Isolation and Characterization of Six Novel Fusobacterium necrophorum Phages.

Introduction: Fusobacterium necrophorum, a human and animal pathogen, is the primary etiologic agent of bovine liver abscesses and a driving factor for prophylactic antibiotic use in the fed cattle industry. Considering calls to reduce agricultural antibiotic use, we isolated phages capable of killing F. necrophorum as an alternative or complementary biocontrol strategy. Methods: Six novel phages (φFN37, φRTG5, φKSUM, φHugo, φPaco, and φBB) were isolated from rumen fluid or ruminal F. necrophorum isolates and subjected to host range testing on both F. necrophorum subspecies. Four F. necrophorum subspecies, necrophorum phages, were tested for cross-resistance and host growth inhibition individually and in pairs. Additionally, genomic sequencing, annotation, and analysis were performed.s. Results: Four of six isolated phages were able to form lysogens, although all six contained lysogeny-related genes. φKSUM and φBB, did not form lysogens and were able to infect both subspecies. Four phages could infect F. necrophorum 8L1 (a liver abscess model challenge strain) in vitro. Genomic analysis showed that these phages belong to class Caudoviricetes with genome sizes ranging from 35 kbp to 111 kbp and GC values ranging from 26% to 36% and have extremely limited similarity to other deposited phage genomes infecting Fusobacterium or other genera. Conclusions: Although all phages isolated contained sequences bearing similarities to genes implicated in lysogeny, the four selected for use in cocktails showed potential in inhibiting host growth, with several demonstrating promising attributes for biocontrol and therapeutic applications. Phage cocktails that may offer enhanced antibacterial activity were also identified, indicating the potential of some lysogenic phages to be adapted for biocontrol or therapeutic purposes when lytic phages are difficult to obtain.

Multidisciplinary oncology clinicians' experiences delivering spiritual care to patients with cancer and their care partners.

PURPOSE: To understand multidisciplinary healthcare clinicians' meaningful and challenging experiences providing spiritual care to patients with cancer and their care partners. METHODS: Multidisciplinary clinicians who participated in a communication training program supported by the National Cancer Institute or a palliative care training for nurses (N = 257) responded to two, open-ended questions about meaningful and challenging experiences of providing spiritual care. A thematic analysis of responses using an iterative, inductive approach was conducted until saturation was reached. RESULTS: Participants from nursing (68%), social work (22%), and chaplaincy (10%) responded to open-ended survey questions. Three themes related to meaningful experiences of providing spiritual care emerged: building authentic interpersonal connection with patients and care partners; creating intentional space for patients and care partners to inform spiritual care; and actively supporting patients and care partners in their processes with spirituality. Three themes related to challenging experiences of providing spiritual care emerged: contextual factors and clinical circumstances complicate provision of spiritual care; facing barriers to providing high-quality, patient-centered care; and navigating ethical and logistical issues that affect spiritual and other care. CONCLUSION: Clinicians derive meaning from a range of experiences throughout their provision of spiritual care to patients with cancer. However, they also face many challenges in delivering person-centered spiritual care in cancer settings, with some challenges reflecting significant gaps in spiritual care knowledge and training. Findings can guide future training and educational endeavors for multidisciplinary clinicians in the domain of spiritual care.

The availability of allergen-friendly food for college students experiencing food insecurity: Exploring current campus practices.

BACKGROUND: The burden of dietary restrictions includes the high cost and limited availability of allergen-friendly products which disproportionately affects people with food insecurity. OBJECTIVE: To better understand access to allergen-friendly food for college students experiencing food insecurity with food allergies or other diet-treated conditions by surveying college campus food pantries. METHODS: A total of 120 randomly selected US colleges/universities were recruited to complete FOODiversity's Food Insecurity Questionnaire about campus food pantry operations, dietary restrictions, and food-insecurity initiatives and provide details about their resources and training dedicated to supporting food-insecure young adults who avoid specific food(s). RESULTS: Of the respondents, 48% ask students about dietary restrictions at food pantry intake, 37% track the number of patrons with restrictions, 30% process allergen-friendly product requests, 17% train staff about dietary restrictions, and 4% modify processes to accommodate dietary restrictions. Of the 48% who inquire about dietary restrictions, follow-up interventions vary in levels of accommodation. Dairy-free and gluten-free products are most frequently requested, and gluten-free products are the most donated/stocked and most difficult to accommodate. CONCLUSION: Food pantries play a critical role in reducing the burden experienced by food-insecure individuals; however, most pantries are unable to provide sufficient accommodations for clients with food allergies or other diet-treated conditions, including staff training, provision of allergen-friendly products, or identifying food-insecure college students with dietary restrictions, and promoting food allergy safety and nutritional impacts.

