Role of magnetic resonance imaging for preoperative prediction of early biochemical failure in localized prostate cancer.

Background: The purpose of our study was to assess preoperative clinical biological and Magnetic Resonance Imaging (MRI) predictive factors of early biochemical failure (BF), defined as persistence of significant post-operative plasmatic prostate specific antigen (PSA) level after radical prostatectomy (RP) in patients with localized prostate cancer (PCa). Methods: In a retrospective cohort study we included 142 patients from our university hospital with newly diagnosed PCa, who underwent 3T multiparametric MRI prior to RP. Only the MRI target lesions [Prostate Imaging Reporting and Data System (PIRADS) ≥3] with histological correspondence were considered significant. Clinical, biological, MRI and pathological preoperative data were studied. We performed univariate and multivariate logistic regression analysis to identify significant parameters associated with early BF. Results: Early BF occurred in 14% of patients (20/142). Patients with BF had higher PSA level at diagnosis, Gleason score, number of positive biopsies, size of the largest positive biopsy and higher National Comprehensive Cancer Network (NCCN) risk score (P<0.001 for all). According to MRI, they also had higher T stage and a higher size of capsular contact (P<0.001 for all). In contrast, there was no difference concerning neither ADC value, perfusion profile and zonal location of the index lesion. In multivariate analysis, the best combination of predictive factors of early BF was the association of preoperative Gleason score ≥4+3 [odds ratio (OR) =6.8 (1.4-32.5); P=0.002] and T stage ≥3 on preoperative MRI [OR =17.4 (3.2-94.9); P<0.001] with an area under the curve (AUC) of 0.89 [99% confidence interval (CI): 0.77-1], a negative predictive value of 94% and a positive predictive value of 75%. Conclusions: Combination of simple preoperative biomarkers as Gleason score and T stage according to MRI accurately stratify the risk of early BF following RP. These results emphasize the pivotal role of preoperative MRI for the management of localized PCa.

Prediction of prostate cancer recurrence after radiation therapy using multiparametric magnetic resonance imaging and spectroscopy: assessment of prognostic factors on pretreatment imaging.

Background: To assess whether data from pre-therapeutic multiparametric magnetic resonance imaging (mpMRI) combined with three-dimensional magnetic resonance spectroscopy (3D MRS) provide prognostic factors of biochemical relapse in patients with localized prostate cancer treated by external radiotherapy or brachytherapy. Methods: In our single institution observational retrospective study we included a cohort of 230 patients treated by external radiotherapy or brachytherapy who had an initial mpMRI with 3D MRS from January 2008 to December 2015 for newly diagnosed localized prostatic cancer, proven histologically. Three trained radiologists recorded tumor characteristics, MRI T-stage and metabolic abnormalities from 3D MRS data. Univariate and multivariate Cox analyzes explored the relationship between clinical and imaging variables to highlight prognostic factors for recurrence, using biochemical relapse as the primary endpoint. Results: mpMRI data analysis allowed to reclassify 21.7% of the patients in a MRI National Comprehensive Cancer Network (NCCN) group higher than their initial clinical T-stage, but also to detect a lesion in 78% of the patients considered as clinically T1c. After a median of follow-up of 8.7 years (IQR, 6.6-10.1) following cancer diagnosis, 36 (16%) patients developed a biochemical relapse. The multivariate Cox analysis demonstrated the existence of 3 independent factors for prediction of biochemical recurrence: extracapsular extension (ECE) (HR =3.33; 95% CI: 1.93-5.73; P<0.01), choline/citrate ratio in healthy tissue in the transition zone (TZ) (HR =2.96; 95% CI: 1.06-8.28; P=0.04) and the NCCN Magnetic Resonance Imaging classification (intermediate versus low-risk, HR =3.06; 95% CI: 1.13-8.30; P<0.01). Conclusions: Combination of mpMRI and 3DMRS could aid in the prognostic stratification of localized prostate cancer treated by radiotherapy or brachytherapy, by combining accurate evaluation of tumor extension, and quantification of prostate metabolism.

Three-dimensional nuclear magnetic resonance spectroscopy: a complementary tool to multiparametric magnetic resonance imaging in the identification of aggressive prostate cancer at 3.0T.

BACKGROUND: The limitations of the assessment of tumor aggressiveness by Prostate Imaging Reporting and Data System (PI-RADS) and biopsies suggest that the diagnostic algorithm could be improved by quantitative measurements in some chosen indications. We assessed the tumor high-risk predictive performance of 3.0 Tesla (3.0T) multiparametric magnetic resonance imaging (mp-MRI) combined with nuclear magnetic resonance spectroscopic sequences (NMR-S) in order to show that the metabolic analysis could bring out an evocative result for the aggressive form of prostate cancer. METHODS: We conducted a retrospective study of 26 patients (mean age, 62.4 years) who had surgery for prostate cancer between 2009 and 2016 after pre-therapeutic assessment with 3.0T mp-MRI and NMR-S. Groups within the intermediate range of the D'Amico risk classification were divided into two categories, low risk (n=20) and high risk (n=6), according to the International Society of Urological Pathology (ISUP) 2-3 limit. Histoprognostic discordances within various risk groups were compared with the corresponding predictive MRI values. The performance of predictive models was assessed based on sensitivity, specificity, and the area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: After prostatectomy, histological analysis reclassified 18 patients as high-risk, including 16 who were T3 MRI grade, of whom 13 (81.3%) were found to be pT3. Among the patients who had cT1 or cT2 digital rectal examinations, the T3 MRI factor multiplied by 8.7 [odds ratio (OR), 8.7; 95% confidence interval (CI), 1.3-56.2; P=0.024] the relative risk of being pT3 and by 5.8 (OR, 5.8; 95% CI, 0.95-35.7; P=0.05) the relative risk of being pGleason (pGS) > GS-prostate biopsy. Spectroscopic data showed that the choline concentration was significantly higher (P=0.001) in aggressive disease. CONCLUSIONS: The predictive model of tumor aggressiveness combining mp-MRI plus NMR-S was better than the mp-MRI model alone (AUC, 0.95 vs. 0.86). Information obtained by mp-MRI coupled with spectroscopy may improve the detection of occult aggressive disease, helping in the discrimination of intermediate risks.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.Methods: In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.Measurements and Main Results: Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (n = 72) or placebo (n = 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68; P = 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).

Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients.

Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont Aeromonas, a puzzling rise in Cp-resistant (Cpr) Aeromonas infections has been reported. We report on the effects of subtherapeutic FQ concentrations on bacteria in an environmental reservoir, the medicinal leech, and describe the presence of multiple antibiotic resistance mutations and a gain-of-function resistance gene. We link the rise of CprAeromonas isolates to exposure of the leech microbiota to very low levels of Cp (0.01 to 0.04 µg/ml), <1/100 of the clinical resistance breakpoint for Aeromonas Using competition experiments and comparative genomics of 37 strains, we determined the mechanisms of resistance in clinical and leech-derived Aeromonas isolates, traced their origin, and determined that the presence of merely 0.01 µg/ml Cp provides a strong competitive advantage for Cpr strains. Deep-sequencing the Cpr-conferring region of gyrA enabled tracing of the mutation-harboring Aeromonas population in archived gut samples, and an increase in the frequency of the Cpr-conferring mutation in 2011 coincides with the initial reports of CprAeromonas infections in patients receiving leech therapy.IMPORTANCE The role of subtherapeutic antimicrobial contamination in selecting for resistant strains has received increasing attention and is an important clinical matter. This study describes the relationship of resistant bacteria from the medicinal leech, Hirudo verbana, with patient infections following leech therapy. While our results highlight the need for alternative antibiotic therapies, the rise of Cpr bacteria demonstrates the importance of restricting the exposure of animals to antibiotics approved for veterinary use. The shift to a more resistant community and the dispersion of Cpr-conferring mechanisms via mobile elements occurred in a natural setting due to the presence of very low levels of fluoroquinolones, revealing the challenges of controlling the spread of antibiotic-resistant bacteria and highlighting the importance of a holistic approach in the management of antibiotic use.

Pathway to accommodate patients' spiritual needs.

Many service users would like their spiritual needs to be taken into account during treatment and doing so has been shown to have positive benefits. However, this rarely happens in practice. Barriers to healthcare professionals providing spiritual care include embarrassment, lack of awareness and training, fear and lack of time. This article describes the development of a spirituality care pathway as part of a wider organisational initiative to offer spiritual support in mental health services. The process highlighted the importance of developing awareness and ownership of the need for spiritual care in all service areas and among service users. A range of spiritual interventions were identified and a process of monitoring and review introduced. The approach was appreciated by service users and staff, and was developed within existing professional and management processes.

Early choline levels from 3-tesla MR spectroscopy after exclusive radiation therapy in patients with clinically localized prostate cancer are predictive of plasmatic levels of PSA at 1 year.

PURPOSE: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. METHODS AND MATERIALS: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. RESULTS: After radiation, the mean normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of ≤0.5 ng/mL at 12 months (4.9 ± 1.7 vs. 7.1 ± 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 ± 2.3 vs. 11.4 ± 4.1, p = 0.0117 for choline level and 3.4 ± 0.7 vs. 16.1 ± 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 ± 1.9 vs. 10.4 ± 3.2, p = 0.014 for choline level and 3.0 ± 0.8 vs. 13.3 ± 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. CONCLUSIONS: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA ≤0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the clinical outcome for patients with or without LTHT.

No effect of glutamine ingestion on indices of oxidative metabolism in stable COPD.

COPD patients have reduced muscle glutamate which may contribute to an impaired response of oxidative metabolism to exercise. We hypothesised that prior glutamine supplementation would enhance V(O2) peak, V(O2) at lactate threshold and speed pulmonary oxygen uptake kinetics in COPD. 13 patients (9 males, age 66±5 years, mean±SD) with severe COPD (mean FEV(1) 0.88±0.23l, 33±7% predicted) performed on separate days ramp cycle-ergometry (5-10 W min(-1)) to volitional exhaustion and subsequently square-wave transitions to 80% estimated lactate threshold (LT) following consumption of either placebo (CON) or 0.125 g kg bm(-1) of glutamine (GLN) in 5 ml kg bm(-1) placebo. Oral glutamine had no effect on peak or V(O2) at LT, {V(O2) peak: CON=0.70±0.1 l min(-1) vs. GLN=0.73±0.2 l min(-1); LT: CON=0.57±0.1 l min(-1) vs. GLN=0.54±0.1 lmin(-1)} or V(O2) kinetics {tau: CON=68±22 s vs. GLN=68±16 s}. Ingestion of glutamine before exercise did not improve indices of oxidative metabolism in this patient group.

N-acetylaspartate/creatine and choline/creatine ratios in the thalami, insular cortex and white matter as markers of hypertension and cognitive impairment in the elderly.

Our objective was to investigate the influence of hypertension on N-acetylaspartate (NAA) and choline (Cho) ratios in brain tissues in a community-dwelling elderly population. Brain flexibility was also evaluated with regard to the same metabolite ratios. Proton magnetic resonance spectroscopy (MRS) and the Trail Making Test (TMT) were performed in 80 subjects (75.7+/-4 years old) from the Three-City Study. Fifty-eight participants had hypertension. The NAA/creatine (Cr) and Cho/Cr ratios were obtained in the insular cortex, the thalami and the deep periventricular white matter. In addition, the B-A score of the TMT was evaluated. Uni- and multi-variate analyses were performed in order to examine the relationships among these data. In the insula and the thalami of the hypertensive group, NAA/Cr ratios were significantly lower (1.39+/-0.23 and 1.52+/-0.23, respectively; p=0.01) than those in the normotensive control group (1.52+/-0.25 and 1.70+/-0.19, respectively; p<0.0001), whereas no such reduction was observed in the periventricular white matter of older hypertensive brains. Moreover, the NAA or Cho ratios were significantly correlated with the TMT B-A scores at the level of the thalami, insula and periventricular white matter. These statistical results were confirmed by the multivariate analysis. In an elderly population, hypertension leads to a reduction in NAA/Cr ratios in the insula and the thalami, possibly due to a decrease in blood flow through small perforating and cortical arteries. The TMT B-A test appears to be relevant not only for the frontal areas but also for more remote areas such as the thalami, the insula and the deep periventricular white matter.

Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients.

PURPOSE: To retrospectively evaluate magnetic resonance (MR) imaging, hydrogen 1 (1H) MR spectroscopy, apparent diffusion coefficient (ADC), T1, and T2 measurements for prediction of late neurologic outcome in term neonates after severe perinatal asphyxia. MATERIALS AND METHODS: This study was approved by the local ethics committee. Informed consent from parents was not required. Thirty term neonates (12 boys, 18 girls; age range, 2-12 days) with severe hypoxic-ischemic encephalopathy were examined during the first 12 days of life with conventional and diffusion-weighted cerebral MR imaging, 1H MR spectroscopy with absolute quantification, and T1 and T2 measurements. Quantitative 1H MR spectroscopy, T1, and T2 data were acquired on one 10-mm slab positioned at the level of the basal ganglia. The neonates were assigned to one of two groups according to their late (>12-month follow-up) neurologic outcome: those with an unfavorable outcome-that is, death or severe disability-and those with a favorable outcome. Clinical data, MR signal intensity abnormalities, ADCs, 1H MR spectroscopy findings, and relaxation times were compared by using Chi2 testing and analysis of variance to individualize the prognostic indicators. RESULTS: The unfavorable (n=16) and favorable (n=14) outcome groups were similar in terms of clinical data (ie, Apgar scores, visceral hypoxic injuries), visualization of brain edema on MR images, and T1 and T2 relaxation times. Late unfavorable neurologic outcome was associated with a mixed pattern of cortical and basal ganglia signal intensity abnormalities on MR images (13 babies with unfavorable vs three babies with favorable outcomes, P=.001) and with decreased absolute N-acetylaspartate (NAA) and choline concentrations in all brain structures, especially the basal ganglia (mean NAA concentration: 2.72 mmol/L in unfavorable outcome group vs 4.66 mmol/L in favorable outcome group, P<5x10(-9)), as measured with MR spectroscopy. In the basal ganglia, an NAA concentration lower than 4 mmol/L indicated an unfavorable individual prognosis with 94% sensitivity and 93% specificity. Significantly reduced ADCs also were noted in the unfavorable outcome group, but only during the first 6 days of life. CONCLUSION: Conventional MR imaging findings, spectroscopically measured absolute NAA and choline concentrations, and ADCs are complementary tools for predicting the individual outcomes of severely asphyxiated term neonates.

Comparison of a static gravity screen-roll press combination separator to a PAM-assisted gravity belt thickener system for swine waste slurry solids separation.

Liquid effluent resulting from solids separation from raw swine slurry (RS) using a static gravity screen-roll press separator (SE) and a polyacrylamide (PAM) flocculant-assisted gravity belt thickener system (BE1 and 2, with BE2 designating an added belt thickening of SE) were compared. Effluent pH was 7.6-7.7. Dissolved oxygen was less than 0.01 mg/l in RS and SE and 0.50 mg/l in BE1 and 2. Solids dry weight and total phosphorus concentrations were reduced significantly (p0.05) in SE (17-27%) and in BE1 and 2 (92-96%), relative to RS. Phosphorus concentration reductions were higher than those previously found. Settleable and suspended solids, total nitrogen and chemical oxygen demand were significantly reduced in BE1 and 2 (63-99%). No significant differences (p>0.05) were found between BE1 and 2. Results indicated that the gravity belt thickener system was more efficient at solids separation than the screen-roll press system.

Palliative care inpatient service in a comprehensive cancer center: clinical and financial outcomes.

PURPOSE: Inpatient palliative care units are unavailable in most cancer centers and tertiary hospitals. The purpose of this article is to review the outcomes of the first 344 admissions to the Palliative Care Inpatient Service (PCIS) at our comprehensive cancer center. PATIENTS AND METHODS: We retrospectively reviewed our computerized database for clinical and demographic information, length of stay, and hospital billing during the first year of the service's operation. RESULTS: Three hundred twenty patients were admitted during the study period. Their median age was 57 years. The main cancer diagnoses were thoracic or head and neck (44%), gastrointestinal (25%), and hematologic malignancy (8%). The main referral symptoms were pain (44%), nausea (41%), fatigue (39%), and dyspnea (38%). The median length of stay in the PCIS was 7 days (range, 1 to 58 days). Fifty-nine patients died while in the PCIS. However, the overall hospital mortality rate was not increased compared with that in the year before the establishment of the PCIS (3.58% v 3.59%). The mean reimbursement rate for all palliative care charges was approximately 57%, and the mean daily charges in the PCIS were 38% lower than the mean daily charges for the rest of the hospital. Symptom intensity data showed severe distress on admission and significant improvement in the main target symptoms. Most patients were discharged to a hospice. CONCLUSION: The PCIS has been accepted in our tertiary cancer center on the basis of its clinical utility and financial viability.

Solids, organic load and nutrient concentration reductions in swine waste slurry using a polyacrylamide (PAM)-aided solids flocculation treatment.

Increased swine production results in concentration of wastes generated within a limited geographical area, which may lead to land application rates exceeding the local or regional assimilatory capacity. This may result in pollutant transfer through surface water or soil-groundwater systems, environmental degradation, and/or odor concerns. Existing swine waste pit storage and lagoon treatment technologies may be inadequate to store or treat waste prior to land application without these concerns resulting. Efficient swine waste solids separation may reduce environmental health concerns and generate a value-added bioresource (solids). This study evaluated the efficiency of a polyacrylamide (PAM) flocculant-aided solids separation treatment to reduce pollution indicator concentrations in raw (untreated) swine waste slurry. Swine waste slurry solids separation efficiency through gravity settling (sedimentation) was evaluated before and after the addition of a proprietary polymeric (PAM) flocculant. Results indicated that polymer amendments at concentrations of 62.5-750 mg/l improved slurry solids separation efficiency and significantly reduced concentrations of other associated aquatic pollution indicators in a majority of analyses conducted (33 of 50 total analyses conducted). Results also suggested that PAM-aided solids separation from swine waste slurry might facilitate further treatment and/or disposal and therefore reduce associated environmental degradation potential.

Flash extraction of pectin from orange albedo by steam injection.

Pectin was acid extracted from orange albedo by steam injection heating under pressure. Extraction times ranged from 2 to 6 min at a pressure of about 15 psi. Solubilized pectin was characterized by HPSEC with online light scattering and viscosity detection. Molar mass (M), radius of gyration (R(g)), and intrinsic viscosity ([eta]) all decreased with increasing extraction time when heating temperature was 120 degrees C. At heating times of 3 min, M(w) ranged from 4.9 to 4.5 x 10(5), R(gz) was about 44 nm, and [eta](w) ranged from 8.4 to 7.9 dL/g. Chromatography revealed that solubilized pectin distributions were bimodal in nature at 3 min extraction time and trimodal when the extraction time was 6 min. Scaling law exponents obtained for the highest molar mass fractions were consistent with a very compact spherical structure. For the intermediate fraction, scaling law exponents were consistent with a less compact spherical structure comparable to a random coil. In the case of the low molar mass fractions, scaling law exponents were consistent with a structure more asymmetric in shape. These results are consistent with earlier results which indicated that pectin distributions were mixtures of two or more of the following due to disaggregation during extraction: spherical aggregates, hydrogen bonded network structures, and partially or fully disaggregated components of network structures which could include branched structures, rods, segmented rods, and kinked rods.