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Introduction The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs. Materials and Methods Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified. Results Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS ( p  = 0.098). While HLN did not impact 5-year OS among MLN patients ( p  = 0.71), the number of MLN was associated with 5-year OS ( p  = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p  < 0.001). Conclusion Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.

Background Pathologically, intrahepatic cholangiocarcinoma (ICC) is classified into small-duct (SD) type and large-duct (LD) type, each with distinct clinicopathological characteristics. The contrast-enhanced ultrasound (CEUS) features of the two ICC types remain insufficiently explored. Purpose To evaluate liver CEUS imaging for differentiating the SD and LD types of ICC and further compare them with poorly differentiated hepatocellular carcinoma (pHCC). Materials and methods A single-center retrospective study enrolled 252 patients with SD-type ICC, LD-type ICC, or pHCC between October 2017 and August 2023. Logistic regression analyses identified independent clinical, pathological, ultrasound, and CEUS predictors. Based on these features, a decision tree-based diagnostic model was developed. The model’s performance was evaluated using receiver operating characteristic (ROC) curve analysis in both the training and validation cohorts, as well as in subgroup stratified by tumor size ≤ 5 cm and > 5 cm. Differences in overall survival (OS) and recurrence-free survival (RFS) based on the model were further analyzed. Results Overall, 252 patients (mean age, 58.4 ± 10.7 years; 174 males) with 140 SD-type ICC, 55 LD-type ICC and 57 pHCC were enrolled. Multivariate analysis revealed that AFP, CEA, CA19-9, HBsAg status, arterial phase enhancement pattern, washout time ≤ 45 s, and marked washout were independent predictors for tumor categories differentiation (all P  <.05). The decision tree-based model incorporating the major features demonstrated excellent performance in both the training cohort (AUC 0.89) and validation cohort (AUC 0.88), as well as in tumor size ≤ 5 cm (AUC 0.90) and > 5 cm (AUC 0.84). OS was significantly worse in LD-type ICC patients compared to SD-type and pHCC ( P  <.05 for both), while RFS showed no significant difference. Conclusions A user-friendly, decision tree-based diagnostic model was developed to accurately predict ICC subtypes and pHCC, facilitating improved clinical decision-making. Summary The decision tree-based diagnostic model effectively diagnosed small-duct type and large-duct type intrahepatic cholangiocarcinoma, as well as poorly differentiated hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2025.1650253.].

Background Intraclass correlation coefficients (ICC) are recommended for the assessment of the reliability of measurement scales. However, the ICC is subject to a variety of statistical assumptions such as normality and stable variance, which are rarely considered in health applications. Methods A Bayesian approach using hierarchical regression and variance-function modeling is proposed to estimate the ICC with emphasis on accounting for heterogeneous variances across a measurement scale. As an application, we review the implementation of using an ICC to evaluate the reliability of Observer OPTION 5 , an instrument which used trained raters to evaluate the level of Shared Decision Making between clinicians and patients. The study used two raters to evaluate recordings of 311 clinical encounters across three studies to evaluate the impact of using a Personal Decision Aid over usual care. We particularly focus on deriving an estimate for the ICC when multiple studies are being considered as part of the data. Results The results demonstrate that ICC varies substantially across studies and patient-physician encounters within studies. Using the new framework we developed, the study-specific ICCs were estimated to be 0.821, 0.295, and 0.644. If the within- and between-encounter variances were assumed to be the same across studies, the estimated within-study ICC was 0.609. If heteroscedasticity is not properly adjusted for, the within-study ICC estimate was inflated to be as high as 0.640. Finally, if the data were pooled across studies without accounting for the variability between studies then ICC estimates were further inflated by approximately 0.02 while formerly allowing for between study variation in the ICC inflated its estimated value by approximately 0.066 to 0.072 depending on the model. Conclusion We demonstrated that misuse of the ICC statistics under common assumption violations leads to misleading and likely inflated estimates of interrater reliability. A statistical analysis that overcomes these violations by expanding the standard statistical model to account for them leads to estimates that are a better reflection of a measurement scale’s reliability while maintaining ease of interpretation. Bayesian methods are particularly well suited to estimating the expanded statistical model.

