Mutant p53 regulates Survivin to foster lung metastasis.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide and evolves often to lung metastasis. P53R175H (homologous to Trp53R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC remains to be investigated. To investigate p53R175H-mediated molecular mechanisms, we used a carcinogen-induced approach in Trp53R172H/- mice to model ESCC. In the primary Trp53R172H/- tumor cell lines, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We identified the YAP-BIRC5 axis as a potential mediator of Trp53R172H -mediated metastasis. We demonstrate that expression of Survivin, an antiapoptotic protein encoded by BIRC5, increases in the presence of Trp53R172H Furthermore, depletion of Survivin specifically decreases Trp53R172H-driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce Survivin expression. Furthermore, Survivin high expression level is associated with increased metastasis in several GI cancers. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.

Use of a convolutional neural network-based mammographic evaluation to predict breast cancer recurrence among women with hormone receptor-positive operable breast cancer.

PURPOSE: We evaluated whether a novel, fully automated convolutional neural network (CNN)-based mammographic evaluation can predict breast cancer relapse among women with operable hormone receptor (HR)-positive breast cancer. METHODS: We conducted a retrospective cohort study among women with stage I-III, HR-positive unilateral breast cancer diagnosed at Columbia University Medical Center from 2007 to 2017, who received adjuvant endocrine therapy and had at least two mammograms (baseline, annual follow-up) of the contralateral unaffected breast for CNN analysis. We extracted demographics, clinicopathologic characteristics, breast cancer treatments, and relapse status from the electronic health record. Our primary endpoint was change in CNN risk score (range, 0-1). We used two-sample t-tests to assess for difference in mean CNN scores between patients who relapsed vs. remained in remission, and conducted Cox regression analyses to assess for association between change in CNN score and breast cancer-free interval (BCFI), adjusting for known prognostic factors. RESULTS: Among 848 women followed for a median of 59 months, there were 67 (7.9%) breast cancer relapses (36 distant, 25 local, 6 new primaries). There was a significant difference in mean absolute change in CNN risk score from baseline to 1-year follow-up between those who relapsed vs. remained in remission (0.001 vs. - 0.022, p = 0.030). After adjustment for prognostic factors, a 0.01 absolute increase in CNN score at 1-year was significantly associated with BCFI, hazard ratio = 1.05 (95% Confidence Interval 1.01-1.09, p = 0.011). CONCLUSION: Short-term change in the CNN-based breast cancer risk model on adjuvant endocrine therapy predicts breast cancer relapse, and warrants further evaluation in prospective studies.

Technology-Based Peer Support Interventions for Adolescents with Chronic Illness: A Systematic Review.

Technology may help adolescents with chronic illnesses overcome barriers to accessing peer support, which has been associated with better quality of life and health outcomes. This review aimed to describe technology-based peer support interventions for adolescents with chronic illness following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3781 articles identified, 32 met inclusion criteria. The most common technologies were websites with discussion forums (n = 18), chat messaging (n = 9), and video conferencing (n = 7). Most studies (69%) focused on feasibility and had small sample sizes. Results support the feasibility and acceptability of these interventions. Results suggested positive effects on social support, but were mixed on isolation, quality of life, and disease self-management. There were too few adequately powered randomized controlled trials to determine efficacy of these interventions at this time. Future work should use rigorous methods to evaluate efficacy and account for rapid shifts in technology for adolescent communication.

Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy.

BACKGROUND: Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets. METHODS: Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables. RESULTS: Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042). CONCLUSIONS: Several innate cytokines were associated with biochemically recurrent prostate cancer.

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

PURPOSE: To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). METHODS: The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. RESULTS: Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. CONCLUSION: The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

Recurrent Fevers, Dysautonomia, and Dehydration in a Patient With Lesch-Nyhan Syndrome.

Lesch-Nyhan syndrome (LNS) is a disease characterized by a reduced ability to recycle purines, leading to increased de novo purine synthesis and uric acid production. Patients classically present with an array of hyperuricemic, neurologic, and behavioral symptoms. In this report, we describe a 26-year-old male with a history of LNS and recurrent fevers of unknown origin who presented to the emergency department (ED) with a fever, hypotension, and hypernatremia. We suspect that our patient's presentation was caused by autonomic instability in the setting of LNS leading to excessive free water loss. This report highlights a rare but life-threatening manifestation of LNS.

