Abdominal fat distribution, particularly visceral fat, is commonly assessed as a marker of obesity-related and metabolic diseases in people. While this relationship may exist, few studies consider the factors related to the relative distribution of visceral and subcutaneous abdominal fat in dogs. This cross-sectional study evaluated associations between measures of abdominal adiposity, visceral and subcutaneous fat distribution (V/SQ), body condition score (BCS), age, sex, neuter status, and breed conformation in 205 dogs presenting to a tertiary veterinary hospital between March 2006 and March 2020. The influence of several disease states on abdominal adiposity and fat distribution was also evaluated. Additionally, the study aimed to assess the criterion validity of average computed tomography (CT) Hounsfield units, and linear and cross-sectional area measures of abdominal adiposity and fat distribution relative to CT-derived volumetric analysis and for intra-observer reliability. Greater total abdominal adiposity was seen in older dogs, with values highest around 10 years of age and lower after 10 years of age, and was lower in terrier breeds and dogs with neoplasia. Greater V/SQ was observed in older dogs, hounds, and terriers, but decreased with increasing BCS, total abdominal adiposity, and thoracic height-width ratio. Additionally, V/SQ was higher in dogs with hyperadrenocorticism. Body condition score was moderately correlated with total abdominal, visceral, and subcutaneous adiposity. Abdominal fat areas measured at L3 overestimated total abdominal and visceral fat percentages but underestimated subcutaneous fat percentages, with increasing bias at higher fat percentages. Linear fat measurements were moderately correlated with total abdominal adiposity, but only weakly correlated with abdominal fat distribution. This study supports the association between abdominal adiposity, age, breed category, and potentially certain diseases like neoplasia. Moreover, it highlights the correlation between V/SQ, age, and total adiposity, while emphasising the preferential distribution of fat to the visceral compartment in dogs with hyperadrenocorticism. The study also identified a novel association between V/SQ, specific breed categories, and body conformation (i.e., thoracic height-width ratio). Importantly, CT volumetric measures are more reliable in determining abdominal fat distribution than area and linear measures, supporting the use of CT volumetric measures in the study's methodology and its implications for future research and clinical practice.
Visceral fat has weaker beige adipogenesis than subcutaneous fat with unclear mechanisms. The Wilms tumour gene (Wt1), a visceral adipocyte marker, is highly expressed in visceral adipose tissue (VAT) and visceral adipose-derived stem cells (vADSCs). In our present study, we found its protein levels in VAT decreased under high-fat diet or dexamethasone treatment, but rised in cold exposure or β3-adrenergic receptor agonist treatment, and positively correlate with uncoupling protein-1 (UCP1). Wt1 knockdown in vADSCs elevated PR domain containing 16 (PRDM16) and UCP1 mRNA but reduced their protein levels, alongside decreased ubiquitin-conjugating enzyme 9 (UBC9). Knockdown of UBC9 did not affect the mRNA levels of Wt1, PRDM16 or UCP1, but significantly reduced PRDM16 and UCP1 protein levels. Glucocorticoids including hydrocortisone, methylprednisolone and dexamethasone (Dex) dose-dependently suppress Wt1, UCP1, Alpha-enolase (ENO1) and Pyruvate kinase muscle isozyme M2 (PKM2) levels, which could be reversed by Wt1 overexpression. These findings explore the effects of Wt1 on beige remodelling of visceral adipose which might be related to the up-regulation of UBC9, and provide clues for treating abdominal obesity caused either by HFD or by glucocorticoids in a non-sympathetic-dependent manner.
