Therapeutic advances in hormone-dependent cancers: focus on prostate, breast and ovarian cancers

Hormonal cancers affect over 400,000 men and women and contribute collectively to over 100,000 deaths in the United States alone. Thanks to advances in the understanding of these cancers at the molecular level and to the discovery of several disease-modifying therapeutics, the last decade has seen a plateauing or even a decreasing trend in the number of deaths from these cancers. These advanced therapeutics not only effectively slow the growth of hormonal cancers, but also provide an insight on how these cancers become refractory and evolve as an altogether distinct subset. This review summarizes the current therapeutic trends in hormonal cancers, with focus on prostate, breast and ovarian cancers. The review discusses the clinical drugs being used now, promising molecules that are going through various stages of development and makes some predictions on how the therapeutic landscape will shift in the next decade

Snakebite Induced Thrombotic Microangiopathy Leading to Renal Cortical Necrosis

Renal complications from snakebite result in high mortality and morbidity. Acute kidney injury (AKI) occurs in 5–30% of cases. Renal manifestation could include acute tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. We present a case of thrombotic microangiopathy (TMA) resulting in renal cortical necrosis. Renal biopsy showed fibrin thrombi in glomeruli and arterioles with cortical necrosis. Our patient progressed to end-stage renal disease

Stenotrophomonas maltophilia: A Case Series and Review for an Uncommon Cause of Peritoneal Dialysis-Associated Infection

Peritonitis is a common and potentially serious complication of peritoneal dialysis (PD). Common organisms include Staphylococcus Aureus, enterococci, and coagulase-negative staphylococcus. However, Stenotrophomonas maltophilia (S. maltophilia) is an uncommon cause of PD-related infection. We describe a series of three cases of S. maltophilia PD infection (two cases of PD peritonitis and one case of PD exit-site infection) that were identified over a seven-week period in a single centre. The cases were treated with antibiotics (the primary antibiotic being co-trimoxazole) for a mean duration of 30 ± 7.9 days. All of the patients required PD catheter removal due to treatment failure with antibiotics. Hospital admission was required in two of the cases and one case resulted in mortality, with the cause of death directly associated with complications from S. maltophilia infection. A multi-disciplinary team using root-cause analysis did not identify a common link between our cases but highlighted possible risk factors contributing to these presentations. Given the relative rarity of S. maltophilia, evidence on its management options remains limited. In this article, we draw upon our own experiences and examine the literature available from previously published case reports and series. These reports highlight S. maltophilia as a complex and challenging organism to treat. Our experience demonstrated the importance of early PD catheter removal in S. maltophilia PD infection, as this is likely more effective than prolonged antibiotic therapy and hence a safer management option, considering the resistant nature of S. maltophilia

Pruritus in Chronic Kidney Disease: An Update

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP

Long-Term Therapeutic Plasma Exchange to Prevent End-Stage Kidney Disease in Adult Severe Resistant Henoch-Schonlein Purpura Nephritis

A 27-year-old man presented with a palpable purpuric skin rash and joint and abdominal pain in April 2010. He had acute kidney injury and his creatinine quickly deteriorated to 687 μmol/L, with associated nephrotic range proteinuria. Kidney biopsy showed crescentic Henoch-Schonlein nephritis. He was treated with intravenous cyclophosphamide and prednisolone despite which his renal function deteriorated; he required haemodialysis for a short duration and seven sessions of therapeutic plasma exchange (TPE). Renal function improved, but after discharge from hospital he suffered 2 further relapses, each with AKI, in 4 months. Cyclophosphamide was not effective and therefore Rituximab was introduced. He initially had a partial response but his renal function deteriorated despite continued therapy. TPE was the only treatment that prevented rapid renal functional deterioration. A novel long-term treatment strategy involving regular TPE every one to two weeks was initiated. This helped to slow his progression to end-stage kidney disease over a 3-year period and to prolong the need for renal replacement therapy over this time