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Emergency department visits and hospitalizations are common among people receiving cancer treatment, accounting for a large proportion of spending in oncology care and negatively affecting quality of life. As oncology care shifts toward value- and quality-based payment models, there is a need to develop interventions that can prevent these costly and low-value events among people receiving cancer treatment. Risk stratification programs have the potential to address this need and optimally would consist of three components: (1) a risk stratification algorithm that accurately identifies patients with modifiable risk(s), (2) intervention(s) that successfully reduce this risk, and (3) the ability to implement the risk algorithm and intervention(s) in an adaptable and sustainable way. Predictive modeling is a common method of risk stratification, and although a number of predictive models have been developed for use in oncology care, they have rarely been tested alongside corresponding interventions or developed with implementation in clinical practice as an explicit consideration. In this article, we review the available published predictive models for treatment-related toxicity or acute care events among people receiving cancer treatment and highlight challenges faced when attempting to use these models in practice. To move the field of risk-stratified oncology care forward, we argue that it is critical to evaluate predictive models alongside targeted interventions that address modifiable risks and to demonstrate that these two key components can be implemented within clinical practice to avoid unplanned acute care events among people receiving cancer treatment.

PURPOSE Tumor next-generation sequencing reports typically generate trial recommendations for patients based on their diagnosis and genomic profile. However, these require additional refinement and prescreening, which can add to physician burden. We wanted to use human prescreening efforts to efficiently refine these trial options and also elucidate the high-value parameters that have a major impact on efficient trial matching. METHODS Clinical trial recommendations were generated based on diagnosis and biomarker criteria using an informatics platform and were further refined by manual prescreening. The refined results were then compared with the initial trial recommendations and the reasons for false-positive matches were evaluated. RESULTS Manual prescreening significantly reduced the number of false positives from the informatics generated trial recommendations, as expected. We found that trial-specific criteria, especially recruiting status for individual trial arms, were a high value parameter and led to the largest number of automated false-positive matches. CONCLUSION Reflex clinical trial matching approaches that refine trial recommendations based on the clinical details as well as trial-specific criteria have the potential to help alleviate physician burden for selecting the most appropriate trial for their patient. Investing in publicly available resources that capture the recruiting status of a trial at the cohort or arm level would, therefore, allow us to make meaningful contributions to increase the clinical trial enrollments by eliminating false positives.

PURPOSE: The use of telemedicine expanded dramatically in March 2020 following the COVID-19 pandemic. We sought to assess oncologist perspectives on telemedicine's present and future roles (both phone and video) for patients with cancer. METHODS: The National Comprehensive Cancer Network (NCCN) Electronic Health Record (EHR) Oncology Advisory Group formed a Workgroup to assess the state of oncology telemedicine and created a 20-question survey. NCCN EHR Oncology Advisory Group members e-mailed the survey to providers (surgical, hematology, gynecologic, medical, and radiation oncology physicians and clinicians) at their home institution. RESULTS: Providers (N = 1,038) from 26 institutions responded in Summer 2020. Telemedicine (phone and video) was compared with in-person visits across clinical scenarios (n = 766). For reviewing benign follow-up data, 88% reported video and 80% reported telephone were the same as or better than office visits. For establishing a personal connection with patients, 24% and 7% indicated video and telephone, respectively, were the same as or better than office visits. Ninety-three percent reported adverse outcomes attributable to telemedicine visits never or rarely occurred, whereas 6% indicated they occasionally occurred (n = 801). Respondents (n = 796) estimated 46% of postpandemic visits could be virtual, but challenges included (1) lack of patient access to technology, (2) inadequate clinical workflows to support telemedicine, and (3) insurance coverage uncertainty postpandemic. CONCLUSION: Telemedicine appears effective across a variety of clinical scenarios. Based on provider assessment, a substantial fraction of visits for patients with cancer could be effectively and safely conducted using telemedicine. These findings should influence regulatory and infrastructural decisions regarding telemedicine postpandemic for patients with cancer.

Purpose To determine risk factors for coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs), characterize symptoms, and evaluate preventive measures against SARS-CoV-2 spread in hospitals. Methods In a cross-sectional study conducted between May 27 and August 12, 2020, after the first wave of the COVID-19 pandemic, we obtained serological, epidemiological, occupational as well as COVID-19-related data at a quaternary care, multicenter hospital in Munich, Germany. Results 7554 HCWs participated, 2.2% of whom tested positive for anti-SARS-CoV-2 antibodies. Multivariate analysis revealed increased COVID-19 risk for nurses (3.1% seropositivity, 95% CI 2.5–3.9%, p = 0.012), staff working on COVID-19 units (4.6% seropositivity, 95% CI 3.2–6.5%, p = 0.032), males (2.4% seropositivity, 95% CI 1.8–3.2%, p = 0.019), and HCWs reporting high-risk exposures to infected patients (5.5% seropositivity, 95% CI 4.0–7.5%, p = 0.0022) or outside of work (12.0% seropositivity, 95% CI 8.0–17.4%, p p = 0.00018) and the symptom taste disorder was strongly associated with COVID-19 (29.8% seropositivity, 95% CI 24.3–35.8%, p Conclusion Awareness of the identified COVID-19 risk factors and successful surveillance strategies are key to protecting HCWs against SARS-CoV-2, especially in settings with limited vaccination capacities or reduced vaccine efficacy.

