When the p Value Doesn't Cut It: The Fragility Index Applied to Randomized Controlled Trials in Colorectal Surgery.

BACKGROUND: The American Statistical Association, among others, has called for the use of statistical methods beyond p ≤ 0.05. The fragility index is a statistical metric defined as the minimum number of patients for whom if an event rather than a nonevent occurred, then the p value would increase to ≥0.05. Previous reviews have demonstrated that many randomized controlled trials have a low fragility index, suggesting they may not be robust. OBJECTIVE: The purpose of this study was to review the fragility indices of randomized controlled trials in colorectal surgery. DATA SOURCES: A PubMed search was performed. STUDY SELECTION: Colorectal surgery randomized controlled trials with a dichotomous primary outcome p ≤ 0.05 and publication between 2016 and 2018 were systematically identified. INTERVENTIONS: All procedural interventions related to colorectal surgery were included. MAIN OUTCOME MEASURES: The main measures were the fragility index and the number of patients lost to follow-up for each trial. The percentage of trials with the number of patients lost to follow-up greater than the fragility index was calculated. RESULTS: In total, 712 abstracts were reviewed, with 90 trials meeting the inclusion criteria. The median fragility index was 3 (interquartile range of 1 to 10). In 51 of the 90 trials (57%), the number of patients lost to follow-up was greater than the fragility index. LIMITATIONS: The fragility index is only one measure of the robustness of a randomized clinical trial. CONCLUSIONS: Most colorectal surgery randomized controlled trials have a low fragility index. In 57% of trials, more patients were lost to follow-up than would be required to change the outcome of the trial from "significant" to "nonsignificant" based on the p value. This emphasizes the importance of assessing the robustness of clinical trials when considering their clinical application, rather than relying solely on the p value. See Video Abstract at http://links.lww.com/DCR/B741.CUANDO EL VALOR-P ES INSUFICIENTE: ÍNDICE DE FRAGILIDAD APLICADO EN ESTUDIOS ALEATORIOS CONTROLADOS EN CIRUGÍA COLORECTAL. ANTECEDENTES: La Sociedad Estadounidense de Estadística, entre otros, ha pedido el uso de métodos estadísticos más allá de p <0,05. El índice de fragilidad es una medida estadística definida como el número de desenlaces que podrían cambiar para revertir, o conseguir, la significación estadística, así el valor p aumentaría a ≥ 0,05. Las revisiones anteriores han demostrado que muchos estudios aleatorios controlados tienen un índice de fragilidad bajo, lo que sugiere que pueden poco sólidos. OBJETIVO: El propósito de la présente investigación fué de revisar los índices de fragilidad de los estudios aleatorios controlados en cirugía colorrectal. FUENTES DE DATOS: PubMed. SELECCIN DE ESTUDIOS: Se identificaron sistemáticamente estudios aleatorios controlados de cirugía colorrectal con un resultado primario dicotómico, valor de p ≤ 0,05 y publicados entre 2016-2018. INTERVENCIONES: Se incluyeron todas aquellas intervenciones con procedimientos relacionados con la cirugía colorrectal. PRINCIPALES MEDIDAS DE RESULTADO: Las principales medidas fueron: el índice de fragilidad y el número de pacientes perdidos durante el seguimiento en cada estudio. Se calculó el el índice de fragilidad en porcentaje de estudios con el mayor número de pacientes perdidos durante el seguimiento mas prolongado. RESULTADOS: En total, se revisaron 712 resúmenes con 90 ensayos que cumplieron con los criterios de inclusión. La mediana del índice de fragilidad fue de 3 (rango intercuartíl de 1 a 10). En 51 de los 90 estudios (57%), el número de pacientes perdidos durante el seguimiento fue mayor que el índice de fragilidad. LIMITACIONES: El índice de fragilidad es solo una medida de la robustez de un estúdio clínico aleatorio. CONCLUSIONES: La mayoría de los estudios aleatorios y controlados en cirugía colorrectal tienen un índice de fragilidad bajo. En el 57% de los estudios, se perdieron más pacientes durante el seguimiento de los que se necesitarían para cambiar el resultado del estudios de grado "significativo" a un grado "no significativo" según el valor-p. Este concepto enfatiza la importancia de evaluar la robustez de los estudios clínicos al considerar su aplicación verdadera aplicación clínica, en lugar de depender únicamente del valor-p. Consulte Video Resumen en http://links.lww.com/DCR/B741. (Traducción-Dr. Xavier Delgadillo).

