Caregiver Nutritional Health Outcomes of the Simple Suppers Study: Results from a 10 Week,Two-Group Quasi-Experimental Family Meals Intervention

Individuals from racial minority backgrounds, especially those in low income situations, are at increased risk for obesity. Family meals positively impact child nutritional health; however, there is limited evidence examining the impact on caregivers, particularly racial minority and income-restricted individuals. The objective of this intervention study was to determine the effect of Simple Suppers, a 10 week family meals program, on caregiver diet and nutrition outcomes. Intervention versus waitlist control participants were compared from baseline (T0) to post-intervention (T1). In addition, intervention participants were assessed at a 10 week follow-up time point (T2). This study was a two-group quasi-experimental intervention trial. Lessons (10 total) were delivered on a weekly basis for 90 min. Data were collected from intervention and waitlist control participants at T0 and T1, and intervention participants at T2. After baseline (T0) data collection, families enrolled in the immediate upcoming session of Simple Suppers (intervention group) or waited for 10 weeks (waitlist control group) to begin the program. Participants were caregivers of children ages 4–10 years. This study was conducted in a faith-based community center for underserved families in Columbus, Ohio. Primary outcomes were: diet quality assessed by Healthy Eating Index (HEI) total and component scores, and total energy intake (kcal/day); body mass index (BMI) (kg/m²), waist circumference (cm), systolic and diastolic blood pressure (BP) (mmHG); and self-efficacy for having healthy meals and menu planning (both scalar). The impact of the intervention (T0:T1) was assessed using generalized mixed-effects linear regression models. Maintenance of change in study outcomes among intervention participants (T1:T2) was examined with paired t-tests. 109 caregivers enrolled in this study. The retention rate at T1 was 90% (i.e., 98 participants). 56 of 68 intervention participants completed T2, resulting in a retention rate of 82%. Almost all (99%) were female, 61% were Black, and 50% were between 31 and 40 years old. In total, 40% had low income and 37% had low or very low food security. At T1, intervention vs. waitlist controls had a lower daily energy intake (p = 0.04), but an HEI-2010 component score for fatty acids (adequacy) that was lower indicating a lower dietary intake of fatty acids (p = 0.02), and a component score for empty calories (moderation) that was significantly lower indicating a higher intake of empty calorie foods (p = 0.03). At T1, intervention vs. waitlist controls also had a lower BMI (p < 0.001) and systolic BP (p = 0.04), and higher self-efficacy (p = 0.03). There were no group differences in other outcomes. At T2, intervention participants maintained the changes in daily energy intake, BMI, systolic BP, and self-efficacy that improved during the intervention period. There was no change (improvement) in the component score for fatty acids; however, the component score for empty calories significantly improved (p = 0.02). Engagement in the Simple Suppers program led to improvements in caregivers’ daily caloric intake, weight status, systolic blood pressure, and self-efficacy for family meals. Future research should further explore the dietary and nutritional health benefits of family meals among caregivers at the highest risk for obesity.     

Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia

Dysregulation of apoptotic machinery is one mechanism by which acute myeloid leukemia (AML) acquires a clonal survival advantage. B-cell lymphoma protein-2 (BCL2) overexpression is a common feature in hematologic malignancies. The selective BCL2 inhibitor, venetoclax (VEN) is used in combination with azacitidine (AZA), a DNAmethyltransferase inhibitor (DNMTi), to treat patients with AML. Despite promising response rates to VEN/AZA, resistance to the agent is common. One identified mechanism of resistance is the upregulation of myeloid cell leukemia-1 protein (MCL1). Pevonedistat (PEV), a novel agent that inhibits NEDD8-activating enzyme, and AZA both upregulate NOXA (PMAIP1), a BCL2 family protein that competes with effector molecules at the BH3 binding site of MCL1. We demonstrate that PEV/AZA combination induces NOXA to a greater degree than either PEV or AZA alone, which enhances VEN-mediated apoptosis. Herein, using AML cell lines and primary AML patient samples ex vivo, including in cells with genetic alterations linked to treatment resistance, we demonstrate robust activity of the PEV/VEN/AZA triplet. These findings were corroborated in preclinical systemic engrafted models of AML. Collectively, these results provide rational for combining PEV/VEN/AZA as a novel therapeutic approach in overcoming AML resistance in current therapies.     

Efferent projections of the paratrigeminal nucleus in the rat

The efferent projections of the paratrigeminal nucleus in the rat were investigated by means of retrograde transport techniques. Injections were made in most of the supraspinal structures known to receive afferents from the spinal cord or the trigeminal nucleus caudalis. Spinal injections were also performed. Dense paratrigeminal efferents were seen to be directed to the nucleus of the solitary tract and to the peribrachial area, the latter including the cuneiformis and parabrachial nuclei. Projections were mostly ipsilateral. These results are discussed in relation to a possible role of the paratrigeminal nucleus in thermoreception and/or vegetative regulation processing.     

The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion.

BACKGROUND CONTEXT: There is mounting evidence supporting the efficacy of bone morphogenetic protein (BMP) for both anterior interbody and posterolateral lumbar fusion. However, the relative cost of BMP remains an important concern for physicians, hospitals, and payers. PURPOSE: The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft (ICBG) supplemented with graft extenders. STUDY DESIGN/SETTING: A prospective randomized controlled trial of rhBMP-2/ACS (Infuse Bone Graft; Medtronic Sofamor Danek, Memphis, TN) versus ICBG+/-graft extender for lumbar spine fusion in patients over 60 years old. PATIENT SAMPLE: One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion randomized between receiving rhBMP-2/ACS or ICBG. OUTCOME MEASURES: All health-care costs over the first 3 months after surgery. METHODS: As part of a prospective randomized trial of rhBMP-2/ACS versus ICBG+/-graft extender for lumbar spine fusion, all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare, Louisville, KY. A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care. RESULTS: Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest. The mean hospital cost for the index admission was $24,736 for the rhBMP-2/ACS group and $21,138 for the ICBG group. Mean inpatient physician costs were $5,082 in the rhBMP-2/ACS group and $5,316 in the ICBG group. Costs associated with posthospital rehabilitation averaged $4,906 in the rhBMP-2/ACS group versus $6,820 in the ICBG group. Total payer expenditure for the 3-month perioperative period averaged $33,860 in the rhBMP-2/ACS group and $37,227 in the ICBG group. CONCLUSIONS: The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS. In contrast, the payer in a Diagnosis-Related Group (DRG) model achieves a net savings, based primarily on the decreased payment for inpatient rehabilitation, but also on decreased hospital reimbursement, physician costs, and other outpatient services.     

Predictive Factors and Patterns of Recurrence in Patients with Triple Negative Breast Cancer

Background

We investigated the outcomes of patients with triple negative breast cancer ([TNBC] = estrogen receptor negative, progesterone receptor negative, and HER2 nonamplified).

Methods

We identified 414 patients with stage I–III TNBC treated between 1999 and 2008. Data included patient/tumor characteristics, surgical, systemic, and radiation treatment received, and breast cancer-specific survival. Data were compared using Chi square, Fisher exact test, and logistic regression. A p value <.05 was considered significant.

Results

The cohort included 414 patients (mean age 53.8 ± 12.5 years) with a mean follow-up of 68.2 ± 36.4 months. Of 414 patients, 304 (73.4 %) had no evidence of recurrence, while 110 (26.6 %) had recurrent disease, including 19 (17.3 %) with isolated locoregional recurrence, 70 (63.6 %) with isolated distant recurrence, and 21 (19.1 %) with both. Of 91 patients with distant recurrences, lung was most common (n = 38), followed by brain (n = 32), bone (n = 31), and liver (n = 29). Factors significantly associated with recurrence included increasing tumor size, positive nodal status, increasing stage, and type of chemotherapy (adjuvant vs neoadjuvant). After controlling for all potential confounders in multivariate stepwise regression, these same factors were also found to be independent predictors of recurrence. In the survival analysis, these same factors, in addition to receipt of radiation were found to be predictive of survival.

Conclusions

Approximately 25 % of patients with TNBC experienced a locoregional and/or distant recurrence, resulting in greater than 75 % breast cancer-specific mortality for those who experienced a distant recurrence. The lack of targeted therapy for this aggressive breast cancer subtype likely contributed to this finding.     

A Retrospective Review of Histopathologic Features Associated with Increased Risk of Recurrence of Non-melanoma Skin Cancer After Mohs Micrographic Surgery

ObjectiveMohs micrographic surgery (MMS) is the gold standard treatment for non-melanoma skin cancer (NMSC). However, NMSC recurrence may occur in a small proportion of patients. The aim of this study was to identify histopathologic features seen on the final stage of previous MMS, which may increase the risk of NMSC recurrence.MethodsThis was a single-institution retrospective study of 39 recurrent basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), which were treated with MMS. Slides from the final stage of previous MMS were reviewed by two board-certified dermatopathologists for the following histopathologic features: perineural inflammation, dense inflammation, mucin, ruptured follicle, actinic keratosis, and missing tissue.ResultsTwenty recurrent BCCs and 19 recurrent SCCs were included. Histopathologic features identified on the final stage of previous MMS included missing tissue from the epidermis, dermis, and/or subcutis (69%), actinic keratosis (51%), perineural inflammation (10%), and dense inflammation (8%). Ruptured follicle was present in one BCC case, and mucin was not identified in any cases.LimitationsLimitations include retrospective study design, small number of recurrent cases, single institution, and lack of a control group consisting of NMSC cases which did not recur after MMS.ConclusionMohs surgeons should carefully evaluate NMSC frozen sections for the presence of missing tissue, actinic keratosis, perineural inflammation, and dense inflammation as these histopathologic features may be associated with tumor recurrence. It is of paramount importance to acquire high quality frozen sections for thorough margin evaluation.     

Menkes Disease Mimicking Child Abuse

Althouygh Menkes disease has well‐recognized neurologic, developmental, and cutaneous features, the initial presentation may resemble child abuse. We describe a 5‐month‐old boy with multiple fractures indicative of nonaccidental trauma who was ultimately diagnosed with Menkes disease. Copper deficiency leads to connective tissue abnormalities and may result in subdural hematomas, wormian bones, cervical spine defects, rib fractures, and spurring of the long bone metaphyses. Several of these findings, including fractures and subdural hematomas, may be misinterpreted as child abuse.     

Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation

Regulation of epidermal proliferation and differentiation is critical for maintenance of cutaneous homeostasis. Interferon Regulatory Factor 6 (Irf6)-deficient mice die perinatally and exhibit ectopic proliferation and defective epidermal differentiation. We sought to determine whether these disruptions of epidermal function were cell autonomous, and used embryonic Irf6(-/-) keratinocytes to understand the specific role of Irf6 in keratinocyte proliferation and differentiation. In the absence of Irf6, keratinocytes exhibited a heterogeneous phenotype with the presence of large cells. Irf6(-/-) keratinocytes displayed increased colony-forming efficiency compared with wild-type cells, suggesting that Irf6 represses long-term proliferation. Irf6 was present at low levels in wild-type keratinocytes in culture, and upregulated after induction of differentiation in vitro, along with upregulation of markers of early differentiation. However, Irf6(-/-) keratinocytes did not express markers of terminal differentiation. Overexpression of Irf6 in wild-type keratinocytes was insufficient to induce expression of markers of differentiation under growing conditions. Together, these results indicated that Irf6 is necessary, but not sufficient, for keratinocyte differentiation. Finally, using a transgenic mouse expressing Lac-Z under the regulation of an enhancer element 9.7 kb upstream of the Irf6 start site, we demonstrated that this element contributes to the regulation of Irf6 in the epidermis and keratinocytes in culture.