Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice.

BACKGROUND: The Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed. METHODS: In a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group (GG), defined as GG1: Gleason score (GS) 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8 and GG5: GS 9-10), magnetic resonance imaging (MRI) and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared with a contemporary cohort that did not undergo phi testing (n=1318). RESULTS: Overall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only three men with phi<27 had cancer of GG⩾2. Phi was superior to PSA for the prediction of any PCa (area under the receiver operating characteristic curve (AUC) 0.72 vs 0.47) and GG⩾2 PCa (AUC 0.77 vs 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS⩽3 had GG⩾2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (P=0.002) and stage (P=0.001). Compared with patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs 48%; P<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, whereas the proportion of biopsies detecting GG⩾2 cancers remained unchanged. CONCLUSIONS: In this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher-grade cancers.

Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis.

BACKGROUND: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer. METHODS: Prostatectomy tissue from 2781 patients were profiled using the Affymetrix HuEx 1.0 ST microarray. Pairwise comparisons were used to identify significant associations between B7-H3 expression and clinicopathologic variables, and survival analyses were used to evaluate the prognostic significance of B7-H3. Pearson's correlation analyses were performed to assess the relationship of B7-H3 expression with molecular subtypes and individual transcripts. Androgen receptor (AR) occupancy at the B7-H3 locus was determined using chromatin immunoprecipitation (ChIP), and androgen-dependent expression changes in B7-H3 was evaluated by quantitative reverse transcription PCR in LNCaP cell lines. Oncomine was queried to evaluate B7-H3 expression in metastatic disease. RESULTS: B7-H3 mRNA expression was positively associated with higher Gleason score (P<0.001), tumor stage (P<0.001), and castrate resistant metastatic disease (P<0.0001). High B7-H3 expression correlated with the development of metastasis and prostate cancer specific mortality, but this was not significant on multi-variable analysis. B7-H3 expression correlated with ERG-positive disease (r=0.99) and AR expression (r=0.36). ChIP revealed an AR-binding site upstream of B7-H3, and the presence of androgens decreased B7-H3 expression in LNCaP suggesting potential direct AR regulation. Gene set enrichment analysis demonstrated an association of B7-H3 with androgen signaling as well as immune regulatory pathways. CONCLUSIONS: Higher B7-H3 expression correlates with Gleason grade, prostate cancer stage and poor oncologic outcomes in prostatectomy cohorts. B7-H3 expression appears to be related to androgen signaling as well as the immune reactome.

Unexplained pulmonary hypertension in peritoneal dialysis and hemodialysis patients.

OBJECTIVES: To compare the prevalence of unexplained pulmonary artery hypertension (PAH) in hemodialysis (HD) and peritoneal dialysis (PD) patients and to compare laboratory parameters between patients with unexplained PAH and those with normal pulmonary artery pressure (PAP). METHODS: We retrospectively reviewed the medical records of 278 chronic HD and 145 chronic PD patients. Laboratory findings including hemoglobin, calcium, phosphorus, alkaline phosphatase, albumin, parathyroid hormone level, serum iron, total iron binding capacity, ferritin, creatinine and blood urea nitrogen were documented. The results of transthoracic Doppler echocardiography were used to determine the pulmonary artery pressure (PAP). PAH was defined as a systolic pulmonary artery pressure (SPAP) ≥35 mmHg. To rule out secondary PAH, patients with cardiac disease, pulmonary disease, collagen vascular disease, volume overload at the time of echocardiography and positive human immunodeficiency virus test were excluded. RESULTS: Data from 34 patients in group HD and 32 individuals in group PD were analyzed. The median age of the study population was 57 (45-68) years. The median SPAP value in patients with PAH was 37.5 (35-45)mmHg. According to the echocardiographic findings, PAH was found in 14 (41.1%) patients of HD group and in 6 (18.7%) patients of PD group (P=0.04). The median serum iron and hemoglobin was significantly lower in patients with PAH compared to those in patients with normal PAP (P<0.05). CONCLUSION: Unexplained PAH seems to be more frequent in patients undergoing HD than patients in PD group. Moreover, hemoglobin and serum iron levels are lower in patients with PAH compared to those in normal PAP group.

Comparison of ketamine and fentanyl for postoperative pain relief in children following adenotonsillectomy.