Introduction The natural history of T1b (4-7 cm) or T2a (> 7-10 cm) kidney cancers managed with observation is not well-understood. The aim of our study was to determine if the addition of histologic subtype to a predictive model of overall survival (OS) that includes covariates for competing risks in observed, biopsy-proven, T1b and T2a renal cell carcinomas (RCCs) improves the model’s performance. Materials and Methods We queried the National Cancer Database for patients with biopsy-proven stage T1b or T2a RCC and managed nonoperatively between 2004 and 2015. OS was estimated by Kaplan-Meier curves based on histologic subtype. The concordance index (c-index) from a Cox proportional hazards model was used to estimate the extent to which histologic subtypes predict survival for each stage when included in a model along with competing risks of age, gender, race/ethnicity, insurance status, area-level socioeconomic indicators, Charlson-Deyo index, and tumor grade. Results A total of 937 patients (754 with T1b and 185 with T2a) with biopsy-proven RCC were identified. Kaplan-Meier analysis suggested differences in OS by histologic subtype where sarcomatoid, followed by clear cell, papillary, and chromophobe, had the highest mortality risk at 1, 3, and 5 years. However, there was marginal improvement in the multivariable model of OS using competing risks and histology (c-index, 0.64 and 0.697) compared with competing risks alone (c-index, 0.631 and 0.671) for T1b and T2a RCCs, respectively. Conclusions In patients with T1b or T2a RCC managed with observation, incorporation of histologic subtype into a risk-stratification model to determine prognostic OS did not improve modeling of OS compared with variables representing competing risks. Histologic subtype of observed T1b and T2a RCC appears to have prognostic OS value when not considering competing risks. These findings may impact the usefulness of renal biopsy to inform decision-making when managing patients with T1b and T2a renal tumors with observation.

Human bornavirus encephalitis is a severe and often fatal infection caused by variegated squirrel bornavirus 1 (VSBV-1) and Borna disease virus 1 (BoDV-1). We conducted a prospective study of bornavirus etiology of encephalitis cases in Germany during 2018-2020 by using a serologic testing scheme applied along proposed graded case definitions for VSBV-1, BoDV-1, and unspecified bornavirus encephalitis. Of 103 encephalitis cases of unknown etiology, 4 bornavirus infections were detected serologically. One chronic case was caused by VSBV-1 after occupational-related contact of a person with exotic squirrels, and 3 acute cases were caused by BoDV-1 in virus-endemic areas. All 4 case-patients died. Bornavirus etiology could be confirmed by molecular methods. Serologic testing for these cases was virus specific, discriminatory, and a practical diagnostic option for living patients if no brain tissue samples are available. This testing should be guided by clinical and epidemiologic suspicions, such as residence in virus-endemic areas and animal exposure.

Introduction: The use of telemedicine in the oncology (Onc) setting expanded after March 2020 due to the COVID-19 pandemic. Patients and providers report satisfaction with telemedicine within the context of acute pandemic needs (Darcourt et al, JOP, 2020). We assessed provider perspectives on the roles of phone- and video-based telemedicine in the Onc setting. Methods: The NCCN EHR Oncology Advisory Group formed a Workgroup to assess the state of Onc telemedicine, creating a 20-question survey distributed to all 30 NCCN Member Institutions. An NCCNmember was responsible for emailing the survey to the Onc providers (surgery, hematology, gynecologic, medical and radiation oncology physicians & APPs) at his/her institution. Results: N51,038 individuals from 26 institutions (institution response rate 87%) responded 7-8/2020. Respondents were largely Onc physicians (58%) with >5 years of practice experience (72%). Few respondents had participated in telemedicine visits of any kind prior to the COVID-19 pandemic (19%;n=198/1038). At the time of the survey, most had participated in both telephone and videobased visits (84%;n=872/1038);5% (n=52/1038) had participated in only phone-based visits and 9% (=93/ 1038) had participated in only video-based visits. Only 2% of respondents (n=21/1038) reported not having conducted any telemedicine visits. The use of telemedicine was based on provider discretion (88%;n=727/826) and patient preference (81%;=669/826). Importantly, 94% (n=753/801) of respondents indicated rarely-to-never encountering adverse outcomes attributable to having had a telemedicine visit rather than an in-person visit. The Figure indicates how telemedicine visits compared to office visits for particular tasks commonly associated with Onc visits. Respondents (n=796) estimated 33% of patients could safely be seen using video visits and 13% using phone visits post-pandemic. Challenges include lack of: 1) patient access to technology for video visits, 2) clinical workflows to support telemedicine, and 3) certainty about future insurance coverage. Conclusion: Based on Onc provider assessment, a substantial fraction of patient visits could be effectively, safely conducted using telemedicine post-pandemic. Overall, video visits were viewed more favorably than phone visits with greater utility over a wider range of clinical scenarios. Careful thought should be given to modifying regulations to maintain telemedicine for use post-pandemic.

Ganglion cysts about the wrist are a common pathology that presents to hand surgeons. The majority is dorsal, originating from the scapholunate ligament, but volar and occult ganglions are also common and symptomatic. Treatment options for these masses include observation, aspiration, or surgical excision. Historically, open surgical excision has been the gold standard of treatment; however, arthroscopic excision is becoming more favorable due to its minimally invasive nature and decreased postoperative recurrence rates. Concerns regarding limited visualization and volar ganglion excision exist; however, newer surgical techniques and data continue to support the arthroscopic technique. This chapter contains a video.

Background High infection rates among healthcare personnel in an uncontained pandemic can paralyze health systems due to staff shortages. Risk constellations and rates of seroconversion for healthcare workers (HCWs) during the first wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are still largely unclear. Methods Healthcare personnel (n = 300) on different organizational units in the LMU Munich University Hospital were included and followed in this prospective longitudinal study from 24 March until 7 July 2020. Participants were monitored in intervals of 2 to 6 weeks using different antibody assays for serological testing and questionnaires to evaluate risk contacts. In a subgroup of infected participants, we obtained nasopharyngeal swabs to perform whole-genome sequencing for outbreak characterization. Results HCWs involved in patient care on dedicated coronavirus disease 2019 (COVID-19) wards or on regular non–COVID-19 wards showed a higher rate of SARS-CoV-2 seroconversion than staff in the emergency department and non-frontline personnel. The landscape of risk contacts in these units was dynamic, with a decrease in unprotected risk contacts in the emergency department and an increase on non–COVID-19 wards. Both intensity and number of risk contacts were associated with higher rates of seroconversion. On regular wards, staff infections tended to occur in clusters, while infections on COVID-19 wards were less frequent and apparently independent of each other. Conclusions Risk of SARS-CoV-2 infection for frontline HCWs was increased during the first pandemic wave in southern Germany. Stringent measures for infection control are essential to protect all patient-facing staff during the ongoing pandemic.

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Five biologics are approved for the treatment of ulcerative colitis (UC): infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. These drugs have varying levels of efficacy and are recommended as first-line treatment of moderate to severe UC. There has been only 1 head-to-head trial comparing the efficacy of the biologics, adalimumab and vedolizumab, which has important implications for management. Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents. The future of treatment may include personalization of medications, based on patient-specific and disease-specific characteristics as well as biomarkers, along with appropriate therapeutic drug monitoring.

This article describes evaluation and treatment considerations for Essex-Lopresti injuries. Specific information about pattern recognition and treatment options is provided.

PURPOSE Because of expanding interoperability requirements, structured patient data are increasingly available in electronic health records. Many oncology data elements (eg, staging, biomarkers, documentation of adverse events and cancer outcomes) remain challenging. The Minimal Common Oncology Data Elements (mCODE) project is a consensus data standard created to facilitate transmission of data of patients with cancer. METHODS In 2018, mCODE was developed through a work group convened by ASCO, including oncologists, informaticians, researchers, and experts in terminologies and standards. The mCODE specification is organized by 6 high-level domains: patient, laboratory/vital, disease, genomics, treatment, and outcome. In total, 23 mCODE profiles are composed of 90 data elements. RESULTS A conceptual model was published for public comment in January 2019 and, after additional refinement, the first public version of the mCODE (version 0.9.1) Fast Healthcare Interoperability Resources (FHIR) implementation guide (IG) was presented at the ASCO Annual Meeting in June 2019. The specification was approved for balloting by Health Level 7 International (HL7) in August 2019. mCODE passed the HL7 ballot in September 2019 with 86.5% approval. The mCODE IG authors worked with HL7 reviewers to resolve all negative comments, leading to a modest expansion in the number of data elements and tighter alignment with FHIR and other HL7 conventions. The mCODE version 1.0 FHIR IG Standard for Trial Use was formally published on March 18, 2020. CONCLUSION The mCODE project has the potential to offer tremendous benefits to cancer care delivery and research by creating an infrastructure to better share patient data. mCODE is available free from www.mCODEinitiative.org . Pilot implementations are underway, and a robust community of stakeholders has been assembled across the oncology ecosystem.

Background Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ) and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis, with respect to response to VDZ. Method Ileal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of 2 biomarkers to VDZ was examined. Results Clinical response in UST was significantly higher than placebo (65% vs 39%; P = 0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs 20% (P = 0.02). For VDZ, clinical response with MVL of 1.35 to 1.55 µm was 82% vs 44% (1.55 µm; P = 0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis Conclusion Ileal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, and combination of the 2 biomarkers enhanced the discriminate ability of responders from nonresponders to VDZ.

The rates of methicillin-resistant infections in the hand and upper extremity approach 50% in many facilities. In addition, multidrug resistance is beginning to include clindamycin. This article discusses the history, prevalence, and treatment of both community-acquired and health care-associated methicillin-resistant Staphylococcus aureus in regard to hand infections.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index–4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index–4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

Introduction: There have been a number of recent advances in the management of advanced clear cell renal cell carcinoma (ccRCC). However, the majority of these studies excluded patients with non-clear cell RCC (nccRCC), and optimal management of nccRCC remains unknown. Materials and Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate systemic treatment options in locally advanced or metastatic nccRCC between 2000-2019. Randomized controlled trials, single-arm phase II–IV trials, and prospective analyses of medication access programs were included. The primary outcome measures were progression free survival (PFS), overall survival (OS), and objective response rate (ORR). Results: A total of 31 studies were included in the final analysis. There was the highest level of evidence to support first-line treatment of nccRCC with sunitinib. Additional single-arm trials support the use of other vascular endothelial growth factor (VEGF) inhibitors with axitinib and pazopanib, as well as mammalian target of rapamycin (mTOR) inhibition with temsirolimus or everolimus +/–bevacizumab. Immune checkpoint inhibition has an emerging role in nccRCC, but optimal sequencing of available options is not clear. Prospective data to support the use of newer immunotherapy combinations are lacking. Treatment for collecting duct carcinoma remains platinum-based chemotherapy. Conclusions: The availability of randomized trials in nccRCC is limited, and most studies include outcomes for nccRCC as a group, making conclusions about efficacy by subtype difficult. This systematic review supports consensus guidelines recommending sunitinib or clinical trial enrollment as preferred first-line treatment options for nccRCC, but also suggests a more nuanced approach to management and new options for therapy such as immune checkpoint inhibition.

This report describes characteristics and selected pregnancy outcomes among mothers with and without confirmed or presumed COVID-19 during pregnancy by maternal age, educational attainment, race and Hispanic origin, and source of payment for the delivery for a 14-state and District of Columbia reporting area.

INTRODUCTION AND OBJECTIVE:Sarcopenia, or severe muscle wasting, has been well documented as a risk factor for mortality, complications, and non-home discharge disposition for patients with bladder...

PURPOSE To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.

Objective Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. Design Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI Results One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis Conclusions Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

Background Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. Methods Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. Results High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). Conclusion Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.

Background Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. Methods We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare. Results The proactive strategy led to fewer flares than the reactive strategy. More patients stayed on IFX in the proactive vs reactive strategy (63.4% vs 58.8% at year 5). From a health sector perspective, a proactive strategy was marginally cost-effective compared with a reactive strategy (incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year), assuming a 40% of the wholesale price of IFX. The results were most sensitive to risk of flaring with a low IFX concentration and the cost of IFX. Conclusions Assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective.

Background Prospectively designed studies assessing the exposure-response profile of vedolizumab are lacking. Observational exposure-response data for vedolizumab are limited and have not been adjusted for potential confounding factors, particularly those that may affect vedolizumab clearance. Aims To (a) investigate the vedolizumab exposure-response relationship after adjusting for potential confounding variables; (b) propose potential target serum vedolizumab concentrations for future study; (c) ascertain whether early vedolizumab serum concentrations were associated with short- and long-term clinical outcomes in adults with ulcerative colitis in GEMINI 1. Methods Propensity-score-based case-matching analysis was performed using data from GEMINI 1 and an earlier large population pharmacokinetic study, with vedolizumab clearance or concentration as predictors of clinical remission and response, adjusted for age, weight, anti-tumour necrosis factor alpha therapy history, serum albumin and faecal calprotectin concentrations. Potential vedolizumab concentration targets at weeks 6, 14 and steady state were proposed. Association between early vedolizumab concentrations at weeks 2, 4 and 6 and clinical remission at weeks 14 and 52 was evaluated. Results Among 693 patients with pharmacokinetic data at week 6, potential target vedolizumab concentrations at weeks 6, 14 and steady state were 37.1, 18.4 and 12.7 µg/mL respectively. Week 6 was identified as the earliest time at which vedolizumab concentrations were consistently associated with clinical remission at weeks 14 and 52. Conclusions In this comprehensively adjusted analysis, vedolizumab concentrations at week 6 were associated with short- and long-term remission. Potential induction and maintenance target concentrations were proposed for further study.

Objective Lung cancer is the leading cancer killer in women, resulting in more deaths than breast, cervical and ovarian cancer combined. Screening for lung cancer has been shown to significantly reduce mortality, with some evidence that women may have a greater benefit. This study demonstrates that a population of women being screened for breast cancer may greatly benefit from screening for lung cancer. Methods Data from 18,040 women who were screened for breast cancer in 2015 at two imaging facilities that also performed lung screening were reviewed. A natural language-processing algorithm followed by a manual chart review identified women eligible for lung cancer screening by U.S. Preventive Services Task Force (USPSTF) criteria. A chart review of these eligible women was performed to determine subsequent enrollment in a lung screening program (2016–2019), current screening eligibility, cancer diagnoses and cancer-related outcomes. Results Natural language processing identified 685 women undergoing screening mammography who were also potentially eligible for lung screening based on age and smoking history. Manual chart review confirmed 251 were eligible under USPSTF criteria. By June 2019, 63 (25%) had enrolled in lung screening, of which three were diagnosed with screening-detected lung cancer resulting in zero deaths. Of 188 not screened, seven were diagnosed with lung cancer resulting in five deaths by study end. Four women received a diagnosis of breast cancer with no deaths. Conclusion Women screened for breast cancer are dying from lung cancer. We must capitalize on reducing barriers to improve screening for lung cancer among high-risk women.

Presents provisional 2020 data on U.S. births, shown by age and race and Hispanic origin of mother. Also presents data on cesarean delivery and preterm births.

Successful containment strategies for the SARS-CoV-2 pandemic will depend on reliable diagnostic assays. Point-of-care antigen tests (POCT) may provide an alternative to time-consuming PCR tests to rapidly screen for acute infections on site. Here, we evaluated two SARS-CoV-2 antigen tests: the STANDARD™ F COVID-19 Ag FIA (FIA) and the SARS-CoV-2 Rapid Antigen Test (RAT). For diagnostic assessment, we used a large set of PCR-positive and PCR-negative respiratory swabs from asymptomatic and symptomatic patients and health care workers in the setting of two University Hospitals in Munich, Germany, i.e. emergency rooms, patient care units or employee test centers. For FIA, overall clinical sensitivity and specificity were 45.4% (n = 381) and 97.8% (n = 360), respectively, and for RAT, 50.3% (n = 445) and 97.7% (n = 386), respectively. For primary diagnosis of asymptomatic and symptomatic individuals, diagnostic sensitivities were 60.9% (FIA) (n = 189) and 64.5% (RAT) (n = 256). This questions these tests’ utility for the reliable detection of acute SARS-CoV-2-infected individuals, in particular in high-risk settings. We support the proposal that convincing high-quality outcome data on the impact of false-negative and false-positive antigen test results need to be obtained in a POCT setting. Moreover, the efficacy of alternative testing strategies to complement PCR assays must be evaluated by independent laboratories, prior to widespread implementation in national and international test strategies.

OBJECTIVE In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children’s Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most. METHODS Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed. RESULTS Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00–69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated). CONCLUSIONS A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

Over the past several decades, adult weight gain and excess weight have emerged as risk factors for cancers of the esophagus, pancreas, liver, colorectal, breast (postmenopausal), endometrium, and kidney, as well as probable evidence for cancers of the stomach (cardia), mouth/pharynx/larynx, gallbladder, ovary, and prostate. In the USA, overweight and obesity account for 55% of cancers in women and 24% in men. The evidence of risks, outcomes, and interventions is most developed in the literature pertaining to women with early breast cancer (Stage I–III). Primarily with the oncology clinician-patient relationship in mind, this chapter provides an overview of weight trajectories in women with early breast cancer, implications for prognosis and survival, nutrition and exercise for weight management, and the role of oncology clinicians. Lessons learned from the breast cancer population are illustrative for other types of cancers. Culturally sensitive, person-centered language about the importance of weight management in survivorship is essential to clinician-patient communication and other interventions to help adults with cancer to understand the importance of weight management and other benefits from exercise and a healthy diet. Equally important, but not within the scope of this chapter, is the urgency of lowering cancer risk and adverse outcomes through effective and widespread community-based obesity interventions.

Background In the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data. Aim We applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata. Methods We investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission. Results We identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions. Conclusions Early spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.

BACKGROUND The completeness and accuracy of the registration of synchronous metastases and recurrences in the Swedish Colorectal Cancer Registry has not been investigated. Knowing how accurate these parameters are in the registry is a prerequisite to adequately measure the current recurrence risk. METHODS All charts for patients diagnosed with stage I-III colorectal cancer (CRC) in two regions were reviewed. In one of the regions, all registrations of synchronous metastases were similarly investigated. After the database had been corrected, recurrence risk in colon cancer was calculated stratified by risk group as suggested by ESMO in 2020. RESULTS In patients operated upon more than five years ago (N = 1235), there were 20 (1.6%) recurrences not reported. In more recent patients, more recurrences were unreported (4.0%). Few synchronous metastases were wrongly registered (3.6%) and, likewise, few synchronous metastases were not registered (about 1%). The five-year recurrence risk in stage II was 6% for low-risk, 11% for intermediate risk, and 23% for high-risk colon cancer patients. In stage III, it was 25% in low- and 45% in high-risk patients. Incorporation of risk factors in stage III modified the risks substantially even if this is not considered by ESMO. Adjuvant chemotherapy lowered the risk in stage III but not to any relevant extent in stage II. CONCLUSION The registration of recurrences in the registry after 5 years is accurate to between 1 and 2% but less accurate earlier. A small number of unreported recurrences and falsely reported recurrences were discovered in the chart review. The recurrence risk in this validated and updated patient series matches what has been recently reported, except for the risk of recurrence in stage II low risk colon cancers which seem to be even a few percentage points lower (6 vs. 9%).

Established and novel radiotracers are under active investigation for patients with bladder cancer. 18F-FDG PET/CT may be useful for lymph node staging or assessment of distant metastatic disease but is of limited utility for primary tumor staging due to urinary excretion of the radiotracer. 11C-choline and 11C-acetate both overcome the issue of urinary excretion, but their short half-life necessitates an onsite cyclotron. Ongoing studies aim to evaluate whether PET imaging can predict or accurately assess treatment response. 99mTc-MDP or 18F-NaF radiotracers permit assessment of bone metastases, with limitations of each modality. Several novel radiotracers are under investigation for future utility.

Background Prediction models are useful tools in the clinical management of colon cancer patients, particularly when estimating the recurrence rate and, thus, the need for adjuvant treatment. However, the most used models (MSKCC, ACCENT) are based on several decades-old patient series from clinical trials, likely overestimating the current risk of recurrence, especially in low-risk groups, as outcomes have improved over time. The aim was to develop and validate an updated model for the prediction of recurrence within 5 years after surgery using routinely collected clinicopathologic variables. Material and methods A population-based cohort from the Swedish Colorectal Cancer Registry of 16,134 stage I–III colon cancer cases was used. A multivariable model was constructed using Cox proportional hazards regression. Three-quarters of the cases were used for model development and one quarter for internal validation. External validation was performed using 12,769 stage II–III patients from the Norwegian Colorectal Cancer Registry. The model was compared to previous nomograms. Results The nomogram consisted of eight variables: sex, sidedness, pT-substages, number of positive and found lymph nodes, emergency surgery, lymphovascular and perineural invasion. The area under the curve (AUC) was 0.78 in the model, 0.76 in internal validation, and 0.70 in external validation. The model calibrated well, especially in low-risk patients, and performed better than existing nomograms in the Swedish registry data. The new nomogram’s AUC was equal to that of the MSKCC but the calibration was better. Conclusion The nomogram based on recently operated patients from a population registry predicts recurrence risk more accurately than previous nomograms. It performs best in the low-risk groups where the risk-benefit ratio of adjuvant treatment is debatable and the need for an accurate prediction model is the largest. publishedVersion

Objective Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors. Methods Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function. Results 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate–severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p p p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course. Conclusion We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.

