Releasing our model T - chimeric antigen receptor (CAR) T-cells for autoimmune indications.

PURPOSE OF REVIEW: This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells. RECENT FINDINGS: To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response. SUMMARY: Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.

Looking Across the Drape: A Novel Quality Improvement Approach to Understanding Surgeon and Anesthesiologist Burnout.

OBJECTIVE: To identify well-being threats for surgeons and anesthesiologists and develop interventions using the Quality of Life Improvement (QOLI) approach. BACKGROUND: Developing feasible perioperative well-being interventions requires identifying shared and specialty-specific well-being needs. The QOLI framework integrates human-centered design, implementation science, and quality improvement to address well-being needs. METHODS: Anesthesia and surgery faculty in eight perioperative departments at an academic medical center completed cross-sectional surveys containing validated measures of well-being and workplace satisfaction, and open-ended questions about professional motivations, pain points, strategies for improvement, and well-being priorities. Using template analysis, we analyzed open-ended survey data and presented resulting themes at a joint-specialty town hall for live-voting to identify well-being priorities. RESULTS: 104 perioperative faculty completed the survey. Across specialties, higher MHC-SF scores (representative of individual global well-being) were associated with higher satisfaction with workplace control, values, decision latitude, and social support. Anesthesiologists reported lower satisfaction and control than surgeons across multiple domains. Template analysis yielded five areas for intervention: (1) Work culture, (2) Work environment/resources, (3) Sources of fulfillment, (4) Work/life harmony, (5) Financial compensation. Surgeons and anesthesiologists both prioritized high-quality patient care but differed in their other top priorities. The most frequently cited well-being threats for surgeons were OR inefficiencies/delays and excessive workload, while anesthesiologists cited understaffing and unpredictable work hours. CONCLUSIONS: Surgeons and anesthesiologists share many needs and priorities, with pain points that are often negatively synergistic. Applying the QOLI approach across specialties allows for well-being interventions that honor complexity and promote the development of feasible solutions.

Development of CARRA/PReS-endorsed consensus Core and Expanded Datasets in childhood-onset systemic lupus erythematosus for international registry-based research.

OBJECTIVES: Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide. METHODS: 21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets. The Core cSLE Dataset was designed to include data essential to meaningful clinical research across many settings. The Expanded cSLE Dataset was designed for centres able to consistently collect data to address broader research questions. Final data items for the Core and Expanded datasets were determined by consensus defined as >80% agreement) using an adapted nominal group technique and voting. RESULTS: The resulting Core cSLE Dataset contains 46 items, including demographics, clinical features, laboratory results, medications and significant adverse events. The Expanded cSLE Dataset adds 26 additional items and includes patient-reported outcomes. Consensus was also achieved regarding the frequency and time points for data collection: baseline, quarterly follow-up visits, annually and flare visits. CONCLUSION: Standardised Core and Expanded cSLE Datasets for registry-based international cSLE research were defined through the consensus of global experts and patient/caregiver representatives, endorsed by CARRA and PReS. These datasets incorporate disease-specific and patient-specific features, optimised for diverse settings to facilitate international collaborative research for children and adolescents with SLE worldwide.

Heterometallic Molecular and Ionic Isomers.

Numerous descriptions of structural isomerism in metal complexes do not list any molecular vs ionic isomers. At the same time, one of the most striking examples of structural isomerism in organic chemistry is molecular urea, which has the same atomic composition as the chemically distinct ionic ammonium cyanate. This iconic organic couple now meets its inorganic heterometallic counterpart. We introduce a new class of structural isomers, molecular vs ionic, that can be consummated in complex and coordinatively unsaturated polynuclear/heterometallic compounds. We report inorganic molecular and ionic isomers of the composition [NaCrFe (acac)3(hfac)3] (acac = acetylacetonate; hfac = hexafluoroacetylacetonate). Heterometallic molecular [CrIII(acac)3-Na-FeII(hfac)3] (1m) and ionic {[CrIII(acac)3-Na-CrIII(acac)3]+[FeII(hfac)3-Na-FeII(hfac)3]-} (1i) isomers have been isolated in pure form and characterized. While both ions are heterobimetallic trinuclear entities, the neutral counterpart is a heterotrimetallic trinuclear molecule. The two isomers exhibit distinctly different characteristics in terms of solubility, volatility, mass spectrometry ionization, and thermal behavior. Unambiguous assignment of the positions and oxidation/spin states of the Periodic Table neighbors, Fe and Cr, in both isomers have been made by a combination of characterization techniques that include synchrotron X-ray resonant diffraction, synchrotron X-ray fluorescence spectroscopy, Mössbauer spectroscopy, and DART mass spectrometry. The transformation between the two isomers that does take place in solutions of noncoordinating solvents has also been tested.

Transition to Adult Rheumatology Care: A Disease-Specific Guide.

ABSTRACT: Young adults with childhood-onset rheumatic diseases are more frequently establishing and continuing care with adult rheumatologists. The transfer of care can be challenging for both the young adult patients and their adult rheumatologists, in large part due to differences between pediatric-onset rheumatic diseases and their adult-onset counterparts, or due to the rarity of some pediatric-onset rheumatic conditions. Other challenges are due to cultural differences between pediatric and adult medical care and to the young adult needing to increasingly perform self-management skills that were previously managed by parents or other caregivers. In this review, we will provide a summary of strategies for working effectively with young adults as they transition to adult care. We will then discuss a subset of childhood-onset rheumatic diseases-including juvenile idiopathic arthritis, localized scleroderma, autoinflammatory diseases, pediatric-onset systemic lupus erythematosus, juvenile-onset dermatomyositis, and autoimmune encephalitis-for which clinical manifestations, management, and prognosis frequently differ between pediatric onset and adult onset. Our aim is to highlight differences that make caring for this population of transitioning young adults unique, providing tools and knowledge to empower the adult rheumatologist to care for these young adults in ways that are evidence-based, effective, efficient, and rewarding.

Patient-Reported Outcomes Among Transition-Age Young Adults With Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To evaluate patient-reported care utilization and outcomes among young adults with juvenile idiopathic arthritis (JIA), including factors associated with complete transfer to adult rheumatology. METHODS: We included young adults with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from 2015 to 2019 with age ≥ 18 years at their last clinical site visit. We used data from the CARRA Registry Long-term Follow-up program, which follows inactive CARRA Registry patients and collects patient-reported information through phone surveys. We compared the characteristics of respondents with complete and incomplete transfer to adult rheumatology care at their first Long-term Follow-up phone survey. RESULTS: We identified 540 young adults with JIA; 187 (35%) responded to the Long-term Follow-up phone survey. The 54% of respondents with complete transfer to adult rheumatology were slightly older and reported more self-assessed disease activity, morning stiffness, and pain compared to those with incomplete transfer. Biologic use was high at both timepoints and did not differ by transfer status. Patients who completed the transfer were more likely to have private insurance and be actively pursuing postsecondary education compared to those with an incomplete transfer. Across the cohort, 65% reported problems with pain or discomfort and 45% with anxiety or depression. CONCLUSION: Young adult respondents with JIA in the CARRA Registry commonly report persistent medication use, but still report more problems with pain as compared to population norms. Additional work is needed to understand how best to address comorbid pain around the period of transition to adult care.

Opioid use in children with inflammatory bowel disease-related arthritis.

OBJECTIVES: Concomitant arthritis may increase risk of chronic opioid use in youngsters with IBD. We aimed to assess trends and clinical features associated with opioid use in children with IBD-related arthritis. METHODS: Adolescents under 18 years of age with IBD-related arthritis, at least 1 year of continuous enrolment, and at least 1 pharmacy claim in the Truven Health MarketScan Claims and Encounter Database were included. Subjects were identified using previously validated algorithms consisting of ICD codes, pharmacy claims and procedure codes. The primary outcome was chronic opioid exposure. Temporal trends in opioid exposure were tested using the Cuzick-Wilcoxon test. The association of chronic opioid use and baseline covariates in the IBD and IBD-arthritis cohorts were examined using multivariable logistic regression models. RESULTS: 14,943 adolescents with IBD, 480 of whom had arthritis, were included. Chronic opioid use was non-trivial in youngsters with IBD-related arthritis, higher than that of total IBD cohort (12.3% vs. 5%) and remained stable over the years of study. Using multivariable regression, joint pain and arthritis were significantly associated with chronic opioid exposure in young people with IBD. Among IBD-related arthritis patients older age, public insurance, gastrointestinal surgery, hospitalisation and psychiatric comorbidities were significantly associated with chronic opioid use. CONCLUSIONS: Chronic opioid use in adolescents with IBD-related arthritis was higher than that of total IBD cohort but stable over the years of study. Future study is needed to explore ways to optimise non-narcotic pain management strategies and ensuring appropriate use of opioids when necessary.

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

Clinical features, treatment patterns and short-term outcomes of children with inflammatory bowel disease evaluated in rheumatology clinic.

OBJECTIVES: This study evaluated the clinical features, treatment patterns, and short-term outcomes of children with inflammatory bowel disease (IBD)-associated musculoskeletal manifestations. METHODS: This was a retrospective cohort study of children with IBD evaluated for joint complaints in a paediatric rheumatology clinic from 2015 to 2020. The index visit was the date of initial rheumatology evaluation. Clinical features were evaluated using standard descriptive statistics. Differences in outcomes over time were compared using rank-sum tests. Univariate logistic regression was used to test associations between clinical features and persistent arthritis or enthesitis. RESULTS: Seventy-five patients met inclusion criteria. 61% had active arthritis or enthesitis at initial evaluation, 1/3 of whom were not yet diagnosed with IBD. Of those with known IBD, over half with joint complaints had arthritis or enthesitis. Active joint disease was common even among patients already receiving tumour necrosis factor (TNF) inhibitors or other immunomodulatory medications for IBD and despite inactive gastrointestinal disease. Treatment escalation was often needed to control articular disease, which included changes in immunomodulatory therapy and NSAIDs. Treatment outcomes for arthritis were good and significant improvements in functional mobility were observed (p<0.01), while enthesitis often persisted at follow-up (11/28, 39%). Moreover, a significant proportion of patients with pain at the index visit reported persistent pain at follow-up (29/44, 65%). CONCLUSIONS: This study provides several findings relevant to the multidisciplinary care of children with IBD, including high rates of active arthritis and enthesitis despite ongoing use of immunomodulatory medications for the management of IBD, responses to treatment, and pain management.

Awake spinal surgery: simplifying the learning curve with a patient selection algorithm.

OBJECTIVE: There is a learning curve for surgeons performing "awake" spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery. METHODS: The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution. RESULTS: A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8. CONCLUSIONS: The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.

Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric-onset systemic lupus erythematosus.

BACKGROUND: Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health. METHODS: Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical-4 chamber (LSA4C ) and midpoint circumferential strain (CSmid ) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health. RESULTS: Average SLE disease duration was 3.2 years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LSA4C was significantly reduced in pSLE subjects compared to controls (mean -18.3 [SD 3.2] vs -21.8% [SD 2.2], P-value <.001). There was no significant difference in CSmid (-24.8 [SD 3.7] vs -25.7% [SD 3.4], P = .29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r -0.59, P = .01). CONCLUSIONS: Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow-up of patients with pSLE.

Applying Conflict Management Strategies to the Pediatric Operating Room.

Effective communication is essential in today's health care environment, and poor communication can lead to conflict among health care providers. Differences in cultures and beliefs can further incite conflict among health care team members, families, and patients. Pediatric patient care has a higher potential for conflict because decision-making responsibilities are shared among patients, parents/guardians, and clinicians. It is important to understand the phases and types of conflict because each conflict situation requires a different approach to optimize management. Equally important is an understanding of styles used by individuals to manage conflict. The Thomas-Kilmann Conflict Mode Instrument and the Dutch Test for Conflict Handling are 2 validated tools used to assess conflict management styles. The different styles include competing/forcing, collaborating/problem solving, compromising, avoiding, and yielding/accommodating. A successful physician should be able to identify the phases and types of conflict to use the conflict management approach most suitable for the given conflict.There are several techniques for managing conflict in the pediatric operating room. Acknowledging and managing one's own emotions during conflict is a pivotal first step toward diffusing the situation. Active listening is an important communication skill that improves team dynamics. Aligning the interests of the parties involved in conflict will encourage collaborative problem solving. Cultural competency training can improve communication and conflict management skills. Effective conflict management through formal education of all perioperative team members can lead to improved communication and teamwork and better patient outcomes.

Increased Echocardiographic Pulmonary Pressure in HIV-infected and -uninfected Individuals in the Veterans Aging Cohort Study.

RATIONALE: The epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described. OBJECTIVES: To examine the prevalence, clinical features, and outcomes of increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals. METHODS: This study evaluated 8,296 veterans referred for echocardiography with reported pulmonary artery systolic pressure (PASP) estimates from the Veterans Aging Cohort study, an observational cohort of HIV-infected and -uninfected veterans matched by age, sex, race/ethnicity, and clinical site. The primary outcome was adjusted mortality by HIV status. MEASUREMENTS AND MAIN RESULTS: PASP was reported in 2,831 HIV-infected and 5,465 HIV-uninfected veterans (follow-up [mean ± SD], 3.8 ± 2.6 yr). As compared with uninfected veterans, HIV-infected veterans with HIV viral load greater than 500 copies/ml (odds ratio, 1.27; 95% confidence interval [CI], 1.05-1.54) and those with CD4 cell count less than 200 cells/µl (odds ratio, 1.28; 95% CI, 1.02-1.60) had a higher prevalence of PASP greater than or equal to 40 mm Hg. As compared with uninfected veterans with a PASP less than 40 mm Hg, HIV-infected veterans with a PASP greater than or equal to 40 mm Hg had an increased risk of death (adjusted hazard ratio, 1.78; 95% CI, 1.57-2.01). This risk persisted even among participants without prevalent comorbidities (adjusted hazard ratio, 3.61; 95% CI, 2.17-6.01). The adjusted risk of mortality in HIV-infected veterans was higher at all PASP values than in uninfected veterans, including at values currently considered to be normal. CONCLUSIONS: HIV-infected people with high HIV viral loads or low CD4 cell counts have a higher prevalence of increased PASP than uninfected people. Mortality risk in HIV-infected veterans increases at lower values of PASP than previously recognized and is present even among those without prevalent comorbidities. These findings may inform clinical decision-making regarding screening and surveillance of pulmonary hypertension in HIV-infected individuals.

Echocardiographic Assessment of Diastolic Function in Children with Incident Systemic Lupus Erythematosus.

The timing and etiology of diastolic impairment in pediatric-onset systemic lupus erythematosus (SLE) are poorly understood. We compared echocardiographic metrics of left ventricular diastolic function in children at SLE diagnosis to controls and identified factors associated with diastolic indices. Echocardiograms of children aged 5-18 years within 1 year of SLE diagnosis and age-/sex-matched controls were retrospectively read by blinded cardiologists. Clinical characteristics were abstracted separately. Z-scores for diastolic indices (E/A, e', E/e', and isovolumetric relaxation time (IVRT)) were calculated using published normative data and study controls, and compared using linear mixed-effects models adjusted for blood pressure. Pericardial effusions and valvular disease were also evaluated. Linear regression was used to identify factors associated with diastolic measures. 85 children with incident SLE had echocardiograms performed a median of 6 days after diagnosis (interquartile range (IQR) 1-70). Prior cumulative prednisone exposure was minimal (median 60 mg, IQR 0-1652). SLE cases had lower E/A, lower e', higher E/e', and longer IVRT compared to controls. Though none met criteria for Grade I diastolic dysfunction, Z-scores for e', E/e', and IVRT were abnormal in 30%, 25%, and 6% of SLE cases, respectively. Greater disease activity was associated with lower septal e' (p < 0.01), higher E/e' (p = 0.02), and longer IVRT (p < 0.01). Children with incident SLE have worse diastolic indices at diagnosis compared to peers without SLE, independent of blood pressure and prior to significant prednisone exposure. Longitudinal studies will determine whether diastolic dysfunction develops in this population over time.

Is Mental Illness a Risk Factor for Hospital Readmission?

People with mental illnesses (MI) receive suboptimal care for medical comorbidities and their high risk for readmission may be addressed by adequate medication management and follow-up care. We examined the association between MI, medication changes, and post-discharge outpatient visits with 30-day readmission in 40,048 Medicare beneficiaries hospitalized for acute myocardial infarction, heart failure or pneumonia. Beneficiaries with MI were more likely to be readmitted than those without MI (14 vs. 11%). Probability of readmission was 13 and 12% when medications were dropped or added, respectively, versus 11% when no change was made. Probability of readmission also increased with outpatient visits.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

Two polymorph modifications of tris(hexafluoroacetylacetonato)iron(III) revealed: is that common for other trivalent metals?

A long-standing issue about the correct identification of an important starting reagent, iron(III) hexafluoroacetylacetonate, Fe(hfac)3 (1), has been resolved. The tris-chelated mononuclear complex was found to crystallize in two polymorph modifications which can be assigned as the low-temperature (1-L) monoclinic P21/n and the high-temperature (1-H) trigonal P-3. Low-temperature polymorph 1-L was found to transform to 1-H upon sublimation at 44 °C. Two modifications are clearly distinguished by powder X-ray diffraction (PXRD), single-crystal X-ray diffraction, differential scanning calorimetry (DSC), and melting-point measurements. On the other hand, the two forms share similar characteristics in direct analysis in real-time mass spectrometry (DART-MS), attenuated total reflection (ATR) spectroscopy, and some physical properties, such as color, volatility, sensitivity, and solubility. Analysis of the literature and some of our preliminary data strongly suggest that the appearance of two polymorph modifications for trivalent metal (both transition and main group) hexafluoroacetylacetonates is a common case for several largely used complexes not yet accounted for in the crystallographic databases.

Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood-Onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood-onset SLE (cSLE) versus adult-onset SLE, negatively impacting school function, self-management, and psychosocial health, as well as lifelong health-related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood-brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted because the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional multiple resonance imaging studies (eg, T2-weighted or fluid-attenuated inversion recovery sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in cSLE is in part due to the harmful impact of a chronic inflammatory insult on a developing CNS. Although the immature status of the CNS may leave patients with cSLE more vulnerable to harboring neuropsychiatric manifestations, the same property may represent a greater urgency to reverse the maladaptive effects associated with a proneuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk among the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted.

Assessing Methotrexate Adherence in Juvenile Idiopathic Arthritis Using Electronic Health Record-Linked Pharmacy Dispensing Data.

OBJECTIVE: We linked pharmacy dispensing data to clinical data in the electronic health record (EHR) to (1) identify characteristics associated with adherence to methotrexate (MTX) and (2) determine the association between adherence and disease activity in patients with juvenile idiopathic arthritis (JIA). METHODS: We conducted a single-center retrospective cohort study of incident MTX recipients with JIA treated between January 2016 and September 2023 for ≥12 months. Using pharmacy dispensing data, complemented by EHR data, we estimated adherence using medication possession ratios (MPRs) over the first 365 days of treatment. We used Fisher's exact and Wilcoxon rank-sum tests to compare patient characteristics between adherent (MPR ≥80%) and nonadherent (MPR <80%) groups and multivariable linear regression to investigate associations between MPR and active joint count. RESULTS: Among 224 patients, 81 (36.2%) were classified as nonadherent. In bivariate analysis, patients of younger age, of Black race, and from areas with lower child opportunity index were more likely to be classified as nonadherent. In multivariable analysis, active joint count changed from baseline to 12-month follow-up by -0.38 joints in the adherent compared to nonadherent group (95% confidence interval [CI] -0.74 to -0.01) and by -1.18 joints in patients with polyarticular course (95% CI -2.23 to -0.13). CONCLUSION: Linking dispense data to clinical EHR data offers a novel, objective method for evaluating adherence to chronic medications. We identified demographic and area-level determinants of adherence, along with small but statistically significant differences in JIA disease activity measures by adherence status. Future work is needed to evaluate adherence as a potential mediator of known outcome disparities for socially disadvantaged populations.