Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool.

Caloric restriction is known to improve inflammatory and autoimmune diseases. However, the mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. Regulation of peripheral monocyte numbers was dependent on dietary glucose and protein levels. Specifically, we found that activation of the low-energy sensor 5'-AMP-activated protein kinase (AMPK) in hepatocytes and suppression of systemic CCL2 production by peroxisome proliferator-activator receptor alpha (PPARα) reduced monocyte mobilization from the bone marrow. Importantly, we show that fasting improves chronic inflammatory diseases without compromising monocyte emergency mobilization during acute infectious inflammation and tissue repair. These results reveal that caloric intake and liver energy sensors dictate the blood and tissue immune tone and link dietary habits to inflammatory disease outcome.

POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies.

Heterozygous pathogenic variants in POLR1A, which encodes the largest subunit of RNA Polymerase I, were previously identified as the cause of acrofacial dysostosis, Cincinnati-type. The predominant phenotypes observed in the cohort of 3 individuals were craniofacial anomalies reminiscent of Treacher Collins syndrome. We subsequently identified 17 additional individuals with 12 unique heterozygous variants in POLR1A and observed numerous additional phenotypes including neurodevelopmental abnormalities and structural cardiac defects, in combination with highly prevalent craniofacial anomalies and variable limb defects. To understand the pathogenesis of this pleiotropy, we modeled an allelic series of POLR1A variants in vitro and in vivo. In vitro assessments demonstrate variable effects of individual pathogenic variants on ribosomal RNA synthesis and nucleolar morphology, which supports the possibility of variant-specific phenotypic effects in affected individuals. To further explore variant-specific effects in vivo, we used CRISPR-Cas9 gene editing to recapitulate two human variants in mice. Additionally, spatiotemporal requirements for Polr1a in developmental lineages contributing to congenital anomalies in affected individuals were examined via conditional mutagenesis in neural crest cells (face and heart), the second heart field (cardiac outflow tract and right ventricle), and forebrain precursors in mice. Consistent with its ubiquitous role in the essential function of ribosome biogenesis, we observed that loss of Polr1a in any of these lineages causes cell-autonomous apoptosis resulting in embryonic malformations. Altogether, our work greatly expands the phenotype of human POLR1A-related disorders and demonstrates variant-specific effects that provide insights into the underlying pathogenesis of ribosomopathies.

Subjective social status, race, and metabolic syndrome in women with breast cancer.

PURPOSE: To evaluate the association of subjective social status (SSS) with metabolic syndrome (MetS) severity and its potential contribution to racial health disparities in women with breast cancer. METHODS: Multicenter cross-sectional study (10 US hospitals) in women (n = 1206) with primary diagnosis of invasive breast cancer received during Mar/2013-Feb/2020. Participants, self-identified as non-Hispanic White or Black, underwent physical and laboratory examinations and survey questions assessing socioeconomic parameters, medical history, and behavioral risks. SSS was measured with the 10-rung MacArthur scale. MetS severity was measured with a validated Z-Score. Generalized linear mixed modeling was used to analyze the associations. Missing data were handled using multiple imputation. RESULTS: Average age was 58 years. On average, the SSS of Black women, given equivalent level of income and education, was lower than the SSS of White women: 6.6 (6.1-7.0) vs 7.7 (7.54-7.79) among college graduates and 6.8 (6.4-7.2) vs 7.6 (7.5-7.8) among women in the high-income category (> $75,000). In multivariable analysis, after controlling for age, income, education, diet, and physical activity, increasing SSS was associated with a decrease in MetS-Z score, - 0.10 (- 0.16 to - 0.04) per every 2 rung increase in the MacArthur scale. CONCLUSION: Black women with breast cancer rank their SSS lower than White women with breast cancer do at each level of income and education. As SSS is strongly associated with MetS severity these results identify potentially modifiable factors that contribute to racial disparities.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.

Isolated frontosphenoidal craniosynostosis: An argument for genetic testing.

Isolated frontosphenoidal craniosynostosis (IFSC) is a rare congenital defect defined as premature fusion of the frontosphenoidal suture in the absence of other suture fusion. Until now, IFSC was regarded as a phenomenon with an unclear genetic etiology. We have identified three cases with IFSC with underlying syndromic diagnoses that were attributable to pathogenic mutations involving FGFR3 and MN1, as well as 22q11.2 deletion syndrome. These findings suggest a genetic predisposition to IFSC may exist, thereby justifying the recommendation for genetic evaluation and testing in this population. Furthermore, due to improved imaging resolution, cases of IFSC are now readily identified. With the identification of IFSC with underlying genetic diagnoses, in combination with significant improvements in imaging resolution, we recommend genetic evaluation in children with IFSC.

