Identification of a heterogeneous and dynamic ciliome during embryonic development and cell differentiation.

Primary cilia are nearly ubiquitous organelles that transduce molecular and mechanical signals. Although the basic structure of the cilium and the cadre of genes that contribute to ciliary formation and function (the ciliome) are believed to be evolutionarily conserved, the presentation of ciliopathies with narrow, tissue-specific phenotypes and distinct molecular readouts suggests that an unappreciated heterogeneity exists within this organelle. Here, we provide a searchable transcriptomic resource for a curated primary ciliome, detailing various subgroups of differentially expressed genes within the ciliome that display tissue and temporal specificity. Genes within the differentially expressed ciliome exhibited a lower level of functional constraint across species, suggesting organism and cell-specific function adaptation. The biological relevance of ciliary heterogeneity was functionally validated by using Cas9 gene-editing to disrupt ciliary genes that displayed dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Collectively, this novel primary cilia-focused resource will allow researchers to explore longstanding questions related to how tissue and cell-type specific functions and ciliary heterogeneity may contribute to the range of phenotypes associated with ciliopathies.

Umbilical Cord Tissue: From Antemortem Monitoring to Postmortem Possibilities.

ABSTRACT: Umbilical cord tissue (UCT) traditionally has been used as an antemortem matrix for identifying and monitoring fetal exposure to drugs suspected to have been used during pregnancy. The specimen offers several advantages as a testable tissue, including accessibility and ease of collection, ample sample volume, a long window of detection, and ability to detect for a wide range of drugs. Despite these advantages, little to no research exists on the use of UCT as a postmortem forensic toxicology specimen. This article aims to provide insights into UCT toxicological testing and infer potential applications for postmortem use, such as investigations into stillbirths and infant abandonment. Umbilical cord tissue offers several benefits as a postmortem toxicological specimen. Importantly, it can be collected with or without an autopsy being performed and may help explain factors that contribute to the underdevelopment and death of the neonate. With the limited sample volumes present in infant investigations, toxicological analysis of UCT could become a valuable tool for neonatal medicolegal death investigations.

Feeding Management and Palate Repair Timing in Infants with Cleft Palate with and without Pierre Robin Sequence: A Multisite Study.

OBJECTIVES: Compare the feeding management practices in infants with cleft palate with and without Pierre Robin sequence (PRS) and determine if specific feeding difficulties or interventions predict delayed palate repair. DESIGN: Retrospective cross-sectional study. SETTING: Seventeen cleft palate teams contributed data. PATIENTS: 414 infants were included in this study: 268 infants with cleft palate only and 146 infants with cleft palate and PRS. PROCEDURES: Data were collected via parent interview and electronic health records. MAIN OUTCOME MEASURES: Outcomes for the primary objective included categorical data for: history of poor growth, feeding therapy, milk fortification, use of enteral feeding, and feeding difficulties. The outcome for the secondary objective was age in months at primary palate repair. RESULTS: Infants with PRS had a significantly higher prevalence of feeding difficulties (81% versus 61%) and poor growth (29% versus 15%) compared to infants with cleft palate only. Infants with PRS received all feeding interventions-including feeding therapy, milk fortification, and enteral feeding-at a significantly higher frequency. Infants with PRS underwent primary palate repair at a mean age of 13.55 months (SD = 3.29) which was significantly (P < .00001) later than infants with cleft palate only who underwent palate repair at a mean age of 12.05 months (SD = 2.36). Predictors of delayed palate repair included diagnosis of PRS as well as Hispanic ethnicity and a history of poor growth. CONCLUSIONS: These findings can be used to establish clinical directives focused on providing early, multimodal feeding interventions to promote optimal growth and timely palate repair for infants with PRS.

Curriculum Guidelines for Graduate and Undergraduate Virology Courses.

Curriculum guidelines for virology are needed to best guide student learning due to the continuous and ever-increasing volume of virology information, the need to ensure that undergraduate and graduate students have a foundational understanding of key virology concepts, and the importance in being able to communicate that understanding to both other virologists and nonvirologists. Such guidelines, developed by virology educators and the American Society for Virology Education and Career Development Committee, are described herein.

Barriers and facilitators of the return-to-school process affecting adolescent recipients of allogeneic hematopoietic cell transplantation: A qualitative interview study of caregivers.

BACKGROUND: Adolescent hematopoietic cell transplant (HCT) recipients remain out of school for a prolonged period of time; navigating their return to school after completion of therapy can be challenging for caregivers. METHODS: Between August 2020 and June 2021, we conducted individual semi-structured interviews of 19 caregivers of adolescent HCT recipients (10-18 years of age at HCT; 1-7 years post HCT) to understand the challenges faced at the time of their child's return to in-person school post HCT. Conventional content analysis was used to analyze interview transcripts, and thematic analysis was used to identify and organize emerging themes. RESULTS: Three themes emerged from the caregivers' experiences. First, caregivers reported facing several challenges related to lack of communication between their child's healthcare and school teams, which was burdensome for them. Second, some caregivers reported receiving support from school and healthcare professionals, as well as their child's peers, which helped reduce the burden of return to school. Caregivers also reported providing motivational, emotional, and spiritual support to patients. Lastly, caregivers made several recommendations regarding the need for better communication between family, healthcare professionals, and school professionals and availability of supportive care such as mental health counseling and neuropsychological testing. Notably, the need for a return-to-school navigator emerged as a key finding from our analysis. CONCLUSIONS: Caregivers of adolescent HCT recipients face several challenges supporting their children's return to school post HCT, which are related to lack of communication between patients' healthcare and school teams. While some reported receiving support from school and healthcare professionals and their child's peers, the need to coordinate the return-to-school process was burdensome for several caregivers. Additional work is needed to optimize support for HCT recipients and their caregivers during their return-to-school process to minimize burden. Our study findings have the potential to serve as a framework for developing and testing supportive care interventions to improve the return-to-school experience of HCT survivors and ultimately their quality of life.

Teaching Old Polymers New Tricks: Improved Synthesis and Anomalous Crystallinity for a Lost Semi-Fluorinated Polyaryl Ether via Interfacial Polymerization of Hexafluoroacetone Hydrate and Diphenyl Ether.

A practical and direct electrophilic polymerization of hexafluoroacetone hydrate with diphenyl ether toward the preparation of semi-fluorinated polyaryl ethers (PAE) is reported. Electrophilic aromatic substitution (EAS) polymerization under interfacial conditions with phase transfer catalyst (Aliquat 336) proceeds in trifluoromethanesulfonic anhydride by generation of trifluoromethanesulfonic acid and the protonated hexafluoroacetone (HFA) in situ affording 1,1,1,3,3,3-hexafluoroisopropylidene (6F) PAE with high regioselectivity (4,4'-DPE) and high molecular weight (≈60 kDa). Although first reported in a 1966 US Patent by DuPont using harsh conditions, improved synthetic methods or modern characterization has not been disclosed until now. Despite the presence of the 6F group, known to impart disordered morphology, this simple semi-fluorinated PAE exhibits anomalous crystallinity with polymorphic melting points (Tm ) ranging from 230-309 °C, high solubility in common organic solvents, a glass transition (Tg ) of 163 °C, and thermo-oxidative stability above 500 °C. Tough optically clear films prepared from solution give transmittance higher than 90% throughout the visible region. Synthesis, mechanistic aspects, and characterization including surface and dielectric properties are discussed.

Standardization of Videorecorded Speech Samples for Children with Cleft Palate: Methods to Facilitate High-Quality Speech Outcomes Data Collection.

BACKGROUND: Collection of high-quality videorecorded speech samples is essential for speech outcomes research. SOLUTION: Cleft palate team SLPs were trained to collect standard videorecorded speech samples in the clinic setting across 20 sites in North America. Standard training and equipment was provided. WHAT WE DID THAT IS NEW: Quality management procedures were developed and utilized to verify video quality and protocol adherence. Over 97% of speech samples collected by trained SLPs met defined quality standards.

Machine Learning-Based Fragment Selection Improves the Performance of Qualitative PRM Assays.

Targeted mass spectrometry-based platforms have become a valuable tool for the sensitive and specific detection of protein biomarkers in clinical and research settings. Traditionally, developing a targeted assay for peptide quantification has involved manually preselecting several fragment ions and establishing a limit of detection (LOD) and a lower limit of quantitation (LLOQ) for confident detection of the target. Established thresholds such as LOD and LLOQ, however, inherently sacrifice sensitivity to afford specificity. Here, we demonstrate that machine learning can be applied to qualitative PRM assays to discriminate positive from negative samples more effectively than a traditional approach utilizing conventional methods. To demonstrate the utility of this method, we trained an ensemble machine learning model using 282 SARS-CoV-2 positive and 994 SARS-CoV-2 negative nasopharyngeal swabs (NP swab) analyzed using a targeted PRM method. This model was then validated using an independent set of 200 positive and 150 negative samples and achieved a sensitivity of 92% relative to results obtained by RT-PCR, which was superior to a traditional approach that resulted in 86.5% sensitivity when analyzing the same data. These results demonstrate that machine learning can be applied to qualitative PRM assays and results in superior performance relative to traditional methods.

Reading Development in Children With Nonsyndromic Cleft Palate With or Without Cleft Lip: Meta-analysis and Systematic Review.

OBJECTIVE: We conducted a meta-analysis and systematic review of literature comparing pre-reading and general reading in school-age children with nonsyndromic cleft palate with or without cleft lip (NSCP/L) to their peers without NSCP/L. METHODS: Our literature search identified 1238 possible records. After screening we identified 11 samples for inclusion for systematic review and eight for meta-analysis. We compared 292 children with NSCP/L to 311 peers for 23 pre-reading effect sizes and 17 general reading effect sizes (EFg). We conducted a random-effects metaregression using robust variance estimation. RESULTS: On average school-age children with NSCP/L scored lower on pre-reading (EFg = -0.36) and general reading measures (EFg = -0.38) compared to their peers. We conducted post-hoc analyses on phonological awareness and word decoding effect sizes; children with NSCP/L performed lower on phonological awareness (EFg = -0.22) and word decoding (EFg = -0.39) compared to their peers. There was weak evidence that hearing status and/or speech-language functioning might moderate reading development. There was limited evidence that age or socioeconomic status moderated reading development. However, samples did not consistently report several characteristics that were coded for this project. CONCLUSIONS: Our findings suggest that school-age children with NSCP/L have persistent reading problems. Further research is needed to explore reading development in children with NSCP/L, as well as the relationships among hearing, speech, language, and reading development.

Screening for Excessive Alcohol Consumption in Emergency Departments: A Nationwide Assessment of Emergency Department Physicians.

OBJECTIVE: To assess current screening practices for excessive alcohol consumption, as well as perceived barriers, perceptions, and attitudes toward performing this screening among emergency department (ED) physicians. DESIGN: A brief online assessment of screening practices for excessive drinking was disseminated electronically to a representative panel of ED physicians from November 2016 to January 2017. Descriptive statistics were calculated on the frequency of alcohol screening, factors affecting screening, and attitudes toward screening. SETTING: An online assessment was sent to a national panel of ED physicians. PARTICIPANTS: A panel of ED physicians who volunteered to be part of the American College of Emergency Physicians Emergency Medicine Practice Research Network survey panel. MAIN OUTCOME MEASURE: The primary outcome measures were the percentage of respondents who reported screening for excessive alcohol consumption and the percentage of respondents using a validated excessive alcohol consumption screening tool. RESULTS: Of the 347 ED physicians evaluated (38.6% response rate), approximately 16% reported "always/usually," 70% "sometimes," and 14% "never" screening adult patients (≥18 years) for excessive alcohol use. Less than 20% of the respondents who screened for excessive drinking used a recommended screening tool. Only 10.5% of all respondents (15.4% "always," 9.5% "sometimes" screened) received an electronic health record (EHR) reminder to screen for excessive alcohol use. Key barriers to screening included limited time (66.2%) and treatment options for patients with drinking problems (43.1%). CONCLUSIONS: Only 1 in 6 ED physicians consistently screened their patients for excessive drinking. Increased use of EHR reminders and other systems interventions (eg, electronic screening and brief intervention) could help improve the delivery of screening and follow-up services for excessive drinkers in EDs.

Glucocorticoids, sodium transport mediators, and respiratory distress syndrome in preterm infants.

BACKGROUND: Antenatal glucocorticoids (GCs) reduce respiratory distress syndrome (RDS) in preterm infants and are associated with reduced lung liquid content. Our aim was to assess whether airway gene expression of mediators of pulmonary epithelial sodium and liquid absorption, and further, respiratory morbidity, associate with cord blood GC concentrations. METHODS: The study included 64 infants delivered <32 weeks gestation. Cortisol and betamethasone in umbilical cord blood were quantified with liquid chromatography-tandem mass spectrometry. The total GC concentration was calculated. Gene expression of the epithelial sodium channel (ENaC), Na,K-ATPase, and serum- and GC-inducible kinase 1 at <2 h and at 1 day postnatally in nasal epithelial cell samples was quantified with reverse transcription-polymerase chain reaction. The mean oxygen supplementation during the first 72 h was calculated. RESULTS: Concentrations of cord blood betamethasone and total GC were significantly lower in infants with RDS and correlated with mean oxygen supplementation. Expression of αENaC and α1- and ß1Na,K-ATPase at <2 h correlated with betamethasone and total GC concentrations. Expression of Na,K-ATPase was lower in infants with RDS. CONCLUSION: Enhancement of lung liquid absorption via increased expression of sodium transporters may contribute to the beneficial pulmonary effects of antenatal GCs. IMPACT: RDS is related to lower umbilical cord blood GC concentrations and lower airway expression of sodium transporters. In addition to the timing of antenatal GC treatment, resulting concentrations may be of importance in preventing RDS. Induction of sodium transport may be a factor contributing to the pulmonary response to antenatal GCs.

Levamisole-a Toxic Adulterant in Illicit Drug Preparations: a Review.

ABSTRACT: Discovered in the 1960s, the common anthelminthic levamisole has seen widespread use in veterinary applications. Its use rapidly expanded thereafter to include human medical treatments for a variety of acute and chronic disorders. Because of reports of severe adverse effects, the US Food and Drug Administration withdrew levamisole's approval for human use in 2000; however, medical options outside the United States and illicit options worldwide allow continued accessibility to levamisole. The compound is rapidly metabolized in the body, with at least 2 known active metabolites. Levamisole has a broad range of immunomodulatory effects, including both stimulatory and inhibitory effects on immune responses. It is generally well tolerated at therapeutic concentrations, although a variety of autoimmune-related adverse effects have been reported, including agranulocytosis, leukopenia, purpura, and visible necrotized skin tissue. Individuals with levamisole-compromised immune systems are more susceptible to infections, including COVID-19. Since the early 2000's, levamisole has been frequently used as an adulterating agent in illicit street drugs, especially cocaine, fentanyl, and heroin. Although its prevalence has varied over time and geographically, levamisole has been detected in up to 79% of the street supply of cocaine at levels up to 74% by weight. Its presence in illicit drug markets also raises concern over the potential for exposure of children and neonates, although this is supported by only limited anecdotal evidence. Levamisole is not currently included in routine drug testing panels, although a variety of confirmatory testing techniques exist across a range of antemortem and postmortem specimen options. Because of its varying presence in illicit drug markets, both the medical and forensic communities need to be aware of levamisole and its potential impact on toxicological investigations.

A Case of Cyclic Neutropenia and Associated Amyloidosis.