Diets composed of various components have been shown to influence inflammatory diseases such as asthma. While most studies have focused on fiber-rich diets to investigate their effects on the immune system and, consequently, on asthma, little is known about the impact of sugar-rich diets, particularly when such diets are consumed over short periods of time. To investigate the short-term effects of a sugar-rich diet on allergic airway inflammation, A/J mice were fed either a standard diet or a sugar-enriched diet and subsequently sensitized and challenged with ovalbumin or PBS. Airway inflammation was assessed by bronchoalveolar lavage (BAL) cell analysis, including eosinophil counts and cytokine levels (IL-4, TNF-α, IL-33), and by lung histology (H&E for inflammatory infiltrate and PAS for mucus). Serum IgE levels were also measured. In addition, glucose tolerance, visceral and subcutaneous adipose tissue mass, and inflammatory markers in visceral adipose tissue were evaluated. Short-term consumption of a sugar-rich diet induced glucose intolerance and expansion of adipose tissue, particularly visceral fat, independent of ovalbumin sensitization. Gonadal adipose tissue analysis revealed a shift toward M1 macrophage polarization, characterized by elevated TNF-α, IL-6, and IL-1β, increased leptin levels, and reduced adiponectin. In OVA-sensitized mice, the sugar-rich diet significantly exacerbated eosinophil infiltration in BAL, increased IL-4, TNF-α, and IL-33, and enhanced PAS-positive mucus accumulation and inflammatory infiltrates in the lung. Moreover, total serum IgE was significantly higher in allergic mice fed the sugar-rich diet compared with allergic mice on the standard diet. Importantly, in non-sensitized mice fed the sugar-rich diet, no pulmonary inflammation was detected by BAL, demonstrating that HSD alone does not induce asthma but amplifies allergic responses when sensitization is present. Our findings demonstrate that short-term consumption of a sugar-rich diet is sufficient to exacerbate, but not initiate, allergic pulmonary inflammation. From a translational perspective, reducing dietary sugar intake may represent a valuable adjuvant strategy in the management of allergic asthma.
Background and Objective: Body mass index (BMI) is a worldwide screening standard but fails to distinguish between fat mass and fat-free mass. This study examines the prevalence and metabolic profile of the normal weight obesity (NWO) phenotype in a large cohort of young adults. Methods: A cross-sectional study of 4793 young adults (18-35 years) was conducted using bioelectrical impedance analysis (BIA). Participants were stratified into four phenotypes: underweight, healthy weight (HW), NWO, and obesity. Anthropometric indices, visceral fat area (VFA), and phase angle (PhA) were analyzed. Results: Within the normal BMI range (n = 2491), 40.6% (n = 1012) of patients were classified as NWO (percentage of body fat (PBF) >30% for women, >20% for men). NWO subjects showed a significantly higher VFA compared to the HW (+33.0 cm2 in men and +24.3 cm2 in women; p < 0.001) with a very large effect size (Cohen's d > 2.0). Furthermore, a state of relative sarcopenia was identified, characterized by significantly lower skeletal muscle mass percentage (SMM%) and PhA (p < 0.001; d = -0.82), indicating compromised cellular integrity despite a normal BMI. Conclusions: BMI misclassifies 4 out of 10 young adults with excess adiposity. NWO is a high-risk phenotype linked to visceral adiposity and early cellular frailty. Incorporating BIA in routine screenings is essential to identify this invisible risk group.
Bangladesh became the first country to achieve World Health Organization (WHO) validation for eliminating visceral leishmaniasis (VL, Kala-azar) as a public-health problem in 2023. Sustaining this milestone demands a post-validation surveillance strategy that concentrates its efforts on residual transmission foci and deploys resources efficiently. We therefore conducted the country's first Mouza-level micro-stratification to refine risk maps and guide targeted interventions. The study used routinely reported VL line-list data (January 2017 - June 2025) from the national DHIS2 platform for every Upazila (sub-districts) that recorded ≥1 VL case. Each Mouza-the smallest administrative unit for land records comprising of one or more villages-was categorised as high (≥3 new VL cases), moderate (2 cases), low (1 case) or non-endemic (0 cases) over the nine-year period. Hot-spot maps were created in Python. Associations between endemicity (endemic vs non-endemic) were tested with chi-squared statistics, yielding odds ratios (OR) with 95% confidence intervals (CI). Among 17,123 Mouzas in 128 case-reporting Upazilas, only 478 (2.8%) reported ≥1 new VL case between 2017 and 2025. High-endemic Mouzas (n = 33; 0.2%) accounted for 35% of total incident cases and clustered primarily in Mymensingh, Dhaka and Rajshahi divisions. However, year-on-year mapping showed reduction in the number of endemic Mouzas with no sustained new foci. VL transmission in Bangladesh is now intensely focal, confined to <3% of Mouzas within historically endemic Upazilas. While broad surveillance coverage remains essential, micro-stratification at the Mouza level can guide the prioritization of targeted interventions, such as indoor residual spraying and active case detection in high-risk areas, improving program efficiency without compromising case detection. Periodic updating of Mouza-level risk maps will be essential to identify emerging hotspots, prevent resurgence, and inform strategies in other countries approaching VL elimination.
Reactive hyperemia of the splanchnic circulation after isolated intra-abdominal organ injury has not been demonstrated in humans. Characterizing this response is essential for understanding postoperative hemodynamics and for validating non-invasive monitoring approaches. The aim of this study was to characterize the splanchnic hemodynamic response to isolated intra-abdominal organ injury and to assess the reliability of Doppler ultrasound for quantifying portal and visceral blood flow in this specific clinical setting. In this prospective observational study, 60 patients were enrolled into three groups: right hemicolectomy (n = 20), radical gastrectomy (n = 20), and ventral hernia repair without organ resection (n = 20). Elective surgery served as a standardized model of isolated intra-abdominal organ injury, with hernia repair as the control condition. Doppler ultrasound was performed preoperatively and daily for five postoperative days to assess flow and diameter of the portal vein (PV), superior mesenteric artery, celiac trunk, and abdominal aorta. Portal venous flow was indexed to body surface area and expressed as the portal flow index (VPI/BSA). Data were analyzed using repeated-measures ANOVA and McNemar's tests. Portal venous flow was successfully obtained in all patients (age 67.4 ± 11.34 years; height 169.25 ± 7.69 cm; males n = 37, females n = 23). Arterial vessel visibility declined significantly over time (p < 0.01). A significant effect of time on ΔVPI/BSA was observed (F(5,53) = 15.99, p < 0.001, ηp² = 0.601), with a significant interaction between surgical group and time (F(10,108) = 5.04, p < 0.001). Right hemicolectomy and gastrectomy were associated with a transient increase in portal flow of up to 21% from baseline values, peaking on postoperative day 1, while minimal changes were observed in controls. PV diameter did not differ significantly between groups, although temporal patterns varied. Standardized isolated intra-abdominal organ injury therefore induces a reproducible, reactive hyperemia-like response in the portal circulation, and Doppler ultrasound represents a reliable, non-invasive modality for monitoring portal venous flow in this context. Arterial assessment is limited postoperatively. These findings provide physiological evidence of reactive splanchnic hyperemia in humans and support the clinical utility of portal flow monitoring after abdominal surgery.
Coinfections involving helminths and protozoan parasites are frequent in endemic regions and can influence host immunity and disease outcomes. Although Schistosoma mansoni is known to modulate immune responses in several infectious and inflammatory diseases, its impact on Leishmania (Leishmania) amazonensis infection remains poorly understood. Here, we investigated how the timing of S. mansoni infection affects the progression of L. amazonensis disease in BALB/c mice. Two experimental settings were established: an early coinfection, in which S. mansoni infection occurred 15 days after L. amazonensis infection, before the development of cutaneous lesion (Leish(15)/Schisto); and a late coinfection, in which S. mansoni infection occurred 45 days after L. amazonensis infection, when lesions were already established (Leish(45)/Schisto). Early coinfection significantly reduced lesion size and footpad inflammation after 5-6 weeks, coinciding with the onset of S. mansoni egg laying and a shift toward Th2-polarized immune profile. Despite the occurrence of smaller lesions, parasite burden remained unchanged, indicating immune-mediated attenuation rather than enhanced parasite clearance. In contrast, late coinfection did not alter lesion progression but was associated with higher parasite burden. L. amazonensis did not affect schistosomiasis, although rare S. mansoni males exhibited atypical morphologies, suggesting systemic effects of chronic coinfection on worm physiology. Visceral dissemination of L. amazonensis occurred in both single- and coinfected mice but was more pronounced in coinfected animals, accompanied by tissue-specific cytokine modulation, particularly in the spleen. Collectively, our results suggest that the outcome of S. mansoni-L. amazonensis coinfection is strongly dependent on the timing and sequence of infection, orchestrated by temporal and immunological factors rather than direct parasite competition - such as disputes over host resources or occupation of shared tissue niches. These findings underscore the complexity of host-parasite-parasite interactions and highlight the importance of considering coinfection dynamics in the diagnosis and management of co-endemic diseases.
暂无摘要（点击查看详情）
(1) To compare the ability of body mass index (BMI), waist-to-height ratio and visceral fat, as measured by bioelectrical impedance analysis (BIA), to predict hypertension and diabetes in men and women and (2) to determine whether the correlation between BMI and visceral fat varies by height quantile. We conducted a cross-sectional analysis of a representative survey that included data on anthropometrics, body composition, glycosylated haemoglobin and blood pressure. We used receiver operating characteristic analysis and DeLong CIs to compare the ability of each adiposity measure to predict diabetes and hypertension in each gender. Tecpán and San Antonio Suchitepéquez, Guatemala. 806 non-pregnant adults from 347 households, primarily of Indigenous ethnicity. Diabetes, defined as a haemoglobin A1c of greater than 6.5% or self-reported history and hypertension, defined as a systolic blood pressure over 140 or a diastolic blood pressure over 90. Among the three adiposity measures, visceral fat was the best predictor of diabetes (area under the curve; AUC 0.73 (95% CI 0.66 to 0.81) (men); AUC 0.75 (95% CI 0.7 to 0.8) (women)) and hypertension (AUC 0.7 (95% CI 0.61 to 0.79) (men); AUC 0.76 (95% CI 0.7 to 0.82) (women)), followed by waist-to-height ratio followed by BMI. All three measures better predicted hypertension in women than in men. In sensitivity analysis, visceral fat and waist-to-height ratio better predicted hypertension and diabetes when BMI was below 30 kg/m2. The correlation between BMI and visceral fat did not vary appreciably by height. Of the three adiposity measures studied, BIA-derived visceral fat best predicted cardiometabolic disease in the population. In clinical practice, alternative techniques beyond BMI need to be considered when assessing adiposity, screening for cardiometabolic disease and diagnosing clinical obesity.
Background and Objective: Previous studies have shown that muscle mass and visceral fat are interrelated and affect metabolic health. However, there is limited research exploring machine learning (ML) models that can help us understand the relationship between muscle mass and the risk of adiposity in the adult population. The objective of this study was to identify predictors of obesity on the basis of data from 13,663 adults assessed via body composition analysis via optimal and interpretable ML algorithms. Methods: A cross-sectional design was used to analyze data from 13,663 adults, comprising men (n = 6877) and women (n = 6786). The variables were obtained via 8-point multifrequency BIA under standardized clinical protocols with an Inbody® Model 770 device validated for the adult population. To illustrate the interaction between body composition components, a probability heatmap was generated on the basis of the values predicted from the logistic model. The decision boundary was defined via the metabolic risk probability gradient, allowing visualization of the two-dimensional transition between low- and high-risk states. Statistical processing and figure generation were performed via Python software v.3.10. Results: The evaluation of the 10 algorithms demonstrated exceptional predictive performance, with the multilayer perceptron (MLP) standing out as the superior model in both sexes. The AUC-ROC was 0.981 for men and 0.993 for women, with F1 scores of 0.912 and 0.969, respectively. Overall, systematically higher accuracy was observed in the female cohort, exceeding 95% accuracy in most models. Conclusions: Muscle mass has been shown to act as a metabolic mediator, modulating and reducing the risk associated with visceral adiposity. It also concludes that the use of ML algorithms, specifically neural networks, is a good model for analyzing the risk associated with excess visceral fat.