Optimal Management of Insulin in Patients Undergoing 18F-Fluorodeoxyglucose Positron Emission Tomography Scans.

OBJECTIVE: The management of insulin injections and insulin pumps before 18F-fluorodeoxyglucose-positron emission tomography integrated computerized tomography (FDG-PET/CT) scans is an important area to investigate given the rising rate of diabetes, the significant association between diabetes and cancer, and the complex relationship among glucose, insulin, and FDG tumor uptake. The purpose of this study was to determine the recommendations around subcutaneous insulin administration, insulin pumps, and hybrid closed-loop systems before FDG-PET scans. METHODS: We examined the websites of 100 hospitals selected from the 2022 US News and World Report top cancer hospitals for specific strategies around diabetes medication management before FDG-PET/CT scans. RESULTS: Of the 100 hospital websites, 61 had instructions addressing patients with diabetes. Of the 61 hospitals, 47.5% (n = 29) referred patients to their provider for further instructions, 18% (n = 11) referred patients to their own internal radiology department for further instructions, 16.4% (n = 10) had instructions on oral diabetic medications, 23% (n = 14) had instructions on insulin, and 3.3% (n = 2) had instructions on insulin pump management. Most commonly, instructions were to stop insulin 3 to 4 hours before the study and direct patients to their referring provider for more detailed instructions (n = 7). CONCLUSION: There is a lack of guidance and consensus among US cancer hospitals on managing insulin and continuous subcutaneous insulin infusions before FDG-PET/CT studies and a majority rely on referring providers to advise patients. However, society guidelines offer inconsistent recommendations and little research has been carried out to help guide referring providers. A multidisciplinary panel of specialists could help to guide practitioners on optimal management.

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.

Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.

Randomized Trial of a Palliative Care Intervention to Improve End-of-Life Care Discussions in Patients With Metastatic Breast Cancer.

BACKGROUND: Studies show that early, integrated palliative care (PC) improves quality of life (QoL) and end-of-life (EoL) care for patients with poor-prognosis cancers. However, the optimal strategy for delivering PC for those with advanced cancers who have longer disease trajectories, such as metastatic breast cancer (MBC), remains unknown. We tested the effect of a PC intervention on the documentation of EoL care discussions, patient-reported outcomes, and hospice utilization in this population. PATIENTS AND METHODS: Patients with MBC and clinical indicators of poor prognosis (n=120) were randomly assigned to receive an outpatient PC intervention (n=61) or usual care (n=59) between May 2, 2016, and December 26, 2018, at an academic cancer center. The intervention entailed 5 structured PC visits focusing on symptom management, coping, prognostic awareness, decision-making, and EoL planning. The primary outcome was documentation of EoL care discussions in the electronic health record (EHR). Secondary outcomes included patient-report of discussions with clinicians about EoL care, QoL, and mood symptoms at 6, 12, 18, and 24 weeks after baseline and hospice utilization. RESULTS: The rate of EoL care discussions documented in the EHR was higher among intervention patients versus those receiving usual care (67.2% vs 40.7%; P=.006), including a higher completion rate of a Medical Orders for Life-Sustaining Treatment form (39.3% vs 13.6%; P=.002). Intervention patients were also more likely to report discussing their EoL care wishes with their doctor (odds ratio [OR], 3.10; 95% CI, 1.21-7.94; P=.019) and to receive hospice services (OR, 4.03; 95% CI, 1.10-14.73; P=.035) compared with usual care patients. Study groups did not differ in patient-reported QoL or mood symptoms. CONCLUSIONS: This PC intervention significantly improved rates of discussion and documentation regarding EoL care and delivery of hospice services among patients with MBC, demonstrating that PC can be tailored to address the supportive care needs of patients with longer disease trajectories. ClinicalTrials.gov identifier: NCT02730858.

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score.

BACKGROUND: Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX™ (ODX) recurrence scores has been observed to explain this health disparity. Black women are also disproportionately affected by insulin resistance. We evaluated whether insulin resistance is associated with a higher ODX recurrence score and whether there is a difference between White and Black women to explain disparate clinical outcomes. METHODS: A subgroup analysis of patients in a multi-institutional cross-sectional study evaluating differences in insulin resistance between White and Black women was performed. Women diagnosed with a new hormone receptor-positive, HER2/neu-negative breast cancer with an ODX recurrence score were identified. Fasting blood glucose and insulin measurements were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) score, a method for assessing insulin resistance, and compared against ODX scores. RESULTS: Overall, 412 women (358 White women, 54 Black women) were identified. Compared with White women, Black women had a higher body mass index (30 vs. 26 kg/m2, p < 0.0001), higher HOMA-IR score (2.4 vs. 1.4, p = 0.004), and more high-grade tumors (30% vs. 16%, p = 0.01). There was a direct positive association with an increasing ODX score and HOMA-IR (p = 0.014). On subset analysis, this relationship was seen in White women (p = 0.005), but not in Black women (p = 0.55). CONCLUSION: In women with newly diagnosed breast cancer, increasing insulin resistance is associated with a higher recurrence score; however, this association was not present in Black women. This lack of association may be due to the small number of Black women in the cohort, or possibly a reflection of a different biological disease process of the patient's tumor.

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19.

OBJECTIVE: To explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: The study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate. RESULTS: Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023). CONCLUSION: Among critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.

Home Language Environment of Children With Orofacial Clefts as a Target for Intervention.

OBJECTIVE: To evaluate the home language environment (HLE) in children with orofacial clefts as a potential modifiable target for language and literacy intervention. DESIGN: Feasibility study examining longitudinal trends in HLE and responses to parent-focused literacy intervention. SETTING: Tertiary care children's hospital. PARTICIPANTS: HLE data were collected for 38 children with orofacial clefts between ages 7 and 23 months. Twenty-seven participants received parent-focused literacy intervention. INTERVENTIONS: Reach Out and Read, a literacy intervention, was introduced during a clinic visit. To assess response, participants were randomized to age at intervention (9, 18, or 24 months). MAIN OUTCOME MEASURES: Primary outcome measures included measurements from recordings in the home language environment of adult word count, child vocalizations, and conversational turns. RESULTS: Baseline (preintervention) results showed lower adult word count and conversational turns for caregivers and children with cleft lip and palate, as well as for those from lower socioeconomic groups. After the literacy intervention was introduced, this cohort showed increasing measures of child and caregiver vocalizations, particularly when introduced at 18 months. CONCLUSIONS: Although these results are preliminary, findings suggest that HLE characteristics vary as a function of children's cleft type as well as family socioeconomic status. Further, our caregiver-focused literacy intervention was feasible and resulted in short-term improvements in HLE. This is the first study to document HLE as a target for intervention in children with oral clefts. These findings support further research on HLE and caregiver-focused intervention to improve language/literacy outcomes for children with oral clefts.

Exploratory Qualitative Analysis of Early Literacy Engagement in Latinx Parents of a Child With a Cleft.

ABSTRACT: Literacy interventions are needed for children born with orofacial clefts, particularly for Latinx children who may experience multiple risk factors. To collect formative data for intervention design, focus groups and interviews were completed with 18 Latinx parents of children ages 13 to 49 months with orofacial clefts. Interviews focused on literacy experiences and practices. Six themes were identified through inductive qualitative analysis: child reading skills were highly valued; parents were motivated to improve on their childhood reading experiences; bilingualism was a goal for all parents; parents noted challenges in building child reading skills; reading engagement was broadly defined; and impact of cleft diagnosis was wide-reaching. Implications for intervention include a bilingual strength-based approach incorporating cleft-specific speech concerns, play, parallel online programming, behavioral strategies, and social support options. Use of telephone and online intervention with mailed materials can also help address family resource and time limitations.

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

BACKGROUND: Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women. METHODS: We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC). RESULTS: Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (ß = 0.04, 95% CI 0.005-0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R >  1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001). CONCLUSIONS: In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.

Catel-Manzke syndrome without Manzke dysostosis.

Catel-Manzke syndrome is characterized by hand anomalies, Robin sequence, cardiac defects, joint hyperextensibility, and characteristic facial features. Approximately 40 patients with Catel-Manzke have been reported, all with the pathognomonic bilateral or unilateral hyperphalangy caused by an accessory bone between the second metacarpal and proximal phalanx known as Manzke dysostosis. Here we present the first case of molecularly confirmed Catel-Manzke syndrome with Robin sequence but without Manzke dysostosis.

The midlife transition and the risk of cardiovascular disease and cancer Part I: magnitude and mechanisms.

Heart disease and cancer are the leading causes of death in the United States. In women, the clinical appearance of both entities-coronary heart disease and cancer (breast, endometrium, and ovary)-escalate during the decades of the midlife transition encompassing the menopause. In addition to the impact of aging, during the interval between the age of 40 and 65 years, the pathophysiologic components of metabolic syndrome also emerge and accelerate. These include visceral adiposity (measured as waist circumference), hypertension, diabetes, and dyslipidemia. Osteoporosis, osteoarthritis, sarcopenia, depression, and even cognitive decline and dementia appear, and most, if not all, are considered functionally related. Two clinical reports confirm the interaction linking the emergence of disease: endometrial cancer and metabolic syndrome. One describes the discovery of unsuspected endometrial cancer in a large series of elective hysterectomies performed in aged and metabolically susceptible populations. The other is from the Women's Health Initiative Observational Study, which found a positive interaction between endometrial cancer and metabolic syndrome regardless of the presence or absence of visceral adiposity. Both provide additional statistical support for the long-suspected causal interaction among the parallel but variable occurrence of these common entities-visceral obesity, heart disease, diabetes, cancer, and the prevalence of metabolic syndrome. Therefore, 2 critical clinical questions require analysis and answers: 1: Why do chronic diseases of adulthood-metabolic, cardiovascular, endocrine-and, in women, cancers of the breast and endometrium (tissues and tumors replete with estrogen receptors) emerge and their incidence trajectories accelerate during the postmenopausal period when little or no endogenous estradiol is available, and yet the therapeutic application of estrogen stimulates their appearance? 2: To what extent should identification of these etiologic driving forces require modification of the gynecologist's responsibilities in the care of our patients in the postreproductive decades of the female life cycle? Part l of this 2-part set of "expert reviews" defines the dimensions, gravity, and interactive synergy of each clinical challenge gynecologists face while caring for their midlife (primarily postmenopausal) patients. It describes the clinically identifiable, potentially treatable, pathogenic mechanisms driving these threats to quality of life and longevity. Part 2 (accepted, American Journal of Obstetrics & Gynecology) identifies 7 objectives of successful clinical care, offers "triage" prioritization targets, and provides feasible opportunities for insertion of primary preventive care initiatives. To implement these goals, a reprogrammed, repurposed office visit is described.

An Algorithm for the Assessment of Facial Asymmetry in Children With Focus on Etiology and Treatment.

BACKGROUND: Facial asymmetry is a common referral indication for craniofacial teams but has a wide range of causes. Prompt identification of etiology is critical to treatment, as medical and surgical interventions vary depending on the cause of asymmetry in each patient. SOLUTION: A standardized diagnostic algorithm. WHAT WE DID THAT IS NEW: We developed an algorithm to assist in the diagnostic evaluation of facial asymmetry with a focus on next steps for medically actionable causes.

Insulin-like growth factor receptor signaling in breast tumor epithelium protects cells from endoplasmic reticulum stress and regulates the tumor microenvironment.

BACKGROUND: Early analyses of human breast cancer identified high expression of the insulin-like growth factor type 1 receptor (IGF-1R) correlated with hormone receptor positive breast cancer and associated with a favorable prognosis, whereas low expression of IGF-1R correlated with triple negative breast cancer (TNBC). We previously demonstrated that the IGF-1R acts as a tumor and metastasis suppressor in the Wnt1 mouse model of TNBC. The mechanisms for how reduced IGF-1R contributes to TNBC phenotypes is unknown. METHODS: We analyzed the METABRIC dataset to further stratify IGF-1R expression with patient survival and specific parameters of TNBC. To investigate molecular events associated with the loss of IGF-1R function in breast tumor cells, we inhibited IGF-1R in human cell lines using an IGF-1R blocking antibody and analyzed MMTV-Wnt1-mediated mouse tumors with reduced IGF-1R function through expression of a dominant-negative transgene. RESULTS: Our analysis of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset revealed association between low IGF-1R and reduced overall patient survival. IGF-1R expression was inversely correlated with patient survival even within hormone receptor-positive breast cancers, indicating reduced overall patient survival with low IGF-1R was not due simply to low IGF-1R expression within TNBCs. Inhibiting IGF-1R in either mouse or human tumor epithelial cells increased reactive oxygen species (ROS) production and activation of the endoplasmic reticulum stress response. IGF-1R inhibition in tumor epithelial cells elevated interleukin (IL)-6 and C-C motif chemokine ligand 2 (CCL2) expression, which was reversed by ROS scavenging. Moreover, the Wnt1/dnIGF-1R primary tumors displayed a tumor-promoting immune phenotype. The increased CCL2 promoted an influx of CD11b+ monocytes into the primary tumor that also had increased matrix metalloproteinase (MMP)-2, MMP-3, and MMP-9 expression. Increased MMP activity in the tumor stroma was associated with enhanced matrix remodeling and collagen deposition. Further analysis of the METABRIC dataset revealed an increase in IL-6, CCL2, and MMP-9 expression in patients with low IGF-1R, consistent with our mouse tumor model and data in human breast cancer cell lines. CONCLUSIONS: Our data support the hypothesis that reduction of IGF-1R function increases cellular stress and cytokine production to promote an aggressive tumor microenvironment through infiltration of immune cells and matrix remodeling.

Sarcopenia Is Associated with Quality of Life and Depression in Patients with Advanced Cancer.

BACKGROUND: Patients with advanced cancer often experience muscle wasting (sarcopenia), yet little is known about the characteristics associated with sarcopenia and the relationship between sarcopenia and patients' quality of life (QOL) and mood. MATERIALS AND METHODS: As part of a randomized trial, we assessed baseline QOL (Functional Assessment of Cancer Therapy-General [FACT-G]) and mood (Hospital Anxiety and Depression Scale [HADS]) in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer, and prior to randomization. Using computed tomography scans collected as part of routine clinical care, we assessed sarcopenia at the level of the third lumbar vertebra with validated sex-specific cutoffs. We used logistic regression to explore characteristics associated with presence of sarcopenia. To examine associations between sarcopenia, QOL and mood, we used linear regression, adjusted for patients' age, sex, marital status, education, and cancer type. RESULTS: Of 237 participants (mean age = 64.41 ± 10.93 years), the majority were male (54.0%) and married (70.5%) and had lung cancer (56.5%). Over half had sarcopenia (55.3%). Older age (odds ratio [OR] = 1.05, p = .002) and education beyond high school (OR = 1.95, p = .047) were associated with greater likelihood of having sarcopenia, while female sex (OR = 0.25, p < .001) and higher body mass index (OR = 0.79, p < .001) correlated with lower likelihood of sarcopenia. Sarcopenia was associated with worse QOL (FACT-G: B = -4.26, p = .048) and greater depression symptoms (HADS-depression: B = -1.56, p = .005). CONCLUSION: Sarcopenia was highly prevalent among patients with newly diagnosed, incurable cancer. The associations of sarcopenia with worse QOL and depression symptoms highlight the need to address the issue of sarcopenia early in the course of illness. IMPLICATIONS FOR PRACTICE: This study found that sarcopenia, assessed using computed tomography scans acquired as part of routine clinical care, is highly prevalent in patients with newly diagnosed, incurable cancer. Notably, patients with sarcopenia reported worse quality of life and greater depression symptoms than those without sarcopenia. These findings highlight the importance of addressing muscle loss early in the course of illness among patients with incurable cancer. In the future, investigators should expand upon these findings to develop strategies for assessing and treating sarcopenia while striving to enhance the quality of life and mood outcomes of patients with advanced cancer.

Associations between laterality of orofacial clefts and medical and academic outcomes.

Patients with oral clefts have an increased risk of other malformations, syndromes, and lower academic performance in school. Few studies have investigated if laterality of clefts is associated with medical and academic outcomes. Oral clefts have nonrandom laterality, with left-sided clefts occurring approximately twice as often as right-sided clefts. Using a retrospective study design, we examined potential associations of cleft attributes and outcomes in patients with cleft lip with or without cleft palate (CL/P) born in 2003-2010 who were treated at the Seattle Children's Craniofacial Center. The following variables were extracted from medical records: cleft type, medical history, maternal hyperglycemia, other malformations, and the need for academic support at school. We used logistic regression to examine risk of associations with outcomes of interest. Relative to patients with left-sided clefts, patients with bilateral CL/P were more likely to have a syndrome. Patients with nonsyndromic right-sided CL/P had a higher risk (OR and 95%CI: 3.5, 1.3-9.5, and 5.5, 1.9-16.0, respectively) of having other malformations and requiring academic support at school, when compared to patients with left-sided CL/P. Understanding the etiology of oral clefts is complicated, in part because both genetic and environmental factors contribute to the risk of developing a cleft. However, the different outcomes associated with cleft laterality suggest that right-sided clefts may have a distinct etiology. Using laterality to study cleft subgroups may advance our understanding of the etiology of this common birth defect.