Adding Blood to Agitated Saline Significantly Improves Detection of Right-to-Left Shunt by Contrast-Transcranial Color-Coded Duplex Sonography

Contrast-transcranial Doppler and contrast-transcranial color-coded duplex sonography (c-TCCD) have been reported to have high sensitivity in detecting patent foramen ovale as compared with transesophageal echocardiography. An international consensus meeting (Jauss and Zanette 2000) recommended that the contrast agent for right-to left-shunt (RLS) detection using contrast-transcranial Doppler be prepared by mixing 9 mL of isotonic saline solution and 1 mL of air. The aim of our study was to determine whether adding blood to the contrast agent results in improved detection of RLS. We enrolled all consecutive patients admitted to our neurosonology laboratory for RLS diagnosis. For each patient, we performed c-TCCD both at rest and during the Valsalva maneuver using two different contrast agents: ANSs (1 mL of air mixed with 9 mL of normal saline) and ANSHBs (1 mL of air mixed with 8 mL of normal saline and 1 mL of the patient's blood). To classify RLS, we used a four-level visual categorization: (i) no occurrence of micro-embolic signals; (ii) grade I, 1–10 signals; (iii) grade II, >10 signals but no curtain; grade III, curtain pattern. We included 80 patients, 33 men and 47 women. RLS was detected in 18.8% at rest and in 35% during the Valsalva maneuver using ANSs, and in 31.3% and in 46.3% using ANSHBs, respectively (p < 0.0001). There was a statistically significant increase in the number of micro-embolic signals with the use of ANSHBs. The use of blood mixed with saline solution and air as a c-TCCD contrast agent produced an increase in positive tests and a higher grade of RLS compared with normal saline and air alone, either with or without the Valsalva maneuver.     

Androgen and oestrogen receptors as potential prognostic markers for patients with ductal carcinoma in situ treated with surgery and radiotherapy

Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has been investigated less extensively than invasive breast cancer. Women with DCIS are mainly treated with conservative surgery almost exclusively followed by radiotherapy. However, as radiation treatment is not always effective, the search for biomarkers capable of identifying DCIS lesions that could progress to invasive cancer is ongoing. Although conventional biomarkers have been thoroughly studied in invasive tumours, little is known about the role played by androgen receptor (AR), widely expressed in DCIS. A series of 42 DCIS patients treated with quadrantectomy and radiotherapy were followed for a period of up to 95 months. Of these, 11 had recurrent DCIS or progressed to invasive cancer. All tumours were analysed for clinical pathological features. Conventional biomarkers and androgen receptor expression were determined by immunohistochemistry. Our results showed that AR was higher in tumours of relapsed patients than non‐relapsed patients (P value: 0.0005). Conversely, oestrogen receptor (ER) was higher, albeit not significantly, in non‐relapsed patients than in relapsed patients. AR/ER ratio was considerably different in the two subgroups (P value: 0.0033). Area under the curve (AUC) values were 0.85 for AR and 0.80 for the AR/ER ratio. These preliminary results highlight the potentially important role of both AR and the AR/ER ratio as prognostic markers in DCIS.     

Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia

In β-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by β-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle–promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X_L. The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.