Insect Flight: State of the Field and Future Directions.

The evolution of flight in an early winged insect ancestral lineage is recognized as a key adaptation explaining the unparalleled success and diversification of insects. Subsequent transitions and modifications to flight machinery, including secondary reductions and losses, also play a central role in shaping the impacts of insects on broadscale geographic and ecological processes and patterns in the present and future. Given the importance of insect flight, there has been a centuries-long history of research and debate on the evolutionary origins and biological mechanisms of flight. Here, we revisit this history from an interdisciplinary perspective, discussing recent discoveries regarding the developmental origins, physiology, biomechanics, and neurobiology and sensory control of flight in a diverse set of insect models. We also identify major outstanding questions yet to be addressed and provide recommendations for overcoming current methodological challenges faced when studying insect flight, which will allow the field to continue to move forward in new and exciting directions. By integrating mechanistic work into ecological and evolutionary contexts, we hope that this synthesis promotes and stimulates new interdisciplinary research efforts necessary to close the many existing gaps about the causes and consequences of insect flight evolution.

The Pathway to Developing a Competency-based Tool for Entry-level Nursing Simulation: A Delphi Study.

BACKGROUND: Simulation-based learning experiences allow undergraduate nursing students to develop competence and confidence through deliberate practice with immediate feedback on the learner's performance through debriefing. With the transition to competency-based nursing education, nursing faculty need more guidance in implementing competency-based evaluations in the simulation setting. PURPOSE: This Delphi study aims to inform the future development of a competency-based tool - SimComp - based on the American Association of Colleges of Nursing (AACN) Essentials. METHODS: A Delphi framework was used to recruit expert nursing faculty to complete the surveys via an online platform. Data analysis occurred through open-ended questions and quantitative methods to ensure that the responses from expert panelists were used to form the results. RESULTS: After four rounds of this Delphi study, a consensus was achieved on 111 appropriate items for assessing competence in the simulation-based learning environment. CONCLUSION: While further research is warranted, this study provides insight for nursing institutions considering implementing or increasing the use of simulation within their program for competency-based evaluations.

Nonsurgical improvement of severe upper airway obstruction in infants with Robin sequence and cleft palate using Stanford Orthodontic Airway Plate treatment.

STUDY OBJECTIVES: Severe respiratory distress of neonates with Robin sequence (RS) is traditionally managed by surgery. Stanford Orthodontic Airway Plate treatment (SOAP) is a nonsurgical option. The study aimed to determine if SOAP can improve polysomnography (PSG) parameters of neonates with RS. METHODS: PSG of neonates with RS treated with SOAP at a single hospital were retrospectively analyzed. Patients without PSG at all 4 time points (pre-, start of-, mid-, and post-treatment) were excluded. Data were analyzed using a linear mixed effects model. RESULTS: Sixteen patients were included. All patients had cleft palate (CP). The median age (min, max) at the start of treatment was 1.1 months (0.5, 2.3) with the treatment duration of 4.5 months (3.5, 6.0). The mean obstructive apnea-hypopnea index (95% confidence interval) decreased from 39.3 events/hour (32.9, 45.7) to 12.2 events/hour (6.7, 17.7) (P < 0.001), obstructive apnea index decreased from 14.1 (11.2, 17.0) events/hour to 1.0 (-1.5, 3.5) events/hour (P < 0.001), and oxygen nadir increased from 79.9% (77.4, 82.5) to 88.2% (85.5, 90.8) (P < 0.001) between pre- and start of treatment. Respiratory improvements were sustained during and after the treatment. All patients avoided mandibular distraction osteogenesis or tracheostomy following SOAP. CONCLUSIONS: As being a rare diagnosis, the number of participants was, as expected, low. However, the current study demonstrates that SOAP can improve PSG parameters, demonstrating its potential utility before surgical interventions for neonates with RS and CP experiencing severe respiratory distress.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes.

Importance: A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking. Objective: To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season. Design, Setting, and Participants: This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024. Exposure: Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records. Main Outcome and Measures: The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed. Results: Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77). Conclusions and Relevance: In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

Defining and Addressing Research Priorities in Cancer Cachexia through Transdisciplinary Collaboration.

For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes.

A Positive Psychology Intervention in Allogeneic Hematopoietic Stem Cell Transplantation Survivors (PATH): A Pilot Randomized Clinical Trial.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience significant psychological distress and low levels of positive psychological well-being, which can undermine patient-reported outcomes (PROs), such as quality of life (QoL). Hence, we conducted a pilot randomized clinical trial to assess the feasibility and preliminary efficacy of a telephone-delivered positive psychology intervention (Positive Affect for the Transplantation of Hematopoietic stem cells intervention [PATH]) for improving well-being in HSCT survivors. METHODS: HSCT survivors who were 100 days post-HSCT for hematologic malignancy at an academic institution were randomly assigned to either PATH or usual care. PATH, delivered by a behavioral health expert, entailed 9 weekly phone sessions on gratitude, personal strengths, and meaning. We defined feasibility a priori as >60% of eligible participants enrolling in the study and >75% of PATH participants completing ≥6 of 9 sessions. At baseline and 9 and 18 weeks, patients self-reported gratitude, positive affect, life satisfaction, optimism, anxiety, depression, posttraumatic stress disorder (PTSD), QoL, physical function, and fatigue. We used repeated measures regression models and estimates of effect size (Cohen's d) to explore the preliminary effects of PATH on outcomes. RESULTS: We enrolled 68.6% (72/105) of eligible patients (mean age, 57 years; 50% female). Of those randomized to PATH, 91% completed all sessions and reported positive psychology exercises as easy to complete and subjectively useful. Compared with usual care, PATH participants reported greater improvements in gratitude (ß = 1.38; d = 0.32), anxiety (ß = -1.43; d = -0.40), and physical function (ß = 2.15; d = 0.23) at 9 weeks and gratitude (ß = 0.97; d = 0.22), positive affect (ß = 2.02; d = 0.27), life satisfaction (ß = 1.82; d = 0.24), optimism (ß = 2.70; d = 0.49), anxiety (ß = -1.62; d = -0.46), depression (ß = -1.04; d = -0.33), PTSD (ß = -2.50; d = -0.29), QoL (ß = 7.70; d = 0.41), physical function (ß = 5.21; d = 0.56), and fatigue (ß = -2.54; d = -0.33) at 18 weeks. CONCLUSIONS: PATH is feasible, with promising signals for improving psychological well-being, QoL, physical function, and fatigue in HSCT survivors. Future multisite trials that investigate PATH's efficacy are needed to establish its effects on PROs in this population.

Does reversible postpartum contraception reduce the risk of pregnancy condition recurrence? A longitudinal claims-based study from Maine.

PURPOSE: To estimate the effect of reversible postpartum contraception use on the risk of recurrent pregnancy condition in the subsequent pregnancy and if this effect was mediated through lengthening the interpregnancy interval (IPI). METHODS: We used data from the Maine Health Data Organization's Maine All Payer Claims dataset. Our study population was Maine women with a livebirth index pregnancy between 2007 and 2019 that was followed by a subsequent pregnancy starting within 60 months of index pregnancy delivery. We examined recurrence of three pregnancy conditions, separately, in groups that were not mutually exclusive: prenatal depression, hypertensive disorders of pregnancy (HDP), and gestational diabetes (GDM). Effective reversible postpartum contraception use was defined as any intrauterine device, implant, or moderately effective method (pills, patch, ring, injectable) initiated within 60 days of delivery. Short IPI was defined as ≤ 12 months. We used log-binomial regression models to estimate risk ratios and 95 % confidence intervals, adjusting for potential confounders. RESULTS: Approximately 41 % (11,448/28,056) of women initiated reversible contraception within 60 days of delivery, the prevalence of short IPI was 26 %, and the risk of pregnancy condition recurrence ranged from 38 % for HDP to 55 % for prenatal depression. Reversible contraception initiation within 60 days of delivery was not associated with recurrence of the pregnancy condition in the subsequent pregnancy (aRR ranged from 0.97 to 1.00); however, it was associated with lower risk of short IPI (aRR ranged from 0.67 to 0.74). CONCLUSION(S): Although initiation of postpartum reversible contraception within 60 days of delivery lengthens the IPI, our findings suggest that it does not reduce the risk of prenatal depression, HDP, or GDM recurrence. This indicates a missed opportunity for providing evidence-based healthcare and health interventions in the intrapartum period to reduce the risk of recurrence.

