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Abstract Background Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid–based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC. Methods In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9–12; safety was assessed at TOC and day 21–30. Results One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%–75%) for TOL-463 insert and 50% (95% CI, 31%–69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%–99%) for TOL-463 insert and 81% (95% CI, 57%–93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%). Conclusions TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials. Clinical Trials Registration NCT02866227. TOL-463 vaginal gel or insert, a boric acid–based anti-infective with enhanced antibiofilm activity, was effective and safe in treating Bacterial Vaginosis and Vulvovaginal Candidiasis, with the vaginal insert demonstrating higher efficacy for both conditions.

Competing interests JOGK owns shares in PledPharma AB and is the main inventor of calmangafodipir (owned by PledPharma AB). Karlsson J, Reineke K, Kurz T, Andersson R, McLaughlin C, Jacobsson S, Näsström J. Calmangafodipir, a new chemical entity, and other metal complexes, method of preparation, compositions, and methods of treatment. POP Trial Investigators Dear, J. Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose—the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial published study protocol for a randomised controlled trial.

The global contamination of water resources with inorganic and organic micropollutants, such as metals and pharmaceuticals, poses a critical threat to the environment and human health. Herein, we report on a bio-derived chitosan-EDTA-β-cyclodextrin (CS-ED-CD) trifunctional adsorbent fabricated via a facile and green one-pot synthesis method using EDTA as a cross-linker, for the adsorption of toxic metals and organic micropollutants from wastewater. In this system, chitosan chain is considered as the backbone, and the immobilized cyclodextrin cavities capture the organic compounds via host-guest inclusion complexation, while EDTA-groups complex metals. The thoroughly characterized CS-ED-CD was employed for batch adsorption experiments. The adsorbent displayed a monolayer adsorption capacity of 0.803, 1.258 mmol g −1 for Pb(II) and Cd(II) respectively, while a heterogeneous sorption capacity of 0.177, 0.142, 0.203, 0.149 mmol g −1 for bisphenol-S, ciprofloxacin, procaine, and imipramine, respectively. The adsorption mechanism was verified by FT-IR and elemental mapping. Importantly, the adsorbent perform is effective in the simultaneous removal of metals and organic pollutants at environmentally relevant concentrations. All these findings demonstrate the promise of CS-ED-CD for practical applications in the treatment of micropollutants. This work adds a new insight to design and preparation of efficient trifunctional adsorbents from sustainable materials for water purification.

The aim of this study was to compare unenhanced MRI, MnDPDP-enhanced MRI, and spiral CT in the detection of hepatic colorectal metastases. Forty-four patients with hepatic colorectal metastases were examined with unenhanced and MnDPDP-enhanced MRI and with unenhanced and contrast-enhanced spiral CT. The MR examination protocol included baseline T1-weighted spin-echo (SE), T1-weighted gradient-recalled-echo (GRE), and T2-weighted fast-SE sequences; and T1-weighted SE and T1-weighted GRE sequences obtained 30-60 min after administration of 0.5 micromol/kg (0.5 ml/kg) mangafodipir trisodium (MnDPDP). Images were interpreted by three blinded readers. Findings at CT and MRI were compared with those at intraoperative US, which were used as term of reference. Intraoperative US detected 128 metastases. In a lesion-by-lesion analysis, the overall detection rate was 71% (91 of 128) for spiral CT, 72% (92 of 128) for unenhanced MRI, and 90% (115 of 128) for MnDPDP-enhanced MRI. MnDPDP-enhanced MRI was more sensitive than either unenhanced MRI ( p<0.0001) or spiral CT ( p=0.0007). In a patient-by-patient analysis, agreement with gold standard was higher for MnDPDP-enhanced MRI (33 of 44 cases) than for spiral CT (22 of 44 cases, p=0.0023) and unenhanced MRI (21 of 44 cases, p=0.0013). MnDPDP-enhanced MRI is superior to unenhanced MRI and spiral CT in the detection of hepatic colorectal metastases.

The aim of the present study was to examine the feasibility of applying the catalytic antioxidant mangafodipir [MnDPDP, manganese (Mn) dipyridoxyl diphosphate] as a cardioprotective adjunct to primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation (STE) myocardial infarction (STEMI). Both MnDPDP and a metabolite (Mn dipyridoxyl ethyldiamine) possess properties as mitochondrial superoxide dismutase mimetics and iron chelators, and combat oxidative stress in various tissues and conditions. The study tested MnDPDP (n = 10) vs. saline placebo (n = 10), given as a brief intravenous (i.v.) infusion prior to balloon inflation during pPCI in patients with STEMI. Mangafodipir was well tolerated and did not affect heart rate or blood pressure. Despite longer ischaemic time (205 vs. 144 min, P = 0.019) in the MnDPDP group, plasma biomarker releases were identical for the two groups. With placebo vs. MnDPDP, mean STE resolutions were 69.8 vs. 81.9% (P = 0.224) at 6 h and 73.1 vs. 84.3% (P = 0.077) at 48 h. Cardiac magnetic resonance revealed mean infarct sizes of 32.5 vs. 26.2% (P = 0.406) and mean left ventricular (LV) ejection fractions of 41.8 vs. 47.7% (P = 0.617) with placebo vs. MnDPDP. More LV thrombi were detected in placebo hearts (5 of 8) than MnDPDP-treated hearts (1 of 10; P = 0.011). Mangafodipir is a safe drug for use as an adjunct to reperfusion therapy. A tendency to benefit of MnDPDP needs confirmation in a larger population. The study revealed important information for the design of a Phase II trial.

Purpose Gallium-68 (Ga-68)-labeled tracers for imaging expression of the prostate-specific membrane antigen (PSMA) such as the [ 68 Ga]Ga-PSMA-HBED-CC have already demonstrated high potential for the detection of recurrent prostate cancer. However, compared to Ga-68, a labeling with fluorine-18 (F-18) would offer advantages with respect to availability, production amount, and image resolution. [ 18 F]DCFPyL is a promising F-18-labeled candidate for PSMA-positron emission tomography (PET) imaging that has been recently introduced. In the current study, we aimed to compare [ 68 Ga]Ga-PSMA-HBED-CC and [ 18 F]DCFPyL for clinical use in biochemically relapsed prostate cancer. Procedures In 14 selected patients with PSA relapse of prostate cancer, [ 18 F]DCFPyL PET/X-ray computed tomography (CT) was performed in addition to [ 68 Ga]Ga-PSMA-HBED-CC PET/CT. A systematic comparison was carried out between results obtained with both tracers with regard to the number of detected PSMA-positive lesions, the standardized uptake value (SUV) max and the lesion to background ratios. Results All suspicious lesions identified by [ 68 Ga]Ga-PSMA-HBED-CC were also detected with [ 18 F]DCFPyL. In three patients, additional lesions were observed using [ 18 F]DCFPyL PET/CT. The mean SUV max in the concordant [ 18 F]DCFPyL PSMA-positive lesions was significantly higher as compared to [ 68 Ga]Ga-PSMA-HBED-CC (14.5 vs. 12.2, p  = 0.028, n  = 15). The mean tumor to background ratios ( n  = 15) were significantly higher for [ 18 F]DCFPyL compared to [ 68 Ga]Ga-PSMA-HBED-CC using kidney, spleen, or parotid as reference organs ( p  = 0.006, p  = 0.002, p  = 0.008), but no significant differences were found using the liver ( p  = 0.167) or the mediastinum ( p  = 0.363) as reference organs. Conclusion [ 18 F]DCFPyL PET/CT provided a high image quality and visualized small prostate lesions with excellent sensitivity. [ 18 F]DCFPyL represents a highly promising alternative to [ 68 Ga]Ga-PSMA-HBED-CC for PSMA-PET/CT imaging in relapsed prostate cancer.

Since the introduction of positron emission tomography (PET) imaging with (68)Ga-PSMA-HBED-CC (=(68)Ga-DKFZ-PSMA-11), this method has been regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). However, published data exist for small patient cohorts only. The aim of this evaluation was to analyse the diagnostic value of (68)Ga-PSMA-ligand PET/CT in a large cohort and the influence of several possibly interacting variables. We performed a retrospective analysis in 319 patients who underwent (68)Ga-PSMA-ligand PET/CT from 2011 to 2014. Potential influences of several factors such as prostate-specific antigen (PSA) level and doubling time (DT), Gleason score (GSC), androgen deprivation therapy (ADT), age and amount of injected tracer were evaluated. Histological verification was performed in 42 patients after the (68)Ga-PSMA-ligand PET/CT. Tracer uptake was measured in 901 representative tumour lesions. In 82.8% of the patients at least one lesion indicative of PCa was detected. Tumor-detection was positively associated with PSA level and ADT. GSC and PSA-DT were not associated with tumor-detection. The average maximum standardized uptake value (SUVmax) of tumour lesions was 13.3 ± 14.6 (0.7-122.5). Amongst lesions investigated by histology, 30 were false-negative in 4 different patients, and all other lesions (n = 416) were true-positive or true-negative. A lesion-based analysis of sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) revealed values of 76.6%, 100%, 91.4% and 100%. A patient-based analysis revealed a sensitivity of 88.1%. Of 116 patients available for follow-up, 50 received local therapy after (68)Ga-PSMA-ligand PET/CT. (68)Ga-PSMA-ligand PET/CT can detect recurrent PCa in a high number of patients. In addition, the radiotracer is highly specific for PCa. Tumour detection is positively associated with PSA and ADT. (68)Ga-PSMA-ligand PET/CT can help delay systemic therapy of PCa.

Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [(68)Ga]Glu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. A cohort of 57 patients with prostate cancer scanned with (68)Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with (68)Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. (68)Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. The presented imaging technique of (68)Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.

Purpose Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in prostate carcinoma (PC) cells. Recently, procedures have been developed to label PSMA ligands with 68 Ga, 99m Tc and 123/124/131 I. Our initial experience with Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)]( 68 Ga-PSMA) suggests that this novel tracer can detect PC relapses and metastases with high contrast. The aim of this study was to investigate its biodistribution in normal tissues and tumour lesions. Methods A total of 37 patients with PC and rising prostate-specific antigen (PSA) levels were subjected to 68 Ga-PSMA positron emission tomography (PET)/CT. Quantitative assessment of tracer uptake was performed 1 and 3 h post-injection (p.i.) by analysis of mean and maximum standardized uptake values (SUV mean/max ) of several organs and 65 tumour lesions. Subsequently, tumour to background ratios were calculated. Results The PET/CT images showed intense tracer uptake in both kidneys and salivary glands. Moderate uptake was seen in lacrimal glands, liver, spleen and in small and large bowel. Quantitative assessment revealed excellent contrast between tumour lesions and most normal tissues. Of 37 patients, 31 (83.8 %) showed at least one lesion suspicious for cancer at a detection rate of 60 % at PSA <2.2 ng/ml and 100 % at PSA >2.2 ng/ml. Median tumour to background ratios were 18.8 (2.4–158.3) in early images and 28.3 (2.9–224.0) in late images. Conclusion The biodistribution of the novel 68 Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients. Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels.

Purpose68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is valuable for detecting primary and recurrent prostatic lesions. This study aimed to evaluate the efficacy of 68Ga-PSMA-11 PET/CT as a triage tool for prostate biopsy (PSMA-TB) and compare with transrectal ultrasound-guided biopsy (TRUS-GB) for the diagnosis of clinically significant prostate cancer (csPCa).MethodsThis single-centre study randomly allocated 120 patients with elevated serum prostate-specific antigen (PSA) levels (> 4 ng/ml) to PSMA-PET or TRUS group. Patients with PSMA-avid lesions (SUVmax ≥ 8.0) underwent PSMA-TB via a single-puncture percutaneous transgluteal approach (n = 25), whilst patients with negative PSMA-PET underwent systematic TRUS-GB (n = 35). All patients in the TRUS group underwent TRUS-GB directly (n = 60).ResultsPCa and csPCa were detected in 26/60 (43.3%) and 24/60 (40.0%) patients in the PSMA-PET group and 19/60 (31.6%) and 15/60 (25.0%) in the TRUS group, respectively. In the PSMA-PET group, the detection rate of PCa and csPCa were significantly higher in PSMA-PET-positive than negative patients (PCa, 23/25 (92.0%) vs 3/35 (8.6%), P < 0.01; csPCa, 22/25 (88.0%) vs 2/35 (5.7%), P < 0.01). PSMA-TB detected significantly more PCa and csPCa than TRUS-GB in the TRUS controls (PCa, 21/25 (84.0%) vs 19/60 (31.6%), P < 0.01; csPCa, 20/25 (80.0%) vs 15/60 (25.0%), P < 0.01). PSMA-PET detected significantly more cases of csPCa amongst patients with PSA 4.0–20.0 ng/ml than TRUS (27.02% vs 8.82%, P < 0.05). No haematuria, urinary retention or pelvic infection was observed after PSMA-TB compare with TRUS-GB.Conclusions68Ga-PSMA-11 PET/CT is a feasible imaging technique that may serve as a triage tool for prostate biopsy, and may improve the detection rate of csPCa compared with TRUS-GB, especially in patients with serum PSA 4.0–20.0 ng/ml.