Breast Cancer Incidence Among US Women Aged 20 to 49 Years by Race, Stage, and Hormone Receptor Status.

Importance: Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known. Objective: To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends. Design, Setting, and Participants: This cross-sectional study used data from Surveillance, Epidemiology, and End Results 17 registries (2000-2019). Women aged 20 to 49 years with a primary invasive breast cancer were included. Data were analyzed between February and June 2023. Main Outcomes and Measures: Age-standardized incidence rates (ASIR), incidence rate ratios (IRR), and average annual percent changes (AAPC) stratified by race and ethnicity, hormone receptor status, tumor stage, and age at diagnosis. Results: Out of 217 815 eligible women (1485 American Indian or Alaska Native [0.7%], 25 210 Asian or Pacific Islander [11.6%], 27 112 non-Hispanic Black [12.4%], 37 048 Hispanic [17.0%], 126 960 non-Hispanic White [58.3%]), the majority were diagnosed with an ER+/PR+ tumor (134 024 [61.5%]) and were diagnosed with a stage I tumor (81 793 [37.6%]). Overall, invasive breast cancer incidence increased (AAPC, 0.79; 95% CI, 0.42 to 1.15), with increasing trends across almost all racial and ethnic groups. ASIR increased for ER+/PR+ (AAPC, 2.72; 95% CI, 2.34 to 3.12) and ER+/PR- tumors (AAPC, 1.43; 95% CI, 1.00 to 1.87), and decreased for ER-/PR+ (AAPC, -3.25; 95% CI, -4.41 to -2.07) and ER-/PR- tumors (AAPC, -0.55; 95% CI, -1.68 to 0.60). For women aged 20 to 29 and 30 to 39 years, ASIRs were highest among non-Hispanic Black women (age 20-29 years: IRR, 1.53; 95% CI, 1.43 to 1.65; age 30-39 years: IRR, 1.15; 95% CI, 1.12 to 1.18). For women aged 40 to 49 years, ASIR was lower for non-Hispanic Black women (IRR, 0.96; 95% CI, 0.94 to 0.97) compared with non-Hispanic White women. Incidence rates increased for stages I and IV tumors but decreased for stage II and III tumors. Age-period-cohort analysis demonstrated both cohort and period effects on breast cancer incidence (P < .001). Conclusions and Relevance: In this population-based cross-sectional analysis, an increase in breast cancer incidence rates among young US women and age-related crossover between non-Hispanic White and Black women were observed. Prevention efforts in young women need to adopt a targeted approach to address racial disparities in incidence rates observed at different age phases.

A Cautionary Note on Using Propensity Score Calibration to Control for Unmeasured Confounding Bias When the Surrogacy Assumption Is Absent.

Conventional propensity score methods encounter challenges when unmeasured confounding is present, as it becomes impossible to accurately estimate the gold-standard propensity score when data on certain confounders are unavailable. Propensity score calibration (PSC) addresses this issue by constructing a surrogate for the gold-standard propensity score under the surrogacy assumption. This assumption posits that the error-prone propensity score, based on observed confounders, is independent of the outcome when conditioned on the gold-standard propensity score and the exposure. However, this assumption implies that confounders cannot directly impact the outcome and that their effects on the outcome are solely mediated through the propensity score. This raises concerns regarding the applicability of PSC in practical settings where confounders can directly affect the outcome. While PSC aims to target a conditional treatment effect by conditioning on a subject's unobservable propensity score, the causal interest in the latter case lies in a conditional treatment effect conditioned on a subject's baseline characteristics. Our analysis reveals that PSC is generally biased unless the effects of confounders on the outcome and treatment are proportional to each other. Furthermore, we identify 2 sources of bias: 1) the noncollapsibility of effect measures, such as the odds ratio or hazard ratio and 2) residual confounding, as the calibrated propensity score may not possess the properties of a valid propensity score.

The impact of green finance and local regulations on industrial green innovation efficiency in China.

When the incentive mechanism of green finance fails to fully promote green technology innovation in industrial enterprises, local government environmental regulations become an important tool in correcting this market failure. However, due to the "follow the cost" hypothesis, the moderating effect of the local government environmental regulation is heterogeneous. In order to explore the impact mechanism of green finance development on the efficiency of green technology innovation in industrial enterprises, spatial effects as well as the heterogeneous moderating effect of local government environmental regulation, this paper systematically evaluates the development level of green finance in 30 provinces in China from 2009 to 2019. It estimates the efficiency of green technology innovation in industrial enterprises using the super-efficiency SBM model, and empirically analyzes the impact mechanism and moderating effect using the spatial Durbin model. The results show that: (1) green finance not only positively impacts the efficiency improvement of green technology innovation in industrial enterprises but also has significant spatial spillover effects; (2) local government environmental regulation has a nonlinear "inverted U-shaped" moderating effect between the green finance development and the efficiency of green technology innovation in industrial enterprises. Based on the research conclusions, this paper proposes policy recommendations from the perspectives of deepening the regional connectivity of green finance and promoting joint regulation by local governments.

Design of innovation ability evaluation model based on IPSO-LSTM in intelligent teaching.

Guided by the development of an innovative economy, students' innovative education has also become the focus of talent training. This research aims to realize the intelligent evaluation of students' innovation ability. In this article, we proposed an innovation ability framework that integrates students' psychological state and innovation evaluation indicators. Firstly, the qualitative description of psychological data is quantified using the Delphi method. Secondly, this article proposes an improved particle swarm optimization-long short-term memory (IPSO-LSTM) model to achieve high-precision evaluation and classification of innovation capabilities. The classification accuracy of this model for excellent, general and failed innovation capabilities is up to 95.3%. Finally, the characteristic contribution analysis of psychological and innovative ability characteristics is carried out. The results show that the evaluation of creative ability contributes more than 50% to the psychological aspects of excellent students. This shows the importance of psychological status on creative ability and provides a theoretical basis for integrating innovative education and psychological education in the future.

Preparation and Study of Antifouling and Fouling-Release Surface Materials from Copolymers with Anchoring Functional Groups.

Marine biofouling is a worldwide problem in marine systems. Nowadays, innovative non-toxic antifouling and fouling-release materials are highly desirable. In this study, a strategy for preparing antifouling and fouling-release materials via one-step dip coating is reported. Copolymers were synthesized via the polymerization of a monomer with catechol sticky functional groups and four monomers with antifouling- or fouling-release functional groups, respectively. The copolymers could assemble onto different material surfaces, such as metals and plastics, using biomimetic catechol groups via multivalent complex bonding. The catechol groups were helpful for adhesion onto the surfaces, while the other functional groups endowed the coatings with antifouling or fouling-release properties. The effects of modifying the substrates using these copolymer coatings were verified via X-ray photoelectron spectroscopy; images of Chlorella cell and Ulva zoospore settlement were taken using a microscope and scanning electron microscope. The copolymer-coated surfaces, especially the surface modified by DOPA-PSPMA, displayed the best antifouling activity, and surface modification via DOPA-PTMETH was shown to be the most effective for producing the fouling-release property in the settlement assay.

Patient and Hospital Characteristics Associated With the Interhospital Transfer of Adult Patients With Sepsis.

IMPORTANCE: The interhospital transfer (IHT) of patients with sepsis to higher-capability hospitals may improve outcomes. Little is known about patient and hospital factors associated with sepsis IHT. OBJECTIVES: We evaluated patterns of hospitalization and IHT and determined patient and hospital factors associated with the IHT of adult patients with sepsis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 349,938 adult patients with sepsis at 329 nonfederal hospitals in California, 2018-2019. MAIN OUTCOMES AND MEASURES: We evaluated patterns of admission and outward IHT between low sepsis-, intermediate sepsis-, and high sepsis-capability hospitals. We estimated odds of IHT using generalized estimating equations logistic regression with bootstrap stepwise variable selection. RESULTS: Among the cohort, 223,202 (66.4%) were initially hospitalized at high-capability hospitals and 10,870 (3.1%) underwent IHT. Nearly all transfers (98.2%) from low-capability hospitals were received at higher-capability hospitals. Younger age (< 65 yr) (adjusted odds ratio [aOR] 1.54; 95% CI, 1.40-1.69) and increasing organ dysfunction (aOR 1.22; 95% CI, 1.19-1.25) were associated with higher IHT odds, as were admission to low-capability (aOR 2.79; 95% CI, 2.33-3.35) or public hospitals (aOR 1.35; 95% CI, 1.09-1.66). Female sex (aOR 0.88; 95% CI, 0.84-0.91), Medicaid insurance (aOR 0.59; 95% CI, 0.53-0.66), home to admitting hospital distance less than or equal to 10 miles (aOR 0.92; 95% CI, 0.87-0.97) and do-not-resuscitate orders (aOR 0.48; 95% CI, 0.45-0.52) were associated with lower IHT odds, as was admission to a teaching hospital (aOR 0.83; 95% CI, 0.72-0.96). CONCLUSIONS AND RELEVANCE: Most patients with sepsis are initially hospitalized at high-capability hospitals. The IHT rate for sepsis is low and more likely to originate from low-capability and public hospitals than from high-capability and for-profit hospitals. Transferred patients with sepsis are more likely to be younger, male, sicker, with private medical insurance, and less likely to have care limitation orders. Future studies should evaluate the comparative benefits of IHT from low-capability hospitals.

Coordination effect enhanced visualization of latent fingerprint with Eu (TTA)3phen-SiO2 microspheres.

Latent fingerprint (LFP) powders are crucial in the detection of LFPs in forensic science. However, it is often plagued by poor image resolution and low contrast. Herein, enhanced LFP fluorescence (FL) visualizations are achieved by doping Eu(III) coordination compound Eu(TTA)3phen directly into SiO2 microspheres instead of Eu(III) ions. Using the synthesized Eu(TTA)3phen-SiO2 microspheres, the fine characteristic structure of LFP can be seen and recognized under 365 nm irradiation, up to Level 3. However, the Eu3+-SiO2 microspheres were difficult to recognize the Level 2,3 fingerprint structure. The difference between the ridge and furrow gray values of Eu(TTA)3phen-SiO2 microspheres is 2.1 times that of Eu3+-SiO2 microspheres. The coordination effect increased the asymmetry around Eu(III) ions, resulting in the ultrasensitive 5D0→7F2 transition, thus increasing the FL intensity, and the uniform doping of the Eu(III) coordination compound into SiO2 also reduced the surface FL quenching due to shielding from oxygen. Under this dual effect, the LFP performance of Eu(TTA)3phen-SiO2 microspheres has been significantly improved. We believe that this novel and easy LFP visualization method is a promising routine in specific target detection including criminal investigation, customhouse check-in, and drug control.

The impact of virtual interviews on the Fellowship Council application and main match process.

BACKGROUND: The COVID-19 pandemic led the Fellowship Council (FC) to transition rapidly from in-person to virtual interviews. We investigated the impact of this transition on the FC application and main match process. METHODS: Five years (2018-2022) of deidentified FC applicant, program, and match rank data were used to assess differences between in-person (2018-2019) and virtual interview (2021-2022) cycles. Data are expressed as mean ± SD and one-way and two-way MANOVA tests were applied. RESULTS: Trainees applied to an average of 30.4 ± 24.3 programs and ranked an average of 10.7 ± 9.7 programs with a 57% match rate and average rank position of 3.6 ± 3.3. Fellowship programs received an average of 64.9 ± 28.6 applications and ranked an average of 15.4 ± 8.8 applicants with a 95% match rate and average applicant rank position of 3.0 ± 3.4. Applicants who interviewed virtually applied to a greater number of programs (32.7 vs. 27.0; p < 0.001) and ranked a greater number of programs (11.5 vs. 10.0; p = 0.004) with no difference in match rates (58% vs. 55%, p = 0.291). Among matched applicants, there was a significant difference in average rank position (3.20 vs. 4.30, p < 0.001), favoring the in-person cohort. Fellowship programs had more applicants per program (69.2 vs. 57.8; p < 0.001) and ranked more applicants (17.4 vs. 13.3; p < 0.001) during the virtual interview cycles. No difference in either match rates (93% vs. 96%, p = 0.178) or applicant rank position (3.09 vs. 2.93, p = 0.561) was seen between in-person and virtual application cycles. CONCLUSION: Virtual interviews were associated with an increased number of applications for fellowship and applicants ranked by programs but did not impact match rates of either group. Rank match position declined somewhat for applicants but not for fellowship programs. Virtual interviews offer more opportunities for applicants and a greater number of candidates for fellowship programs with only a slight decrement in fellow match rank position.

