The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination.

Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super-enhancer, 3' regulatory region (3'RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here, we identify the chromatin reader ZMYND8 as an essential regulator of the 3'RR. In B cells, ZMYND8 binds promoters and super-enhancers, including the Igh enhancers. ZMYND8 controls the 3'RR activity by modulating the enhancer transcriptional status. In its absence, there is increased 3'RR polymerase loading and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3'RR. Thus, ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3' Igh super-enhancer.

Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution.

BACKGROUND: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. METHODS: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. RESULTS: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. CONCLUSIONS: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.

Developing the OpenFlexure Microscope towards medical use: technical and social challenges of developing globally accessible hardware for healthcare.

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

Temperature-Controlled Reversible Formation and Phase Transformation of 3D Nanocrystal Superlattices Through In Situ Small-Angle X-ray Scattering.

For decades, the spontaneous organization of nanocrystals into superlattices has captivated the scientific community. However, achieving direct control over the formation of the superlattice and its phase transformations has proven to be a grand challenge, often resulting in the generation of multiple symmetries under the same experimental conditions. Here, we achieve direct control over the formation of the superlattice and its phase transformations by modulating the thermal energy of a nanocrystal dispersion without relying on solvent evaporation. We follow the temperature-dependent dynamics of the self-assembly process using synchrotron-based small-angle X-ray scattering. When cooled below -24.5 °C, lead sulfide nanocrystals form micrometer-sized three-dimensional phase-pure body-centered cubic superlattices. When cooled below -35.1 °C, these superlattices undergo a collective diffusionless phase transformation that yields denser body-centered tetragonal phases. These structural changes can be reversed by increasing the temperature of the dispersion and may lead to the direct modulation of the optical properties of these artificial solids.

Self-Assembly of Atomically Aligned Nanoparticle Superlattices from Pt-Fe3O4 Heterodimer Nanoparticles.

Multicomponent nanoparticle superlattices (SLs) promise the integration of nanoparticles (NPs) with remarkable electronic, magnetic, and optical properties into a single structure. Here, we demonstrate that heterodimers consisting of two conjoined NPs can self-assemble into novel multicomponent SLs with a high degree of alignment between the atomic lattices of individual NPs, which has been theorized to lead to a wide variety of remarkable properties. Specifically, by using simulations and experiments, we show that heterodimers composed of larger Fe3O4 domains decorated with a Pt domain at one vertex can self-assemble into an SL with long-range atomic alignment between the Fe3O4 domains of different NPs across the SL. The SLs show an unanticipated decreased coercivity relative to nonassembled NPs. In situ scattering of the self-assembly reveals a two-stage mechanism of self-assembly: translational ordering between NPs develops before atomic alignment. Our experiments and simulation indicate that atomic alignment requires selective epitaxial growth of the smaller domain during heterodimer synthesis and specific size ratios of the heterodimer domains as opposed to specific chemical composition. This composition independence makes the self-assembly principles elucidated here applicable to the future preparation of multicomponent materials with fine structural control.

Synthesis and Characterization of Stable Cu-Pt Nanoparticles under Reductive and Oxidative Conditions.

We report a synthesis method for highly monodisperse Cu-Pt alloy nanoparticles. Small and large Cu-Pt particles with a Cu/Pt ratio of 1:1 can be obtained through colloidal synthesis at 300 °C. The fresh particles have a Pt-rich surface and a Cu-rich core and can be converted into an intermetallic phase after annealing at 800 °C under H2. First, we demonstrated the stability of fresh particles under redox conditions at 400 °C, as the Pt-rich surface prevents substantial oxidation of Cu. Then, a combination of in situ scanning transmission electron microscopy, in situ X-ray absorption spectroscopy, and CO oxidation measurements of the intermetallic CuPt phase before and after redox treatments at 800 °C showed promising activity and stability for CO oxidation. Full oxidation of Cu was prevented after exposure to O2 at 800 °C. The activity and structure of the particles were only slightly changed after exposure to O2 at 800 °C and were recovered after re-reduction at 800 °C. Additionally, the intermetallic CuPt phase showed enhanced catalytic properties compared to the fresh particles with a Pt-rich surface or pure Pt particles of the same size. Thus, the incorporation of Pt with Cu does not lead to a rapid deactivation and degradation of the material, as seen with other bimetallic systems. This work provides a synthesis route to control the design of Cu-Pt nanostructures and underlines the promising properties of these alloys (intermetallic and non-intermetallic) for heterogeneous catalysis.

Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics.

BACKGROUND: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women. METHODS: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates. RESULTS: A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma. CONCLUSION: The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.

Advances in radiation therapy for testicular seminoma.

PURPOSE: Novel techniques and advances in radiation therapy (RT) have been explored to treat testicular seminoma, a highly radiosensitive and curable histology. We evaluated the historical and current indications for radiation therapy (RT) in testicular seminoma. METHODS: A narrative literature review was performed. Studies of RT for testicular seminoma were included. Additionally, recent trials testing the use of combination or surgical therapies for clinical stage (CS) II were included. Search parameters included radiation therapy, testicular seminoma, surgery, and chemoradiation. Parameters and outcomes assessed were progression-free survival (PFS), overall survival (OS), acute toxicities, long-term sequelae, and rates of secondary malignancies. RESULTS: Practice defining and changing studies in the use or omission of radiation therapy for testicular seminoma were identified along with resultant changes in National Comprehensive Cancer Network (NCCN) and European guidelines. Recent trials in combined chemoradiation and upfront surgical approaches to CS II disease were reviewed. CONCLUSION: RT has historically been used as adjuvant treatment for CS I disease and is highly effective at treating CS II (A/B) testicular seminoma. The drive to maintain therapeutic efficacy and reduce acute and long-term side effects, namely secondary malignancies, is being tested using new radiation technologies, combined modality therapy in the form of chemoradiation and with upfront surgical approaches. Also, as guidelines now "strongly prefer" surveillance instead of adjuvant RT for CS I disease, the current CS II population comprises patients presenting with CS II disease ("de novo") and those who present with CSII after relapsing post orchiectomy for CS I ("relapsed"). Emerging evidence suggests that these two groups have different outcomes with respect to RT and chemoradiation. Consequently, future trials may need to sub-stratify according to these groups.

Synthesis and Characterization of Core-Shell Cu-Ru, Cu-Rh, and Cu-Ir Nanoparticles.

Optimizing the use of expensive precious metals is critical to developing sustainable and low-cost processes for heterogeneous catalysis or electrochemistry. Here, we report a synthesis method that yields core-shell Cu-Ru, Cu-Rh, and Cu-Ir nanoparticles with the platinum-group metals segregated on the surface. The synthesis of Cu-Ru, Cu-Rh, and Cu-Ir particles allows maximization of the surface area of these metals and improves catalytic performance. Furthermore, the Cu core can be selectively etched to obtain nanoshells of the platinum-group metal components, leading to a further increase in the active surface area. Characterization of the samples was performed with X-ray absorption spectroscopy, X-ray powder diffraction, and ex situ and in situ transmission electron microscopy. CO oxidation was used as a reference reaction: the three core-shell particles and derivatives exhibited promising catalyst performance and stability after redox cycling. These results suggest that this synthesis approach may optimize the use of platinum-group metals in catalytic applications.

Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response.

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope.

Prevalence and Predictors of Missed Dysplasia on Index Barrett's Esophagus Diagnosing Endoscopy in a Veteran Population.

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis. METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up EGD within 3-18 months after index EGD. We used logistic regression models to estimate odds ratios and 95% confidence intervals for risk factors of dysplasia on follow-up EGD. RESULTS: We identified 614 patients who had BE on index EGD. Among those with NDBE and follow-up EGD within 3-18 months (n = 271), 4.1% had definite dysplasia on follow-up, and an additional 14.0% had indefinite dysplasia. Proportions of definite or indefinite dysplasia at follow-up within 3-18 months significantly decreased from 32.6% among patients with index EGD before 2009 to 11.7% among patients with index EGD after 2013 (P for trend = .068). Those with any indefinite or definite dysplastic BE at follow-up within 3-18 months after index EGD (n = 49) were more likely to have BE length ≥3 cm on index EGD (odds ratio, 3.39; 95% confidence interval, 1.63-7.08) than those with persistent NDBE or no BE on follow-up. CONCLUSIONS: The occurrence of missed dysplasia on an index EGD has decreased over time. However, those with long segment BE were more than 3 times as likely to have missed dysplasia, and this group could benefit from dysplasia surveillance within 18 months of BE diagnosis.

Cytokine response over the course of COVID-19 infection in pregnant women.

