The neural circuitry of social homeostasis: Consequences of acute versus chronic social isolation.

Social homeostasis is the ability of individuals to detect the quantity and quality of social contact, compare it to an established set-point in a command center, and adjust the effort expended to seek the optimal social contact expressed via an effector system. Social contact becomes a positive or negative valence stimulus when it is deficient or in excess, respectively. Chronic deficits lead to set-point adaptations such that reintroduction to the previous optimum is experienced as a surplus. Here, we build upon previous models for social homeostasis to include adaptations to lasting changes in environmental conditions, such as with chronic isolation.

Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome.

Cristae are high-curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae-shaping proteins have been defined, analogous lipid-based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi-scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein-mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low-oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.

Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing.

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

Deciphering human macrophage development at single-cell resolution.

Macrophages are the first cells of the nascent immune system to emerge during embryonic development. In mice, embryonic macrophages infiltrate developing organs, where they differentiate symbiotically into tissue-resident macrophages (TRMs)1. However, our understanding of the origins and specialization of macrophages in human embryos is limited. Here we isolated CD45+ haematopoietic cells from human embryos at Carnegie stages 11 to 23 and subjected them to transcriptomic profiling by single-cell RNA sequencing, followed by functional characterization of a population of CD45+CD34+CD44+ yolk sac-derived myeloid-biased progenitors (YSMPs) by single-cell culture. We also mapped macrophage heterogeneity across multiple anatomical sites and identified diverse subsets, including various types of embryonic TRM (in the head, liver, lung and skin). We further traced the specification trajectories of TRMs from either yolk sac-derived primitive macrophages or YSMP-derived embryonic liver monocytes using both transcriptomic and developmental staging information, with a focus on microglia. Finally, we evaluated the molecular similarities between embryonic TRMs and their adult counterparts. Our data represent a comprehensive characterization of the spatiotemporal dynamics of early macrophage development during human embryogenesis, providing a reference for future studies of the development and function of human TRMs.

The UCSC Genome Browser database: 2024 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides annotation data on thousands of genome assemblies, ranging from human to SARS-CoV2. This year, we have introduced new data from the Human Pangenome Reference Consortium and on viral genomes including SARS-CoV2. We have added 1,200 new genomes to our GenArk genome system, increasing the overall diversity of our genomic representation. We have added support for nine new user-contributed track hubs to our public hub system. Additionally, we have released 29 new tracks on the human genome and 11 new tracks on the mouse genome. Collectively, these new features expand both the breadth and depth of the genomic knowledge that we share publicly with users worldwide.

Some viruses need to phase-separate to replicate.

Replication of rotavirus, an important cause of gastroenteritis in children, proceeds in large, easily discernible cytoplasmic structures, called viroplasms or viral factories, but mechanisms underlying their formation and function in infected cells have remained mysterious. In this issue, Geiger et al (2021) used a combination of in silico, in vitro, and cell-based approaches to define how two essential rotavirus nonstructural proteins, NSP2 and NSP5, form liquid-liquid phase-separated condensates as the structural foundation of rotavirus factories.

Biology of resident tissue macrophages.

Although best known for their phagocytic and immunological functions, macrophages have increasingly been recognised as key players in the development, homeostasis and regeneration of their host tissues. Early during development, macrophages infiltrate and colonise all tissues within the body, developing symbiotically with their host tissues and acquiring unique functional adaptations based on the tissue microenvironment. These embryonic resident tissue macrophages (RTMs) are ontogenically distinct from the later adult bone marrow-derived monocytes, and in some tissues are self-maintained independently of general circulation at a steady state. In this article, we briefly discuss the ontogeny, maintenance and unique tissue adaptions of RTMs focusing on microglia, Kupffer cells, Langerhans cells, intestinal macrophages, cardiac macrophages and tumour-associated macrophages, and highlight their role in development, homeostasis and dysfunction.

The UCSC Genome Browser database: 2023 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is an omics data consolidator, graphical viewer, and general bioinformatics resource that continues to serve the community as it enters its 23rd year. This year has seen an emphasis in clinical data, with new tracks and an expanded Recommended Track Sets feature on hg38 as well as the addition of a single cell track group. SARS-CoV-2 continues to remain a focus, with regular annotation updates to the browser and continued curation of our phylogenetic sequence placing tool, hgPhyloPlace, whose tree has now reached over 12M sequences. Our GenArk resource has also grown, offering over 2500 hubs and a system for users to request any absent assemblies. We have expanded our bigBarChart display type and created new ways to visualize data via bigRmsk and dynseq display. Displaying custom annotations is now easier due to our chromAlias system which eliminates the requirement for renaming sequence names to the UCSC standard. Users involved in data generation may also be interested in our new tools and trackDb settings which facilitate the creation and display of their custom annotations.

Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma. METHODS: We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual. FINDINGS: Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66-75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3-27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4-21·3] with pembrolizumab vs 16·1 months [13·1-18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64-0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20-33%) with pembrolizumab and 17% (13-24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group. INTERPRETATION: In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma. FUNDING: The Canadian Cancer Society and Merck & Co.

