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Two letters to the editor are presented in response to an interview with Katherine Murphy, the actress who plays the transgender female character Nuala in the controversial TV sitcom "The Center" aired by the Irish national radio and television broadcaster Raidió Teilfís Éireann (RTE), published in Issue 295 of "Gay Community News," and another letter commending the organizers of the Gold Tea Party, held after the Dublin Pride Parade on June 28, 2014.

Accumulation of iron in the heart leads to myocardial dysfunction and in severe cases heart failure. Myocardial hemosiderosis occurs in many hematological diseases treated with blood transfusions, including sickle cell anemia (SCA) and beta thalassemia (β-thal). MRI T2* can quantify myocardial iron non-invasively and can be compared to functional studies (e.g., echocardiography). Multiple MRI readers can introduce variation in the measurement. We investigated the relationship of myocardial MRI T2* with echo measurements of both systolic and diastolic function, and the variability introduced by different MRI reviewers. Patients were selected if they received ≥ 18 transfusions, or had a serum ferritin ≥ 1000 ng/mL. Study participants underwent 1.5 Tesla MRI T2* and echocardiography testing within 30 days. Echo measurements included left ventricular ejection fraction (LVEF), mitral annular tissue Doppler (TDV) e' velocity (a measure of LV diastolic function), left ventricular myocardial performance index (a measure of both systolic and diastolic function - LVMPI), and left ventricular mass index (LVMI). Regions of interest (ROI) were drawn in a homogeneous area of the intraventricular septum. Three independent reviewers, blinded to the patients' clinical status and the other 2 reviewers' results, performed the ROI analysis. Agreement among the 3 raters was assessed using interclass correlation coefficient (ICC). Echo findings were associated with heart T2* both as continuous and categorical (normal vs abnormal) variables. Forty-seven patients, median age 14 years (range 7 – 37), participated; 24 (51.1%) were female. Thirty-five (74.5%) had SCA, 8 (17%) had β-thal (major or intermedia), and 4 (8.5%) had bone marrow failure syndromes. Mean (±1SD) echo results were LVEF (±5.8) %, LVMI 86 (±20.4) g/m2, LVMPI 0.3 (±0.1), and TDV e' velocity 16.2 (±3.4) cm/sec. Only one patient had low LVEF, but 8 (17%) had high LVMPI and 20 (42%) had low TDV e' velocity. All patients had normal LVMI. The mean myocardium T2* ranged among the 3 reviewers from 27 to 33 (±6.9 to 8.7) msec. Agreement among the 3 raters had an ICC = 0.64. Median T2* values were significantly lower among patients with lower LVMI (32 versus 42 msec, p= 0.019). No other comparisons among echo and T2* results were significant. Median echo findings were compared with T2* values above and below 20 msec: lower LVMI (71 vs 89 g/m2, p=0.04), and higher LVMPI (0.48 versus 0.28, p=0.015) were found among patients with T2* < 20 msec. Mean serum ferritin was 2917 (±2239) ng/mL. Serum ferritin was significantly negatively associated with T2* values (ρ=−0.33, p=0.031). We conclude:

Iron overload is an inevitable consequence of multiple transfusions and occurs in many hematological diseases including sickle cell anemia (SCA) and beta thalassemia (β-thal). Liver biopsy provides quantification of iron content in the liver, but is not without risks such as bleeding, pain, and infection. MRI R2* has the advantage of quantifying liver iron without the risks of invasive procedures, however, this technique has not been fully investigated or validated. Furthermore, the variability introduced by multiple MRI readers has not been investigated to date. Patients with hematological diseases were selected to participate in this prospective IRB-approved study if they received ≥ 18 transfusions or had a serum ferritin ≥ 1000 ng/mL. All study participants completed 1.5 Tesla MRI R2* testing (Siemens Symphony), serum ferritin, and liver biopsy with quantification of liver iron content (LIC) within 30 days. Regions of interest (ROI) were drawn on R2* maps in a homogeneous area of the right hepatic lobe, avoiding blood vessels and obvious bile ducts. Three independent reviewers, blinded to the patients' clinical status and the other 2 reviewers' results, performed the ROI analysis. The correlation between LIC and liver R2* was calculated using the Spearman's Rank-Order Correlation Coefficient. Due to possible outliers in the data, robust simple linear regression methods were used to fit a regression line to scatter plots. All liver biopsy samples were sent to Mayo Laboratories for LIC quantification. The agreement among the 3 raters was assessed using the interclass correlation coefficient (ICC). Forty-seven patients, median age 14 years (range 7 – 37) participated; 24 were female. Thirty-five of them had SCA, 8 had β-thal (major or intermedia), and 4 had bone marrow failure syndromes. Total table time for R2* MRI testing was between 20 to 30 minutes. All patients tolerated the liver biopsy without complications. The mean (±1SD) ferritin was 2917ng/mL (±2239), mean LIC was 12.139 mg/ 100g of dry weight liver (±8.269), and mean liver R2* ranged from 425 to 432 Hz (±257 to 249 Hz). All 3 raters produced R2* values strongly associated with LIC, with correlation coefficients from 0.93 to 0.95 (p<0.00005). There was a significant positive association between serum ferritin and R2* liver values (correlation among the 3 reviewers ranged from 0.39 to 0.50 with all p<0.009). The agreement among the 3 raters was 0.98. To summarize: 1) 1.5 T MRI R2* liver values are highly associated with LIC in patients with iron overload. This is the largest sample of MRI R2* liver measurements correlated with LIC obtained by liver biopsy; 2) The three raters had excellent agreement which suggests that, in our study, R2* liver values do not differ greatly among qualified readers; 3) R2* measurements of the liver were significantly associated with serum ferritin, however, the correlation coefficients were relatively low (0.39 to 0.50), documenting a weak relationship; and 4) MRI R2* of the liver is a feasible and valid technique to assess LIC non-invasively, and appears to be reproducible when performed by qualified reviewers. We conclude that liver MRI R2* can be incorporated into clinical research protocols for safe, painless, and accurate liver iron quantitation.

Several letters to the editor are presented in response to several issues on GLBT people, including one on the celebration of the 25th anniversary of the Border Area Group (BAG), another on gay abuses and yet another on a study on personal development of gays.

A phase I study to determine safety, maximum tolerated dose, and biologic response during multiple once-a-week administration of oral imiquimod, an immune response modifier, was conducted in 12 adults with early human immunodeficiency virus (HIV) infection. All completed the dose-escalation phase of weekly dosing at 100-mg increments and received at least one maintenance dose, 100 mg below the patient's toxic dose, for 12 weeks. Dose-limiting toxicity occurred in 3 patients at 200-mg, 5 at 300-mg, and 3 at 400-mg dose levels. One tolerated the 500-mg dose without dose-limiting toxicity. Dose-limiting toxicities included fatigue, fever, malaise, increased transaminases, hypotension, vomiting, and depression. Seven of 12 completed 12 weeks of maintenance. At 200 mg of imiquimod, all patients had biologic responses, measured by elevations in serum interferon, β2-microglobulin, and neopterin levels. Imiquimod induced pronounced levels of circulating interferon in asymptomatic HIV-infected persons, with variable effect on virus load.