Identifying barriers and enablers to rigorous conduct and reporting of preclinical laboratory studies.

Use of rigorous study design methods and transparent reporting in publications are 2 key strategies proposed to improve the reproducibility of preclinical research. Despite promotion of these practices by funders and journals, assessments suggest uptake is low in preclinical research. Thirty preclinical scientists were interviewed to better understand barriers and enablers to rigorous design and reporting. The interview guide was informed by the Theoretical Domains Framework, which is a framework used to understand determinants of current and desired behavior. Four global themes were identified; 2 reflecting enablers and 2 reflecting barriers. We found that basic scientists are highly motivated to apply the methods of rigorous design and reporting and perceive a number of benefits to their adoption (e.g., improved quality and reliability). However, there was varied awareness of the guidelines and in implementation of these practices. Researchers also noted that these guidelines can result in disadvantages, such as increased sample sizes, expenses, time, and can require several personnel to operationalize. Most researchers expressed additional resources such as personnel and education/training would better enable the application of some methods. Using existing guidance (Behaviour Change Wheel (BCW); Expert Recommendations for Implementing Change (ERIC) project implementation strategies), we mapped and coded our interview findings to identify potential interventions, policies, and implementation strategies to improve routine use of the guidelines by preclinical scientists. These findings will help inform specific strategies that may guide the development of programs and resources to improve experimental design and transparent reporting in preclinical research.

Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States.

Microglia, the resident immune-competent cells of the brain, become dysfunctional in Alzheimer's disease (AD), and their aberrant immune responses contribute to the accumulation of pathological proteins and neuronal injury. Genetic studies implicate microglia in the development of AD, prompting interest in developing immunomodulatory therapies to prevent or ameliorate disease. However, microglia take on diverse functional states in disease, playing both protective and detrimental roles in AD, which largely overlap and may shift over the disease course, complicating the identification of effective therapeutic targets. Extensive evidence gathered using transgenic mouse models supports an active role of microglia in pathology progression, though results vary and can be contradictory between different types of models and the degree of pathology at the time of study. Here, we review microglial immune signaling and responses that contribute to the accumulation and spread of pathological proteins or directly affect neuronal health. We additionally explore the use of induced pluripotent stem cell (iPSC)-derived models to study living human microglia and how they have contributed to our knowledge of AD and may begin to fill in the gaps left by mouse models. Ultimately, mouse and iPSC-derived models have their own limitations, and a comprehensive understanding of microglial dysfunction in AD will only be established by an integrated view across models and an appreciation for their complementary viewpoints and limitations.

Dopaminergic lesions of the anterior cingulate cortex of rats increase vulnerability to salient distractors.

The anterior cingulate cortex (ACC) has been shown to be critical to many aspects of executive function including filtering irrelevant information, updating response contingencies when reinforcement contingencies change and stabilizing task sets. Nonspecific lesions to this region in rats produce a vulnerability to distractors that have gained salience through prior associations with reinforcement. These lesions also exacerbate cognitive fatigue in tests of sustained attention but do not produce global attentional impairments nor do they produce distractibility to novel distractors that do not have a prior association with reinforcement. To determine the neurochemical basis of these cognitive impairments, dopaminergically selective lesions of the ACC were made in both male and female Long-Evans, hooded rats prior to assessment in two attentional tasks. Dopaminergic lesions of the ACC increase the vulnerability of subjects to previously reinforced distractors and impede formation of an attentional set. Lesioned rats were not more susceptible to the effects of novel, irrelevant stimuli in a test of sustained attention as has been previously shown. Additionally, the effects of dopaminergic lesions were found to differ based on sex. Lesioned female, but not male, rats were more vulnerable than sham-lesioned females to the effects of prolonged testing and the removal of reinforcement during a test of sustained attention. Together, these data support the hypothesis that dopamine in the ACC is critical to filtering distractors whose salience has been gained through reinforcement.

Breaching Confidentiality in Genetic and Non-Genetic Cases: Two Problematic Distinctions.

Ethical questions about confidentiality arise when patients refuse to inform relatives who are at risk of a genetic condition. Specifically, healthcare providers may struggle with the permissibility of breaching confidentiality to warn patients' at-risk relatives. In exploring this issue, several authors have converged around the idea that genetic cases differ from non-genetic cases (e.g., involving a threat of violence or the spread of an infectious disease) along two related dimensions: (1) In genetic cases, the risk of harm is already present in an at-risk third party, whereas in non-genetic cases, it is not; and (2) In genetic cases, the patient does not create a risk of harm to a third party, whereas in non-genetic cases, the patient does. I argue that these distinctions do not exclusively differentiate genetic from non-genetic cases and should not bear on the permissibility of breaching confidentiality. Instead, such determinations should be based on other considerations.

Apolipoprotein E ε4 modulates astrocyte neuronal support functions in the presence of amyloid-ß.

Apolipoprotein E (APOE) is a lipid transporter produced predominantly by astrocytes in the brain. The ε4 variant of APOE (APOE4) is the strongest and most common genetic risk factor for Alzheimer's disease (AD). Although the molecular mechanisms of this increased risk are unclear, APOE4 is known to alter immune signaling and lipid and glucose metabolism. Astrocytes provide various forms of support to neurons, including regulating neuronal metabolism and immune responses through cytokine signaling. Changes in astrocyte function because of APOE4 may therefore decrease neuronal support, leaving neurons more vulnerable to stress and disease insults. To determine whether APOE4 alters astrocyte neuronal support functions, we measured glycolytic and oxidative metabolism of neurons treated with conditioned media from APOE4 or APOE3 (the common, risk-neutral variant) primary astrocyte cultures. We found that APOE4 neurons treated with conditioned media from resting APOE4 astrocytes had similar metabolism to APOE3 neurons treated with media from resting APOE3 astrocytes, but treatment with astrocytic conditioned media from astrocytes challenged with amyloid-ß (Aß), a key pathological protein in AD, caused APOE4 neurons to increase their basal mitochondrial and glycolytic metabolic rates more than APOE3 neurons. These changes were not because of differences in astrocytic lactate production or glucose utilization, but instead correlated with increased glycolytic ATP production and a lack of cytokine secretion in response to Aß. Additionally, we identified that astrocytic cytokine signatures could predict basal metabolism of neurons treated with the astrocytic conditioned media. Together, these findings suggest that in the presence of Aß, APOE4 astrocytes alter immune and metabolic functions that result in a compensatory increase in neuronal metabolic stress.

In-frame deletion of SPECC1L microtubule association domain results in gain-of-function phenotypes affecting embryonic tissue movement and fusion events.

Patients with autosomal dominant SPECC1L variants show syndromic malformations, including hypertelorism, cleft palate and omphalocele. These SPECC1L variants largely cluster in the second coiled-coil domain (CCD2), which facilitates association with microtubules. To study SPECC1L function in mice, we first generated a null allele (Specc1lΔEx4) lacking the entire SPECC1L protein. Homozygous mutants for these truncations died perinatally without cleft palate or omphalocele. Given the clustering of human variants in CCD2, we hypothesized that targeted perturbation of CCD2 may be required. Indeed, homozygotes for in-frame deletions involving CCD2 (Specc1lΔCCD2) resulted in exencephaly, cleft palate and ventral body wall closure defects (omphalocele). Interestingly, exencephaly and cleft palate were never observed in the same embryo. Further examination revealed a narrower oral cavity in exencephalic embryos, which allowed palatal shelves to elevate and fuse despite their defect. In the cell, wild-type SPECC1L was evenly distributed throughout the cytoplasm and colocalized with both microtubules and filamentous actin. In contrast, mutant SPECC1L-ΔCCD2 protein showed abnormal perinuclear accumulation with diminished overlap with microtubules, indicating that SPECC1L used microtubule association for trafficking in the cell. The perinuclear accumulation in the mutant also resulted in abnormally increased actin and non-muscle myosin II bundles dislocated to the cell periphery. Disrupted actomyosin cytoskeletal organization in SPECC1L CCD2 mutants would affect cell alignment and coordinated movement during neural tube, palate and ventral body wall closure. Thus, we show that perturbation of CCD2 in the context of full SPECC1L protein affects tissue fusion dynamics, indicating that human SPECC1L CCD2 variants are gain-of-function.

Multicenter study of pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders.

BACKGROUND: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorder [EBV(-)M-PTLD] comprises approximately 10% of M-PTLD. No large multi-institutional pediatric-specific reports on treatment and outcome are available. METHODS: A multi-institutional retrospective review of solid organ recipients diagnosed with EBV(-)M-PTLD aged ≤21 years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data. RESULTS: Thirty-six patients were identified with EBV(-)M-PTLD. Twenty-three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(-)M-PTLD, and interval from transplant to PTLD were 2.2 years (0.1-17), 14 years (3.0-20), and 8.5 years (0.6-18.3), respectively. Kidney (n = 17 [47.2%]) and heart (n = 13 [36.1%]) were the most commonly transplanted organs. Most were Murphy stage III (n = 25 [69.4%]). Lactate dehydrogenase was elevated in 22/34 (64.7%) and ≥2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B-cell lymphoma (n = 31 [86.1%]) and B-non-Hodgkin lymphoma (B-NHL) not otherwise specified (NOS) (n = 5 [13.9%]). Of nine different regimens used, the most common were: pediatric mature B-NHL-specific regimen (n = 13 [36.1%]) and low-dose cyclophosphamide, prednisone, and rituximab (n = 9 [25%]). Median follow-up from diagnosis was 3.0 years (0.3-11.0 years). Three-year event-free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease. CONCLUSIONS: EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B-NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi-institutional registry to design prospective studies. PLAIN LANGUAGE SUMMARY: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(-)M-PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B-cell lymphoma in immunocompetent pediatric patients. The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes. The impact of treatment regimen on relapse risk could not be assessed because of small numbers. In the intensive pediatric B-non-Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11 years.

"We're always an afterthought"- Designing tobacco control campaigns for dissemination with and to LGBTQ +-serving community organizations: a thematic analysis.

PURPOSE: Evidence-based health communication campaigns can support tobacco control and address tobacco-related inequities among lesbian, gay, bisexual, transgender, and queer (LGBTQ +) populations. Community organizations focused on LGBTQ + health (e.g., nonprofits, community centers, and community health centers) can be prime channels for delivering evidence-based health communication campaigns. However, it is unclear how to balance the goals of a) designing campaigns to support broad adoption/uptake and b) adaptation addressing the needs of diverse communities and contexts. As part of an effort to support "designing for dissemination," we explored the key challenges and opportunities staff and leaders of LGBTQ + -serving community organizations encounter when adopting or adapting evidence-based health communication campaigns. METHODS: A team of researchers and advisory committee members conducted this study, many of whom have lived, research, and/or practice experience with LGBTQ + health. We interviewed 22 staff members and leaders of community organizations serving LGBTQ + populations in the US in early 2021. We used a team-based, reflexive thematic analysis approach. RESULTS: The findings highlight the challenges of attempting to use health communication campaigns misaligned with the assets and needs of organizations and community members. The three major themes identified were as follows: (1) available evidence-based health communication campaigns typically do not sufficiently center LGBTQ + communities, (2) negotiation regarding campaign utilization places additional burden on practitioners who have to act as "gatekeepers," and (3) processes of using health communication campaigns often conflict with organizational efforts to engage community members in adoption and adaptation activities. CONCLUSIONS: We offer a set of considerations to support collaborative design and dissemination of health communication campaigns to organizations serving LGBTQ + communities: (1) develop campaigns with and for LGBTQ + populations, (2) attend to the broader structural forces impacting campaign recipients, (3) support in-house testing and adaptations, and (4) increase access to granular data for community organizations.

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis.

OBJECTIVE: The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). DATA SOURCES: A literature search of MEDLINE (PubMed) was performed for articles from inception through end-March 2022 using the following search terms: atopic dermatitis, abrocitinib, PF-04965842, methotrexate, cyclosporine, dupilumab, ruxolitinib, and JAK-STAT pathway. STUDY SELECTION AND DATA EXTRACTION: English articles relating to pharmacology, pharmacokinetics, efficacy, and safety of abrocitinib, and other conventional systemic medications for AD, were included. DATA SYNTHESIS: Across phase IIb and phase III clinical trials, abrocitinib was efficacious with an average of 47.5% patients on 200 mg abrocitinib and 32.0% on 100 mg abrocitinib achieving an Investigator's Global Assessment (IGA) of 0 or 1 at 12 weeks. In comparison with dupilumab 300 mg subcutaneously every other week, patients on abrocitinib 200 mg once daily had improved disease severity and itch response. The majority of adverse events were not severe and self-limited. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Prior to Food and Drug Administration (FDA) approval of abrocitinib, prednisone was the only FDA-approved oral medication for AD. Although biologics such as dupilumab have revolutionized care, some patients prefer oral medications. Compared with clinical trials of conventional AD treatments, abrocitinib appears more effective. CONCLUSIONS: Abrocitinib is an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who have not responded to systemic medications or when contraindicated otherwise.

Prosocial behavior and psychopathology: An 11-year longitudinal study of inter- and intraindividual reciprocal relations across childhood and adolescence.

