Idiopathic recurrent pericarditis (IRP) is considered an autoinflammatory disease, and interleukin 1 inhibitors, such as anakinra, are used to treat resistant cases. Constrictive pericarditis, a feared complication, continues to be a critical concern. In the biologic era, evidence on long-term transthoracic echocardiographic (TTE) findings following anakinra treatment remains limited. We conducted a cross-sectional study that included 18 patients with IRP treated with anakinra who had been attack-free for at least 3 months. TTE was performed on all patients and 21 healthy controls, and findings were compared between the groups. Pericardial thickness was significantly increased in patients compared with controls (3.1 mm (interquartile range (IQR):3.0-3.4) vs 2.1 mm (IQR: 1.9-2.4), P < 0.001). None of the patients exhibited echocardiographic signs of constrictive pericarditis. Mild pericardial effusion was present in nine patients (50%) despite being attack-free. Pericardial hyperechogenicity was observed in 61.1% of the patient group and 23.8% of the control group (P = 0.018). In the subgroup analysis of patients receiving ongoing anakinra treatment and those who had discontinued, there were no significant differences in pericardial thickness (P = 0.573), pericardial effusion (P = 0.637) or pericardial hyperechogenicity (P = 0.066). In conclusion, despite the refractory course of the disease, no cases of constrictive pericarditis were identified. TTE evaluation revealed increased pericardial thickness in patients who received anakinra compared with healthy controls, despite being attack-free. Further studies are needed to clarify whether the presence of pericardial thickening or ongoing pericardial effusion should influence treatment planning.

ABSTRACT This perspective considers the role of X‐ray crystallography for the study of metalloproteins in the era of cryogenic electron microscopy and machine learning models. While X‐ray crystallography may in the future play a smaller role in the routine structural analysis of all but the smallest metalloproteins, it is well suited for “multi‐messenger” studies combining structure and spectroscopy on the same sample, time resolved studies, and deriving charge densities, the electrostatic potential and other properties from accurate diffraction data. Sunney Chan's approach of keeping his research fresh by working on complex and important problems, while remaining connected to the fundamentals, provides excellent guidance for moving forward in this new era of structural biology.

Myasthenia gravis (MG) is a heterogenous autoimmune disease affecting the neuromuscular junction, which in many patients leads to devastating symptoms significantly influencing patients' lives or causing life-threatening episodes. The incidence and prevalence of myasthenia are growing worldwide. By definition, MG is characterized by muscle weakness exacerbated with activity and improving with rest. A total of 15-20% of patients during the course of the disease develop myasthenic crisis (MC), defined as respiratory insufficiency requiring intubation, with a high mortality rate. Approximately 30-50% of patients have unsatisfactory response to the standard treatment. Moreover, the standard of care (SoC), although efficient in most of patients, may be complicated by significant side effects, in most cases resulting from long-term treatment with glucocorticosteroids. In recent decades, new therapies have been approved for MG, including neonatal Fc receptor (FcRn) antagonists and complement component 5 (C5) inhibitors, as add-on to standard therapy. They showed efficacy and safety, even in patients previously considered as resistant MG. In several cases their rapid onset of action led to successful use as rescue treatments in impending crisis. Furthermore, it is noteworthy that new biologics show relevant steroid-sparing effects. This review summarizes new therapeutic approaches already approved for MG and introduces upcoming ones.

The management of non-infectious uveitis and scleritis continues to evolve. These conditions are often characterized by recurrent, uncontrolled inflammatory flare-ups that can progressively damage the eye’s structure and function in a “sawtooth” pattern, potentially leading to irreversible vision loss and even blindness. As such, treatment should aim to provide sustained control of inflammation while minimizing the long-term adverse effects of therapy. The success of tumor necrosis factor-alpha (TNF-α) inhibitors in treating rheumatologic inflammatory diseases marked the beginning of a new “biologic era” in medicine. Biologic therapies are designed to target inflammation at the molecular level, offering effective immunomodulation with a relatively low risk of serious side effects. This article reviews the current understanding of biologic treatments for non-infectious uveitis and scleritis, highlighting recent pharmacological developments and clinical research findings.

Modern cardiology is entering a phase where improving the prevention, diagnosis, and treatment of cardiovascular diseases (CVD) necessitates a deeper understanding of the underlying biological mechanisms. The traditional clinical model, relying primarily on analysis of risk factors and phenotypic presentation, is limited in its ability to account for the biological heterogeneity and individual progression of CVD. Advancements in systems biology, molecular medicine, and multiomics technologies allow for viewing CVD as a long-term dynamic biological process that begins well before clinical manifestation. Genomic, proteomic, and metabolomic research is uncovering the molecular and metabolic phenotypes that dictate individual vulnerability of the cardiovascular system, disease progression rates, and variability in therapeutic response. Among multiomics approaches, metabolomics is uniquely positioned to reflect the real-time functional state of biological systems, capturing the interplay between genetic, metabolic, and environmental factors. By identifying early biological signals of disease progression, metabolomic profiling enables precise risk stratification and personalized preventive and therapeutic interventions. Integrating these multiomics insights with clinical data, imaging, and digital monitoring establishes a new paradigm in clinical cardiology: biologically-oriented medicine. Given the high complexity of biological data, artificial intelligence and machine learning methods are essential for uncovering latent correlations between molecular and clinical variables, ultimately enhancing personalized clinical decision support. The transition toward biologically-oriented cardiology carries profound scientific, clinical, and socioeconomic implications. By identifying adverse biological traits early and utilizing personalized prevention of complications, we can substantially reduce the burden of CVD on healthcare systems and society. Ultimately, multiomics and metabolomics are establishing the scientific foundation for a new clinical paradigm focused on early detection of biological risk signals, precise patient phenotyping, and personalized treatment of CVD.

Gastrointestinal stricture can occur in the esophagus, stomach, small intestine, colon, and anorectum. Most of the strictures are benign. The prevalence of esophageal strictures (ES) secondary to eosinophilic esophagitis has increased. Pyloric stenosis (PS) is rarely seen in clinical practice. Sleeve stenosis (SS) and stomal stenosis or gastrojejunal anastomotic stricture (GJAS) are increasingly seen due to bariatric surgery. Crohn's disease (CD) remains a significant challenge even in the biologic era. The symptomatology of strictures depends on the location, severity, and underlying cause. Imaging studies and endoscopic procedures are the primary investigations to diagnose and evaluate strictures. Various treatment modalities are available to treat gastrointestinal strictures. Successful stricture treatment can significantly improve a patient's quality of life. Benign strictures carry a much better prognosis than malignant strictures. Multiple other factors influence response to treatment.

Development and external validation of a predictive model for postoperative recurrence of Crohn's disease in the biologic era.

Microproteins encoded by small open reading frames are a pivotal blind spot redefining the conventional protein-coding assumptions. However, the annotation of the "dark proteome" remains time- and labor-consuming due to the limited efficiency, sensitivity, and comprehensiveness of existing validation methods. To address these issues, we developed a comprehensive toolbox called CLAIMID to achieve accelerated and ultrasensitive validation at multiple biological scales. As the core of CLAIMID, molecularly imprinted polymers (MIPs), which are synthesized artificial antibodies toward putative microproteins, provide ultrasensitive and precise annotation in combination with surface-enhanced Raman scattering (SERS) detection. The excellent specificity, comparable to antibodies, of MIPs enables high anti-interference against biological matrix. The adaptability of MIPs engineering confers the rigorous validations by CLAIMID at multiple scales (single living cells, cell populations, and tissues) and diverse detection formats (SERS-based immunoassay and imaging, and mass spectrometric identification). Through CLAIMID, we rapidly confirmed the protein-level translation of four predicted microproteins-previously supported only by computational or ribosome profiling data-across various cell lines, and further identified three as potential tumor biomarkers, thereby demonstrating its university to putative microproteins. Together, we present an annotation toolbox with unparalleled efficiency, sensitivity, and scalability, moving forward for the advent of intriguing microprotein biology era.

Ileocolic resections (ICRs) are the most common resections for Crohn's disease. Historical control groups have often been used for comparison when assessing postoperative recurrence, usually with temporal bias. This study aimed to (1) report contemporary rates of postoperative recurrence requiring repeat surgery (surgical recurrence at anastomosis [surgical recurrence at the ileocolic resection site (SR-ICR)] or surgical recurrence at any site) and the rates of endoscopic recurrence (ER) in the "biologic era"; and (2) determine risk factors for SR-ICR and ER. A retrospective multicenter study involving 12 tertiary Australian centers was performed. Patients (of any age) who had undergone an ICR for Crohn's disease between 2007 and 2023 were included. Cox proportional hazards modeling was used to evaluate clinicopathological risk factors for SR-ICR and ER (defined as Rutgeerts grade ≥i2b). Overall, 875 patients were included (mean 38.7 ± 15.1 years, 51% female). Median follow-up was 63.9 months. Rates of SR-ICR were 4.5% (95% confidence interval [CI], 2.8%-6.1%) and 12.8% (95% CI, 8.8%-16.5%) at 5 and 10 years, respectively. Rates of surgical recurrence at any site were 5.6% (95% CI, 3.8%-7.5%) and 15.1% (95% CI, 11.0%-19.1%) at 5 and 10 years, respectively. Early (within 12 months) ER occurred in 24.7%. On multivariable analysis, smoking (adjusted hazard ratio, 3.49; 95% CI, 1.93-6.29) was the only factor significantly associated with SR-ICR. Smoking, positive microscopic margins, and granulomas were associated with ER, and prophylactic therapy and younger age at diagnosis (<17 years) were protective. The rate of SR at the ileocolic anastomosis in this large Australian cohort was low, recorded to be 1 in 20 at 5 years. Smoking remains the strongest risk factor for both ER and SR. Histopathological factors influence ER and should be considered in future risk prediction models.

BackgroundSevere asthma is associated with poor asthma control, leading to poor outcomes. However, few studies have evaluated asthma control status in patients with severe asthma in the biologic era. This study aimed to evaluate baseline asthma control in patients with severe asthma using phase 2 of the Korean Severe Asthma Registry (KoSAR-2).MethodsAdult subjects meeting the international consensus definition of severe asthma were prospectively enrolled from 41 hospitals in Korea (March 2022 to June 2023). Data on demographics, comorbidities, lung function, inflammation and healthcare utilisation were collected. Using asthma control test (ACT) scores, patients were classified into a well-controlled asthma group (ACT ≥20) and poorly controlled asthma group (ACT <20).ResultsAmong 594 severe asthma patients, 51.9% had poorly controlled asthma. Multivariable analysis showed that medical aid (adjusted odds ratio (aOR)=5.515, 95% confidence interval (CI) 2.614–13.110, p<0.001), being underweight (aOR=4.129, 95% CI 1.081–20.192), forced expiratory volume in 1 s <60% predicted (aOR=1.854, 95% CI 1.090–3.175) and prior exacerbations (aOR=3.400, 95% CI 1.987–6.012) were associated with poorly controlled asthma, while T2 inflammation was associated with well-controlled asthma (aOR=0.560, 95% CI 0.316–0.977). However, biologic use was not associated with asthma control status.ConclusionsAbout half of patients with severe asthma in KoSAR-2 had poorly controlled asthma at baseline. While poor socioeconomic status reflected by medical aid was a key factor underlying poor asthma control, T2 inflammation was associated with better asthma control in severe asthma. These findings underscore the importance of both clinical management and socioeconomic support to improve asthma control outcomes.

Biophysics at the interface: Shaping the next era of quantitative biology

Older adults represent a growing proportion of patients with Crohn's disease (CD). We compared outcomes after ileocecal resection between older and younger patients with CD. We conducted a retrospective cohort study of patients who underwent ileocecal resection. Older adults were defined as those aged 60 years and older. Outcomes at one and five years were extracted from medical records. Among 86 older and 169 younger patients, older adults had lower odds of clinical recurrence at 1 year (OR 0.26) and 5 years (OR 0.40) but higher 5-year mortality (OR 20.55). Older adults had lower symptom-based clinical recurrence rates but higher mortality.

Melphalan, a bifunctional alkylating agent derived from nitrogen mustard, remains a cornerstone in the treatment of multiple hematological and solid malignancies – most notably multiple myeloma – and continues to serve as a key component of conditioning regimens in hematopoietic stem cell transplantation. Despite the rapid emergence of novel therapeutic classes including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and cellular therapies, melphalan remains the standard conditioning regimen for autologous stem cell transplantation due to its potent, broad-spectrum antitumor activity and predictable myeloablative properties. This review focuses on the current understanding of melphalan’s historical development, molecular mechanisms, pharmacokinetic characteristics, clinical applications across hematologic malignancies, safety considerations, and its evolving role alongside contemporary treatment modalities. We conducted systematic literature searches across major medical databases, including PubMed, Google Scholar, and the recent IMWG and Mayo Clinic Guidelines for myeloma, focusing on publications from 2000 to 2025 that provided insights into melphalan’s clinical utility, pharmacological properties, and therapeutic optimization.

Prurigo nodularis enters the biologic era: what has changed and what vixarelimab still must prove

Predictors of early immunosuppression at ulcerative colitis onset in the biological era

Predictors of early immunosuppression at ulcerative colitis onset in the biological era.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), follow heterogeneous clinical trajectories. Although therapeutic options have expanded substantially over the past two decades, the extent to which modern treatment modifies long-term structural outcomes remains uncertain. We performed a targeted review focusing on high-quality population-based inception cohorts and large registries that report long-term outcomes in adult- and pediatric-onset IBD. Outcomes of interest included phenotype or extent progression, surgery, extraintestinal manifestations (EIMs), and colorectal neoplasia. CD consistently emerged as the more structurally progressive condition. Approximately one third of adults' progress from inflammatory to stricturing or penetrating disease within 5 years, and around half do so over longer follow-up. Perianal disease develops in 10%-20% of patients, with higher rates in pediatric-onset CD. Despite declines in surgical rates in the biologic era, intestinal resection remains frequent. In UC, proximal extension is the dominant progression pattern, affecting roughly one third of patients with limited disease over the first decade; pediatric UC shows even higher extension rates. Colectomy risks have markedly decreased in contemporary cohorts, and colorectal cancer incidence has declined compared with historical estimates, reflecting improved inflammation control and surveillance. Across IBD, EIMs occur in approximately one quarter of patients and cluster with extensive colonic involvement and higher systemic inflammatory burden. Population-based evidence reveals that IBD remains progressive in a substantial subset of patients, with notable differences between CD and UC and between adult and pediatric disease. Declining surgical and colorectal cancer rates suggest a measurable therapeutic era effect, supporting the importance of early, sustained inflammation control. However, high-quality prospective disease-modification trials are still needed to further characterize how current strategies can durably alter the natural history of IBD.

Psoriasis is a chronic immune-mediated inflammatory skin disease. The advent of biologics has significantly improved treatment efficacy. However, with their increasing application, numerous drawbacks—such as adverse reactions, the generation of anti-drug antibodies, immune deviation, disruption of skin barrier function, and high recurrence rates after discontinuation—have limited their broader use. In the current era of biologics, Traditional Chinese Medicine (TCM) offers not only traditional advantages like synergistic effects, reduced adverse reactions, and lower relapse rates, but also features multi-angle, multi-target, and broad-spectrum therapeutic actions. Furthermore, it plays a significant role in the clinical management of psoriasis comorbidities.

Tuberculosis is once again the most fatal global infectious disease and has killed many more humans than any other pathogen. Despite the identification of Mycobacterium tuberculosis (Mtb) over 140 years ago, we have yet to control the epidemic. A central issue is the complexity of the host-pathogen interaction, with multiple underlying pathways leading to tuberculosis disease. This intricate relationship stems from the prolonged co-evolution of the pathogen with humans, resulting in diverse immunological processes leading to tuberculosis disease. Conversely, Mtb exposure may give a survival advantage through innate immune training, thereby providing selective pressure over millennia. Emerging methodologies, such as single-cell and spatial transcriptomics, offer a golden opportunity to understand the immunology unpinning this host-pathogen interaction at unprecedented resolution. However, these analyses will be fundamentally flawed if they do not consider the intricacies of human Mtb infection. Here, we propose that attempts to find single immunological mechanisms leading to tuberculosis are hindering progress, and we must embrace the complexity of multiple paths to disease to allow the systems biology era to deliver transformative solutions.

Occasionally, pediatric Crohn's disease (CD) may develop after diagnosis of orofacial granulomatosis (OFG), which is characterized by chronic granulomatous lesions of the oral mucosa, lips, and perioral area. This study aimed to clarify clinical characteristics, treatment responses, and potential genetic contributors in pediatric patients with CD complicating OFG. We studied pediatric patients with CD complicating OFG who were treated from 2013 to 2022 at 7 Japanese institutions specializing in pediatric inflammatory bowel disease. Their clinical courses were analyzed retrospectively, and analyses of 71 genes associated with monogenic inflammatory bowel disease were performed. Among 13 patients, 8 were girls. Median ages at diagnosis of OFG and CD were 9.2 (3.8-15.3) and 10.3 (6.4-15.3) years old, respectively. Upper gastrointestinal lesions were frequent in 8 cases (62%), while perianal lesions were present in 7 (54%). OFG failed to improve or relapsed despite remission of intestinal lesions in about half of the patients (n = 7, 54%). During follow-up, OFG went into remission in 7 patients, including 6 of the 9 who were treated with biologics (66%) and 1 of the 4 who were not (25%). In 8 patients, the NCF1 p.Arg90His allele was detected by genetic analysis; 7 were heterozygous and 1 homozygous, a higher prevalence than in the general Japanese population. Clinical features of OFG associated with pediatric CD are diverse, and biologic agents were beneficial for OFG patients. NCF1 p.Arg90His mutation may contribute to the pathogenesis of pediatric CD complicating OFG.