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Purpose: Depressive symptoms during the perinatal period have broad and enduring health implications for birthing parents and their offspring. Rising prevalence rates of perinatal depression highlight the need for research examining factors influencing depressive symptoms during pregnancy, and trajectories during the early postnatal period. Grounded in bioecological systems theory, this longitudinal multimethod study examined whether prenatal bioecological factors predict depressive symptoms from pregnancy to 36 months postpartum., Methods: Participants were 162 pregnant individuals, oversampled for high emotion dysregulation, who completed a life stress interview and physiological assessment during the 3rd trimester and a self-report measure of depression at five time-points (3rd trimester, within 48 h of birth, 7, 18, and 36 months postpartum). Multilevel models were used to test study aims., Results: Participants exhibited the highest levels of depressive symptoms at 3rd trimester, and substantial variability in depressive symptom trajectories over time. Lower resting respiratory sinus arrhythmia (RSA), an index of parasympathetic nervous system functioning, in the 3rd trimester was associated with higher concurrent depressive symptoms. Higher levels of stress related to partner relationships, finances, and health were concurrently associated with more depressive symptoms during pregnancy and decreases in depressive symptoms over time. Specifically, depressive symptoms decreased only for individuals who reported high levels of stress during pregnancy., Limitations: Although grounded in bioecological systems theory, this study did not assess the macrosystem., Conclusions: Results of this study underscore the importance of multilevel predictors of perinatal health and highlights potential targets for preventing depression and promoting well-being during the perinatal transition., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Infant growth predicts long-term obesity and cardiovascular disease. Previous interventions designed to prevent obesity in the first 2 years of life have been largely unsuccessful. Obesity prevalence is high among traditional racial and ethnic minority groups., Objective: To compare the effectiveness of adding a digital childhood obesity prevention intervention to health behavior counseling delivered by pediatric primary care clinicians., Design, Setting, and Participants: Individually randomized, parallel-group trial conducted at 6 US medical centers and enrolling patients shortly after birth. To be eligible, parents spoke English or Spanish, and children were born after 34 weeks' gestational age. Study enrollment occurred between October 2019 and January 2022, with follow-up through January 2024., Interventions: In the clinic-based health behavior counseling (clinic-only) group, pediatric clinicians used health literacy-informed booklets at well-child visits to promote healthy behaviors (n = 451). In the clinic + digital intervention group, families also received health literacy-informed, individually tailored, responsive text messages to support health behavior goals and a web-based dashboard (n = 449)., Main Outcomes and Measures: The primary outcome was child weight-for-length trajectory over 24 months. Secondary outcomes included weight-for-length z score, body mass index (BMI) z score, and the percentage of children with overweight or obesity., Results: Of 900 randomized children, 86.3% had primary outcome data at the 24-month follow-up time point; 143 (15.9%) were Black, non-Hispanic; 405 (45.0%) were Hispanic; 185 (20.6%) were White, non-Hispanic; and 165 (18.3%) identified as other or multiple races and ethnicities. Children in the clinic + digital intervention group had a lower mean weight-for-length trajectory, with an estimated reduction of 0.33 kg/m (95% CI, 0.09 to 0.57) at 24 months. There was also an adjusted mean difference of -0.19 (95% CI, -0.37 to -0.02) for weight-for-length z score and -0.19 (95% CI, -0.36 to -0.01) for BMI z score. At age 24 months, 23.2% of the clinic + digital intervention group compared with 24.5% of the clinic-only group had overweight or obesity (adjusted risk ratio, 0.91 [95% CI, 0.70 to 1.17]) based on the Centers for Disease Control and Prevention criteria of BMI 85th percentile or greater. At that age, 7.4% of the clinic + digital intervention group compared with 12.7% of the clinic-only group had obesity (adjusted risk ratio, 0.56 [95% CI, 0.36 to 0.88])., Conclusions and Relevance: A health literacy-informed digital intervention improved child weight-for-length trajectory across the first 24 months of life and reduced childhood obesity at 24 months. The intervention was effective in a racially and ethnically diverse population that included groups at elevated risk for childhood obesity., Trial Registration: ClinicalTrials.gov Identifier: NCT04042467.

Hypotension following induction of general anaesthesia has been shown to result in increased complications and mortality postoperatively. Patients admitted to the hospital undergoing urgent surgery are often fasted from fluids for significant periods compared to elective patients subject to Enhanced Recovery After Surgery protocols despite guidelines stating that a two-hour fast is sufficient. The aim of this prospective, observational study was to compare fasting times and intravascular volume status between elective surgery patients subject to enhanced recovery protocols and inpatient, urgent surgery patients and to assess differences in the incidence of post-induction hypotension. Fasting data was obtained by questionnaire in the preoperative area in addition to inferior vena cava collapsibility index, a non-invasive measure of intravascular volume. Blood pressure readings and drug administration for the ten minutes following induction were obtained from patients' charts. Inpatients undergoing urgent surgery were fasted significantly longer than enhanced recovery patients and had lower intravascular volume. However, no difference was found in the incidence of post-induction hypotension.

Background: We conducted a quantitative analysis of the microbial burden and prevalence of epidemiologically important pathogens (EIP) found on long-term care facilities (LTCF) environmental surfaces., Methods: Microbiological samples were collected using Rodac plates (25cm2/plate) from resident rooms and common areas in five LTCFs. EIP were defined as MRSA, VRE, C. difficile and multidrug-resistant (MDR) Gram-negative rods (GNRs)., Results: Rooms of residents with reported colonization had much greater EIP counts per Rodac (8.32 CFU, 95% CI 8.05, 8.60) than rooms of non-colonized residents (0.78 CFU, 95% CI 0.70, 0.86). Sixty-five percent of the resident rooms and 50% of the common areas were positive for at least one EIP. If a resident was labeled by the facility as colonized with an EIP, we only found that EIP in 30% of the rooms. MRSA was the most common EIP recovered, followed by C. difficile and MDR-GNR., Discussion: We found frequent environmental contamination with EIP in LTCFs. Colonization status of a resident was a strong predictor of higher levels of EIP being recovered from his/her room.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease., (© 2024. The Author(s).)

In this issue, Sinha et al. 1 use cellular chromatin reporter assays along with CRISPR gene editing to reveal that the histone H3.3K36M oncohistone mutation disrupts epigenetic memory and stability of H3K9me3 domains by blocking transitions into a stably repressed state., Competing Interests: Declaration of interests N.A.H. is a founder and shareholder of Epigenos Biosciences, Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The accurate diagnosis of haematolymphoid malignancies is crucial for effective cancer care, but major obstacles to diagnosis exist in low- and middle-income countries (LMICs). This article explores the global applicability of current haematolymphoid classification systems, which are predominantly derived from data generated in high-income countries (HICs). Although disproportionately burdened with poor cancer outcomes, LMICs are generally faced with limited diagnostic resources, suboptimal access to therapeutics, and inadequate healthcare infrastructure. The article highlights the challenges faced by LMICs, including inconsistent access to high-quality pathology services, limited availability of advanced diagnostic techniques, and a lack of population-based cancer registry data. It also discusses the progress made in narrowing the gap between LMICs and HICs, such as the introduction of resource-adapted classifications, improved guidance on essential diagnostic tools, and strengthening of in-country professional pathology networks. Innovative diagnostic approaches, including gene expression profiling and machine learning, represent potential solutions for improving the diagnostic accuracy in LMICs, but addressable gaps remain. Recommendations are suggested for sustainable investments in diagnostic infrastructure, capacity-building, and population-based cancer registries to enhance the global applicability of haematolymphoid classification systems and improve outcomes for patients in LMICs., (© 2024 John Wiley & Sons Ltd.)

Background: Society of Thoracic Surgeons Congenital Heart Surgery Database is the largest congenital heart surgery database worldwide but does not provide information beyond primary episode of care. Linkage to hospital electronic health records would capture complications and comorbidities along with long-term outcomes for patients with CHD surgeries. The current study explores linkage success between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health record data in North Carolina and Georgia., Methods: The Society of Thoracic Surgeons Congenital Heart Surgery Database was linked to hospital electronic health records from four North Carolina congenital heart surgery using indirect identifiers like date of birth, sex, admission, and discharge dates, from 2008 to 2013. Indirect linkage was performed at the admissions level and compared to two other linkages using a "direct identifier," medical record number: (1) linkage between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health records from a subset of patients from one North Carolina institution and (2) linkage between Society of Thoracic Surgeons data from two Georgia facilities and Georgia's CHD repository, which also uses direct identifiers for linkage., Results: Indirect identifiers successfully linked 79% (3692/4685) of Society of Thoracic Surgeons Congenital Heart Surgery Database admissions across four North Carolina hospitals. Direct linkage techniques successfully matched Society of Thoracic Surgeons Congenital Heart Surgery Database to 90.2% of electronic health records from the North Carolina subsample. Linkage between Society of Thoracic Surgeons and Georgia's CHD repository was 99.5% (7,544/7,585)., Conclusions: Linkage methodology was successfully demonstrated between surgical data and hospital-based electronic health records in North Carolina and Georgia, uniting granular procedural details with clinical, developmental, and economic data. Indirect identifiers linked most patients, consistent with similar linkages in adult populations. Future directions include applying these linkage techniques with other data sources and exploring long-term outcomes in linked populations.

In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity. Nanomaterials can play a pivotal role in addressing targeting and other challenges in cancer immunotherapy. Dendritic mesoporous silica nanoparticles (DMSNs) can enhance the efficacy of cancer vaccines by enhancing the effective loading of immune modulatory agents owing to their tunable pore sizes. In this work, an emulsion-based method is optimized to customize the pore size of DMSNs and loaded DMSNs with ovalbumin (OVA) and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (CpG-OVA-DMSNs). The immunotherapeutic effect of DMSNs is achieved through controlled chemical release of OVA and CpG in antigen-presenting cells (APCs). The results demonstrated that CpG-OVA-DMSNs efficiently activated the immune response in APCs and reduced tumor growth in the murine B16-OVA tumor model., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Chronic musculoskeletal pain is highly prevalent and poses a significant personal, societal, and economic burden. Management of chronic musculoskeletal pain remains a challenge. Long-term use of common analgesic medications such as nonsteroidal anti-inflammatory drugs and opioids is associated with adverse events, and in the case of opioids, drug addiction. Additionally, many individuals do not experience sufficient pain relief with these therapeutic approaches. Thus, there is an urgent need to develop clinically efficacious and safe therapeutics for musculoskeletal pain. Recent advances in our understanding of musculoskeletal pain neurobiology have helped identify the role of neurotrophic factors, specifically, the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFL) and their associated signaling pathways. This review outlines our current understanding of the GFL signaling systems, discusses their role in inflammatory and chronic musculoskeletal pain and sensitivity, and comments on the analgesic therapeutic potential of targeting the GFL signaling system., Competing Interests: Declaration of competing interest BDXL has received consulting fees from Regeneron. AG and SKM have no conflicts to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hospitalized patients living with dementia (PLWD) age 65+ generally experience poor outcomes. This study's purpose was to implement dementia-friendly training with staff, track patient outcomes, and implement sustainable system changes., Methods: We conducted a prospective study in five hospitals. The hospitals adopted HealthCare Interactive's CARES® Dementia 5-Step Method for Hospitals Online Training and Certification Program . After on-line modules completion, a didactic session was offered, and a retrospective pre/post survey was completed. Patient falls, length of stay, and readmission rates were collected., Results: 1,836 (41 %) staff completed the training. Positive changes in staff ratings from pre- to post- intervention were observed. Number of falls and readmissions did not change. The average number of stays per patient decreased by .24 (p=0.01). Hospitals made system changes including innovative identification for PLWD., Conclusions: Dementia-friendly hospital training is effective in improving staff recognition of the symptoms and needs of PLWD, and responding appropriately., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting. Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to 2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]). Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p  < 0.0001). The frequency of thromboembolic events over 12 months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy ( p  = 0.352); although, event numbers were low. Conclusion: A pre-emptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