Ewing sarcoma is a highly aggressive pediatric bone tumor that most commonly affects children and adolescents. It is characterized by the chromosomal translocation t(11;22)(q24;q12), resulting in the EWSR1-FLI1 fusion gene, and is typically associated with strong CD99 immunopositivity. Involvement of visceral organs, particularly the gastrointestinal tract, is extremely rare and remains underreported in literature. We present a case of a 5-year-old female with an unusual retro-gastric extraosseous Ewing sarcoma (EES). The diagnosis was confirmed via histopathological analysis following clinical and radiological evaluation The patient was treated with systemic chemotherapy followed by surgical management. This case highlights a rare and atypical presentation of visceral EES originating from the stomach in the pediatric age group. Also, this case demonstrates the feasibility of laparoscopic resection in pediatric visceral EES following neoadjuvant chemotherapy.
Computed tomography-based body composition assessment enables the quantification of clinically relevant prognostic conditions such as sarcopenia, myosteatosis, and visceral adiposity; the manual segmentation process limits its routine implementation in clinical practice. We developed FocusedON-BC, an automated deep learning tool for opportunistic screening of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) across the T12-L5 range; Methods: Validated on a multicenter cohort of 518 patients (3280 slices) with diverse body mass index (12.7-47.7 kg/m2) from different computed tomography manufacturers. Performance was benchmarked against expert segmentation using the Dice coefficient score (DSC) and the mean absolute error (MAE); Results: FocusedON-BC achieved expert-level accuracy: mean DSC was 0.974±0.010 (SM), 0.959±0.032 (VAT), and 0.986±0.014 (SAT). Clinical MAE remained <5% for all compartments. Performance was robust, independent of body mass index and computed tomography scanner model. Qualitative assessment confirmed the tool's capability to isolate intermuscular adipose tissue for radiodensity analysis; Conclusions: FocusedON-BC provides accurate, vendor-agnostic body composition and muscle quality analysis. Its reliability across diverse phenotypes supports implementation for routine nutritional screening.
The phenotypic variability of classic congenital adrenal hyperplasia (CAH) demands tailored management to optimize disease control and attenuate long-term consequences. Although sex-specific differences have been recognized, real-world evidence in adults remains limited and inconsistent. Therefore, this study aimed to compare the clinical, metabolic, and hormonal profiles of adult male and female patients with classic CAH and identify sex-specific predictors of biochemical control. In this multicenter, real-world analysis, records from adult CAH patients followed at four Italian tertiary centers, focusing on anthropometry, glucocorticoid (GC) therapy, biochemical and hormonal parameters, were retrospectively collected. Whole cohort and sex-stratified predictors of uncontrolled disease were then identified. Overall, 123 patients [77 females, 30.5 (24-37) years; 46 males, 32 (23-40) years] were enrolled. Males showed greater overweight/obesity rates (75.6% vs. 46.7%, p = 0.001), BMI (26.6 vs. 24.4 kg/m2, p = 0.003) and visceral adiposity indices [waist-to-height ratio (WHtR) 0.55 vs. 0.51, p = 0.006]. GC formulations and total daily doses were comparable between the sexes. Uncontrolled disease occurred in 26.2% of males and 17.6% of females (p = 0.271). WHtR was the strongest predictor of androstenedione (β = 0.311, p = 0.003). Sex-stratified analysis revealed that visceral adiposity and glucose metabolism abnormalities were critical predictors of poor control among males but not females. Adult males with CAH may face a vicious cycle of adiposity-driven metabolic and hormonal dysregulation, hindering disease control; however, estrogens may counteract these effects in well-controlled females. These results advocate for prioritizing metabolic health for long-term CAH management.
Tunisia represents the perfect example of a Mediterranean Country where different Leishmania species may express their infectivity causing Visceral leishmaniasis by Leishmania (L.) infantum, Zoonotic Cutaneous Leishmaniasis by L. major and chronic cutaneous leishmaniasis by L. tropica. The recent detection of L. major in two dogs living in Tunisia confirms how this animal may host both visceral and cutaneous Leishmania species. The present study reports the results of 4 field surveys performed in central and southern districts of Tunisia: Zaghouan (ZA); Kairouan (2 surveys, K1 and K2); Tataouine (TA), to assess the prevalence of Leishmania species in dog. One hundred and sixteen dogs were enrolled. Blood, lymph node and skin samples were collected with theowner' consent. Thirty-two were enrolled during 2021 in ZA (n = 32), fifty-four were enrolled in KA during 2022 (K1; n = 22) and 2024 (K2, n = 32) and thirty were enrolled in TA during 2024 (n = 30). All dogs correspond to new surveys other than those investigated in a previous study. In total 218 biological samples were analyzed by qPCR (kDNA), end-point PCR (ITS-1) and nested-PCR (SSUrRNA). The purified positive PCR products were sequenced. All dogs were classified as asymptomatic or with mild clinical signs, not specifically attributable to Canine Leishmaniosis due to the presence of fleas and tick infestation. Thirty-eight dogs tested positive by molecular techniques (32.75%%). Leishmania infantum was the most identified species (31/116, 26.72%). Extremely high prevalence was found in K2 (23/32, 71.87%) compared with the previous study K1 (10/22, 45.45%). One dog (K1) was positive to L. tropica, the first detection of this species in Tunisia, while two dogs (ZA and K2) confirmed the presence of L. major. Interestingly, we found for the first time a dog positive to L. infantum/donovani in TA, an arid area where no VL cases have been previously recorded. This study pointed out the high circulation of L. infantum in north and central Tunisia and underlines as the dog can host all the 3 Leishmania species present in this country.
Obesity is a main cause of morbidity worldwide, and its incidence has incredibly grown in recent years, leading to an increased risk for comorbidities, including cardiovascular and metabolic diseases. Timely intervention is essential and natural products can be useful in a preventive/therapeutic perspective. In this context, some vegetables belonging to the Brassicaceae family have been successfully studied. The aim of this experimental work was the evaluation of the positive effects of the glucosinolate glucoerucin (GER), extracted from vegetables of the Brassicaceae family, on the metabolic profile of high-fat diet (HFD) fed mice. GER (10 mg/kg) was orally supplemented to wild-type mice with metabolic disorder obtained by 10-week HFD. GER contained the body weight gain and positively influenced the triacylglycerols levels and glycemic profile in HFD mice. GER contributed to contain visceral white adipose tissue (vWAT) deposition, white adipocyte size, and inflammation, in favor of an increased metabolic activity. Worthy of note, an increase in irisin pathway was observed; indeed, beside the increase of myokine in the blood, upstream an increase of the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and of fibronectin type III domain-containing protein 5 (FNDC5) levels were observed; downstream of irisin, a positive effect on expression and levels of mitochondrial uncoupling protein 1 (UCP1) was reported. The obtained results reveal that the preventive effects of GER on metabolic profile may be related to its ability to promote thermogenesis in vWAT, probably through the browning process.
This study evaluated the effects of dietary phospholipid (PL) source and supplementation level on growth performance, antioxidant capacity, and lipid metabolism in Atlantic salmon (Salmo salar) fry. A 56-day feeding trial was conducted using a basal diet containing 1.76% PL and six experimental diets with an additional 1.5%, 3.0%, or 4.5% PL provided by soybean lecithin (SL) or krill oil phospholipids (KOP). Dietary supplementation with 3.0-4.5% SL and 1.5-4.5% KOP significantly improved growth performance, whereas feed conversion ratio was significantly reduced in the 3.0-4.5% SL and 3.0% KOP groups (p < 0.05). At equivalent inclusion levels, no significant differences were observed between SL and KOP in growth performance parameters (p > 0.05). PL supplementation also reduced whole-body lipid deposition and enhanced visceral lipase activity in all groups except the 1.5% SL group, while antioxidant capacity was improved in all PL-supplemented groups (p < 0.05). SL had no significant effect on whole-body fatty acid composition (p > 0.05), whereas moderate to high levels of KOP significantly altered the fatty acid profile, characterized by reduced monounsaturated fatty acids and n-6 polyunsaturated fatty acids, along with increased eicosapentaenoic acid (EPA) levels (p < 0.05). Transcriptomic analysis indicated that PL supplementation affected hepatic lipid metabolism, with both PL sources downregulating apoa2-like, while KOP induced stronger hepatic transcriptional responses related to lipid utilization and innate immune signaling than SL (padj < 0.05). However, gut microbiota analysis revealed no significant differences in the relative abundances of the dominant phyla or in α- and β-diversity among the control, 3.0% KOP, and 4.5% SL groups (p > 0.05). Overall, dietary PL supplementation promoted growth, improved antioxidant capacity, enhanced lipid metabolism, and reduced lipid deposition in Atlantic salmon fry, with KOP exerting stronger effects than SL on fatty acid composition and hepatic gene expression.
Cancer-related pain remains one of the most prevalent and distressing symptoms across the disease trajectory, significantly impairing function and quality of life. Although opioids are central to managing moderate to severe pain, their limitations, including adverse effects, dependence risk, and societal concerns, highlight the need for more individualized and comprehensive strategies. This review aims to synthesize current approaches to cancer pain management within a palliative care framework, emphasizing multimodal, mechanism-based, and patient-centered care. A narrative review was conducted using literature searches of PubMed, Scopus, and Google Scholar. Articles published between 2010 and 2026, with emphasis on recent literature (2020-2026), were included. Search terms included combinations of "cancer pain," "palliative care," "multimodal analgesia," "opioids," "adjuvant analgesics," and "neuropathic pain." Peer-reviewed studies, clinical guidelines, systematic reviews, and meta-analyses relevant to cancer pain mechanisms and management were considered. Cancer pain is heterogeneous, arising from tumor progression and treatment-related injury, and includes neuropathic, visceral, and somatic components. Effective management requires mechanism-based assessment and multimodal strategies. Adjuvant analgesics, such as antidepressants, anticonvulsants, corticosteroids, and topical agents, enhance pain control and reduce opioid reliance. Non-pharmacological interventions and early integration of palliative care further improve symptom management and quality of life. Emerging therapies, including cannabinoid-based treatments and gene-targeted approaches, show promise but require further clinical validation. A multidisciplinary, patient-centered approach that integrates pharmacologic and non-pharmacologic strategies is essential for optimizing cancer pain management. Advancing toward personalized and multimodal care models may improve outcomes, reduce opioid-related risks, and enhance quality of life for patients with cancer.
While visceral adiposity and lipid dysregulation are established drivers of metabolic dysfunction-associated steatotic liver disease (MASLD), the clinical utility of the lipid accumulation product (LAP) for identifying prevalent MASLD in patients with type 2 diabetes mellitus (T2DM) remains insufficiently characterized. This study aimed to characterize the dose-response relationship between LAP and MASLD in T2DM, establish optimal sex-specific diagnostic thresholds, and evaluate its clinical net benefit to guide non-invasive screening. This study included 495 inpatients with T2DM. log10LAP was prioritized using the Boruta algorithm. Diagnostic cut-offs were determined via ROC analysis. The mathematical reliability of these thresholds was evaluated using 1,000-run stratified bootstrapping (internal validation), while the biological generalizability of LAP was further examined in an independent NHANES cohort (external validation). The dose-response relationship was characterized by restricted cubic splines (RCS). Clinical utility and stability were assessed using decision curve analysis (DCA) and subgroup analyses. Through a systematic feature-selection approach using the Boruta algorithm, log10LAP was objectively identified as the most robust indicator for MASLD.log10LAP was independently associated with MASLD (OR 1.83, 95% CI 1.43-2.35). Optimal sex-specific cut-offs were 20.4 for men and 27.0 for women, yielding a positive predictive value of 85.93%. RCS analysis revealed a significant linear association, with MASLD probability increasing monotonically with log10LAP. DCA demonstrated a consistently higher net benefit for the LAP-based model over the "screen-all" strategy at threshold probabilities > 0.20. Subgroup analyses confirmed robustness across age and BMI strata, with the highest discriminative power in patients aged < 55 years (AUC 0.855) and reliable performance in non-obese individuals (AUC 0.711). External analysis in the NHANES cohort (N = 630) demonstrated consistent independent associations between LAP and MASLD risk (P < 0.05). log10LAP is a robust linear predictor of MASLD in T2DM. Implementing tailored thresholds provides superior diagnostic precision and clinical net benefit, particularly for younger and non-obese populations, supporting its use as a prioritized non-invasive screening tool.
Seizure semiology is usually interpreted through two main frameworks: anatomical localisation and network dynamics. Both are indispensable, but neither fully explains why certain cortical regions consistently produce particular classes of ictal phenomena, or why the same anatomical structure can generate different semiologies across seizures. To examine cortical evolutionary lineage as a complementary level of explanation for seizure semiology, and to explore its implications for intracranial EEG, presurgical hypothesis generation, and epilepsy surgery. This narrative review synthesises evidence from comparative neuroanatomy, cortical cytoarchitecture, stimulation studies, intracranial EEG propagation analyses, developmental myelination research, and surgical outcome literature, organised around Sanides' dual-origin model of cortical development. In the dual-origin model, mammalian neocortex emerges from two allocortical epicentres-archicortical and paleocortical-forming dorsal and ventral gradients of increasing laminar differentiation. Viewed through this framework, seizures recruiting the ventral paleocortical gradient may preferentially produce autonomic, olfactory, visceral, and affective phenomena, whereas seizures engaging the dorsal archicortical gradient may be more likely to produce spatial, mnemonic, and complex motor features. This perspective offers a potential explanation for intrastructural semiological heterogeneity, patterns of seizure propagation, developmental changes in localising semiology, and a possible sampling blind spot in intracranial EEG implantation. It also suggests that some temporal lobe surgical failures may reflect misclassification of onset zone architecture rather than incomplete resection alone. Cortical evolutionary lineage may offer a biologically grounded and testable framework for understanding seizure semiology. Rather than replacing localisationist or network-based models, it may help to anchor them within a broader account of how cortical structure, connectivity, and function are organised across evolutionary gradients.
Circumferential reconstruction is required for total hypopharyngeal defects to restore swallowing. Reconstructive options differ in conduit biology and anastomotic configuration, particularly the presence of a distal alimentary anastomosis. This study compared postoperative complications, dietary recovery, and survival among three reconstructive strategies. This retrospective cohort study included 102 patients who underwent total hypopharyngeal reconstruction between 2015 and 2025 using a free anterolateral thigh (ALT) fasciocutaneous flap (n = 57), gastric pull-up (n = 24), or free ileocolonic flap (n = 21). Postoperative complications, long-term dietary outcomes, and 5-year survival were evaluated. Time to regular diet was analyzed using multivariable Cox proportional hazards models adjusting for age, body mass index, length of hospitalization, and endocrine comorbidities. Baseline characteristics were similar across groups. Early pharyngocutaneous fistulas were most common in the ileocolonic flap group (23.8%), whereas late fistulas occurred mainly after gastric pull-up reconstruction (12.5%). At 3 years, regular diet was achieved by 63.2% of ALT flap patients, compared with 100% of gastric pull-up and 90.5% of ileocolonic flap patients. After adjustment, gastric pull-up (adjusted HR 1.79; 95% CI, 1.05-3.07) and ileocolonic flap reconstruction (adjusted HR 2.00; 95% CI, 1.06-3.79) were independently associated with faster dietary recovery compared with ALT flaps. Five-year survival did not differ significantly among groups. Visceral reconstructions yield superior dietary recovery compared with fasciocutaneous flaps for total hypopharyngeal defects. The absence of a distal anastomosis alone did not confer a clear functional benefit, underscoring the importance of conduit biology over anastomotic number.