Hypoplastic Left Heart Syndrome With Low Birth Weight or Prematurity: What Is the Optimal Approach?

BACKGROUND: Hypoplastic left heart syndrome with low birth weight or prematurity comprises a high-risk population with no optimal treatment pathway. Using the Pediatric Health Information System, we compared management approaches across the United States. METHODS: We analyzed neonates (≤30 days) with birth weight <2500 grams or gestational age <36 weeks between 2012 and 2021. Four strategies were identified: Norwood procedure, ductus arteriosus stent + pulmonary artery banding, pulmonary artery banding + prostaglandin infusion, or comfort care. Outcomes included hospital survival, discharge disposition, staged palliation completion, and 1-year transplant-free survival. RESULTS: Of 383 infants identified, 36.4% (n = 134) received comfort care, 43.9% (n = 165) Norwood, 12.4% (n = 49) ductal stent + pulmonary artery bands, and 8.8% (n = 34) pulmonary artery bands + prostaglandins. Neonates receiving comfort care had the lowest gestational age (35 weeks; interquartile range [IQR], 31.5-37 weeks) and birth weight (2.0 kg; IQR, 1.5-2.3 kg); 24.6% (33 of 134) had chromosomal anomalies. Infants undergoing primary Norwood had the highest birth weight (2.4 kg; IQR, 2.2-2.5 kg) and gestational age (37 weeks; IQR, 35-38 weeks). Glenn palliation was performed in 66.1% (109 of 165) compared with ductal stent + pulmonary artery band in 18.4% (9 of 49) and pulmonary artery band + prostaglandins in 35.3% (12 of 34). Only 11.3% (6 of 53) born <2 kg survived to 1 year, all after Norwood. Primary Norwood yielded higher hospital and 1-year transplant-free survival than hybrid strategies. CONCLUSIONS: Comfort care is routinely provided, particularly for infants with low birth weight, gestational age, or chromosomal anomalies. Primary Norwood offered the lowest hospital and 1-year mortality and highest palliation completion rates; birth weight was the most important factor determining 1-year survival.

Factors influencing the prevalence of cervical cancer screening in Malaysia: a nationwide survey.

BACKGROUND: In 2020, cervical cancer ranked fourth in terms of both frequency of diagnosis and the leading cause of cancer-related deaths among women globally. Among Malaysian women, it was the third most prevalent form of cancer. Published data on nationally representative cervical cancer screening in Malaysia have been limited. Therefore, this study aimed to determine the prevalence of receiving a Pap smear test in the past three years, its relationship with socio-demographic factors and physical activity. METHODS: Using a subset of survey data from the National Health and Morbidity Survey (NHMS) 2019, a secondary data analysis was performed. Trained research assistants collected data through face-to-face method using a mobile tablet questionnaire system application. Logistic regression analysis was performed to examine the relationship between sociodemographic factors, physical activity, and cervical cancer screening. The analyses were conducted using STATA version 14 (Stata Corp, College Station, Texas, USA), accounting for sample weighs and complex sampling design. RESULTS: The analysis included 5,650 female respondents, representing an estimated 10.3 million Malaysian female adults aged 18 and above. Overall, 35.2% (95%CI 33.2, 37.4) respondents had a Pap smear test within the past three years. Respondents who were physically active were 1.41 times more likely to have a Pap smear test. Similarly, respondents aged 35-59 (OR 1.84; 95%CI 1.46, 2.34) and those living in rural localities (OR 1.38; 95%CI 1.13, 1.70) had higher odds of receiving a Pap smear test. Compared to married respondents, single respondents (OR 0.04; 95%CI 0.02, 0.07) and widowed/divorcee respondents (OR 0.72; 95%CI 0.56, 0.82) were less likely to receive a Pap smear test. Educated respondents were more likely to have had a Pap smear test. CONCLUSIONS: The overall prevalence of cervical cancer screening in Malaysia remains low (35.2%). Efforts should be made to strengthen health promotion programs and policies in increasing awareness on the significance of cervical cancer screening. These initiatives should specifically target younger women, single women, and widowed/divorced individuals. The higher cervical screening uptake among rural women should be studied further, and the enabling factors in the rural setup should be emulated in urban areas whenever possible.

Malaysian burden of disease: years of life lost due to premature deaths.

BACKGROUND: In Malaysia, the previous mortality burden has been a significant concern, particularly due to the high prevalence of noncommunicable diseases (NCDs) as the leading cause of death. Estimates of mortality are key indicators for monitoring population health and determining priorities in health policies and health planning. The aim of this study was to estimate the disease burden attributed to 113 major diseases and injuries in Malaysia in 2018 using years of life lost (YLL) method. METHODS: This study included all deaths that occurred in Malaysia in 2018. The YLL was derived by adding the number of deaths from 113 specific diseases and multiplying it by the remaining life expectancy for that age and sex group. Data on life expectancy and mortality were collected from the Department of Statistics Malaysia. RESULTS: In 2018, there were 3.5 million YLL in Malaysia. Group II (NCDs) caused 72.2% of total YLL. Ischaemic heart disease was the leading cause of premature mortality among Malaysians (17.7%), followed by lower respiratory infections (9.7%), road traffic injuries (8.7%), cerebrovascular disease (stroke) (8.0%), and diabetes mellitus (3.9%). CONCLUSIONS: NCDs are a significant health concern in Malaysia and are the primary contributor to the overall burden of disease. These results are important in guiding the national health systems on how to design and implement effective interventions for NCDs, as well as how to prioritise and allocate healthcare resources. Key strategies to consider include implementing health promotion campaigns, adopting integrated care models, and implementing policy and regulatory measures. These approaches aim to enhance health outcomes and the managements of NCDs in Malaysia.

The Relationship Between Hospital Capability and Mortality in Sepsis: Development of a Sepsis-Related Hospital Capability Index.

OBJECTIVES: Regionalized sepsis care could improve sepsis outcomes by facilitating the interhospital transfer of patients to higher-capability hospitals. There are no measures of sepsis capability to guide the identification of such hospitals, although hospital case volume of sepsis has been used as a proxy. We evaluated the performance of a novel hospital sepsis-related capability (SRC) index as compared with sepsis case volume. DESIGN: Principal component analysis (PCA) and retrospective cohort study. SETTING: A total of 182 New York (derivation) and 274 Florida and Massachusetts (validation) nonfederal hospitals, 2018. PATIENTS: A total of 89,069 and 139,977 adult patients (≥ 18 yr) with sepsis were directly admitted into the derivation and validation cohort hospitals, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We derived SRC scores by PCA of six hospital resource use characteristics (bed capacity, annual volumes of sepsis, major diagnostic procedures, renal replacement therapy, mechanical ventilation, and major therapeutic procedures) and classified hospitals into capability score tertiles: high, intermediate, and low. High-capability hospitals were mostly urban teaching hospitals. Compared with sepsis volume, the SRC score explained more variation in hospital-level sepsis mortality in the derivation (unadjusted coefficient of determination [ R2 ]: 0.25 vs 0.12, p < 0.001 for both) and validation (0.18 vs 0.05, p < 0.001 for both) cohorts; and demonstrated stronger correlation with outward transfer rates for sepsis in the derivation (Spearman coefficient [ r ]: 0.60 vs 0.50) and validation (0.51 vs 0.45) cohorts. Compared with low-capability hospitals, patients with sepsis directly admitted into high-capability hospitals had a greater number of acute organ dysfunctions, a higher proportion of surgical hospitalizations, and higher adjusted mortality (odds ratio [OR], 1.55; 95% CI, 1.25-1.92). In stratified analysis, worse mortality associated with higher hospital capability was only evident among patients with three or more organ dysfunctions (OR, 1.88 [1.50-2.34]). CONCLUSIONS: The SRC score has face validity for capability-based groupings of hospitals. Sepsis care may already be de facto regionalized at high-capability hospitals. Low-capability hospitals may have become more adept at treating less complicated sepsis.

Identification of an Arylnaphthalene Lignan Derivative as an Inhibitor against Dengue Virus Serotypes 1 to 4 (DENV-1 to -4) Using a Newly Developed DENV-3 Infectious Clone and Replicon.

Dengue virus (DENV) is the most widespread arbovirus, causing symptoms ranging from dengue fever to severe dengue, including hemorrhagic fever and shock syndrome. Four serotypes of DENV (DENV-1 to -4) can infect humans; however, no anti-DENV drug is available. To facilitate the study of antivirals and viral pathogenesis, here we developed an infectious clone and a subgenomic replicon of DENV-3 strains for anti-DENV drug discovery by screening a synthetic compound library. The viral cDNA was amplified from a serum sample from a DENV-3-infected individual during the 2019 epidemic; however, fragments containing the prM-E-partial NS1 region could not be cloned until a DENV-3 consensus sequence with 19 synonymous substitutions was introduced to reduce putative Escherichia coli promoter activity. Transfection of the resulting cDNA clone, plasmid DV3syn, released an infectious virus titer of 2.2 × 102 focus-forming units (FFU)/mL. Through serial passages, four adaptive mutations (4M) were identified, and addition of 4M generated recombinant DV3syn_4M, which produced viral titers ranging from 1.5 × 104 to 6.7 × 104 FFU/mL and remained genetically stable in transformant bacteria. Additionally, we constructed a DENV-3 subgenomic replicon and screened an arylnaphthalene lignan library, from which C169-P1 was identified as exhibiting inhibitory effects on viral replicon. A time-of-drug addition assay revealed that C169-P1 also impeded the internalization process of cell entry. Furthermore, we demonstrated that C169-P1 inhibited the infectivity of DV3syn_4M, as well as DENV-1, DENV-2, and DENV-4, in a dose-dependent manner. This study provides an infectious clone and a replicon for the study of DENV-3 and a candidate compound for future development against DENV-1 to -4 infections. IMPORTANCE Dengue virus (DENV) is the most prevalent mosquito-transmitted virus, and there is no an anti-dengue drug. Reverse genetic systems representative of different serotype viruses are invaluable tools for the study of viral pathogenesis and antiviral drugs. Here, we developed an efficient infectious clone of a clinical DENV-3 genotype III isolate. We successfully overcame the instability of flavivirus genome-length cDNA in transformant bacteria, an unsolved issue for construction of cDNA clones of flaviviruses, and adapted this clone to efficiently produce infectious viruses following plasmid transfection of cell culture. Moreover, we constructed a DENV-3 subgenomic replicon and screened a compound library. An arylnaphthalene lignan, C169-P1, was identified as an inhibitor of virus replication and cell entry. Finally, we demonstrated that C169-P1 exhibited a broad-spectrum antiviral effect against the infections with DENV-1 to -4. The reverse genetic systems and the compound candidate described here facilitate the study of DENV and related RNA viruses.

Bendamustine/Rituximab Plus Cytarabine/Rituximab, With or Without Acalabrutinib, for the Initial Treatment of Transplant-Eligible Mantle Cell Lymphoma Patients: Pooled Data From Two Pilot Studies.

INTRODUCTION: Mantle cell lymphoma (MCL) is a moderately aggressive lymphoma subtype, generally viewed as incurable. For younger, fit patients, the standard of care remains various high-dose cytarabine-based induction regimens followed by autologous hematopoietic cell transplant and 3 years of rituximab maintenance. Despite reasonably good outcomes, with median progression-free survival in the range of 7 to 9 years, most patients eventually relapse, indicating a need to improve the safety and tolerability of remission induction strategies. METHODS: Given the impressive activity of bendamustine/rituximab (BR) in older patients with MCL, we developed an induction regimen modeled after the Nordic Regimen but substituted BR in place of R-CHOP. In a second pilot study, we incorporated the second-generation Bruton tyrosine kinase inhibitor (BTKi), acalabrutinib, into the regimen. The primary endpoint of both studies was stem cell mobilization success rate. RESULTS: All patients successfully underwent stem cell harvest in both studies. CONCLUSION: The experience from our single institution pilot study suggested that sequential rather than alternating BR and cytarabine/rituximab (CR) was easier to administer from the standpoint of toxicities and subsequent dose modifications. Safety and efficacy data from the 2 pilot studies, FitMCL 1.0 and 2.0, were similar. The pilot studies provided preliminary safety data supporting the development of the NCTN trial EA4181, assessing three different induction regimens with or without acalabrutinib.

Virome Analysis and Association of Positive Coxsackievirus B Serology during Pregnancy with Congenital Heart Disease.

BACKGROUND: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown. METHODS: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD-affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB). We performed CVB IgG/IgM serological assays on plasma. We also used ViroCap sequencing and PCR to test for viral nucleic acid in plasma, circulating leukocytes from the buffy coat, and in the media of a co-culture system. RESULTS: CVB IgG/IgM results indicated that prior exposure was 7.8 times more common in the CHD group (95% CI, 1.14-54.24, adj. p-value = 0.036). However, the CVB viral genome was not detected in plasma, buffy coat, or co-culture supernatant by molecular assays, although other viruses were detected. CONCLUSION: Detection of viral nucleic acid in plasma was infrequent and specifically no CVB genome was detected. However, serology demonstrated that prior CVB exposure is higher in CHD-affected pregnancies. Further studies are warranted to understand the magnitude of the contribution of the maternal blood virome to the pathogenesis of CHD.

Outcomes of Treatment for Infective Endocarditis Following Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Recipients of transcatheter pulmonary valve replacement (TPVR) have shown increased risk of infective endocarditis (IE). Little is known about the outcomes of different management strategies, particularly surgery, for IE after TPVR. METHODS: We queried the Pediatric Health Information System database for cases of IE after TPVR performed from 2010-2020. We described patient demographics, hospital courses, admission complications, and treatment outcomes based on therapy offered, surgical or medical only. We compared outcomes of initial therapy. Data are expressed as median or percent. RESULTS: Sixty-nine cases of IE were identified, accounting for 98 related hospital admissions; 29% of patients recorded IE-related readmissions. Of those readmitted after initial medical therapy only, 33% had relapse IE. Rates of surgery were 22% during initial admission and 36% overall. Likelihood of surgical intervention increased with each subsequent admission. Renal and respiratory failure were more common in those given initial surgery. Mortality rate was 4.3% overall and 8% in the surgical cohort. CONCLUSION: Initial medical therapy may result in relapses/readmissions and possible delay of surgical therapy, which appears to be most effective for treatment of IE. For those treated only medically, a more aggressive course of therapy may be more likely to prevent relapse. Mortality following surgical therapy for IE after TPVR appears higher than reported for surgical pulmonary valve replacement generally.

Eliciting Opinions on Health Messaging During the COVID-19 Pandemic: Qualitative Survey Study.

BACKGROUND: Effective public health messaging has been necessary throughout the COVID-19 pandemic, but stakeholders have struggled to communicate critical information to the public, especially in different types of locations such as urban and rural areas. OBJECTIVE: This study aimed to identify opportunities to improve COVID-19 messages for community distribution in rural and urban settings and to summarize the findings to inform future messaging. METHODS: We purposively sampled by region (urban or rural) and participant type (general public or health care professional) to survey participants about their opinions on 4 COVID-19 health messages. We designed open-ended survey questions and analyzed the data using pragmatic health equity implementation science approaches. Following the qualitative analysis of the survey responses, we designed refined COVID-19 messages incorporating participant feedback and redistributed them via a short survey. RESULTS: In total, 67 participants consented and enrolled: 31 (46%) community participants from the rural Southeast Missouri Bootheel, 27 (40%) community participants from urban St Louis, and 9 (13%) health care professionals from St Louis. Overall, we found no qualitative differences between the responses of our urban and rural samples to the open-ended questions. Participants across groups wanted familiar COVID-19 protocols, personal choice in COVID-19 preventive behaviors, and clear source information. Health care professionals contextualized their suggestions within the specific needs of their patients. All groups suggested practices consistent with health-literate communications. We reached 83% (54/65) of the participants for message redistribution, and most had overwhelmingly positive responses to the refined messages. CONCLUSIONS: We suggest convenient methods for community involvement in the creation of health messages by using a brief web-based survey. We identified areas of improvement for future health messaging, such as reaffirming the preventive practices advertised early in a crisis, framing messages such that they allow for personal choice of preventive behavior, highlighting well-known source information, using plain language, and crafting messages that are applicable to the readers' circumstances.