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE. METHODS: We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy. RESULTS: We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001). CONCLUSIONS: In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.

Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis.

INTRODUCTION: Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. METHODS: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. RESULTS: Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). DISCUSSION: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations and Cost.

BACKGROUND: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost. METHODS: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes. RESULTS: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients. CONCLUSIONS: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.

EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis.

BACKGROUND: This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR. METHODS: This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization. RESULTS: One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (ß = -0.24), achieving response (ß = 0.86), attaining remission (ß = 1.05), or reducing treatment dropout rates (ß = -0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females. CONCLUSION: The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

Burden of disease and treatment patterns in patients with vitiligo: findings from a national longitudinal retrospective study in the UK.

BACKGROUND: UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. OBJECTIVE: To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. METHODS: This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. RESULTS: Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years [PY; range 0.10 (2020-COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%) and sleep disturbance (12.7%), and recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5% and 3.9%, respectively. Mental health comorbidities were more common in White (e.g. depression and/or anxiety 29.0%) than in Black (18.8%) and Asian (16.1%) patients. In adolescents, depression and/or anxiety was most commonly diagnosed after a vitiligo diagnosis than before (7.4% vs. 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 PY) and general practitioner consultations (97.9/100 PY). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatment (i.e. topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids or phototherapy), increasing to 82.0% the next year; median time from diagnosis to first treatment was 34.0 months (95% confidence interval 31.6-36.4). Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments. CONCLUSION: Most patients were not on vitiligo-related treatments within a year of diagnosis, with the time to first treatment exceeding 2 years, suggesting that vitiligo may be dismissed as unimportant. New effective treatments, early initiation and psychological intervention and support are needed to reduce the vitiligo burden on patients.

Vitiligo is a chronic disease in which cells that produce the skin pigment called melanin are attacked, resulting in white or pale patches of skin. It is diagnosed in an estimated 0.2­0.8% of people in Europe. This study aimed to describe how many new cases of vitiligo were recorded between 2010 and 2021 in the UK and the overall percentage of people with vitiligo. Linked national general practitioner (GP) and hospital-based records containing information on medical diagnoses, admissions and hospital visits were used. Records of other diseases and conditions, including mental health conditions, in combination with healthcare service use and treatment prescribed to patients with vitiligo, were studied to describe the impact of living with vitiligo. It was found that 0.16 new cases of vitiligo were recorded per 1000 person-years (for example, 0.16 new cases would have been recorded if 1000 people were followed for 1 year or if 100 people were all followed for 10 years) between 2010 and 2021. In 2021, 0.4% of the population studied had vitiligo. In the 5 years after a new diagnosis of vitiligo, the most common other diseases recorded were diabetes (19%), eczema (9%), thyroid disease (8%) and rheumatoid arthritis (7%), and the most common mental health conditions were depression and/or anxiety (25%). In the year after diagnosis, GP and dermatology outpatient visits were the most common type of medical services used. In 2019, 85% of all individuals with vitiligo were not receiving any vitiligo-related treatment (such as creams or phototherapy). It took approximately 34 months from diagnosis of vitiligo to the start of first treatment. The results suggest that new effective treatments and psychological interventions are needed to reduce the burden of vitiligo.

Increasing Age at the Time of Diagnosis and Evolving Phenotypes of Eosinophilic Esophagitis Over 20 Years.

BACKGROUND: The presentation of eosinophilic esophagitis (EoE) is heterogeneous, but trends over time are not known. AIM: To determine whether clinical and endoscopic phenotypes at EoE diagnosis have changed over the past 2 decades. METHODS: In this retrospective cohort study, adults and children with newly diagnosed EoE were phenotyped as follows: (1) inflammatory vs fibrostenotic vs mixed on endoscopy; (2) atopic vs non-atopic; (3) age at symptom onset; (4) age at diagnosis; (5) presence of autoimmune or connective tissue disease; and (6) responsive to steroids. The prevalence of different phenotypes was categorized by 5-year intervals. Multivariate analysis was performed to assess for changes in patient features over time. RESULTS: Of 1187 EoE patients, age at diagnosis increased over time (from 22.0 years in 2002-2006 to 31.8 years in 2017-2021; p < 0.001) as did the frequency of dysphagia (67% to 92%; p < 0.001). Endoscopic phenotypes were increasingly mixed (26% vs 68%; p < 0.001) and an increasing proportion of patients had later onset of EoE. However, there were no significant trends for concomitant autoimmune/connective tissue disease or steroid responder phenotypes. On multivariate analysis, after accounting for age, dysphagia, and food impaction, the increase in the mixed endoscopic phenotype persisted (aOR 1.51 per each 5-year interval, 95% CI 1.31-1.73). CONCLUSION: EoE phenotypes have changed over the past two decades, with increasing age at diagnosis and age at symptom onset. The mixed endoscopic phenotype also increased, even after controlling for age and symptomatology. Whether this reflects changes in provider recognition or disease pathophysiology is yet to be elucidated.

Changes in intraocular pressure following intravitreal dexamethasone implant in patients with history of glaucoma filtration surgery.

PURPOSE: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. METHODS: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure. RESULTS: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%). CONCLUSION: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma.