Epithelial-myoepithelial neoplasms of the breast are biphasic tumors composed of both epithelial and myoepithelial cell populations. Their rarity, broad morphologic spectrum, and evolving molecular characterization pose substantial diagnostic challenges, underscoring the need for an integrated review of their diagnostic and molecular features. This review aims to provide a comprehensive overview of epithelial-myoepithelial neoplasms of the breast, emphasizing their morphologic spectrum, diagnostic challenges, and emerging molecular features.

This narrative review is based on a review of the pertinent English-language literature and the author’s firsthand experience as a practicing breast pathologist.

Benign epithelial-myoepithelial tumors include pleomorphic adenoma and classic adenomyoepithelioma. Pleomorphic adenoma of the breast closely resembles its salivary gland counterpart as well as the benign mixed tumor of the skin. In contrast, adenomyoepithelioma is unique to the breast and exhibits a broad spectrum of histomorphologic patterns. Most adenomyoepitheliomas follow a benign clinical course; however, atypical adenomyoepitheliomas may demonstrate more aggressive behavior, including local recurrence, malignant transformation, and, rarely, metastasis. Molecular studies have identified PLAG1/HMGA2 rearrangements in a subset of pleomorphic adenomas and recurrent HRAS Q61 and PI3K-AKT pathway alterations in adenomyoepitheliomas. In malignant adenomyoepithelioma, the malignant component may arise from the ductal epithelial cells, the myoepithelial cells, or both.

The rarity of epithelial-myoepithelial tumors, together with their marked histologic heterogeneity, makes them diagnostically challenging and underscores the potential for diagnostic pitfalls.

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.

A common feature of severe COVID-19 and two common metabolic comorbidities, type 2 diabetes mellitus (T2DM) and obesity, is a persistent inflammatory response. Heat shock proteins (HSPs) are key regulators of cell proteostasis under stressful conditions, including inflammation, oxidative stress, hyperglycemia, and hyperlipidemia. The aim of the present study was to investigate associations between polymorphic variants in genes encoding HSPs and T2DM or obesity among patients with severe or critical COVID-19.

A total of 195 patients with severe or critical COVID-19 were included, of whom 39 had T2DM and 101 had obesity. T2DM and obesity were analyzed as separate, non-mutually-exclusive outcomes. Genotyping was performed using a TaqMan probe-based real-time polymerase chain reaction assay to detect single nucleotide polymorphisms (SNPs). Bioinformatics resources, including GTExPortal, eQTLGen, atSNP, and Gene Ontology, were used for functional annotation. Associations between HSP genetic variants and T2DM or obesity were analyzed. This study was conducted as a case-control analysis within a severe COVID-19 cohort and is reported in accordance with the STROBE guidelines.

Among patients with severe or critical COVID-19, SNP rs1043618 HSPA1A (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.01–3.27, Pperm = 0.04), rs910652 HSPA12B (OR = 2.23, 95% CI = 1.18–4.21, Pperm = 0.01), and rs4926222 DNAJB1 (OR = 2.15, 95% CI = 1.08–4.27, Pperm = 0.03) were associated with higher odds of T2DM, whereas rs13161158 HSPA4 (OR = 0.11, 95% CI = 0.01–0.91, Pperm = 0.0075) and rs7189628 DNAJA2 (OR = 0.08, 95% CI = 0.01–0.65, Pperm = 0.001) were associated with lower odds of T2DM. In addition, SNP rs753856 HSPA6 (effect allele G) was associated with higher odds of obesity (OR = 2.11, 95% CI = 1.07–4.19, Pperm = 0.03).

Selected HSP SNPs are associated with T2DM or obesity among patients with severe or critical COVID-19. Functional annotation suggests plausible biological mechanisms, including cell proteostasis, inflammatory pathways, glucose metabolism, and adipogenic differentiation; however, independent and functional validation 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.

Ascites is the most frequent complication of cirrhosis, signaling the transition from compensated to decompensated liver disease. While traditionally linked to portal hypertension, arterial vasodilation, and renal sodium retention, previous research has broadened our understanding of its pathophysiology. The hepatic and splanchnic lymphatic systems are increasingly recognized as potential contributors to decompensation in cirrhosis. The elevated sinusoidal pressure in cirrhosis markedly increases lymph production, which is initially compensated by expanded lymphatics and lymphangiogenesis. However, progressive cirrhosis impairs lymphatic function by inducing abnormal lymphangiogenesis, vessel dilation, and poor contractility, which collectively reduce drainage. When lymph overproduction exceeds the maximum drainage capacity of the lymphatic system, the fluid leaks through the subcapsular lymphatics, leading to leakage of protein-rich lymph through the liver surface into the peritoneal cavity—a phenomenon often referred to as a “weeping liver.” The osmotic gradient of this protein-rich fluid, combined with hydrostatic pressures and lymphatic failure, may draw additional fluid from the splanchnic circulation and contribute to ascites development and progression. Simultaneously, dysfunction of the gut-splanchnic lymphatic axis may promote intestinal edema, bacterial translocation, and systemic inflammation, thereby reinforcing portal hypertension and contributing to downstream manifestations such as intestinal lymphangiectasia and refractory ascites. Yet, despite its pathophysiological relevance, the contribution of lymphatic failure to the complications of cirrhosis remains widely underappreciated. Recognizing this critical axis may help identify novel therapeutic targets in patients with cirrhosis. This review provides a detailed overview of lymphatic failure as a contributor to altered fluid dynamics and secondary complications in cirrhosis, offering a contextual evaluation of its therapeutic implications.

Despite the 2012 Berlin definition standardizing acute respiratory distress syndrome (ARDS) diagnosis, pharmacological therapies have consistently failed in phase 3 trials, partly reflecting the syndrome’s profound biological heterogeneity. We synthesize evidence on ARDS subphenotyping to evaluate prospects for precision medicine. This narrative review was informed by targeted searches of PubMed/MEDLINE, Embase, and Web of Science from database inception through February 2026, supplemented by an updated PubMed/MEDLINE search through September 2026. Representative clinical trials, multicenter cohorts, mechanistic studies, and methodological reports were selected to support a critical synthesis of ARDS subphenotyping, its therapeutic implications, and barriers to clinical translation. Hyperinflammatory and hypoinflammatory subphenotypes—originally identified using plasma biomarkers (IL-6, IL-8, and soluble tumor necrosis factor receptor 1) in the ARMA and ALVEOLI cohorts—demonstrate reproducible differences in mortality, with worse outcomes in the hyperinflammatory subphenotype, and have shown potential treatment-effect heterogeneity in secondary analyses. Approximately 30%–35% of patients exhibit the hyperinflammatory profile, characterized by greater vasopressor requirements and organ failure. Radiological phenotypes (focal versus non-focal) on computed tomography imaging have been associated with differences in lung recruitability and physiological responses to ventilatory interventions, although the LIVE trial did not demonstrate an overall survival benefit from morphology-guided ventilation. Recent multi-omics studies (transcriptomic, proteomic, and metabolomic) reveal distinct endotypes involving dysregulated innate immunity, endothelial activation, and aberrant coagulation. Machine learning algorithms, particularly unsupervised clustering and deep learning-based computed tomography radiomics, have been investigated for more rapid phenotyping, but reported performance varies by task, cohort, and validation design. However, prospective, phenotype-guided randomized trials remain limited. Subphenotype stratification offers a mechanistically grounded framework for re-evaluating therapies that were ineffective in unselected populations and for investigating phenotype-informed ventilatory strategies. Clinical implementation requires standardized, bedside-compatible biomarker panels and definitive trials demonstrating that phenotype-specific interventions improve patient-centered outcomes.

Pegylated interferon alpha (PegIFNα) has been associated with altered lipid metabolism, but long-term lipid trajectories in chronic hepatitis B remain poorly characterized. We evaluated lipid profiles and virological parameters during 144 weeks of PegIFNα-based therapy.

This single-center retrospective cohort study included 129 patients with chronic hepatitis B who completed 144 weeks of PegIFNα monotherapy, PegIFNα plus tenofovir alafenamide, or PegIFNα plus entecavir. Serum lipids, hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and hepatitis B virus DNA were assessed at baseline and weeks 24, 48, 72, 96, and 144. Within-patient changes were analyzed with paired tests. Associations between early lipid changes and on-treatment HBsAg seroclearance at week 144 were examined with logistic regression.

From baseline to week 144, mean high-density lipoprotein cholesterol (HDL-C) increased by 0.10 ± 0.25 mmol/L (95% confidence interval, 0.06 to 0.15; P < 0.001) and mean total cholesterol decreased by 0.15 ± 0.41 mmol/L (95% confidence interval, −0.22 to −0.08; P < 0.001). Changes in triglycerides, low-density lipoprotein cholesterol, and the triglyceride-to-HDL-C ratio were not significant. HDL-C declined early and later recovered above baseline. At week 144, 37 patients (28.7%) achieved on-treatment HBsAg seroclearance (≤ 0.05 IU/mL). Of the 34 patients with HBsAg seroclearance at week 96, 13 had detectable HBsAg again at week 144. Early lipid changes were not associated with this endpoint.

HDL-C shows an early decline followed by recovery above baseline, whereas total cholesterol decreases modestly, with no significant net changes in triglycerides, low-density lipoprotein cholesterol, or the triglyceride-to-HDL-C ratio. Early lipid changes are not significantly associated with on-treatment HBsAg seroclearance. The durability of HBsAg loss requires post-treatment follow-up.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a rapidly increasing global health concern, driven by metabolic stress, chronic inflammation, and progressive fibrotic remodeling. Myeloid-derived suppressor cells (MDSCs) have emerged as pivotal yet context-dependent modulators of MAFLD pathogenesis. This review summarizes the biological characteristics of MDSCs, their immunosuppressive mechanisms, and their multifaceted roles in MAFLD progression, including hepatic steatosis, chronic inflammation, and fibrogenesis. Quantitative synthesis reveals that murine models demonstrate MDSC expansion (∼3-fold with a high-fat diet, P < 0.05) and suppression of MDSC-associated proinflammatory mediators (e.g., MitoTEMPO reduced hepatic S100A8 mRNA by 5.9-fold, P < 0.001). In one human cohort (n = 98), hepatic CD33+/HLA-DR− MDSC density correlated with inflammation grade (Spearman r = 0.610, P < 0.001) and fibrosis stage (r = 0.687, P < 0.001), though this cross-sectional dataset lacked MAFLD-specific stratification and longitudinal validation. We further discuss emerging MDSC-targeted strategies and explicitly acknowledge current translational gaps. Collectively, this review provides a mechanistic and critically appraised framework positioning MDSCs as both promising therapeutic targets and potential biomarkers for MAFLD.