Effect of Level of Urology Training on Gleason Score and Prostate Volume Estimation Agreement between Transrectal Ultrasound Guided Biopsy and Radical Prostatectomy Specimen

Introduction Transrectal ultrasound guided prostate biopsy may be performed by operators with various levels of training. Little is known about the impact of training level on biopsy results. We evaluated the effect of training level on the accuracy of transrectal ultrasound guided prostate biopsy findings. Methods We retrospectively reviewed 500 consecutive patients who underwent transrectal ultrasound guided prostate biopsy and subsequent radical prostatectomy. Transrectal ultrasound operators were stratified based on level of training as junior, senior, chief, fellow or staff. Linear regression was performed to analyze the effect of training level on volume estimates. A weighted Kappa statistic evaluated agreement between biopsy and pathological Gleason scores while an adjusted cumulative logistic regression model analyzed the effects of training level. Results A total of 482 patients were included in the final analysis. Transrectal ultrasound guided biopsy was performed by staff in 78 (16%) patients, by fellows in 18 (4%), chief residents in 48 (10%), senior residents in 126 (26%) and junior residents in 212 (44%). There was no significant difference between transrectal ultrasound and radical prostatectomy specimen volume estimates among the training levels. Level of training was not significantly associated with pathological features, including Gleason score, primary Gleason grade, highest single Gleason grade and estimated tumor volume. Study limitations include the retrospective design and the variability among members of the same group. Conclusions Agreement between biopsy and pathological Gleason scores is high for all levels of training. Training level has no impact on prostate volume estimations or the prediction of pathological features

Novi pristup spektrofotometrijskom određivanju metronidazola i tinidazola koristeći p-dimetilaminobenzaldehid

A new approach to the spectrophotometric determination of metronidazole (MZ) and tinidazole (TZ) has been developed. The procedure involves coupling of diazotized nitroimidazoles with p-dimethylaminobenzaldehyde (DMAB) to form a greenish-yellow solution. Optimal temperature and time for diazotization were 0 oC (iced) and 3 minutes and 30 oC and 2 minutes for coupling was, respectively, for both MZ and TZ. Coloured adducts of MZ and TZ showed peaks at 406 nm and 404 nm, respectively, which were selected as analytical wavelengths. The reaction with p-DMAB occurred in a 1:1 mole ratio. Beer’s law was obeyed within the 4.8–76.8 µg mL1 concentration range with low limits of detection. The azo adducts were stable for over a week. Molar absorptivities were 1.10 x 103 (MZ) and 1.30 x 103 L mol1 cm1 (TZ). Overall recoveries of MZ and TZ from quality control samples were 103.2 ± 1.3 and 101.9 ± 1.3 % over three days. There was no interference from commonly utilized tablet excipients. No significant difference was obtained between the results of the new method and the BP titrimetric procedures. The azo approach using the p-dimethylaminobenzaldehyde procedure described in this paper is simple, fast, accurate and precise. It is the first application of DMAB as a coupling component in the diazo coupling reaction.U radu je opisan novi način spektrofotometrijskog određivanja metronidazola (MZ) i tinidazola (TZ). Postupak uključuje reakciju diazotiranog nitroimidazola s p-dimetilaminobenzaldehidom (DMAB), pri čemu nastaje zelenkasto-žuta otopina. Optimalna temperatura i vrijeme za diazotaciju su 0 oC (ledena kupelj) i 3 minute, a za reakciju kondenzacije 30 oC i 2 minute. Obojeni adukti imaju maksimum apsorpcije pri 406, odnosno 404 nm pa su te valne duljine izabrane za analitički postupak. Reakcija s p-DMAB zbiva se u množinskom omjeru 1:1. Reakcija slijedi Beerov zakon u koncentracijskom rasponu 4,8–76,8 µg mL1 s niskim granicama detekcije. Azo adukti su stabilni preko tjedan dana. Molarna apsorptivnost bila je 1,10 × 103 (MZ), odnosno 1,30 × 103 L mol1 cm1 (TZ). Ukupni povrat MZ i TZ iz kontrolnih uzoraka bio je 103,2 ± 1,3, odnosno 101,9 ± 1,3 % tijekom tri dana. Nije zamijećena nikakva interferencija uobičajenih pomoćnih tvari koje se koriste za tabletiranje. Ne postoji značajna razlika između rezultata dobivenih novom metodom i rezultata dobivenih BP titrimetrijskim postupkom. Metoda određivanja opisana u ovom radu je jednostavna, brza, pogodna, točna i precizna i po prvi puta uključuje DMAB u reakciji diazo kopulacije

From Big Data to Precision Medicine.

For over a decade the term "Big data" has been used to describe the rapid increase in volume, variety and velocity of information available, not just in medical research but in almost every aspect of our lives. As scientists, we now have the capacity to rapidly generate, store and analyse data that, only a few years ago, would have taken many years to compile. However, "Big data" no longer means what it once did. The term has expanded and now refers not to just large data volume, but to our increasing ability to analyse and interpret those data. Tautologies such as "data analytics" and "data science" have emerged to describe approaches to the volume of available information as it grows ever larger. New methods dedicated to improving data collection, storage, cleaning, processing and interpretation continue to be developed, although not always by, or for, medical researchers. Exploiting new tools to extract meaning from large volume information has the potential to drive real change in clinical practice, from personalized therapy and intelligent drug design to population screening and electronic health record mining. As ever, where new technology promises "Big Advances," significant challenges remain. Here we discuss both the opportunities and challenges posed to biomedical research by our increasing ability to tackle large datasets. Important challenges include the need for standardization of data content, format, and clinical definitions, a heightened need for collaborative networks with sharing of both data and expertise and, perhaps most importantly, a need to reconsider how and when analytic methodology is taught to medical researchers. We also set "Big data" analytics in context: recent advances may appear to promise a revolution, sweeping away conventional approaches to medical science. However, their real promise lies in their synergy with, not replacement of, classical hypothesis-driven methods. The generation of novel, data-driven hypotheses based on interpretable models will always require stringent validation and experimental testing. Thus, hypothesis-generating research founded on large datasets adds to, rather than replaces, traditional hypothesis driven science. Each can benefit from the other and it is through using both that we can improve clinical practice.Wellcome Trus

The Frequency of Pathogenic Variation in the All of Us Cohort Reveals Ancestry-Driven Disparities

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities

The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities.

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities

PRN OPINION PAPER: Application of precision medicine across pharmacy specialty areas

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149551/1/jac51107_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149551/2/jac51107.pd

Position statement for the diagnosis and management of anogenital warts

Background: Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. ----- Objective: To provide guidance to physicians on the diagnosis and management of AGW. ----- Methods: Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. ----- Results: A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. ----- Conclusion: The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW

Gastric adenocarcinoma in a patient re-infected with H. pylori after regression of MALT lymphoma with successful anti-H. pylori therapy and gastric resection: a case report

BACKGROUND: Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection. CASE PRESENTATION: We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence. CONCLUSIONS: Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high

High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet