The relationship between sarcopenic obesity and changes in quadriceps muscle thickness and echo intensity in patients with stroke.

BACKGROUND: Research findings on skeletal muscle degeneration in post-stroke sarcopenic obesity are limited. Thus, this study aimed to investigate the association between post-stroke sarcopenic obesity and quantitative and qualitative changes in skeletal muscles. METHODS: This was a cross-sectional study conducted on patients with stroke admitted to the convalescent rehabilitation ward. For skeletal muscle assessment, an ultrasound system was used to measure quadriceps muscle thickness and echo intensity (QMT and QEI) on the paretic and non-paretic sides. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multiple regression analysis was performed to determine the relationships between sarcopenic obesity and QMT and QEI. RESULTS: A total of 130 patients with stroke were included in this study (mean age: 69.4 ± 12.7 years). The prevalence of sarcopenic obesity was 23.1%. The multiple regression analysis showed that sarcopenic obesity was significantly negatively associated with QMT on both the paretic and non-paretic sides (paretic side: ß = -0.28, p < 0.001; non-paretic side: ß = -0.37, p < 0.001) and significantly positively associated with QEI (paretic side ß = 0.21, p = 0.034; non-paretic side: ß = 0.20, p = 0.029). CONCLUSIONS: Post-stroke sarcopenic obesity was independently associated with quantitative and qualitative changes in skeletal muscles on both the paretic and non-paretic sides.

The Validity of Quadriceps Muscle Thickness as a Nutritional Risk Indicator in Patients with Stroke.

This study aimed to investigate whether quadriceps muscle thickness (QMT) is useful for nutritional assessment in patients with stroke. This was a retrospective cohort study. Nutritional risk was assessed using the Geriatric Nutritional Risk Index (GNRI), with GNRI < 92 indicating a risk of malnutrition and GNRI ≥ 92 indicating normal conditions. Muscle mass was assessed using QMT and calf circumference (CC). The outcome was Functional Independence Measure (FIM) effectiveness. The cutoff values of QMT and CC for discriminating between high and low GNRI were determined using the receiver operating characteristic curve. The accuracy of the nutritional risk discrimination model was evaluated using the Matthews correlation coefficient (MCC). Multiple regression analysis was performed to assess the relationship between nutritional risk, as defined by QMT and CC, and FIM effectiveness. A total of 113 patients were included in the analysis. The cutoff values of QMT and CC for determining nutritional risk were 49.630 mm and 32.0 cm for men (MCC: 0.576; 0.553) and 41.185 mm and 31.0 cm for women (MCC: 0.611; 0.530). Multiple regression analysis showed that only nutritional risk defined by QMT was associated with FIM effectiveness. These findings indicate that QMT is valid for assessing nutritional risk in patients with stroke.

Efficacy and Postoperative Outcomes of Laparoscopic Retrosternal Route Creation for the Gastric Conduit: Propensity Score-Matched Comparison to Posterior Mediastinal Reconstruction.

BACKGROUND: Retrosternal reconstruction has lower risks for severe postoperative morbidities, such as gastro-tracheal fistula or esophageal hiatal hernia. We have previously reported the laparoscopic retrosternal route creation (LRRC) method, but its safety and efficacy remain unclear. METHODS: In total, 374 patients with esophageal carcinoma who underwent minimally invasive McKeown esophagectomy in the prone position between 2010 and 2021 were retrospectively reviewed. We performed a propensity score-matched analysis with the simple, nearest-neighbor method and no calipers to compare postoperative outcomes and reconstructed gastric conduit functionality between patients who underwent LRRC and counterparts who underwent posterior mediastinal reconstruction. RESULTS: After matching, 62 patients were included in the laparoscopic retrosternal group (LR group) or posterior mediastinal group (PM group). No significant differences were observed between the groups, apart from the number of robot-assisted surgeries, the extent of lymph node dissection, and the method of cervical anastomosis. There were no significant differences in the incidence of Clavien-Dindo grade ≥ 2 complications. Gastro-tracheal fistula (n = 1) and esophageal hiatal hernia (n = 2) occurred in the PM group but not in the LR group. There were no differences in the incidence of pulmonary embolism between the groups (5% vs. 5%). The postoperative anastomotic stenosis rate was similar (16% vs. 27%, p = 0.192). Endoscopic findings of reflux esophagitis (modified Los Angeles classification ≥ M) at 1 year after surgery were significantly better in the LR group (p = 0.037). CONCLUSIONS: LRRC for gastric conduit reconstruction is safe and valuable. It is associated with good reconstructed gastric conduit function.

