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Background Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality. Methods A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n  = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n  = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP). Results The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality. Conclusions Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM. Plain Language Summary Malnourished children are at a high risk of dying when exposed to an acute illness. They often have symptoms like diarrhea that indicate their gut is not working properly. It is unclear whether these gut problems contribute to their deaths. Feces contain numerous small molecules processed by the gut that reflect gut health. We compare these fecal molecules between malnourished children who died during hospitalization to those who survived, and relate them to signs of inflammation in the body. We show that the fecal molecules are different between children who died and those who survived. These differences reveal that poor gut health could increase risk of death, potentially by perturbing the body’s defensive response to an acute illness. These findings underscore that treatment for ill severely malnourished children should focus on improving gut health. Wen et al. investigate associations between intestinal disturbances and mortality in children hospitalized with complicated severe malnutrition. Differences are seen in the fecal metabolome of children who die compared with those who are discharged, with integrative analyses suggesting an indirect role for intestinal inflammation in mortality.

Introduction: Dermatofibrosarcoma protuberans (DFSP) is a slow-growing cutaneous neoplasm with high cure rates following complete surgical resection. However, 5-15% of classic DFSP cases undergo fibrosarcomatous transformation, resulting in fibrosarcomatous DFSP (FS-DFSP), a more aggressive variant with significantly higher rates of local recurrence, metastasis, and mortality. This case presents a rare myxoid variant of FS-DFSP with complex anatomical involvement requiring multidisciplinary management. Case Presentation: A 56-year-old female presented with a giant recurrent chest mass measuring 15 × 12 × 6 cm, initially misdiagnosed as fibroma 19 years prior. Advanced imaging revealed an 8 × 13 × 12 cm poorly defined soft tissue mass involving the pectoralis major and extending to the sternocleidomastoid muscles, with compression of the proximal right jugular vein. Histopathological examination confirmed FS-DFSP with myxoid differentiation, characterized by diffuse spindle cell infiltration in a herringbone pattern. Immunohistochemistry revealed CD34+, EMA+, and Actin+ staining with negative desmin, S100, and STAT-6. COL1A1-FISH analysis demonstrated COL1A1/PDGFB fusion in 8% of cells. Management included tumor vascular embolization, surgical resection with 3 cm margins, skin grafting, local flap repair, and adjuvant radiation therapy due to anatomical constraints and residual tumor involvement of the anterior sternum. Conclusion: This case highlights the myxoid variant of FS-DFSP, emphasizing the importance of comprehensive histopathological evaluation, multidisciplinary treatment planning, and long-term surveillance. The successful management with combined surgical and radiation therapy demonstrates the need for individualized treatment approaches in complex anatomical locations. Four-year follow-up shows no evidence of recurrence, supporting the efficacy of aggressive multimodal therapy in preventing local recurrence in FS-DFSP.

Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic “clocks” can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state. Deviations of predicted from expected age (epigenetic age dysregulation) have been associated with numerous complex diseases, increased all-cause mortality and higher cancer risk. We investigated the ability of these algorithms to detect molecular changes associated with chronic arsenic exposure in the context of associated skin lesions. To accomplish this, we utilized a multi-algorithmic approach incorporating seven “clocks” ( Horvath, Skin&Blood, PhenoAge, PCPhenoAge, GrimAge, DNAmTL and epiTOC2 ) to analyze peripheral blood of pediatric and adult cohorts of arsenic-exposed (n = 84) and arsenic-naïve (n = 33) individuals, among whom n = 18 were affected by skin lesions. Arsenic-exposed adults with skin lesions exhibited accelerated epigenetic ( Skin&Blood : + 7.0 years [95% CI 3.7; 10.2], q  = 6.8 × 10 –4 ), biological ( PhenoAge:  + 5.8 years [95% CI 0.7; 11.0], q  = 7.4 × 10 –2 , p  = 2.8 × 10 –2 ) and mitotic age ( epiTOC2:  + 19.7 annual cell divisions [95% CI 1.8; 37.7], q  = 7.4 × 10 –2 , p  = 3.2 × 10 –2 ) compared to healthy arsenic-naïve individuals; and accelerated epigenetic age ( Skin&Blood:  + 2.8 years [95% CI 0.2; 5.3], q  = 2.4 × 10 –1 , p  = 3.4 × 10 –2 ) compared to lesion-free arsenic-exposed individuals. Moreover, lesion-free exposed adults exhibited accelerated Skin&Blood age (+ 4.2 [95% CI 1.3; 7.1], q  = 3.8 × 10 –2 ) compared to their arsenic-naïve counterparts. Compared to the pediatric group, arsenic-exposed adults exhibited accelerated epigenetic (+ 3.1 to 4.4 years (95% CI 1.2; 6.4], q  = 2.4 × 10 –4 –3.1 × 10 –3 ), biological (+ 7.4 to 7.8 years [95% CI 3.0; 12.1] q  = 1.6 × 10 –3 –2.8 × 10 –3 ) and mitotic age (+ 50.0 annual cell divisions [95% CI 15.6; 84.5], q  = 7.8 × 10 –3 ), as well as shortened telomere length (− 0.23 kilobases [95% CI − 0.13; − 0.33], q  = 2.4 × 10 –4 ), across all seven algorithms. We demonstrate that lifetime arsenic exposure and presence of arsenic-associated skin lesions are associated with accelerated epigenetic, biological and mitotic age, and shortened telomere length, reflecting altered immune signaling and genomic regulation. Our findings highlight the usefulness of DNA methylation-based algorithms in identifying deleterious molecular changes associated with chronic exposure to the heavy metal, serving as potential prognosticators of arsenic-induced cutaneous malignancy.