Relationship Between Rhabdomyolysis and SARS-CoV-2 Disease Severity.

Background Rhabdomyolysis has historically been associated with viral infections, of which influenza A is the most common. A literature review suggests that up to 1/3 of patients hospitalized with COVID-19 develop acute kidney injury (AKI), and of those, nearly half are admitted to the ICU. AKI complicating COVID-19 infection is attributed to several pathogeneses, including sepsis, direct cytopathic effects on the kidneys, and rhabdomyolysis. Objective We aimed to link COVID-19 infection to the development of rhabdomyolysis via creatine kinase (CK) measurement to assess whether this association increases ICU admission, length of stay (LOS), and mortality. Design and setting In this single-center, retrospective cohort study, we enrolled 984 adult patients with confirmed COVID-19 infection requiring admission to a community hospital between March 2020 and May 2021. Measurements Demographic data, laboratory values, and clinical outcomes were collected. The primary outcome measured was the development of rhabdomyolysis and/or AKI. Secondary outcomes included associations of rhabdomyolysis with ICU admission, length of hospital stay, and mortality, utilizing multivariable logistic regression methods. Results Out of the 984 patients included, 39 met the clinical criteria for rhabdomyolysis (4%). The incidence of rhabdomyolysis was higher in patients with AKI (38.3%) and in those who required ICU admission (53.8%) (p<0.001). There was an insignificant difference in death in this cohort (11 patients, 52.4%, p=0.996). However, the mean LOS in patients who had rhabdomyolysis was 18.2 days versus 9.8 days in patients who did not develop rhabdomyolysis (p<0.001). Conclusion Objectively tracking CK levels in COVID-19-infected patients can assist in diagnosing rhabdomyolysis, identifying AKI etiology, and accordingly making a preliminary prognosis for COVID-19 infection, which could direct physicians to initiate more intensive treatment earlier.

Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa.

BACKGROUND: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study. METHODS: Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed. RESULTS: Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). CONCLUSION: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.

Neoadjuvant androgen deprivation therapy with or without Fc-enhanced non-fucosylated anti-CTLA-4 (BMS-986218) in high risk localized prostate cancer: a randomized phase 1 trial.

Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218 - a next-generation non-fucosylated anti-CTLA-4 antibody engineered for enhanced antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/P) - depletes intratumoral Tregs and augments the response to ADT. In this single-center, two-arm, open-label study, 24 men with high-risk localized prostate cancer were randomized to receive a single dose of ADT with or without two pre-operative doses of BMS-986218 (anti-CTLA4-NF) prior to radical prostatectomy. Treatment was well tolerated and feasible in the neoadjuvant setting. A secondary clinical outcome was the rate of disease recurrence, which was lower than predicted in both arms. Mechanistically, anti-CTLA4-NF reduced ADT-induced Treg accumulation through engagement of CD16a/FCGR3A on tumor macrophages, and depth of Treg depletion was quantitatively associated with clinical outcome. Increased intratumoral dendritic cell (DC) frequencies also associated with lack of recurrence, and pre-clinical data suggest ADCC/P-competent anti-CTLA-4 antibodies elicit activation and expansion of tumor DCs. Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming. In total, this study provides the first-in-human evidence of Treg depletion by glycoengineered antibodies targeting CTLA-4 in humans and their potential in combination with ADT in prostate cancer patients with high-risk of recurrence.

A rare case of long-term dialysis catheter-associated Agromyces mediolanus bacteremia: A case report and literature review.

Agromyces mediolanus is a catalase-positive gram-positive rod typically found in the soil and not commonly known to be pathogenic. We present a rare case of Agromyces mediolanus bacteremia with aortic valve endocarditis in a patient who required prolonged inpatient care with a tunneled dialysis catheter for renal replacement therapy (RRT). Infection is the second leading cause of mortality among patients with end-stage renal disease and vascular access. The incidence of bacteremia is higher in patients with indwelling tunneled catheters than in those with an arteriovenous fistula or graft. The most critical risk factor is its prolonged use. Anticipation of the need for long-term definitive renal replacement therapy and planning for the best approach is crucial in preventing catheter-related bloodstream infections (CRBSIs). Human infections caused by Agromyces mediolanus are rare; it has been reported twice, and both cases were associated with prolonged use of catheters, not only parenteral catheter but also peritoneal catheter, which is of special importance for patients with end-stage renal disease (ESRD). Limited data is available for the appropriate antibiotic therapy.

Candida endocarditis: Update on management considerations.

The rise in incidence rates of invasive candidiasis warrants an increase in attention and efforts toward preventing and treating this virulent infection. Cardiac involvement is one of the most feared sequelae and has a poor prognosis. Despite the introduction of several novel antifungal agents over the past quarter century, complications and mortality rates due to Candida endocarditis have remained high. Although fungal endocarditis has a mechanism similar to bacterial endocarditis, no specific diagnostic criteria or algorithm exists to help guide its management. Furthermore, recent data has questioned the current guidelines recommending a combined approach of antifungal agents with surgical valve or indwelling prostheses removal. With the emergence of multidrug-resistant Candida auris, a focus on improved prophylactic measures and management strategies is necessary.

Cognitive and emotional factors related to COVID-19 among high-risk ethnically diverse adults at the onset of the New York City outbreak: A cross-sectional survey.

A cross-sectional survey was conducted among high-risk, racially/ethnically diverse adults at the point in time when New York City (NYC) became the COVID-19 pandemic's global epicenter. The study objective was to assess the threat and coping appraisals (cognitive factors known to correspond with people's willingness to adopt behaviorally focused interventions) and levels of distress, anxiety, and intolerance for uncertainty (emotional factors). Survey respondents were recruited in April 2020 using an online survey with unpaid recruitment on the GetHealthyHeights.org community-oriented website. We also recruited participants that engaged in previous research studies to gain survey responses from community members at higher risk for COVID-19 complications due to comorbidities compared to the general population. Analysis was performed to test for differences in survey responses by comorbidities, age, race, ethnicity, and employment status. Results show that the devastating effects of the pandemic appear to have uniquely impacted minority respondents, who reported significantly higher levels of anxiety and were significantly more likely to report having little control over whether they will get COVID-19 compared with White/non-Hispanic respondents. Minority respondents also had significantly higher mean scores on the behaviorally focused dimension of the intolerance of uncertainty (IU) scale, which measures avoidance and paralysis in the face of uncertainty. In multivariate analysis, IU predicted anxiety levels, and this association was not mediated by cognitive factors (threat and coping appraisals). By conducting this survey early in the pandemic, our study uniquely evaluated cognitive and emotional factors among a racially/ethnically diverse group of NYC residents during the height of the COVID-19 pandemic. Our findings suggest the need to acknowledge the disparities that appear to exist in pandemic response and for culturally tailored messaging and interventions. Few studies have reported differences by race and ethnicity during pandemic exposure. Therefore, further research on factors that may influence pandemic response among minority populations is needed.

Self-Renewing CD8+ T-cell Abundance in Blood Associates with Response to Immunotherapy.

Treatment with immune checkpoint blockade (ICB) often fails to elicit durable antitumor immunity. Recent studies suggest that ICB does not restore potency to terminally dysfunctional T cells, but instead drives proliferation and differentiation of self-renewing progenitor T cells into fresh, effector-like T cells. Antitumor immunity catalyzed by ICB is characterized by mobilization of antitumor T cells in systemic circulation and tumor. To address whether abundance of self-renewing T cells in blood is associated with immunotherapy response, we used flow cytometry of peripheral blood from a cohort of patients with metastatic non-small cell lung cancer (NSCLC) treated with ICB. At baseline, expression of T-cell factor 1 (TCF1), a marker of self-renewing T cells, was detected at higher frequency in effector-memory (CCR7-) CD8+ T cells from patients who experienced durable clinical benefit compared to those with primary resistance to ICB. On-treatment blood samples from patients benefiting from ICB also exhibited a greater frequency of TCF1+CCR7-CD8+ T cells and higher proportions of TCF1 expression in treatment-expanded PD-1+CCR7-CD8+ T cells. The observed correlation of TCF1 frequency in CCR7-CD8+ T cells and response to ICB suggests that broader examination of self-renewing T-cell abundance in blood will determine its potential as a noninvasive, predictive biomarker of response and resistance to immunotherapy.

IFN-γR/STAT1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease.

The absence of IFN-γ receptor (IFN-γR) or STAT1 signaling in donor cells has been shown to result in reduced induction of acute graft-versus-host disease (GVHD). In this study, we unexpectedly observed increased activation and expansion of donor lymphocytes in both lymphohematopoietic organs and GVHD target tissues of IFN-γR/STAT1-deficient recipient mice, leading to rapid mortality following the induction of GVHD. LPS-matured, BM-derived Ifngr1-/- Stat1-/- DCs (BMDCs) were more potent allogeneic stimulators and expressed increased levels of MHC II and costimulatory molecules. Similar effects were observed in human antigen-presenting cells (APCs) with knockdown of Stat1 by CRISPR/Cas9 and treatment with a JAK1/2 inhibitor. Furthermore, we demonstrated that the absence of IFN-γR/STAT1 signaling in hematopoietic APCs impaired the presentation of exogenous antigens, while promoting the presentation of endogenous antigens. Thus, the indirect presentation of host antigens to donor lymphocytes was defective in IFN-γR/STAT1-deficient, donor-derived APCs in fully donor chimeric mice. The differential effects of IFN-γR/STAT1 signaling on endogenous and exogenous antigen presentation could provide further insight into the roles of the IFN-γ/STAT1 signaling pathway in the pathogenesis of GVHD, organ rejection, and autoimmune diseases.

Analysis of Circulating Immune Biomarkers by Race in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Sipuleucel-T.

Among racial subgroups, Black men have the highest prostate cancer-specific death rate, yet they also exhibit prolonged overall survival compared with White men when treated with standard therapies, including sipuleucel-T. Differential immune responses may play a role in these observations. We compared circulating immune markers from 54 men (18 Black and 36 White) with metastatic castrate-resistant prostate cancer who received sipuleucel-T and were enrolled on an immune monitoring registry. Markers included longitudinal serum cytokine concentrations, humoral responses, and cellular immunity from baseline until 52 weeks after sipuleucel-T administration. Black men had statistically significantly higher median concentrations of TH2-type (interleukin [IL]-4, IL-10, and IL-13) and inflammatory cytokines (IL-2, IL-12, and IL-6) compared with prostate-specific antigen-matched White men both at baseline and 52 weeks after sipuleucel-T (2-sided P < .05). No differences by race were seen in either the antigen-specific T-cell response or the humoral responses to the immunizing antigen PA2024 and select secondary antigens.

Inactivation of Notch4 Attenuated Pancreatic Tumorigenesis in Mice.

Expression of the Notch family of receptors is often upregulated in pancreatic ductal adenocarcinoma (PDAC). In this study, we focused on Notch4, which had not been investigated in PDAC. We generated KC (LSL-KrasG12D;p48-Cre), N4 - / - KC (Notch4- / -;LSL-KrasG12D;p48-Cre), PKC (p16fl/fl;LSL-KrasG12D;p48-Cre), and N4 - / - PKC (Notch4-/ -; p16fl/f l;LSL-KrasG12D;p48-Cre) genetically engineered mouse models (GEMM). We performed caerulein treatment in both KC and N4 - / - KC mice, and the development of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) lesions were significantly diminished in the N4 - / - KC than in the KC GEMM (P = 0.01). This in vivo result was validated by in vitro ADM induction of the explant cultures of pancreatic acinar cells from the N4 - / - KC and KC mice (P < 0.001), confirming that Notch4 is an important contributor to early pancreatic tumorigenesis. To evaluate the role of Notch4 in the later stage of pancreatic tumorigenesis, we compared the PKC and N4 - / - PKC mice. The N4 - / - PKC mice had better overall survival (P = 0.012) and significantly reduced tumor burden (PanIN: P = 0.018 at 2 months, PDAC: P = 0.039 at 5 months) compared with the PKC GEMM. RNA-sequencing analysis of pancreatic tumor cell lines derived from the PKC and N4 - / - PKC GEMMs revealed that 408 genes were differentially expressed (FDR < 0.05) and Pcsk5 is a potential downstream effector of the Notch4 signaling pathway (P < 0.001). Low expression of Pcsk5 positively correlates with good survival in patients with PDAC (P = 0.028). We have identified a novel role for Notch4 signaling with tumor-promoting function in pancreatic tumorigenesis. Our study also uncovered a novel association between Pcsk5 and Notch4 signaling in PDAC. Significance: We demonstrated that global inactivation of Notch4 significantly improved the survival of an aggressive mouse model for PDAC and provided preclinical evidence that Notch4 and Pcsk5 are novel targets for PDAC therapies.

Patient and Clinician Decision Support to Increase Genetic Counseling for Hereditary Breast and Ovarian Cancer Syndrome in Primary Care: A Cluster Randomized Clinical Trial.

Importance: To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk. Objective: To examine the effects of patient and clinician decision support about BRCA1/2 genetic testing compared with standard education alone. Design, Setting, and Participants: This clustered randomized clinical trial was conducted at an academic medical center including 67 clinicians (unit of randomization) and 187 patients. Patient eligibility criteria included women aged 21 to 75 years with no history of breast or ovarian cancer, no prior genetic counseling or testing for hereditary breast and ovarian cancer syndrome (HBOC), and meeting family history criteria for BRCA1/2 genetic testing. Interventions: RealRisks decision aid for patients and the Breast Cancer Risk Navigation Tool decision support for clinicians. Patients scheduled a visit with their clinician within 6 months of enrollment. Main Outcomes and Measures: The primary end point was genetic counseling uptake at 6 months. Secondary outcomes were genetic testing uptake at 6 and 24 months, decision-making measures (perceived breast cancer risk, breast cancer worry, genetic testing knowledge, decision conflict) based upon patient surveys administered at baseline, 1 month, postclinic visit, and 6 months. Results: From December 2018 to February 2020, 187 evaluable patients (101 in the intervention group, 86 in the control group) were enrolled (mean [SD] age: 40.7 [13.2] years; 88 Hispanic patients [46.6%]; 15 non-Hispanic Black patients [8.1%]; 72 non-Hispanic White patients [38.9%]; 35 patients [18.9%] with high school education or less) and 164 (87.8%) completed the trial. There was no significant difference in genetic counseling uptake at 6 months between the intervention group (20 patients [19.8%]) and control group (10 patients [11.6%]; difference, 8.2 percentage points; OR, 1.88 [95% CI, 0.82-4.30]; P = .14). Genetic testing uptake within 6 months was also statistically nonsignificant (13 patients [12.9%] in the intervention group vs 7 patients [8.1%] in the control group; P = .31). At 24 months, genetic testing uptake was 31 patients (30.7%) in intervention vs 18 patients (20.9%) in control (P = .14). Comparing decision-making measures between groups at baseline to 6 months, there were significant decreases in perceived breast cancer risk and in breast cancer worry (standard mean differences = -0.48 and -0.40, respectively). Conclusions and Relevance: This randomized clinical trial did not find a significant increase in genetic counseling uptake among patients who received patient and clinician decision support vs those who received standard education, although more than one-third of the ethnically diverse women enrolled in the intervention underwent genetic counseling. These findings suggest that the main advantage for these high-risk women is the ability to opt for screening and preventive services to decrease their cancer risk. Trial Registration: ClinicalTrials.gov Identifier: NCT03470402.

Lymphogranuloma Venereum Mimicking Locally Metastatic Rectal Cancer in an HIV-Negative Man.

Lymphogranuloma venereum (LGV) can present as a sexually transmitted anorectal syndrome and is caused by Chlamydia trachomatis serotypes L1, L2, and L3. It was rare in the western world until a recent outbreak among men who have sex with men (MSM) in Europe and North America. Limited availability of diagnostic tests differentiating LGV from non-LGV C. trachomatis can make the diagnosis challenging. We present a 33-year-old MSM with high-risk sexual behavior and anal atypical squamous cells of undetermined significance (ASCUS), who was evaluated for rectal pain, bleeding, constipation, and weight loss. Computed tomography of the abdomen and pelvis showed rectal wall thickening with pelvic adenopathy, concerning rectal carcinoma, also seen on colonoscopy as a 50% circumferential ulcerating rectal mass. The rectal swab was positive for C. trachomatis by immunofluorescence assay. Pathology confirmed severe active proctitis, but no malignancy. He was treated for presumed LGV proctitis with marked improvement. The case highlights an unusual presentation of LGV with severe inflammation and mass formation mimicking rectal carcinoma. Early identification of possible LGV especially in high-risk patients allows early appropriate treatment.