CT Imaging Findings in Patients with Ovarian Cancer and Acute Abdominal Symptoms: Experience at a Tertiary Cancer Center.

PURPOSE: To evaluate computed tomography (CT) findings in patients with ovarian cancer presenting to a comprehensive cancer center's urgent care unit with acute abdominal symptoms. METHODS: This retrospective study included consecutive patients with ovarian cancer who underwent abdominal CT at a comprehensive cancer center's urgent care unit between January 1, 2018, and January 14, 2020, due to acute abdominal symptoms. Two abdominal radiologists reviewed the abdominal CT reports, categorizing imaging findings as follows: (a) no new or acute finding, (b) new or increased bowel or gastric obstruction, (c) new or increased ascites, (d) new or increased peritoneal carcinomatosis, (e) new or increased nonperitoneal metastases, (f) new inflammatory or infectious changes, (g) new or increased hydronephrosis, (h) new or increased biliary dilatation, (i) new vascular complications, or (j) new bowel perforation. RESULTS: A total of 200 patients (mean age, 59 years; range, 22-87) underwent a total of 259 abdominal CT scans, of which 217/259 (83.8%) scans were found to have new or increased findings. A total of 115/259 (44.4%) scans had only one finding while 102/259 (39.4%) scans had 2 or more findings. Altogether, 382 new or increased findings were detected: findings were most commonly related to bowel or gastric obstruction (92/382, 24.1%) with small bowel obstruction being the most common finding (80/382, 20.9%); ascites (78/382, 20.4%); peritoneal carcinomatosis (62/382, 16.2%); and nonperitoneal metastases (62/382, 16.2%). Inflammatory or infectious findings accounted for 30/382 (7.9%) findings. CONCLUSION: Most patients with ovarian cancer presenting with acute abdominal had relevant positive findings on abdominal CT, with small bowel obstruction being the most common finding.

Automatic Forecasting of Radiology Examination Volume Trends for Optimal Resource Planning and Allocation.

The aim of the study was to evaluate the performance of the Prophet forecasting procedure, part of the Facebook open-source Artificial Intelligence portfolio, for forecasting variations in radiological examination volumes. Daily CT and MRI examination volumes from our institution were extracted from the radiology information system (RIS) database. Data from January 1, 2015, to December 31, 2019, was used for training the Prophet algorithm, and data from January 2020 was used for validation. Algorithm performance was then evaluated prospectively in February and August 2020. Total error and mean error per day were evaluated, and computational time was logged using different Markov chain Monte Carlo (MCMC) samples. Data from 610,570 examinations were used for training; the majority were CTs (82.3%). During retrospective testing, prediction error was reduced from 19 to < 1 per day in CT (total 589 to 17) and from 5 to < 1 per day (total 144 to 27) in MRI by fine-tuning the Prophet procedure. Prospective prediction error in February was 11 per day in CT (9934 predicted, 9667 actual) and 1 per day in MRI (2484 predicted, 2457 actual) and was significantly better than manual weekly predictions (p = 0.001). Inference with MCMC added no substantial improvements while vastly increasing computational time. Prophet accurately models weekly, seasonal, and overall trends paving the way for optimal resource allocation for radiology exam acquisition and interpretation.

Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.

Estimating the impact of treatment and imaging modalities on 5-year net survival of 11 cancers in 200 countries: a simulation-based analysis.

BACKGROUND: Accurate survival estimates are important for cancer control planning. Although observed survival estimates are unavailable for many countries, where they are available, wide variations are reported. Understanding the impact of specific treatment and imaging modalities can help decision makers to effectively allocate resources to improve cancer survival in their local context. METHODS: We developed a microsimulation model of stage-specific cancer survival in 200 countries and territories for 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) comprising 60% of global diagnosed cancer cases. The model accounts for country-specific availability of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy) and imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), as well as quality of care. We calibrated the model to reported survival estimates from CONCORD-3 (which reports global trends in cancer survival in 2000-14). We estimated 5-year net survival for diagnosed cancers in each country or territory and estimated potential survival gains from increasing the availability of individual treatment and imaging modalities, and more comprehensive packages of scale-up of these interventions. We report the mean and 95% uncertainty intervals (UIs) for all outcomes, calculated as the 2·5 and 97·5 percentiles of the simulation results. FINDINGS: The estimated global 5-year net survival for all 11 cancers combined is 42·6% (95% uncertainty interval 40·3-44·3), with survival in high-income countries being an average of 12 times (range 4-17) higher than that in low-income countries. Expanding availability of surgery or radiotherapy or improving quality of care would yield the largest survival gains in low-income (2·5-3·4 percentage point increase in survival) and lower-middle-income countries (2·4-6·1 percentage point increase), whereas upper-middle-income and high-income countries are more likely to benefit from improved availability of targeted therapy (0·7 percentage point increase for upper-middle income and 0·4 percentage point increase for high income). Investing in medical imaging will also be necessary to achieve substantial survival gains, with traditional modalities estimated to provide the largest gains in low-income settings, while MRI and PET would yield the largest gains in higher-income countries. Simultaneous expansion of treatment, imaging, and quality of care could improve 5-year net survival by more than ten times in low-income countries (3·8% [95% UI 0·5-9·2] to 45·2% [40·2-52·1]) and could more than double 5-year net survival in lower-middle-income countries (20·1% [7·2-31·7] to 47·1% [42·8-50·8]). INTERPRETATION: Scaling up both treatment and imaging availability could yield synergistic survival gains for patients with cancer. Expanding traditional modalities in lower-income settings might be a feasible pathway to improve survival before scaling up more modern technologies. FUNDING: Harvard T H Chan School of Public Health.

The role and contribution of treatment and imaging modalities in global cervical cancer management: survival estimates from a simulation-based analysis.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, causing more than 300 000 deaths globally each year. In addition to screening and prevention, effective cancer treatment is needed to reduce cervical cancer mortality. We discuss the role of imaging in cervical cancer management and estimate the potential survival effect of scaling up imaging in several different contexts. METHODS: Using a previously developed microsimulation model of global cancer survival, we estimated stage-specific cervical cancer 5-year net survival in 200 countries and territories. We evaluated the potential survival effect of scaling up treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), and imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single photon emission CT [SPECT]) to the mean level of high-income countries, both individually and in combination. FINDINGS: We estimate global cervical cancer 5-year net survival as 42·1% (95% uncertainty interval [UI] 33·8-48·5). Among individual imaging modalities, expanding MRI would yield the largest 5-year survival gains globally (data are absolute percentage point increase in survival 0·6, 95% UI 0·1-2·1), scaling up ultrasound would yield the largest gains in low-income countries (0·5, 0·0-3·7), expanding CT and x-ray would have the greatest effect in Latin America (0·8, 0·0-3·4) and Oceania (0·4, 0·0-3·2), and expanding PET would yield the largest gains in high-income countries (0·2, 0·0-0·8). Scaling up SPECT did not show major changes in any region. Among individual treatment modalities, scaling up radiotherapy would yield the largest absolute percentage point gains in low-income countries (5·2, 0·3-13·5), and expanding surgery would have the largest effect in lower-middle-income countries (7·4, 0·3-21·1) and upper-middle-income countries (0·8, 0·0-2·9). Estimated survival gains in high-income countries were very modest. However, the gains from expanding any single treatment or imaging modality individually were small across all income levels and geographical settings. Scaling up all treatment modalities could improve global 5-year net survival to 52·4% (95% UI 44·6-62·0). In addition to expanding treatment, improving quality of care could raise survival to 57·5% (51·2-63·5), and the cumulative effect of scaling up all imaging modalities together with expanded treatment and quality of care could improve 5-year net survival for cervical cancer to 62·5% (57·7-67·8). INTERPRETATION: Comprehensive scale-up of treatment, imaging, and quality of care could substantially improve global cervical cancer 5-year net survival, with quality of care and imaging improvements each contributing about 25% of the total potential gains. These findings suggest that a narrow focus on the availability of treatment modalities could forgo substantial survival gains. Investments in imaging equipment, personnel, and quality of care efforts will also be needed to successfully scale up cervical cancer treatment worldwide. FUNDING: Harvard T H Chan School of Public Health and National Cancer Institute.

Utility of Routine Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography in Identifying Pathological Lymph Node Metastases at Radical Cystectomy.

PURPOSE: We determined the diagnostic performance of 18F-FDG (fluorodeoxyglucose) positron emission tomography/computerized tomography for detecting nodal metastases in patients with muscle invasive urothelial bladder cancer before radical cystectomy. MATERIALS AND METHODS: Preoperative 18F-FDG positron emission tomography/computerized tomography scans (208) were retrospectively reviewed. Scans were routinely performed in 185 patients with muscle invasive urothelial bladder cancer between August 2012 and February 2017, all of whom underwent radical cystectomy and pelvic lymph node dissection. Analyses were stratified by clinical node involvement and chemotherapy status. The diagnostic performance of 18F-FDG positron emission tomography/computerized tomography was assessed according to sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Lymph node metastases at time of pelvic lymph node dissection were present in 21.8% of those without suspicious nodes on computerized tomography (clinically node negative) and 52.6% of those with suspicious nodes on computerized tomography (clinically node positive). Median metastatic focus size was 5 mm. In clinically node negative cases 18F-FDG positron emission tomography/computerized tomography rarely detected nodal metastases (sensitivity 7% to 23%). In clinically node positive cases negative 18F-FDG positron emission tomography/computerized tomography was useful in ruling out lymph node metastases (sensitivity 92% to 100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS: 18F-FDG positron emission tomography/computerized tomography appears to be most useful for better characterization of enlarged nodes identified by computerized tomography. Routine preoperative 18F-FDG positron emission tomography/computerized tomography has limited utility in clinically node negative cases.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Interactive, Up-to-date Meta-Analysis of MRI in the Management of Men with Suspected Prostate Cancer.

The aim of this study was to test an interactive up-to-date meta-analysis (iu-ma) of studies on MRI in the management of men with suspected prostate cancer. Based on the findings of recently published systematic reviews and meta-analyses, two freely accessible dynamic meta-analyses (https://iu-ma.org) were designed using the programming language R in combination with the package "shiny." The first iu-ma compares the performance of the MRI-stratified pathway and the systematic transrectal ultrasound-guided biopsy pathway for the detection of clinically significant prostate cancer, while the second iu-ma focuses on the use of biparametric versus multiparametric MRI for the diagnosis of prostate cancer. Our iu-mas allow for the effortless addition of new studies and data, thereby enabling physicians to keep track of the most recent scientific developments without having to resort to classical static meta-analyses that may become outdated in a short period of time. Furthermore, the iu-mas enable in-depth subgroup analyses by a wide variety of selectable parameters. Such an analysis is not only tailored to the needs of the reader but is also far more comprehensive than a classical meta-analysis. In that respect, following multiple subgroup analyses, we found that even for various subgroups, detection rates of prostate cancer are not different between biparametric and multiparametric MRI. Secondly, we could confirm the favorable influence of MRI biopsy stratification for multiple clinical scenarios. For the future, we envisage the use of this technology in addressing further clinical questions of other organ systems.

Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial.

BACKGROUND: Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC. METHODS: All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated. RESULTS: A total of 133 randomized patients were analysed. Median follow-up was 41·4 (95 per cent c.i. 36·6 to 45·2) months. Thirty-one patients (23·3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0·015). After induction chemotherapy, a larger tumour volume on MRI (P = 0·019), tumour volume regression of 60 per cent or less (P = 0·002), involvement of the CRM (P = 0·037), mrEMVI (P = 0·026) and a poor mrTRG (P = 0·023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0·004), mrEMVI (P = 0·038) and a poor mrTRG (P = 0·005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0·011), sphincter involvement (P = 0·009), mrEMVI at baseline (P = 0·002) and early tumour volume regression of 60 per cent or less after induction (P = 0·007) were associated with relapse. CONCLUSION: Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.

ANTECEDENTES: El tratamiento neoadyuvante personalizado del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) puede mejorar los resultados. El objetivo de este estudio fue determinar factores pronósticos precoces mediante RMN para estratificar el tratamiento neoadyuvante en pacientes con LARC. MÉTODOS: Todos los pacientes de un eensayo prospectivo de fase II, multicéntrico y aleatorizado (GRECCAR4-NCT01333709) se incluyeron en este estudio y se les realizó una RMN antes del tratamiento, 4 semanas después de la quimioterapia de inducción y después de completar la quimiorradioterapia (chemoradiation, CRT). Se evaluó la volumetría tumoral, el grado de regresión tumoral mediante RMN (MRI Tumor Regression Grade, mrTRG), la estadificación T, la estadificación N, el estado del margen de resección circunferencial (circumferential resection margin, CRM) y la presencia de invasión extramural vascular en la RMN (extramural vascular invasion, mrEMVI). RESULTADOS: Se analizaron 133 pacientes aleatorizados. La mediana de seguimiento fue de 41,4 meses (i.c. del 95%: 36,6-45,2). En 31 pacientes (23%) se diagnosticó una recidiva. En el análisis univariado de la situación basal, mrEMVI fue el único factor pronóstico asociado con un peor resultado (P = 0,0152). Después de la quimioterapia de inducción, un volumen tumoral más alto en la RMN (P = 0,019), una regresión del volumen tumoral ≤ 60% (P = 0,002), la afectación del CRM (P = 0,037), mrEMVI (P = 0,026) y un grado escaso mrTRG (P = 0,023) se asociaron con un mal resultado. Después de completar la CRT, la ausencia de respuesta completa en la RMN (P = 0,004), la presencia de mrEMVI (P = 0,04) y una insuficiente mrTRG (P = 0,005) se asociaron con una supervivencia libre de enfermedad más corta. En el modelo multivariable final en el que se incluyeron todas las variables significativas (basales, postinducción, post-CRT), el estado de ECOG (P = 0,011), la afectación esfinteriana (P = 0,009), la presencia de EMVI al inicio (P = 0,002) y una regresión precoz del volumen tumoral ≤ 60% después de la inducción (P = 0,007) se asociaron con una recidiva. CONCLUSIÓN: Los parámetros basales y post-tratamiento precoces de la RMN se asocian con el pronóstico en el LARC. La estrategia terapéutica preoperatoria futura deberá estratificar el tratamiento de acuerdo con la presencia de EMVI al inicio y la regresión precoz del volumen tumoral.

Value of MRI in medicine: More than just another test?

There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high-end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:e14-e25.

Isolation on a remote island: genetic and morphological differentiation of a cosmopolitan odonate.

Although low levels of genetic structure are expected in highly widespread species, geographical and/or ecological factors can limit species distributions and promote population structure and morphological differentiation. In order to determine the effects of geographical isolation on population genetic structure and wing morphology, 281 individuals of the cosmopolitan odonate Pantala flavescens were collected from four continental (Central and South America) and five insular sites (Polynesian islands and the Maldives). COI sequences and eight microsatellite loci were used to characterize genetic diversity and genetic structure between and within locations. Linear and geometric morphometry were used to evaluate differences in the size and shape of wings. Genetic analysis showed a global genetic difference between the continental and insular sites. American locations did not show genetic structure, even in locations separated by a distance of 5000 km. Easter Island showed the lowest values of genetic diversity (mainly mitochondrial diversity) and the highest values of genetic differences compared to other insular and continental sites. Individuals from Easter Island showed smaller forewings, a different abdomen length to thorax length ratio, and a different configuration of anal loop in the hindwings. Thus, the greater isolation, smaller area, and young geological age seem to have determined the genetic and morphological differences in P. flavescens of Easter Island, where selection could promote a loss of migratory behavior and may improve other life history traits, such as reproduction. This work provides new insight into how microevolutionary processes operate in isolated populations of cosmopolitan species.

Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study.

Waitlist time for kidney transplantation is long but may be shortened with the utilization of hepatitis C positive allografts. We retrospectively reviewed the course of 36 hepatitis C positive patients awaiting kidney transplantation at 2 large centers within the same health system, with near-identical care delivery models with the exception of timing of hepatitis C treatment, to determine the impact of timing of hepatitis C treatment on access to transplant, waitlist time, and treatment efficacy and tolerability. The majority of patients had hepatitis C genotype 1a or 1b, and all received direct acting antiviral therapy with 100% treatment response. One patient underwent transplantation in the pretransplant treatment group. The 1-year transplantation rate was 12.5% vs 67.9% (P = .0013) in those treated posttransplantation. The median waitlist time in the posttransplant group was 122 (interquartile range [IQR] 21.5, 531.0) days, which was significantly shorter than the center's regional and national wait time. Pathologic review revealed no difference in allograft quality. Overall treatment related adverse events were not different between the 2 groups. A strategy of posttransplant hepatitis C treatment increased access to transplant and reduced waitlist time. Delaying treatment until after transplant did not appear to adversely affect recipients' kidney allograft or overall survival.

Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children.

BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ coactivator-1α (PGC1α), nuclear respiratory factors 1 and 2 (NRF1, NRF2) and mitochondrial transcription factor A (TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by western blot. Citrate synthase (CS), complex I (CI) activity, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) content and oxidative stress end points were also determined. RESULTS: Most MB proteins were significantly decreased in samples from children with obesity except complex I, V and superoxide dismutase-2 (SOD2). Similarly, CS and CI activity showed a significant reduction, as well as ATP levels and mtDNA content. PPARγ, PGC1α, complex I and V and SOD2 were hyperacetylated compared with lean samples. Concurrently, in samples from children with obesity, we found decreased SOD2 activity and redox state imbalance highlighted by decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and significant increases in protein carbonylation. CONCLUSIONS: Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.

Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes.

OBJECTIVES: The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival. METHODS: North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival. RESULTS: 653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality. CONCLUSIONS: Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.

Unravelling tumour heterogeneity using next-generation imaging: radiomics, radiogenomics, and habitat imaging.

Tumour heterogeneity in cancers has been observed at the histological and genetic levels, and increased levels of intra-tumour genetic heterogeneity have been reported to be associated with adverse clinical outcomes. This review provides an overview of radiomics, radiogenomics, and habitat imaging, and examines the use of these newly emergent fields in assessing tumour heterogeneity and its implications. It reviews the potential value of radiomics and radiogenomics in assisting in the diagnosis of cancer disease and determining cancer aggressiveness. This review discusses how radiogenomic analysis can be further used to guide treatment therapy for individual tumours by predicting drug response and potential therapy resistance and examines its role in developing radiomics as biomarkers of oncological outcomes. Lastly, it provides an overview of the obstacles in these emergent fields today including reproducibility, need for validation, imaging analysis standardisation, data sharing and clinical translatability and offers potential solutions to these challenges towards the realisation of precision oncology.

The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer.

OBJECTIVES: To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities. METHODS: We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer. RESULTS: 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician's prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT. CONCLUSIONS: FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference.

OBJECTIVES: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. METHODS: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. RESULTS: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. CONCLUSIONS: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. KEY POINTS: • PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL • PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL • DCE-MRI offered limited added value to T2WI+DW-MRI.