Update on options for treatment of metastatic castration-resistant prostate cancer

Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA) testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC), the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16) in CRPC, several newer cytotoxic drugs (epothilones, satraplatin), targeted agents (abiraterone, MDV3100) and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cell

AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral Therapy

In economically developed countries, AIDS-related lymphoma (ARL) accounts for a large proportion of malignances in HIV-infected individuals. Since the introduction of highly active anti-retroviral therapy (HAART) in 1996, epidemiology and prognosis of ARL have changed. While there is a slight increase in the incidence of Hodgkin's lymphoma in HIV-infected individuals, use of HAART has contributed to a decline in the incidence of non-Hodgkin's lymphoma (NHL) and also a decrease in the overall incidence of ARL. Strategies that employ HAART, improved supportive care, and the use of Rituximab with multi-agent chemotherapy have contributed to improved rates of complete remission and survival of patients with ARL that rival those seen in stage and histology matched HIV negative NHL patients. Most recent clinical trials demonstrate better outcomes with the use of rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center origin) is associated with lymphoma-specific outcomes in the setting of AIDS-related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT) and autologous stem cell rescue (ASCT) can be effective for a subset of patients with relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in the setting of ARL relapse. Clinical trials investigating the role of allogeneic hematopoietic stem cell transplant in ARL are currently underway

SSI ANALYSIS OF TALL CHIMNEYS WITH ANNULAR RAFT CONSIDERING VARIABLE SOIL PROFILE

SSI analysis of a 200m reinforced concrete chimney with annular raft foundation under along-wind load is carried out in the present study. To study the effect of geometrical properties of chimney, different ratios of height to base diameter(slenderness ratio) are selected. The ratio of outer diameter to thickness of raft were also varied. To understand the effect of flexibility of soil, variable soil profile is considered below the foundation. Three different soil layers were considered below the foundation.Along-wind loads are calculated as per IS:4998-1992. Three dimensional analysis of chimney was carried out using ANSYS software. Lateral tip deflection in chimney and the settlement in raft were obtained in the analysis. The results show that the responses in chimney are affected by the flexibility of soil, slenderness ratio of chimney and thickness of raft

Formulation and Evaluation of Chitosan Based Hydrogel Matrix of Licorice for Targeting Helicobacter Pylori

In present investigation an attempt has been made to formulate and evaluate chitosan based hydrogel of matrix of Licorice for targeting Helicobacter pylori. Licorice was evaluated for its physical characteristics, analytical profiles and drug polymer compatibility study. The prepared Hydrogel granules were evaluated for pre formulation characteristics like Angle of repose, Bulk density, Tapped density and Carr’s index. The results obtained were found to be satisfactory and within the specified limits. A Stomach retentive licorice loaded chitosan hydrogel was prepared successfully by chemical crosslinking method. Glutaraldehyde was used as chemical crosslinking agent. After compression parameters like Thickness, Hardness, Weight variation, Friability, content uniformity and In-Vitro release studies were evaluated. Mucoadhesive study showed that, licorice loaded hydrogel have good mucoadhesion property and retained in gastric environment tof stomach for prolonged period of time. The results of In-vitro studies showed that by chitosan concentration the extent of swelling and rate of drug release can be modulated. In the present study the effect of concentration of polymer are studied through In-Vitro drug release. It shows that increase in concentration of polymer leads to the controlled drug release from hydrophilic chitosan hydrogelfor12 hrs, which means release rate from hydrophilic chitosan hydrogel depends on type and concentration of polymer used in the formulation. Hydrogel formulation (F5), containing chitosan and Crosslinking agent of Glutaraldehyde is probably showing release upto 96.2±0.65% within 12 hrs. The hydrogel prepared maintain drug concentration in stomach for prolonged period of time, can be used as a drug delivery system for treatment of H. pylori infection and in management of peptic ulcer. According to stability study it was found that there was no significant change in average weight, drug content and in vitro dissolution of optimized formulation (F5). This can be expected to reduced the frequency of administration and decrease the dose dependent side effects. The efficacy and safety of Licorice hydrogel dosage form are expected to offer optimum therapeutic efficacy and improved patient compliance

All-Trans Retinoic Acid-Induced Pseudotumor Cerebri during Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review

All-trans retinoic acid (ATRA), a derivative of vitamin A, is an essential component in the treatment of acute promyelocytic leukemia (APL). Though considered to be a relatively safe drug, use of ATRA can lead to several side effects such as retinoic acid syndrome and pseudotumor cerebri (PC). PC is a rare disorder characterized by neurologic and ocular signs and symptoms of increased intracranial pressure, but with normal cerebrospinal fluid composition and normal brain imaging. Most of the previous studies suggest that PC, as a complication of ATRA therapy, occurs predominantly in the pediatric age group. Herein, we report a rare case of ATRA-induced PC in a 38-year-old woman undergoing induction treatment for APL. Symptoms improved with discontinuation of ATRA and treatment with acetazolamide. Concomitant administration of medications such as triazole antifungals which influence the cytochrome P-450 system can exacerbate this potential complication of ATRA. In this paper, we also review the current literature, provide a descriptive analysis of clinical features, and discuss the principles of management of ATRA-induced PC

COVID-19 Vaccination-Associated Spontaneous Heparin-Induced Thrombocytopenia Syndrome

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has emerged as the deadliest outbreak in recent American history, surpassing the estimated U.S. fatalities from the 1918 influenza pandemic. Since its identification in December 2019 in Wuhan, China, COVID-19 has contributed to the death of nearly six million people worldwide. The United States (U.S.) Food and Drug Administration (FDA) initially issued emergency use authorization for three vaccines for prevention of COVID-19, and currently two have received full FDA approval. Herein, we report a case of severe thrombocytopenia in a man following heterologous booster vaccination with the Pfizer-BioNTech COVID-19 vaccine with concomitant presence of a heparin-P4 antibody but without proximate heparin exposure. The degree of thrombocytopenia was severe, but the patient had a natural recovery of platelet count over the next 2 weeks without need for any immunomodulatory therapies. This is the first case report of COVID vaccine-associated heparin-induced thrombocytopenia (HIT)-like platelet disorder without proximate heparin exposure, also called spontaneous HIT syndrome. Keywords: Thrombocytopenia, Co