Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

Biosimilar Uptake In The US: Patient And Prescriber Factors.

Among 196,766 commercially insured and Medicare Advantage patients who newly initiated biologic drugs with available biosimilar versions, biosimilar initiation increased from 1 percent in 2013 to 34 percent in 2022. Patients were less likely to initiate biosimilars if they were younger than age eighteen or the drug was prescribed by a specialist or administered in a hospital outpatient facility.

Safety and efficacy of biologic drugs in children or adolescents with atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Children and adolescents suffering from moderate-to-severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p-value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08-8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71-10.02), EASI 50 (OR 8.89; 95% CI 6.18-12.78) and EASI 90 (8.30; 95% CI 4.81-14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34-9.90) or 4 points or more (OR 8.09; 95% CI 5.19-12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58-1.07), and conjunctivitis (OR 2.08; 95% CI 1.00-4.33). In this meta-analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population.

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Introduction: Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. Objective: This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Methods: Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. Results: A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Conclusion: Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. Level of Evidence: 4.

Real-life treatment persistence and treatment outcomes of Finnish patients with inflammatory bowel disease receiving vedolizumab as first-line biological treatment.

Purpose: To analyze treatment persistence and treatment outcomes of vedolizumab as first-line biological treatment in Crohn's disease (CD) and ulcerative colitis (UC) patients in a Finnish real-world setting. Methods: Observational, retrospective, multi-center chart review study that included adult CD and UC patients initiating vedolizumab as first-line biological treatment between 2014 and 2020. Results: The cohort consisted of 54 CD and 69 UC patients. At month 12, treatment persistence was 84.9 % in CD and 64.7 % in UC. Most vedolizumab discontinuations (CD, n = 11; UC, n = 26) were due to inefficacy. Discontinuations due to adverse events were rare (n < 5). Efficacy improvements were observed in treatment persistent patients at 12 months vs. baseline in the Harvey-Bradshaw Index (CD, 1.8 vs. 3.9, p = 0.001), Partial Mayo Score (UC, 1.0 vs. 4.9, p < 0.001), Physician's Global Assessment (CD, 0.9 vs. 1.8, p < 0.001; UC, 0.4 vs. 2.1, p < 0.001), along with positive endoscopic and biochemical outcomes. Clinical remission was 90.9 % vs. 63.0 % for CD, and 81.6 % vs. 12.3 % for UC, while corticosteroid use was 15.9 % vs. 53.7 % for CD, and 14.6 % vs. 92.8 % for UC at 12 months and baseline, respectively. Conclusion: Vedolizumab was associated with improvements in efficacy, endoscopic activity, biochemical parameters, and decreased corticosteroid burden when used as a first-line biological treatment.

Clinical impacts of immunomodulator withdrawal from anti-tumor necrosis factor combination therapy in pediatric inflammatory bowel disease.

OBJECTIVES: Combination therapy consists of both anti-tumor necrosis factor (anti-TNF) and an immunomodulator (IMM) and has been shown to improve outcomes in patients with inflammatory bowel disease (IBD). This study assesses the impacts of IMM withdrawal from combination therapy to anti-TNF monotherapy in children with IBD. METHODS: This single-center retrospective cohort study included children with IBD initiated on combination therapy between 2014 and 2019 who discontinued the IMM. We evaluated whether IMM withdrawal impacts laboratory values and disease activity. Linear mixed effects models with random intercepts were used to compare differences between groups. Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation of therapy. RESULTS: One hundred and fifty-two patients discontinued the IMM which did not significantly affect disease activity. However, 18% of patients escalated therapy after IMM withdrawal, primarily due to low anti-TNF levels. Lower anti-TNF and higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels before IMM withdrawal were associated with subsequent escalation of therapy. Overall, there was no statistically significant effect on anti-TNF drug levels. Patients with Crohn's disease (CD) on infliximab (IFX) and methotrexate (MTX) who discontinued the IMM had an increase in mean ESR and CRP (p < 0.05). CONCLUSIONS: IMM withdrawal from anti-TNF combination therapy may be considered safe in the setting of higher anti-TNF levels and normal serum inflammatory markers. Clinicians should consider assessing anti-TNF levels and inflammatory markers after IMM withdrawal, especially in patients with CD receiving IFX who discontinued MTX.

Exploration of Stress and Inflammatory Biomarkers Among Non-Hispanic Black and Hispanic Cancer Survivors.

OBJECTIVES: To evaluate associations among social determinants of health (SDOH), stress, interleukin-6 (IL-6), and quality of life among non-Hispanic Black and Hispanic cancer survivors. SAMPLE & SETTING: Individuals who had completed cancer treatment and did not identify as White (N = 46) were recruited through community partnerships in western Massachusetts and a state cancer registry. METHODS & VARIABLES: This descriptive cross-sectional study used questionnaires and morning salivary samples to collect data between June 2022 and September 2023. RESULTS: Most participants were breast cancer survivors, were female, identified as African American or Black, and reported moderate levels of stress and low physical activity. Cortisol levels were higher among African American or Black participants, those with lower body mass index, and those with less consumption of fruit and vegetables. Higher symptom experience was associated with higher IL-6 levels. No associations were identified between IL-6 and cortisol or perceived stress and cortisol levels. IMPLICATIONS FOR NURSING: Incorporating SDOH in self-reported outcomes, including health behaviors and associated biologic indicators, can facilitate early identification and interventions to improve symptom experience and health outcomes of cancer survivors.

Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.

Biologics and small molecules treatment for moderate-to-severe atopic dermatitis patients with comorbid conditions and special populations: an Italian perspective.

This comprehensive review offers a detailed look at atopic dermatitis (AD) treatment in Italy, focusing primarily on the use of biologics and small molecules. In response to advancing knowledge of AD's causes and treatments, there's a global need for updated guidelines to provide physicians with a more comprehensive clinical perspective, facilitating personalized treatment strategies. Dupilumab, a groundbreaking biologic, gained approval as a significant milestone. Clinical trials demonstrated its ability to significantly reduce AD severity scores, with an impressive 37% of patients achieving clear or nearly clear skin within just 16 weeks of treatment. Real-world studies further support its efficacy across various age groups, including the elderly, with a safety profile akin to that of younger adults. Tralokinumab, a more recent approval, shows promise in clinical trials, particularly among younger populations. However, its real-world application, especially in older individuals, lacks comprehensive data. Janus Kinases inhibitors like Upadacitinib, Baricitinib, and Abrocitinib hold substantial potential for AD treatment. Nevertheless, data remains limited for patients over 75, with older adults perceived to carry a higher risk profile. Integrated safety analyses revealed individuals aged 60 and above experiencing major adverse cardiovascular events and malignancies, underscoring the need for cautious consideration. While these therapies offer promise, especially among younger patients, further research is essential to determine their safety and efficacy in various populations, including pediatric, geriatric, and those with comorbidities. Biologics and small molecules are improving AD treatment, as shown in this review.

A Successful Switch From Ustekinumab to an Extended Dosing Interval of Guselkumab Without Induction in a Patient With Psoriasis Vulgaris.

Psoriasis vulgaris, also known as plaque-type psoriasis, is the most common form of psoriasis. It is characterized by erythematous plaques covered with scales. Among the available treatments, the fully human monoclonal antibodies ustekinumab (UST) and guselkumab (GUS) have low immunogenicity. Additionally, GUS has not been found to have a significant risk of inducing the development of clinically relevant neutralizing antibodies. Therefore, we sometimes consider switching to GUS when UST is insufficiently effective. However, switching to another biological agent usually requires an induction phase, potentially incurring additional costs. We herein present the first case of a successful transition from UST 90 mg to an extended dosing interval of GUS without an induction phase. This approach may be a viable and cost-saving option, especially for patients with relatively low disease activity.

Deciphering Microbial Composition in Patients with Inflammatory Bowel Disease: Implications for Therapeutic Response to Biologic Agents.

Growing evidence suggests that alterations in the gut microbiome impact the development of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD often requires the use of immunosuppressant drugs and biologic therapies to facilitate clinical remission and mucosal healing, some patients do not benefit from these drugs, and the reasons for this remain poorly understood. Despite advancements, there is still a need to develop biomarkers to help predict prognosis and guide treatment decisions. The aim of this study was to investigate the gut microbiome of IBD patients using biologics to identify microbial signatures associated with responses, following standard accepted criteria. Microbiomes in 66 stool samples from 39 IBD patients, comprising 20 CD and 19 UC patients starting biologic therapies, and 29 samples from healthy controls (HCs) were prospectively analyzed via NGS and an ensemble of metagenomics analysis tools. At baseline, differences were observed in alpha and beta metrics among patients with CD, UC and HC, as well as between the CD and UC groups. The degree of dysbiosis was more pronounced in CD patients, and those with dysbiosis exhibited a limited response to biological drugs. Pairwise differential abundance analyses revealed an increasing trend in the abundance of an unannotated genus from the Clostridiales order, Gemmiger genus and an unannotated genus from the Rikenellaceae family, which were consistently identified in greater abundance in HC. The Clostridium genus was more abundant in CD patients. At baseline, a greater abundance of the Odoribacter and Ruminococcus genera was found in IBD patients who responded to biologics at 14 weeks, whereas a genus identified as SMB53 was more enriched at 52 weeks. The Collinsella genus showed a higher prevalence among non-responder IBD patients. Additionally, a greater abundance of an unclassified genus from the Barnesiellaceae family and one from Lachnospiraceae was observed in IBD patients responding to Vedolizumab at 14 weeks. Our analyses showed global microbial diversity, mainly in CD. This indicated the absence or depletion of key taxa responsible for producing short-chain fatty acids (SCFAs). We also identified an abundance of pathobiont microbes in IBD patients at baseline, particularly in non-responders to biologic therapies. Furthermore, specific bacteria-producing SCFAs were abundant in patients responding to biologics and in those responding to Vedolizumab.

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis.

Atopic dermatitis (AD) is a skin condition characterized by significant challenges and a substantial deterioration in the life quality for affected patients. The therapeutic landscape for AD has witnessed a transformative shift with the emergence of biologic therapies. Our focus centers on biologics currently undergoing phase III and IV clinical trials, deeming them to hold the highest potential for significant clinical relevance. To identify biologic drugs under development in phase III and IV clinical trials, we searched ClinicalTrials.gov. Additional relevant trials were identified through JapicCTI/ Japan Registry of Clinical Trials (jRCT) with a citation search. A search in MEDLINE and EMBASE was performed. There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). A search in MEDLINE revealed 132 articles concerning phase III and IV clinical trials for AD treatment. A total of 39 articles concerned biologic drugs covering 23 clinical trials. A search in EMBASE revealed 268 relevant articles, allowing us to identify results of an additional six clinical trials. The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions.

Monoclonal Antibodies in the Management of Inflammation in Wound Healing: An Updated Literature Review.

Chronic wounds pose a significant clinical challenge due to their complex pathophysiology and the burden of long-term management. Monoclonal antibodies (mAbs) are emerging as a novel therapeutic option in managing difficult wounds, although comprehensive data on their use in wound care are lacking. This study aimed to explore existing scientific knowledge of mAbs in treating chronic wounds based on a rationale of direct inhibition of the main molecules involved in the underlying inflammatory pathophysiology. We performed a literature review excluding primary inflammatory conditions with potential ulcerative outcomes (e.g., hidradenitis suppurativa). mAbs were effective in treating wounds from 16 different etiologies. The most commonly treated conditions were pyoderma gangrenosum (treated with 12 different mAbs), lipoid necrobiosis, and cutaneous vasculitis (each treated with 3 different mAbs). Fourteen mAbs were analyzed in total. Rituximab was effective in 43.75% of cases (7/16 diseases), followed by tocilizumab (25%, 4/16 diseases), and both etanercept and adalimumab (18.75%, 3/16 conditions each). mAbs offer therapeutic potential for chronic wounds unresponsive to standard treatments. However, due to the complex molecular nature of wound healing, no single target molecule can be identified. Therefore, the use of mAbs should be considered as a translational approach for limited cases of multi-resistant conditions.

Real-World Safety Profile of Biologic Drugs for Severe Uncontrolled Asthma: A Descriptive Analysis from the Spanish Pharmacovigilance Database.

Background: The present investigation provides a thorough analysis of adverse drug reactions (ADRs) reported in the Database of the Spanish Pharmacovigilance System (FEDRA) for biologic medications primarily indicated for severe refractory asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Our main objective was to identify ADRs not documented in the drugs' Technical Sheets (summary of product characteristics, SmPC), potentially indicating unrecognized risks meriting pharmacovigilance attention. Methods: Data spanning from each drug's market introduction until 22 January 2024, were analyzed, sourced from direct submissions to the Spanish Pharmacovigilance System, industry communications, and literature reviews. We evaluated notifications impartially to ensure a comprehensive review of all the ADRs associated with these medications. Results: This investigation underlines the critical role of post-marketing surveillance in enhancing patient safety. It emphasizes the necessity for healthcare professionals to report ADRs comprehensively to foster a robust pharmacovigilance system. Furthermore, the study highlights gaps between the reported ADRs and the information provided in SmPCs, signaling potential areas for improvement in drug safety monitoring and regulatory oversight. Conclusions: Finally, these findings may contribute to informed decision making in clinical practice and regulatory policy, ultimately advancing patient care and safety in the management of severe uncontrolled asthma.

Efficacy and safety of pharmacological treatments for autoimmune disease-associated interstitial lung disease: A systematic review and network meta-analysis.

BACKGROUND: Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. RESULTS: The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. CONCLUSIONS: MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.

Interleukin(IL)-1/IL-6-inhibitor-associated drug reaction with eosinophilia and systemic symptoms (DReSS) in systemic inflammatory illnesses.

BACKGROUND: After introducing interleukin(IL)-1/IL-6 inhibitors, some Still and Still-like patients developed unusual often fatal pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: We sought to facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not-stopping IL-1/IL-6-inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6-inhibitors to 37 cases not-stopping these drugs. RESULTS: Before reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease onset age for reaction cases with pre-existing cardiothoracic comorbidities. After reaction began, increased rates of pulmonary complications and macrophage activation syndrome (MAS), differentiated drug-reaction cases from drug-tolerant controls (p=4.7x10-35; p=1.1x10-24, respectively). Initial DReSS feature was typically reported 2-8 weeks after initiating IL-1/IL-6-inhibition. In drug-reaction cases stopping versus not-stopping IL-1/IL-6-inhibitor treatment, reaction related features were indistinguishable, including pulmonary complication rates [75%(39/52] versus [76%(28/37)]. Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of MAS, and improved survival (p=0.005, multivariate regression). Resolution of pulmonary complications occurred in 67%(26/39) of drug-reaction cases who stopped and in none who continued inhibitors. CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6-inhibitors significantly improved outcomes.

Janus Kinase Inhibitors as Successful Treatment Alternative in Dupilumab-Induced Psoriasis.

Introduction: After the introduction of dupilumab as systemic treatment for atopic dermatitis, an increasing number of patients have been successfully treated. However, reports of patients developing psoriasis as a secondary skin condition have been accumulating. The most likely reason is assumed to be an immune shift from Th2- to Th1-mediated auto-inflammatory processes. Case Presentation: Our patient is a 38-year-old male suffering from head-neck type atopic dermatitis since childhood. As one of the first patients in Switzerland, he received dupilumab in 2018 leading to a significant improvement of his skin lesions. One year later he developed progressing circular erythematous-squamous plaques which correlated histologically with psoriasis. In 2021, 3 years after initiating dupilumab, we switched systemic therapy to baricitinib. Three months after initiation, his psoriatic lesions were completely healed, while the atopic lesions remained stable with low inflammatory activity. Conclusion: In patients treated with dupilumab for atopic dermatitis immune shift needs to be considered in case of newly appearing skin lesions. With a growing number of described cases, we conclude that baricitinib is a good alternative treatment for atopic dermatitis in patients suffering from biologic-induced psoriasis.

Mode of delivery predicts postpartum maternal leukocyte telomere length.

BACKGROUND: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging. STUDY DESIGN: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma). RESULTS: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction. CONCLUSION: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.

Single-center real-world data and technical considerations from 100 consecutive patients treated with the Perceval aortic bioprosthesis.

Objectives: Although the Perceval sutureless aortic valve bioprosthesis presents a feasible alternative to conventional aortic valve prostheses, the extent of its applicability with respect to technical considerations for a real-world patient collective is still under debate. Methods: One hundred patients received the Perceval prosthesis [males: 59; age: 72.5 (7.3-79) years] between December 2015 and February 2023 [EuroSCORE II: 2.8 (1.7-5.4)] for an aortic valve replacement (AVR), with additional concomitant procedures, for underlying severe aortic valve stenosis [n = 93 (93)], endocarditis [n = 5 (5)], and redo AVR [n = 7 (7)] including a prior surgical AVR [n = 4 (4)] and a failed transcatheter aortic valve implantation [n = 3 (3)]. Surgery was conducted primarily by median sternotomy [n = 71 (71)] and, alternatively, by the upper hemisternotomy approach [n = 29 (29)]. Results: Over a median follow-up time of 36.5 (16.5-53) months, eight patients (8%) underwent postoperative pacemaker implantation, with five (5%) due to high-grade atrioventricular block, while nine patients experienced a stroke (9%). The median values of maximum and mean gradients across all valve sizes were 22 (18-27.5) mmHg and 10 (13-18) mmHg, respectively. Two patients (2%) had moderate and one (1%) had severe paravalvular leakage, with the latter presenting the only case of underlying valve migration and induced redo AVR with valve explantation 2 days following initial surgery. Thirty-day mortality (and overall mortality) was 5% and 26%, respectively. Conclusion: The implantation of the Perceval bioprosthesis is feasible for a variety of indications, with excellent hemodynamic results and low complication rates in a real-world high-risk patient collective.