Graphical abstract, Highlights • There may be long-term consequences of delaying procedures in response to COVID-19. • Electronic health record data can help us understand the impact of procedure delay. • Our high-throughput approach identifies procedures impacted by COVID-19. • Impact of procedure delay on patient outcomes are evaluated with retrospective data. • Our results can help hospital systems minimize adverse patient outcomes from delays., Objective During the COVID-19 pandemic, health systems postponed non-essential medical procedures to accommodate surge of critically-ill patients. The long-term consequences of delaying procedures in response to COVID-19 remains unknown. We developed a high-throughput approach to understand the impact of delaying procedures on patient health outcomes using electronic health record (EHR) data. Materials and Methods We used EHR data from Vanderbilt University Medical Center’s (VUMC) Research and Synthetic Derivatives. Elective procedures and non-urgent visits were suspended at VUMC between March 18, 2020 and April 24, 2020. Surgical procedure data from this period were compared to a similar timeframe in 2019. Potential adverse impact of delay in cardiovascular and cancer-related procedures was evaluated using EHR data collected from January 1, 1993 to March 17, 2020. For surgical procedure delay, outcomes included length of hospitalization (days), mortality during hospitalization, and readmission within six months. For screening procedure delay, outcomes included 5-year survival and cancer stage at diagnosis. Results We identified 416 surgical procedures that were negatively impacted during the COVID-19 pandemic compared to the same timeframe in 2019. Using retrospective data, we found 27 significant associations between procedure delay and adverse patient outcomes. Clinician review indicated that 88.9% of the significant associations were plausible and potentially clinically significant. Analytic pipelines for this study are available online. Conclusion Our approach enables health systems to identify medical procedures affected by the COVID-19 pandemic and evaluate the effect of delay, enabling them to communicate effectively with patients and prioritize rescheduling to minimize adverse patient outcomes.

BACKGROUND: The treatment landscape for metastatic clear cell renal cell carcinoma (mRCC) is rapidly changing. It is unknown how adoption of new types of therapies may differ by patient age. OBJECTIVE: To compare trends in first-line therapy use for older (≥70 years) and younger (

Background The use of routine immunization data by health care professionals in low- and middle-income countries remains an underutilized resource in decision-making. Despite the significant resources invested in developing national health information systems, systematic reviews of the effectiveness of data use interventions are lacking. Applying a realist review methodology, this study synthesized evidence of effective interventions for improving data use in decision-making. Methods We searched PubMed, POPLINE, Centre for Agriculture and Biosciences International Global Health, and African Journals Online for published literature. Grey literature was obtained from conference, implementer, and technical agency websites and requested from implementing organizations. Articles were included if they reported on an intervention designed to improve routine data use or reported outcomes related to data use, and targeted health care professionals as the principal data users. We developed a theory of change a priori for how we expect data use interventions to influence data use. Evidence was then synthesized according to data use intervention type and level of the health system targeted by the intervention. Results The searches yielded 549 articles, of which 102 met our inclusion criteria, including 49 from peer-reviewed journals and 53 from grey literature. A total of 66 articles reported on immunization data use interventions and 36 articles reported on data use interventions for other health sectors. We categorized 68 articles as research evidence and 34 articles as promising strategies. We identified ten primary intervention categories, including electronic immunization registries, which were the most reported intervention type (n = 14). Among the research evidence from the immunization sector, 32 articles reported intermediate outcomes related to data quality and availability, data analysis, synthesis, interpretation, and review. Seventeen articles reported data-informed decision-making as an intervention outcome, which could be explained by the lack of consensus around how to define and measure data use. Conclusions Few immunization data use interventions have been rigorously studied or evaluated. The review highlights gaps in the evidence base, which future research and better measures for assessing data use should attempt to address.

Skin and soft tissue infections (SSTIs) are a common presenting complaint to acute care centers. SSTIs include folliculitis, furuncle, carbuncle, impetigo, ecthyma, erysipelas, cellulitis, and abscess. These infections are caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus and streptococcus species. This chapter reviews nonpurulent and purulent SSTIs in pediatric patients; the bacterial etiology of these infections; clinical presentation and complications; antibiotic choice for treatment; and disposition of the patient, including when to obtain laboratory studies and decision to hospitalize. In addition, this chapter describes the diagnostic use of ultrasound for abscesses, pain management for incision and drainage of purulent infections, and follow-up care.

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 &mu, g/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration &lt, 7.4 &mu, g/mL responded versus 52% of those with a vedolizumab trough concentration &ge, g/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration &lt, g/mL was 3.7 (95% CI, 1.1&ndash, 13, p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

A fraction of COVID-19 patients progress to a severe disease manifestation with respiratory failure and the necessity of mechanical ventilation. Identifying patients at risk is critical for optimized care and early therapeutic interventions. We investigated the dynamics of SARS-CoV-2 shedding relative to disease severity. We analyzed nasopharyngeal and tracheal shedding of SARS-CoV-2 in 92 patients with diagnosed COVID-19. Upon admission, standardized nasopharyngeal swabs or sputum were collected. If patients were mechanically ventilated, tracheal aspirates were additionally obtained. Viral shedding was quantified by real-time PCR detection of SARS-CoV-2 RNA. 45% (41 of 92) of COVID-19 had a severe disease course with the need for mechanical ventilation (severe group). At week 1, the initial viral shedding determined from nasopharyngeal swabs showed no significant difference between non-severe and severe cases. At week 2, a difference could be observed as the viral shedding remained elevated in severely ill patients. A time course of C-reactive-Protein (CRP), Interleukin-6 (Il-6), and Procalcitonin (PCT) revealed an even more protracted inflammatory response following the delayed drop of virus shedding load in severely ill patients. A significant proportion (47.8%) of patients showed evidence of prolonged viral shedding (>17 days), which was associated with severe disease courses (73.2%). We report that viral shedding does not differ significantly between severe and non-severe cases upon admission to the hospital. Elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between second and third week and prolonged viral shedding are associated with a more severe disease course., We report that elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between second and third week and prolonged viral shedding are associated with a more severe disease course.

Successful cardiac surgery and recovery typically requires significant treatment adherence. For adults who undergo cardiac surgery and have diabetes mellitus (DM), the complex nature of behavior adherence is unique and especially demanding. Thus, we hypothesized that cardiac surgery patients with comorbid DM (CSDM) would report poorer treatment adherence than cardiac surgery patients without DM (CS). In this secondary data analysis, we assessed self-reported adherence (diet, medications, appointments) among CSDM (N=51) and CS (N=240) pre- and 3 months post-operatively. Participants were predominately male (64%), middle aged (M=63, SD=14), and presented for valve (N=137), coronary artery bypass graft (CABG; N=42), valve + CABG (N=57), or another cardiac (N=55) surgeries. Chi-square analyses assessed differences in self-reported adherence (adherent/not adherent/not applicable) by DM diagnosis (yes/no). Pre-operatively, CSDM were more likely to endorse that following any specific diet was applicable to them (70% vs. 50%), yet reported higher rates of dietary nonadherence (42%) than CS (29%), x2(2)=7.2, p=.027. Rates of medication (p=.420) or appointment (p=.875) adherence did not differ by DM diagnosis. At follow-up, a greater proportion of participants reported that dietary adherence was applicable to them (CSDM: 94%; CS: 74%), still with greater rates of non-adherence for CSDM (81%) compared to CS (55%), x2(2)=7.7, p=.021. Medication adherence (p=.570) and appointment attendance (p=.054) did not differ between groups. In this sample, CSDM seemed more aware of the importance of healthy diet, but were less likely to adhere to a diet (low sugar, sodium) than CS. This pattern may be due to greater awareness of dietary restrictions among patients with DM, as well as additional burden. Cardiac surgery patients with comorbid DM may benefit from additional support from dieticians and psychologists to address the complex psychosocial nature of dietary adherence in comorbid health conditions. Disclosure A. Vela: None. A.J. Carroll: None. P. McCarthy: None. G. Osterman: None. K. Grady: None. K. Feingold: None.

ObjectiveTherapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ), and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis with respect to response to VDZ.DesignIleal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of two biomarkers to VDZ was examined.ResultsClinical response in UST was significantly higher than placebo (65% vs. 39%, p=0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs. 20% (p=0.02). For VDZ, clinical response with MVL of 1.35-1.55 µm was 82% vs. 44% (1.55 µm) (p=0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis < 14 positive cells/1000 IECs or MVL of 1.35-1.55 µm could identify 84% of responders and 67% of non-responders (p=0.001).ConclusionsIleal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, combination of the two biomarkers enhanced the discriminate ability of responders from non-responders to VDZ.

Background & Aims Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib in patients with moderate to severe UC, up to 1 year, have been reported. We investigated maintenance of efficacy in patients in remission after 52 weeks of maintenance treatment in the pivotal phase 3 study (OCTAVE Sustain); these patients received open-label, long-term treatment with tofacitinib 5 mg twice daily. Methods Patients with moderate to severe UC who completed a 52-week, phase 3 maintenance study (OCTAVE Sustain) were eligible to enroll into the ongoing, phase 3, multicenter, open-label, long-term extension (OCTAVE Open). We analyzed data from 142 patients who were in remission following tofacitinib treatment in OCTAVE Sustain who received tofacitinib 5 mg twice daily during OCTAVE Open. We assessed efficacy (including remission [based on total Mayo score], endoscopic improvement, clinical response, and partial Mayo score up to month 36 of OCTAVE Open) and safety data. Results After 12 months of tofacitinib 5 mg twice daily in OCTAVE Open, 68.3% of patients were in remission, 73.9% had endoscopic improvement, and 77.5% had a clinical response. At month 36, 50.4%, of the patients were in remission, 55.3% had endoscopic improvement, and 56.0% had a clinical response. The safety profile of tofacitinib 5 mg twice daily revealed no new safety risks associated with long-term exposure up to 36 months. Conclusions Efficacy endpoints were maintained for up to 36 months, regardless of prior tofacitinib dose, including patients who reduced from tofacitinib 10 mg to 5 mg twice daily upon OCTAVE Open entry. No new safety risks were identified. ClinicalTrials.gov: OCTAVE Sustain (NCT01458574); OCTAVE Open (NCT01470612).

Objective It is difficult to predict relapse in quiescent ulcerative colitis (UC), but newer endoscopic and histological indices could improve this. This study aimed to determine in UC patients in clinical remission (1) the prevalence of active endoscopic and histological disease; (2) the correlation between endoscopic and histological scores; and (3) the predictive power of these scores for clinical relapse. Design This multicenter prospective cohort study conducted by the Crohn’s and Colitis Foundation Clinical Research Alliance included 100 adults with UC in clinical remission undergoing surveillance colonoscopy for dysplasia. Endoscopic activity was assessed using the Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and ulcerative colitis colonoscopic index of severity (UCCIS). Histology was assessed with the Riley index subcomponents, total Riley score, and basal plasmacytosis. Results Only 5% of patients had an MES of 0, whereas 38% had a score of 2 to 3; using the UCEIS, the majority of patients had at least mild activity, and 15% had more severe activity. Many patients also had evidence of histological disease activity. The correlations among endoscopic indices, histological subcomponents, and total score were low; the highest correlations occurred with the subcomponent architectural irregularity (ρ = 0.43–0.44), total Riley score (ρ = 0.35–0.37), and basal plasmacytosis (ρ = 0.35–0.36). Nineteen patients relapsed clinically over 1 year, with the subcomponent architectural irregularity being the most predictive factor (P = 0.0076). Conclusions This multicenter prospective study found a high prevalence of both endoscopic and histological disease activity in clinically quiescent UC. The correlations between endoscopy and histology were low, and the power to predict clinical relapse was moderate.

Background The purpose of this study was to investigate whether pT3–4 and pN-subclassifications, lymph-node ratio (LNR), tumour deposits, pre- and postoperative carcinoembryonic antigen (CEA), and C-reactive protein (CRP)—all parameters commonly collected in clinical management—add information about recurrence risk against a background of routine clinicopathological parameters as defined by the NCCN. Methods The prospective cohort consisted of all 416 patients diagnosed with colon cancer stage I–III in Uppsala County between 2010 and 2015. Cox proportional hazard models were used to calculate hazard ratios for time to recurrence and overall survival. The results were compared with the entire Swedish population concerning parameters recorded in the national quality registry, SCRCR, during the same time period. Results The Uppsala cohort was representative of the entire Swedish cohort. In unadjusted analyses, pT3-subclassification, pN-subclassification, LNR, tumour deposits, elevated postoperative CEA, and preoperative CRP correlated with recurrence. After adjusting for T-, N-stage, and NCCN risk factors, pN-subclassification, sidedness, and elevated postoperative CEA levels correlated with recurrence. Survival correlated with parameters associated with recurrence, LNR, and elevated postoperative CRP. Conclusions Additional information on recurrence risk is available from several routinely recorded parameters, but most of the risk is predicted by the commonly used clinicopathological parameters.

Thoracic outlet syndrome is a controversial entity. Diagnosis requires a thorough examination and is primarily clinical. Three main presentations exist: Neurogenic, arterial, and venous. Most cases can be managed non-operatively. Surgical decompression of the thoracic outlet space can be helpful in recalcitrant cases.

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub-Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial cancers, the relationship between FGM/C and cervical cancer is not well known. We performed a secondary analysis using combined data from six research studies conducted in and around Dakar, Senegal from 1994 to 2012. Study subjects included both asymptomatic women who presented to outpatient clinics but were screened for cervical cancer, and women with cancer symptoms who were referred for cervical cancer treatment. We used unconditional logistic regression to estimate adjusted pooled odds ratios (ORs) and 95% confidence intervals (CI) for associations between FGM/C and (1) Invasive cervical cancer (ICC) and (2) noninvasive cervical abnormalities. After adjusting for confounding, women with ICC were 2.50 times more likely to have undergone FGM/C than women without cervical abnormalities (95% CI, 1.28-4.91). Restricting to HPV-positive women increased the strength of the association (OR = 4.23; 95% CI 1.73-10.32). No significant associations between FGM/C and noninvasive cervical abnormalities were observed, except in commercial sex workers with FGM/C (OR = 2.01; 95% CI 1.19-3.40). The potential increased risk for ICC suggested by our study warrants further examination. Study results may impact cancer prevention efforts in populations where FGM/C is practiced and draw awareness to the additional health risks associated with FGM/C.

BACKGROUND: Developments in the quality of care of patients with colon cancer have improved surgical outcome and thus the need for adjuvant chemotherapy. OBJECTIVE: To investigate the recurrence rate in a large population-based cohort after modern staging, surgery, and pathology have been implemented. DESIGN: This was a retrospective registry study. SETTINGS: Data from patients included in the Swedish Colorectal Cancer Registry covering 99% of all cases and undergoing surgery for colon cancer stages I to III between 2007 and 2012 were obtained. PATIENTS: In total, 14,325 patients who did not receive any neoadjuvant treatment, underwent radical surgery, and were alive 30 days after surgery were included. MAIN OUTCOME MEASURES: Tumor and node classification and National Comprehensive Cancer Network-defined risk factors for recurrence were used to assess overall and stage-specific 5-year recurrence rates. RESULTS: The median follow-up of nonrecurrent cases was 77 months (range, 47-118 mo). The 5-year recurrence rate was 5% in stage I, 12% in stage II, and 33% in stage III patients. In patients classified as having pT3N0 cancer with no or 1 risk factor, the 5-year recurrence rates were 9% and 11%. Risk factors for shorter time to recurrence were male sex, more advanced pT and pN classification, vascular and perineural invasion, emergency surgery, lack of central ligature, short longitudinal resection margin, postoperative complications, and, in stage III, no adjuvant chemotherapy. LIMITATIONS: The registry does not contain some recently identified factors of relevance for recurrence rates, and some late recurrences may be missing. CONCLUSIONS: The recurrence rate is less than that previously observed in historical materials, but current, commonly used risk factors are still useful in evaluating recurrence risks. Stratification by pT and pN classification and the number of risk factors enables the identification of large patient groups characterized by such a low recurrence rate that it is questionable whether adjuvant treatment is motivated. See Video Abstract at http://links.lww.com/DCR/A663.

Background and Aims Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease [IBD]. Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared with reactive testing alone in patients with IBD. Methods This was a retrospective multicenter cohort study of consecutive IBD patients on infliximab maintenance therapy receiving a first reactive testing between September 2006 and January 2015. Patients were divided into two groups; Group A [proactive infliximab monitoring after reactive testing] and Group B [reactive testing alone]. Patients were followed through December 2015. Time-to-event analysis for treatment failure and IBD-related surgery and hospitalization was performed. Treatment failure was defined as drug discontinuation due to either loss of response or serious adverse event. Results The study population consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n = 69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4–3.8] years. Multiple Cox regression analysis identified proactive following reactive TDM as independently associated with less treatment failure (hazard ratio [HR] 0.15; 95% confidence interval [CI] 0.05–0.51; p = 0.002) and fewer IBD-related hospitalizations [HR: 0.18; 95% CI 0.05–0.99; p = 0.007]. Conclusions This study showed that proactive infliximab monitoring following reactive testing was associated with greater drug persistence and fewer IBD-related hospitalizations than reactive testing alone.