Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms.

CFI-400945 is a selective oral polo-like kinase 4 (PLK4) inhibitor that regulates centriole duplication. PLK4 is aberrantly expressed in patients with acute myeloid leukemia (AML). Preclinical studies indicate that CFI-400945 has potent in vivo efficacy in hematological malignancies and xenograft models, with activity in cells harboring TP53 mutations.

Magnetic Resonance Imaging (MRI) Analysis of Tissue Sodium Concentration in Chronic Kidney Disease.

Human body sodium is regulated by the kidneys and extrarenal mechanisms. Stored skin and muscle tissue sodium accumulation is associated with kidney function decline, hypertension, and a pro-inflammatory and cardiovascular disease profile. In this chapter, we describe the use of sodium-hydrogen magnetic resonance imaging (Na/H MRI) to dynamically quantify tissue sodium concentration in the lower limb of humans.

Skin regulation of salt and blood pressure and potential clinical implications.

Sodium chloride, as salt, gives rise to hypertension. Nevertheless, individual susceptibility to the ramifications of sodium chloride is heterogeneous. The conventional nephron-centric regulation of sodium with neurohormonal inputs and responses is now expanded to include an intricate extrarenal pathway including the endothelium, skin, lymphatics, and immune cells.

Total Body Sodium Balance in Chronic Kidney Disease.

Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium.

Magnetic resonance imaging determination of tissue sodium in patients with chronic kidney disease.

Excess sodium is a major modifiable contributor to hypertension and cardiovascular risk. Knowledge of sodium storage and metabolism has derived mainly from indirect measurements of dietary sodium intake and urinary sodium excretion, however both attempt to measure body sodium and fluid in a two-compartment model of intracellular and extracellular spaces. Our understanding of total body sodium has recently included a storage pool in tissues.

Prolonged immunosuppression does not improve risk of sensitization or likelihood of retransplantation after kidney transplant graft failure.

The optimum approach towards immunosuppression withdrawal following kidney transplant failure is unclear. Prolonged weaning may be associated with reduced sensitization, less graft nephrectomy and greater likelihood of retransplantation, but conversely increased risk of infection, malignancy and death. We conducted a single-centre retrospective analysis of patients experiencing graft failure between 2007 and 2017, comparing rates of sensitization, retransplantation, nephrectomy, infection, malignancy and death between patients who had immunosuppression weaned over <90 vs.

Maternity connect: Evaluation of an education program for rural midwives and nurses.

Background: Rural and regional health services often find it difficult to maintain their maternity service and skills of their maternity workforce and enable women to give birth close to home. The Maternity Connect Program is a professional development initiative aimed at supporting and upskilling rural and regional maternity workforces to meet their maternity population care needs.

Aim: To evaluate the Maternity Connect Program from the perspectives and experiences of participating midwives/nurses and health services.

Colonic mucosa-associated lymphoid tissue in a renal transplant recipient: a case report.

Background: Extra-gastric (particularly colonic) lymphoma of mucosa-associated lymphoid tissue in the immunosuppressed solid organ transplant recipient is rare. We report a case of low-volume mucosa-associated lymphoid tissue lymphoma with colonic and bone marrow involvement in a renal transplant recipient that has been managed conservatively.

Case Presentation: A 62-year-old Caucasian man, 14 years after kidney transplantation, was diagnosed as having extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue with bone marrow and colonic involvement, after a colonoscopy identified mucosa-associated lymphoid tissue lymphoma in a sessile sigmoid polyp following surveillance fecal occult blood testing that returned a positive result.

Clinical Outcomes and Risk Factors for Tunneled Hemodialysis Catheter-Related Bloodstream Infections.

Diabetes and left internal jugular vein insertion site were significantly associated with increased risk of a catheter-related bloodstream infection from a tunneled hemodialysis catheter. Ex-smoker status was significantly associated with reduced risk.

Cocaine-associated atypical haemolytic uraemic syndrome in a genetically susceptible individual.

Atypical haemolytic uraemic syndrome (aHUS) is a severe, life-threatening condition that requires early recognition and urgent treatment. In aHUS rare genetic variants in CFH, CFI, CD46, C3 and CFB predispose to complement over activation. This case describes a case of aHUS in which there was a strong temporal association between disease onset and the use of smoked cocaine.

Eculizumab therapy in gemcitabine-induced thrombotic microangiopathy in a renal transplant recipient.

A renal transplant recipient 7 years post-transplantation, diagnosed with locally advanced pancreatic adenocarcinoma developed thrombotic microangiopathy (TMA) after treatment with gemcitabine and nab-paclitaxel. Gemcitabine was the most likely cause for TMA and was ceased. He received methylprednisolone and plasma exchange with fresh frozen plasma and albumin.

Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss.

p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult.