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Background There was a fluctuation in medication demand and supply during COVID-19 pandemic. This study aimed to assess the trend of drug utilisation in Malaysia in 2018–2022 and evaluate the impact of COVID-19 on drug utilisation rates.Methods We conducted a repeated cross-sectional study of pharmaceutical sales data from public and private sectors in Malaysia from 2018 to 2022. Drug utilisation rates for the period after the onset of COVID-19 (2020–2022) was compared with the earlier period (2018–2019). Interrupted time-series regression analyses evaluated level and slope changes compared to pre-COVID-19 pandemic level for quarterly rates of drugs utilisation in public and private sectors.Results There was an immediate reduction in the utilisation rates for all drugs after COVID-19 in public (−20.4%; p = 0.043) and private sectors (−22.4%; p = 0.003). In both sectors, significant level changes were observed for anti-infectives, musculoskeletal, neurological, respiratory, and sensory organs preparations following COVID-19 pandemic, followed by a sustained increase in trend from 2020 to 2022. Public sector had a 22.2% reduction in the utilisation of cardiovascular drugs (p = 0.002), particularly for renin–angiotensin system (RAS) agents (−47.4%, p = 0.019). Private sector had large changes for anti-infectives (−53.6%, p

Agriculture in the 21st century faces challenges in adopting efficient and sustainable production methods to feed the growing population. In this context, seaweed offers greater advantages over terrestrial plants. This study investigated the nutritional composition and antioxidant properties of six edible seaweeds found in Malaysia. The seaweeds studied were brown (Padina australis, Sargassum binderi, Sargassum polycystum), green (Caulerpa racemosa, Caulerpa sertularioides), and red (Garcilaria changgi) seaweeds. The moisture, ash, protein, fat, and total dietary fibre contents of the seaweeds were analysed according to the Association of Official Analytical Chemists methods. Total available carbohydrate content was assessed using the Clegg-anthrone method. Mineral, amino acid, and fatty acid contents were determined through atomic absorption spectroscopy, high-performance liquid chromatography, and gas chromatography methods, respectively. Results revealed that the seaweeds were all high in total dietary fibre (53.96–76.97 g/100 g dried weight, dw) and ash (4.46–18.53 g/100 g dw) whereas their fat (0.05–4.62 g/100 g dw) content was generally low. The brown seaweeds were good sources of calcium. Red seaweed G. changii had the highest content of essential amino acids whereas brown seaweed S. binderi had the highest polyunsaturated fatty acid and lowest saturated fatty acid contents. Fucoxanthin could only be detected in brown seaweeds. Methanolic extracts of seaweeds showed good antioxidant activities measured using 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH-RSA), ferric reducing antioxidant power (FRAP), and trolox equivalent antioxidant activity (TEAC) assays. Overall, this study contributed knowledge on underexploited Malaysian seaweeds and proposed them as an alternative source of nutrients for humans to meet food security challenges.

Sugar is one of the key factors affecting sensory perception and consumers’ acceptance towards healthy foods and beverages. This study aimed to determine the sensory characteristics of three sugar reduced yoghurt drinks [0S0.02T0.6P, 2S0.02T0.3P, 4S0.01T0.3P where S, sugar percentage (0%, 2%, 4%); T, stevia dosage (0.01%, 0.02%); P, pectin dosage (0.3%, 0.6%)] through Check-All-That-Apply (CATA) analysis, evaluated by 151 consumer panellists. Significant differences (p

Abstract Objective Cardiac alterations represent a potential epilepsy‐associated comorbidity. Whether cardiac changes occur as a function of epilepsy duration is not well understood. We sought to evaluate whether cardiac alterations represented a time‐dependent phenomenon in pediatric epilepsy. Methods We retrospectively followed pediatric epilepsy patients without preexisting cardiac conditions or ion channelopathies who had history of pediatric intensive care unit admission for convulsive seizures or status epilepticus between 4/2014 and 7/2017. All available 12‐lead electrocardiograms (ECGs) from these patients between 1/2006 and 5/2019 were included. We examined ECG studies for changes in rhythm; PR, QRS, or corrected QT intervals; QRS axis or morphology; ST segment; or T wave. Data were analyzed using multivariable models containing covariates associated with ECG changes or epilepsy duration from the univariate analyses. Results 127 children with 323 ECGs were included in the analyses. The median epilepsy duration was 3.9 years (IQR 1.3‐8.4 years) at the time of an ECG study and a median of 2 ECGs (IQR 1‐3) per subject. The clinical encounters associated with ECGs ranged from well‐child visits to status epilepticus. We observed changes in 171 ECGs (53%), with 83 children (65%) had at least 1 ECG with alterations. In a multivariable logistic regression model adjusting for potentially confounding variables and accounting for clustering by patient, epilepsy duration was independently associated with altered ECGs for each year of epilepsy (OR: 1.1, 95% CI: 1.0‐1.2, P = .002). Extrapolating from this model, children with epilepsy durations of 10 and 15 years had 2.9 and 4.9 times the odds of having ECG changes, respectively. Significance Cardiac alterations may become more common with increasing epilepsy duration in select pediatric epilepsy patients. Future studies are needed to determine the potential clinical implications and the generalizability of these observations.

This study aimed to determine the prevalence of pediatric chronic pain by household food sufficiency status and examine whether food insufficiency would be associated with greater risk for chronic pain. We analyzed data from the 2019–2020 National Survey of Children’s Health of 48,410 children (6–17 years) in the United States. Across the sample, 26.1% (95% CI: 25.2–27.0) experienced mild food insufficiency and 5.1% (95% CI: 4.6–5.7) moderate/severe food insufficiency. The prevalence of chronic pain was higher among children with mild (13.7%) and moderate/severe food insufficiency (20.6%) relative to children in food-sufficient households (6.7%, p < 0.001). After adjusting for a priori covariates (individual: age, sex, race/ethnicity, anxiety, depression, other health conditions, adverse childhood events; household: poverty, parent education, physical and mental health; community: region of residence), multivariable logistic regression revealed that children with mild food insufficiency had 1.6 times greater odds of having chronic pain (95% CI: 1.4–1.9, p < 0.0001) and those with moderate/severe food insufficiency, 1.9 higher odds (95% CI: 1.4–2.7, p < 0.0001) relative to food-sufficient children. The dose–response relationship between food insufficiency and childhood chronic pain highlights the importance of further research to identify underlying mechanisms and evaluate the impact of food insufficiency on the onset and persistence of chronic pain across the lifespan.

A randomised controlled trial to measure the effects of integrating real-time continuous glucose monitor (rtCGM) into a low glycaemic index (GI) and glycaemic load (GL) dietary intervention on dietary intake, body composition and specific metabolic parameters was carried out. A total of 40 overweight young adults [(means ± SD) age: 26.4 ± 5.3 years, BMI: 29.4 ± 4.7 kg/m2] were randomised into an intervention and control groups for a period of eight weeks. Both groups received nutrition education on low GI and GL foods. The intervention group also received an rtCGM system to monitor their glucose levels 24 h a day. While controlling for physical activities and GI and GL nutrition knowledge, the results indicated that the rtCGM system further improved body weight, BMI, fat mass, fasting plasma glucose, HbA1c, total cholesterol, HDL cholesterol and LDL cholesterol in the intervention group (p < 0.05). This trial unveils the robustness of the rtCGM where non-diabetic overweight and obese young adults can benefit from this device and utilise it as a management tool for overweight and obesity and a primary prevention tool for type 2 diabetes, as it provides real-time and personalised information on physiological changes.

Understanding the causes of obesity epidemic requires examination of what contributes to preference of palatable foods. Using a sensorial-consumer approach, this research examined the relationship between the sensation of the hedonic liking of fat with psychological and weight profiles. The study began with preliminary testing of the hedonic ratings of 24 food items (12 low fat (LF), 12 high fat(HF)) and completion of the Three Factor Eating Questionnaire (TFEQ-R18) investigating cognitive restraint, uncontrolled eating and emotional eating aspects. Eight (8) out of the twelve (12) food pairs that had discriminating characteristics were selected, for inclusion in the study, by 347 panellists. Results showed that overweight individuals had significantly lower liking towards LF sensation (4.27±2.13, p= 0.001) but significantly higher liking towards HF sensation (5.26±2.33, p= 0.001), compared to normal BMI individuals who had a significantly higher liking towards LF sensation (5.69±2.35, p= 0.001) but significantly lower liking towards HF sensation (4.17±2.40, p= 0.001). The Pearson product-moment correlation revealed similar trends on the association between liking of fat sensation and eating behaviour regardless of weight statuses. Specifically, cognitive restrainers were found to prefer the LF sensation while HF sensation were more favoured among uncontrolled and emotional eaters. This highlights the importance of investigating the combined effect of psychological aspects of eating behaviour and weight profiles towards liking of fat sensation.

Postprandial hyperglycaemia is associated with an increased risk of type-2 diabetes. This study aims to determine the glycaemic index (GI) of three varieties of rice-based mixed meals and their effects on glycaemic variability (GV), 24 h mean glucose levels and target ranges, and rice variety preferences among overweight and obese young adults using real-time continuous glucose monitoring (rtCGM). In a randomised controlled crossover design, 14 participants (22.8 ± 4.6 years, 32.9 ± 5.8 kg/m2) were randomly assigned to receive 3 rice-based mixed meals containing 50 g of available carbohydrates (white rice meal = WRM; brown rice meal = BRM; and parboiled basmati rice meal = PBRM) and 50 g of a glucose reference drink on alternate days. GI, GV, 24 h mean glucose levels and target ranges were measured. Rice variety preferences were compared with those of baseline data and determined at the end of the study period. Results: The analysis found that PBRM was low in GI (45.35 ± 2.06), BRM medium in GI (56.44 ± 2.34), and WRM high in GI (83.03 ± 2.19). PBRM had a significantly (p < 0.05) lower 24 h mean glucose level, higher in-target 24 h glucose level percentage and non-significantly (p > 0.05) lower GV compared to WRM. Prior to observing their postprandial glucose levels generated by rtCGM, the participants preferred WRM (64.3%) over other meals, whereas this preference changed significantly (p < 0.05) at the endpoint (PBRM, 71.4%). PBRM reduced 24 h glucose level and GV of overweight and obese young adults. The rtCGM is proven to be reliable in measuring GI, while providing robust continuous glycaemic information. This may serve as an educational tool that motivates eating behaviour changes among overweight and obese young adults.

Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors. Identification of medical comorbidities that contribute to these concerns may elucidate mechanisms through which psychiatric concerns arise, as well as offer additional avenues for intervention. Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population. In this paper, we draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection to characterize the unique contributions of (1) autism symptoms, (2) psychosocial factors (child's age, sex, verbal and nonverbal IQ, adaptive behavior, race, and household income), and (3) GI concerns with respect to multiple psychiatric outcomes. Multiple regression models revealed unique contributions of ASD symptoms and multiple psychosocial factors such as verbal IQ, adaptive behavior, and family income to internalizing, externalizing, and self-injurious behavior. In general, higher levels of psychiatric symptoms were associated with more ASD symptoms, higher verbal IQ, lower adaptive behavior skills, and lower family income. Furthermore, levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD. Taken together, results indicate that the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD, and that treatment of GI conditions may be an important component in alleviating a broad array of mental health concerns in this group.

Two ladies with history of carcinoma of tongue presenting with un-resolving pneumonia were ultimately diagnosed to have lipoid pneumonia, and both were subsequently found to be associated with the practice of oil pulling which is a popular complementary therapy. Apart from cessation of oil pulling, they were treated with repeated therapeutic lobar broncho-alveolar lavage. despite the potential benefits of oil pulling on oral health, people especially those at risk of aspiration, should be properly informed of this potential risk when considering this form of complementary therapy.

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still largely neglected. To address this gap, we used gene expression data from 17 protist species to create protist.guru: an online database equipped with tools for identifying co-expressed genes, gene families, and co-expression clusters enriched for specific biological functions. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AVAILABILITY: The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: There remains limited data as to the feasibility, safety, and efficacy of higher doses of elective radiation therapy to the pelvic lymph nodes in men with high-risk prostate cancer. We conducted a phase II study to evaluate moderate dose escalation to the pelvic lymph nodes using a simultaneous integrated boost to the prostate., Methods and Materials: Patients were eligible with biopsy-proven adenocarcinoma of the prostate, a calculated lymph node risk of at least 25%, Karnofsky performance scale ≥70, and no evidence of M1 disease. Acute and late toxicity were prospectively collected at each follow-up using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The pelvic lymph nodes were treated to a dose of 56 Gy over 28 fractions with a simultaneous integrated boost to the prostate to a total dose of 70 Gy over 28 fractions using intensity-modulated radiation therapy., Results: Thirty patients were prospectively enrolled from October 2010 to August 2014. Median patient age was 70 years (57-83), pretreatment prostate-specific antigen was 11.5 ng/mL (3.23-111.5), T stage was T2c (T1c-T3b), and Gleason score was 9 (6-9). CTCAE v4.0 rate of any grade 1 or 2 genitourinary and gastrointestinal toxicity were 55% and 44%, respectively, and there was 1 reported acute grade 3 genitourinary and gastrointestinal toxicity, both unrelated to protocol therapy. With a median follow-up of 6.4 years, the biochemical failure free survival rate was 80.2%, and mean biochemical progression free survival was 8.3 years (95% confidence interval [CI], 7.2-9.4). The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free survival was 96%. Medians were not reached., Conclusions: In this single arm, small, prospective feasibility study, nodal radiation therapy dose escalation was safe, feasible, and seemingly well tolerated. Rates of progression free survival are highly encouraging in this population of predominately National Comprehensive Cancer Network very high-risk patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: Accurate staging at the time of prostate cancer diagnosis is fundamental to risk stratification and management counseling. Digital rectal exam (DRE) is foundational in clinical staging of prostate cancer, even with a known limited interexaminer agreement and poor sensitivity for detecting extraprostatic disease. We sought to evaluate the prognostic value of DRE for the presence of advanced pathologic features (APFs) following radical prostatectomy (RP)., Methods: All patients undergoing RP as primary treatment for clinically localized prostate cancer in the National Cancer Database between 2008 and 2014 were identified. Patients with additional malignancies, prior treatment with radiation or systemic therapy, incongruent clinical staging and DRE findings or without fully evaluable clinical staging were excluded. The primary outcome was the presence of postsurgical APFs, defined as positive surgical margins, nodal disease, or pathologic stage T3 or greater. Multivariable logistic regression analysis was performed to account for prostate-specific antigen (PSA), biopsy grade group, percent of positive biopsy cores, and clinical stage., Results: In total, 91,525 patients consisting of 69,182 cT1, 20,641 cT2, and 1702 cT3-T4 were included. The average age was 61.1 ± 7.0 years, and the average PSA was 8.6 ± 10.3 ng/ml. On multivariable analysis, cT3 and T4 were associated with the presence of APFs (odds ratio [OR] 11.12, p < .01 and 5.28, p = .04), however, cT2 was only slightly associated with the presence of APFs when compared with cT1 (OR 1.15, p < .01). Furthermore, cT2 was associated with more node-positive disease (OR 1.63, p < .01), positive margins (OR 1.06, p < .01), and more than or equal to pT3 disease (OR 1.22, p < .01)., Conclusions: Overall, advanced clinical stage as assessed by DRE was independently associated with an increasing risk of APFs. For individual APFs, the greatest effect is noticed between clinical stage and nodal positivity and less so between clinical stage and positive margins. DRE continues to hold value, particularly for patients with locally advanced disease and potential lymph node disease., (© 2021 Wiley Periodicals LLC.)

Purpose: Prostate cancer primarily arises from the glandular epithelium. Histomophometric techniques have been used to assess the glandular epithelium in automated detection and classification pipelines; however, they are often rigid in their implementation, and their performance suffers on large datasets where variation in staining, imaging, and preparation is difficult to control. The purpose of this study is to quantify performance of a pixelwise segmentation algorithm that was trained using different combinations of weak and strong stroma, epithelium, and lumen labels in a prostate histology dataset. Approach: We have combined weakly labeled datasets generated using simple morphometric techniques and high-quality labeled datasets from human observers in prostate biopsy cores to train a convolutional neural network for use in whole mount prostate labeling pipelines. With trained networks, we characterize pixelwise segmentation of stromal, epithelium, and lumen (SEL) regions on both biopsy core and whole-mount H&E-stained tissue. Results: We provide evidence that by simply training a deep learning algorithm on weakly labeled data generated from rigid morphometric methods, we can improve the robustness of classification over the morphometric methods used to train the classifier. Conclusions: We show that not only does our approach of combining weak and strong labels for training the CNN improve qualitative SEL labeling within tissue but also the deep learning generated labels are superior for cancer classification in a higher-order algorithm over the morphometrically derived labels it was trained on., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Objective: To describe the factors affecting patients' selection of a urologist, and the utilization of the Internet and social media., Materials and Methods: All new patients presenting to a single-institution for evaluation were invited to complete an anonymous 26-item questionnaire between April 2018 and October 2018, including demographic information, use of Internet and social media resources, and relative importance of factors when selecting a urologist. Descriptive statistics were reported, and a stratified analysis was performed for age, gender, and education., Results: A total of 238 patients responded. More than half (53%) of patients searched their medical condition prior to presentation. When stratified by age, younger patients were 3 times as likely to utilize Internet resources (Group 1 vs Group 2; OR 3.3, 95%CI 1.5-7.2, P <.01). Few patients utilized Facebook (7%) or Twitter (1%). The 3 most important surveyed urologist selection factors included hospital reputation (4.3 ± 1.0), in-network providers (4.0 ± 1.3), and appointment availability (3.9 ± 1.0). The 3 least important included medical school attended (2.7 ± 1.3), urologist on social media (1.9 ± 1.2), and TV, radio, and/or billboard advertisements (1.7 ± 1.3)., Conclusion: This study suggests a significant proportion of patients search the Internet regarding their medical condition prior to presenting to clinic. Further, younger patients utilize this methodology significantly more than the senior population. Important factors when selecting a urologist may be driven by a hospital's reputation, in addition to scheduling convenience., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The second-generation antiandrogen, enzalutamide, is approved for castrate-resistant prostate cancer (CRPC) and targets androgen receptor (AR) activity in CRPC. Despite initial clinical activity, acquired resistance to enzalutamide arises rapidly and most patients develop terminal disease. Previous work has established Stat5 as a potent inducer of prostate cancer growth. Here, we investigated the significance of Jak2-Stat5 signaling in resistance of prostate cancer to enzalutamide. The levels of Jak2 and Stat5 mRNA, proteins and activation were evaluated in prostate cancer cells, xenograft tumors, and clinical prostate cancers before and after enzalutamide therapy. Jak2 and Stat5 were suppressed by genetic knockdown using lentiviral shRNA or pharmacologic inhibitors. Responsiveness of primary and enzalutamide-resistant prostate cancer to pharmacologic inhibitors of Jak2-Stat5 signaling was assessed in vivo in mice bearing prostate cancer xenograft tumors. Patient-derived prostate cancers were tested for responsiveness to Stat5 blockade as second-line treatment after enzalutamide ex vivo in tumor explant cultures. Enzalutamide-liganded AR induces sustained Jak2-Stat5 phosphorylation in prostate cancer leading to the formation of a positive feed-forward loop, where activated Stat5, in turn, induces Jak2 mRNA and protein levels contributing to further Jak2 activation. Mechanistically, enzalutamide-liganded AR induced Jak2 phosphorylation through a process involving Jak2-specific phosphatases. Stat5 promoted prostate cancer growth during enzalutamide treatment. Jak2-Stat5 inhibition induced death of prostate cancer cells and patient-derived prostate cancers surviving enzalutamide treatment and blocked enzalutamide-resistant tumor growth in mice. This work introduces a novel concept of a pivotal role of hyperactivated Jak2-Stat5 signaling in enzalutamide-resistant prostate cancer, which is readily targetable by Jak2 inhibitors in clinical development., (©2019 American Association for Cancer Research.)

Loss of target antigens in tumor cells has become one of the major hurdles limiting the efficacy of adoptive cell therapy (ACT)-based immunotherapies. The optimal approach to overcome this challenge includes broadening the immune response from the initially targeted tumor-associated antigen (TAA) to other TAAs expressed in the tumor. To induce a more broadly targeted antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on the synergistic effect of pathogen-based immunotherapy and ACT. In this study, we showed that ReACT induced a sufficient endogenous CD8 + T-cell response beyond the initial target to prevent the outgrowth of antigen loss variants in a B16-F10 melanoma model. Sequentially, selective depletion experiments revealed that Batf3-driven cDC1s were essential for the activation of endogenous tumor-specific CD8 + T cells. In ReACT-treated mice that eradicated tumors, we observed that endogenous CD8 + T cells differentiated into memory cells and facilitated the rejection of local and distal tumor rechallenge. By targeting one TAA with ReACT, we provided broader TAA coverage to counter antigen escape and generate a durable memory response against local relapse and metastasis. See related Spotlight on p. 2 ., (©2019 American Association for Cancer Research.)

Background: A significant fraction of prostate cancer patients experience post-radical prostatectomy (RP) biochemical recurrence (BCR). New predictive markers are needed for optimizing postoperative prostate cancer management. STAT5 is an oncogene in prostate cancer that undergoes amplification in 30% of prostate cancers during progression., Methods: We evaluated the significance of a positive status for nuclear STAT5 protein expression versus STAT5 locus amplification versus combined positive status for both in predicting BCR after RP in 300 patients., Results: Combined positive STAT5 status was associated with a 45% disadvantage in BCR in Kaplan-Meier survival analysis in all Gleason grade patients. Patients with Gleason grade group (GG) 2 and 3 prostate cancers and combined positive status for STAT5 had a more pronounced disadvantage of 55% to 60% at 7 years after RP in univariate analysis. In multivariate analysis, including the Cancer of the Prostate Risk Assessment Postsurgical nomogram (CAPRA-S) variables, combined positive STAT5 status was independently associated with a shorter BCR-free survival in all Gleason GG patients (HR, 2.34; P = 0.014) and in intermediate Gleason GG 2 or 3 patients (HR, 3.62; P = 0.021). The combined positive STAT5 status improved the predictive value of the CAPRA-S nomogram in both ROC-AUC analysis and in decision curve analysis for BCR., Conclusions: Combined positive status for STAT5 was independently associated with shorter disease-free survival in univariate analysis and was an independent predictor for BCR in multivariate analysis using the CAPRA-S variables in prostate cancer., Impact: Our results highlight potential for a novel precision medicine concept based on a pivotal role of STAT5 status in improving selection of prostate cancer patients who are candidates for early adjuvant interventions to reduce the risk of recurrence., (©2019 American Association for Cancer Research.)

Background: Prostate cancer clinical stage T2 (cT2) subclassifications, as determined by digital rectal examination (DRE), are a historic method of staging prostate cancer. However, given the potential discomfort associated with prostate examination and the wide availability of other prognostic tests, the necessity of DRE is uncertain. This study sought to determine the prognostic value of the prostate cancer cT2 subclassifications in a contemporary cohort of patients., Methods: The National Cancer Database was used to identify a cohort of men with high-risk clinical T2N0M0 prostate cancer treated with external-beam radiotherapy and androgen deprivation therapies ± surgery from 2004 to 2010. We assessed overall survival from a landmark time of 10 months using Kaplan-Meier and log-rank test analysis. A multivariate proportional hazards model was used to estimate the simultaneous effects of multiple factors, including cT2 subclassification and other well-established prognostic indicators of overall survival in prostate cancer., Results: A total of 5,291 men were included in the final analysis, with a median follow-up of 5.4 years. The cT2a, cT2b, and cT2c subclassifications demonstrated increasing hazard ratios of 1.00 (reference), 1.25 (95% CI, 1.07-1.45; P=.0046), and 1.43 (95% CI, 1.25-1.63; P<.0001), respectively, reflecting a higher probability of death with each incremental increase in cT2 subclassification. This finding was independent of other known prognostic variables on multivariate analysis., Conclusions: Results show that cT2 subclassifications had independent prognostic value in a large and contemporary cohort of men. cT2 classification remains an important, low-cost prognostic tool for men with prostatic adenocarcinoma. The clinical relevance of this test should be appreciated and accounted for by providers treating prostate adenocarcinoma.

Prostate cancer is the most common noncutaneous cancer in men in the United States. The current paradigm for screening and diagnosis is imperfect, with relatively low specificity, high cost, and high morbidity. This study aims to generate new image contrasts by learning a distribution of unique image signatures associated with prostate cancer. In total, 48 patients were prospectively recruited for this institutional review board-approved study. Patients underwent multiparametric magnetic resonance imaging 2 weeks before surgery. Postsurgical tissues were annotated by a pathologist and aligned to the in vivo imaging. Radiomic profiles were generated by linearly combining 4 image contrasts (T2, apparent diffusion coefficient [ADC] 0-1000, ADC 50-2000, and dynamic contrast-enhanced) segmented using global thresholds. The distribution of radiomic profiles in high-grade cancer, low-grade cancer, and normal tissues was recorded, and the generated probability values were applied to a naive test set. The resulting Gleason probability maps were stable regardless of training cohort, functioned independent of prostate zone, and outperformed conventional clinical imaging (area under the curve [AUC] = 0.79). Extensive overlap was seen in the most common image signatures associated with high- and low-grade cancer, indicating that low- and high-grade tumors present similarly on conventional imaging.

Purpose: This study aims to combine multiparametric magnetic resonance imaging (MRI) and digitized pathology with machine learning to generate predictive maps of histologic features for prostate cancer localization., Methods and Materials: Thirty-nine patients underwent MRI prior to prostatectomy. After surgery, tissue was sliced according to MRI orientation using patient-specific 3-dimensionally printed slicing jigs. Whole-mount sections were annotated by our pathologist and digitally contoured to differentiate the lumen and epithelium. Slides were co-registered to the T2-weighted MRI scan. A learning curve was generated to determine the number of patients required for a stable machine-learning model. Patients were randomly stratified into 2 training sets and 1 test set. Two partial least-squares regression models were trained, each capable of predicting lumen and epithelium density. Predicted density values were calculated for each patient in the test dataset, mapped into the MRI space, and compared between regions confirmed as high-grade prostate cancer., Results: The learning-curve analysis showed that a stable fit was achieved with data from 10 patients. Maps indicated that regions of increased epithelium and decreased lumen density, generated from each independent model, corresponded with pathologist-annotated regions of high-grade cancer., Conclusions: We present a radio-pathomic approach to mapping prostate cancer. We find that the maps are useful for highlighting high-grade tumors. This technique may be relevant for dose-painting strategies in prostate radiation therapy., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Over the past 25 years, Pediatric Urology fellowship programs accredited by the Accreditation Council for Graduate Medical Education (ACGME) have more than doubled. This increase may lead to a significant decrease in the number of operative cases per surgeon and therefore impact the current practice of pediatric urology., Objective: The objective in conducting this study is to try and predict the effect of the current number of pediatric urology fellowship training positions on future case volume per surgeon using a mathematical model and to discuss future management of the pediatric urology workforce., Design: The current study employed a mathematical model to predict the effect of the number of fellowship graduates on future "case volume per surgeon". We incorporated population growth rates, to calculate incidence rates of key procedures/conditions and the anticipated retirement rate of the current pool of pediatric urologists to help calculate this., Results: There is a possibility to increase the number of practicing board-certified pediatric urologists in the next 30 years from approximately 325 to 900 (figure). There will be a twofold reduction in case volume per surgeon compared to the present in model 1. In model 2 the decrease in case volumes is less significant. The annual number of fellows needed to obtain a future-to-current ratio equal to 1 is 16 for model 1, and 26 for model 2., Discussion: Our study demonstrates, by using two different models that the current number of pediatric urology fellowship training positions in the United States will ultimately lead to a significant decrease in the case volume per surgeons. Our model has limitations as it relies on multiple assumptions. We are assuming that all fellowship positions would be filled every year and that all fellows would graduate, establish their practices in the United States, and devote 100% of their assumed 30-year professional career to pediatric urology. We also made assumptions of disease occurrence and need for surgical correction. The final assumption we made was that the birth rate would stay static over the next 30 years even though it has been declining for many decades., Conclusion: This exercise, even with its inherent limitations, is still sufficient to demonstrate that fellowship expansion warrants thoughtful discussion., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Multiparametric magnetic resonance imaging (MP-MRI), including diffusion-weighted imaging, is commonly used to diagnose prostate cancer. This radiology-pathology study correlates prostate cancer grade and morphology with common b -value combinations for calculating apparent diffusion coefficient (ADC). Thirty-nine patients undergoing radical prostatectomy were recruited for MP-MRI prior to surgery. Diffusion imaging was collected with seven b -values, and ADC was calculated. Excised prostates were sliced in the same orientation as the MRI using 3-D printed slicing jigs. Whole-mount slides were digitized and annotated by a pathologist. Annotated samples were aligned to the MRI, and ADC values were extracted from annotated peripheral zone (PZ) regions. A receiver operating characteristic (ROC) analysis was performed to determine accuracy of tissue type discrimination and optimal ADC b -value combination. ADC significantly discriminates Gleason (G) G4-5 cancer from G3 and other prostate tissue types. The optimal b -values for discriminating high from low-grade and noncancerous tissue in the PZ are 50 and 2000, followed closely by 100 to 2000 and 0 to 2000. Optimal ADC cut-offs are presented for dichotomized discrimination of tissue types according to each b -value combination. Selection of b -values affects the sensitivity and specificity of ADC for discrimination of prostate cancer.

Objectives: To evaluate the rate of perioperative complications after plasmakinetic bipolar and monopolar transurethral resection of bladder tumor (BTURB and MTURB). In addition, the study identifies patient and procedure characteristics associated with early complications., Patients and Methods: Retrospective review was conducted on patients undergoing transurethral resection of bladder tumor procedures at a single institution from 2003 to 2013 to assess the 30-day complication rates associated with BTURB and MTURB., Results: Four hundred twenty-seven patients met inclusion criteria and underwent 586 procedures (379 BTURB and 207 MTURB). Baseline patient demographics, tumor stage, and tumor grade were similar in BTURB and MTURB cohorts. The overall complication rate was 34.3% for MTURB and 26.7% for BTURB. The most frequent complications were acute urinary retention (AUR) 11%, hematuria 8%, and urinary tract infection (UTI) 7%. There was no statistical difference in rates of AUR, hematuria, UTI, or readmission for continuous bladder irrigation or hemostasis procedures between BTURB and MTURB cohorts. There was a trend toward lower perforation rate during BTURB (2.6% vs 5.8%). In multivariate logistic regression analysis, MTURB, male gender, and large resections were predictive of overall complications. Male gender was associated with hematuria and AUR. Large bladder tumor resection size was also associated with increased risk of overall complications and AUR., Conclusion: BTURB was associated with a lower risk of overall complications, but there was no difference in the rate of hematuria in the two cohorts. Male gender and large tumor size are associated with higher risk of early complications.

Purpose: Attenuated mycobacterium bacillus Calmette-Guérin is widely used as intravesical immunotherapy of nonmuscle invasive urothelial carcinoma. Currently there are limited data on the relationship between bacillus Calmette-Guérin dose intensity and tumor response. We evaluated the dose-response relationship of bacillus Calmette-Guérin to nonmuscle invasive bladder cancer in vitro using urothelial carcinoma cell lines and in vivo using an orthotopic mouse model., Materials and Methods: Two human urothelial carcinoma cell lines were used to study the effect of bacillus Calmette-Guérin dose on the tumor cell response. Internalization, activation of signaling pathways, gene transactivation, cell viability, lactate dehydrogenase and HMGB1 release were study end points. An orthotopic tumor model was used to compare the effect of different doses on the antitumor efficacy of bacillus Calmette-Guérin., Results: Bacillus Calmette-Guérin internalization by urothelial carcinoma cells increased as a function of time and dose with a plateau at higher doses and/or long exposure times. Intracellular signaling demonstrated a similar direct, dose dependent increase. Cytokine expression by urothelial carcinoma cells as a function of dose was variable. Some genes increased progressively but others showed a decrease at the highest dose. While nonviable cell number increased in proportion to dose, the number of cells undergoing necrotic cell death decreased at higher doses. A higher dose of bacillus Calmette-Guérin (1:200) showed a better antitumor effect than a standard dose (1:50) (p <0.01)., Conclusions: Bacillus Calmette-Guérin dose has a direct impact on urothelial carcinoma cell biology. Increased dose intensity, particularly in nonresponders, may represent a strategy to increase bacillus Calmette-Guérin treatment efficacy., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Thermoacoustics has the potential to provide quantitative images of intrinsic tissue properties, most notably electrical conductivity in Siemens/meter, much as shear wave elastography provides tissue stiffness in kilopascal. Although thermoacoustic imaging with optical excitation has been commercialized for small animals, it has not yet made the transition to clinic for whole organ imaging in humans. The purpose of this work was to develop and validate specifications for a clinical ultrasound array for quantitative whole organ thermoacoustic imaging. Imaging a large organ requires exciting thermoacoustic pulses throughout the volume and broadband detection of those pulses because tomographic image reconstruction preserves frequency content. Applying the half-wavelength limit to a [Formula: see text] inclusion inside a 7.5-cm diameter organ requires measurement sensitivity to frequencies ranging from 4 MHz to 10 kHz, respectively. A dual-transducer system utilizing a P4-1 array connected to a Verasonics V1 system as well as a focused single-element transducer sensitive to lower frequencies was developed. Very high-frequency (VHF) irradiation generated thermoacoustic pulses throughout a [Formula: see text] volume. In the VHF regime, electrical conductivity drives thermoacoustic signal production. Simultaneous acquisition of thermoacoustic pulses by both transducers enabled comparison of transducer performance. Data from the clinical array generated a stack of 96 images with a separation of 0.3 mm, whereas the single-element transducer imaged only in a single plane. In-plane resolution and quantitative accuracy were quantified at isocenter. The array provided volumetric imaging capability with superior resolution whereas the single-element transducer provided superior quantitative accuracy in axial images. Combining axial images from both transducers preserved resolution of the P4-1 array and improved image contrast. Neither transducer was sensitive to frequencies below 50 kHz, resulting in a dc offset and low-frequency shading over fields of view exceeding 15 mm. Fresh human prostates were imaged ex vivo and volumetric reconstructions reveal structures rarely seen in diagnostic images. In conclusion, quantitative whole-organ thermoacoustic tomography will be feasible by sparsely interspersing transducer elements sensitive to the low end of the ultrasonic range.

Introduction: We instituted a ketamine-predominant analgesic regimen in the peri- and postoperative periods to limit the effects of narcotic analgesia on bowel function in patients undergoing radical cystectomy. The primary end points of interest were time to return of bowel function, time to discharge, and efficacy of the analgesic regimen., Methods: We performed a retrospective chart review of patients undergoing robotic-assisted laparoscopic cystectomy (RARC) with urinary diversion by a single surgeon at our institution from January 1, 2011 to June 30, 2012. Patients receiving the opioid-minimizing ketamine protocol were compared to a cohort of patients undergoing RARC with an opioid-predominant analgesic regimen., Results: In total, 15 patients (Group A) were included in the ketamine-predominant regimen and 25 patients (Group B) in the opioid-predominant control group. Three patients (19%) in Group A discontinued the protocol due to ketamine side effects. The mean time to bowel movement and length of stay in Group A versus Group B was 3 versus 6 days (p < 0.001), and 4 versus 8 days, respectively (p < 0.001). Group A patients received an average of 13.0 mg of morphine versus 97.5 mg in Group B (p < 0.001)., Conclusions: Patients who received our ketamine pain control regimen had a shorter time to return of bowel function and length of hospitalization after RARC. Our study has its limitations as a retrospective, single surgeon, single institution study and the non-randomization of patients. Notwithstanding these limitations, this study was not designed to show inferiority of one approach, but instead to show that our protocol is safe and efficacious, warranting further study in a prospective fashion.

Objective: To compare perioperative morbidity and oncological outcomes of robot-assisted laparoscopic radical cystectomy (RARC) to open RC (ORC) at a single institution., Patients and Methods: A retrospective analysis was performed on a consecutive series of patients undergoing RC (100 RARC and 100 ORC) at Wake Forest University with curative intent from 2006 until 2010. Complication data using the Clavien system were collected for 90 days postoperatively. Complications and other perioperative outcomes were compared between patient groups., Results: Patients in both groups had comparable preoperative characteristics. The overall and major complication (Clavien ≥ 3) rates were lower for RARC patients at 35 vs 57% (P = 0.001) and 10 vs 22% (P = 0.019), respectively. There were no significant differences between groups for pathological outcomes, including stage, number of nodes harvested or positive margin rates., Conclusion: Our data suggest that patients undergoing RARC have perioperative oncological outcomes comparable with ORC, with fewer overall or major complications. Definitive claims about comparative outcomes with RARC require results from larger, randomised controlled trials., (Copyright © 2014 Elsevier Inc. All rights reserved.)