The current study investigated whether prosocial behavior and emotional problems, peer problems, conduct problems, and hyperactivity and inattention problems were long-term longitudinally and bidirectionally related at inter- and or intra-individual levels from early childhood through mid-adolescence. Parents in the United Kingdom reported their child's prosocial behavior and multidimensional psychopathology at ages 3, 5, 7, 11, and 14 years (N = 16,984, 51% male, 83% White). Four random intercepts cross-lagged panel models were fitted. Higher levels of earlier prosocial behavior were associated with greater than expected decrements in psychopathology. At an intraindividual, within-person level, prosocial behavior was negatively bidirectionally associated with peer, conduct, and hyperactivity and inattention problems. Also at an intraindividual, within-person level, prosocial behavior was unidirectionally protective against emotional problems. At an interindividual level, prosocial behavior and each dimension of psychopathology were negatively associated. Therefore, engaging in prosocial behavior can reduce psychopathological symptoms over time (and vice versa), and youth who are more prosocial also tend to experience fewer psychopathological symptoms. Intraindividual associations were small while interindividual associations were moderate to large. Implications for theory, future research, and evidence-based interventions are discussed.

Cidofovir in the Management of Non-Genital Warts: A Review.

INTRODUCTION: Cutaneous warts are one of the most frequent reasons for visits to the dermatologist. While there are many treatment options available and commonly used to treat warts, recurrence of lesions is common and complete clearance is rarely achieved. Cidofovir is an antiviral agent that has activity against various DNA viruses, including HPV, the virus that results in verrucae. OBJECTIVE: We examined the literature on the use of cidofovir in the treatment of non-genital warts to further assess its safety and efficacy.  Methods: A review of the literature using PubMed and Google Scholar databases was conducted to find relevant case reports and studies on the use of cidofovir in the treatment of non-genital warts.  Results: Thirteen case reports, five case series, six retrospective chart reviews, and one clinical study were reviewed and included. There were a total of 603 patients, 46.2% males and 53.7% females. Of 603 patients included in this review, 212 (35.2%) were treated with topical cidofovir for their warts. Clearance was achieved in 55.2%. There was no recurrence of lesions after clearance at two months to three years post-treatment (mean of 15.8 months). Of the 212 patients treated with topical cidofovir, 37 (17.4%) reported local side effects such as erythema, pruritus, and burning.  Discussion/Conclusion: Treatment options for recalcitrant non-genital warts are limited and have varying efficacy. Topical cidofovir may serve as an effective, safe, and affordable alternative for the clearance of recalcitrant non-genital warts, but controlled clinical trials are needed.J Drugs Dermatol. 2023;22(10):1009-1016  doi:10.36849/JDD.7258.

Topical Ivermectin Is Associated With Improved Erythematotelangiectatic, Papulopustular, and Phymatous Rosacea in a Secondary Analysis.

Rosacea has variable clinical presentation consisting of four overlapping phenotypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1 Rosacea's pathogenesis involves increased cutaneous density of Demodex folliculorum mites, which drive inflammation through activation of Toll-like receptor-2.1,2 Thus, topical ivermectin (IVM) 1.0% cream's anti-inflammatory and acaricidal activity provides an effective and targeted treatment for moderate-to-severe rosacea. However, literature assessing IVM is limited to efficacy in treating the papulopustular presentation, limiting generalizability.1,3,4 Although our primary endpoint was to assess patient adherence, the objective of this secondary analysis was to assess IVM efficacy in rosacea, regardless of clinical presentation.

The Patient-Physician Relationship and Adherence: Observations From a Clinical Study.

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.

Topical Moisturizer Meaningfully Reduces Disease Severity in Atopic Patients With Xerosis.

BACKGROUND: Repairing the epidermal barrier is critically important in atopic dermatitis (AD), but the effect of moisturizer on quality of life (QOL) is not well characterized.  Objective: To assess whether the use of a moisturizer improves QOL in atopic patients with xerosis.  Methods: Thirty-five (35) adults with xerosis and AD received a moisturizer designed for AD to apply daily for three months. Adherence was assessed with electronic monitors. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI) at baseline and follow-up.  Results: Mean adherence to the moisturizer was 46%. Dryness improved from 1.9 at baseline to 1.4 at follow-up (P=0.02). DLQI improved from 3.3 at baseline to 1.5 at 3 months (P=0.005). The "feeling self-conscious or embarrassed due to their skin condition" DLQI item improved from 0.79 at baseline to 0.14 at 3 months (P=0.0009).  Conclusion: Moisturizers are the foundation of AD treatment. Even non-medicated topical emollients can improve QOL in patients with AD.  J Drugs Dermatol. 2023;22(12):e51-e52.     doi:10.36849/JDD.7036e.

Dermatology through the lens of social media: A qualitative study among adolescents.

