Citations

BACKGROUND: Data registries lack a definitive classification system that distinguishes different locations of colon cancer from one another. OBJECTIVE: To establish an international consensus on the definition of primary colon cancer segment locations. DESIGN: Between December 2022 and June 2023, Delphi survey study was conducted to seek opinions from relevant international experts and eventually develop a consensus definition of each colon cancer segment. SETTING: Three-round online-based Delphi survey study. INTERVENTIONS: Online survey included 17 questions. In the first two rounds, participating experts were asked to rank each statement on a scale of 1–9 (9 is the most relevant). Consensus statements and definitions were revised according to results, obtaining a consensus score of 7–9. During the third round and online meeting, definitions and statements reached a moderate or high consensus(above 4 in more than 70% of participants) were included. MAIN OUTCOME AND MEASURE: Primary goal of our project was focused on precisely localizing the specific segment affected by primary colon cancer, rather than to identify surgical treatment or type of resection needed for particular segment. RESULTS: The first round included 331 experts, 301 (91%) completed the second round, and 295 (98%) completed the final round. Experts strongly supported the use of a “10 cm rule” to describe colon cancer sites at the flexures and anatomical landmarks for other segments. Regarding the definition of rectosigmoid cancer, experts from America and Europe reached a high consensus that the term rectosigmoid as a colon cancer location must be abolished in contrast to experts from Asia. Description of cancers overlapping segments achieved a consensus of 64%. LIMITATIONS: Subjective decisions are based on individual expert clinical experience. CONCLUSIONS: This Delphi survey, the first internationally conducted consensus study, achieved a remarkable level of consensus among a panel of global experts. Ambiguity still exists regarding overlapping lesions. See Video Abstract .

Abstract While tissue-resident memory CD8+ T cells (TRM cells) provide superior frontline defense against pathogens, the molecular mechanisms governing their persistence and functional regulation remain poorly defined. Our study reveals that the costimulatory receptors CD27 and ICOS coordinately sustain PD-1high CD8+ TRM cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD-1/PD-L1 blockade, thereby facilitating the rejuvenation of PD-1high TRM cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27/ICOS, governing proliferative renewal and maintenance of PD-1high TRM cells. Therapeutic administration of a CD27 agonist not only amplified this TRM cell subset in late-stage memory but also conferred cross-protective immunity against heterosubtypic viral challenges. Clinically, the expression of CD27 and ICOS is enriched in CD8+ T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, our findings establish the "CD27/ICOS-NR4A1-Proliferation" axis as a linchpin of PD-1/PD-L1-mediated TRM cell homeostasis, revealing druggable targets for intercepting infection-associated fibrotic progression.

Summary Amyloid light‐chain (AL) amyloidosis is a systemic clonal plasma cell disorder characterized by the production and deposition of misfolded immunoglobulin light chains (LCs), resulting in multiorgan dysfunction. Due to its intricate molecular mechanisms and diverse organ involvement, the disease poses significant diagnostic and therapeutic challenges. This review explores the molecular landscape of AL amyloidosis, emphasizing genetic, transcriptomic and proteomic alterations. Key findings include chromosomal abnormalities, somatic mutations, aberrant gene expression, disrupted protein folding pathways and the role of cytokine and chemokine secretion. These factors collectively drive the overproduction and destabilization of amyloidogenic LCs, leading to organ‐specific amyloid deposition, clinical heterogeneity and variable patient outcomes. Despite therapeutic advancements, the disease's complexity challenges the development of effective biological models. Progressing towards personalized therapies requires the development of preclinical models and the identification of biomarkers and molecular data to design targeted interventions. This review highlights the importance of integrating DNA, RNA and protein‐level analyses to deepen the understanding of AL amyloidosis pathogenesis. Such insights are pivotal for improving diagnostics, prognostics and therapeutic strategies, ultimately advancing precision medicine for this challenging disease.

AbstractObjectiveThis study aims to evaluate the impact of parity on the severity and recurrence rates of idiopathic subglottic stenosis (iSGS) in premenopausal females.Study DesignA retrospective cohort study.SettingTwo tertiary care centers from 2002 to 2024.MethodsWe analyzed premenopausal iSGS patients under 40 years who underwent balloon dilation or laser wedge excision. Clinical features, including demographics and pregnancy history, were examined. Recurrence rates between nulliparous and parous patients were compared using Poisson regression, adjusting for age and follow‐up duration. Linear regression assessed the relationship between pregnancy and iSGS recurrence.ResultsForty‐eight patients were included, with 36 parous and 12 nulliparous. Adjusting for age and follow‐up, the mean recurrence rate was 2.6 times higher in parous patients (95% confidence interval [CI]: [1.5, 4.8], P = .0008). Each additional pregnancy was associated with 0.81 additional recurrences (95% CI: [0.05, 1.57], P = .0375). No significant differences in surgery‐free time were observed between groups.ConclusionParity and pregnancy significantly increase the risk of iSGS recurrence, although they do not accelerate subsequent recurrences. Health care providers should counsel women of childbearing age about these risks in family planning discussions, emphasizing shared decision‐making regarding potential surgical interventions.Level of evidence3.

AbstractThe immune system and sleep are inextricably linked in both health and pathological conditions. Tightly regulated neuroimmune processes are critical for the physiological maintenance of healthy sleep. Reciprocally, sleep disturbances can detrimentally affect immune homeostasis and predispose to increased risk of autoimmune conditions, which themselves are bidirectionally associated with a higher risk of sleep disturbances. Autoimmune diseases of the central nervous system (CNS), particularly conditions that affect neuroanatomical regions involved in sleep homeostasis and nocturnal respiration, are associated with an increased risk sleep disorders that may impact diagnosis, clinical course, and management. This review summarizes the bidirectional relationship between sleep and immunity and highlights several exemplar autoimmune conditions of the CNS that include sleep disorders as a consequence or diagnostic feature of the disorder.

AbstractA thorough understanding of normal biliary anatomy, common variants, and surgically altered anatomy is essential for the success of biliary interventions. Variations in biliary anatomy are seen in up to 40% of patients and frequently influence procedural planning and outcomes. This review highlights classical biliary anatomy, its common variations, and the challenges posed by surgical modifications, such as those encountered after cholecystectomy, liver resection, or biliary reconstructions. Case-based examples are used to explore the implications of these variations and modifications on interventional approaches, including the management of bile leaks, strictures, and complex obstructions. Strategies incorporating advanced imaging and procedural techniques, such as rendezvous interventions, are discussed to address complications and optimize outcomes. This article provides a practical framework for interventional radiologists to navigate challenging biliary cases with confidence and precision.

Mitral regurgitation (MR) in lung transplant (LTx) recipients is a rare but complex cardiopulmonary phenomenon. The overlap between symptoms of MR and post-LTx complications, such as primary graft dysfunction, complicates its diagnosis and management. This systematic review aims to characterize the incidence, pathophysiology, presentation, and management of MR in LTx patients. We conducted a literature search in PubMed, Web of Science, Scopus, and Embase. The search yielded 133 studies, of which 11 were included. Data regarding MR development, clinical presentation, echocardiographic findings, and management strategies were extracted and analyzed. Perioperative MR, occurring during or immediately post-LTx, was frequently attributed to the systolic anterior motion of the mitral valve (MV) occurring in the setting of hypovolemia and/or inotrope usage. Later postoperative MR, on the other hand, was associated with reverse ventricular remodeling and mitral annular dilation, although some variability in the literature was present. Preexisting MR or ventricular dysfunction, elongated MV leaflets, and bilateral LTx procedure appeared to be risk factors for MR development. Management was dependent on the timing of MR and its pathophysiology, where systolic anterior motion–related MR was treated with medical therapy, whereas postoperative MR often required MV interventions. In conclusion, the diagnosis of MR in LTx patients is complicated by its symptomatic overlap with other post-LTx complications. Echocardiographic monitoring in patients with preexisting MR, regardless of severity, is essential for early identification and management. Further research is needed to better understand the underlying mechanisms and refine management strategies for MR in this population.

Chronic cholestatic cholangiopathies present a therapeutic challenge due to their complex pathophysiology, where the accumulation of bile acids plays a crucial role. In this study, we found that dimethyl fumarate attenuated cholestatic liver damage in a murine model through its significant anti-inflammatory and antifibrotic activity supported by reduced bile acid accumulation in the plasma and liver via their increased fecal excretion.