Purpose Multilevel mixed effects models are widely used in organizational behavior and organizational psychology to test and advance theory. At times, however, the complexity of the models leads researchers to draw erroneous inferences or otherwise use the models in less than optimal ways. We present nine take-away points intended to enhance the theoretical precision and utility of the models. Approach We demonstrate our points using two types of simulated data: one in which group membership is irrelevant, and the other in which relationships exist only because of group membership. We then demonstrate that the effects we observe in simulated data replicate in organizational data. Findings Little that we address will be new to methodology experts; nonetheless, we draw together a variety of points that we believe will help advance both theory and analytic rigor in multilevel analyses. Implications We make two points that run somewhat counter to conventional norms. First, we argue that mixed-effects models are appropriate even when ICC(1) values associated with the outcome data are small and non-significant. Second, we show that high ICC(2) values are not a prerequisite for detecting emergent multilevel relationships. Originality/Value The article is designed to be a resource for researchers who are learning about and applying mixed-effects (i.e., multilevel) models.

Despite the success of combination antiretroviral therapy (cART) to suppress HIV replication, HIV persists in a long-lived reservoir that can give rise to rebounding viremia upon cART cessation. The translationally active reservoir consists of HIV-infected cells that continue to produce viral proteins even in the presence of cART. These active reservoir cells are implicated in the resultant viremia upon cART cessation and likely contribute to chronic immune activation in people living with HIV (PLWH) on cART. Methodologies to quantify the active reservoir are needed. Here, an automated immunocytochemistry (ICC) assay coupled with computational image analysis to detect and quantify intracellular Gag capsid protein (CA) is described (CA-ICC). For this purpose, fixed cells were deposited on microscopy slides by the cytospin technique and stained with antibodies against CA by an automated stainer, followed by slide digitization. Nuclear staining was used to count the number of cells in the specimen, and the chromogenic signal was quantified to determine the percentage of CA-positive cells. In comparative analyses, digital ELISA, qPCR, and flow cytometry were used to validate CA-ICC. The specificity and sensitivity of CA-ICC were assessed by staining a cell line that expresses CA (MOLT IIIB) alongside a control cell line (Jurkat) devoid of this marker, as well as peripheral blood mononuclear cells (PBMCs) from HIV seronegative donors before or after ex vivo infection with an HIV laboratory strain. The sensitivity of CA-ICC was further assayed by spiking MOLT IIIB cells into uninfected Jurkat cells in limiting dilutions. In those analyses, CA-ICC could detect down to 10 CA-positive cells per million with a sensitivity superior to flow cytometry. To demonstrate the application of CA-ICC in pre-clinical research, bulk PBMCs obtained from mouse and non-human primate animal models were stained to detect HIV CA and SIV p27, respectively. The level of intracellular CA quantified by CA-ICC in PBMCs obtained from animal models was associated with plasma viral loads and cell-associated CA measured by qPCR and ELISA, respectively. The application of CA-ICC to evaluate the activity of small-molecule targeted activator of cell-kill (TACK) in clinical specimens is presented. Overall, CA-ICC offers a simple imaging method for specific and sensitive detection of CA-positive cells in bulk cell preparations.

Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.

Background/Objectives: Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) and exhibits a more aggressive clinical course; however, its risk factors and outcomes remain largely undefined. Methods: This study is a single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC who underwent surgical resection from June 2011 to January 2023. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. Results: The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 U/L vs. 46 U/L; ALT median 165.5 U/L vs. 48 U/L; p = 0.012 and p = 0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 U/L vs. 104 U/L; p = 0.03). CA 19-9 values (76 U/mL vs. 22 U/mL; p = 0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (7.3 ng/mL vs. 3.2 ng/mL; p = 0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p = 0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p = 0.007). In multivariate analysis, patients with resected ICC had a significantly reduced risk of recurrence by 73% compared to their counterparts (HR 0.27 [0.10–0.73], p = 0.01). Conclusions: cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Further studies are warranted and may suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.