Demographic Comparison of the Burden of Endoscopically Screenable Cancers in the United States.

Background and Aims: Gastrointestinal cancer incidence varies by race and ethnicity. In the United States (US), there are screening guidelines for esophageal cancer (EC) and colorectal cancer (CRC), but not gastric cancer (GC). We compared GC, CRC, and EC incidence among the most populous racial and ethnic groups to inform US interception strategies. Methods: We used SEER∗Stat to compare GC, CRC, and EC incidence rates across non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 8 largest Asian American populations using the Surveillance, Epidemiology, and End Results 9 registries (2010-2014). Results: Noncardia GC incidence was highest among Korean (18.7 cases per 100,000) and lowest among NHW (1.4 cases per 100,000) Americans. CRC incidence was highest among non-Hispanic Black, Southeast Asian, and Japanese (35.9, 34.2, and 33.8 per 100,000, respectively) Americans and lowest among South Asian Americans (18.9 per 100,000). EC incidence was greatest in NHW (4.7 per 100,000) and lowest in Filipino (1.2 per 100,000) Americans. The incidence of noncardia GC slightly exceeded colon cancer in Korean American men (25.5 vs 22.4 per 100,000). GC surpassed EC incidence in all non-White racial and ethnic groups. Conclusion: The burden of GC, CRC, and EC differs based on race and ethnicity. Non-White racial and ethnic groups experience a disproportionate burden of GC for which systematic programs for cancer interception, similar to CRC and EC, are needed.

Extended nnU-Net for Brain Metastasis Detection and Segmentation in Contrast-Enhanced Magnetic Resonance Imaging With a Large Multi-Institutional Data Set.

PURPOSE: The purpose of this study was to investigate an extended self-adapting nnU-Net framework for detecting and segmenting brain metastases (BM) on magnetic resonance imaging (MRI). METHODS AND MATERIALS: Six different nnU-Net systems with adaptive data sampling, adaptive Dice loss, or different patch/batch sizes were trained and tested for detecting and segmenting intraparenchymal BM with a size ≥2 mm on 3 Dimensional (3D) post-Gd T1-weighted MRI volumes using 2092 patients from 7 institutions (1712, 195, and 185 patients for training, validation, and testing, respectively). Gross tumor volumes of BM delineated by physicians for stereotactic radiosurgery were collected retrospectively and curated at each institute. Additional centralized data curation was carried out to create gross tumor volumes of uncontoured BM by 2 radiologists to improve the accuracy of ground truth. The training data set was augmented with synthetic BMs of 1025 MRI volumes using a 3D generative pipeline. BM detection was evaluated by lesion-level sensitivity and false-positive (FP) rate. BM segmentation was assessed by lesion-level Dice similarity coefficient, 95-percentile Hausdorff distance, and average Hausdorff distance (HD). The performances were assessed across different BM sizes. Additional testing was performed using a second data set of 206 patients. RESULTS: Of the 6 nnU-Net systems, the nnU-Net with adaptive Dice loss achieved the best detection and segmentation performance on the first testing data set. At an FP rate of 0.65 ± 1.17, overall sensitivity was 0.904 for all sizes of BM, 0.966 for BM ≥0.1 cm3, and 0.824 for BM <0.1 cm3. Mean values of Dice similarity coefficient, 95-percentile Hausdorff distance, and average HD of all detected BMs were 0.758, 1.45, and 0.23 mm, respectively. Performances on the second testing data set achieved a sensitivity of 0.907 at an FP rate of 0.57 ± 0.85 for all BM sizes, and an average HD of 0.33 mm for all detected BM. CONCLUSIONS: Our proposed extension of the self-configuring nnU-Net framework substantially improved small BM detection sensitivity while maintaining a controlled FP rate. Clinical utility of the extended nnU-Net model for assisting early BM detection and stereotactic radiosurgery planning will be investigated.

Endoscopic Surveillance of Gastric Intestinal Metaplasia: A Retrospective Cohort Study.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precancerous condition. Limited data exist on real-world clinical practice relative to guidelines. AIM: The aim of this study was to evaluate adherence to GIM risk stratification and identify factors associated with follow-up endoscopy. MATERIALS AND METHODS: We conducted manual chart review of patients with histologically confirmed GIM at an urban, tertiary medical center were identified retrospectively and details of their demographics, Helicobacter pylori, biopsy protocol, endoscopic/histologic findings, and postendoscopy follow-up were recorded. Multivariable logistic regression was used to identify factors independently associated with follow-up endoscopy. RESULTS: Among 253 patients, 59% were female, 37% non-Hispanic White (NHW), 26% Hispanic, 16% non-Hispanic Black (NHB). The median age at index endoscopy was 63.4 years (IQR: 55.9 to 70.0), with median follow-up of 65.1 months (IQR: 44.0 to 72.3). H. pylori was detected in 21.6% patients at index EGD. GIM extent and subtype data were frequently missing (22.9% and 32.8%, respectively). Based on available data, 26% had corpus-extended GIM and 28% had incomplete/mixed-type GIM. Compared with NHW, Hispanic patients had higher odds of follow-up EGD (OR=2.48, 95% CI: 1.23-5.01), while NHB patients had 59% lower odds of follow-up EGD (OR=0.41, 95% CI: 0.18-0.96). Corpus-extended GIM versus limited GIM (OR=2.27, 95% CI: 1.13-4.59) was associated with follow-up EGD, but GIM subtype and family history of gastric cancer were not. CONCLUSIONS: We observed suboptimal risk stratification among patients with GIM and notable race and ethnic disparities with respect to endoscopic surveillance. Targeted interventions are needed to improve practice patterns and mitigate observed disparities.

Identification of Priorities for Colorectal Cancer Screening Interventions Among US Hispanic/Latino Populations.

Objectives. To identify nationwide census tract‒level areas where improving colorectal cancer (CRC) screening uptake via targeted local preventive intervention may benefit Hispanic or Latino/a (H/L) groups defined by region or country of origin. Methods. Using 2021 Centers for Disease Control and Prevention PLACES and American Community Survey data, we applied geographically weighted regression and Getis-Ord Gi* hot spot procedures to identify CRC screening priority zones for H/L groups in the United States. Priority zones can be conceptualized as census tracts with strong inverse associations between percentage of a particular H/L group in the population and CRC screening rate, after adjusting for socioeconomic deprivation and lack of insurance. Results. We identified 6519, 3477, 3522, 1069, and 1424 census tract CRC screening priority zones for H/L communities of Mexican, Puerto Rican, Central/South American, Dominican, and Cuban heritage, respectively. Priority zones for H/L groups had strong spatial heterogeneity, and overlap of geographic patterns among H/L groups varied by region. Conclusions. Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefitting specific H/L communities in the United States. (Am J Public Health. 2024;114(S6):S515-S524. https://doi.org/10.2105/AJPH.2024.307733) [Formula: see text].

What the Fika? Implementation of Swedish Coffee Breaks During Emergency Medicine Conference.

Introduction: In this study we aimed to investigate the effects of incorporating Swedish-style fika (coffee) breaks into the didactic schedule of emergency medicine residents on their sleepiness levels during didactic sessions. Fika is a Swedish tradition that involves a deliberate decision to take a break during the workday and usually involves pastries and coffee. We used the Karolinska Sleepiness Scale to assess changes in sleepiness levels before and after the implementation of fika breaks. Methods: The study design involved a randomized crossover trial approach, with data collected from emergency medicine residents over a specific period. This approach was done to minimize confounding and to be statistically efficient. Results: Results revealed the average sleepiness scale was 4.6 and 5.5 on fika and control days, respectively (P = 0.004). Conclusion: Integration of fika breaks positively influenced sleepiness levels, thus potentially enhancing the educational experience during residency didactics.

Differences in health-related quality of life and somatic symptoms in employed and unemployed patients with epilepsy.

This study compared overall and specific aspects of health-related quality of life (HRQOL) and self-report of somatic, anxiety, and depressive symptoms between employed (n = 71) and unemployed (n = 48) patients with epilepsy (PWE). The Quality of Life in Epilepsy (QOLIE-89) and the Personality Assessment Inventory (PAI) were examined. The unemployed group reported significantly worse overall HRQOL including aspects of HRQOL related to epilepsy, physical health, mental health, and cognitive function. Among these four, physical health related HRQOL revealed the most difference between groups. While there were no differences between the groups in the level of social support and social isolation, the unemployed group reported worse social function with respect to work and driving. The unemployed group reported significantly greater somatic symptoms, but not anxiety and depressive symptoms. When specifically examining the subscales of the Somatic Concerns scale, conversion and health concerns, but not somatization, were greater in the unemployed group. Among the Depression subscales, the unemployed group reported greater physiologically manifested depressive symptoms. These findings suggest that along with optimizing seizure control, identifying and addressing presence of physical limitations, dysfunction, and somatic symptoms are also of importance in the care of PWE, particularly for those who are unemployed.

Sessile serrated polyp detection rates after fecal immunochemical test or multitarget stool DNA test: Systematic review and meta-analysis.

Background and study aims Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for sessile serrated polyp (SSP) detection. We performed a meta-analysis to evaluate the performance of FIT and FIT-DNA testing for SSP detection rate (SSPDR) in patients undergoing colonoscopy for follow up of positive noninvasive tests. Methods A comprehensive literature search of multiple databases (until September 2022) was performed to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA tests. The outcome was overall colonoscopy detection of any SSPs and advanced serrated polyps (ASP: SSP ≥ 10 mm and/or dysplasia). Results Included were 482,405 patients (52.4% females) with a mean age of 62.3 ± 4.4 years from 23 studies. The pooled SSPDR for all positive stool-based tests was 5.3% and higher for FIT-DNA (15.0%, 95% confidence interval [CI] 8.3-25.7) versus FIT (4.1%, 95% CI 3.0-5.6; P = 0.0002). The overall pooled ASP detection rate was 1.4% (95% CI 0.81-2.3) and higher for FIT-DNA (3.8 %, 95% CI 1.7-8.6) compared with FIT (0.71%, 95% CI 0.36-1.4; P <0.01). SSPDR with FIT-DNA was also significantly higher than FIT when the FIT cutoff was >10 ug/g and in FIT-positive patients in studies conducted in North America ( P <0.05). Conclusions FIT-DNA outperformed FIT in both SSP and ASP detection including FIT with a lower threshold cutoff of >10 ug/g. Further comparative studies are needed to assess the impact of our findings on colorectal cancer reduction.

Adipocyte-released adipomes in Chagas cardiomyopathy: Impact on cardiac metabolic and immune regulation.

Chronic Trypanosoma cruzi infection leads to Chagas cardiomyopathy (CCM), with varying manifestations such as inflammatory hypertrophic cardiomyopathy, arrhythmias, and dilated cardiomyopathy. The factors responsible for the increasing risk of progression to CCM are not fully understood. Previous studies link adipocyte loss to CCM progression, but the mechanism triggering CCM pathogenesis remains unexplored. Our study uncovers that T. cruzi infection triggers adipocyte apoptosis, leading to the release of extracellular vesicles named "adipomes". We developed an innovative method to isolate intact adipomes from infected mice's adipose tissue and plasma, showing they carry unique lipid cargoes. Large and Small adipomes, particularly plasma-derived infection-associated L-adipomes (P-ILA), regulate immunometabolic signaling and induce cardiomyopathy. P-ILA treatment induces hypertrophic cardiomyopathy in wild-type mice and worsens cardiomyopathy severity in post-acute-infected mice by regulating adipogenic/lipogenic and mitochondrial functions. These findings highlight adipomes' pivotal role in promoting inflammation and impairing myocardial function during cardiac remodeling in CD.

Integrating multi-modal imaging in radiation treatments for glioblastoma.

Advances in diagnostic and treatment technology along with rapid developments in translational research may now allow the realization of precision radiotherapy. Integration of biologically informed multimodality imaging to address the spatial and temporal heterogeneity underlying treatment resistance in glioblastoma is now possible for patient care, with evidence of safety and potential benefit. Beyond their diagnostic utility, several candidate imaging biomarkers have emerged in recent early-phase clinical trials of biologically based radiotherapy, and their definitive assessment in multicenter prospective trials is already in development. In this review, the rationale for clinical implementation of candidate advanced magnetic resonance imaging and positron emission tomography imaging biomarkers to guide personalized radiotherapy, the current landscape, and future directions for integrating imaging biomarkers into radiotherapy for glioblastoma are summarized. Moving forward, response-adaptive radiotherapy using biologically informed imaging biomarkers to address emerging treatment resistance in rational combination with novel systemic therapies may ultimately permit improvements in glioblastoma outcomes and true individualization of patient care.

Practice Trends among US Gastroenterologists following the 2020 American Gastroenterological Association Guidelines on Gastric Intestinal Metaplasia: Data from a Tertiary Care Center.

BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.

Endoscopic Surveillance of Intestinal Metaplasia of the Esophagogastric Junction: A Decision Modeling Analysis.

INTRODUCTION: The incidence of esophagogastric junction adenocarcinoma (EGJAC) has been rising. Intestinal metaplasia of the esophagogastric junction (EGJIM) is a common finding in gastroesophageal reflux (irregular Z-line) and may represent an early step in the development of EGJAC in the West. Worldwide, EGJIM may represent progression along the Correa cascade triggered by Helicobacter pylori . We sought to evaluate the cost-effectiveness of endoscopic surveillance of EGJIM. METHODS: We developed a decision analytic model to compare endoscopic surveillance strategies for 50-year-old patients after diagnosis of non-dysplastic EGJIM: (i) no surveillance (standard of care), (ii) endoscopy every 3 years, (iii) endoscopy every 5 years, or (iv) 1-time endoscopy at 3 years. We modeled 4 progression scenarios to reflect uncertainty: A (0.01% annual cancer incidence), B (0.05%), C (0.12%), and D (0.22%). RESULTS: Cost-effectiveness of endoscopic surveillance depended on the progression rate of EGJIM to cancer. At the lowest progression rate (scenario A, 0.01%), no surveillance strategies were cost-effective. In moderate progression scenarios, 1-time surveillance at 3 years was cost-effective, at $30,989 and $16,526 per quality-adjusted life year for scenarios B (0.05%) and C (0.12%), respectively. For scenario D (0.22%), surveillance every 5 years was cost-effective at $77,695 per quality-adjusted life year. DISCUSSION: Endoscopic surveillance is costly and can cause harm; however, low-intensity longitudinal surveillance (every 5 years) is cost-effective in populations with higher EGJAC incidence. No surveillance or 1-time endoscopic surveillance of patients with EGJIM was cost-effective in low-incidence populations. Future studies to better understand the natural history of EGJIM, identify risk factors of progression, and inform appropriate surveillance strategies are required.

Microbiome Depletion Increases Fentanyl Self-Administration and Alters the Striatal Proteome Through Short-Chain Fatty Acids.

Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increased rates of use and overdose of synthetic opioids, primarily fentanyl. Therefore, the identification of novel biomarkers and treatment strategies to reduce problematic fentanyl use and relapse to fentanyl taking is critical. In recent years, there has been a growing body of work demonstrating that the gut microbiome can serve as a potent modulator of the behavioral and transcriptional responses to both stimulants and opioids. Here, we advance this work to define how manipulations of the microbiome drive fentanyl intake and fentanyl-seeking in a translationally relevant drug self-administration model. Depletion of the microbiome of male rats with broad spectrum antibiotics leads to increased drug administration on increased fixed ratio, progressive ratio, and drug seeking after abstinence. Utilizing 16S  sequencing of microbiome contents from these animals, specific populations of bacteria from the gut microbiome correlate closely with levels of drug taking. Additionally, global proteomic analysis of the nucleus accumbens following microbiome manipulation and fentanyl administration to define how microbiome status alters the functional proteomic landscape in this key limbic substructure. These data demonstrate that an altered microbiome leads to marked changes in the synaptic proteome in response to repeated fentanyl treatment. Finally, behavioral effects of microbiome depletion are reversible by upplementation of the microbiome derived short-chain fatty acid metabolites. Taken together, these findings establish clear relevance for gut-brain signaling in models of OUD and lay foundations for further translational work in this space.

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2 < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.

Detection of tick-borne bacterial DNA (Rickettsia sp.) in reptile ticks Amblyomma moreliae from New South Wales, Australia.

Ticks are major arthropod vectors of disease, transmitting tick-borne pathogens during blood meal episodes. Rickettsia spp. and Borrelia spp. are two tick-borne pathogens of zoonotic concern previously identified in DNA isolates from the tick genera Amblyomma and Bothriocroton associated with reptilian hosts in Australia. Some reports suggest that these reptile ticks bite and attach to humans via accidental parasitism and transmit disease, with the tick Bothriocroton hydrosauri known to transmit Rickettsia honei or Flinders Island Spotted Fever Rickettsia to humans. This descriptive study aims to identify the ticks collected from wild reptiles submitted to veterinary clinics and captured by snake rescuers from New South Wales (NSW), Australia, and detect the presence of tick-borne bacterial DNA using quantitative polymerase chain reaction (qPCR) to detect Rickettsia spp. and Bartonella spp. and conventional nested-PCR to detect Borrelia spp. Morphological identification revealed ticks removed from one eastern blue-tongued lizard (Tiliqua scincoides scincoides) from North-Eastern NSW (Lismore), one eastern blue-tongued lizard from the Greater Sydney area (Canley Heights), one diamond python (Morelia spilota spilota) from the Greater Sydney area (Woronora Heights) and one red-bellied black snake (Pseudechis porphyriacus) from the Greater Sydney Area (Cronulla) in New South Wales were Amblyomma moreliae. No ticks were positive for Bartonella spp. and Borrelia spp. DNA using real-time PCR targeting ssrA gene and nested PCR targeting Borrelia-specific 16S rRNA gene, respectively. Real-time PCR targeting gltA, ompA, ompB and 17kDa gene of Rickettsia spp. revealed 14 out of 16 ticks were positive. The undescribed Rickettsia sp. DNA was identical to that previously recovered from reptile ticks in Australia and closely related to Rickettsia tamurae and Rickettsia monacensis, both of which are aetiologic pathogens of the Spotted Fever Group Rickettsiosis (SFGR). These results accentuate the ongoing need for increased study efforts to understand zoonotic potential of bacteria from reptile ticks and the tick-reptile-human relationship.

Clinical significance of prostate cancer identified by transperineal standard template biopsy in men with nonsuspicious multiparametric magnetic resonance imaging.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csCaP). However, whether a negative mpMRI in patients with a clinical suspicion of CaP can omit a confirmatory biopsy remains less understood and without consensus. Transperineal (TP) standard template biopsy (SBx) provides an effective approach to CaP detection. Our aim is to provide a comprehensive understanding of the CaP characteristics detected through TP SBx that are systematically overlooked by mpMRI. METHODS: We conducted a retrospective analysis of all men who underwent prebiopsy mpMRI and subsequent a 20-core TP SBx at our hospital from September 2019 to February 2021. Patients with suspicious mpMRI received a combined TP SBx and targeted biopsy (TBx) (suspicious group), while those without suspicious (negative) mpMRI and who proceeded to biopsy, received TP SBx only (nonsuspicious group). A negative mpMRI was defined as the absence of suspicious findings and/or the presence of low-risk areas with a PI-RADS score of ≤2. Subsequently, we compared and evaluated the clinical and biopsy characteristics between these 2 groups. RESULTS: We identified 301 men in suspicious group and 215 men in nonsuspicious group. The overall CaP detection rate and csCaP detection rate by TP SBx were 74.1%, 38.9% for suspicious group and 43.3%, 14.9% for nonsuspicious group, respectively. csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. The greatest percentage of cancer involvement (GPC) in biopsy core from nonsuspicious group was significantly lower than those of suspicious group (40% vs. 50%, p = 0.005), In multivariate logistic analysis, only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. CONCLUSION: Within our cohort, false-negative rates of mpMRI for csCaP are substantial, reaching 15%. Nonsuspicious cases may contain a large volume tumor since the high GPC of SBx. For cases with nonsuspicious imaging and higher PSAD, a confirmatory biopsy may be necessary due to the increased risk of missed csCaP by mpMRI.

Differential effects of OATP2B1 on statin accumulation and toxicity in a beta cell model.

An increased risk of new-onset diabetes mellitus has been recently reported for statin therapy, and experimental studies have shown reduced glucose-stimulated insulin secretion (GSIS) and mitochondrial dysfunction in beta cells with effects differing among agents. Organic anion transporting polypeptide (OATP) 2B1 contributes to hepatic uptake of rosuvastatin, atorvastatin and pravastatin, three known substrates. Since OATP2B1 is present in beta cells of the human pancreas, we investigated if OATP2B1 facilitates the local accumulation of statins in a rat beta cell model INS-1 832/13 (INS-1) thereby amplifying statin-induced toxicity. OATP2B1 overexpression in INS-1 cells via adenoviral transduction showed 2.5-, 1.8- and 1.4-fold higher cellular retention of rosuvastatin, atorvastatin and pravastatin, respectively, relative to LacZ control, while absolute intracellular concentration was about twice as high for the lipophilic atorvastatin compared to the more hydrophilic rosuvastatin and pravastatin. After 24 h statin treatment at high concentrations, OATP2B1 enhanced statin toxicity involving activation of intrinsic apoptosis (caspase 3/7 activation) and mitochondrial dysfunction (NADH dehydrogenase activity) following rosuvastatin and atorvastatin, which was partly reversed by isoprenoids. OATP2B1 had no effect on statin-induced reduction in GSIS, mitochondrial electron transport chain complex expression or caspase 9 activation. We confirmed a dose-dependent reduction in insulin secretion by rosuvastatin and atorvastatin in native INS-1 with a modest change in cellular ATP. Collectively, our results indicate a role of OATP2B1, which is abundant in human beta cells, in statin accumulation and statin-induced toxicity but not insulin secretion of rosuvastatin and atorvastatin in INS-1 cells.

Challenges in and Opportunities for Electronic Health Record-Based Data Analysis and Interpretation.

Electronic health records (EHRs) have been increasingly adopted in clinical practices across the United States, providing a primary source of data for clinical research, particularly observational cohort studies. EHRs are a high-yield, low-maintenance source of longitudinal real-world data for large patient populations and provide a wealth of information and clinical contexts that are useful for clinical research and translation into practice. Despite these strengths, it is important to recognize the multiple limitations and challenges related to the use of EHR data in clinical research. Missing data are a major source of error and biases and can affect the representativeness of the cohort of interest, as well as the accuracy of the outcomes and exposures. Here, we aim to provide a critical understanding of the types of data available in EHRs and describe the impact of data heterogeneity, quality, and generalizability, which should be evaluated prior to and during the analysis of EHR data. We also identify challenges pertaining to data quality, including errors and biases, and examine potential sources of such biases and errors. Finally, we discuss approaches to mitigate and remediate these limitations. A proactive approach to addressing these issues can help ensure the integrity and quality of EHR data and the appropriateness of their use in clinical studies.

Estimated Prostate Volume by Semiautomatic Segmentation of MRI Is More Accurately Correlated with Radical Prostatectomy Specimen Weight than the Volume Calculated by Ellipsoid Formula.

INTRODUCTION: Accurate in vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI)-estimated PV compared to both volume and weight of radical prostatectomy (RP). METHODS: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. RP PV was calculated using the prolate ellipsoid formula (length × width × height × π/6). Formula (prostate weight = [actual weight-3.8 g]/1.05 g/mL) was applied, and the resulting volume was used in further analysis. RESULTS: The median PV from MRI, RP, and RP weight were 39 mL, 38 mL, and 44 mL, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs. RP weight), 0.758 (RP PV vs. RP weight), and 0.707 (MRI PV vs. RP PV) (all p < 0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55 mL) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs. 57.6% vs. 45.4%). CONCLUSION: MRI PV is correlated better with RP weight than calculated RP PV, especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.