Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability.

Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains. Protein interactomes of RPA and Alt-RPA reveal unique and shared partners, including modifiers of CAG instability and disease presentation. RPA enhances in vitro melting, FAN1 excision, and repair of slipped-CAGs and protects against CAG expansions in human cells. RPA overexpression in SCA1 mouse brains ablates expansions, coincident with decreased ATXN1 aggregation, reduced brain DNA damage, improved neuron morphology, and rescued motor phenotypes. In contrast, Alt-RPA inhibits melting, FAN1 excision, and repair of slipped-CAGs and promotes CAG expansions. These findings suggest a functional interplay between the two RPAs where Alt-RPA may antagonistically offset RPA's suppression of disease-associated repeat expansions, which may extend to other DNA processes.

Influence of various factors on the legal outcome of cases of child abuse-experiences gathered at an interdisciplinary forensic examination center in Vienna, Austria.

BACKGROUND AND OBJECTIVE: To improve the currently low conviction rate in cases of child abuse a forensic examination center for children and adolescents (FOKUS) was established in Vienna, Austria. Besides a state of the art treatment combined with forensic documentation, one of FOKUS' key goals is to identify potential areas for improvements within the process legal proceedings in cases of child abuse through constant scientific monitoring. The accompanying study at hand includes all patients referred to FOKUS within a two year timeframe (n = 233), monitoring their progression from first contact with the medical professionals from FOKUS to the end of criminal proceedings. A detailed analysis of case files was performed in those cases that were reported to the legal authorities by the clinicians of FOKUS (n = 87). Aim of the study is to investigate which factors contribute to the initiation of legal proceedings and a successful conviction. RESULTS: Multivariate logistic regression analyses showed that main proceedings were opened more often in cases where the offender was an adult (p < 0.001) or admitted his guilt (p < 0.001) and if digital traces were available (p = 0.001) or trial support (p = 0.024) present. Furthermore, the combined occurrence of medical documentation and victim disclosure was related to a higher probability of opening main trials. CONCLUSION: These findings underline how challenging the successful persecution of an offender in cases of child abuse is.

Narrative review: food as medicine across the pediatric age continuum.

PURPOSE OF REVIEW: Poor diet and food insecurity contribute to the dramatic rise in diet-related chronic disease and increasing cost of healthcare. The Food as Medicine (FAM) framework describes food-based interventions designed to prevent, manage, and treat diet-related diseases. However, FAM interventions have not been widely implemented or evaluated in pediatric populations, so critical questions remain about their optimal delivery and design, efficacy, and funding opportunities. We have reviewed the recent literature and offer insights into potential funding and implementation strategies for pediatric healthcare providers. RECENT FINDINGS: Data from adult and population-level interventions provide evidence that FAM interventions positively impact diet quality, food security, health outcomes, and healthcare utilization and cost in adults and households with children. Evidence from recent pediatric-based FAM interventions and population data from recent changes to federal nutrition programs support the use of food-based interventions to improve child diet quality, food insecurity, and potentially impact long-term health and healthcare utilization and cost. SUMMARY: Applying the entire spectrum of evidence-based FAM interventions in pediatric settings from prenatal to adolescent stages will offer the greatest opportunity to ensure all children have access to enough healthful food so they can achieve their highest potential in life.

Measuring social exclusion and its distribution in England.

BACKGROUND: Social exclusion is a multidimensional concept referring processes which restrict the ability of individuals or groups to participate fully in society. While social exclusion has been used to explore patterns of disadvantage, it has been difficult to measure. Thus, we aimed to use population-based data to measure social exclusion and its constituent domains and to describe its distribution in England. METHODS: We used data from Understanding Society in 2009/2010 develop a multidimensional measurement approach, replicated in 2018/2019. We defined five domains of social exclusion from the literature and expert consultation: material, relational, political, digital, and structural. In both waves, we identified measures for each domain, then conducted principal component analysis to identify the components. We generated domain scores and an overall social exclusion score. We described the distribution of social exclusion and its domains by sex, region, age, and ethnicity. RESULTS: We found the level of social exclusion was higher in the youngest age group and decreased by age. We found elevated levels of overall social exclusion for ethnic minoritised groups including African, Arab, and Caribbean groups compared to White British groups. We found distinct patterns within each domain. DISCUSSION: We developed an overall measure of social exclusion with five domains, and finding distinct patterns of social exclusion by age, ethnicity, and region which varied across domain. These findings suggest that attention should be paid to the separate domains due to different population distributions. This measurement approach moves beyond conceptual discussions of social exclusion and demonstrates the utility of a quantitative measure of social exclusion for use in health and social research.

Vaccinating with Valor: A Risk Preventive Model to Explain Factors in Parents' Choice to Vaccinate Their Children for COVID-19.

Childhood immunization can effectively control and prevent infectious diseases; however, not all parents choose to vaccinate their children against vaccines, including COVID-19. This study aimed to determine potential factors influencing people's willingness to vaccinate their children. An online survey was conducted with 509 adult parents/guardians of children to test our hypotheses. Based on the TPB model with the RISP model as the antecedent, results indicated that people's systematic risk information processing, trust in science, and concerns about the disease positively influenced their cognitive structure, further impacting their attitude toward vaccinating their children. The results also verified that attitude toward vaccination and perceived behavioral control are both significant predictors of parents/guardians' intention to vaccinate their children. The results contribute to health risk communicators creating effective strategies to better communicate with adults and increase intentions to vaccinate their children.

Pediatric produce prescription initiatives in the U.S.: a scoping review.

BACKGROUND: To describe pediatric Produce Prescription (PRx) interventions and their study designs, outcomes, and opportunities for future research. METHODS: A scoping review framework was used to describe PRx interventions published between January 2000 and September 2023. Articles from online databases were uploaded into Covidence. Data on study characteristics, outcomes of interest (health, food insecurity (FI), nutritional and culinary efficacy, and fruit and vegetable (F/V) consumption), and feasibility were extracted. The Mixed Methods Appraisal Tool (MMAT) was used for quality assessment. RESULTS: 19 articles met inclusion criteria. Ten studies were quantitative, five were qualitative, and four used mixed-methods. Interventions included food vouchers (n = 14) or food box/pantries (n = 5). Four studies allowed food items in addition to F/Vs. Six studies measured changes in FI and five reported a statistically significant decrease. Seven studies measured changes in F/V consumption and five reported a statistically significant increase. One study reported a statistically significant reduction in child BMI z-score. Most studies reported high feasibility. Few studies used high-quality methods. CONCLUSIONS: Pediatric PRx interventions show promising potential to reduce FI and improve diet quality and health-related outcomes. Future studies should utilize rigorous study designs and validated assessment tools to understand the impact of pediatric PRx on health. IMPACT: This work offers a summary of programmatic outcomes including retention, redemption, incentives, nutrition education, study design and quality limitations to help inform future work. We found positive impacts of pediatric produce prescriptions (PRx) on FI, F/V consumption, and nutritional knowledge and culinary skills. More high-quality, rigorous studies are needed to understand the best delivery and design of PRx and their impact on child behavior and health outcomes. This work provides support for the need for rigorous studies and the potential for PRx to play a role in multi-pronged strategies that address pediatric FI and diet-related disease.

Prevalence and risk factors for secondary hyperparathyroidism (SHPT) in patients undergoing bariatric surgery.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) after bariatric surgery has significant adverse implications for bone metabolism, increasing the risk for osteoporosis and fracture. Our aim was to characterize prevalence and identify risk factors for SHPT in bariatric surgery patients. METHODS: We performed a single-institution, retrospective chart review of patients who underwent bariatric surgery from June 2017 through December 2021. Demographic and clinical data were collected, including serum parathyroid hormone, calcium, and vitamin D3 at enrollment and 3, 6, and 12-months postoperatively. Chi-square or Fisher's exact tests were used to analyze categorical data and Mann-Whitney U test for continuous data. Multivariable analysis using binomial logistic regression assessed risk factors for SHPT. P-values ≤ 0.05 were considered significant. RESULTS: 350 patients were analyzed. SHPT prevalence at any time point was 72.9%. 65.8% had SHPT at enrollment; 45.9% resolved with intensive vitamin supplementation; and 19.7% had recurrent SHPT. New-onset SHPT occurred in 8.6%. Persistent SHPT was present in 42.4% at 1-year. Baseline SHPT correlated with black race and T2DM. SHPT at any time point correlated with T2DM and higher baseline BMI. 1-year SHPT correlated with RYGB, depression, and longer time in program. SHPT was not correlated with %TBWL at any time point. In patients with SHPT, vitamin D3 deficiency prevalence was significantly higher at baseline (77.0%) compared to all post-bariatric time points (16.7%, 17.3%, and 23.1%; P < 0.0001). CONCLUSIONS: SHPT is highly prevalent in patients with obesity seeking weight loss surgery. 42% had persistent SHPT at 1-year despite appropriate vitamin supplementation. Current vitamin D3 and calcium supplementation protocols may not effectively prevent SHPT in many post-bariatric patients. Low prevalence of concomitant vitamin D3 deficiency with SHPT after bariatric surgery suggests that there may be alternative mechanisms in this population. Further studies are needed to develop effective treatment strategies to mitigate the adverse effects of bariatric surgery on bone metabolism.