OBJECTIVE: To study how severity and progression of coronavirus disease (COVID-19) affect cytokine profiles in pregnant women. MATERIALS AND METHODS: 69 third-trimester, pregnant women were tested for COVID-19 infection and SARS-CoV-2 specific IgM and IgG antibodies. Patients were stratified according to SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) status and serology (IgM and IgG) status. Cytokines G-CSF, HGF, IL-18, IL-1Ra, IL-2Ra, IL-8, and IP-10 were measured via ELISA. Retrospective chart review for COVID-19 symptoms and patient vitals was conducted, and cytokine levels were compared between SARS-CoV-2 positive and negative cohorts, by seronegative and seropositive infection, by time course since onset of infection, and according to NIH defined clinical severity. RESULTS: IL-18, IL-1Ra, and IP-10 increased in the 44 RT-PCR positive pregnant women compared to the 25 RT-PCR negative pregnant controls. Elevated cytokine levels were found in early infections, defined by positive RT-PCR and seronegative status, and higher cytokine levels were also associated with more severe disease. By IgM seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, while IL-18 levels remained significantly elevated. CONCLUSION: Cytokine profiles of third-trimester pregnant women vary with the time course of infection and are correlated with clinical severity.

External validation of a model determining risk of neoplastic progression of Barrett's esophagus in a cohort of U.S. veterans.

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients. METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence of high-grade dysplasia (HGD) or EAC on initial EGD. We performed an external validation study of a risk model containing sex, smoking, BE length, and low-grade dysplasia (LGD) status and assessed discriminatory ability using the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 608 BE patients, 24 progressed to HGD/EAC. The points-based model discriminated well with an AUROC of .72 (95% confidence interval [CI], .63-.82). When categorized into low-, intermediate-, and high-risk groups according to published cutoffs, the AUROC was poor at .57. Restructured into low-risk versus high-risk groups, the AUROC was .72 (95% CI, .64-.80). Excluding baseline LGD did not reduce discriminatory ability (AUROC, .73; 95% CI, .64-.82). CONCLUSIONS: This external validation provides further evidence that the model including sex, LGD status, smoking status, and BE length may help to risk stratify BE patients. A simplified version excluding LGD status and/or reducing the number of risk groups has increased utility in clinical practice without loss of discriminatory ability.

Robot-assisted vs ultrasonography-guided transversus abdominis plane (TAP) block vs local anaesthesia in urology: results of the UROTAP randomized trial.

OBJECTIVES: To prospectively analyse robotically administered transperitoneal transversus abdominis plane (robot-assisted transversus abdominis plane [RTAP]) compared with both ultrasonography-guided transversus abdominis plane (UTAP) and local anaesthesia (LA) with regard to pain control and narcotic use in patients undergoing robot-assisted prostatectomy (RARP) or robot-assisted partial nephrectomy (RAPN). SUBJECTS/PATIENTS AND METHODS: Patients undergoing RARP or RAPN were randomized in a single-blind 2:2:1 fashion to RTAP:UTAP:LA, with the study powered to evaluate superiority of UTAP to LA and non-inferiority of RTAP to UTAP. We compared time to deliver the block, operating room time, postoperative pain scores using the visual analogue scale, and intra-operative and postoperative analgesia consumption. RESULTS: A total of 143 patients were randomized and received treatment. There was no significant difference in patient baseline characteristics. UTAP did not demonstrate superiority to LA in terms of pain control. RTAP and LA were faster to administer than UTAP (time to perform block 2.5 vs 2.5 vs 6.25 min; P < 0.001). There was no difference in postoperative narcotic, acetaminophen, ketorolac or ondansetron requirements among the three groups (P > 0.05). The study was terminated early due to the unexpected efficacy of LA. CONCLUSION: This study showed that UTAP and RTAP do not provide superior pain control to LA. The efficiency, effectiveness, and ease of administration of LA make it an excellent option for first-line therapy for postoperative analgesia.

Centering Culture in Mental Health: Differences in Diagnosis, Treatment, and Access to Care Among Older People of Color.