Importance: More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis., Observations: Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis., Conclusions and Relevance: In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.

Purpose: Maintaining a robust healthcare workforce in underserved rural communities continues to be a challenge. To better meet healthcare needs in rural areas, training programs must develop innovative ways to foster transition to, and integration into, these communities. Mountain Area Health Education Center designed and implemented a 12-month post-residency Rural Fellowship program to enhance placement, transition, and retention in rural North Carolina. Utilizing a '6 Ps' framework, the program targeted physicians and pharmacists completing residency with the purpose of recruiting and supporting their transition into the first year of rural practice., Method: To better understand Rural Fellows' experiences and the immediate impact of their Fellowship year, we conducted a semi-structured interview using a narrative technique and evaluated retention rates over time. Interviews with the eight participants, which included Fellowship alumni and current Fellows, demonstrated the impact and influence of the key curricular '6 Ps' framework., Results: An early retention rate of 100% and a long-term retention rate of 87%, combined with expressed clarity of curricular knowledge, skills, and attitudes related to the '6 Ps', demonstrate the potential and effectiveness of this Rural Fellowship model. Participants indicated the Rural Fellowship experience supports the transition to rural practice communities and expands their clinical skills., Conclusion: The Rural Fellowship program demonstrates an effective model to support early career healthcare providers as they begin practice in rural communities in western North Carolina through academic opportunities, personal growth, and professional development. Implementation of this model has demonstrated the success of a rural retention model over a 6-year period. This model has the potential to target an array of clinical providers and disciplines. We started with family medicine and have expanded to psychiatry, obstetrics, pharmacy, and nursing. This study demonstrated that this model supports clinical providers during the critical transition period from residency to practice. Targeting the most important stage of one's medical training, the commencement of professional practice, this is a scalable model for other rural-based health professions education sites where rural recruitment and retention remain a problem.

Background and Objective: Valproic acid (VPA) demonstrates nonlinear pharmacokinetics (PK) due to a capacity-limited protein binding, which has potential implications on its total and unbound plasma concentrations, especially during hypoalbuminemia. A physiologically based pharmacokinetic (PBPK) model was developed to assess the nonlinear dose-exposure relationship of VPA with special emphasis on pediatric patients with hypoalbuminemia., Methods: A PBPK model was first developed and evaluated in adults using PK-Sim ® and MoBi ® (v.11) and the scaled to children 1 year and older. The capacity-limited protein binding was characterized by second-order kinetics between VPA and albumin with a 2:1 molar ratio. All drug-specific parameters were informed by literature and optimized using published PK data of VPA. PK simulations were performed in virtual populations with normal and low albumin levels., Results: The reported concentration-time profiles of total and unbound VPA were adequately predicted by the PBPK model across the age and dose range (3-120 mg/kg). The model was able to characterize the nonlinear PK, as the concentration-dependent fraction unbound (f u ) and the related dose-dependent clearance values were well predicted. Simulated steady-state trough concentrations of total VPA were less than dose-proportional and were within the therapeutic drug monitoring range of 50-100 mg/L for doses between 30 and 45 mg/kg per day in children with normal albumin concentrations. However, virtual children with hypoalbuminemia largely failed to achieve the target exposure., Conclusion: The PBPK model helped assess the nonlinear dose-exposure relationship of VPA and the impact of albumin concentrations on the achievement of target exposure., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: We examined characteristics associated with financial barriers to healthcare and the association of financial barriers with adverse healthcare events among US adult cancer survivors enrolled in Medicare., Methods: We used nationally representative Medicare Current Beneficiary Survey data (2011-2013, 2015-2017) to identify adults with a history of non-skin cancer. We defined financial barriers as cost-related trouble accessing and/or delayed care in the prior year. Using propensity-weighted multivariable logistic regression, we examined associations between financial barriers and adverse healthcare events (any ED visits, any inpatient hospitalizations)., Results: Overall, 11.0% of adult Medicare beneficiaries with a history of cancer reported financial barriers in the prior year, with higher burden among beneficiaries < 65 years of age vs. ≥ 65 (32.5% vs. 8.2%, p < 0.0001) and with annual income < $25,000 vs. ≥ $25,000 (18.1% vs. 6.9%, p < 0.0001). In bivariate models, financial barriers were associated with a 7.8 percentage point (95% CI: 1.5-14.0) increase in the probability of ED visits. In propensity-weighted models, this association was not statistically significant. The association between financial barriers and hospitalizations was not significant in the overall population; however, financial barriers were associated with a decreased probability of hospitalization among Black/African American beneficiaries., Conclusions: Despite Medicare coverage, beneficiaries with a history of cancer are at risk for experiencing financial barriers to healthcare. In the overall population, financial barriers were not associated with ED visits or hospitalizations., Implications for Cancer Survivors: Policies limiting Medicare patient out-of-pocket spending and care models addressing health-related social needs are needed to reduce financial barriers experienced., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Academic specialists in general obstetrics and gynecology are clinicians practicing the full breadth of the specialty while also contributing to medical education and scientific discovery. Residency programs in obstetrics and gynecology provide exposure to research training that is variable but frequently limited. This creates challenges for junior faculty and in many cases limits their research productivity, typically measured by published original research articles and grant funding. This frequently disadvantages academic specialists in promotion compared with their subspecialty fellowship-trained colleagues. A few research fellowship programs were recently launched to address this issue. However, these programs are not uniform and encounter challenges such as sustainable funding. In this article, building on knowledge from current academic specialist fellowship programs, we discuss the needs, challenges, and proposed solutions. We also propose some details needing further discussion among the academic obstetrics and gynecology community. We discuss how such fellowships can integrate with current development and training opportunities such as the Women's Reproductive Health Research award, Building Interdisciplinary Research Careers in Women's Health award, other K and K-type career development programs, NIH T32 grants, and clinical research courses for obstetricians and gynecologists. Academic specialist fellowship programs can have synergy with other women's health fellowship programs offered by other specialties. They can additionally leverage institutional resources. We conclude by summarizing a proposed model for academic specialist research fellowship programs., Competing Interests: Financial Disclosure Andrea K. Knittel's institution received funding form the NIH, Doris Duke Foundation, Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, North Carolina Department of Health and Human Services NIMHD, and the FORE Foundation. She serves as a DEI Task Force Member, SASGOG Board Member, and she serves on the Academic Consortium on Criminal Justice Health. She is also ACOG's liaison to the National Commission on Correctional Health Care. Jeffrey F. Peipert's institution received support from Bayer, Merck, and CooperSurgical. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The implementation of digital breast tomosynthesis has increased the detection of radial scar (RS). Managing this finding may be experienced as a clinical dilemma in daily practice. Breast Contrast-Enhanced MRI (CE-BMR) is a known modality in case of problem-solving tool for mammographic abnormalities. However, the data about AD and CE-BMR are scant., Objective: The purpose was to estimate the benefit of CE-BMR in the setting of RS detected mammographically through a systematic review and meta-analysis of the literature., Methods: A search of MEDLINE and EMBASE databases were conducted in 2022. Based on the PRISMA guidelines, an analysis was performed. The primary endpoint was the correlation between CE-BMR findings and definite outcome for RS (pure RS versus RS associated with atypia or malignancy)., Results: Three studies were available. The negative predictive value (NPV) was 100% for each., Conclusion: The high NPV could allow for deferral of a biopsy in favor of a short-interval imaging follow-up in the setting of a negative CE-BMR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: To assess the characteristics of patients enrolled in the ILD-PRO Registry., Methods: The ILD-PRO Registry is a multicentre US registry of patients with progressive pulmonary fibrosis. This registry is enrolling patients with an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis who have reticular abnormality and traction bronchiectasis on HRCT, and who meet criteria for ILD progression within the prior 24 months. Patient characteristics were analysed based on the number of patients with available data., Results: Of the first 491 patients enrolled, the majority were white (75.4%) and female (60.6%); 47.4% had a history of smoking. Reported ILDs were autoimmune disease-associated ILDs (47.2%), hypersensitivity pneumonitis (17.5%), idiopathic non-specific interstitial pneumonia (9.1%), interstitial pneumonia with autoimmune features (8.9%), unclassifiable ILD (7.6%), other ILDs (9.7%). At enrolment, median (Q1, Q3) FVC % predicted was 62.2 (49.4, 72.4) and DLco % predicted was 39.2 (30.2, 49.2). Median (Q1, Q3) total score on the St. George's Respiratory Questionnaire was 50.8 (35.9, 64.7). The most common comorbidities were gastroesophageal reflux disease (61.1%) and sleep apnoea (29.6%). Overall, 64.5% of patients were receiving immunosuppressive or cytotoxic therapy, 61.1% proton-pump inhibitors, 53.2% oral steroids, 19.8% nintedanib and 3.6% pirfenidone., Conclusions: Patients enrolled into the ILD-PRO Registry have a variety of ILD diagnoses, marked impairment in lung function and health-related quality of life, and high medication use. Longitudinal data from this registry will further our knowledge of the course of progressive pulmonary fibrosis., Trial Registration: ClinicalTrials.gov, NCT01915511; registered August 5, 2013., (© 2024. The Author(s).)

Aims: Serum, liver and urinary bile acids are increased, and hepatic transport protein levels are decreased in a non-clinical model of polycystic kidney disease. Similar changes in patients with autosomal dominant polycystic kidney disease (ADPKD) may predispose them to drug-induced liver injury (DILI) and hepatic drug-drug interactions (DDIs). Systemic coproporphyrin-I (CP-I), an endogenous biomarker for hepatic OATP1B function and MRP2 substrate, is used to evaluate OATP1B-mediated DDI risk in humans. In this clinical observational cohort-comparison study, bile acid profiles and CP-I concentrations in healthy volunteers and patients with ADPKD were compared., Methods: Serum and urine samples from healthy volunteers (n = 16) and patients with ADPKD (n = 8) were collected. Serum bile acids, and serum and urine CP-I concentrations, were quantified by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)., Results: Patients with ADPKD exhibited increased serum concentrations of total (1.3-fold) and taurine-conjugated (2.8-fold) bile acids compared to healthy volunteers. Specifically, serum concentrations of six bile acids known to be more hydrophobic/hepatotoxic (glycochenodeoxycholate, taurochenodeoxycholate, taurodeoxycholate, lithocholate, glycolithocholate and taurolithocholate) were increased (1.5-, 2.9-, 2.8-, 1.6-, 1.7- and 2.7-fold, respectively) in patients with ADPKD. Furthermore, serum CP-I concentrations were elevated and the renal clearance of CP-I was reduced in patients with ADPKD compared to healthy volunteers., Conclusions: Increased exposure to bile acids may increase susceptibility to DILI in some patients with ADPKD. Furthermore, the observed increase in serum CP-I concentrations could be attributed, in part, to impaired OATP1B function in patients with ADPKD, which could increase the risk of DDIs involving OATP1B substrates compared to healthy volunteers., (© 2024 British Pharmacological Society.)

The creation of ex vivo human liver models has long been a critical objective in academic, clinical, and pharmaceutical research, particularly for drug development, where accurate evaluation of hepatic metabolic dynamics is crucial. We have developed a bioengineered, perfused, organ-level human liver model that accurately replicates key liver functions, including metabolic activities, and protein synthesis, thus addressing some of the limitations associated with traditional liver monolayers, organoids, and matrix-embedded liver cells. Our approach utilizes liver-specific biomatrix scaffolds, prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions. These scaffolds, when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines, enable the formation of three-dimensional (3D) human livers with enhanced cellular organization. The "recellularized tissue-engineered livers" (RCLs) have undergone various analyses, demonstrating the capability for establishing liver microenvironments ex vivo . Within 7-14 days, the RCLs exhibit evidence of liver differentiation and metabolic capabilities, underscoring the potential for use in drug metabolism and toxicity studies. Although our study represents a significant step forward, we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses. The high drug-metabolizing enzyme activity of RCLs, as demonstrated in our study, provides a promising avenue for investigating drug-induced liver injury mechanisms, contributing to a more detailed understanding of early drug discovery processes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Oral fluids provide ready detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to evaluate relationships between oral virus, oral and systemic anti-SARS-CoV-2-specific antibodies, and symptoms. Oral fluids (saliva/throat wash (saliva/TW)) and serum were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+ human participants (n = 45). SARS-CoV-2 RT-qPCR and N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR for subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA and ELISA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. At time of enrollment (baseline, BL), LFA-detected N-antigen in 86% of TW and was immunoblot-confirmed. However, only 3/17 were saliva/TW qPCR+ . Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three anti-spike sero-negative participants suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At enrollment, symptomatic participants demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (63%/54%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral and serum IgG correlated 100% with NP+ PCR status. Cough and fatigue severity (p = 0.010 and 0.018 respectively), and presence of weakness, nausea, and composite upper respiratory symptoms (p = 0.037, 0.005, and 0.017, respectively) were negatively associated with saliva IgM but not TW or serum IgM. Throat wash IgM levels were higher in women compared to men, although the association did not reach statistical significance (median: 290 (female) versus 0.697, p = 0.056). Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms and early oral IgM responses during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objectives : Despite CTAs being critical for preoperative planning in autologous breast reconstruction, experienced plastic surgeons may have differing preferences for which side of the abdomen to use for unilateral breast reconstruction. Large language models (LLMs) have the potential to assist medical imaging interpretation. This study compares the perforator selection preferences of experienced plastic surgeons with four popular LLMs based on CTA images for breast reconstruction. Materials and Methods : Six experienced plastic surgeons from Australia, the US, Italy, Denmark, and Argentina reviewed ten CTA images, indicated their preferred side of the abdomen for unilateral breast reconstruction and recommended the type of autologous reconstruction. The LLMs were prompted to do the same. The average decisions were calculated, recorded in suitable tables, and compared. Results : The six consultants predominantly recommend the DIEP procedure (83%). This suggests experienced surgeons feel more comfortable raising DIEP than TRAM flaps, which they recommended only 3% of the time. They also favoured MS TRAM and SIEA less frequently (11% and 2%, respectively). Three LLMs-ChatGPT-4o, ChatGPT-4, and Bing CoPilot-exclusively recommended DIEP (100%), while Claude suggested DIEP 90% and MS TRAM 10%. Despite minor variations in side recommendations, consultants and AI models clearly preferred DIEP. Conclusions : Consultants and LLMs consistently preferred DIEP procedures, indicating strong confidence among experienced surgeons, though LLMs occasionally deviated in recommendations, highlighting limitations in their image interpretation capabilities. This emphasises the need for ongoing refinement of AI-assisted decision support systems to ensure they align more closely with expert clinical judgment and enhance their reliability in clinical practice.

Little is known about HIV testing, pre-exposure prophylaxis (PrEP) awareness and uptake among adolescent and young men who have sex with men (AYMSM) in Vietnam. We conducted an online survey among AYMSM in Vietnam to determine the prevalence of HIV testing, PrEP awareness, uptake and their correlates. From December 2022-March 2023, 120 HIV-negative AYMSM from 15 to 19 years old in Hanoi and Ho Chi Minh city, Vietnam were recruited through peer referral to complete an online survey, which included questions on demographics, sexual behaviors, HIV risk perception and knowledge, HIV and sexually transmitted infections (STI) testing, PrEP awareness and uptake. Separate multivariable models were used to determine the correlates of HIV testing, PrEP awareness and uptake. Only 58% of participants had ever been tested for HIV. The majority of participants had heard of PrEP before (82%), but only 36% had ever used PrEP. HIV knowledge (aPR (adjusted prevalence ratio) = 1.59; 95%CI:1.06-2.39), a history of STI testing (aPR = 1.32; 95%CI:1.06-1.64), having had anal sex with another man (aPR = 4.49; 95%CI:1.40-14.38) and lower HIV risk perception (aPR = 0.62; 95%CI:0.47-0.83) were associated with HIV testing. HIV knowledge (aPR = 1.38; 95%CI:1.06-1.78) and a history of STI testing (aPR = 1.16; 95%CI:1.03-1.32) were also associated with PrEP awareness. Higher HIV risk perception was negatively associated with PrEP use (aPR = 0.59; 95%CI:0.35-0.99). Our findings underscored the urgent need for further research to explore the causes of the gaps in HIV testing and PrEP use as well as to design innovative interventions tailored to the needs of AYMSM to support HIV testing and PrEP use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The authors explored whether neighborhood context is associated with psychotropic polypharmacy and psychotherapy among a cohort of children with high needs for psychiatric and general medical care., Methods: Electronic health record data from a large health care system were used in a cross-sectional design to examine psychotropic polypharmacy and psychotherapy in 2015-2019 among children ages 2-17 years (N=4,017) with geocoded addresses. Inclusion criteria were a diagnosis of a mental health condition, an intellectual and developmental disability, or a complex medical condition and one or more clinical encounters annually over the study period. Polypharmacy was defined as two or more psychotropic drug class prescriptions concurrently for ≥60 days. Psychotherapy was defined as receipt of any psychotherapy or adaptive behavior treatment. Neighborhood context (health, environment, education, and wealth) was measured with the Child Opportunity Index. Multilevel generalized linear mixed models with random intercept for census tracts were used to assess the associations between individual and neighborhood characteristics and psychotropic polypharmacy and psychotherapy., Results: Moderate (vs. low) child opportunity was associated with higher odds of polypharmacy (adjusted OR [AOR]=1.79, 95% CI=1.19-2.67). High (vs. low) child opportunity was associated with higher odds of psychotherapy (AOR=2.15, 95% CI=1.43-3.21). Black (vs. White) race (AOR=0.51, 95% CI=0.37-0.71) and Hispanic ethnicity (AOR=0.44, 95% CI=0.26-0.73) were associated with lower odds of polypharmacy., Conclusions: Among high-need children, neighborhood Child Opportunity Index, race, and ethnicity were significantly associated with treatment outcomes in analyses adjusted for clinical factors. The findings underscore concerns about structural disparities and systemic racism and raise questions about access., Competing Interests: The authors report no financial relationships with commercial interests.

Wholly defined ex vivo expansion conditions for biliary tree stem cell (BTSC) organoids were established, consisting of a defined proliferative medium (DPM) used in combination with soft hyaluronan hydrogels. The DPM consisted of commercially available Kubota's Medium (KM), to which a set of small molecules, particular paracrine signals, and heparan sulfate (HS) were added. The small molecules used were DNA methyltransferase inhibitor (RG108), TGF- β Type I receptor inhibitor (A83-01), adenylate cyclase activator (Forskolin), and L-type Ca 2+ channel agonist (Bay K8644). A key paracrine signal proved to be R-spondin 1 (RSPO1), a secreted protein that activates Wnts. Soluble hyaluronans, 0.05 % sodium hyaluronate, were used with DPM to expand monolayer cultures. Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology [ G* ] of less than 100 Pa. The combination is called the BTSC-Expansion-Glycogel-System (BEX-gel system) for expanding BTSCs as a monolayer or as organoids. The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors. Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah -/- mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions. The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases., Competing Interests: All authors declare that there are no competing interests., (© 2024 The Authors.)

A novel wall-mounted far ultraviolet-C (UV-C) light technology providing automated delivery of far UV-C only when people are not present reduced methicillin-resistant Staphylococcus aureus in a patient room and equipment room. The safety feature that discontinues far UV-C output when people are detected was effective in preventing far UV-C exposure., Competing Interests: C.J.D has received research grants from Clorox, Pfizer, and Ecolab. All other authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Introduction: Evaluating physician perceptions of telemedicine use and its impact on care quality among physician providers is critical to sustaining telemedicine programs, given the uncertainty of reimbursement policy, preferences, inadequate training, and technical difficulties. Physicians reported technical barriers to effectively practicing integrated medicine using telemedicine as patient volumes increased during the pandemic. The objective of this work was to examine whether perceived practice barriers and facilitators were associated with physician respondents' perceptions of telemedicine care quality compared with in-person care. Methods: This cross-sectional study analyzed the 2021 National Electronic Health Record Survey. The sample comprised 1,857 nonfederally employed physicians (weighted n = 403,013) delivering integrated patient care. Of those physicians, 1,630 (weighted n = 346,646) reported providing care through telemedicine. We reported frequencies and percentages of reported practice characteristics. Generalized ordinal logistic regressions examined relationships between practice factors and care quality for telemedicine care. Results: Most of the sample ( n = 1,630) were male (66.1%), >50 years of age (66.1%), and worked in a single location (73.5%). A total of 70% of respondents reported that patients had difficulty using telemedicine platforms, and 64% reported limitations in patients' access to technology. Most respondents indicated having provided quality care to some extent (45%) and to a great extent (26%) during telemedicine visits compared to in-person visits. Associations between barriers, facilitators, and care quality perceptions were positive, underscoring resiliency in telemedicine programs among practices. Conclusion: Care modalities and the organizational, environmental, and personal facilitators drive quality perceptions among physicians. Perceived fit and usability determine perceptions of care quality for providers integrating telemedicine into their practice.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer of neuroendocrine origin that is typically associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet (UV) light. We report a case of relapsed MCC that presented with new symptoms of fatigue, back pain, and myeloid left shift identified during scheduled follow-up. The patient was found to have circulating neoplastic cells in the peripheral blood and bone marrow metastasis. Immunohistochemistry for synaptophysin, CD56, INSM-1, CK20, CD117 were positive, whereas CD34, TdT, Chromogranin, CD10, myeloperoxidase, CD3 and CD19 were negative. Flow cytometry of the peripheral blood confirmed the presence of an abnormal nonhematopoietic cell population expressing CD56 positivity. A next-generation sequencing (NGS) panel revealed the presence of variants in RB1, TP53, and other genes, some of which have not been previously described in MCC. This rare presentation highlights the challenges in the diagnosis and management of MCC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, persons ≥65 years of age and healthcare personnel represented the most vulnerable groups with respect to risk of infection, severe illness, and death. However, as the pandemic progressed, there was an increasingly detrimental effect on young children and adolescents. Severe disease and hospitalization increased over time in pediatric populations, and containment measures created substantial psychosocial, educational, and economic challenges for young people. Vaccination of children against COVID-19 has been shown to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and severe outcomes in pediatric populations and may also help to prevent the spread of variants of concern and improve community immunity. This review discusses the burden of COVID-19 on children throughout the pandemic, the role of children in disease transmission, and the impact of COVID-19 vaccination., Competing Interests: D.J.W. has received consulting fees from Pfizer, Germitac, PDI, and BD in relation to vaccines and disinfection products, was a member of a Data Safety Monitoring Board/Advisory Board at GlaxoSmithKline, and is a member on the board at Society for Healthcare Epidemiology of America (SHEA). K.O.Z. receives salary support from the US National Institutes of Health (NIH) and the US Food and Drug Administration (FDA) through Duke University, has received an honorarium from Pediatric Grand Rounds (Ohio State University) and for an NMA COVID-19 report on provider perspectives, and is on the membership committee for USP. S.Y.T. has received grants from Pfizer Inc., paid directly to the institution, for work unrelated to this manuscript. J.M.M. is an employee and holds stock options at Pfizer Inc. S.P. is an employee of BioNTech SE.

Introduction: Significant progress has been made in reducing maternal exposure to tobacco smoke and subsequent adverse birth outcomes, however, reductions may require strategies that reduce the availability of tobacco retailers. In this study, we investigated the relationship between tobacco retailer density and birth outcomes across the USA and predicted the potential impact of a tobacco retailer density cap on these outcomes., Methods: Annual US county (n=3105), rates of preterm birth, low birth weight, small-for-gestational age, all-cause infant mortality and sudden infant death syndrome (SIDS) were calculated using National Vital Statistics System data. Tobacco retailers were identified from the National Establishment Time-Series Database. We used Poisson regression to estimate the effect of capping retailer density at 1.4 retailers per 1000 population, controlling for county demographics and air pollution, using propensity score weighting., Results: Tobacco retailer density was positively associated with most adverse birth outcomes. We estimate that a nationwide cap on tobacco retailer density, implemented in 2016, would have resulted in a reduction of 4275 (95% CI 2210 to 6392) preterm births, 6096 (95% CI 4421 to 7806) small-for-gestational-age births, 3483 (95% CI 2615 to 4378) low birthweight births, 538 (95% CI 345 to 733) all-cause infant deaths and 107 (95% CI 55 to 158) SIDS deaths in that year., Conclusion: Higher rates of adverse birth outcomes were seen in counties with high tobacco retailer density compared with those with low density. These results provide further support for regulating tobacco retail density to reduce adverse health outcomes associated with tobacco use., Competing Interests: Competing interests: KMR and AYK serve as paid expert consultants in litigation against the tobacco industry., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Therapeutic hypothermia is the standard treatment for hypoxic-ischemic encephalopathy (HIE), but despite its widespread use, the rates of mortality and neurodevelopmental impairment for moderate to severe HIE remain around 30%. Methylxanthines, such as caffeine and aminophylline, have potential neuroprotective effects in the setting of hypoxic-ischemic injury. However, data on the safety and efficacy of methylxanthines in the setting of therapeutic hypothermia for HIE are limited. This retrospective multicenter study examined in-hospital outcomes in 52 infants with HIE receiving methylxanthines and therapeutic hypothermia. The frequency of mortality and in-hospital morbidities were similar to those of infants enrolled in clinical trials undergoing therapeutic hypothermia without adjunctive therapies. Clinical trials of methylxanthines for neuroprotection in HIE are needed to determine safety and efficacy and should explore optimal dosing and timing of methylxanthine administration., (© 2024. The Author(s).)

Background: Recent advances in single cell sequencing have led to an increased focus on the role of cell-type composition in phenotypic presentation and disease progression. Cell-type composition research in the heart is challenging due to large, frequently multinucleated cardiomyocytes that preclude most single cell approaches from obtaining accurate measurements of cell composition. Our in silico studies reveal that ignoring cell type composition when calculating differentially expressed genes (DEGs) can have significant consequences. For example, a relatively small change in cell abundance of only 10% can result in over 25% of DEGs being false positives., Methods: We have implemented an algorithmic approach that uses snRNAseq datasets as a reference to accurately calculate cell type compositions from bulk RNAseq datasets through robust data cleaning, gene selection, and multi-sample cross-subject and cross-cell-type deconvolution. We applied our approach to cardiomyocyte-specific α1A adrenergic receptor (CM-α1A-AR) knockout mice. 8-12 week-old mice (either WT or CM-α1A-KO) were subjected to permanent left coronary artery (LCA) ligation or sham surgery (n=4 per group). Transcriptomes from the infarct border zones were collected 3 days later and analyzed using our algorithm to determine cell-type abundances, corrected differential expression calculations using DESeq2, and validated these findings using RNAscope., Results: Uncorrected DEGs for the CM-α1A-KO X LCA interaction term featured many cell-type specific genes such as Timp4 (fibroblasts) and Aplnr (cardiomyocytes) and overall GO enrichment for terms pertaining to cardiomyocyte differentiation (P=3.1E-4). Using our algorithm, we observe a striking loss of cardiomyocytes and gain in fibroblasts in the α1A-KO + LCA mice that was not recapitulated in WT + LCA animals, although we did observe a similar increase in macrophage abundance in both conditions. This recapitulates prior results that showed a much more severe heart failure phenotype in CM-α1A-KO + LCA mice. Following correction for cell-type, our DEGs now highlight a novel set of genes enriched for GO terms such as cardiac contraction (P=3.7E-5) and actin filament organization (P=6.3E-5)., Conclusions: Our algorithm identifies and corrects for cell-type abundance in bulk RNAseq datasets opening new avenues for research on novel genes and pathways as well as an improved understanding of the role of cardiac cell types in cardiovascular disease.

The ability to visualize and track multiple biological processes in vivo in real time is highly desirable. Bioluminescence imaging (BLI) has emerged as an attractive modality for non-invasive cell tracking, with various luciferase reporters enabling parallel monitoring of several processes. However, simultaneous multiplexed imaging in vivo is challenging due to suboptimal reporter intensities and the need to image one luciferase at a time. We report a multiplexed BLI approach using a single substrate that leverages bioluminescence resonance energy transfer (BRET)-based reporters with distinct spectral profiles for triple-color BLI. These luciferase-fluorophore fusion reporters address light transmission challenges and use optimized coelenterazine substrates. Comparing BRET reporters across two substrate analogs identified a green-yellow-orange combination that allows simultaneous imaging of three distinct cell populations in vitro and in vivo . These tools provide a template for imaging other biological processes in vivo during a single BLI session using a single reporter substrate., Competing Interests: T.A.K. is an employee of Promega Corporation. J.R.W. and T.A.K. are inventors on a patent describing furimazine and furimazine derivatives. A.L.A. is a Global Advisory Board member and paid consultant for LG Chem Life Sciences Innovation Center., (© 2024 The Author(s).)

Introduction: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey., Methods: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed., Results: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime., Discussion: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies., Conclusion: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers., (© 2024 The Author(s). Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

Background To address rural physician workforce shortages, the Health Resources and Services Administration funded multiple Rural Residency Planning and Development (RRPD) awards, beginning in 2019, to develop rural residency programs in needed specialties. Objective To describe early resident recruitment outcomes of the RRPD grants program. Methods A cross-sectional survey of program directors or administrators of these 25 new rural residency training programs across the United States was administered at RRPD award conclusion in 2022. We performed descriptive analyses of applicant and Match data, including applications and interviews per resident position, positions filled in the main Match vs the Supplemental Offer and Acceptance Program (SOAP), and recruitment of residents from the program's state. Results The 25 Cohort 1 RRPD programs ranged from 2 to 8 residents per year. Most programs (16 of 25, 64.0%) were rural expansion tracks of an urban program. Most programs were sufficiently developed to participate in the 2022 (N=17) or 2023 (N=20) Match; we report on 13 of 17 (76.5%) programs for 2022 and 14 of 20 (70.0%) programs for 2023. Programs completed a median of 14.8 interviews per position. Most positions were filled in the Match (43 of 58, 74.1% in 2022; 45 of 58, 77.6% in 2023); most others were filled in the SOAP. On average, 34.4% of enrolled residents were from the same state as the program (range 0-78.6%). Conclusions The early resident recruitment outcomes of the RRPD model for developing new physician training in rural communities had sufficient recruitment success to support program continuation.

Purpose: In patients with a need for frequent but intermittent apheresis, vascular access can prove challenging. We describe the migration of the use of a Vortex LP dual lumen port (Angiodynamics, Latham, NY) to one Powerflow and one ClearVUE power injectable port (Becton Dickinson, Franklin Lakes, NJ) in a series of patients undergoing intermittent apheresis., Materials and Methods: All patients had a need for long-term intermittent apheresis. Eight had double lumen Vortex port (pre) and were exchanged for one Powerflow port and one conventional subcutaneous venous port with 90° needle entry (post) while 12 did not have any port in place and received the same configuration. IRB approval was granted. We recorded the treatment time, flow rate, and tissue plasminogen activator (tPA) use for five treatment sessions after placement. When available, we compared five treatments with the Vortex port and the new configuration., Results: The mean treatment time is reduced with the new configuration (P = 0.0033). The predicted mean treatment time, adjusting for gender, race, BMI and age and accounting for correlations within a patient is 91.18 min pre and 77.96 min post. The flow rate is higher with the new configuration (P < 0.0001). The predicted mean flow rate in mL/min is 61.59 for the Vortex port and 71.89 for the new configuration. tPA use was eliminated in the population converted from Vortex ports and had a 48% reduction when compared to all other configurations in the study., Conclusion: The introduction of a novel device configuration of venous access ports for intermittent apheresis resulted in higher flow rates and less total time for treatment. Use of tPA was greatly reduced. These results suggest that the new configuration could result in less expense for the hospital and better throughput in a busy pheresis practice. Clinical trial registration with ClinicalTrials.gov: NCT04846374., (© 2024 Wiley Periodicals LLC.)