Urinary incontinence in women who have undergone bariatric surgery.

INTRODUCTION: Obesity is a known risk factor for urinary incontinence (UI). As bariatric surgery can result in significant and sustainable weight loss, many chronic diseases closely linked to obesity have likewise shown improvement after surgical weight loss. We propose that bariatric surgery may significantly improve obesity-related UI symptoms as well as improve quality of life. METHODS AND PROCEDURES: This is an interim analysis of an ongoing, prospective, single-institution observational study looking at UI in women enrolled in a bariatric surgery program. Participants completed the Pelvic Floor Distress Inventory (PFDI-20), International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), King's Health Questionnaire (KHQ), and Patient Global Impression of Improvement (PGI-I). Questionnaires were administered upon enrollment, pre-operatively, and at 3, 6, and 12 months post-operatively. Demographic data were collected at each interval and analyzed with descriptive statistics. RESULTS: At analysis, 108 patients had enrolled in the study and 60% had progressed to surgery. We analyzed the following surveys: enrollment (n = 108), pre-operative (n = 43), 3-month (n = 29), 6-month (n = 26), and 1-year (n = 27). Mean BMI decreased from 49.8 to 31.1 at 1-year. All surveys showed significant improvement in UI symptoms over time. Overall, UI symptoms (PDFI-20) are correlated with BMI at time of survey and %TBWL (p = 0.03, p = 0.019). Additionally, perception of symptom improvement with surgery (PGI-I) improved over time (3-month p = 0.0289, 6-month p = 0.0024, 12-month p = 0.0035). Quality of life related to UI symptoms (KHQ) significantly improved after surgery (p = 0.0047 3-month, p = 0.0042 6-month, p = 0.0165 1-year). CONCLUSIONS: Although the relationship is complex and likely depends on many factors, weight loss after bariatric surgery is associated with improvement in UI symptoms and UI-related quality of life. Bariatric surgery can play a role in the long-term treatment of UI in women with obesity that may negate the need for further invasive UI procedures.

Public perspectives on inequality and mental health: A peer research study.

INTRODUCTION: Associations between structural inequalities and health are well established. However, there is limited work examining this link in relation to mental health, or that centres public perspectives. This study explores people's experience and sense-making of inequality in their daily lives, with particular consideration of impacts on mental health. METHODS: We conducted a peer research study. Participants had to live in one of two London Boroughs and have an interest in inequalities and mental health. Using social media, newsletters, local organisations and our peer researchers' contacts, we recruited 30 participants who took photos representing their experience of inequality and discussed them during semi-structured interviews. Data were analysed using reflexive thematic analysis. RESULTS: Three themes were identified in this study: (1) inequalities are unjust, multilayered and intertwined with mental health. Accounts demonstrated a deep understanding of inequalities and their link to mental health outcomes, describing inequalities as 'suffering' and 'not good for anyone'. Financial, housing, immigration and healthcare problems exacerbated poor mental health, with racism, gender-based violence and job loss also contributing factors for both poor mental health and experiences of inequality; (2) inequalities exclude and have far-reaching mental health consequences, impacting personal sense of belonging and perceived societal value and (3) moving forwards-addressing long-standing inequality and poor public mental health necessitated coping and resilience strategies that are often unacknowledged and undervalued by support systems. CONCLUSION: Lived experience expertise was central in this study, creating an innovative methodological approach. To improve public mental health, we must address the everyday, painful structural inequalities experienced by many as commonplace and unfair. New policies and strategies must be found that involve communities, redistributing resources and power, building on a collective knowledge base, to coproduce actions combatting inequalities and improving population mental health. PATIENT OR PUBLIC CONTRIBUTION: This study was peer-led, designed and carried out by researchers who had experiences of poor mental health. Six authors of the paper worked as peer researchers on this study.

Building capacity for citizen science communication of water quality risks: Exploring the enhancement of the communication infrastructure in Letcher County, Kentucky.

In the coal mining regions of Eastern Kentucky, access to potable water has been diminished due to industrial pollution and aging infrastructure. Current communications regarding contaminated water are often too inaccessible and too infrequent to appropriately address the issues in target communities. To explore possible improvements to the community's communication infrastructure, the researchers explored what types of stories should be used to communicate about water quality risks, who should communicate about these stories, and how these stories should be communicated. Researchers enlisted a key community member to conduct 24 individual interviews with community members, using snowball sampling. Open and axial coding was used to conduct a constant comparative analysis of the data for emergent themes. Analyzing the verbatim interviews, the researchers concluded communication infrastructure should be enhanced to engage the public about water quality risks. Risk messaging should share water quality information through stories that are designed to be easily digested and frequently distributed using laypeople's terms, visuals, graphs, and maps. These stories should be shared using an integrated communication infrastructure where key community storytellers, such as local news, social media, and interstitial agents, work together to share risk information across platforms and channels.

Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3.

BACKGROUND: The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour. METHODS: The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS. RESULTS: Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31). CONCLUSIONS: In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC. CLINICAL TRIAL: FIRE-3 (NCT00433927).

Fear of fatness and desire for thinness as distinct experiences: A qualitative exploration.

OBJECTIVE: The pursuit of thinness and fear of gaining weight have been found to play an important role in eating disorder symptomatology. While these dimensions have typically been considered conjointly, emerging evidence suggests they may be distinct dimensions. The aim of this study was to explore the subjective experiences of fear of fatness and drive for thinness in young women with body image concerns. METHOD: Young women endorsing weight concerns (N = 29, mean age = 20.86, SD = 2.70 years) were interviewed and asked to describe an experience of fear of fat and drive for thinness, respectively. RESULTS: Qualitative analysis was conducted and identified four themes: (1) precipitating events; (2) physiological, emotional, cognitive, and proprioceptive experiences; (3) coping strategies; and (4) sociocultural influences. While similarities emerged, the experiences of fear of fatness, and of drive for thinness also evidenced clear differences situating the former in the context of fear-based avoidance patterns, and the latter in approach-based reward models. DISCUSSION: These findings provide additional support for the usefulness of considering fear of fat and drive for thinness as distinct constructs. Further research examining the contributions of each of these constructs to eating pathology is warranted.

Conceptualising public mental health: development of a conceptual framework for public mental health.

BACKGROUND: Numerous determinants have been linked to public mental health; however, they have not been brought together in a comprehensive conceptual framework. The goal of this work was to bring together academic research, practitioner expertise, and public perspectives to create a public mental health conceptual framework. METHODS: The development process proceeded in four stages. First, we identified a comprehensive list of potential determinants through a state-of-the-art academic literature review, grey literature review, and created mind maps created by peer researchers. Next, we conducted in-person workshops, consultations, and an online survey with academics, practitioners, policy makers, and members of the public to review the potential determinants, nominate additional determinants, and prioritise determinants by importance for understanding public mental health. This iterative process resulted in the final list of determinants contained in the framework. We then conducted rapid reviews to define each determinant and to identify key research, interventions, and resources. Finally, we worked with a design team to visualise the conceptual framework as an online tool and printable infographic. RESULTS: We found substantial overlap between sources reflecting a shared understanding of the key drivers of public mental health. The unique determinants that emerged from each data source highlighted the importance of using multiple sources to create a comprehensive model. 72 potential determinants were prioritised through stakeholder consultations, resulting in a final list of 55 determinants and organised into four levels: individual, family, community, and structural. CONCLUSIONS: This is the most complete conceptual framework for public mental health to date, bringing together academic research, policy and practitioner views, and lived experience perspectives. The co-production processes and tools we used provides a template for researchers looking to include multiple perspectives in their research. The conceptual framework draws together current knowledge on each determinant, but also highlights areas where further research is needed to better understand the relationship between each factor and mental health, which can inform the research agenda. This online tool and infographic can be used by practitioners to identify interventions for promoting mental health, and by the general public as a resource to increase awareness of the broad factors which shape public mental health.

Partner influences, breastfeeding, and body image and eating concerns: An expanded biopsychosocial model.

BACKGROUND: Recent research among postpartum women has considered body image and eating attitudes as well as exclusive breastfeeding within common theoretical models. However, these efforts have so far neglected to include partner-related constructs, which constitutes an important gap. Thus, the aim of this study was to examine an integrated model of body image and eating concerns, and exclusive breastfeeding among mothers of infants six months and younger, that included partner appearance influences as well as general postpartum support. METHODS: A sample of new mothers (N = 156), aged 20-47 years, mean = 32.7 (SD = 4.7) years, reported on postpartum partner support and appearance pressures, thin-ideal internalization and body dissatisfaction, symptoms of disordered eating, depression, breastfeeding self-efficacy and exclusive breastfeeding. Path analyses were conducted to test the hypothetical model. RESULTS: Findings revealed that the final model was a good fit to these data. Postpartum partner support was associated with lower depression and higher breastfeeding self-efficacy, through which it was related to higher reports of exclusive breastfeeding and lower eating disorder symptoms. In addition, partner appearance pressures and thin-ideal internalization were associated with higher body dissatisfaction, and thin-ideal internalization was also related to lower breastfeeding self-efficacy. CONCLUSIONS: Partner influences may be important to account for in models of body image and eating concerns among postpartum women, and exclusive breastfeeding, and further research on ways in which they can support mothers of young infants is warranted.

Changes in Hydrocodone Misuse Exposures Reported to U.S. Poison Centers Following Rescheduling in 2014.

BACKGROUND: In 2014, the Drug Enforcement Administration rescheduled hydrocodone combination products to Schedule II to reduce nonmedical use and diversion. METHODS: The impact of rescheduling was assessed using quarterly data from 2011 through 2019 from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program and IQVIATM Longitudinal Prescription Data. Trends and immediate changes in prescriptions dispensed and misuse exposures before and after rescheduling involving hydrocodone, oxycodone, and other Schedule II opioid analgesics were calculated using segmented regression. RESULTS: Hydrocodone prescriptions were stable pre-rescheduling, decreased by 2.7% (95% CI: -3.6%, -1.8%, p < 0.0001) per quarter post-rescheduling. Misuse exposures involving hydrocodone were decreasing by 3.2% (95% CI: -3.9%, -2.4%, p < 0.0001) per quarter pre-rescheduling and decreased by 4.9% (95% CI: -5.5%, -4.2%, p < 0.0001) post-rescheduling. Immediate decreases in hydrocodone prescriptions and misuse exposure rates in 2014Q4 compared to 2014Q3 were significant and different from oxycodone or other Schedule II opioids. Schedule II opioid analgesics prescriptions in aggregate were stable prior to rescheduling, decreased by 10.8% (95%CI: -14.0%, -7.6%, p < 0.0001) immediately after the rescheduling, and decreased by 2.3% per quarter (95% CI: -3.1%, -1.5%, p < 0.0001) subsequently. Misuse exposures involving these opioids were decreasing by 3.3% (95% CI: -4.1%, -2.5%, p < 0.0001) prior to rescheduling then by 2.8%, (95% CI: -3.4%, -2.2%, p < 0.0001) after rescheduling. The immediate change in misuse was not significant. CONCLUSIONS: Rescheduling corresponded with changes in hydrocodone prescribing and misuse not offset by increases in other Schedule II opioid analgesics. Misuse exposures for hydrocodone and comparators were decreasing prior to rescheduling with little change post-intervention.

Cones and sleeves present good survival and clinical outcome in revision total knee arthroplasty: a meta-analysis.

PURPOSE: The fixation of revision total knee arthroplasties (rTKA) tends to be difficult, leading to a reduction in implant survival. One option for achieving a more stable anchorage is to use metaphyseal cones and sleeves. The objective of the present paper is to provide a current comparative meta-analysis on survival and clinical results of cones vs. sleeves, with a differentiation between the short- and long-term outcome. METHODS: A search of the literature was conducted systematically to include original papers from 2010 to June 2021. The following parameters were taken into account: revision for aseptic loosening, revision for any reason, periprosthetic joint infections (PJI), KSS as well as KSFS. Studies with a mean follow-up of at least 60 months were defined to be long-term follow-up studies (LT). All other studies were included in the short-term (ST) study analysis. A pooled incidence was used as a summary statistic using a random intercept logistic regression model. RESULTS: The present meta-analysis included 43 publications with 3008 rTKA. Of these, 23 publications with 1911 cases were allocated to the sleeve group (SG) and 20 papers with 1097 cases to the cone group (CG). CG showed overall numerically higher complication rates in short- and long-term follow-up, compared with SG. Aseptic loosening occurred at a rate of 0.4% in SG (LT) and 4.1% in CG (LT) (p = 0.09). Periprosthetic joint infection (PJI) was more frequent in the cone group (7% in ST and 11.7% in LT) than in the sleeve group (3.4% in ST and 4.9% in LT, p = 0.02 both). The total revision rate was 5.5% in SG (LT) and 14.4% in CG (LT) (p = 0.12). The clinical scores were also comparable between the two groups. Hinged prothesis were used more frequent in the cone group (ST p < 0.001; LT p = 0.10), whereas CC type protheses were used more frequently in the sleeve group (ST p < 0.001; LT p < 0.11). CONCLUSIONS: This meta-analysis takes into account the longest follow-up periods covered to date. Both cones and sleeves represent a reliable fixation method in the case of severe bone loss in rTKA, although the higher rate of PJI after cone fixation remains a source of concern. A metaphyseal fixation of hinged implants should be taken into account. LEVEL OF EVIDENCE: II (meta-analysis).

Monitoring and treating hypoglycemia during meal-based rapid nutritional rehabilitation in patients with extreme anorexia nervosa.

PURPOSE: Hypoglycemia, a complication of prolonged starvation, can be life-threatening and is presumed to contribute to the high mortality of anorexia nervosa. Furthermore, early refeeding in severe anorexia nervosa can precipitate paradoxical post-prandial hypoglycemia. Few studies have analyzed the course of hypoglycemia during nutritional rehabilitation in patients with extremely low-weight anorexia nervosa. No standard practice guidelines exist and recommended strategies for managing hypoglycemia (i.e., nasogastric feeds, high-fat diets) have limitations. METHODS: This cohort study assessed prevalence and correlates of hypoglycemia in 34 individuals with very low body mass index (BMI < 14.5 kg/m2) anorexia nervosa treated in an intensive eating disorders program with an exclusively meal-based rapid weight gain nutritional protocol. Hypoglycemia was monitored with frequent point of care (POC) glucose testing and treated with oral snacks and continuous slow intravenous 5% dextrose in 0.45% saline (IV D5 1/2 NS) infusion. RESULTS: POC hypoglycemia was detected in 50% of patients with highest prevalence noted on the day of admission. Hypoglycemia resolved during the first week of hospitalization in most cases and was generally asymptomatic. Seven patients (20.6%) experienced at least one episode of severe hypoglycemia with POC glucose < 50 mg/dl. Lower admission BMI was associated with higher likelihood of developing hypoglycemia and longer duration of hypoglycemia. CONCLUSION: Meal-based management of hypoglycemia supplemented by continuous IV D5 1/2 NS appears a viable alternative to alternate strategies such as enteral tube feeding. We discuss recommendations for hypoglycemia monitoring during nutritional rehabilitation and directions for future research. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Mutational profiles of metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab before and after secondary resection (AIO KRK 0306; FIRE-3).

Secondary resection of metastases is recommended in metastatic colorectal cancer (mCRC). Data describing changes in mutational profiles of corresponding primary tumor and metastatic tissue after conversion treatment are limited. Next generation sequencing was performed in formalin-fixed mCRC samples from patients of the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab) before treatment start (baseline) and after secondary resection of metastases (post baseline). Changes of mutational profiles and tumor mutational burden (TMB) were assessed within a post-hoc analysis. Median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between treatment arms. Paired tumor samples were obtained from 25 patients (19 RAS wild-type, 6 RAS mutant by pyrosequencing). ORR (92.0% vs 58.0%) and OS (60.8 vs 35.4 months, hazard ratio = 0.39 [95% CI 0.14-1.12], P = .08) were higher for patients receiving cetuximab. After conversion therapy, 56 alterations (42 in the cetuximab and 14 in the bevacizumab arm) were newly observed in 18 patients (9 each treated with cetuximab or bevacizumab). Gains (n = 21) and losses (n = 21) of alterations occurred during cetuximab-based treatment, while mainly gains of alterations occurred during bevacizumab (n = 10). Three of nine patients treated with cetuximab that presented a change of mutational profiles, developed resistance to cetuximab. Mutational profiles were largely comparable before and after treatment with anti-VEGF or anti-EGFR directed monoclonal antibodies after secondary resection. Mutations associated with resistance to anti-EGFR antibodies were observed in only one-third of patients.

"Waste not and stay at home" evidence of decreased food waste during the COVID-19 pandemic from the U.S. and Italy.

The COVID-19 pandemic has profoundly disrupted household food purchasing and preparation, including elements identified as important drivers of household food waste. The two main aims of this study were (1) to examine changes in food waste behaviors since the start of the COVID-19 pandemic in the U.S. and Italy; and (2) to investigate potential predictors of food waste behavior, including avoidance of supermarkets, increased home cooking, and increased role of health concerns in food choices. A sample of n = 478 (79% female) individuals from the U.S., mean (SD) age = 30.51 (10.85), and n = 476 individuals from Italy, (78% female), mean (SD) age = 33.84 (12.86), completed an online survey between April 8th and April 28th 2020. Just under half of respondents (49%) reported decreased food waste since the start of the pandemic. Rates were significantly higher among the U.S. sample (61.5%, n = 294) compared to the Italian sample (38%, n = 180). Controlling for the time since restrictions were introduced, age, gender, and perceived financial security, logistic regression revealed greater reduction in food waste since the beginning of the pandemic for U.S. individuals relative to participants from Italy (OR = 0.47, p < .001). In addition, increased importance of health concerns when making food choices (OR = 1.34, p < .005) as well as more frequent cooking (OR = 1.35, p < .001), and greater avoidance of supermarkets (OR = 1.15, p = .049) were associated with greater probability of less food waste. Scarcity and greater reliance on cooking may encourage individuals to reflect on food waste practices. Further research should explore how these factors may be targeted to reduce food waste beyond the pandemic.

Immune Thrombocytopenic Purpura Splenectomy in the Context of New Medical Therapies.

BACKGROUND: As medical therapy improves, splenectomy has been relegated to third- or fourth-line therapy for immune thrombocytopenic purpura (ITP) in many hematologic practices. However, these medications have well-known associated morbidity and changes in treatment algorithms may affect the timing and degree of response to splenectomy as well as complications in heavily treated ITP patients. MATERIALS AND METHODS: This is a retrospective study of consecutive patients who underwent ITP splenectomy from January 1994 to June 2017. Nonresponders after splenectomy and those with recurrent disease were compared to complete responders. RESULTS: The cohort included 84 patients. Median number of medications received before splenectomy was 3 (1-6). 14.3% of patients had a medication-related complication, including heart failure, adrenal insufficiency, diabetes mellitus, infection, and osteoporosis. After splenectomy, 83.5% had a complete response, 7.5% partial response, and 9% no response. Complete response was associated with response to steroids before surgery (P < 0.01). Among responders, 19% had recurrent disease, which was associated with lower platelet count at diagnosis (P < 0.01). Forty-four patients (52.0%) had nonelective splenectomies for persistent bleeding or dangerously low platelets despite maximal medical therapy. Ten patients had Clavien-Dindo grade II or higher surgical complications (11.9%). Seven of these complications were related to recurrent or refractory ITP. CONCLUSIONS: Many ITP patients have complications related to medication use, and 52.0% required nonelective splenectomy despite maximal medical therapy. Earlier splenectomy may avoid medication-related complications and may reduce the complications from splenectomy. Splenectomy remains an effective and safe treatment for ITP.