Social media (SM) use has accelerated at an unprecedented pace and dermatology literature evaluating SM use is primarily centered on the quality and quantity of dermatologic content, with minimal research on how adolescent patients experience such content. We recruited 15 patients between the ages of 13-18 years from the Atrium Health Wake Forest Baptist Department of Dermatology to interview regarding their experience with dermatologic content on SM. Despite most participants' insightful comments on SM use and the relative lack of dermatologic content validation on SM, many participants adopted skin care advice from SM. Adolescents are particularly vulnerable to social influence and it is important dermatologists understand how pervasive skin-related content is on these platforms.

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans.

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved "closure motif" region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

A descriptive literature review of early research on COVID-19 and close relationships.

This in-depth critical review investigates the impact of COVID-19 on personal relationships from the start of the pandemic in early 2020 to September 2021. Research examining six themes are identified and described in detail: the impact of COVID-19 on (1) family and intimate relationships; (2) LGBTQ+ relationships; (3) how COVID-19 is linked to technologically mediated communication and personal relationships; (4) potential shifts in sexual behaviors and desire; (5) potential shifts in relational conflict and intimate partner violence; and (6) constructive aspects of personal relationships, which is a broad theme that includes outcomes such as resilience, relational quality, coping, and social support. Findings for overarching patterns are offered to highlight implications for current research and identify future directions to consider when continuing to study personal relationships during the COVID-19 pandemic and similar future crises.

Lung transplantation after ex vivo lung perfusion versus static cold storage: An institutional cost analysis.

Ex vivo lung perfusion (EVLP) is a novel lung preservation strategy that facilitates the use of marginal allografts; however, it is more expensive than static cold storage (SCS). To understand how preservation method might affect postoperative costs, we compared outcomes and index hospitalization costs among matched EVLP and SCS preserved lung transplant (LTx) recipients at a single, high-volume institution. A total of 22 EVLP and 66 matched SCS LTx recipients were included; SCS grafts were further stratified as either standard-criteria (SCD) or extended-criteria donors (ECD). Median total preservation time was 857, 409, and 438 min for EVLP, SCD, and ECD lungs, respectively (p < .0001). EVLP patients had similar perioperative outcomes and posttransplant survival compared to SCS SCD and ECD recipients. Excluding device-specific costs, total direct variable costs were similar among EVLP, SCD, and ECD recipients (median $200,404, vs. $154,709 vs. $168,334, p =  .11). The median direct contribution margin was positive for EVLP recipients, and similar to that for SCD and ECD graft recipients (all p > .99). These findings demonstrate that the use of EVLP was profitable at an institutional level; however, further investigation is needed to better understand the financial implications of EVLP in facilitating donor pool expansion in an era of broader lung sharing.

Textbook surgical outcome in lung transplantation: Analysis of a US national registry.

INTRO: Textbook surgical outcome (TO) is a novel composite quality measure in lung transplantation (LTx). Compared to 1-year survival metrics, TO may better differentiate center performance, and motivate improvements in care. To understand the feasibility of implementing this metric, we defined TO in LTx using US national data, and evaluated its ability to predict post-transplant outcomes and differentiate center performance. METHODS: Adult patients who underwent isolated LTx between 2016 and 2019 were included. TO was defined as freedom from post-transplant length of stay > 30 days, 90-day mortality, intubation or extracorporeal membrane oxygenation at 72 h post-transplant, post-transplant ventilator support lasting ≥5 days, postoperative airway dehiscence, inpatient dialysis, pre-discharge acute rejection, and grade 3 primary graft dysfunction at 72 h. Recipient and donor characteristics and post-transplant outcomes were compared between patients who achieved and failed TO. RESULTS: Of 8959 lung transplant recipients, 4664 (52.1%) achieved TO. Patient and graft survival were improved among patients who achieved TO (both log-rank P < .0001). Among 62 centers, adjusted rates of TO ranged from 27.0% to 72.4% reflecting a wide variability in center-level performance. CONCLUSION: TO defined using national data may represent a novel composite metric to guide quality improvement in LTx across US transplant centers. SUMMARY: In this study we defined textbook outcome (TO) for lung transplantation (LTx) using US national data. We found that achievement of TO was associated with improved post-transplant survival, and wide variability in center-level LTx performance. These findings suggest that TO could be readily implemented to compare quality of care among US LTx centers.

The relationship between physical activity states and depressive symptoms: Using ambulatory assessment to characterize day-to-day associations among individuals with and without bipolar spectrum disorder.

INTRODUCTION: The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD. METHODS: Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily. RESULTS: There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype. CONCLUSIONS: Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD.