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Aims In this protocol-predefined sub-study of the RHAPSODY trial, the primary aim was to assess whether pericardial late gadolinium enhancement (LGE) was associated with time to pericarditis recurrence. Methods and Results RHAPSODY was a Phase 3 double-blind, placebo-controlled, randomized-withdrawal trial which demonstrated the efficacy of rilonacept in recurrent pericarditis (RP). Patients with a history of multiple RP and an active recurrence were enrolled and had the option to participate in a cardiac magnetic resonance (CMR) imaging sub-study. CMRs were interpreted by a blinded independent core laboratory with pre-specified criteria to define pericardial LGE. Compared to patients with trace or mild pericardial LGE (n=9), patients with moderate or severe pericardial LGE (n=16) generally had a higher number of recurrent episodes per year (5.3 vs. 3.9) and a higher mean CRP level (3.6 vs 1.1 mg/dL). Overall, 10/14 (71.4%) who received placebo had a recurrence compared to 0/11 (0%) who received rilonacept. In patients randomized to placebo who had moderate or severe pericardial LGE, the median time to recurrence was 4.2 weeks compared to 10.7 weeks in patients who had trace or mild pericardial LGE. At the conclusion of the event-driven randomized withdrawal period, among patients receiving placebo, 5/7 (71.4%) with trace or mild pericardial LGE and 5/7 (71.4%) with moderate or severe pericardial LGE had a recurrence. Conclusions Among patients with multiple RP, these preliminary findings support the concept of pericardial LGE as an imaging biomarker that may inform duration of treatment and risk of recurrence with cessation of therapy, and larger studies should be considered. ClinicalTrials.gov Identifier: NCT03737110

Opioid use disorder (OUD) remains a major public health problem for which comprehensive treatment strategies are warranted. This chapter reviews the empirical literature supporting various behavioral strategies to engage patients with OUD. First, it reviews the impact of engagement in treatment and individualized treatment planning on patient success in treatments. It then reviews several core behavioral therapies, including Cognitive Behavioral Therapy, Mindfulness-Based Cognitive Therapy, and Peer Recovery Support Services, as well as self-directed treatments such as 12-Step programs, Self-Management and Recovery Training, and Celebrate Recovery. It also discusses holistic wellness, including Mindfulness in Recovery and physical activity such as yoga and aerobic fitness. Finally, we provide a case example of how behavioral strategies may enhance and enrich a patient’s recovery process.

A clear need exists to understand the role that water table fluctuations play in mobilizing nutrients in soils and shallow groundwater near streams, particularly in dry Mediterranean watersheds, which experience marked wetting and drying seasonal patterns. As groundwater level varies, so does the supply of inorganic nitrogen and organic carbon from different soil layers, which affects processes such as coupled nitrification-denitrification and the chemistry of groundwater that flows to streams. Along discharging groundwater flow paths, carbon-rich soils release dissolved organic carbon (DOC), which biogeochemically reacts with nitrogen (N) and oxygen (O) as groundwater levels rise and become saturated. For understanding the biogeochemical dynamics in N at the interface between soils and groundwater, a cylindrical, meter-long polyvinyl chloride (PVC) soil column was constructed and filled with heterogeneous soil and aquifer layers of decreasing organic matter with depth. A cyclical water level cycle was imposed for 16 days using influent to the column from local groundwater at the experimental site with < 1 mg nitrate-N/L. Water table dynamics were monitored with a pressure sensor, tensiometer, and two soil moisture sensors. Vertical arrays of redox sensors and pore water samplers were used to observe changes in pore water chemistry. Water samples were analysed for pH, ammonium-N (NH4-N), nitrate-N (NO3-N), nitrite-N (NO2-N), and DOC. Soil samples were taken for microbial activity and solid chemistry analysis. Near the soil-aquifer transition, nitrate accumulates under aerobic conditions and DOC from organic matter is mobilized under anaerobic conditions. Preliminary pore water analysis shows that during wetting cycles, there is an increase in dissolved inorganic N (NO3+NO2) near the surface (57 mg N/L at 40 cm depth) but a decrease in DIN concentrations in deeper layers (0.92 mg N/L at 55-100 cm depth), suggesting that nitrification and denitrification processes stratified with depth. The results illustrate the significance of groundwater level fluctuations on DIN and DOC cycling and mobilization in Mediterranean riparian soils during wetting events.

Water tables in floodplain aquifers rise and fall over a variety of timescales in response to changes in recharge, discharge, floods, and water use. To investigate the effects of water table fluctuations on DOC delivery to groundwater, an experiment was conducted at two Mediterranean sites: a pristine forested stream and an urban coastal floodplain. Groundwater was pumped into and out of the bottom of the soil column at varying rates to simulate water table fluctuations over a period of 16 days. Flooding events were imitated by inundating the top of the column with water sourced from nearby surface water features. The effects of repeated wetting and drying events on carbon mobilization, DOM quality, and geochemical responses were measured. Preliminary analysis reveals strong downward movement of DOC from soil layers after wetting events. SUVA at 254 nm increased with DOC concentrations compounds within pore waters during wetting events. During initial water table fluctuations, redox potential near the soil-aquifer interface was relatively stable but declined after subsequent wettings. Forthcoming analyses will also examine changes in the humification, fluorescence, and freshness indices of DOM from excitation-emission matrices. This study shows the influence of multiple saturation events on carbon mobilization and shallow groundwater biogeochemistry in unique floodplains.

Water tables in coastal aquifers respond to a variety of hydrologic forcings, including precipitation, coastal flooding, and tides. The water table response to these forcings has the potential to impact water quality by affecting the fate and transport of nitrogen, particularly in coastal environments where nitrogen can accumulate in soils and water. To investigate the urban and agricultural reactions involving N that occur near the water table, a meter-long column containing reconstructed coastal soil and aquifer layers from a Mediterranean site was made. We continuously monitored in-situ redox potential, soil moisture, and water pressure and collected frequent pore water samples for analysis of dissolved organic carbon (DOC) and dissolved inorganic nitrogen species over 16 days while imposing water table fluctuations by injecting local groundwater rich in nitrate-N (~15 mg/L). In-situ redox potential in shallow soils (40 cm depth) ranged from -600-600 mV, which is indicative of alternating conditions favorable for aerobic and anaerobic respiration. Redox potential increased upon saturation and declined again as soils drained, with more subtle changes occurring during the first wetting and drying cycle and greater changes occurring during repeated cycles. Pore water analysis shows mobilization of DOC and ammonium-N in shallow soils and removal of nitrate-N in sandy aquifer layers. More specifically, DOC, nitrate-N, ammonium-N, and nitrite-N were greatest in the organic soils and decreased down the column into the sandy aquifer layers. Toward the end of the experiment, the column was inundated with seawater collected from the Mediterranean to simulate a flooding event, causing an increase in all N-species concentrations below 10 cm as seawater transported the nitrogen and DOC contaminants to depth. In contrast, when the column was flooded from the bottom, nitrate-N concentrations decreased as the soils became saturated, oxygen was depleted, and denitrification occurred. Overall, we see how water table dynamics impact the fate and transport of nitrogen in groundwater as soils are repeatedly saturated from above and below.

Background: The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results. Methods: Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the related area under the curve (AUC) were elaborated for the overall population and each subgroup. Results: The pooled analysis was carried out on 25 cohorts for a total of 1966 patients. The overall ctDNA sensitivity and specificity were 0.73 (95% CI: 0.70–0.77) and 0.87 (95% CI: 0.85–0.89). The AUC was 0.93. Pooled concordance, negative predictive value and positive predictive value values were 0.87 (95% CI: 0.82–0.92), 0.86 (95% CI: 0.81–0.90), and 0.89 (95% CI: 0.81–0.95) with pooled PLR, NLR, and DOR of 7.94 (95% CI: 4.90–12.86), 0.33 (95% CI: 0.25–0.45), and 33.41 (95% CI: 17.23–64.79), respectively. The pooled results consistently favored next-generation sequencing (NGS)- over polymerase chain reaction-based methodologies. The best ctDNA performance in terms of sensitivity, specificity, and AUC (0.85, 0.99, and 0.94, respectively) was observed in the low-time sampling subgroup (⩽18 days between tissue and plasma collection). Meta-regression and subgroup analyses highlighted sampling time as a possible major cause of heterogeneity. Conclusions: These findings reliably estimate the high ctDNA accuracy for the detection of PIK3CA mutations. A ctDNA-first approach for the assessment of PIK3CA mutational status by NGS may accurately replace tissue tumor sampling, representing the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.

Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p=0.42), between low- and high-penetrance mutations (p=0.62), and according to different dosages (p=0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach.

ObjectiveThe aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management. The Registry may potentially communicate with other on-line tools dedicated to VEXAS syndrome, thus enhancing international collaboration and data sharing for research purposes. The Registry is practical enough to be easily modified to meet future needs regarding VEXAS syndrome.ResultsTo date (April 22nd, 2022), 113 Centers from 23 Countries in 4 continents have been involved; 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) are currently able to access the registry for data entry (or data sharing) and collection. The Registry includes 4,952 fields organized into 18 instruments designed to fully describe patient's details about demographics, clinical manifestations, symptoms, histologic details about skin and bone marrow biopsies and aspirate, laboratory features, complications, comorbidities, therapies, and healthcare access.ConclusionThis international Registry for patients with VEXAS syndrome will allow the achievement of a comprehensive knowledge about this new disease, with the final goal to obtain real-world evidence for daily clinical practice, especially in relation to the comprehension of this disease about the natural history and the possible therapeutic approaches. This Project can be found on https://clinicaltrials.gov NCT05200715.

Supplemental material, sj-docx-1-vaw-10.1177_10778012231163577 for Knowledge, Perceived Competence, and Behaviors Relative to Traumatic Brain Injury Among a Sample of Domestic Violence Emergency Shelter Advocates in a New England State by Julia K. Campbell, Jonathan Howland, Brie Insalaco and Gabriela Lawrence-Soto in Violence Against Women

Relationships as a Protective and Growth Factor Being in a relationship can act as a protective factor against multiple Covid-19 concerns such as loneliness and death anxiety (Bruce et al., 2019; Lauder et al., 2004; Mayer and Vanderheiden, 2022; Mikulincer et al., 2004; Shiovitz-Ezra & Leitsch, 2010). Being in a relationship also serves as a protective factor against loneliness. Many studies have found people that are married or cohabitate with their partner experience less loneliness (Bruce et al., 2019; Lauder et al., 2004; Shiovitz-Ezra & Leitsch, 2010). Lastly, Mikulincer et al. (2004) found that having close relationships, such as a partner, family or friends, is a coping mechanism against death anxiety. Specifically in a study of death anxiety in women during the covid-19 pandemic, close relationships were the most important coping factor against death anxiety (Mayer and Vanderheiden, 2022). Resilience as a Protective Factor When one measures resilience, they are measuring “the ability to bounce back or recover from stress” (Smith et al., 2008, p. 194). Higher resilience has been associated with lower depression, anxiety, and overall lower negative affect even when social support was controlled (Smith et al., 2008). Resilience has also been theorized to be a fairly stable construct that adapts to a person’s environment depending on how stressful it is (Cusack et al., 2022). For example, during the stress of the Covid-19 pandemic, a resilient person may adapt to the increase in stress. Specifically, a study found that resilience is a protective factor against PTSD symptoms that are because of the COVID-19 pandemic (Cusack et al., 2022). This is important because high levels of loneliness during the COVID-19 quarantine is significantly associated with clinical levels of PTSD symptoms(Liu et al. 2020). Relationship Status, Resilience, and Post-Pandemic Wellness Both being in a relationship and being resilient acts as a protective factor that leads to and fosters wellness. This has been found to occur before and as a result of the COVID-19 pandemic. However, these factors may impact each other. For example, resilience is a predictor of higher marital satisfaction (Bradley and Hojjat, 2017). Therefore in this study I seek to uncover if resilience and relationship status each impact Post-Pandemic Wellness separately. My first research question is when accounting for resilience, does being in a relationship lead to a higher Post-Pandemic Wellness Score for Social Stress and/or Existential Impact? My second research question is, when accounting for relationship status, does having a higher level of resilience lead to a higher Post-Pandemic Wellness Score for Social Stress and/or Existential Impact?

SUMMARY: Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small- and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

Introduction/Purpose Obesity increases significantly every year worldwide. Since 1980, the prevalence of individuals with obesity has practically doubled. Obesity plays an important role in the pathophysiology of diseases that arise from a complex interaction of nutritional, genetic, and metabolic factors, characterizing a chronic inflammatory state. This study aimed to verify the systemic inflammatory response through the analysis of IGF-1, IL-23, and resistin levels and the lipid profile in severely obese women undergoing surgery for obesity and weight-related diseases. Materials and Methods This randomized controlled clinical trial includes female patients clinically diagnosed with severe obesity with an indication for bariatric surgery. Results In the initial evaluation, no significant difference was observed between the control (CG) and bariatric surgery (BSG) groups. The weight, BMI, systolic and diastolic blood pressures, total cholesterol, LDL, HDL, total non-HDL cholesterol, and glucose in BSG patients showed a significant change after surgery. Pre- and post-surgery levels of resistin, IGF-1, and IL-23 showed a significant difference in the BSG group, but only IL-23 was changed after 6 months in the CG. Conclusion The results of this study confirmed that weight loss induced by surgery for obesity and weight-related diseases improved the lipid profile and reduced the chronic inflammatory status in women with severe obesity.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved ( P Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient‐reported health‐related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03737110.

IntroductionProspective comparative effectiveness research in chronic nonbacterial osteomyelitis (CNO) is lacking.ObjectivesStudy objectives were to: 1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, 2) the feasibility of usingchronic nonbacterialosteomyelitis international registry (CHOIR) data for comparative effectiveness research, and 3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR.MethodsConsenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants.Results140 (76%) CHOIR participants enrolled between August 2018 and September 2020 received at least one CTP regimen. Baseline characteristics from the three groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement. The CDAS significantly decreased after initiating second-line treatments from median 12 (8-15.5) to 5 (3-12). While second-line treatments were well tolerated, psoriasis was the most common adverse event.ConclusionThe CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future comparative effectiveness research.Key messagesThechronic nonbacterialosteomyelitis international registry (CHOIR) provides comprehensive prospective data for comparison of treatment effectivenessThe clinical disease activity score (CDAS) has content and construct validity to assess CNO

The inclusion of 5G cellular communication system into vehicles, combined with other connected-vehicle technology, such as sensors and cameras, makes connected and advanced vehicles a promising application in the Cooperative Intelligent Transport Systems. One of the most challenging task is to provide resilience against misbehavior i.e., against vehicles that intentionally disseminate false information to deceive receivers and induce them to manoeuvre incorrectly or even dangerously. This calls for misbehaviour detection mechanisms, whose purpose is to analyze information semantics to detect and filter attacks. As a result, data correctness and integrity are ensured. Misbehaviour and its detection are rather new concepts in the literature; there is a lack of methods that leverage the available information to prove its trustworthiness. This is mainly because misbehaviour techniques come with several flavours and have different unpredictable purposes, therefore providing precise guidelines is rather ambitious. Moreover, dataset to test detection schemes are rare to find and inconvenient to customize and adapt according to needs. This work presents a misbehaviour detection scheme that exploits information shared between vehicles and received signal properties to investigate the behaviour of transmitters. Differently from most available solutions, this is based on the data of the on-board own resources of the vehicle. Computational effort and resources required are minor concerns, and concurrently time efficiency is gained. Also, the project addresses three different types of attack to show that detecting misbehaviour methods are more vulnerable to some profile of attacker than others. Moreover, a rich dataset was set up to test the scheme. The dataset was created according to the latest standardised evaluation methodologies and provides a valuable starting point for any further development and research.

ObjectivesTo determine the patterns of storing, using and disposing of opioids among patients with advanced cancer followed at home.MethodsPatients who were prescribed opioids were selected. Prescribed opioids and their doses used for background pain and breakthrough pain were collected, as well as CAGE (cut down, annoyed, guilty and eye opener) for alcohol and drugs, smoking and history of illicit substance use. Questions regarding the opioid use, storage and disposal were posed.Results100 patients were surveyed. Fifty-one patients had unused opioids at home, 25 patients did not throw away the drugs, 40 patients saved opioids for future use and 35 patients were unaware of proper opioid disposal methods. A total of 28 patients reported unsafe use by sharing or losing their opioids; 12 patients were unaware that their opioid could be fatal when taken by others. Most patients acknowledged that pain medications could be dangerous when taken by others. Patients with a partner and who were married were more likely to keep their opioids locked (p=0.028 and p=0.025, respectively).ConclusionA large number of patients with advanced cancer followed at home do not store, use and dispose of opioids safely. Patient education programmes should be incorporated to decrease the availability of opioids at home for abuse, diversion, and accidental poisoning.