Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

An Update on MR Spectroscopy in Cancer Management: Advances in Instrumentation, Acquisition, and Analysis.

MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As metabolic reprogramming is a hallmark of cancer, MRS provides valuable metabolic and molecular information for cancer diagnosis, prognosis, treatment monitoring, and patient management. This review provides an update on the use of MRS for clinical cancer management. The first section includes an overview of the principles of MRS, current methods, and conventional metabolites of interest. The remainder of the review is focused on three key areas: advances in instrumentation, specifically ultrahigh-field-strength MRI scanners and hybrid systems; emerging methods for acquisition, including deuterium imaging, hyperpolarized carbon 13 MRI and MRS, chemical exchange saturation transfer, diffusion-weighted MRS, MR fingerprinting, and fast acquisition; and analysis aided by artificial intelligence. The review concludes with future recommendations to facilitate routine use of MRS in cancer management. Keywords: MR Spectroscopy, Spectroscopic Imaging, Molecular Imaging in Oncology, Metabolic Reprogramming, Clinical Cancer Management © RSNA, 2024.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Adolescents' Love Lives: Heterogeneity in Relationship Status Trajectories and Links with Affect.

Romantic experiences are more fluid and heterogeneous during middle adolescence than at any other life stage, but current understanding of this heterogeneity and flux is limited because of imprecise measurement. A sample of 531 adolescents (55% female; 28% non-Hispanic White; 32% Black; 27% Hispanic; 14% Other) recruited from an ongoing birth cohort study (Mean age = 16.7 years, SD = 0.358), was administered bi-weekly diaries over 52 weeks to prospectively record transitions in and out of romantic and sexual relationships and to assess links with positive affect (frequency of happiness) and negative affect (frequency of sadness). Relationship statuses considered included not only dating, but also liminal and asymmetrical statuses such as talking/flirting and crushes. Latent profile analyses revealed six relationship status trajectories, or love life profiles, based on the number of intra-year partners and on the extent of involvement in each of the relationship statuses. Approximately half of teens either were in stable dating relationships or uninvolved romantically during the year; however, half experienced variable levels of flux in their love lives. Relationship instability, not romantic involvement per se, was associated with higher levels of sadness and lower levels of happiness. Snapshots of teen romantic involvement based on one or two points in time obscure the extent of relationship heterogeneity and flux and how relationship status trajectories are associated with positive and negative affect.

Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals.

PURPOSE: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants. METHODS: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies. RESULTS: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. CONCLUSION: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders.

Characteristics and Predictors of Late Right Heart Failure After Left Ventricular Assist Device Implantation.

Late right heart failure (LRHF) following left ventricular assist device (LVAD) implantation remains poorly characterized and challenging to predict. We performed a multicenter retrospective study of LRHF in 237 consecutive adult LVAD patients, in which LRHF was defined according to the 2020 Mechanical Circulatory Support Academic Research Consortium guidelines. Clinical and hemodynamic variables were assessed pre- and post-implant. Competing-risk regression and Kaplan-Meier survival analysis were used to assess outcomes. LRHF prediction was assessed using multivariable logistic and Cox proportional hazards regression. Among 237 LVAD patients, 45 (19%) developed LRHF at a median of 133 days post-LVAD. LRHF patients had more frequent heart failure hospitalizations ( p < 0.001) alongside other complications. LRHF patients did not experience reduced bridge-to-transplant rates but did suffer increased mortality (hazard ratio 1.95, 95% confidence interval [CI] 1.11-3.42; p = 0.02). Hemodynamically, LRHF patients demonstrated higher right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR), but no difference in pulmonary arterial wedge pressure. History of early right heart failure, blood urea nitrogen (BUN) > 35 mg/dl at 1 month post-LVAD, and diuretic requirements at 1 month post-LVAD were each significant, independent predictors of LRHF in multivariable analysis. An LRHF prediction risk score incorporating these variables predicted LRHF with excellent discrimination (log-rank p < 0.0001). Overall, LRHF post-LVAD is more common than generally appreciated, with significant morbidity and mortality. Elevated PVR and precapillary pulmonary pressures may play a role. A risk score using early right heart failure, elevated BUN, and diuretic requirements 1 month post implant predicted the development of LRHF.

Adolescent Partnership Quality and Emotional Health: Insights from an Intensive Longitudinal Study.

Prior research has documented an association between adolescents' romantic experiences and poor emotional health. However, lack of intensive longitudinal measurement and an emphasis on negative affect have limited understanding about the extent to which adolescent relationship quality influences the emotional health of adolescents in partnerships, including the potential benefits of high-quality partnerships. Previous research has also been limited in its ability to account for factors that select adolescents into lower or higher quality partnerships. Using biweekly intensive longitudinal data from the mDiary Study of Adolescent Relationships linked to six waves of birth cohort data from the Fragile Families and Child Wellbeing Study, this paper uses multilevel mixed-effects models to address three questions: (1) How are changes in partnership quality (defined as validation, frequency of disagreements, and global quality) associated with changes in both positive and negative affect; (2) Do observed associations persist net of factors that potentially select adolescents into lower or higher quality partnerships (e.g., childhood family experiences); and (3) Do associations between partnership quality and affect differ by gender? Results show that higher quality partnerships are associated with both decreases in negative affect and increases in positive affect. There were no significant gender differences on average. The study's findings highlight the importance of partnership quality as a key source of temporal variation in adolescents' emotional states.

Financial Toxicity and Its Association With Prostate and Colon Cancer Screening.

BACKGROUND: The term "financial toxicity" or "hardship" is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening. METHODS: This cross-sectional survey-based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively. RESULTS: Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867-0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941-0.998; P=.039). CONCLUSIONS: Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.

What Is Digital Parenting? A Systematic Review of Past Measurement and Blueprint for the Future.

Concerns about parenting adolescents are not new, but the rapid diffusion of digital technologies has heightened anxieties over digital parenting. Findings are decidedly mixed regarding the impact of digital technologies on adolescent well-being, and parents are left to navigate their concerns without an empirically based road map. A missing link for understanding the state of the science is a clear characterization of how digital parenting is measured, including an evaluation of which areas demand an outsized share of scientific attention and which have been overlooked. To address this gap, we undertook two interdisciplinary systematic reviews of the digital-parenting literature and characterized measurement across (a) quantitative surveys (n = 145 studies) and (b) qualitative focus groups, interviews, codesign studies, and user studies (n = 49). We describe previously popular areas of survey measurement that are of decreasing relevance to parenting of digital spaces (e.g., co-use, hovering). We likewise highlight areas that have been overlooked, including consideration of positive uses of digital technologies, acknowledgment of bidirectional influence, and attention to heterogeneity among families and to extraparental social ecologies of support and monitoring. We provide recommendations for the future of digital-parenting research and propose a more comprehensive approach to measuring how modern adolescents are parented.

Adolescents' Partner Search in the Digital Age: Correlates and Characteristics of Relationships Initiated Online.

Digital technology and social media platforms have transformed the ways adolescents communicate and cultivate romantic relationships, but few studies consider whether relationships initiated online are less salutary than those formed in person. A sample of 531 adolescents (Mean age = 16.7 years, SD = 0.358; 55% female) was recruited from an ongoing birth cohort study and administered bi-weekly diaries over a year to evaluate the circumstances associated with adolescents' romantic relationship formation and relationship quality. Two-thirds of respondents initiated one or more romantic relationships during the study, of which 15% were initiated online. Girls who did not fit in well at school and who had difficulty making friends were more likely to initiate romantic relationships online than their more sociable peers who fit in well at school; for boys, however, access to mobile devices increased the odds that romantic relationships were initiated online. The diaries captured considerable flux in the evolution of romantic relationships, but there was limited evidence that relationships initiated online involved greater risks, with the notable exception of greater age asymmetry.

Association of Race With Cancer-Related Financial Toxicity.

PURPOSE: We investigated the association between race and FT among previous patients with cancer. Studies show that patients with cancer experience financial toxicity (FT) because of their cancer treatment. METHODS: Data on individuals with a cancer history were collected in this cross-sectional study during 2012, 2014, and 2017, from the US Health Information National Trends Survey. This survey is conducted by mail with monetary compensation as an incentive. We specifically assessed responses to two questions: Has cancer hurt you financially? Have you been denied health insurance because of cancer? Multivariable logistic regression analyses were used to assess the associations between these questions and race. RESULTS: Of 10,592 individuals participating, 1,328 men and women (12.5%) with a cancer history were assessed. Compared with Blacks, Whites were found to have a higher rate of insurance (95.4% v 90.0%), were more likely to receive cancer treatment (93.9% v 85%), and had a higher rate of surgical treatment than Blacks (77% v 60%), Hispanics (55%), and others (77%, 60%, 55%, and 74.2%, respectively, P < .001). On multivariable analysis, Blacks were more than five times as likely to be denied insurance (odds ratio, 5.003; 95% CI, 2.451 to 10.213; P < .001) and more than twice as likely to report being hurt financially because of cancer (odds ratio, 2.448; 95% CI, 1.520 to 3.941; P < .001) than Whites. Of all cancer groups analyzed (genitourinary, gynecologic, gastrointestinal, and breast), genitourinary malignancies were the only group in which the rate of reporting being hurt financially varied in a statistically significant manner (Whites 36.7%, Hispanics 62.5%, and Blacks 59.3%, P = .004). CONCLUSION: Our data suggest that race is significantly associated with FT because of cancer. Awareness of racial inequality with regards to FT should be raised among health care workers.

Angiotensin Receptor-Neprilysin Inhibition Improves Blood Pressure and Heart Failure Control in Left Ventricular Assist Device Patients.

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients.

Weight Gain in Incarcerated Individuals Living With HIV After Switching to Integrase Strand Inhibitor-Based Therapy.

INTRODUCTION: Post-marketing data have demonstrated the potential for weight gain with integrase inhibitors (INSTI) use in antiretroviral (ART) therapy. METHODS: A medical chart review evaluated virologically suppressed adult prisoners living with HIV and on a non-INSTI regimen before switching or adding an INSTI. Primary outcome assessed average weight change; Secondary outcomes evaluated change in body mass index (BMI), fasting lipid panel, and development of hypertension. Statistical analysis included paired t-tests and descriptive statistics. RESULTS: Among 103 study participants, 95% were men with a median age of 44 years. Each INSTI was associated with an average weight increase of 4.3 kg (p < 0.025). Bictegravir and dolutegravir were also associated with significant increases in BMI, +1.4kg/m2 and +2.8kg/m2, respectively (p = 0.011 and p = 0.001). CONCLUSION: Patients receiving HIV care in a correctional setting and on INSTI-based treatments experienced weight gain and increases in BMI. Future research should focus on the mechanism of development and interventions to prevent weight gain.

Impact of medical assistance in dying (MAiD) on family caregivers.

Medical assistance in dying (MAiD) is a globally polarising topic which often sparks debate surrounding the ethical and moral dilemmas that arise with a life-ending intervention. To gain a better understanding of this intervention, it is important to explore the experience of those most intimately affected by MAiD. Family caregivers of those with a terminal illness are the backbone of the healthcare and support team, often providing a substantial amount of informal care while at the same time coping with their own distress and anticipatory grief. However, we know the least about how MAiD impacts the psychosocial well-being of these same individuals. The aim of this article is to explore the experience of MAiD from the family caregiver perspective, namely their beliefs and opinions about the intervention, how the process of MAiD impacts them, how the intervention shapes their view of their loved one's quality of death, and the psychosocial outcomes after the passing of their loved one. Beyond the literature, challenges within both the clinical and research realms will be discussed and future directions will be offered. While MAiD is currently legal in only a small number of countries, a better understanding of the impact of MAiD will help inform policy and legislation as they are developed in other jurisdictions. Further, this article aims to inform future research and clinical interventions in order to better understand and support those seeking MAiD and their families.

The Social Significance of Interracial Cohabitation: Inferences Based on Fertility Behavior.

Interracial couples cohabit at higher rates than same-race couples, which is attributed to lower barriers to interracial cohabitation relative to intermarriage. This begs the question of whether the significance of cohabitation differs between interracial and same-race couples. Using data from the 2006-2017 National Survey of Family Growth, we assessed the meaning of interracial cohabitation by comparing the pregnancy risk, pregnancy intentions, and union transitions following a pregnancy among women in interracial and same-race cohabitations. The pregnancy and union transition behaviors of women in White-Black cohabitations resembled those of Black women in same-race cohabitations, suggesting that White-Black cohabitation serves as a substitute to marriage and reflecting barriers to the formation of White-Black intermarriages. The behaviors of women in White-Hispanic cohabitations fell between those of their same-race counterparts or resembled those of White women in same-race cohabitations. These findings suggest that White-Hispanic cohabitations take on a meaning between trial marriage and substitute to marriage and support views that Hispanics with White partners are a more assimilated group than Hispanics in same-race unions. Results for pregnancy intentions deviated from these patterns. Women in White-Black cohabitations were less likely than Black women in same-race cohabitations to have an unintended pregnancy, suggesting that White-Black cohabitations are considered marriage-like unions involving children. Women in White-Hispanic cohabitations were more likely than White and Hispanic women in same-race cohabitations to have an unintended pregnancy, reflecting possible concerns about social discrimination. These findings indicate heterogeneity in the significance of interracial cohabitation and continuing obstacles to interracial unions.

GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma.

Disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells. Here, we demonstrated that GULP1 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequester NRF2 in the cytoplasm. In urothelial carcinoma of the bladder (UCB), silencing of GULP1 facilitated the nuclear accumulation of NRF2, led to constitutive activation of NRF2 signaling, and conferred resistance to the platinum drug cisplatin. Knockdown of GULP1 in UCB cells promoted tumor cell proliferation in vitro and enhanced tumor growth in vivo. In primary UCB, GULP1 silencing was more prevalent in muscle-invasive UCB compared to nonmuscle-invasive UCB. GULP1 knockdown cells showed resistance to cisplatin treatment. In parallel with decreased GULP1 expression, we observed increased expression of NRF2, HMOX1, and other candidate antioxidant genes in cisplatin-resistant cells. Furthermore, low or no expression of GULP1 was observed in most cisplatin nonresponder cases. Silencing of GULP1 was associated with GULP1 promoter hypermethylation in cell lines and primary tumors, and a high frequency of GULP1 promoter methylation was observed in multiple sets of primary clinical UCB samples. Together, our findings demonstrate that GULP1 is a KEAP1-binding protein that regulates KEAP1-NRF2 signaling in UCB and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.

The omentum of obese girls harbors small adipocytes and browning transcripts.

Severe obesity (SO) affects about 6% of youth in the United States, augmenting the risks for cardiovascular disease and type 2 diabetes. Herein, we obtained paired omental adipose tissue (omVAT) and abdominal subcutaneous adipose tissue (SAT) biopsies from girls with SO undergoing sleeve gastrectomy (SG), to test whether differences in cellular and transcriptomic profiles between omVAT and SAT depots affect insulin sensitivity differently. Following weight loss, these analyses were repeated in a subgroup of subjects having a second SAT biopsy. We found that omVAT displayed smaller adipocytes compared with SAT, increased lipolysis through adipose triglyceride lipase phosphorylation, reduced inflammation, and increased expression of browning/beiging markers. Contrary to omVAT, SAT adipocyte diameter correlated with insulin resistance. Following SG, both weight and insulin sensitivity improved markedly in all subjects. SAT adipocytes' size became smaller, showing increased lipolysis through perilipin 1 phosphorylation, decreased inflammation, and increased expression in browning/beiging markers. In summary, in adolescent girls with SO, both omVAT and SAT depots showed distinct cellular and transcriptomic profiles. Following weight loss, the SAT depot changed its cellular morphology and transcriptomic profiles into more favorable ones. These changes in the SAT depot may play a fundamental role in the resolution of insulin resistance.

The Practicalities and Perils of Ambulatory Assessment's Promise: Introduction to a Special Section.

Ambulatory assessment (AA) offers one of the most exciting approaches for opening the dynamic "black box" of adolescents' daily lives. In this introduction, we spotlight AA's surprisingly restricted market share within adolescent scholarship. We describe thorny challenges these intense methods can pose when conducting adolescent research "in situ" and underscore that capturing quality AA data means placing adolescents' developmental stage at the forefront. The novel research reported in this special section speaks to these challenges and underscores the promise of AA for conducting developmentally salient science. The nine articles included in the section span multiple disciplines (Sociology, Psychology, Public Health) and reflect diverse viewpoints, approaches, and theories. All provide multiple novel best-practice strategies for conducting AA scholarship with adolescents.