Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma.

Importance: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. Objective: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. Design, Setting, and Participants: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. Main Outcomes and Measures: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. Results: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. Conclusions and Relevance: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

Photoacoustic imaging to monitor outcomes during hyperbaric oxygen therapy: validation in a small cohort and case study in a bilateral chronic ischemic wound.

Hyperbaric oxygen therapy (HBO2) is a common therapeutic modality that drives oxygen into hypoxic tissue to promote healing. Here, ten patients undergoing HBO2 underwent PA oximetry of the left radial artery and forearm pre- and post-HBO2; this cohort validated the use of PA imaging in HBO2. There was a significant increase in radial artery oxygenation after HBO2 (p = 0.002) in the validation cohort. We also include a case study: a non-diabetic male in his 50s (HB 010) presenting with bilateral ischemic and gangrenous wounds. HB 010 showed higher perfusion and oxygen saturation on the right foot than the left after HBO2 which correlated with independent surgical observations. Imaging assisted with limb salvage treatment. Hence, this work shows that PA imaging can measure changes in arterial oxygen saturation due to HBO2; it can also produce 3D maps of tissue oxygenation and evaluate response to therapy during HBO2.

Effects of different concentration of organic and inorganic trace minerals (zinc, selenium, and chromium) supplementation on expression of chTLR4 gene and humoral immune response in broilers.

BACKGROUND AND AIM: Poultry production is the fastest-growing livestock sector in developing countries. In the poultry diet, trace minerals (zinc [Zn], selenium [Se], and chromium [Cr]) are normally administered in the inorganic form which has been traditionally considered as the most cost-effective and easily available but organic forms of these trace minerals have a higher bioavailability, lower dietary inclusion and cause less environmental pollution as compared to inorganic form. This study aimed to investigate the effect of different concentrations of organic and inorganic forms of trace minerals (Zn, Se, and Cr) supplementation (0-35 days) on expression of chTLR4gene and humoral immune response in broilers. MATERIALS AND METHODS: A total of 216 broilers were randomly divided into 12 groups and each group divided into three replicates consisting of six broilers each. T1 (R1, R2, and R3) group was kept as control. T2, T3, and T4 (R1, R2, and R3) groups were supplemented with inorganic form of Zn at 40 mg/kg of feed, organic form of Zn at 40 mg/kg of feed, and 50% organic form of Zn at 20 mg/kg of feed, respectively. T5, T6, and T7 (R1, R2, and R3) groups were supplemented with inorganic form of Se at 0.3 mg/kg of feed, organic form of Se at 0.3 mg/kg of feed, and 50% organic form of Se at 0.15 mg/kg of feed, respectively. T8, T9, and T10 (R1, R2, and R3) groups were supplemented with inorganic form of Cr at 2 mg/kg of feed, organic form of Cr at 2 mg/kg of feed, and 50% organic form of Cr at 1 mg/kg of feed, respectively. T11 and T12 (R1, R2, and R3) groups were supplemented with a combination of all three minerals from inorganic and organic forms, respectively. RESULTS: Reverse transcriptase-polymerase chain reaction gene expression analysis revealed that in bursa of Fabricius, maximum upregulation of chTLR4 (3.0214 fold) was observed in T6 group, and in spleen, maximum upregulation of chTLR4 (3.2140 fold) was observed in T3 group as compared to control group. On day 35, the maximum plasma immunoglobulin G concentration was observed in organic trace minerals (OTMs) supplemented, whereas the minimum concentration was recorded in control group. On day 28 and 35, the overall mean heterophil:lymphocyte ratio showed a significant difference (p<0.05) between control and OTM supplemented groups. A significantly higher immune organ weight (spleen and bursa of Fabricius) was recorded in OTM supplemented group as compared to control and other supplemented group. CONCLUSION: Supplementation of organic form of Zn, Se, and Cr either alone or in combination increase humoral immune response and upregulation of chTLR4 gene expression in bursa and spleen indicates a beneficial effect of OTM in augmentation of immune system in broilers.