Caspase-8 activity mediates TNFα production and restricts Coxiella burnetii replication during murine macrophage infection.

Coxiella burnetii is an obligate intracellular bacteria that causes the global zoonotic disease Q Fever. Treatment options for chronic infection are limited, and the development of novel therapeutic strategies requires a greater understanding of how C. burnetii interacts with immune signaling. Cell death responses are known to be manipulated by C. burnetii, but the role of caspase-8, a central regulator of multiple cell death pathways, has not been investigated. In this research, we studied bacterial manipulation of caspase-8 signaling and the significance of caspase-8 to C. burnetii infection, examining bacterial replication, cell death induction, and cytokine signaling. We measured caspase, RIPK, and MLKL activation in C. burnetii-infected tumor necrosis factor alpha (TNFα)/cycloheximide-treated THP-1 macrophage-like cells and TNFα/ZVAD-treated L929 cells to assess apoptosis and necroptosis signaling. Additionally, we measured C. burnetii replication, cell death, and TNFα induction over 12 days in RIPK1-kinase-dead, RIPK3-kinase-dead, or RIPK3-kinase-dead-caspase-8-/- bone marrow-derived macrophages (BMDMs) to understand the significance of caspase-8 and RIPK1/3 during infection. We found that caspase-8 is inhibited by C. burnetii, coinciding with inhibition of apoptosis and increased susceptibility to necroptosis. Furthermore, C. burnetii replication was increased in BMDMs lacking caspase-8, but not in those lacking RIPK1/3 kinase activity, corresponding with decreased TNFα production and reduced cell death. As TNFα is associated with the control of C. burnetii, this lack of a TNFα response may allow for the unchecked bacterial growth we saw in caspase-8-/- BMDMs. This research identifies and explores caspase-8 as a key regulator of C. burnetii infection, opening novel therapeutic doors.

Vectored Thermal Pulsation as a Treatment for Meibomian Gland Dysfunction: A Review Spanning 15 Years.

The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13 years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15 years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101 patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041 patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3 years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date.

Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. METHODS: We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. RESULTS: In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). CONCLUSION: No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy.

Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors.

Background: Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB subtype accounts for about 25% of MB diagnoses and is associated with the most unfavorable outcomes. Herein, we report that more than half of group 3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are tumor antigens, expressed in several types of adult cancers and associated with poorer prognosis and therapy resistance; however, their expression in pediatric cancers is mostly unknown. The aim of this study was to determine whether MAGEs are activated in pediatric MB. Methods: To determine MAGE frequency in pediatric MB, we obtained formalin-fixed paraffin-embedded tissue (FFPE) samples of 34 patients, collected between 2008 - 2015, from the Children's Medical Center Dallas pathology archives and applied our validated reverse transcription quantitative PCR (RT-qPCR) assay to measure the relative expression of 23 MAGE cancer-testis antigen genes. To validate our data, we analyzed several published datasets from pediatric MB patients and patient-derived orthotopic xenografts, totaling 860 patients. We then examined how MAGE expression affects the growth and oncogenic potential of medulloblastoma cells by CRISPR-Cas9- and siRNA-mediated gene depletion. Results: Our RT-qPCR analysis suggested that MAGEs were expressed in group 3/4 medulloblastoma. Further mining of bulk and single-cell RNA-sequencing datasets confirmed that 50-75% of group 3 tumors activate a subset of MAGE genes. Depletion of MAGEAs, B2, and Cs alter MB cell survival, viability, and clonogenic growth due to decreased proliferation and increased apoptosis. Conclusions: These results indicate that targeting MAGEs in medulloblastoma may be a potential therapeutic option for group 3 medulloblastomas. Key Points: Several Type I MAGE CTAs are expressed in >60% of group 3 MBs. Type I MAGEs affect MB cell proliferation and apoptosis. MAGEs are potential biomarkers and therapeutic targets for group 3 MBs. Importance of the Study: This study is the first comprehensive analysis of all Type I MAGE CTAs ( MAGEA , -B , and -C subfamily members) in pediatric MBs. Our results show that more than 60% of group 3 MBs express MAGE genes, which are required for the viability and growth of cells in which they are expressed. Collectively, these data provide novel insights into the antigen landscape of pediatric MBs. The activation of MAGE genes in group 3 MBs presents potential stratifying and therapeutic options.

Need for Behavioral Interventions for Young Adults Living with Advanced Cancer in the U.S.

The population of young adults (YAs) aged 18-39 living with advanced cancer is growing and faces a compounded set of challenges at the intersection of age and disease. Despite these substantial challenges, behavioral interventions tailored to YAs living with advanced cancer remain scarce. This commentary aims to (1) discuss the unmet psychological, social, and behavioral needs of YAs living with advanced cancer; (2) highlight the paucity of behavioral interventions tailored to this growing population; (3) offer recommendations for the development of behavioral interventions targeting the unique needs of YAs living with advanced cancer; and (4) describe potential far-reaching public health benefits of these targeted behavioral interventions.

Beyond Survival: A Scoping Review on the Sexual Health of Sexual and Gender Minority Women Following Curative Cancer Treatment.

INTRODUCTION: To explore the existing research on sexual health experiences of sexual and gender minority women (SGMW) post-curative cancer treatment. METHODOLOGY: This scoping review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Four articles that focused on sexual health experiences of SGMW post-curative cancer treatment were included. RESULTS: Four themes were identified: (a) sexual function; (b) sexual orientation and gender identity, including disclosure and health care provider reactions; (c) relationship dynamics, such as relationship status and the quality of romantic relationships; and (d) body image. DISCUSSIONS: The findings underscore substantial challenges faced by SGMW cancer survivors in achieving optimal sexual well-being, impacting their access to post-treatment care. This study advocates for more expansive research efforts involving diverse participant cohorts, extending beyond breast cancer, to gain deeper insights into these critical issues.

Becoming Endemic: Anaplasmosis Imported Across State Borders.

Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis (HGA), a tick-borne illness with increasing incidence since being described in the 1990s. Importantly, the presentation can be vague, yet prompt treatment is paramount. An 81-year-old Caucasian female was hospitalized in Cincinnati, Ohio, for fever and confusion following prolonged outdoor exposure in Emlenton, Pennsylvania. She initially was treated for sepsis from presumed community-acquired pneumonia; however, the combination of leukopenia, thrombocytopenia, and elevated liver enzymes prompted empiric tick-borne illness consideration and treatment with rapid resolution in symptoms. Early recognition of HGA can reduce unnecessary treatments and improve patient outcomes.

Blood Pressure, Readmission, and Mortality Among Patients Hospitalized With Acute Kidney Injury.