Adenotonsillectomy has a high incidence of postoperative pain. Therefore, the purpose of this study was to evaluate the effectiveness and safety of either ketamine or fentanyl for postoperative pain relief in children following adenotonsillectomy. Sixty children aged 3-12 years, scheduled for adenotonsillectomy, were enrolled in this randomized, double-blind study. Patients were divided into two groups of 30 cases and received intravenous ketamine (0.5 mg kg(-1)) or fentanyl (1 microg kg(-1)). Modified Hannallah pain scale or Observational Pain Scores (OPS), nausea, vomiting, bleeding, rescue analgesia, sedation and post-anesthesia recovery scores were recorded both at first and 15th minute postoperatively. Moreover, patients receiving ketamine (group 1) or fentanyl (group 2) had comparable OPS and sedation score both on arrival and at 15th minute in the recovery room (p > 0.05). Although rescue analgesics were similarly required in both groups (p > 0.05), the time to reach rescue analgesia was shorter in group 1 (p = 0.001). Only one patient in fentanyl group had nausea and vomiting in the first 15 min that needed antiemetic in the recovery room. In conclusion, intravenous fentanyl (1 microg kg(-1)) compared with intravenous ketamine (0.5 mg kg(-1)) might provide extended time to first analgesic in children undergoing adenotonsillectomy. Interestingly, fentanyl and ketamine did not differ in post-operative vomiting.

Diagnostic accuracy of Doppler ultrasonography in differentiation between malignant and benign cervical lymphadenopathies in pediatric age group.

Cervical lymphadenopathy is a relatively common finding in pediatric age group and is caused by a wide spectrum of diseases from transient infections to malignancies especially lymphomas. The present study was aimed at evaluating the diagnostic performance of grey-scale ultrasonography, color Doppler ultrasonography and power Doppler ultrasonography in differentiation of reactively and metastatically enlarged cervical lymph nodes in pediatric age group. Fifty children with cervical lymphadenopathies were assessed by ultrasonographic methods. In each patient, the longest (L) and transverse (T) diameters, L/T ratio and presence or absence of the normal hilar pattern were checked by grey-scale ultrasonography. Spectral parameters (resistive and pulsatility indices) and vascular distribution pattern of nodes were recorded by color and power Doppler ultrasonography, respectively. Following the ultrasonographic evaluations, biopsy and/or clinical follow up was applied for six months, based on the clinical and paraclinical findings. Statistical analyses were performed by chi-square test, independent t-test and receiver operator characteristic curves. The mean age of patients was 12.42 +/- 2.42 years. Twenty eight patients (56%) had malignant enlargement of lymph nodes. The mean value of L/T ratio in malignant group was 1.70 +/- 0.22 and 2.40 +/- 0.38 in non-malignant nodes (p < 0.001). Sensitivity, specificity and accuracy of combined grey-scale and power Doppler ultrasonography were 70, 86 and 81%, respectively. Combination of grey-scale and power Doppler ultrasonography is recommended for the differentiation between the malignant and benign lymphadenopathies in children. Moreover, our findings revealed no diagnostic role of color Doppler ultrasonography in the selection of malignant cervical lymph nodes in children.

Polymorphisms in GDF9 and BMP15 associated with fertility and ovulation rate in Moghani and Ghezel sheep in Iran.

The genetic base of fertility and ovulation rate in Moghani and Ghezel sheep in northwestern Iran and northeastern Turkey is important because of their fat-tailed meat and carpet quality wool. The genes encoding bone morphogenetic (BM) protein 15 and growth differentiation (GD) factor 9, respectively BMP15 and GDF9 have been shown to affect female productivity in domesticated sheep. Recently, numerous investigations have been performed on a variety of breeds to determine the association between mutations in these genes and fertility. Thus, in this study, we assessed such mutations in the Moghani and Ghezel breeds using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) with appropriate enzymes. Our data were similar to those of the previous studies showing that the genotypes were heterozygous for GD (G -->A) and BM (C -->T) mutations. These heterozygous genotypes resulted in higher ovulation rates, illustrating that one copy of each of the BMP15 and GDF9 mutations had equivalent effects on the ovulation rate. We demonstrate for the first time that the BM variant may not be sufficient on its own for infertility. In addition, although the previous studies have shown no notable relationship between the GD variant, known as the non-effecting mutation and sterility, we report that this mutation has an important role in the Moghani and Ghezel breeds.

Can Doppler ultrasonographic indices of the renal artery predict the presence of supernumerary renal arteries?

BACKGROUND: Variations of the renal arteries, including the presence of supernumerary renal arteries, are important to be identified prior to renal transplant. Angiography has been the gold standard test for the pretransplant evaluation of the renal vasculature. However, this modality is expensive and invasive. The aim of this study was to assess whether Doppler ultrasonographic (DU) indices of the renal artery could predict the presence of supernumerary renal arteries. METHODS AND MATERIALS: Retrospectively, we analyzed multidetector computed tomography angiography (presence or absence of the supernumerary renal artery), DU (peak systolic velocity, resistive index, pulsatility index, end-diastolic velocity, and acceleration time) findings of 30 healthy potential renal transplant donors. Recipient operator characteristic (ROC) curves were used to examine the predictive values of the available DU indices for supernumerary renal arteries. RESULTS: The mean age of donors was 28.4 +/- 4.1 years. Of 60 kidneys evaluated, a supernumerary renal artery was found in 10%. The ROC curve analysis revealed an area under the curve of noninformative (below 0.5) for all DU parameters, indicating that none of the studied parameters could predict the presence of a supernumerary renal artery. CONCLUSIONS: Although the smaller diameter of the main renal artery has previously been found to predict the presence of supernumerary renal arteries, the present study revealed that DU indices of the renal artery may not indicate the presence of supernumerary renal arteries.

Screening for thoracoabdominal aortic aneurysms in patients with aortoiliac atherosclerosis: a preliminary study.

Thoracoabdominal aortic aneurysms (TAAs) usually present with rupture and carry a high morbidity and mortality rate. Early detection of TAAs with screening methods and elective surgical repair could potentially diminish these complications. The present study was aimed at screening for TAA in patients with angiography-proven aortoiliac atherosclerosis (n=43). A group of patients without aortoiliac atherosclerosis was used as controls (n=15). Age, sex and aortic diameter at the level of the T12 vertebra were recorded. The subjects were divided into two age categories, the first made up of those aged less than 65 years and the second those aged 65 years or more. A T12 aortic diameter greater than 35 mm was used to indicate TAA. Statistical analyses were performed by independent t-test and general linear model with age category, sex and atherosclerosis as factors. The mean T12 aortic diameters were greater in patients with atherosclerosis than in the control group (25.2+/-5.0 vs. 22.9+/-2.4 mm; p=0.034). Two out of 43 patients (4.7%) with aortoiliac atherosclerosis had TAA, while no one in the control group had TAA. A general linear model showed that the interaction of age category and sex significantly affected the T12 aortic diameter [F (1.49)=4.044, p=0.050]. Post hoc (LSD) tests revealed that male patients aged over 65 had greater T12 aortic diameters than other patients. We conclude that patients with aortoiliac atherosclerosis may be at greater risk for developing TAA. Ageing and male sex may also be associated with thoracoabdominal aortic enlargement.

Black tea improves endothelial function in renal transplant recipients.

BACKGROUND: Endothelial damage and dysfunction are commonplace in renal transplant recipients. Impaired endothelial function is an important contributor to cardiovascular diseases. We hypothesized that short-term black tea consumption may improve endothelium-dependent arterial dilation in kidney recipients. METHODS: Fifteen recipients were studied on an outpatient basis in a single, university-affiliated clinic. Inclusion criteria were stable and good allograft function. The main exclusion criteria were uncontrolled hypertension, smoking, alcohol consumption, coffee drinking, diabetes mellitus, and coronary artery disease, or a history of upper limb vascular manipulations. After overnight fasting, the brachial artery diameter (BAD) was measured at the end of diastole using an ultrasound machine before (basal BAD) and 1 minute after temporary ( approximately 3 minutes) external occlusion (posthyperemia BAD). Flow-mediated vasodilation (FMV) and percent of FMV (FMV%) were calculated by appropriate formula. FMV and FMV% were determined at baseline and 2 hours after consuming 0.5 L freshly brewed black tea. For control, the study was repeated for each patient the next day and FMV and FMV% were determined before and 2 hours after consuming 0.5 L of water. RESULTS: The men age of patients was 37.2 +/- 9.7 years (range, 25 to 50) with a male:female ratio of 3:2. Patients were 26.8 +/- 10.6 months postrenal transplantation. Black tea consumption significantly increased posthyperemia BAD, FMV, and FMV% (P<.05). However, water consumption did not alter the basal or posthyperemia BAD, FMV, or FMV% (P>.05). CONCLUSION: Based on our study, short-term consumption of black tea may improve endothelial function and endothelium-dependent arterial vasodilation in renal transplant recipients.