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The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID) mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy) to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

Supplementary Table 1 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

Supplementary Table 2 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

Supplementary Figure 2 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

Using an integrated approach of epigenomic scanning and gene expression profiling, we found aberrant methylation and epigenetic silencing of a small neighborhood of contiguous genes—the HOXA gene cluster in human breast cancer. The observed transcriptional repression was localized to ∼100 kb of the HOXA gene cluster and did not extend to genes located upstream or downstream of the cluster. Bisulfite sequencing, chromatin immunoprecipitation, and quantitative reverse transcription-PCR analysis confirmed that the loss of expression of the HOXA gene cluster in human breast cancer is closely linked to aberrant DNA methylation and loss of permissive histone modifications in the region. Pharmacologic manipulations showed the importance of these aberrant epigenetic changes in gene silencing and support the hypothesis that aberrant DNA methylation is dominant to histone hypoacetylation. Overall, these data suggest that inactivation of the HOXA gene cluster in breast cancer may represent a new type of genomic lesion—epigenetic microdeletion. We predict that epigenetic microdeletions are common in human cancer and that they functionally resemble genetic microdeletions but are defined by epigenetic inactivation and transcriptional silencing of a relatively small set of contiguous genes along a chromosome, and that this type of genomic lesion is metastable and reversible in a classic epigenetic fashion. (Cancer Res 2006; 66(22): 10664-70)

Supplementary Table 4 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

Supplementary Figure 3 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

Supplementary Table 3 from Epigenetic Inactivation of the HOXA Gene Cluster in Breast Cancer

The Western Canadian Gastrointestinal Cancer Consensus Conference (WC-5) convened virtually on 10 February 2021. The WC-5 is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular cancer (HCC). Recommendations have been made for the transition from local to systemic therapy and the optimal sequencing of systemic regimens in the management of HCC.

Ultrasound-stimulated microbubbles (USMB) cause localized vascular effects and sensitize tumors to radiation therapy (XRT). We investigated acoustic parameter optimization for combining USMB and XRT. We treated breast cancer xenograft tumors with 500 kHz pulsed ultrasound at varying pressures (570 or 740 kPa), durations (1 to 10 minutes), and microbubble concentrations (0.01 to 1% (v/v)). Radiation therapy (2 Gy) was administered immediately or after a 6-hour delay. Histological staining of tumors 24 hours after treatment detected changes in cell morphology, cell death, and microvascular density. Significant cell death resulted at 570 kPa after a 1-minute exposure with 1% (v/v) microbubbles with or without XRT. However, significant microvascular disruption required higher ultrasound pressure and exposure duration greater than 5 minutes. Introducing a 6-hour delay between treatments (USMB and XRT) showed a similar tumor effect with no further improvement in response as compared to when XRT was delivered immediately after USMB.

Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma.We sought to quantify the effect of race/ethnicity, socioeconomic status (SES), and healthcare systems on melanoma-specific mortality within an insured population of patients.Using a retrospective cohort study, we identified insured adults diagnosed with Stage I-IV melanoma from 1/1/2009 through 12/31/2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated healthcare system in California, Kaiser Permanente Southern California (KPSC), and insured patients with outside private insurance (OPI).Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while SES was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in KPSC have no increased risk.Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans.Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated healthcare systems.

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive hereditary cancer syndrome due to biallelic germline mutation involving one of the four DNA mismatch repair genes. Here we present a case of a young female with CMMRD, homozygous for the c.2002A>G mutation in the PMS2 gene. She developed an early stage adenocarcinoma of the colon at the age of 14. Surveillance MRI of the brain at age 18 resulted in the detection of an asymptomatic brain cancer. On resection, this was diagnosed as an anaplastic astrocytoma. Due to emerging literature suggesting benefit of immunotherapy in this patient population, she was treated with adjuvant dual immune checkpoint inhibition, avoiding radiation. The patient remains stable with no evidence of progression 20 months after resection. The patient’s clinical course, as well as the rational for considering adjuvant immunotherapy in patients with CMMRD are discussed in this report.

Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer–Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median (range) age, 56.1 (36.0–76.4 years)]. Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed.Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.

SUMMARYMultiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike—specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.

Storage of trametinib tablets outside of 2-8°C protected from moisture may lead to loss of dimethyl sulfoxide (DMSO) and adversely impact trametinib bioavailability. In this open-label, phase 1, single-dose, randomized, 2-treatment, 2-period crossover study in healthy volunteers, bioavailability of a single 2-mg tablet of trametinib containing 9% DMSO (test formulation), corresponding to the lowest DMSO content in the tablet after storage at 25°C for 36 months, was evaluated vs bioavailability of a 2-mg tablet containing 11% DMSO (reference formulation). Sixty-five percent of subjects (n = 39/65) were men, and mean (standard deviation) age was 45.6 (11.17) years. Time to reach maximum plasma concentration occurred at 1.5 hours after dosing. The geometric mean ratio (90%CI) comparing 2-mg trametinib containing 9% DMSO with 2-mg trametinib containing 11% DMSO for area under the concentration-time curve from time 0 to the last measurable plasma concentration sampling time was 0.890 (0.848-0.935), suggesting the 2 formulations have similar bioavailability. The majority of adverse events were mild, with 1 subject experiencing 1 grade 3 headache. These results indicated that storage of trametinib at room temperatures ≤25°C during the overall shelf life of 36 months would not negatively impact trametinib bioavailability.

KEY POINTS A 49-year-old premenopausal woman underwent lumpectomy and sentinel lymph node biopsy for grade 1 invasive ductal carcinoma of the right breast. The tumour measured 1.6 cm and was positive for estrogen receptor and progesterone receptor, and negative for human epidermal receptor 2. The

Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown.Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia.Methods: ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at Embryonic Day 20 to simulate antenatal models of chorioamnionitis and preeclampsia, respectively. Pups were delivered by cesarean section at Embryonic Day 22 and treated with rhIGF-1/BP3 (0.02-20 mg/kg/d intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts (RACs), vessel density, and right ventricular hypertrophy (RVH). Direct effects of rhIGF-1/BP3 (250 ng/ml) on fetal lung endothelial cell proliferation and tube formation and alveolar type 2 cell proliferation were studied by standard methods in vitro.Measurements and Main Results: Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation.Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.

Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low–added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

OBJECTIVES Limited evidence exists for chemotherapy selection in advanced pancreatic cancer (APC) after first-line FOLFIRINOX. Second-line gemcitabine/nab-paclitaxel (GEMNAB) is publicly funded in the Canadian provinces of Alberta (AB) and Manitoba (MB), but not in British Columbia (BC). We compared population-based outcomes by region to examine the utility of second-line GEMNAB versus gemcitabine (GEM) alone. METHODS We identified patients treated with first-line FOLFIRINOX between 2013 and 2015 across BC, AB, and MB. Baseline characteristics and treatment regimens were compared between AB/MB and BC. Survival outcomes were assessed by the Kaplan-Meier method and compared with log-rank test. RESULTS A total of 368 patients were treated with first-line FOLFIRINOX (143 AB/MB, 225 BC): median age 61 (interquartile range: 55 to 68) years, 42% comprising female individuals, and 67% with metastatic disease. Receipt of second-line therapy was 48% in AB/MB versus 44% in BC (P=0.35), and time from diagnosis to second-line therapy was 7.7 (AB/MB) versus 9.4 months (BC; P=0.1). Distribution of second-line GEM use: 73% GEMNAB, 23% GEM (AB/MB) versus 27% GEMNAB, 66% GEM (BC; P

In public health emergencies, caregivers are a crucial but often overlooked human resource. The purpose of this longitudinal study was to assess the well-being of caregivers and non-caregivers over the first 18 months of the COVID-19 pandemic. We used three waves of data from the Survey of the Health of Wisconsin’s COVID-19 Community Impact Survey (Wave 1: May-June 2020; Wave 2: January-February 2021; Wave 3: June 2021; n=2,434 observations of 1,653 unique respondents). Caregivers were identified as those providing care for an adult with an illness or disability. Perceived stress (Global Stress Scale; mean=5.08, SD=4.81) was regressed on caregiver status and covariates in mixed models accounting for repeated measures. On average, caregivers had higher stress than non-caregivers (beta=2.10, p< 0.0001). Across the sample, stress increased between summer 2020 and winter 2021 (mean of 4.8 versus 5.8, p

Background and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) are proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and four 2DSWE studies, and for diagnosing NASH in four MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.Lay summary:Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy in assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20–21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.

Patients with advanced pancreatic cancer (APC) experience many disease-related symptoms. ESAS-r measures the severity of 9 symptom domains and has been validated for use in the ambulatory oncology setting. We aimed to describe symptom burden at baseline for patients with APC treated with modern chemotherapy (CT), and to determine whether symptom burden at baseline is prognostic. Patients diagnosed with APC between 2012–2016, treated with ≥1 cycle of CT, who completed ≥1 ESAS-r were identified. Descriptive statistics were used to report symptom burden and common moderate-to-severe symptoms. A joint model was used to describe the trajectory of ESAS-r during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Of 123 patients identified, the median age was 65 and 61% had metastatic disease. The median baseline ESAS-r total symptom distress score (TSDS) was 24. A total of 86% of patients had at least one symptom score of ≥4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Median overall survival was 10.2 months. Baseline TSDS was not predictive for worse survival in the era of modern CT. Patients with APC have a high burden of cancer-associated symptoms and a high prevalence of moderate-to-severe symptoms. Early intervention has the potential to improve quality of life in this group of patients and should be investigated.

Identification of Lynch syndrome (LS) followed by annual/biannual surveillance colonoscopy markedly reduces the risk of developing new colorectal cancer (CRC) among those with LS. (1) To determine the current practice of identifying LS in the USA and Canada, and current surveillance and management practices for those diagnosed with LS; (2) to determine whether variances in current practice are physician/region dependent or influenced by ease of access to specialist clinics. An online survey request was sent to practicing gastroenterologists through the Canadian Association of Gastroenterology and the American College of Gastroenterology. Fisher’s exact tests were performed to determine the factors associated with screening for LS and separately for follow-up, surveillance, and management. A total of 249 participants were recruited, of which 237 were gastroenterologists and included in the analysis. Less than one-third of practicing gastroenterologists indicated that their CRC patients were undergoing screening tests to identify LS. While 42% (65/153) of participants from the USA stated that their patients were undergoing universal LS screening (i.e., among all diagnosed with CRC), only 12% (6/49) of participants from Canada reported this practice (p

not available.

Objective The current study investigates associations between parents’ perceived coronavirus disease 2019 (COVID-19) psychological impacts and experiences of parental burnout, children’s behaviors, and income. Methods Data were collected during an online survey of parents’ (N = 1000) pandemic experiences in April 2020. Parents (M = 36.5 years old, SD = 6.0; 82.1% White) with at least one child 12 years or younger reported on measures of mental health, perceived COVID-19 impacts, parental burnout, and perceived increases in children’s stress and positive behaviors. Results Path model analyses revealed that parents who perceived increased psychological impacts from COVID-19 reported higher levels of parental burnout, greater increases in children’s stress behaviors, and less positive behavior in children. Additionally, there were significant indirect effects of parental burnout on the link between COVID-19 psychological impacts and children’s behaviors. Finally, family income moderated associations between psychological impacts and children’s stress behaviors, such that the association was stronger for families with lower income. Conclusions These results suggest parents’ perceptions of how the COVID-19 pandemic has impacted their mental health has implications for parent and child well-being, with stronger associations for low-income families. Given the potential for spillover effects between parents and children, promoting family well-being through practice and policy initiatives is crucial, including providing financial and caregiving relief for parents, and mental and behavioral health support for families.

Background Capecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is commonly used in the treatment of colorectal cancer. Adverse cardiac side effects are reported in 1–18% of patients receiving Capecitabine. The most commonly proposed mechanism of cardiotoxicity in the setting of Capecitabine use is vasospasm of the coronary arteries. However, cardiotoxicity can also present as an acute coronary syndrome, arrhythmia, hypertension, and/or sudden cardiac death. Profound non-vasospastic cardiotoxicity is rare. Case summary We describe two cases of acute heart failure leading to cardiogenic shock in patients shortly after exposure to Capecitabine. Both patients did not demonstrate the characteristic transient ST elevation seen in patients with coronary artery vasospasms secondary to Capecitabine. Both patients required admission to the Acute Cardiac Care Unit requiring vasopressor and inotropic support. Thorough diagnostic investigations including echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography did not identify infarction, myocarditis, or any infiltrative process to explain their symptoms. Both patients had complete resolution of cardiac function, with no long-term sequalae. Discussion In patients receiving Capecitabine, reversible heart failure leading to cardiogenic shock should be considered as a potential cardiotoxic side effect.

The experience of sexual harassment (SH) may exacerbate the drive toward an ideal and often unattainable physical appearance, creating the foundation of unhealthy eating, and greater shape and weight concerns. This systematic review aimed to synthesize evidence on the relationship between SH and eating disorder psychopathology, as well as mediating and moderating factors that contribute to this relationship.Six key databases were searched from inception to August 2020; including CINAHL, PsycInfo, PubMed, Medline, Scopus, and Web of Science.Overall, 15 studies meeting inclusion criteria were found, with 14 reporting a statistically significant relationship between SH and eating disorder psychopathology. A meta-analysis with 12 cross-sectional studies confirmed a small but significant effect for this concurrent association. Moderators of this relationship included gender, posttraumatic stress, and anxiety. No studies in this review conducted true mediation.Conclusions about causal and mediating relationship between SH and eating disorder psychopathology are constrained by the preponderance of cross-sectional design (14 of the 15 studies). Therefore, it is recommended that future studies focus on the use of longitudinal design, and also on adolescent populations, where first experiences of SH are usually reported, and which is also the peak age of onset for eating disorders.La experiencia del acoso sexual puede exacerbar el impulso hacia una apariencia física ideal y a menudo inalcanzable, creando la base de una alimentación poco saludable, y mayores preocupaciones con la figura y peso corporal. Esta revisión sistemática tuvo como objetivo sintetizar la evidencia sobre la relación entre el acoso sexual y la psicopatología del trastorno alimentario, así como mediar y moderar los factores que contribuyen a esta relación. MÉTODO: Se buscó en seis bases de datos clave, desde el inicio hasta agosto de 2020; incluyendo CINAHL, PsycInfo, PubMed, Medline, Scopus, Web of Science.En total, se encontraron 15 estudios que cumplían con los criterios de inclusión, y 14 reportaron una relación estadísticamente significativa entre el acoso sexual y la psicopatología de trastornos de la conducta alimentaria. Un metanálisis con 12 estudios transversales confirmó un pequeño pero significativo efecto para esta asociación simultánea. Los moderadores de esta relación incluyeron género, estrés postraumático y ansiedad. Ningún estudio en esta revisión llevó a cabo una verdadera mediación. DISCUSIÓN: Las conclusiones sobre la relación causal y mediadora entre el acoso sexual y la psicopatología de los trastornos de la conducta alimentaria están limitadas por la preponderancia del diseño transversal (14 de los 15 estudios). Por lo tanto, se recomienda que los futuros estudios se centren en el uso del diseño longitudinal, y también en las poblaciones adolescentes, donde por lo general se reportan las primeras experiencias de acoso sexual, y que también son la edad pico de inicio para los trastornos de la conducta alimentaria.

Background Pancreatic cancer primarily affects older adults and is associated with a high morbidity and mortality. Identifying frail patients with advanced pancreatic cancer (APC) helps to mitigate the risks of chemotherapy (CT). The modified Frailty Index (mFI) is an 11-point deficit measure used to identify frail patients. Although validated in surgical fields, it has not been assessed in an APC population. Methods A retrospective cohort study evaluated consecutive patients, aged ≥65 years, diagnosed with APC from 2011 to 2016 and treated with first line palliative-intent CT. mFI was categorized as: 0, 1, 2 and ≥ 3. Descriptive analysis was completed comparing patient characteristics, CT toxicity, response to treatment, and overall survival (OS) by mFI score. Results 87 patients with APC received palliative CT. Median age was 71 (65–88), 54% male. A mFI score of 0, 1, 2, and ≥ 3 occurred for 20 (23%), 28 (32.2%), 25 (28.7%) and 14 (16.1%) patients respectively. Patients with mFI scores of 0–1 were more likely to receive: 5-fluorouracil, irinotecan and oxaliplatin. CT toxicity, emergency room (ED) and urgent cancer clinic (UCC) presentation, and hospitalization length did not differ by mFI. Longer OS was associated with better ECOG and receipt of combination CT. Conclusion This is the first assessment of the mFI in an APC population receiving CT. The mFI score did not correlate with toxicity, ED/UCC visits, hospitalization length or OS. Ongoing assessment of tools that accurately identify frailty in patients with APC is critical to help better select candidates for aggressive CT.

Over the past 25 years, pediatric minimally invasive surgery (MIS) has grown in volume and complexity. Initially, MIS consisted of purely laparoscopic cases. Multiple series have demonstrated low complication rates with pediatric laparoscopy. In the twenty-first century, robotically-assisted laparoscopy grew in popularity and expanded the breadth of MIS cases performed in both adults and in children.