Importance: Acute kidney injury (AKI) complicates 20% to 25% of hospital admissions and is associated with long-term mortality, especially from cardiovascular disease. Lower systolic blood pressure (SBP) following AKI may be associated with lower mortality, but potentially at the cost of higher short-term complications. Objective: To determine associations of SBP with mortality and hospital readmissions following AKI, and to determine whether time from discharge affects these associations. Design, Setting, and Participants: This retrospective cohort study of adults with AKI during a hospitalization in Veteran Healthcare Association (VHA) hospitals was conducted between January 2013 and December 2018. Patients with 1 year or less of data within the VA system prior to admission, severe or end-stage liver disease, stage 4 or 5 chronic kidney disease, end-stage kidney disease, metastatic cancer, and no blood pressure values within 30 days of discharge were excluded. Data analysis was conducted from May 2022 to February 2024. Exposure: SBP was treated as time-dependent (categorized as <120 mm Hg, 120-129 mm Hg, 130-139 mm Hg, 140-149 mm Hg, 150-159 mm Hg, and ≥160 mm Hg [comparator]). Time spent in each SBP category was accumulated over time and represented in 30-day increments. Main Outcomes and Measures: Primary outcomes were time to mortality and time to all-cause hospital readmission. Cox proportional hazards regression was adjusted for demographics, comorbidities, and laboratory values. To evaluate associations over time, hazard ratios (HRs) were calculated at 60 days, 90 days, 120 days, 180 days, 270 days, and 365 days from discharge. Results: Of 237 409 admissions with AKI, 80 960 (57 242 aged 65 years or older [70.7%]; 77 965 male [96.3%] and 2995 female [3.7%]) were included. The cohort had high rates of diabetes (16 060 patients [20.0%]), congestive heart failure (22 516 patients [28.1%]), and chronic lung disease (27 682 patients [34.2%]), and 1-year mortality was 15.9% (12 876 patients). Overall, patients with SBP between 130 and 139 mm Hg had the most favorable risk level for mortality and readmission. There were clear, time-dependent mediations on associations in all groups. Compared with patients with SBP of 160 mm Hg or greater, the risk of mortality for patients with SBP between 130 and 139 mm Hg decreased between 60 days (adjusted HR, 1.20; 99% CI, 1.00-1.44) and 365 days (adjusted HR, 0.58; 99% CI, 0.45-0.76). SBP less than 120 mm Hg was associated with increased risk of mortality at all time points. Conclusions and Relevance: In this retrospective cohort study of post-AKI patients, there were important time-dependent mediations of the association of blood pressure with mortality and readmission. These findings may inform timing of post-AKI blood pressure treatment.

Gestational carrier cycles: embryology trends, national guideline compliance, and resultant perinatal outcomes in the United States, 2014-2020.

BACKGROUND: The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations. OBJECTIVE: Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and 2017. STUDY DESIGN: This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time. RESULTS: Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to 2020. CONCLUSION: Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates.

Alzheimer's disease-related biomarkers and cancer-related cognitive decline: the thinking and living with cancer study.

PURPOSE: We evaluated whether plasma Alzheimer's Disease (AD)-related biomarkers were associated with cancer-related cognitive decline (CRCD) among older breast cancer survivors. METHODS: We included survivors 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched non-cancer controls (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (pre-systemic therapy) and annually for up to 60-months. Cognition was measured using tests of attention, processing speed and executive function (APE) and learning and memory (LM); perceived cognition was measured by the FACT-Cog PCI. Baseline plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), beta-amyloid 42/40 (Aß42/40) and phosphorylated tau (p-tau181) were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD-biomarkers, time, group (survivor vs control) and their two- and three-way interactions, controlling for age, race, WRAT4 Word Reading score, comorbidity and BMI; two-sided 0.05 p-values were considered statistically significant. RESULTS: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline NfL levels than controls (p = .013). Survivors had lower adjusted longitudinal APE than controls starting from baseline and continuing over time (p = <0.002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except controls had lower APE scores with higher GFAP levels (p = .008). CONCLUSION: The results do not support a relationship between baseline AD-related biomarkers and CRCD. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers and examine other mechanisms and factors affecting cognition pre-systemic therapy.