Abstract Context Different types of behavioural, dietary, interventional, pharmacologic, and surgical therapies have been used to treat painful bladder syndrome/interstitial cystitis (PBS/IC). ...Because of the paucity of randomised placebo-controlled studies on different treatments, an evidence-based management approach has not yet been developed. Objective To critically review and synthesize data from a wide range of current therapeutic approaches to PBS/IC, to quantify the effect size from randomised controlled trials (RCTs), and to reach clinical agreement on the efficacy of treatments for PBS/IC. Evidence acquisition We performed a systematic review of the literature to identify articles published between 1990 and September 2010 on the management of PBS/IC. We included articles restricted to the English language published since 1990 to date that reported on oral and intravesical treatment, multimodal or combined treatment, and surgical treatment. For all RCTs, standardised mean differences (SMDs) were extracted and combined in a meta-analysis applying a random-effect model that incorporated the heterogeneity of effects. The four outcomes assessed in all studies were a change in the Interstitial Cystitis Symptom Index (ICSI), pain, urgency, and frequency. Non-RCTs (nRCTs) were analysed with a narrative synthesis of the evidence from all research designs. Evidence synthesis We included 7709 adult patients from 29 RCTs and 57 nRCTs. Meta-analysis of RCTs showed that only cyclosporine A provided a simultaneous great effect size of SMD on ICSI, pain, and frequency. Amitriptyline at different dosages showed a great effect size of SMD on pain and urgency or on ICSI and frequency. The remaining RCTs showed sporadic significant changes in only one of the four considered parameters. The attributed levels of evidence for treatments reported in RCTs were 1b; grades of recommendations ranged from A to C. According to the Jadad score, 11 RCTs were high-quality studies. Meta-analysis of RCTs showed a great heterogeneity in the applied methodologies, clinical outcomes assessed, and the obtained results in different studies. The results from the nRCTs showed that the most frequently adopted treatment is oral pentosan polysulfate and that the use of botulinum A toxin intradetrusorial injections in PBS/IC is increasing. A high heterogeneity in drugs and treatment modalities, clinical outcomes, and obtained results was also found for nRCTs. Conclusions Limited evidence exists for the few treatments for PBS/IC. The lack of definitive conclusions is due to the great heterogeneity in methodology, symptoms assessment, duration of treatment, and follow-up in both RCTs and nRCTs.
Abstract Background Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New ...biomarkers would be welcome. Objective Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP. Design, setting, and participants An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP. Measurements We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml. Intervention Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeon's judgement. Results and limitations The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading (all p values <0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume <0.5 ml ( p < 0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum. Conclusions We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.
Background:
Hydrogen sulfide (H2S) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative ...pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous H2S release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P).
Methods:
Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on H2S metabolism and related pathways.
Results:
Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate (P = .03), reporting on the activity of CAT that provides the substrate for H2S release within mitochondria by 3MPST, decreased lanthionine (P = .024), reporting the release of H2S from CBS, and had no significant effect of H2S release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of H2S-induced pathways including 5-MethylTHF (P = .001) and SAME (P = .022), reporting on methylation capacity, and of BH4 (P = .021) and BH2 (P = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of H2S.
Conclusions:
Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the H2S endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a H2S boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.
Objective To estimate the prevalence and the characteristics of intrauterine adhesions after cold loop resectoscopic myomectomy. Design Retrospective study. Setting Endoscopic gynecologic center. ...Patient(s) 688 women with one or more G1–G2 myomas. Intervention(s) Cold loop resectoscopic myomectomy and diagnostic hysteroscopy in all patients 2 months after surgery. Main Outcome Measure(s) Integrity of the uterine cavity and prevalence of intrauterine synechiae. Result(s) A total of 806 myomas were removed, ranging from a minimum of one to a maximum of five fibroids removed for each surgical procedure. Complications were reported in eight cases (1.16%). No hemorrhage, intravasation clinical syndrome, or perforation with the thermal loop were registered. Synechiae were found in 29 patients (4.23%): in 2 patients a new surgical hysteroscopic treatment was required to remove fibrous synechiae, and in 27 patients light adhesions were removed with the tip of the instrument in outpatient hysteroscopy. Neither intrauterine device nor anti-adherence mixtures were used at the end of surgery. Conclusion(s) The cold loop hysteroscopic myomectomy is a safe and effective procedure that seems to be associated with a lower rate of intrauterine adhesions in comparison with the reported literature. The issue appears to be of notable importance for fertility patients.
Aims
This retrospective study reports outcomes after stereotactic body radiation therapy (SBRT) as delivered by helical tomotherapy (HT) for lung lesions. It promotes a dose escalation program.
...Methods
Histological and/or radiological findings and/or case histories identified 41 primary and 15 metastatic lesions. Thirty patients received 40 Gy in 5 fractions (BED 72 Gy
10Gy
) and 26 50 Gy in 5 fractions (BED 100Gy
10Gy
). Primary end point was lung toxicity. Secondary end points were respiratory function, local control and local progression-free survival.
Results
Acute toxicity developed in 18/56 patients and late toxicity in 8/54. Median FEV-1 variations versus baseline were − 0.5% (range − 16 to + 43%) at 6 months and − 4.00% (range − 42 to + 18%) at 24 months. Median DLCO variations versus baseline were − 1% (range − 38 to + 36%) at 6 months and − 12.2% (range − 48 to + 11%) at 24 months. At 6 months, a significant positive correlation emerged between FEV-1 change and KPS (
p
= 0.047). At 24 months, a significant negative correlation emerged between FEV-1 change and the ipsilateral lung V5 (
p
= 0.006). A low baseline DLCO correlated with more marked DLCO worsening at 6 months (
p
= 0.012). At 24 months, DLCO worsening correlated significantly with the median contralateral lung dose (
p
= 0.003). At the last checkup, 23 patients were in complete remission, 16 were in partial remission, 5 had stable disease, and 7 were in relapse. Median follow-up was 12 months (range 5–56).
Conclusions
In patients with lung disease, SBRT, as delivered by HT, was well tolerated and provided good local control.
Purpose We developed and validated a Prostate Health Index (Beckman Coulter, Brea, California) based nomogram to predict prostate cancer at extended prostate biopsy. Materials and Methods The study ...population consisted of 729 patients who were scheduled for prostate biopsy following suspicious digital rectal examination and/or increased prostate specific antigen. Total and free prostate specific antigen, percent free-to-total prostate specific antigen, –2proPSA and the prostate health index (–2proPSA/free prostate specific antigen) × √total prostate specific antigen) were determined. Logistic regression models were fitted to test prostate cancer predictors. Predictive accuracy estimates of biopsy outcome predictions were quantified. Regression coefficients were used to create a decision making tool to predict prostate cancer. A calibration plot was used to evaluate the extent of overestimating or underestimating the observed prostate cancer rate. Decision curve analysis provided an estimate of the net benefit obtained using the prostate health index based nomogram. Results Overall 280 of 729 patients (38.4%) were diagnosed with prostate cancer at extended prostate biopsy. On accuracy analyses prostate health index emerged as the most informative predictor of prostate cancer (AUC 0.70) compared to established predictors, such as total prostate specific antigen (0.51) and percent free-to-total prostate specific antigen (0.62). Including the prostate health index in a multivariable logistic regression model based on patient age, prostate volume, digital rectal examination and biopsy history significantly increased predictive accuracy by 7% from 0.73 to 0.80 (p <0.001). Nomogram calibration was good. Decision curve analysis showed that using the prostate health index based nomogram resulted in the highest net benefit. Conclusions The prostate health index based nomogram can assist clinicians in the decision to perform biopsy by providing an accurate estimation of an individual risk of prostate cancer.
Opera singers are continuously subjected to cardiopulmonary exercise. The impact on cardiac performance has not been studied. Our aim was to verify the impact of singing on heart performance, ...particularly by the evaluation of ECG and deformation parameters as strain, rotation and twist.
A population of 17 OS (opera singers) underwent a 12-lead ECG and 2D echocardiographic evaluation. A post-processing analysis of the images to obtain the deformation parameters was included. The data expressed as mean as SD were compared to a group of 15 high-level athletes (A).
In both groups, the ECG parameters, 2D standard systodiastolic parameters and pulmonary pressure were normal, and in the OS group-LVDd: 47 ± 2.75 mm, LVSd: 31 ± 3.38 mm, E/A: 1.08 ± 0.23, RV: 27.63 ± 3.38 mm; in the A group-LVDd: 51 ± 1.50 mm, LVSd: 32 ± 2.50 mm, E/A: 2.37 ± 0.73, RV: 25.00 ± 3.00 mm. Indexed LV mass was significantly greater in athletes, while ejection fraction (EF) results were higher in OS. Deformation parameters did not differ among the two groups, with the exclusion of GLS expressing a major value in athletes. Rotational parameters resulted in the OS group similar to the athletes.
OS show myocardial performance as high as the athletes. The data obtained suggest a positive impact of regular training as an opera singer. Deformation parameters highlight the fitness status in this group with a specific remodeling in RV in the presence of normal PP. Classic music singing appears to have a training effect on the heart. Further studies are necessary to confirm this hypothesis.
Context:
Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it appears to exert an immunosuppressive function as ...part of an acquired mechanism of immune escape mediated by the inhibition of lymphocyte proliferation and survival and by the induction of FoxP3+ T regulatory cells.
Objective:
The objective of the study was to evaluate IDO1 expression in thyroid carcinoma and demonstrate its immunosuppressive function in the context of thyroid tumors.
Setting:
IDO1 expression was evaluated by quantitative PCR in 105 papillary thyroid carcinomas (PTCs), 11 medullary thyroid carcinomas, six anaplastic thyroid carcinomas, and five thyroid carcinoma cell lines (TCCLs), by immunohistochemistry in 55 PTCs and by Western blotting in five TCCLs. FoxP3+ Treg lymphocyte density was evaluated by immunohistochemistry in 29 PTCs. IDO1 inhibitory effect on lymphocyte proliferation was tested in coculture experiments of TCCLs and activated lymphocytes.
Results:
IDO1 mRNA expression resulted significantly higher in all the analyzed thyroid carcinoma histotypes compared with normal thyroid. Interestingly, an increase of IDO1 mRNA expression magnitude could be observed with gain of aggressiveness (PTCs and medullary thyroid carcinomas ≪ anaplastic thyroid carcinomas). In PTCs, IDO1 mRNA expression magnitude correlated with IDO1 immunostaining intensity in cancer cells and with FoxP3+ Treg lymphocyte density in the tumor microenvironment. IDO1 was expressed in human thyroid cancer cell lines in vitro, and FTC-133 cells showed high kynurenine concentration in the conditioned medium and a strong suppressive action on the proliferation of activated lymphocytes in coculture experiments.
Conclusions:
For the first time, this study demonstrates a pivotal role of IDO1 in the suppression of lymphocyte function in thyroid carcinoma microenvironment.
In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), ...and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls.
Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies.
Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies.
This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.
Purpose We tested the hypothesis that serum isoform -2proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy. Materials and ...Methods The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × √total prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. Results Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients. Conclusions Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies.
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