Minimizing higher-order aggregation maximizes iron mobilization by small molecules.

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol3:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization. Guided by this understanding and systematic structure-function studies enabled by modular synthesis, we identified FeM-1269, which minimally aggregates and dose-dependently mobilizes iron across lipid bilayers even at very high concentrations. In contrast to hinokitiol, FeM-1269 is also well-tolerated in animals at high doses for extended periods of time. In a mouse model of anemia of inflammation, FeM-1269 increases serum iron, transferrin saturation, hemoglobin and hematocrit. This rationally developed iron-mobilizing small molecule has enhanced potential as a molecular prosthetic for understanding and potentially treating iron transporter deficiencies.

Age estimates for hominin fossils and the onset of the Upper Palaeolithic at Denisova Cave.

Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans1,2, and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations3. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations. Here we present 50 radiocarbon determinations from the late Middle and Upper Palaeolithic layers of the site. We also report three direct dates for hominin fragments and obtain a mitochondrial DNA sequence for one of them. We apply a Bayesian age modelling approach that combines chronometric (radiocarbon, uranium series and optical ages), stratigraphic and genetic data to calculate probabilistically the age of the human fossils at the site. Our modelled estimate for the age of the oldest Denisovan fossil suggests that this group was present at the site as early as 195,000 years ago (at 95.4% probability). All Neanderthal fossils-as well as Denisova 11, the daughter of a Neanderthal and a Denisovan4-date to between 80,000 and 140,000 years ago. The youngest Denisovan dates to 52,000-76,000 years ago. Direct radiocarbon dating of Upper Palaeolithic tooth pendants and bone points yielded the earliest evidence for the production of these artefacts in northern Eurasia, between 43,000 and 49,000 calibrated years before present (taken as AD 1950). On the basis of current archaeological evidence, it may be assumed that these artefacts are associated with the Denisovan population. It is not currently possible to determine whether anatomically modern humans were involved in their production, as modern-human fossil and genetic evidence of such antiquity has not yet been identified in the Altai region.

Benefits of Aerosolized, Point-of-care, Autologous Skin Cell Suspension (ASCS) for the Closure of full Thickness Wounds from Thermal and Non-Thermal Causes: Learning Curves from the first 50 Consecutive cases at an Urban, Level 1 Trauma Center.

OBJECTIVE: To determine the utility of Autologous Skin Cell Suspension (ASCS) in closing full-thickness (FT) defects from injury and infection. SUMMARY BACKGROUND DATA: Although ASCS has documented success in closing partial-thickness burns, far less is known about the efficacy of ASCS in FT defects. METHODS: Fifty consecutive patients with FT defects (burn 17, necrotizing infection 13, crush 7, degloving 5, other 8) underwent closure with the bilayer technique of 3:1 widely-meshed, thin, split-thickness skin graft and 80:1 expanded ASCS. End points were limb salvage rate, donor site reduction, operative and hospital throughput, incidence of complications, and re-epithelialization by 4, 8, and 12 weeks. RESULTS: Definitive wound closure was achieved in 76%, 94%, and 98% of patients, at 4, 8, and 12 weeks, respectively. Limb salvage occurred in 42/43 patients (10 upper, 33 lower extremities). Mean area grafted was 435 cm2; donor site size was 212 cm2, representing a potential reduction of 50%. Mean surgical time was 71 minutes; total OR time was 124 minutes. Mean length-of-stay was 26.4 days; time from grafting to discharge was 11.2 days. 4/50 patients (8%) required 6 reoperations for bleeding (1), breakdown (4), and amputation (1). 4/50 patients (8%) developed hypertrophic scarring, which responded to silicone sheeting (2) and laser resurfacing (2). Mean follow-up was 92.7 days. CONCLUSION: When used for closure of FT wounds, point-of-care ASCS is effective and safe. Benefits include rapid re-epithelialization, high rate of limb salvage, reduction of donor site size and morbidity, and low incidence of hypertrophic scarring.

A data processing pipeline for the AACR project GENIE biopharma collaborative data with the {genieBPC} R package.

MOTIVATION: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC) represent comprehensive clinical data linked to high-throughput sequencing data, providing a multi-institution, pan-cancer, publicly available data repository. GENIE BPC data provide detailed demographic, clinical, treatment, genomic and outcome data for patients with cancer. These data result in a unique observational database of molecularly characterized tumors with comprehensive clinical annotation that can be used for health outcomes and precision medicine research in oncology. Due to the inherently complex structure of the multiple phenomic and genomic datasets, the use of these data requires a robust process for data integration and preparation in order to build analytic models. RESULTS: We present the {genieBPC} package, a user-friendly data processing pipeline to facilitate the creation of analytic cohorts from the GENIE BPC data that are ready for clinico-genomic modeling and analyses. AVAILABILITY AND IMPLEMENTATION: {genieBPC} is available on CRAN and GitHub.

Germinal center activity and B cell maturation are associated with protective antibody responses against Plasmodium pre-erythrocytic infection.

Blocking Plasmodium, the causative agent of malaria, at the asymptomatic pre-erythrocytic stage would abrogate disease pathology and prevent transmission. However, the lack of well-defined features within vaccine-elicited antibody responses that correlate with protection represents a major roadblock to improving on current generation vaccines. We vaccinated mice (BALB/cJ and C57BL/6J) with Py circumsporozoite protein (CSP), the major surface antigen on the sporozoite, and evaluated vaccine-elicited humoral immunity and identified immunological factors associated with protection after mosquito bite challenge. Vaccination achieved 60% sterile protection and otherwise delayed blood stage patency in BALB/cJ mice. In contrast, all C57BL/6J mice were infected similar to controls. Protection was mediated by antibodies and could be passively transferred from immunized BALB/cJ mice into naïve C57BL/6J. Dissection of the underlying immunological features of protection revealed early deficits in antibody titers and polyclonal avidity in C57BL/6J mice. Additionally, PyCSP-vaccination in BALB/cJ induced a significantly higher proportion of antigen-specific B-cells and class-switched memory B-cell (MBCs) populations than in C57BL/6J mice. Strikingly, C57BL/6J mice also had markedly fewer CSP-specific germinal center experienced B cells and class-switched MBCs compared to BALB/cJ mice. Analysis of the IgG γ chain repertoires by next generation sequencing in PyCSP-specific memory B-cell repertoires also revealed higher somatic hypermutation rates in BALB/cJ mice than in C57BL/6J mice. These findings indicate that the development of protective antibody responses in BALB/cJ mice in response to vaccination with PyCSP was associated with increased germinal center activity and somatic mutation compared to C57BL/6J mice, highlighting the key role B cell maturation may have in the development of vaccine-elicited protective antibodies against CSP.

Treatment for Opioid Use Disorder: Population Estimates - United States, 2022.

In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year. Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality. However, only a small proportion of persons with OUD receive these medications. Data from the 2022 National Survey on Drug Use and Health were applied to a cascade of care framework to estimate and characterize U.S. adult populations who need OUD treatment, receive any OUD treatment, and receive medications for OUD. In 2022, 3.7% of U.S. adults aged ≥18 years needed OUD treatment. Among these, only 25.1% received medications for OUD. Most adults who needed OUD treatment either did not perceive that they needed it (42.7%) or received OUD treatment without medications for OUD (30.0%). Compared with non-Hispanic Black or African American and Hispanic or Latino adults, higher percentages of non-Hispanic White adults received any OUD treatment. Higher percentages of men and adults aged 35-49 years received medications for OUD than did women and younger or older adults. Expanded communication about the effectiveness of medications for OUD is needed. Increased efforts to engage persons with OUD in treatment that includes medications are essential. Clinicians and other treatment providers should offer or arrange evidence-based treatment, including medications, for patients with OUD. Pharmacists and payors can work to make these medications available without delays.

The genome of the offspring of a Neanderthal mother and a Denisovan father.

Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago1,2. Here we present the genome of 'Denisova 11', a bone fragment from Denisova Cave (Russia)3 and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave4-6. The mother came from a population more closely related to Neanderthals who lived later in Europe2,7 than to an earlier Neanderthal found in Denisova Cave8, suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal-Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met.

Maternal Sleep Quality and Executive Function are Associated with Perceptions of Infant Sleep.

OBJECTIVES: This study examined the associations among maternal sleep quality, executive function, and perceptions of infant sleep in a sample of families recruited from human service and public health systems. METHODS: Seventy-three mothers of infants 5-14 months old were included in the study. Mothers racially and ethnically identified as American Indian/Alaskan Native (4.1%), Asian (4.1%), Black/African American (12.3%), Latina (23.3%), more than one race (12.3%), Pacific Islander (1.4%), and White (42.5%). Mothers completed questionnaires assessing their own sleep (Pittsburgh Sleep Quality Index) and executive function (Behavior Rating Inventory of Executive Function) as well as their perceptions about their infant's sleep (Brief Infant Sleep Questionnaire). RESULTS: Results of the path analysis indicated significant direct effects among maternal sleep quality, executive function, and perceptions of infant sleep. Significant indirect effects were found such that poor maternal sleep quality was linked to poorer perceptions of infant sleep through maternal executive dysfunction, adjusting for infant sleep patterns, infant age, and maternal race and ethnicity. CONCLUSIONS: The current study highlights the potential role of maternal behavioral and cognitive factors in shaping mothers' perceptions about infant sleep. These findings support the need for health professionals and researchers to consider maternal sleep quality and executive function when addressing mothers' concerns about infant sleep.

The Simplified Comorbidity Index predicts non-relapse mortality in reduced-intensity conditioning allogeneic haematopoietic cell transplantation.

Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.

Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019.

OBJECTIVES: Many biomarkers have been studied to assist in the risk stratification and prognostication of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Procalcitonin (PCT), a circulating precursor of the hormone calcitonin, has been studied with mixed results as a predictor of severe coronavirus disease 2019 (COVID-19) in the general population; however, to date, no studies have focused on the utility of PCT in predicting disease severity and death from COVID-19 in the cancer population. METHODS: We conducted a retrospective study of cancer patients hospitalized with COVID-19 at a comprehensive cancer center over a 10-month period who had PCT recorded on admission. We assessed associations between variables of clinical interest and the primary outcomes of progression of COVID-19 and death during or within 30 days of hospitalization using univariable and multivariable logistic regression. RESULTS: The study included 209 unique patients. In the univariate analysis, elevated PCT on admission was associated with higher odds of progression of COVID-19 or death (Odds ratio [OR] 1.40, 95% CI 1.08-1.93) and mortality alone (OR 1.53, 95% CI 1.17-2.11). In multivariate regression, PCT remained significantly associated with progression or death after holding chronic kidney disease (CKD) status constant (OR 1.40, 95% CI: 1.08, 1.93, p=0.003). Similarly, the association of PCT and death remained significant after adjusting for age (OR 1.54, 95% CI: 1.17-2.15). CONCLUSIONS: In hospitalized COVID-19 patients with underlying cancer, initial PCT levels on admission may be associated with prognosis, involving higher odds of progression of COVID-19 and/or mortality.

Tailored Nurse Support Program Promoting Positive Parenting and Family Preservation.

BACKGROUND: Public health nurse home visiting is a promising approach for addressing the complex needs of families at risk of child maltreatment. The Colorado Nurse Support Program advances service provision by using evidence-based practices to provide tailored assessment and intervention to low-income, primiparous, and multiparous families with children under 18 years of age identified as high risk by county human service systems. OBJECTIVES: This study aimed to test the effects of the Nurse Support Program on child protective services case characteristics between Nurse Support Program families and a demographically comparable reference group of families and evaluate changes in parenting outcomes from pre- to postprogram involvement for Nurse Support Program families. METHODS: We used a matched comparison group quasi-experimental design in which families in the Nurse Support Program ( n = 48) were compared to families ( n = 150) who were identified using administrative data from Colorado's Comprehensive Child Welfare Information System. Outcomes were child protective case characteristics (child protection referrals, open assessments, founded assessments, open cases, and children's placement in out-of-home care) and parenting outcomes. RESULTS: Nurse Support Program families were less likely to have a child protection case opened or have their child placed in out-of-home care. There were no significant between-group differences in child protection referrals, open assessments, or founded assessments. Families in the Nurse Support Program showed improvements in parenting outcomes over time. DISCUSSION: Findings suggest that the Nurse Support Program is a successful public health nurse home-visiting approach to promote positive parenting and family preservation among families with complex needs. Implementing tailored public health nurse home-visiting programs, such as the Nurse Support Program, should continue to be evaluated and supported to mitigate the public health risk of child maltreatment.

Impact of COVID-19 on Referral Patterns and Service Delivery for an Integrated Behavioral Health Program.

The emergence and rapid spread of COVID-19 led to unprecedented changes for families and systems of care. This study sought to understand the needs of families participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) before and during the pandemic and considers the impact remote service delivery has on access to an integrated behavioral health intervention to support the psychosocial needs of children and caregivers. Needs for referral varied significantly pre- and post-pandemic onset. Analyses revealed that significantly more referrals were made regarding social determinants of health after the onset of COVID-19 (13.8%) compared with prior to the COVID-19 pandemic (4.1%, p < .05). Providers' transition to telehealth services sufficiently served WIC families.

Pain and Prescription Opioid Use Among US Construction Workers: Findings From the 2011‒2018 Medical Expenditure Panel Survey.

Objectives. To examine prescription opioid and nonopioid analgesic use among US construction workers and their associations with pain conditions and sociodemographic factors. Methods. We analyzed data for about 9000 (weighted 11.5 million per year) construction workers who responded to the Medical Expenditure Panel Survey from 2011 to 2018. We applied both descriptive statistics and multiple logistic regression procedures in the analyses. Results. An estimated 1.2 million (10.0%) of construction workers used prescription opioid analgesics annually. The adjusted odds of prescription opioid use were significantly higher for workers suffering from work-related injuries (adjusted odds ratio [AOR] = 3.82; 95% confidence interval [CI] = 2.72, 5.37), non‒work-related injuries (AOR = 3.37; 95% CI = 2.54, 4.46), and musculoskeletal disorders (AOR = 2.31; 95% CI = 1.80, 2.95) after we controlled for potential confounders. Adjusted odds of prescription opioid use were also higher among workers with poorer physical health (AOR = 1.95; 95% CI = 1.42, 2.69) or mental health disorders (AOR = 1.95; 95% CI = 1.41, 2.68). Conclusions. Work- and non‒work-related injuries and musculoskeletal disorders significantly increased prescription opioid use among construction workers. To prevent opioid use disorders, multipronged strategies should be approached. (Am J Public Health. 2022;112(S1):S77-S87. https://doi.org/10.2105/AJPH.2021.306510).

Psychosocial distress is dynamic across the spectrum of cancer care and requires longitudinal screening for patient-centered care.

PURPOSE: Screening for cancer-related psychosocial distress is recommended for patients with cancer; however, data on the long-term prevalence of distress and its natural history in survivors are scarce, preventing recommendations for screening frequency and duration. We sought to evaluate longitudinal distress in cancer patients. METHODS: We evaluated longitudinal distress screening data for patients with cancer treated or surveilled at our institution from 2010 to 2018. Anxiety, depression, insurance/financial, family, memory, and strength-related distress were separately assessed and analyzed. Multivariable logistic regression was utilized to evaluate factors associated with distress subtypes. RESULTS: In 5660 patients, distress was the highest at diagnosis for anxiety, depression, financial, and overall distress. On multivariable analysis, factors independently associated with distress at diagnosis included younger age, female gender, disease site/stage, payor, and income, varying by subtype-specific analyses. Severe distress in at least one subtype persisted in over 30% of survivors surveyed through 10 years after diagnosis. Over half of patients with initially severe distress at diagnosis improved within 12 months; however, distress worsened in 20-30% of patients with moderate, low, and no initial distress, regardless of the distress subtype. CONCLUSION: Psychosocial distress in cancer survivors is a long-lasting burden with implications for quality of life and oncologic outcomes. Severe distress remains prevalent through 10 years after diagnosis in survivors receiving continued care at cancer centers and results from both persistent and new sources of distress in a variety of psychosocial domains. Longitudinal distress screening is an invaluable tool for providing comprehensive patient-centered cancer care and is recommended to detect new or recurrent distress in cancer survivors.

Development of a model to measure the effect of off-balancing vectors on the delivery of high-quality CPR in a moving vehicle.

AIM: We sought to develop a model to measure the acceleration and jerk vectors affecting the performance of High-Quality Cardiopulmonary Resuscitation (HQ-CPR) during patient transport. METHODS: Three participants completed a total of eighteen rounds of compression only HQ-CPR in a moving vehicle. The vehicle was driven in a manner that either minimized or increased linear and angular vectors. The HQ-CPR variables measured were compression fraction (CF%), and percentages of compressions with correct depth > 5 cm (D%), rate 100-120 (R%), full recoil (FR%), and hand position (HP%). A composite HQ-CPR score was calculated: ((D% + R% + FR% + HP%)/4) * CF%). Linear and gyroscopic data were measured in the X, Y, and Z axes. The perceived difficulty in performing HQ-CPR was measured with the Borg Rating of Perceived Exertion Scale. RESULTS: HQ-CPR data, linear vector data, and gyroscopic data were successfully recorded in all trial evolutions. Univariate regression analysis demonstrated that HQ-CPR was negatively affected by increasing magnitudes of linear acceleration (B = -0.093%/m/s2, 95% CI [-0.17 - -0.02), p = 0.02], linear jerk (B = -0.134%/m/s3, 95% CI [-0.26 - -0.01], p = 0.04), angular velocity (B = -0.543%/radian/s, 95% CI [-0.98 - -0.11], p = 0.02), and angular acceleration (B = 0.863%/radian/s2, 95% CI [-1.69 - -0.03], p = 0.04). Increasing vectors were negatively associated with FR% and R%. No difference was seen in D%, HP%, or CF%. Borg Rating of Perceived Exertion was greater in dynamic driving evolutions (8 ± 1 vs 3.5 ± 1.53, p = 0.02). CONCLUSION: This model reliably measured linear and angular off-balancing vectors experienced during the delivery of HQ-CPR in a moving vehicle. In this preliminary report, compression rate and full recoil appear to be HQ-CPR variables most affected in a moving vehicle.

Psychological distress and suicidal ideation among male construction workers in the United States.

BACKGROUND: Male workers in the US construction industry have a higher suicide rate than other workers in the nation. However, related research on this population remains sparse. This study evaluated psychological distress and suicidal ideation in these workers, and possible underlying factors. METHODS: Data from the National Survey of Drug Use and Health from 2008 to 2014 were analyzed. Stratified and multiple logistic regression analyses were conducted to examine factors associated with psychological distress and suicidal ideation among male construction workers aged ≥18 years (n = 12,034). RESULTS: Nearly one-third (29.6%) of male construction workers in the United States experienced psychological distress (23.8% graded as moderate, 5.8% as severe), and 2.5% reported suicidal ideation in the past year. Higher odds of serious psychological distress and suicidal ideation were found among workers who were younger, worked part-time, missed workdays due to injury or illness, or were in poor health. Illicit opioid use (odds ratio [OR] = 1.87, 95% confidence interval [CI]: 1.22-2.89) and alcohol dependence or abuse (OR = 2.64, 95% CI: 1.74-3.99) significantly escalated the odds of suicidal ideation. The odds of suicidal ideation among workers with serious psychological distress were 33 times higher than those having no or minor psychological distress (OR = 32.91, 95% CI: 19.82-54.65) when other factors were constant. CONCLUSIONS: Occupational and nonoccupational factors were associated with constructionworkers' psychological distress and suicidal ideation. Both illicit opioid use and alcohol dependence or abuse were risk factors, and psychological distress was a strong predictor for suicidal ideation. To improve workers' mental health, it is necessary to integrate workplace injury prevention with illicit opioid-use reduction programs and suicide prevention.

A Review of Self-Compassion as an Active Ingredient in the Prevention and Treatment of Anxiety and Depression in Young People.

Previous meta-analyses have found higher self-compassion is associated with lower anxiety and depression. The aim of this study was to investigate the efficacy of self-compassion as an active ingredient in the treatment and prevention of anxiety and depression in youth. This was conducted through (i) a systematic review of the literature and (ii) qualitative consultation with young people and researchers in self-compassion. Fifty studies met our inclusion criteria. Eight studies evaluated self-compassion interventions among youth aged 14-24, and the remaining studies measured the association between self-compassion and anxiety, and/or depression among this age group. Qualitative interviews were conducted with four self-compassion researchers. Interviews were also conducted in two rounds of consultation with 20 young people (M age = 18.85 years, age range 14-24 years). Higher self-compassion was related to lower symptoms of anxiety, r = - 0.49, 95% CI (- 0.57, - 0.42), and depression, r = - 0.50, 95% CI (- 0.53, - 0.47). There was evidence for self-compassion interventions in decreasing anxiety and depression in young people. Consultation with young people indicated they were interested in self-compassion interventions; however, treatment should be available in a range of formats and tailored to address diversity. Self-compassion experts emphasised the importance of decreasing self-criticism as a reason why self-compassion interventions work. The importance of targeting self-criticism is supported by the preferences of young people who said they would be more likely to engage in a treatment reducing self-criticism than increasing self-kindness. Future research is required to add to the emerging evidence for self-compassion interventions decreasing symptoms of anxiety and depression in young people.

The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes.

OBJECTIVE: Radiation therapy is a cornerstone of brain metastasis (BrM) management but carries the risk of radiation necrosis (RN), which can require resection for palliation or diagnosis. We sought to determine the relationship between extent of resection (EOR) of pathologically-confirmed RN and postoperative radiographic and symptomatic outcomes. METHODS: A single-center retrospective review was performed at an NCI-designated Comprehensive Cancer Center to identify all surgically-resected, previously-irradiated necrotic BrM without admixed recurrent malignancy from 2003 to 2018. Clinical, pathologic and radiographic parameters were collected. Volumetric analysis determined EOR and longitudinally evaluated perilesional T2-FLAIR signal preoperatively, postoperatively, and at 3-, 6-, 12-, and 24-months postoperatively when available. Rates of time to 50% T2-FLAIR reduction was calculated using cumulative incidence in the competing risks setting with last follow-up and death as competing events. The Spearman method was used to calculate correlation coefficients, and continuous variables for T2-FLAIR signal change, including EOR, were compared across groups. RESULTS: Forty-six patients were included. Most underwent prior stereotactic radiosurgery with or without whole-brain irradiation (N = 42, 91%). Twenty-seven operations resulted in gross-total resection (59%; GTR). For the full cohort, T2-FLAIR edema decreased by a mean of 78% by 6 months postoperatively that was durable to last follow-up (p < 0.05). EOR correlated with edema reduction at last follow-up, with significantly greater T2-FLAIR reduction with GTR versus subtotal resection (p < 0.05). Among surviving patients, a significant proportion were able to decrease their steroid use: steroid-dependency decreased from 54% preoperatively to 15% at 12 months postoperatively (p = 0.001). CONCLUSIONS: RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR; and reduced steroid dependency.

Salvage resection of recurrent previously irradiated brain metastases: tumor control and radiation necrosis dependency on adjuvant re-irradiation.

PURPOSE: The efficacy of salvage resection (SR) of recurrent brain metastases (rBrM) following stereotactic radiosurgery (SRS) is undefined. We sought to describe local recurrence (LR) and radiation necrosis (RN) rates in patients undergoing SR, with or without adjuvant post-salvage radiation therapy (PSRT). METHODS: A retrospective cohort study evaluated patients undergoing SR of post-SRS rBrM between 3/2003-2/2020 at an NCI-designated cancer center. Cases with histologically-viable malignancy were stratified by receipt of adjuvant PSRT within 60 days of SR. Clinical outcomes were described using cumulative incidences in the clustered competing-risks setting, competing risks regression, and Kaplan-Meier methodology. RESULTS: One-hundred fifty-five rBrM in 135 patients were evaluated. The overall rate of LR was 40.2% (95% CI 34.3-47.2%) at 12 months. Thirty-nine (25.2%) rBrM treated with SR + PSRT trended towards lower 12-month LR versus SR alone [28.8% (95% CI 17.0-48.8%) versus 43.9% (95% CI 36.2-53.4%), p = .07 by multivariate analysis]. SR as re-operation (p = .03) and subtotal resection (p = .01) were independently associated with higher rates of LR. On univariate analysis, tumor size (p = .48), primary malignancy (p = .35), and PSRT technique (p = .43) bore no influence on LR. SR + PSRT was associated with an increased risk of radiographic RN at 12 months versus SR alone [13.4% (95% CI 5.5-32.7%) versus 3.5% (95% CI 1.5-8.0%), p = .02], though the percentage with symptomatic RN remained low (5.1% versus 0.9%, respectively). Median overall survival from SR was 13.4 months (95% CI 10.5-17.7). CONCLUSION: In this largest-known series evaluating SR outcomes in histopathologically-confirmed rBrM, we identify a significant LR risk that may be reduced with adjuvant PSRT and with minimal symptomatic RN. Prospective analysis is warranted.

Child Maltreatment Severity and Sleep Variability Predict Mother-Infant RSA Coregulation.

Regulatory processes underlie maternal-infant interactions and may be disrupted in adverse caregiving environments. Child maltreatment and sleep variability may reflect high-risk caregiving, but it is unknown whether they confer vulnerability for poorer mother-infant parasympathetic coordination. The aim of this study was to examine mother-infant coregulation of respiratory sinus arrhythmia (RSA) in relation to child maltreatment severity and night-to-night sleep variability in 47 low-income mother-infant dyads. Maternal and infant sleep was assessed with actigraphy and daily diaries for seven nights followed by a mother-infant Still Face procedure during which RSA was measured. Higher maltreatment severity was associated with weakened concordance in RSA coregulation related to the coupling of higher mother RSA with lower infant RSA, suggesting greater infant distress and lower maternal support. Additionally, higher infant sleep variability was associated with infants' lower mean RSA and concordance in lagged RSA coregulation such that lower maternal RSA predicted lower infant RSA across the Still Face procedure, suggesting interrelated distress. Findings indicate that adverse caregiving environments differentially impact regulatory patterns in mother-infant dyads, which may inform modifiable health-risk behaviors as targets for future intervention.