healthy cells. While radiotherapy has yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side effects from the treatment, which can lead to dose reduction or even cessation of treatment. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities; however, neuroinflammation is widely considered as one of the major mechanisms responsible for radiotherapy-induced toxicities. The present study reviews the different types of radiotherapy available for the treatment of various types of cancers and their associated neurological complications. It also summarizes the doses of radiations used in the variety of radiotherapy, and their early and delayed side effects. Special emphasis is given to the effects of various types of radiations or late side effects on cognitive impairments.

STEM-22. TARGETING KIF11 TO RADIOSENSITIZE GLIOBLASTOMA

Glioblastoma (GBM) is the most common primary brain tumor, and is incredibly lethal, with less than 10% of patients surviving more than 5 years after diagnosis. These tumors are routinely treated with radiotherapy, although we and others have shown that there is a subpopulation of GBM cells, called cancer stem-like cells (CSCs), that are radio-resistant, and do not respond to this standard therapy. We aim to overcome the radio-resistance of GBM CSCs by using radiotherapy in combination with a KIF11 inhibitor. We previously reported that the mitotic kinesin KIF11, required for bipolar spindle formation during mitosis, is elevated in GBM and portends poor prognosis. We also demonstrated that invasiveness and self-renewal of CSCs could be targeted with ispinesib, a small molecule inhibitor to KIF11. Furthermore, survival of mice bearing orthotopic glioblastoma was prolonged with KIF11 inhibition, although tumor burden increased with cessation of treatment. To combat tumor recurrence after treatment cessation, we proposed to use a KIF11 inhibitor with radiotherapy. KIF11 inhibitors will arrest cells in G2/M, where they are most sensitive to radiotherapy. By enriching CSCs in G2/M, we hypothesized that we would overcome CSC radio-resistance to decrease CSC viability and improve survival. We first tested the efficacy of combining a KIF11 inhibitor and irradiation in vitro. We found that using combination therapy to treat CSCs significantly decreased CSC survival over vehicle or either treatment used as a monotherapy. We then investigated the effects of combination therapy in vivo. Using a KIF11 inhibitor combined with irradiation increased survival of mice bearing orthotopic glioblastoma. Our results suggest that targeting KIF11 in combination with radiotherapy is a promising technique to overcome the radio-resistance of CSCs, and holds potential to significantly improve treatment outcomes and extend survival of patients with GBM.

Rapid Resolution of Non-Effusive Feline Infectious Peritonitis Uveitis with an Oral Adenosine Nucleoside Analogue and Feline Interferon Omega

This is the first report of a successful treatment of a non-effusive feline infectious peritonitis (FIP) uveitis case using an oral adenosine nucleoside analogue drug and feline interferon omega, and alpha-1 acid glycoprotein (AGP) as an indicator of recovery. A 2-year-old male neutered Norwegian Forest Cat presented with uveitis, keratic precipitates, mesenteric lymphadenopathy and weight loss. The cat was hypergammaglobulinaemic and had a non-regenerative anaemia. Feline coronavirus (FCoV) RNA was detected in a mesenteric lymph node fine-needle aspirate by a reverse-transcriptase polymerase chain reaction—non-effusive FIP was diagnosed. Prednisolone acetate eye drops were administered three times daily for 2 weeks. Oral adenosine nucleoside analogue (Mutian) treatment started. Within 50 days of Mutian treatment, the cat had gained over one kilogram in weight, his globulin level reduced from 77 to 51 g/L and his haematocrit increased from 22 to 35%; his uveitis resolved and his sight improved. Serum AGP level reduced from 3100 to 400 μg/mL (within normal limits). Symmetric dimethylarginine (SDMA) was above normal at 28 μg/dL, reducing to 14 μg/dL on the cessation of treatment; whether the SDMA increase was due to FIP lesions in the kidney or Mutian is unknown. Mutian treatment stopped and low-dose oral recombinant feline interferon omega begun—the cat’s recovery continued.