Mental healthcare disparities are routinely documented, yet they remain wider than in most other areas of healthcare services and common mental disorders (depression and anxiety) continue to be one of the highest health burdens for older people of color. To address disparities in mental health services for older people of color, the narrative must move beyond simply documenting these inequities and attain a better understanding of the internalized, interpersonal, systemic, and medical racism that have harmed these communities and excluded them from its services in the first place. It is imperative that researchers, clinicians, and policymakers acknowledge the realities of racism and discrimination as leading causes of mental healthcare disparities. Therefore, this review is a call-to-action. Authors adopt an antiracist and health equity lens in evaluating the differing needs of Blacks/African-Americans, Asian Americans, and Latinos by exploring psychiatric comorbidity, experiences with seeking, accessing, and engaging in treatment, and the unique cultural and psychosocial factors that affect treatment outcomes for these diverse groups. Further, authors offer researchers and practitioners tangible tools for developing and implementing culturally-sensitive, mental health focused interventions for older people of color with special attention placed on cultural adaptations, models of care, prevention, and practical strategies that can be implemented to reduce disparities and increase equity in mental healthcare.

From Vaccines to Vitality: The Progression of a Community-Academic Collaboration.

In this practice note, we document the progression of the Community Vaccine Collaborative (CVC), on which we first published in 2021. The CVC convened to address deep COVID-19-related disparities affecting the Black, Latine, immigrant/refugee, and lesbian, gay, bisexual, transgender, queer, (questioning), intersex, asexual, and (agender) (LGBTQIA+) communities. The COVID-19 pandemic is rooted in centuries of oppression and marginalization leading to inequities and required dedicated focus to support marginalized communities in times of crisis. The CVC comprises community members, community-based organizations, health care providers, researchers, health systems leaders, and public health practitioners (among others), all of whom are dedicated to promoting COVID-19 vaccine equity. As the pandemic shifts and changes, so too has our group, to remain relevant to community needs and priorities. This article details Year 2 of the CVC, focusing on how we have grown and sustained this unique partnership. We also share results from an evaluation of the CVC, documenting participation in the collaborative space and alignment with CVC core principles. Finally, we discuss next steps and implications for the CVC including our pivot from vaccines to community vitality as we expand and sustain our collaborative efforts to address the ongoing COVID-19 pandemic and intersecting public health crises.

Real-World Burden of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is associated with an increase in healthcare resource use and poor health-related quality of life (HRQoL). We assessed the humanistic and economic burden of NASH, disease management, and patient journey. METHODS: We performed a cross-sectional analysis of data, collected from July through November 2017, from the Growth from Knowledge Disease Atlas Real-World Evidence program, reported by physicians in United States, France, and Germany. We extracted demographic and medical data from medical records. Some patients voluntarily completed a survey that provided information on disease history, treatment satisfaction, and patient-reported outcomes. RESULTS: We analyzed data from 1216 patients (mean age, 54.9±12.3 years; 57.5% male; mean body mass index, 31.7±6.9); 64.6% had biopsy-confirmed NASH and comorbidities were recorded for 41.3%. Treatments included lifestyle modification (64.6%) or use of statins (25.0%), vitamin E (23.5%), or metformin (20.2%). Patients with biopsy-confirmed NASH reported more physician (4.5 vs 3.7) and outpatient visits (1.8 vs1.4) than patients with suspected NASH not confirmed by biopsy. Among the 299 patients who completed the survey, 47.8% reported various symptoms associated to their NASH. Symptomatic patients reported significantly lower HRQoL than patients without symptoms. CONCLUSIONS: In an analysis of data from 3 countries, we found NASH to be associated with regular use of medical resources; patients with symptoms of NASH had reduced HRQoL. The burden of NASH appears to be underestimated. Studies are needed to determine the burden of NASH by fibrosis stage and disease severity.

The impact of metabolic syndrome components on urinary parameters and risk of stone formation.

PURPOSE: To investigate the relationship between metabolic syndrome (MS) and urinary abnormalities in stone-forming patients. Additionally, to delineate whether severity of urinary derangements is impacted by the number of co-occurring MS components. METHODS: Stone-forming patients who underwent initial metabolic workup prior to medical intervention at a comprehensive stone clinic were retrospectively reviewed and included in the study. Patients were given a six point (0-5) Metabolic Syndrome Severity Score (MSSS) based on the number of co-occurring MS components and split into six respective groups. Baseline clinical characteristics and metabolic profiles were compared between groups. RESULTS: Four-hundred-ninety-five patients were included in the study. Median age and median BMI was 58 years and 27.26 kg/m2, respectively. Several significant metabolic differences were noted, most notably a downward trend in median urinary pH (p < 0.001) and an upward trend in median urinary supersaturation uric acid (p < 0.001) across groups as MSSS increased. Multivariate analysis demonstrated an independent association between higher MSSS and increasing number of urinary abnormalities. A second multivariate analysis revealed that all MS components except hyperlipidemia were independently associated with low urinary pH. Additionally, obesity was independently associated with the greatest number of urinary abnormalities and had the strongest association with hyperuricosuria. CONCLUSIONS: Prior research has attributed the strong association of nephrolithiasis and MS to high prevalence of UA nephrolithiasis and low urinary pH. Our findings indicate that all MS components with the exception of hyperlipidemia were independently associated with low urinary pH suggesting a mechanism independent from insulin resistance.

Functional Dyspepsia and Duodenal Eosinophil Count and Degranulation: A Multiethnic US Veteran Cohort Study.

BACKGROUND: Duodenal eosinophilia may play a role in functional dyspepsia (FD), but existing study results are conflicted. We investigated the association between duodenal eosinophils (count and degranulation) and FD symptoms, accounting for atopic conditions, medications, and seasonal variations. METHODS: In a cross-sectional study conducted in the Michael E. DeBakey VA Medical Center in Houston, Texas, we analyzed duodenal histopathology of 436 patient samples from a prospective cohort with a validated symptom survey data and chart reviews. FD was defined using Rome II symptom criteria. Eosinophil count was number per 5 high-power fields (HPF), and eosinophil degranulation was eosinophilic granules in the stroma both determined by two independent investigators. RESULTS: The study cohort was predominantly male (87.4%) with a mean age of 59.3 (standard deviation (SD) ± 9.8). Mean and median eosinophil counts were 75.5 (± 47.8) and 63 (IQR: 43, 101) per five HPF, respectively. Duodenal eosinophilia (defined as ≥ 63 per 5 HPF) and eosinophil degranulation were present in 50.5% and 23.1% of patient samples, respectively. FD was observed in 178 patients (41.7%), but neither the mean eosinophil count nor duodenal eosinophilia was associated with FD. Eosinophil degranulation was independently associated with FD overall (OR 1.74; 95% CI 1.08, 2.78; p = 0.02) and early satiety (OR 2.04; 95% CI 1.26, 3.30; p = 0.004). CONCLUSIONS: In this large, ethnically diverse cohort of adult patients, we found no significant association between duodenal eosinophilia and FD. However, the presence of duodenal eosinophilic degranulation, an activated eosinophil marker, was significantly associated with FD, especially early satiety.

Integrated Psychosocial Group Treatment: A Randomized Pilot Trial of a Harm Reduction and Preventive Approach for Patients with Chronic Pain at Risk of Opioid Misuse.

OBJECTIVE: To examine the benefits of an integrated psychosocial group treatment (IPGT) model for patients with chronic pain at risk of opioid misuse. DESIGN: This study was a small-scale, single-blinded, two-group randomized controlled trial. SETTING: Outpatient. SUBJECTS: Adults with chronic pain of >3 months' duration who were currently prescribed opioid medication and were at risk of opioid misuse. METHODS: Patients with chronic pain who were at risk of opioid misuse (n = 30) were randomly assigned to IPGT or treatment as usual. IPGT consists of six group sessions of psychoeducation, motivational interviewing, cognitive behavioral therapy, mindfulness, and peer support. Participants were assessed at baseline, first follow-up at 6 weeks, and a posttreatment follow-up at 9 weeks. Outcomes included feasibility, acceptability, and preliminary efficacy. Data were analyzed with descriptive and multivariate analyses. RESULTS: All intervention components were delivered to 87% of the participants, and IPGT recipients reported a high level of satisfaction. Results of the multivariate analyses demonstrated nonsignificant improvements in pain severity (ß = 0.22, 95% CI: -0.24 to 0.66, P = 0.35). However, we observed significant treatment × time interactions on pain interference (ß = 3.32, 95% confidence interval [CI]: 0.01 to 6.65, P = 0.05) and pain catastrophizing (ß = 2.74, 95% CI: 0.49 to 4.99, P = 0.02). Lastly, we detected no significant differences in opioid misuse (adjusted odds ratio = 0.69, 95% CI: -0.26 to 1.64, P = 0.16). CONCLUSION: This study provides support for the IPGT intervention being acceptable and feasible for delivery in patients with chronic pain at risk of opioid misuse. Efficacy was achieved in pain interference and pain catastrophizing.