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ABSTRACTIntroductionAndrogen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality.AimThe current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT.MethodsA PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution.Main Outcome MeasuresReported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported.ResultsADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy.ConclusionsPatients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy.

PurposeThe goal of this work was to detect disease‐related microstructural changes to the liver using magnetic resonance imaging. Chronic liver disease can cause microstructural changes in the liver that reduce plasma access to the perisinusoidal space—the site of exchange between the blood plasma and the hepatic parenchyma. The reduced plasma access to the perisinusoidal space inhibits hepatic function and contributes to the ∼30,000 chronic liver disease‐related deaths per year.MethodsThe extracellular matrix‐specific cationized ferritin magnetic resonance imaging probe was injected intravenously into healthy rats and a rat model of the chronic liver disease non‐alcoholic steatohepatitis. Rats were subsequently imaged with ‐weighted magnetic resonance imaging.ResultsThis work demonstrates that the binding of cationized ferritin to the perisinusoidal extracellular matrix is reduced by 55% in a rat model of non‐alcoholic steatohepatitis compared to healthy controls. This reduced binding is detectable in vivo with magnetic resonance imaging. Immunofluorescence and electron microscopy indicated that the reduced binding is due to inhibited macromolecular access to the perisinusoidal space caused by non‐alcoholic steatohepatitis‐related microstructural changes.ConclusionsThe reduced accumulation of intravenously injected cationized ferritin may report on changes in macromolecular access to the liver parenchyma in chronic liver disease. Magn Reson Med 70:1728–1738, 2013. © 2013 Wiley Periodicals, Inc.

Iron homeostasis is dysregulated in primary myelofibrosis (PMF), given the high prevalence of anemia, need for red blood cell (RBC) transfusions, and disease‐associated inflammatory state. We measured plasma hepcidin levels in 203 consecutive PMF patients at the time of first referral; hepcidin levels were significantly higher as compared to healthy controls ( P < 0.0001), and were correlated with hemoglobin of <10 g/dL, RBC transfusion requirement, serum ferritin of >500 µg/L, higher dynamic international prognostic scoring system (DIPSS)‐plus risk category, the presence of circulating blasts, age of >65 years, and leukocyte count of <4 × 10 9 /L. Increased hepcidin levels predicted for inferior survival independent of six out of the eight DIPSS‐plus prognostic parameters (hazard ratio [HR] = 1.8; P = 0.02), but not when RBC transfusion requirement, hemoglobin of <10 g/dL, or increased serum ferritin were included in the Cox model. Multivariable analysis that considered the four overlapping prognostic variables revealed that increased hepcidin (HR = 1.9; P = 0.03) and increased ferritin (HR = 2.3; P = 0.04), but not hemoglobin of <10 g/dL or RBC transfusion requirement, independently retained their significance for predicting survival. Accordingly, increased levels of both hepcidin and serum ferritin (seen in 29% of patients) predicted inferior survival independent of DIPSS‐plus or increased inflammatory cytokine levels (HR = 2.4; P = 0.002), and could be considered in future prognostic models for PMF. Am. J. Hematol. 88:312–316, 2013. © 2013 Wiley Periodicals, Inc.

Summary Background Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis ( PSC ), but published studies are limited. Aims To investigate the safety and efficacy of oral vancomycin and metronidazole in patients with PSC . Methods Thirty‐five patients with PSC were randomised in a double‐blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase ( ALK ) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects ( AE s). Nonparametric tests were used for analysis. Results The primary endpoint was reached in the low‐dose (−43% change in ALK , P = 0.03) and high‐dose (−40%, P = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low‐dose metronidazole group (−20%, P = 0.03) and trended towards significance in the low‐dose vancomycin group (−33%, P = 0.06). Mayo PSC risk score decreased significantly in the low‐dose vancomycin (−0.55, P = 0.02) and low‐dose metronidazole group (−0.16, P = 0.03). Pruritus decreased significantly in the high‐dose metronidazole group (−3.4, P = 0.03). AE s led to medication discontinuation in six patients, four of whom were receiving metronidazole. Conclusions Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer‐term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis ( clinicaltrials.gov NCT01085760 ).

Background/Aim: Despite existing diagnostic criteria for Charles Bonnet syndrome (CBS), clinical manifestations vary greatly. We examined the clinical course and mortality of patients diagnosed with CBS. Methods: We conducted a retrospective chart review of patients with CBS. We collected demographic and clinical information and medical burden scores. Kaplan-Meier mortality curves were compared using log-rank test. Cox proportional hazard model was used for multivariate analysis and hazard ratio (HR). Mortality was compared to expected mortality from Minnesota population. Results: Seventy-seven patients with CBS had a mean age of 79.5 (standard deviation ± 13.0) and were predominantly Caucasian (97%) and female (73%). In all, 20 (26%) subsequently developed a dementia syndrome, most often Lewy body. A total of 46 (60%) deaths occurred with an average follow-up time of 33.0 months. Characteristics associated with mortality included older age (75-84 [HR 3.34, P = .029], >85 [HR 4.58, P = .007]) and renal disease (HR 3.39 with 95% confidence interval 1.31-8.80, P = .012). Medical burden scores were not associated with overall mortality. Mortality was high compared to Minnesota population ( P < .0001). Conclusions: A large proportion of patients with CBS developed dementia, and there was a high mortality rate associated with older age and renal disease. Medical burden was not associated with mortality.

Guillain-Barré syndrome is an immune-mediated polyneuropathy that frequently presents with progressive muscle weakness. Hyponatremia has recently been described as a feature of this condition, generally appearing over the course of the illness and following the diagnosis of this demyelinating process. We report a case of Guillain-Barré syndrome presenting with severe hyponatremia that is further exacerbated by intravenous immune globulin therapy. Awareness should be raised for consideration of both Guillain-Barré syndrome and its treatment with intravenous immune globulin therapy as the cause of hyponatremia.