Energy and Protein Intake After Return Home in Colorectal Surgery Patients With an Enhanced Recovery Program: A Prospective Observational Study.

[en] BACKGROUND: In patients scheduled for colorectal surgery with an enhanced recovery program (ERP), feeding after returning home has been insufficiently investigated. The aim of this study was to measure energy and protein intake during the first month at home. METHODS: Seventy adult patients scheduled for colorectal surgery with ERP were included. Calorie and protein intakes were calculated, and body weight was measured preoperatively and 3, 7, 15, and 30 days after discharge home. Data are mean ± SD or median (interquartile range). RESULTS: Patient characteristics were age 60.0 ± 15.0 years, BMI = 25.9 ± 5.5 kg/m2 , and colon/rectum of 56/14. The duration of hospitalization was 3 (2-5) days. Calorie and protein intakes (21.9 [17.7-28.6] kilocalorie per kilogram of ideal body weight [kcal/kg IBW] and 0.81 [0.61-1.14] g/kg IBW) were significantly reduced (P < .01) by 15% on day 3, compared with preoperative values, and then increased gradually to reach preoperative values after 1 month. Almost 50% of the patients failed to reach the calorie intake target of 25 kcal/kg IBW, and almost no patient reached the protein intake target of 1.5 g/kg IBW 30 days after discharge home. Weight loss after 30 days at home remained at -1.8 ± 2.7 kg. CONCLUSIONS: Colorectal surgery, even in an ERP, is associated with energy and protein intake below the targets recommended for the rehabilitation phase and results in weight loss. Whether nutrition counseling and prolonged administration of protein-enriched oral supplements could accelerate weight gain needs to be explored

mTor inhibitor GDC-0349 improves ASO induced SAMMSON knock down resulting in enhanced anti-tumor efficacy in uveal melanoma

Uveal melanoma (UM) is the most common intraocular malignancy in adults. The lack of an effective treatment results in a median survival time of less than one year for patients with metastatic disease and shows the high unmet need for the development of effective treatments. Recently, the melanoma-specific lncRNA SAMMSON was shown to be essential for skin melanoma survival. Analysis of a PAN cancer RNA-sequencing dataset revealed consistent expression of SAMMSON in uveal melanoma tumors. Targeting SAMMSON by means of antisense oligonucleotides (ASOs) results in a strong reduction in cell viability with induction of apoptosis of UM cells and slows down tumor growth in multiple UM PDX models. These effects were driven by impaired mitochondrial function and protein translation, resulting in cell death. To identify potential synergistic combinations, we combined SAMMSON knockdown with a library of 2911 FDA-approved drugs and quantified cell viability in a uveal melanoma cell line. The strongest synergy was obtained with the mTOR inhibitor GDC-0349. Combining SAMMSON knockdown with mTOR inhibition resulted in enhanced impairment of mitochondrial function and protein synthesis. Interestingly, we observed a more pronounced knockdown of SAMMSON when combining SAMMSON targeting ASOs with GDC-0349, suggesting mTOR inhibition facilitates ASO uptake in uveal melanoma cells. Further experiments are ongoing to confirm this mechanism. Taken together, these results demonstrate that SAMMSON inhibition in combination with mTOR inhibition could be a novel treatment option for uveal melanoma patients

The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival

Cancer Signaling networks and Molecular Therapeutic

Energy and Protein Intake After Return Home in Colorectal Surgery Patients With an Enhanced Recovery Program: A Prospective Observational Study

[en] BACKGROUND: In patients scheduled for colorectal surgery with an enhanced recovery program (ERP), feeding after returning home has been insufficiently investigated. The aim of this study was to measure energy and protein intake during the first month at home. METHODS: Seventy adult patients scheduled for colorectal surgery with ERP were included. Calorie and protein intakes were calculated, and body weight was measured preoperatively and 3, 7, 15, and 30 days after discharge home. Data are mean ± SD or median (interquartile range). RESULTS: Patient characteristics were age 60.0 ± 15.0 years, BMI = 25.9 ± 5.5 kg/m2 , and colon/rectum of 56/14. The duration of hospitalization was 3 (2-5) days. Calorie and protein intakes (21.9 [17.7-28.6] kilocalorie per kilogram of ideal body weight [kcal/kg IBW] and 0.81 [0.61-1.14] g/kg IBW) were significantly reduced (P < .01) by 15% on day 3, compared with preoperative values, and then increased gradually to reach preoperative values after 1 month. Almost 50% of the patients failed to reach the calorie intake target of 25 kcal/kg IBW, and almost no patient reached the protein intake target of 1.5 g/kg IBW 30 days after discharge home. Weight loss after 30 days at home remained at -1.8 ± 2.7 kg. CONCLUSIONS: Colorectal surgery, even in an ERP, is associated with energy and protein intake below the targets recommended for the rehabilitation phase and results in weight loss. Whether nutrition counseling and prolonged administration of protein-enriched oral supplements could accelerate weight gain needs to be explored

The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival

Long non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of the SAMMSON lncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effective treatments for UM patients with metastatic disease, resulting in a median survival time of 6-12 months. We aimed to investigate the therapeutic potential of SAMMSON inhibition in UM. Antisense oligonucleotide (ASO)-mediated SAMMSON inhibition impaired the growth and viability of a genetically diverse panel of uveal melanoma cell lines. These effects were accompanied by an induction of apoptosis and were recapitulated in two uveal melanoma patient derived xenograft (PDX) models through subcutaneous ASO delivery. SAMMSON pulldown revealed several candidate interaction partners, including various proteins involved in mitochondrial translation. Consequently, inhibition of SAMMSON impaired global, mitochondrial and cytosolic protein translation levels and mitochondrial function in uveal melanoma cells. The present study demonstrates that SAMMSON expression is essential for uveal melanoma cell survival. ASO-mediated silencing of SAMMSON may provide an effective treatment strategy to treat primary and metastatic uveal melanoma patients