Early histological changes of pulmonary arterial hypertension disclosed by invasive cardiopulmonary exercise testing.

Early diagnosis of pulmonary artery hypertension (PAH) is diagnostically challenging given the extent of pulmonary vascular remodeling required to bring about clinical signs and symptoms. Exercise testing can be invaluable in this setting, as stressing the cardiopulmonary system may unmask early disease. This report describes a young patient with a positive family history of PAH in whom contemporaneous invasive cardiopulmonary exercise testing and surgical lung biopsy reveal the novel association between exercise pulmonary hypertension (ePH) and early histological changes of PAH. Exercise PH currently carries no pathological correlates which means the hemodynamic effects of early pulmonary vascular remodeling remain unknown. Following the recent proceedings from the World Symposium in Pulmonary Hypertension 2018, which broaden the hemodynamic definition of PAH, this report suggests an important association between ePH and early pulmonary vascular remodeling supporting a role for exercise hemodynamic evaluation in patients at increased familial risk of PAH.

Preoperative Brimonidine Tartrate 0.2% Does not Prevent an Intraocular Pressure Rise During Prostatectomy in Steep Trendelenburg Position.

PURPOSE: This study evaluated the effect of preoperative brimonidine tartrate 0.2% on intraocular pressure (IOP) during robotic-assisted laparoscopic radical prostatectomy in steep Trendelenburg position (sTBURG). MATERIALS AND METHODS: In this prospective randomized controlled masked interventional trial, eligible patients scheduled for robotic-assisted laparoscopic radical prostatectomy in sTBURG at the Toronto General Hospital had one eye randomized to placebo (artificial tears) or drug (brimonidine tartrate 0.2%) preoperatively. Visual acuity (VA), tonometry, disc photography, visual field (VF), and retinal nerve fiber layer (RNFL) assessments were performed preoperatively and postoperatively. A standardized anesthetic protocol was followed intraoperatively. IOP was measured using Tono-Pen AVIA (Reichert Inc., New York, NY) as follows: preanesthesia supine, anesthetized supine, hourly in sTBURG and awake supine. The primary outcome was IOP in sTBURG in the drug group compared with the placebo group. Secondary outcomes were changes in VA, VF, RNFL thickness, mean arterial pressure, and ocular perfusion pressure. This study was approved by University Health Network Research Ethics Board. RESULTS: In total, 26 eligible patients, mean age 61.9±5.1 years, were randomized to brimonidine (11 patients) and placebo (15 patients). Baseline IOP was not significantly different between the drug and placebo groups (P=0.42). Significant and sustained IOP elevation of >1.5X baseline in the sTBURG was noted in both groups. The mean IOP 1 hour after sTBURG was 29.4±6.9 and 27.2±3.4 mm Hg in the drug and placebo groups, respectively (P=0.35). No significant changes were noted in VA, VF, or RNFL. CONCLUSIONS: Significant and sustained IOP increases occur during sTBURG. Preoperative brimonidine does not prevent IOP spikes in sTBURG.

Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis.

OBJECTIVE: To investigate whether expression of regulatory components of the cell division cycle can be used independently to predict survival and response to adjuvant therapy in glioblastomas. METHOD: A tissue micro-array, constructed using glioblastomas (n = 66), was stained using antibodies against minichromosome maintenance protein-2 (Mcm-2), expressed throughout the cell-division cycle; geminin, a protein that prevents re-initiation of DNA replication; and cyclin A, an S-phase cyclin. A semi-quantitative labelling index (LI) was calculated using an average of 18 high-power fields (hpf) in three replicate cores. The patients were divided into two groups: Group 1 (n = 50) underwent surgery and radiotherapy with 24 patients receiving temozolomide, and Group 2 (n = 16) received surgical treatment only. RESULTS: The LIs (median +/- IQR) for Group 1 were as follows: Mcm-2, 36.7% (22.9%-51.8%); geminin, 7.8% (5.8%-10.5%); and cyclin A, 4.2% (2.4%-6.9%). Elevated LIs, higher than the median, for geminin and cyclin A correlated with prolonged survival when the tumours received adjuvant therapy (Kaplan-Meier curves, p = 0.0046 and p = 0.0063 for geminin and cyclin A, respectively). Linear regression analysis revealed positive correlations with survival for Mcm-2 (p = 0.0376), geminin (p = 0.0006) and cyclin A (p = 0.004). In Group 2, there was no relationship between the patient survival and the LI for any marker. CONCLUSIONS: Geminin and cyclin A, each show potential as independent prognostic markers in glioblastomas receiving adjuvant therapy. This may reflect the fact that both geminin and cyclin A estimate proliferating tumour cell subpopulations sensitive to radio/chemotherapy. These markers could provide valuable prognostic information, even in small biopsies, especially if combined with O(6)MGMT expression and 1p;19q deletion status.