This paper uses microfluidics to implement genetic algorithms (GA) to discover new homogeneous catalysts using the oxidation of methane by molecular oxygen as a model system. The parameters of the GA were the catalyst, a cocatalyst capable of using molecular oxygen as the terminal oxidant, and ligands that could tune the catalytic system. The GA required running hundreds of reactions to discover and optimize catalyst systems of high fitness, and microfluidics enabled these numerous reactions to be run in parallel. The small scale and volumes of microfluidics offer significant safety benefits. The microfluidic system included methods to form diverse arrays of plugs containing catalysts, introduce gaseous reagents at high pressure, run reactions in parallel, and detect catalyst activity using an in situ indicator system. Platinum(II) was identified as an active catalyst, and iron (II) and the polyoxometalate H 5 PMo 10 V 2 O 40 (POM-V2) were identified as active cocatalysts. The Pt/Fe system was further optimized and characterized using NMR experiments. After optimization, turnover numbers of approximately 50 were achieved with approximately equal production of methanol and formic acid. The Pt/Fe system demonstrated the compatibility of iron with the entire catalytic cycle. This approach of GA-guided evolution has the potential to accelerate discovery in catalysis and other areas where exploration of chemical space is essential, including optimization of materials for hydrogen storage and CO 2 capture and modifications.
Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.
In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of PCa, PHID outperformed PHI and other PSA derivatives in the diagnosis of clinically significant cancer. Incorporating age, PNB status and PI-RADS score led to even further gains in the diagnostic performance of PHID. Furthermore, PI-RADS score was found to be complementary to PHID. Using 0.44 as a threshold for PHID, 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.
BACKGROUNDThe 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.METHODSIn 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 to a contemporary cohort that did not undergo phi testing (n=1318).RESULTSOverall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only 3 men with phi<27 had cancer of GG≥2. Phi was superior to PSA for the prediction of any PCa (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 to 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, while the proportion of biopsies detecting GG≥2 cancers remained unchanged.CONCLUSIONSIn 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.
To estimate the proportion of oncocytic renal neoplasms diagnosed on renal mass biopsy (RMB) confirmed on surgical pathology, a systematic review of MEDLINE, Embase, and the Cochrane databases (1997 to 1 July 2016) was conducted quantifying all cases of reported oncocytic renal neoplasms on RMB suggestive of an oncocytoma. In addition, institutional data was assessed to identify additional cases. Concordance with surgical histopathology (positive predictive value [PPV]) was evaluated for patients undergoing surgery by performing a meta-analysis. In all, 10 RMB series, including institutional data, were included in the meta-analysis with 205 RMBs identifying oncocytic renal neoplasms and 46 (22.4%) proceeding to surgery. One additional study identified two neoplasms not captured by the primary RMB series for a total of 48 unique lesions included in the analysis. Surgical pathology showed oncocytoma (64.6%), chromophobe renal cell carcinoma (RCC; 12.5%), other RCC (12.5%), hybrid oncocytic/chromophobe tumour (6.3%), and other benign lesions (4.2%). PPV of oncocytoma on RMB was 67% (95% confidence interval 34-94%) with significant heterogeneity between studies (I = 71.8%, P < 0.01). Risk of bias was judged to be low for four of the 10 series. Confidently diagnosing a localised renal mass as a benign lesion, such as an oncocytoma, has implications for the ultimate management strategy a patient will undergo. RMB was found to be unreliable in confidently diagnosing a localised renal mass as an oncocytoma, with one in four found to be RCC on surgical pathology. Patients and physicians should be aware of the uncertainty in diagnosis when considering management strategies.
In an editorial board-moderated debate format, two experts in prostate cancer surgery are challenged with presenting the key strategies in radical prostatectomy that improve urinary functional outcomes. Dr Bernardo Rocco was tasked with arguing the facts that support the anatomical preservation and reconstruction steps that improve urinary continence. Drs Christian Pavlovich and Sasha Druskin were tasked with arguing the facts supporting neurovascular bundle and high anterior release surgical planes that improve urinary continence. Associate Editor John Davis moderates the debate, and outlines the current status of validated patient questionnaires that can be used to evaluate urinary continence, and recent work that allows measuring what constitutes a 'clinically significant' difference that either or both of these surgical techniques could influence. A review of raw data from a publication from Dr Pavlovich's team demonstrates how clinically relevant differences in patient-reported outcomes can be correlated to technique. A visual atlas is presented from both presenting teams, and Dr Davis demonstrates further reproducibility of technique. A linked video on this concept is available as a supplementary file.
ObjectivesThe aim of this study was to assess the positive surgical margin (PSM) and nerve sparing (NS) rates in patients who underwent prostate MRI (pMRI) prior to radical prostatectomy (RP) and compare them with matched, nonimaged control RP patients.MethodsWe identified 204 men who underwent preoperative pelvic MRI (pelMRI), of whom 176 (86.3%) underwent pMRIs, within 60 days of RP, and compared them (1:1) with a nonim-aged control group matched by surgeon, age, race, body mass index (BMI), prostate-specific antigen (PSA), pathological Gleason score, prostate specimen weight, and RP year.ResultsThe rates of nonfocal extracapsular extension (nfECE) on RP pathology in the MRI and control groups were similar. PSM rates were lower in the MRI group (13.7% vs 19.3%; P=0.14), but the difference did not meet statistical significance; this was also the case in patients with nfECE on RP pathology (27.7% vs 39.5%; P=0.3). NS rates were similar between groups. In the MRI group, 54 (26.5%) patients had an MRI suspicious for nfECE; their PSM rate (20.4%) was higher than that of patients with an MRI not suspicious for nfECE (11.3%; P=0.11), but the difference lacked statistical significance; the former group had significantly lower rates of NS. Limitations of the study include sample power and nonuniform heeding of MRI results by each surgeon.ConclusionMRI did not significantly decrease the rates of PSM, including in the subset of patients with nfECE on final pathology. Even wider resection may be necessary in patients with MRIs suggesting locally-advanced disease. Studies with greater power are needed.
For men on AS, older age at time of diagnosis was positively associated with BGR to GG≥3, and RPGR. These observations imply that for many older men, AS (as opposed to watchful waiting) remains a more appropriate management strategy.
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