CXC chemokine receptor 2 (CXCR2) expression has been observed in normal neuroendocrine cells, but its role in neuroendocrine neoplasms is less well established. We aimed to evaluate CXCR2 expression with somatostatin receptor type 2 (SSTR2) expression in pancreatic neuroendocrine tumors (PanNETs) and small intestinal neuroendocrine tumors (SI-NETs).

This was a cross-sectional study. Pathology archives were searched for PanNETs with ≥2 resected liver metastases and SI-NETs with resected liver metastases, mesenteric tumor deposits (MTDs), and/or peritoneal metastases. Immunohistochemistry for CXCR2 was performed on de-identified tissue microarrays containing PanNETs and SI-NETs. SSTR2 and CXCR2 immunohistochemistry was also performed on tumor blocks from primary and metastatic PanNETs and SI-NETs. Based on H-scores, expression was scored as negative (<50), weak (50–100), moderate (>100–200), or strong (>200). Marker expression was descriptively reported among primary tumors, liver metastases, MTDs, and peritoneal metastases.

Among 12 primary PanNETs and 38 liver metastases, mean CXCR2 H-scores were 269.6 ± 36.7 and 254.6 ± 75.5, respectively, and mean SSTR2 H-scores were 261.5 ± 61.9 and 259.3 ± 70.9, respectively. All 84 SI-NET lesions showed moderate/strong CXCR2 expression, whereas 12 showed negative/weak SSTR2 expression. CXCR2 H-scores were 284.0 ± 26.5 in primary tumors, 272.5 ± 28.7 in MTDs, 269.6 ± 42.8 in liver metastases, and 265.0 ± 51.5 in peritoneal metastases. SSTR2 expression appears to be lower in MTDs than in primary tumors (182.2 ± 76.5 vs 235.9 ± 55.9).

CXCR2 is moderately/strongly expressed in most sampled PanNETs and all sampled SI-NETs. In SI-NETs, moderate/strong CXCR2 expression is less heterogeneous than SSTR2 expression.

The widespread assumption that “natural” equals “safe” has been repeatedly challenged by adverse events associated with medicinal plant-derived products. Unlike synthetic pharmaceuticals, these natural products present distinct safety concerns because of their compositional complexity, inherent variability, and batch-to-batch inconsistency. Consequently, a one-size-fits-all approach to toxicological assessment is insufficient. In this narrative review, we propose a pragmatic “classify-then-evaluate” framework that stratifies natural products into three operational categories according to compositional complexity and degree of chemical characterization—TCM compound formulae, active fractions/extracts, and purified single compounds. This framework enables safety evaluations to be tailored to product complexity by integrating conventional toxicological assays with emerging new approach methodologies. By linking chemical characterization, hazard identification, quality control, and risk assessment within a tiered system, this framework bridges the gap between evidence generation and regulatory decision-making, offering a scientifically grounded and proportionate pathway for evaluating the safety of natural products used in integrative medicine, with a primary focus on herbal and TCM-related products. The review does not aim to provide a comprehensive systematic evidence map; further validation of the proposed framework is required

Therapeutic hypothermia (TH) is widely used as a neuroprotective strategy, but variability in bedside implementation may limit its optimal application. This study aimed to develop a standardized TH management protocol for patients with neurocritical illness and evaluate the clinical outcomes associated with its implementation.

An evidence-based TH protocol was developed through a two-round Delphi consensus process. A subsequent observational before-and-after study included 244 patients with neurocritical illness receiving TH. The historical control group (n = 120) received routine care, whereas the TH protocol group (n = 124) was managed according to the standardized protocol. No single primary endpoint was prespecified for the final comparative analysis. Outcomes were interpreted as exploratory and included temperature-management process indicators, individual TH-related complications requiring intervention, and neurological outcomes assessed using the Glasgow Outcome Scale.

Protocol implementation was associated with more favorable temperature-management process indicators, including earlier TH initiation, a shorter recorded time to target temperature, fewer unplanned treatment interruptions, a longer controlled rewarming phase, and greater adherence to rewarming criteria. In exploratory analyses, the TH protocol group had lower incidences of selected TH-related complications and more favorable Glasgow Outcome Scale outcomes at discharge than the historical control group.

Implementation of a consensus-derived TH management protocol was associated with more consistent temperature-management processes, fewer selected TH-related complications, and more favorable short-term neurological outcomes. These findings support prospective evaluation of protocolized TH management in larger multicenter cohorts.

Large-scale critical care databases have expanded opportunities for clinical research. Previous reviews have summarized open-access intensive care unit databases and specific analytical methods, but integrated, practice-oriented guidance on commonly used and emerging methods and their selection remains limited. The objective of this narrative review is to provide a practice-oriented overview of commonly used and emerging statistical and modeling methods in critical care database research, with emphasis on their appropriate applications, strengths, limitations, and considerations for method selection. This narrative review summarizes commonly used and emerging methods in critical care database research, focusing on their applications, strengths, limitations, and practical considerations. The methods reviewed range from descriptive and regression analyses to prediction modeling, longitudinal analysis, causal inference, and artificial intelligence-based approaches. Common problems include missing data, temporal bias, confounding, overfitting, and limited external validation. Careful method selection and appropriate validation are therefore important when working with complex critical care data. Closer coordination of clinical questions, data structures, analytical methods, and reporting standards can strengthen research using intensive care unit databases. Paying closer attention to data quality, causal hypotheses, validation, reproducibility, and generalizability may improve the methodological rigor and translational value of these studies.

Extensive burn injuries are associated with a profound systemic response, the severity of which increases with the extent of tissue damage. Beyond local destruction, extensive burns induce a sustained immune-inflammatory disturbance that alters immune regulation and contributes to secondary organ failure and infectious complications. These mechanisms are major determinants of adverse outcomes in critically ill patients with burns. In this context, therapeutic strategies targeting immune dysregulation have gained increasing attention. Immunomodulatory approaches aim to limit excessive inflammatory signaling while maintaining effective host defense. Among extracorporeal blood purification techniques, hemoadsorption has emerged as a potential adjunctive therapy designed to reduce circulating inflammatory mediators, particularly cytokines, and to attenuate systemic inflammatory burden. Rather than providing another general overview of extracorporeal blood purification, this review focuses specifically on the cellular and mechanistic basis of burn-induced immune dysregulation and offers a stratified, critical appraisal of the experimental and clinical evidence for hemoadsorption in burns, together with current safety considerations and unresolved questions that should guide future research. Experimental studies and early clinical observations suggest that hemoadsorption may contribute to hemodynamic stabilization and modulation of inflammation in critically ill patients, including those with severe burns. However, clinical evidence in this specific population remains scarce, and its impact on patient-centered outcomes has not yet been established. Although available data suggest that this technique is generally well tolerated, the non-selective removal of circulating molecules underscores the need for careful patient selection and close monitoring. Future investigations should focus on defining the appropriate indications, optimal timing, and treatment duration of hemoadsorption for burn care. Comparative studies with other immunomodulatory strategies are required to clarify its role within the therapeutic armamentarium for burn-induced immune dysfunction.