Impact of tumor stage and neoadjuvant chemotherapy in fluorescence-guided lymphadenectomy during laparoscopic gastrectomy for gastric cancer: A propensity score-matched study in a western center.

BACKGROUND: The use of indocyanine green fluorescence has been shown to be a safe and effective method for improving lymph node retrieval in patients with gastric cancer. However, previous studies have focused on early-stage tumors and/or the Asian population and excluded patients who received neoadjuvant treatment. METHODS: In this study, 142 patients with gastric adenocarcinoma underwent laparoscopic gastrectomy at a Spanish hospital between January 2017 and December 2022. Of these, 42 patients received preoperative indocyanine green injection to guide lymphadenectomy. Their outcomes were compared to a retrospective cohort of 42 patients after 1:1 propensity score matching. RESULTS: The feasibility of indocyanine green lymphatic mapping was 95.5%. No complications associated with indocyanine green injection were observed. The indocyanine green group had a significantly higher number of retrieved lymph nodes than the non-indocyanine green group (32.67 vs 25.14; P = .013). This statistically significant difference was maintained across subgroups of neoadjuvant treatment, non-obese patients, pT0 to 2 stage, and pN0 stage. In 47.6% of patients from the indocyanine green group, lymphadenectomy was extended outside the standard D2 dissection area based on indocyanine green uptake, but none of the retrieved lymph nodes were metastatic. There were no differences in postoperative complications and length of hospital stay between the 2 groups. CONCLUSION: Indocyanine green-guided lymphadenectomy is safe and feasible and increases the number of retrieved lymph nodes compared to conventional lymphatic dissection, as well as in patients receiving neoadjuvant chemotherapy. The use of indocyanine green should be routine if available for guiding lymph node dissection in gastric cancer, regardless of tumor stage or previous neoadjuvant treatment. However, further studies are needed to determine the impact of this technique on disease-free and overall survival.

Myelodysplastic syndromes with 20q deletion: incidence, prognostic value and impact on response to azacitidine of ASXL1 chromosomal deletion and genetic mutations.

In myelodysplastic syndromes (MDS), the 20q deletion [del(20q)] may cause deletion of the ASXL1 gene. We studied 153 patients with MDS and del(20q) to assess the incidence, prognostic value and impact on response to azacitidine (AZA) of ASXL1 chromosomal alterations and genetic mutations. Additionally, in vitro assay of the response to AZA in HAP1 (HAP1WT ) and HAP1 ASXL1 knockout (HAP1KN ) cells was performed. ASXL1 chromosomal alterations were detected in 44 patients (28·5%): 34 patients (22%) with a gene deletion (ASXL1DEL ) and 10 patients (6·5%) with additional gene copies. ASXL1DEL was associated with a lower platelet count. The most frequently mutated genes were U2AF1 (16%), ASXL1 (14%), SF3B1 (11%), TP53 (7%) and SRSF2 (6%). ASXL1 alteration due to chromosomal deletion or genetic mutation (ASXL1DEL /ASXL1MUT ) was linked by multivariable analysis with shorter overall survival [hazard ratio, (HR) 1·84; 95% confidence interval, (CI): 1·11-3·04; P = 0·018] and a higher rate for acute myeloid leukaemia progression (HR 2·47; 95% CI: 1·07-5·70, P = 0·034). ASXL1DEL /ASXL1MUT patients were correlated by univariable analysis with a worse response to AZA. HAP1KN cells showed more resistance to AZA compared to HAP1WT cells. In conclusion, ASXL1 alteration exerts a negative impact on MDS with del(20q) and could become useful for prognostic risk stratification and treatment decisions.

Impact on Longevity of Genetic Cardiovascular Risk and Lifestyle including Red Meat Consumption.

BACKGROUND: Cardiovascular risk (CVR) underlies aging process and longevity. Previous work points to genetic and environmental factors associated with this risk. OBJECTIVES: The aim of this research is to look for any CVR gene-gene and gene-multifactorial/lifestyle interactions that may impact health and disease and underlie exceptional longevity. METHODS: A case-control study involving 521 both gender individuals, 253 centenarians (100.26 ± 1.98 years), and 268 controls (67.51 ± 3.25 years), low (LCR, n = 107) and high (HCR, n = 161) CVR. Hypertension, diabetes, obesity (BMI, kg·m-2), and impaired kidney function were defined according to standard criteria. CVR was calculated using Q risk®. DNA was genotyping (ACE-rs4646994, AGT-rs4762, AGR1-rs5182, GRK4-rs2960306, GRK4-rs1024323, NOS3-rs1799983, and SLC12A3-rs13306673) through iPlex-MassARRAY®, read by MALDI-TOF mass spectrometry, and analyzed by EARTDECODE®. RESULTS: Antilongevity factors consisted (OR 95% CI, p < 0.05) BMI 1.558 (1.445-1.680), hypertension 2.358 (1.565-3.553), smoking habits 4.528 (2.579-7.949), diabetes 5.553 (2.889-10.675), hypercholesterolemia 1.016 (1.010-1.022), and regular consumption of red meat 22.363 (13.987-35.755). Genetic aspects particularly for HCR individuals ACE II (OR: 3.96 (1.83-8.56), p < 0.0001) and NOS3 TT (OR: 3.11 (1.70-5.70), p < 0.0001) genotypes were also risk associate. Obesity, smoking, hypercholesterolemia, and frequent consumption of red meat have an additive action to hypertension in the longevity process. There was a synergistic interaction between the endothelial NOS3 genotypes and the severity of arterial hypertension. An epistatic interaction between functional genetic variants of GRK4 and angiotensinogen was also observed. CONCLUSIONS: Cardiovascular risk-related genetic and multifactorial or predominantly lifestyle aspects and its interactions might influence the aging process and contribute to exceptional longevity in Portuguese centenarians. Besides lifestyle, the activity of nitrite oxide synthase may be one of the main physiologic regulators of cardiovascular protection in the path of longevity.

Material selection and prediction of solar irradiance in plastic devices for application of solar water disinfection (SODIS) to inactivate viruses, bacteria and protozoa.

Solar water disinfection (SODIS) is a simple, inexpensive and sustainable Household Water Treatment (HWT) that is appropriate for low-income countries or emergency situations. Usually, SODIS involves solar exposure of water contained in transparent polyethylene terephthalate (PET) bottles for a minimum of 6 h. Sunlight, especially UVB radiation, has been demonstrated to photoinactivate bacteria, viruses and protozoa. In this work, an in-depth study of the optical and mechanical properties, weathering and production prices of polymeric materials has been carried out to identify potential candidate materials for manufacturing SODIS devices. Three materials were ruled out (polystyrene (PS), polyvinyl chloride (PVC) and polyethylene (PE)) and four materials were initially selected for study: polymethylmethacrylate (PMMA), polypropylene (PP), polycarbonate (PC) and polyethylene terephthalate (PET). These plastics transmit sufficient solar radiation to kill waterborne pathogens with production costs compensated by their durability under solar exposure. A predictive model has been developed to quantitatively estimate the radiation available for SODIS inside the device as a function of the material and thickness. This tool has two applications: to evaluate design parameters such as thickness, and to estimate experimental requirements such as solar exposure time. In this work, this model evaluated scenarios involving different plastic materials, device thicknesses, and pathogens (Escherichia coli bacterium, MS2 virus and Cryptosporidium parvum protozoon). The developed Solar UV Calculator model is freely available and can be also applied to other customized materials and conditions.