Cyclic neutropenia has been rarely associated with chronic inflammation and development of reactive AA amyloidosis. We report a family with cyclic neutropenia with associated renal and thyroid amyloid. A 12-year-old female presented with thyromegaly, recurrent aphthous ulcers, severe neutropenia, and renal failure. Renal and thyroid biopsies revealed abundant amyloid deposition. Presence of a heterozygous ELANE c.358 A>T gene mutation p.I120F variant with autosomal dominant inheritance confirmed the diagnosis of cyclic neutropenia. The patient's father also had neutropenia and amyloidosis with renal failure. We started filgrastim to attenuate neutropenia and thereby reduce chronic inflammation and minimize further amyloid deposition.

Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging.

To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing "papillary carcinoma" was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.

Examining Reduced Opioid Prescriptions after Gynecologic Laparoscopy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To examine whether prescribing 5 tablets, as opposed to 10 tablets, of 5-mg oxycodone adequately treats pain after gynecologic laparoscopy. DESIGN: Single-blinded randomized trial. SETTING: Academically affiliated ambulatory surgery center. PATIENTS: One hundred twenty women scheduled to undergo minor gynecologic laparoscopy. INTERVENTIONS: Patients scheduled for ambulatory gynecologic laparoscopy were allocated to the standard tablet or low-tablet number prescription groups (10 tablets or 5 tablets of 5-mg oxycodone). The patients also received prescriptions for acetaminophen and ibuprofen. MEASUREMENTS AND MAIN RESULTS: Telephone surveys were conducted on postoperative days 1 and 7 to assess medication use and pain. The primary outcome was the number of oxycodone tablets used by days 1 and 7. Prespecified secondary outcomes included unscheduled patient contacts and pain scores. With N = 50 in each group and assuming standardized effect sizes, the study was powered to detect a 0.6 difference or greater when comparing the primary outcome between the groups. Forty-five and 47 patients in the 5-tablet and 10-tablet groups, respectively, completed the day-7 survey. The median number of oxycodone tablets taken by day 7 was 2.0 (interquartile range 0.0, 4.0) in the 5-tablet group and 2.5 (interquartile range 0.0, 5.0) in the 10-tablet group (p = .36). Most of the patients in both groups reported taking 3 oxycodone tablets or fewer by day 7. There were no significant differences in unscheduled patient contacts, need for additional prescriptions, or pain scores. There were significantly fewer unused tablets in the 5-tablet group by day 7. CONCLUSION: Prescribing 5 tablets of 5-mg oxycodone, acetaminophen, and ibuprofen is likely sufficient for most patients after minor laparoscopic surgery.

RZ Interval as an Impedance Cardiography Indicator of Effort-Related Cardiac Sympathetic Activity.

Research on effort and motivation commonly assesses how the sympathetic branch of the autonomic nervous system affects the cardiovascular system. The cardiac pre-ejection period (PEP), assessed via impedance cardiography, is a common outcome, but assessing PEP requires identifying subtle points on cardiac waveforms. The present research examined the psychometric value of the RZ interval (RZ), which has recently been proposed as an indicator of sympathetic activity, for effort research. Also known as the initial systolic time interval (ISTI), RZ is the time (in ms) between the ECG R peak and the dZ/dt Z peak. Unlike PEP, RZ involves salient waveform points that are easily and reliably identified. Data from two experiments evaluated the suitability of RZ for effort paradigms and compared it to a popular automated PEP method. In Studies 1 (n = 89) and 2 (n = 71), participants completed a standard appetitive task in which each correct response earned a small amount of cash. As expected, incentives significantly affected PEP and RZ in both experiments. PEP and RZ were highly correlated (all rs ≥ 0.89), and RZ consistently yielded a larger effect size than PEP. In Study 3, a quantitative synthesis of the experiments indicated that the effect size of RZ's response to incentives (Hedges's g = 0.432 [0.310, 0.554]) was roughly 15% larger than PEP's effect size (g = 0.376 [0.256, 0.496]). RZ thus appears promising for future research on sympathetic aspects of effort-related cardiac activity.

Self-Report Measures of Anhedonia and Approach Motivation Weakly Correspond to Anhedonia and Depression Assessed via Clinical Interviews.

Self-report scales are popular tools for measuring anhedonic experiences and motivational deficits, but how well do they reflect clinically significant anhedonia? Seventy-eight adults participated in face-to-face structured diagnostic interviews: 22 showed clinically significant anhedonia, and 18 met criteria for depression. Analyses of effect sizes comparing the anhedonia and depression groups to their respective controls found large effects, as expected, for measures of depressive symptoms, but surprisingly weak effect sizes (all less than d=.50) for measures of general, social, or physical anhedonia, behavioral activation, and anticipatory and consummatory pleasure. Measures of Neuroticism and Extraversion distinguished the anhedonic and depressed groups from the controls at least as well as measures of anhedonia and motivation. Taken together, the findings suggest that caution is necessary when extending self-report findings to populations with clinically significant symptoms.

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.

Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.

Computational analysis of kinase inhibitor selectivity using structural knowledge.

Motivation: Kinases play a significant role in diverse disease signaling pathways and understanding kinase inhibitor selectivity, the tendency of drugs to bind to off-targets, remains a top priority for kinase inhibitor design and clinical safety assessment. Traditional approaches for kinase selectivity analysis using biochemical activity and binding assays are useful but can be costly and are often limited by the kinases that are available. On the other hand, current computational kinase selectivity prediction methods are computational intensive and can rarely achieve sufficient accuracy for large-scale kinome wide inhibitor selectivity profiling. Results: Here, we present a KinomeFEATURE database for kinase binding site similarity search by comparing protein microenvironments characterized using diverse physiochemical descriptors. Initial selectivity prediction of 15 known kinase inhibitors achieved an >90% accuracy and demonstrated improved performance in comparison to commonly used kinase inhibitor selectivity prediction methods. Additional kinase ATP binding site similarity assessment (120 binding sites) identified 55 kinases with significant promiscuity and revealed unexpected inhibitor cross-activities between PKR and FGFR2 kinases. Kinome-wide selectivity profiling of 11 kinase drug candidates predicted novel as well as experimentally validated off-targets and suggested structural mechanisms of kinase cross-activities. Our study demonstrated potential utilities of our approach for large-scale kinase inhibitor selectivity profiling that could contribute to kinase drug development and safety assessment. Availability and implementation: The KinomeFEATURE database and the associated scripts for performing kinase pocket similarity search can be downloaded from the Stanford SimTK website (https://simtk.org/projects/kdb). Supplementary information: Supplementary data are available at Bioinformatics online.

Cosmetic Outcomes Following Breast-Conservation Surgery and Radiation for Multiple Ipsilateral Breast Cancer: Data from the Alliance Z11102 Study.

BACKGROUND: Diagnoses of multiple ipsilateral breast cancer (MIBC) are increasing. Historically, the primary treatment for MIBC has been mastectomy due to concerns about in-breast recurrence risk and poor cosmetic outcome. The Alliance Z11102 study prospectively assessed cosmetic outcomes in women with MIBC treated with breast-conserving therapy (BCT). PATIENTS AND METHODS: Z11102 was a multicenter trial enrolling women with two or three separate sites of biopsy-proven malignancy separated by ≥ 2 cm within the same breast. Cosmetic outcome was a planned secondary endpoint. Data were collected with a four-point cosmesis survey (1 = excellent, 4 = poor) and the BREAST-Q (scored 0-100). All patients undergoing successful breast-conserving therapy were treated with whole-breast radiation. Associations were assessed with Chi square or Fisher's exact tests as appropriate. RESULTS: Cosmetic outcome data for 216 eligible women who completed therapy are included in this analysis. Of the 136 patients who completed the survey 2 years postoperatively, 70.6% (N = 96) felt the result was good or excellent, while 3.7% (N = 5) felt the result was poor. We found no significant differences in patient-reported cosmetic outcomes when stratifying by patient age, number of lesions (two or three), number of incisions, number of lumpectomies, or size of largest area of disease. Mean satisfaction score on the BREAST-Q was 77.2 at 6 months following whole-breast radiation and 73.7 at 3 years following surgery. CONCLUSIONS: BCT performed for MIBC results in good or excellent cosmesis for the majority of women. From a cosmetic perspective, BCT is a valid surgical approach to women with MIBC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01556243.