Can Genomic Testing Help Refine Choosing Wisely the Omission of Axillary Staging in cN0 Breast Cancer?

INTRODUCTION: Choosing Wisely (CW) recommends women age ≥70 y with cT1-2cN0 ER+/HER2-invasive breast cancer (BC) should forgo routine axillary staging with sentinel lymph node biopsy (SLN) at the time of breast surgery. Despite this longstanding recommendation, acceptance of SLN omission has not been widely adopted. Genomic assays, such as MammaPrint (MP), may supplement the decision to apply CW. We hypothesized that having MP on BC core needle biopsy (CNB) meeting CW could provide additional information to aid in decision-making about the need for axillary staging with SLN. METHODS: A retrospective single-institution review was conducted for women with BC meeting CW criteria, who also had MP performed on CNB from 2020 to 2021. Categorical characteristics were compared using the chi-square test. Continuous variables were compared using the Mann-Whitney U-test. RESULTS: MP was available on CNB for 238 BC meeting CW criteria: 70% low risk and 30% high risk. Axillary staging was performed in 195 (82%). Eighty-one percent were pathologically node-negative and 19% were pathologically node-positive. The MP score did not correlate with pathologic nodal stage (P = 0.52). The rate of high nodal burden (pN2) was extremely low (n = 1, 0.5%). The only significant correlation with pathological node positivity was older age (P = 0.03). Appropriately, high-risk MP was strongly associated with increased recurrence risk (n = 4, P = 0.008). CONCLUSIONS: Having MP on CNB does not provide clinically meaningful information about the pN stage and does not further refine which BC patients within CW could benefit from escalation to SLN or delineate a group more likely to be pathologically node-negative.

Common patient-reported sources of cancer-related distress in adults with cancer: A systematic review.

BACKGROUND: Cancer-related distress (CRD) is widely experienced by people with cancer and is associated with poor outcomes. CRD screening is a recommended practice; however, CRD remains under-treated due to limited resources targeting unique sources (problems) contributing to CRD. Understanding which sources of CRD are most commonly reported will allow allocation of resources including equipping healthcare providers for intervention. METHODS: We conducted a systematic review to describe the frequency of patient-reported sources of CRD and to identify relationships with CRD severity, demographics, and clinical characteristics. We included empirical studies that screened adults with cancer using the NCCN or similar problem list. Most and least common sources of CRD were identified using weighted proportions computed across studies. Relationships between sources of CRD and CRD severity, demographics, and clinical characteristics were summarized narratively. RESULTS: Forty-eight studies were included. The most frequent sources of CRD were worry (55%), fatigue (54%), fears (45%), sadness (44%), pain (41%), and sleep disturbance (40%). Having enough food (0%), substance abuse (3%), childbearing ability (5%), fevers (5%), and spiritual concerns (5%) were infrequently reported. Sources of CRD were related to CRD severity, sex, age, race, marital status, income, education, rurality, treatment type, cancer grade, performance status, and timing of screening. CONCLUSIONS: Sources of CRD were most frequently emotional and physical, and resources should be targeted to these sources. Relationships between sources of CRD and demographic and clinical variables may suggest profiles of patient subgroups that share similar sources of CRD. Further investigation is necessary to direct intervention development and testing.

"I Often Just Don't Know what to Say!": Variations in Multidisciplinary Palliative Care Clinicians' Confidence and Needs Related to Spiritual Care.

BACKGROUND: Spiritual care is a core component of high-quality palliative care, yet gaps exist in spiritual care provision. Understanding clinicians' levels of confidence around spiritual care and their perceptions of necessary knowledge/skills to enhance their ability to provide spiritual care is foundational for improving delivery of spiritual care in practice. OBJECTIVES: To understand confidence levels with providing spiritual care and perceived needs in relation to the provision of spiritual care among palliative clinicians (nurses, social workers, chaplains). DESIGN: N = 260 clinicians participating in interprofessional communication and end-of-life care training programs completed a structured survey. MEASUREMENTS: Clinicians responded to 42 closed-ended questions assessing their confidence in engaging in spiritual care across 6 dimensions, and one open-ended question: "What areas of knowledge or skill would best help to improve your ability to provide spiritual care across diverse populations?" RESULTS: Findings reveal varied levels of confidence with spiritual care across dimensions. Chaplains reported the highest levels of confidence compared with nurses and social workers. Key areas of knowledge/skills to improve spiritual care provision were: (1) Training and support for clinicians in spiritual care; (2) Strategies for providing spiritual care to patients from diverse cultural and/or religious backgrounds; (3) Better understanding of specific populations and contexts that may affect spiritual care provision; and (4) Clinicians' personal growth & practices to improve spiritual care. CONCLUSIONS: Additional support with spiritual care provision is needed, especially among spiritual care generalists. A focus on culturally attuned care is needed, honoring unique patient contexts and centering patient and family priorities.

The use of parenteral nutrition in patients with inflammatory bowel disease: A detailed guide on the indications, risks, and benefits.

Malnutrition is estimated to affect roughly 30%-80% of patients with inflammatory bowel disease (IBD). In those patients who cannot tolerate sufficient oral nutrition or there is no possibility for placing an enteral nutrition tube, parenteral nutrition offers a lifesaving alternative. However, this is not without risk. For patients with IBD, understanding the indications, contraindications, and complications associated with parenteral nutrition is crucial. In this review, we will discuss the indications and contraindications for parenteral nutrition in patients with IBD, the common complications associated with intravenous nutrition, the use of parenteral nutrition in special populations, such as in pediatric and perioperative patients, and the impact of parenteral nutrition on IBD-related outcomes.

Perceived injustice and pain-related outcomes in children with pain conditions: A systematic review.

OBJECTIVE: Research indicates that perceived injustice significantly influences pain-related outcomes and is associated with delayed recovery in adults. This systematic review examines the relationship between perceived injustice and pain-related outcomes in children with pain conditions. METHODS: A search of published studies in English in PubMed, PsychInfo and Cochrane Database of Systematic Reviews from database inception through December 2022 was performed. The search criteria focused on studies that measured perceived injustice and pain-related outcomes in children with pain conditions. Out of 56 articles screened, 8 met the inclusion criteria, providing data on 1240 children with pain conditions. RESULTS: The average age of participants across all studies was 14.12 years (SD = 2.25), with 68.2% being female. There was strong evidence that higher perceived injustice is associated with worse pain intensity, functional disability, mental health outcomes, and emotional, social and school functioning. CONCLUSION: The results of this study underscore how perceptions of injustice are associated various pain-related outcomes across different domains of children's lives. The findings highlight the need for screening and treatments targeting injustice appraisals in pediatric populations with pain conditions. The discussion addresses possible determinants and mechanisms of perceived injustice, along with implications for research and clinical practice.

Maternal COVID-19 vaccination status and association with neonatal congenital anomalies.

Introduction: Despite recommendations for COVID-19 vaccination in pregnant people, the effect of vaccination on neonatal outcomes remains unknown. We sought to determine the association between COVID-19 vaccination status in pregnancy and presence of neonatally diagnosed congenital anomalies. Methods: A comprehensive vaccine registry was combined with a delivery database to create a cohort including all patients aged 16-55 years with a delivery event between December 10, 2020 and December 31, 2021 at a hospital within the Mayo Clinic Health System. Pregnancy and neonatal outcomes were analyzed in relation to vaccination status and timing, including a composite measure of congenital anomalies diagnosed in neonatal life. Comparisons between cohorts were conducted using chi-square test for categorical and Kruskal-Wallis test for continuous variables. A multivariable logistic regression was modeled to assess the association with congenital anomalies. Results: 5,096 mother-infant pairs were analyzed. A total of 1,158 were vaccinated, with 314 vaccinated in the first trimester. COVID-19 vaccination status, including vaccination during the first trimester of pregnancy, was not associated with an increased risk of composite congenital anomalies. When further examining congenital anomalies by organ system, we did demonstrate a significant difference in eye, ear, face, neck anomalies between vaccinated and not vaccinated groups (Table 3, Not vaccinated = 2.3%, Vaccinated = 3.3%, p-value 0.04) however we did not demonstrate this difference between the 1st trimester and not vaccinated groups (Not vaccinated = 2.3%, 1st Trimester = 2.5%, p-value 0.77). No differences were found between not vaccinated, vaccinated, or 1st trimester vaccinated groups for any other organ systems. There were no differences in birthweight by gestational age, APGAR scores, incidence of NICU admission, or living status of the neonate by vaccination status. Conclusion: We add additional information regarding the safety of COVID-19 vaccination status and timing as it pertains to neonatal composite congenital anomalies, with no association demonstrated. Our findings agree with prior literature that COVID-19 vaccination is not associated with adverse pregnancy outcomes or small for gestational age neonates. Further research is needed to elucidate the association between COVID-19 vaccination and eye, ear, face, neck, anomalies.

Growing together: Optimization of care through quality improvement for the mother/infant dyad affected by perinatal opioid use.

The care of the dyad affected by opioid use disorder (OUD) requires a multi-disciplinary approach that can be challenging for institutions to develop and maintain. However, over the years, many institutions have developed quality improvement (QI) initiatives aimed at improving outcomes for the mother, baby, and family. Over time, QI efforts targeting OUD in the perinatal period have evolved from focusing separately on the mother and baby to efforts addressing care of the dyad and family during pregnancy, delivery, and postpartum. Here, we review recent and impactful QI initiatives that serve as examples of work improving outcomes for this population. Further, we advocate that this work be done through a racial equity lens, given ongoing inequities in the care of particularly non-white populations with substance use disorders. Through QI frameworks, even small interventions can result in meaningful changes to the care of babies and families and improved outcomes.

Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

Exercise and Dietary Recommendations for Women with Chronic Pain: What's Weight and Race Got To Do with It?

Exercise and diet are beneficial for pain, yet many patients do not receive such recommendations from providers. This may be due to biases related to gender, race, and weight. We recruited medical students (N = 90) to view videos of women with chronic back pain performing a functional task; patients varied by weight (overweight/obese) and race (Black/White). For each woman patient, providers rated their likelihood of recommending exercises or dietary changes. Ratings significantly differed across recommendations (F(2.75, 244.72) = 6.19, P < .01) in that providers were more likely to recommend flexibility exercises than aerobic exercises and dietary changes and were more likely to recommend strength exercises than dietary changes. Results also indicated that women with obesity were more likely to receive aerobic (F(1,89) = 17.20, P < .01), strength (F(1,89) = 6.08, P = .02), and dietary recommendations (F(1,89) = 37.56, P < .01) than were women with overweight. Additionally, White women were more likely to receive a recommendation for flexibility exercises (F(1,89) = 4.92, P = .03) than Black women. Collectively, these findings suggest that providers' exercise and dietary recommendations for women with chronic pain are influenced by the weight status and racial identity of the patient. Future studies are needed to identify the reasons underlying these systematic differences, including the stereotypes and attitudes that may be driving these effects. PERSPECTIVE: This article presents results on how patient weight and race impact providers' exercise and diet recommendations for women with chronic back pain. Provider recommendations for these modalities may be systematically biased in a way that impedes care and impacts patient functioning.

The role of spirituality in pain experiences among adults with cancer: an explanatory sequential mixed methods study.

PURPOSE: Foundational research demonstrates that spirituality may affect the way people with cancer experience pain. One potential route is through alterations in thoughts and beliefs, such as pain-related catastrophizing. The purpose of this study is to understand whether spirituality impacts pain experiences through pain-related catastrophizing. METHODS: This explanatory sequential mixed methods study was informed by an adapted Theory of Unpleasant Symptoms. Data were collected via online surveys (N = 79) and follow-up qualitative interviews (N = 25). Phase 1 employed Empirical Bayesian analysis. Phase 2 used deductive content analysis. Phase 3 involved creating a mixed methods joint display to integrate findings and draw meta inferences. RESULTS: Results indicate that total spiritual well-being was directly negatively associated with pain-related catastrophizing, and indirectly negatively associated with the outcomes of pain interference, pain severity, and pain-related distress. Qualitative categories highlight the supportive role of spirituality when facing pain, while also shedding light on the limitations of spirituality in the context of some pain (i.e., severe, neuropathic, and/or chronic). Mixed methods findings reveal the importance of spirituality for some people as they face cancer and cancer-related pain, as well as the need for integrating spirituality as part of a larger pain management plan. CONCLUSIONS: This research advances supportive cancer care by exploring the complex role of spirituality in pain experiences. Findings will inform further exploration into the role of spirituality in supporting holistic symptom management in the context of cancer, as well as developing and testing interventions to enhance spirituality and address symptom-related suffering.

An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis.

BACKGROUND: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production. METHODS: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16. RESULTS: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups. CONCLUSIONS: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).

Comparative evaluation of assay performance for SARS-CoV-2 detection in animal oral samples, lung homogenates, and phosphate-buffered saline using the TaqPath COVID-19 Combo kit.

A One Health approach has been key to monitoring the COVID-19 pandemic, as human and veterinary medical professionals jointly met the demands for an extraordinary testing effort for SARS-CoV-2. Veterinary diagnostic laboratories continue to monitor SARS-CoV-2 infection in animals, furthering the understanding of zoonotic transmission dynamics between humans and animals. A RT-PCR assay is a primary animal screening tool established within validation and verification guidelines provided by the American Association of Veterinary Laboratory Diagnosticians (AAVLD), World Organisation for Animal Health (WOAH), and the U.S. Food and Drug Administration (FDA). However, differences in sample matrices, RNA extraction methods, instrument platforms, gene targets, and cutoff values may affect test outcomes. Therefore, targeted validation for a new sample matrix used in any PCR assay is critical. We evaluated a COVID-19 assay for the detection of SARS-CoV-2 in feline and canine lung homogenates and oral swab samples. We used the commercial Applied Biosystems MagMAX Viral/Pathogen II (MVP II) nucleic acid isolation kit and TaqPath COVID-19 Combo kit, which are validated for a variety of human samples, including nasopharyngeal and oropharyngeal swab samples. Our masked test showed a high detection rate and no false-positive or false-negative results, supporting sample extension to include feline oral swab samples. Our study is a prime example of One Health, illustrating how a COVID-19 assay designed for human testing can be adapted and used to detect SARS-CoV-2 in oral swab samples from cats and likely dogs, but not lung homogenates.

Comparing the Efficacy of Targeted and Blast Portal Messaging in Message Opening Rate and Anticoagulation Initiation in Patients With Atrial Fibrillation in the Preventing Preventable Strokes Study II: Prospective Cohort Study.

BACKGROUND: The gap in anticoagulation use among patients with atrial fibrillation (AF) is a major public health threat. Inadequate patient education contributes to this gap. Patient portal-based messaging linked to educational materials may help bridge this gap, but the most effective messaging approach is unknown. OBJECTIVE: This study aims to compare the responsiveness of patients with AF to an AF or anticoagulation educational message between 2 portal messaging approaches: sending messages targeted at patients with upcoming outpatient appointments 1 week before their scheduled appointment (targeted) versus sending messages to all eligible patients in 1 blast, regardless of appointment scheduling status (blast), at 2 different health systems: the University of Massachusetts Chan Medical School (UMass) and the University of Florida College of Medicine-Jacksonville (UFL). METHODS: Using the 2 approaches, we sent patient portal messages to patients with AF and grouped patients by high-risk patients on anticoagulation (group 1), high-risk patients off anticoagulation (group 2), and low-risk patients who may become eligible for anticoagulation in the future (group 3). Risk was classified based on the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age between 65 and 74 years, and sex category (CHA2DS2-VASc) score. The messages contained a link to the Upbeat website of the Heart Rhythm Society, which displays print and video materials about AF and anticoagulation. We then tracked message opening, review of the website, anticoagulation use, and administered patient surveys across messaging approaches and sites using Epic Systems (Epic Systems Corporation) electronic health record data and Google website traffic analytics. We then conducted chi-square tests to compare potential differences in the proportion of patients opening messages and other evaluation metrics, adjusting for potential confounders. All statistical analyses were performed in SAS (version 9.4; SAS Institute). RESULTS: We sent 1686 targeted messages and 1450 blast messages. Message opening was significantly higher with the targeted approach for patients on anticoagulation (723/1156, 62.5% vs 382/668, 57.2%; P=.005) and trended the same in patients off anticoagulation; subsequent website reviews did not differ by messaging approach. More patients off anticoagulation at baseline started anticoagulation with the targeted approach than the blast approach (adjusted percentage 9.3% vs 2.1%; P<.001). CONCLUSIONS: Patients were more responsive in terms of message opening and subsequent anticoagulation initiation with the targeted approach.

The Impact of Age, Sex, and Position on Visual-Motor Processing Speed and Reaction Time as Measured by the Vision CoachTM.

Occupational therapists are in a unique position to screen and evaluate fitness to drive with both visual-motor processing speed and reaction time being important factors to consider when determining fitness to drive. This study uses the Vision CoachTM to investigate the differences in visual-motor processing speed and reaction time across age and sex of healthy adults. It also explores whether the position of sitting or standing made any difference. The results showed no difference between male/female or standing/sitting positions. However, there was a statistically significant difference between age groups, with older adults demonstrating slower visual-motor processing speed and reaction times. These findings can be used for future studies to explore the impact of injury or disease on visual-motor processing speed and reaction times and its relation to fitness to drive.

Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis.

INTRODUCTION: The benefit/risk profiles of biologics can be affected by comorbidities, certain demographic characteristics, and concomitant medications; therefore, it is important to evaluate the long-term safety profiles of biologics across broad patient populations. Guselkumab was well tolerated and efficacious across individual pivotal clinical studies in adults with moderate-to-severe psoriasis and/or active psoriatic arthritis (PsA). OBJECTIVES: The objective of the current analysis was to evaluate guselkumab safety in a large population of patients with psoriatic disease by pooling adverse event (AE) data from 11 phase II/III studies (seven in psoriasis; four in PsA). METHODS: Guselkumab was generally administered as 100 mg subcutaneous injections at Week 0, Week 4, then every 8 weeks (Q8W) in psoriasis studies and at Week 0, Week 4, then every 4 weeks (Q4W) or Q8W in PsA studies. Safety data were summarized for the placebo-controlled period (Weeks 0-16 in psoriasis; Weeks 0-24 in PsA) and through the end of the reporting period (up to 5 years in psoriasis; up to 2 years in PsA). Using the integrated data, incidence rates of key AEs were determined post hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PYs). AE rates were also determined in subgroups of patients defined by sex, age, body mass index (BMI), and prior biologic use. RESULTS: During the placebo-controlled period, 1061 patients received placebo (395 PYs) and 2257 received guselkumab (856 PYs). Through the end of the reporting period, 4399 guselkumab-treated patients contributed 10,787 PYs of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of AEs were 281 versus 272/100 PYs, and infections were 76.0 versus 72.2/100 PYs. Rates of serious AEs (5.6 vs. 7.8/100 PYs), AEs leading to discontinuation (4.9 vs. 6.6/100 PYs), serious infections (1.0 vs. 2.3/100 PYs), malignancy (0.59 vs. 0.25 patients/100 PYs), and major adverse cardiovascular events (MACE; 0.35 vs. 0.25/100 PYs) were low and comparable between guselkumab and placebo. Among guselkumab-treated patients, safety event rates through the end of the reporting period were numerically lower than or comparable with rates observed during the placebo-controlled period: AEs, 164/100 PYs; infections, 61.2/100 PYs; serious AEs, 5.4/100 PYs; AEs leading to discontinuation, 1.8/100 PYs; serious infections, 1.0/100 PYs; malignancy, 0.6/100 PYs; and MACE, 0.3/100 PYs. No AEs of Crohn's disease, ulcerative colitis, or active tuberculosis were reported among guselkumab-treated patients. In the psoriasis studies, no opportunistic infections were reported among guselkumab-treated patients. Three AEs of opportunistic infections were reported in guselkumab-treated patients with PsA (0.14/100 PYs; all after Week 52 in DISCOVER-2). AE rates were largely consistent across subgroups of guselkumab-treated patients defined by sex, age, BMI, and prior biologic use. CONCLUSIONS: In this analysis of 4399 guselkumab-treated patients with psoriatic disease followed for 10,787 PYs, guselkumab had a favorable AE profile. AE rates were similar between guselkumab- and placebo-treated patients and were consistent throughout long-term guselkumab treatment and across broad subgroups of patients with psoriatic disease. CLINICAL TRIALS REGISTRATIONS: Clinicaltrials.gov identifiers: NCT01483599, NCT02207231, NCT02207244, NCT02203032, NCT02905331, NCT03090100, NCT02325219, NCT02319759, NCT03162796, NCT03158285, and NCT03796858.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery.

BACKGROUND: At present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. However, many women are diagnosed when pathologic node status-negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor-positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status-negative. METHODS: A single-institution database was queried for all women with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. RESULTS: A total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status-negative and pathologic node status-positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status-negative vs 91 [69.5%] pathologic node status-positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status-positive (P = .377). CONCLUSION: Low-risk MammaPrint does not predict lower risk of pathologic node status-positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.