Microsatellite Instability Testing and Prognostic Implications in Colorectal Cancer.

Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan-Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026-0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001-1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.

The Road Less Traveled: Perspective From an Australian Oncologist.

Diverse factors and beliefs define treatment decisions of culturally and linguistically diverse patients. Recognizing, understanding and respecting these enable us to walk with them on their cancer journey, even if it may be the road less traveled.

Screening for Bacterial Vaginosis Prior to Delivery: A Cost-Effectiveness Study.

OBJECTIVE: The objective of this study was to compare the cost and effectiveness of three strategies for screening and/or treating bacterial vaginosis (BV) during pregnancy prior to delivery: (1) the current standard of care was neither test nor treat for BV (Treat None); (2) test all patients for BV at 36 weeks' gestation; treat if positive (Test Treat); and (3) treat all patients undergoing cesarean delivery with intravenous metronidazole at time of surgery (Treat All Cesarean). Effectiveness was defined as avoidance of postpartum surgical site infection (SSI). STUDY DESIGN: A decision analytic cost-effectiveness model was designed from a third-party payer perspective using clinical and cost estimates obtained from the literature, American College of Surgeons National Surgical Quality Improvement Program participant use file (2005-2019), 2019 National Vital Statistics, Medicare costs, and wholesale drug costs. Cost estimates were inflated to 2020 U.S. dollars. For this study, effectiveness was defined as avoidance of postpartum SSIs. RESULTS: The base case analysis that is the current standard of care of not routinely testing and treating patients for BV (Treat None) was the most expensive and least effective strategy, with a mean cost of $59.16 and infection rate of 3.71%. Empirically treating all patients for BV without testing (Treat All Cesarean) was the most effective and the least expensive strategy, with a mean cost of $53.50 and an infection rate of 2.75%. Testing all patients for BV and treating those positive for BV (Test Treat) was also relatively inexpensive and effective, with an infection rate of 2.94% and mean cost of $57.05. Compared with Treat None, we would expect the Treat All Cesarean strategy to reduce the infection rate by 26%. CONCLUSION: These findings suggest that treating pregnant patients with intravenous metronidazole at time of cesarean delivery could be an effective and cost-saving strategy. Testing and treating for BV could also be considered a reasonable strategy, as it has the added benefit of preserving antibiotic stewardship. In no analysis was the standard of care strategy of neither testing nor treating for BV before delivery the preferred strategy. KEY POINTS: · BV colonization may increase surgical site infection risk after cesarean section.. · Treatment of BV before or during delivery may be cost-saving strategies as treatment could prevent costs associated with infection.. · Further study is needed to best balance the risk of surgical site infection with antibiotic stewardship..

Sowing the Seeds of Recovery: A Qualitative Study of Women in Recovery From Addiction and Victimization.

The purpose of this study was to understand the lived experiences of women with histories of victimization and addiction who were recently admitted to a sober living home (SLH). From the 17 interviews conducted, five themes (i.e., experiences of violence, challenges leaving an abusive relationship, chaos, using substances to cope, and social support) and one constitutive pattern (i.e., sowing the seeds of recovery) emerged from the data. These results highlight the importance of social support in promoting recovery and that social support may foster positive relationships with safe and trustworthy individuals as well as empower and support others with similar experiences.

Examination of the Multilevel Sexual Stigma Model of Intimate Partner Violence Risk Among LGBQ+ College Students: A Prospective Analysis Across Eighteen Institutions of Higher Education.

Sexual stigma operates at multiple levels (institutional, group, individual), which serves to disadvantage sexual minority (LGBQ+) individuals and increases risk for deleterious outcomes. The current study evaluated a novel multilevel sexual stigma model of intimate partner violence (MLSSM-IPV) that incorporates multiple levels of sexual stigma as related to IPV risk via several pathways (e.g. hazardous drinking, affective symptoms). We evaluated this model in a longitudinal study of LGBQ+ undergraduate college students (n = 2,415) attending 18 universities who completed surveys in the Fall and Spring semesters. Group-level sexual stigma on each campus was assessed via surveys with heterosexual students (n = 8,517) and faculty, staff, and administrators (n = 2,865), and institutional-level stigma was evaluated via a campus climate assessment. At the campus level, institutional stigma was related to LGBQ+ students' self-stigma and identity concealment. Moreover, self-stigma prospectively predicted IPV victimization, and hazardous drinking mediated the relations between self-stigma and IPV perpetration and victimization. Results suggest that interventions addressing stigma and hazardous drinking may be efficacious in reducing IPV among LGBQ+ students. Further, comprehensive efforts to improve campus climate for LGBQ+ students are likely to produce a plethora of benefits for these students.

p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.

The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells' behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.

Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study.

BACKGROUND: P47phox (neutrophil cytosolic factor-1) deficiency is the most common cause of autosomal recessive chronic granulomatous disease (CGD) and is considered to be associated with a milder clinical phenotype. Allogeneic hematopoietic cell transplantation (HCT) for p47phox CGD is not well-described. OBJECTIVES: We sought to study HCT for p47phox CGD in North America. METHODS: Thirty patients with p47phox CGD who received allogeneic HCT at Primary Immune Deficiency Treatment Consortium centers since 1995 were included. RESULTS: Residual oxidative activity was present in 66.7% of patients. In the year before HCT, there were 0.38 CGD-related infections per person-years. Inflammatory diseases, predominantly of the lungs and bowel, occurred in 36.7% of the patients. The median age at HCT was 9.1 years (range 1.5-23.6 years). Most HCTs (90%) were performed after using reduced intensity/toxicity conditioning. HCT sources were HLA-matched (40%) and -mismatched (10%) related donors or HLA-matched (36.7%) and -mismatched (13.3%) unrelated donors. CGD-related infections after HCT decreased significantly to 0.06 per person-years (P = .038). The frequency of inflammatory bowel disease and the use of steroids also decreased. The cumulative incidence of graft failure and second HCT was 17.9%. The 2-year overall and event-free survival were 92.3% and 82.1%, respectively, while at 5 years they were 85.7% and 77.0%, respectively. In the surviving patients evaluated, ≥95% donor myeloid chimerism at 1 and 2 years after HCT was 93.8% and 87.5%, respectively. CONCLUSIONS: Patients with p47phox CGD suffer from a significant disease burden that can be effectively alleviated by HCT. Similar to other forms of CGD, HCT should be considered for patients with p47phox CGD.

Patients' perception of the benefits of palliative systemic therapy for advanced cancer.

BACKGROUND: Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy. AIM: To determine patient perceptions of palliative systemic therapy benefits in advanced cancer. METHODS: We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0-10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4-7 QOL and LOL equal; >7 LOL most important). Patient-oncologist discordance was defined as a ≥4-point difference. RESULTS: The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient-oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%). CONCLUSION: At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions.

Real-world tolerance and outcomes of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer-Does dose intensity matter?

INTRODUCTION: Fluoropyrimidine and oxaliplatin-based adjuvant chemotherapy delivered as 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin (CAPOX) is the standard of care for resected stage III colon cancer. Without randomized trial data, we compared real-world dose intensity, survival outcomes, and tolerability of these regimens. METHODS: Records of patients treated with FOLFOX or CAPOX in the adjuvant setting for stage III colon cancer across four institutions in Sydney during 2006-2016 were reviewed. The relative dose intensity (RDI) of fluoropyrimidine and oxaliplatin of each regimen, disease-free survival (DFS), overall survival (OS), and incidence of grade ≥2 toxicities were compared. RESULTS: Characteristics of patients receiving FOLFOX (n = 195) and CAPOX (n = 62) were evenly matched. FOLFOX patients had a higher mean RDI for both fluoropyrimidine (85% vs. 78%, p < 0.01) and oxaliplatin (72% vs. 66%, p = 0.06). In spite of a lower RDI, CAPOX patients trended toward a better 5-year DFS (84% vs. 78%, HR = 0.53, p = 0.068) and similar OS (89% vs. 89%, HR = 0.53, p = 0.21) compared to the FOLFOX group. This difference was most pronounced in the high-risk (T4 or N2) group where 5-year DFS was 78% versus 67% (HR = 0.41, p = 0.042). Patients receiving CAPOX experienced more grade ≥2 diarrhea (p = 0.017) and hand-foot syndrome (p < 0.001) but not peripheral neuropathy or myelosuppression. CONCLUSION: In a real-world setting, patients who received CAPOX had similar OS rates when compared to those receiving FOLFOX in the adjuvant setting in spite of lower RDI. In the high-risk population, CAPOX appears to demonstrate a superior 5-year DFS over FOLFOX.

The Role of Minority Stress in Psychological Distress and Hazardous Drinking Among Sexual Minority College Student Victims of Intimate Partner Violence.

Sexual minority, individuals who are not heterosexual, college students experience high rates of intimate partner violence (IPV), which is linked to a myriad of deleterious outcomes. However, little work has evaluated whether there are differences in IPV outcomes among sexual minority college students as compared to heterosexual college students. Further, the extent to which minority stress at the institutional and individual level relates to IPV outcomes among sexual minority students is understudied. As such, the purpose of the current study was to evaluate IPV outcomes in a large sample of undergraduate students attending 18 medium- to large-sized universities across the contiguous U.S. Results supported that sexual minority victims of IPV had more anxious and depressive symptoms than heterosexual victims of IPV but were not more likely to engage in hazardous drinking. Further, analyses supported that several campus-level (but not individual-level) indicators of minority stress moderated the relation between IPV victimization and negative outcomes among sexual minority students, such that the association between IPV and negative outcomes was stronger among students embedded in campuses with higher levels of minority stressors. Results support the critical importance of interventions addressing campus-level minority stressors to reduce deleterious IPV outcomes among sexual minority college student victims.

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort.

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014-2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.

Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population.

BACKGROUND: Next generation sequencing (NGS) is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT[E]) Tier I-V & X. Allele frequency is also increasingly recognised as an important prognostic tool in advanced cancer. The aim of this study was to determine the genomic mutations in metastatic colorectal cancer (CRC) in an Australian multicultural population and their influence on survival outcomes. METHODS: Next generation sequencing with the 50-gene panel Oncomine Precision Assay™ was used on 180 CRC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022. RESULTS: From 180 samples, 147 (82%) had at least one gene mutation identified with 68 (38%) having two or more concurrent mutations. Tier I variants included RAS wild-type [EI] in 73 (41%) and BRAF V600E [EIA] in 27 (15%). Non-tier I variants include 2 (1%) ERBB2 amplification [EIIB], 26 (15%) PIK3CA hotspot mutations [EIIIA] and 9 (5%) MET focal amplifications [EIIIA]. NGS testing revealed an additional 22% of cases with Tier II & III mutations. 43% of patients also presented with potentially actionable Tier III & IV mutations. Patients with concurrent TP53 and RAS mutations had significantly reduced overall survival (6.1 months versus 21.1 months, p <0.01). High KRAS allele frequency, as defined by those with over 20% variant allele frequency (VAF), also demonstrated reduced overall survival (12.1 months versus 42.9 months, p = 0.04). CONCLUSIONS: In addition to identifying patients with genomic alterations suitable for clinically proven standard of care therapeutic options, the 50 gene NGS panel has significant potential in identifying potentially actionable non-tier 1 mutations and therefore may become future standard clinical practice.

The Impact of COVID-19 on Values and Religiosity in a Multi-Ethnic Population.

We investigated the COVID-19 pandemic's impact on values and religiosity in multi-ethnic Malaysia. Values were measured as changes in values, daily activities, and life priorities using a 5-point Likert scale (-2 to +2). Centrality of Religiosity Scale measured changes in religiosity. Around 176 predominantly female (66.5%), Chinese (68.2%) respondents, aged 35.5 ± 14.1 completed the survey. Most life values changed positively: a sense of security at home (2, interquartile range [IQR]: 1-2), connection with family (1, 1-2), and contribution to society (1, 1-2). Certain life priorities' importance increased: health (2, IQR 2-2), family (2, 2-2), and happiness (2, 1-2); except power and money. These significant positive changes in values and religiosity varied between genders and ethnicities.

Implementation of a validated post-operative opioid nomogram into clinical gynecologic surgery practice: A quality improvement initiative.

Objectives: The Gynecologic Oncology Postoperative Opioid use Predictive (GO-POP) calculator is a validated tool to provide evidence-based guidance on post-operative opioid prescribing. The objective of this study was to evaluate the impact of the implementation of GO-POP within an academic Gynecologic Oncology division. Methods: Two cohorts of patients (pre-implementation and post-implementation) who underwent surgery were compared with reference to GO-POP calculator implementation. All patients were included in the post-implementation group, regardless of GO-POP calculator use. An additional expanded-implementation cohort was used to compare pain control between GO-POP users and non-GO-POP users prospectively. Wilcoxon rank sum tests or ANOVA for continuous variables and Chi-square or Fisher's exact tests were used to categorical variables. Results: The median number of pills prescribed post-operatively decreased from 15 pills (Q1: 10, Q3: 20) to 10 pills (Q1: 8, Q3: 14.8) after implementation (p < 0.001). In the expanded-implementation cohort (293 patients), 41% patients were prescribed opioids using the GO-POP calculator. An overall median of 10 pills were prescribed with no difference by GO-POP calculator use (p = 0.26). Within the expanded-implementation cohort, refill requests (5% vs 9.2%; p = 0.26), clinician visits (0.8% vs 0.6%, p = 1), ED or urgent care visits (0% vs 2.3%, p = 0.15) and readmissions (0% vs 1.7%, p = 0.27) for pain did not differ between those prescribed opioids with and without the GO-POP calculator. Conclusions: A 33% reduction in post-operative opioid pills prescribed was seen following implementation of the GO-POP calculator into the Gynecologic Oncology division without increasing post-operative pain metrics or encounters for refill requests.

Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

Outcomes and Complications for Concurrent Hernia Repair Among Women Undergoing Hysterectomy.

OBJECTIVE: To assess whether concurrent hernia repair at time of hysterectomy is associated with increased complications. METHODS: In this retrospective cohort study, patients who underwent hysterectomy and hysterectomy with concurrent hernia repair were queried using the American College of Surgeons' National Surgical Quality Improvement Program participant use file (2005-2019). Propensity score matching was performed 1:1 with respect to preoperative and operative characteristics. Outcomes were operation time, length of stay (LOS), and major and minor complications. A secondary analysis of patients who underwent hysterectomy for malignancy was performed. RESULTS: A total of 369,010 patients underwent hysterectomy, and 5,071 of those underwent hysterectomy with concurrent hernia repair. After propensity score matching, there were 5,071 patients in each arm. Hysterectomy with concurrent hernia repair had a longer operation time by 46 minutes (95% CI 42.6-49.6; P <.001) and longer LOS after surgery by 0.71 days (95% CI 0.59-0.84; P <.001). Hysterectomy with concurrent hernia repair was associated with a 21.9% higher risk (15.6% vs 12.8%; 95% CI 1.11-1.34, P <.001) of major complications and was associated with a 34.5% higher risk (7.4% vs 5.5%; 95% CI 1.16-1.56, P <.001) of minor complications. In subgroup analyses, there was no significant increase in risk among patients with body mass indexes (BMIs) lower than 40, those who were younger than age 40 years or older than age 60 years, and those with tobacco use, diabetes, or a minimally invasive surgical approach. For patients undergoing hysterectomy for malignancy, hysterectomy with concurrent hernia repair was associated with a 32-minute longer operation time (95% CI 25.2-38.8; P <.001) and a 0.35-day longer LOS (95% CI 0.04-0.67, P =.027), but there was no significant difference in major and minor complications. CONCLUSION: Hysterectomy with concurrent hernia repair is associated with increased operation time, LOS, and risk of major and minor complications compared with hysterectomy without hernia repair. The subgroup analyses suggest that hysterectomy with concurrent hernia has a similar complication risk as hysterectomy without hernia repair in select populations, such as those with BMIs lower than 40 or with known malignancy.

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/- chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.

Gender-neutral bathrooms on campus: a multicampus study of cisgender and transgender and gender diverse college students.

Objective: This study examined cisgender and transgender and gender diverse (TGD) college students' perceptions of gender-neutral bathroom availability across eight U.S. campuses, TGD students' fear of harassment related to (lack of) availability of gender-neutral bathrooms, and the relation between fear of harassment and TGD students' psychological distress. Methods: Participants were 4,328 college students (4,195 cisgender, 30 binary transgender, 103 gender diverse) from eight U.S. institutions of higher education. Results: The majority (84.2%) of TGD students and 34.6% of cisgender students perceived there were too few gender-neutral bathrooms on their campus. Further, TGD students' fear of harassment related to a lack of availability of gender-neutral bathrooms on campus was positively associated with psychological distress (i.e., symptoms of depression and anxiety). Conclusion: This study highlights the significance of increasing accessibility of gender-neutral bathrooms on campuses to help mitigate TGD students' fear of harassment and psychological distress.

Genotype, oxidase status, and preceding infection or autoinflammation do not affect allogeneic HCT outcomes for CGD.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score <90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Prognostic Significance of MRE11 Overexpression in Colorectal Cancer Patients.

Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan-Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS; p = 0.045) and overall survival (OS; p = 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p = 0.005) and OS (p = 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034-2.785; p = 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122-3.293; p = 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p = 0.006) and LVI/PNI (p = 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients.