Su-Min Lee

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum.

Background Tuberculous sputum provides a sample of bacilli that must be eliminated by chemotherapy and that may go on to transmit infection. A preliminary observation that Mycobacterium tuberculosis cells contain triacylglycerol lipid bodies in sputum, but not when growing in vitro, led us to investigate the extent of this phenomenon and its physiological basis. Methods and Findings Microscopy-positive sputum samples from the UK and The Gambia were investigated for their content of lipid body–positive mycobacteria by combined Nile red and auramine staining. All samples contained a lipid body–positive population varying from 3% to 86% of the acid-fast bacilli present. The recent finding that triacylglycerol synthase is expressed by mycobacteria when they enter in vitro nonreplicating persistence led us to investigate whether this state was also associated with lipid body formation. We found that, when placed in laboratory conditions inducing nonreplicating persistence, two M. tuberculosis strains had lipid body levels comparable to those found in sputum. We investigated these physiological findings further by comparing the M. tuberculosis transcriptome of growing and nonreplicating persistence cultures with that obtained directly from sputum samples. Although sputum has traditionally been thought to contain actively growing tubercle bacilli, our transcript analyses refute the hypothesis that these cells predominate. Rather, they reinforce the results of the lipid body analyses by revealing transcriptional signatures that can be clearly attributed to slowly replicating or nonreplicating mycobacteria. Finally, the lipid body count was highly correlated (R2 = 0.64, p < 0.03) with time to positivity in diagnostic liquid cultures, thereby establishing a direct link between this cytological feature and the size of a potential nonreplicating population. Conclusion As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis.

Predictive value of pretreatment inflammation-based prognostic scores (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio) for invasive bladder carcinoma

Purpose Inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are associated with oncologic outcomes in diverse malignancies. We evaluated the predictive value of pretreatment prognostic scores in differentiating nonmuscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). Materials and Methods Consecutive transurethral resection of bladder tumour (TURBT) cases from January 2011 to December 2013 were analysed retrospectively. Patient demographics, tumour characteristics and prognostic scores results were recorded. Receiver operating characteristics curves were used to determine prognostic score cutoffs. Univariate and multivariate binomial logistic regression analysis was performed to evaluate the association between variables and MIBC. Results A total of 226 patients were included, with 175 and 51 having NMIBC (stages Ta and T1) and MIBC (stage T2+) groups, respectively. Median age was 75 years and 174 patients were male. The NLR cutoff was 3.89 and had the greatest area under the curve (AUC) of 0.710, followed by LMR (cutoff<1.7; AUC, 0.650) and PLR (cutoff>218; AUC, 0.642). Full blood count samples were taken a median of 12 days prior to TURBT surgery. Multivariate logistic regression analysis identified tumour grade G3 (odds ration [OR], 32.848; 95% confidence interval [CI], 9.818-109.902; p=0.000), tumour size≥3 cm (OR, 3.353; 95% CI, 1.347-8.345; p=0.009) and NLR≥3.89 (OR, 8.244; 95% CI, 2.488-27.316; p=0.001) as independent predictors of MIBC. Conclusions NLR may provide a simple, cost-effective and easily measured marker for MIBC. It can be performed at the time of diagnostic flexible cystoscopy, thereby assisting in the planning of further treatment.

A Two-Tube Combined TaqMan/SYBR Green Assay to Identify Mycobacteria and Detect Single Global Lineage-Defining Polymorphisms in Mycobacterium tuberculosis

We have developed a novel real-time PCR assay to identify and perform preliminary genotyping of mycobacteria in a manner tailored to our local service. Within a single thermocycler run, mycobacterial 16S rDNA and the Mycobacterium tuberculosis global lineage-defining RD750 polymorphism are targeted in separate reaction tubes, each of which includes both TaqMan and SYBR Green chemistries. The results of this 16S-RD assay differentiate M. tuberculosis complex (MTBC) from nontuberculous mycobacteria (NTM) and recognize whether or not MTBC isolates belong to the East African-Indian lineage, the single most frequently isolated global MTBC lineage in our service. If required, NTM amplicons may be sequenced to provide more specific identities. We report the technical performance of this assay on 88 mycobacteria-positive cultures and discuss its use in the initial management of mycobacterial infections. The 16S-RD assay correctly identified all 70 MTBC-positive cultures and 17 NTM-positive cultures while contemporaneously recognizing 26 MTBC isolates as within and 44 outside the East African-Indian lineage. In artificial samples, the combined assay also showed limited potential to detect mixed mycobacterial infections (MTBC/NTM) and tuberculosis infections involving more than one global MTBC lineage. The approach we have established can be readily tailored to targets of particular value for any mycobacterial diagnostic service, thereby optimizing the value of the results for local clinical and public health management of mycobacterial infections.

Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma

We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

Recent advances in the understanding and management of underactive bladder

Underactive bladder (UAB) is an important and complex urological condition resulting from the urodynamic finding of detrusor underactivity. It can manifest in a wide range of lower urinary tract symptoms, from voiding to storage complaints, and can overlap with other conditions, including overactive bladder and bladder outlet obstruction. However, UAB continues to be poorly understood and inadequately researched. In this article, we review the contemporary literature pertaining to recent advances in defining, understanding, and managing UAB.

Toward an MRI-based nomogram for the prediction of transperineal prostate biopsy outcome: A physician and patient decision tool

PURPOSE To develop and internally validate a nomogram using biparametric magnetic resonance imaging (B-MRI)-derived variables for the prediction of prostate cancer at transperineal sector-guided prostate biopsy (TPSB). SUBJECTS/PATIENTS AND METHODS Consecutive patients referred to our institution with raised prostate-specific antigen (PSA), abnormal prostate examination, or persistent suspicion of prostate cancer after previous transrectal biopsy between July 2012 and November 2015 were reviewed from a prospective database. All patients underwent prebiopsy B-MRI with T2-weighted and diffusion-weighted imaging sequences, followed by 24 to 40 core TPSB with additional targeted cores using cognitive registration. Univariable and multivariable logistic regression analysis was used to determine predictors of prostate cancer outcomes. Multivariable coefficients were used to construct 2 MRI-based nomograms to predict any and significant (Gleason 4 or maximum cancer core length ≥6mm) prostate cancer at TPSB. Bootstrap resamples were used for internal validation. Accuracy was assessed by calculating the concordance index. RESULTS In total, 615 men were included in the study. Prostate cancer was diagnosed in 317 (51.5%) men with significant cancer diagnosed in 237 (38.5%) men. Age, Prostate Imaging Reporting and Data System (PI-RADS) score, PSA, PSA density, and primary biopsy were predictors of prostate cancer at TPSB on univariable analysis (P<0.0001). PSA showed strong correlation with PSA density and was excluded. The remaining variables were all independent predictors of prostate cancer on multivariable analysis (P<0.0001) and used to generate the nomograms. Both nomograms showed good discrimination for prostate cancer, with a concordance index of 87% for any cancer and 92% for significant disease. Using a nomogram-derived probability threshold of<15%, 111 (18.0%) biopsies can be saved, at the expense of 3 missed significant prostate cancers. CONCLUSIONS These internally validated MR-based nomograms were able to accurately predict TPSB outcomes for prostate cancer, especially significant disease. Our findings support the combination of prebiopsy MRI results and clinical factors as part of the biopsy decision-making process.

Contemporary outcomes and prediction of adherent perinephric fat at partial nephrectomy: a systematic review.

Abstract Objective: Current guidelines recommend partial nephrectomy for the management of T1a tumours. Adherent perinephric fat (APF) has been recognized as a complicating feature of such surgery. The objective of this article was to present a systematic review of the published literature investigating APF aetiology, risk factors and outcomes. Materials and methods: To identify relevant studies, the PubMed, MEDLINE, Web of Science and Google Scholar databases were searched from 1990 to 2017. Results: Eight studies studying APF were identified. The aetiology of APF appears to be multifactorial, but is thought to be associated with a systemic, chronic inflammatory state secondary to metabolic syndrome. Several risk factors have been identified. Clinically, APF is more prevalent in ageing and male populations, particularly those with high body mass index and waist measurements. Radiological risk factors for APF include increased perinephric fat thickness and stranding, which can be combined to produce the Mayo Adhesive Probability (MAP) score, a predictive index that has been validated in small, external cohorts. The presence of APF at partial nephrectomy is associated with increased operative time and estimated blood loss. However, there is no documented increase in warm ischaemia time or perioperative complications in patients with APF. Conclusions: More studies are required to identify outcomes and risk factors for APF. Early identification of patients with APF can allow surgeons to guide preoperative planning and patient assessment.

Laparoscopic vs robotic nephroureterectomy: Is it time to re-establish the standard? Evidence from a systematic review

Abstract Objective: To conduct a systematic review of comparative studies of laparoscopic nephroureterectomy (LNU), the standard management for upper urothelial tumours, and robot-assisted NU (RANU) that has emerged as a viable alternative. Methods: MEDLINE, EMBASE and the Cochrane Library were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all studies reporting on both LNU and RANU for upper urothelial tract tumours. Results: In all, 1630 patients were included, of which 838 underwent LNU and 792 RANU. Three studies reported on mean operative time and found it to be less in LNU, with two reporting this to be significant (RANU 298 vs LNU 251 min, P = 0.03; 306 vs 234 min, respectively, P < 0.001). Both studies reporting on median node count found this to be higher in the robotic groups: RANU 5.5 vs LNU 1.0 and RANU 21 vs LNU 11. Positive surgical margins (RANU 1.69% vs LNU 7.06%, P = 0.18), bladder recurrence (24.6% vs 36.89%, P = 0.09), and distant metastases (27.50% vs 17.50%, P = 0.29) were not significantly different between the two techniques. Disease-specific mortality did not differ between the two techniques (RANU 7.5% vs LNU 12.5%, P = 0.46), but postoperative mortality was reduced in RANU (0.14% vs 1.32%, P = 0.03). Overall complication rates were statistically lower in RANU, at 12.5% vs 18.8% (P < 0.001). Conclusions: This review suggests these techniques are equivalent in terms of perioperative and oncological performance. Furthermore, there may be a lower overall complication rate, as well as postoperative mortality in the robotic group. Further research in the form of a randomised controlled trial is warranted.

Stomal varices: a cause for intermittent haematuria post-radical cystectomy

A 74-year-old man presented to hospital with intermittent episodes of frank, painless haematuria, 2 years post-radical cystectomy with ileal conduit. Stoma examination revealed dilated stomal varices and peri-stomal ecchymoses (figure 1). An abdominal CT scan confirmed a thickened distal ileal conduit and a cirrhotic liver with dilated portal venous system. A diagnosis of stomal varices secondary to portal hypertension and liver cirrhosis was made. The patient underwent suture ligation of the bleeding varices. …