Identification of a tomato UDP-arabinosyltransferase for airborne volatile reception.

Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl ß-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl ß-D-glucopyranoside arabinosylation to produce HexVic in planta.

Transgenic Forsythia plants expressing sesame cytochrome P450 produce beneficial lignans.

Lignans are widely distributed plant secondary metabolites that have received attention for their benefits to human health. Sesamin is a furofran lignan that is conventionally extracted from Sesamum seeds and shows anti-oxidant and anti-inflammatory activities in the human liver. Sesamin is biosynthesized by the Sesamum-specific enzyme CYP81Q1, and the natural sources of sesamin are annual plants that are at risk from climate change. In contrast, Forsythia species are widely distributed perennial woody plants that highly accumulate the precursor lignan pinoresinol. To sustainably supply sesamin, we developed a transformation method for Forsythia leaf explants and generated transgenic Forsythia plants that heterologously expressed the CYP81Q1 gene. High-performance liquid chromatography (HPLC) and LC-mass spectrometry analyses detected sesamin and its intermediate piperitol in the leaves of two independent transgenic lines of F. intermedia and F. koreana. We also detected the accumulation of sesamin and piperitol in their vegetatively propagated descendants, demonstrating the stable and efficient production of these lignans. These results indicate that CYP81Q1-transgenic Forsythia plants are promising prototypes to produce diverse lignans and provide an important strategy for the cost-effective and scalable production of lignans.

Albumin and Derived Neutrophil-to-Lymphocyte Ratio is a Novel Prognostic Factor for Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Multidisciplinary treatment combining neoadjuvant treatment (NAT) and surgery has slightly improved the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Although various biomarkers targeting nutrition and inflammation are associated with cancer prognosis, most studies have focused on conditions prior to NAT. Developing real-time and sensitive biomarkers that monitor changes in systemic conditions during NAT is important. We established a novel nutritional and inflammatory index, represented as the albumin to derived neutrophil-to-lymphocyte ratio (Alb-dNLR), and calculated the change in Alb-dNLR (ΔAlb-dNLR) during neoadjuvant chemotherapy (nCT). In this study, we aimed to evaluate whether ΔAlb-dNLR is associated with prognosis in patients with ESCC. METHODS: We investigated 172 patients who underwent nCT before esophagectomy between April 2010 and March 2018. The dNLR was calculated as the ratio of neutrophil count to (white blood cell count - neutrophil count), Alb-dNLR was calculated by dividing the serum albumin level by the dNLR, and ΔAlb-dNLR was evaluated by dividing the post-Alb-dNLR by the pre-Alb-dNLR. Patients were divided into 'high' and 'low' groups according to the ΔAlb-dNLR. RESULTS: Thirty-nine patients (22.7%) had a low ΔAlb-dNLR (≤ 0.8), and the 5-year overall survival (OS) rates in patients with low and high ΔAlb-dNLR were 38.1% and 53.6%, respectively (p = 0.0072). Multivariate analyses demonstrated that estimated blood loss (p = 0.044), pathological T stage (p = 0.0005), pathological N stage (p = 0.017), and ΔAlb-dNLR (p = 0.005) were independent prognostic factors for OS. CONCLUSIONS: ΔAlb-dNLR is a useful prognostic factor for OS in patients with ESCC receiving nCT.

Thoracic cavity-to-cage ratio is a predictor of technical difficulties in minimally invasive esophagectomy.

BACKGROUND: Technical difficulties are occasionally encountered when performing conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy in patients with a narrow thoracic cavity. Thoracic cavity-to-cage ratio is an indicator of thoracic cavity length. We hypothesized that the thoracic cavity-to-cage ratio could be a predictor of technical difficulties in conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy. METHODS: We evaluated 340 patients who underwent minimally invasive esophagectomy for esophageal squamous cell carcinoma between April 2010 and March 2021. Thoracic cavity-to-cage ratio was calculated as the diameter of the thoracic cavity to that of the thoracic cage at the brachiocephalic vein, tracheal bifurcation, and inferior right pulmonary vein levels. Moreover, thoracic cavity-to-cage ratio score, which is an indicator of the whole thoracic cavity length based on the thoracic cavity-to-cage ratio at the 3 levels, was defined. The thoracic procedure time was considered an indicator of surgical difficulty. RESULTS: We divided the patients into the conventional minimally invasive esophagectomy (n = 295) and robot-assisted minimally invasive esophagectomy (n = 45) groups. The patients in each group were divided into 2 cohorts according to median thoracic procedure time. Based on multivariate analysis, body mass index (P = .0007), clinical N stage (P = .0191), and thoracic cavity-to-cage ratio score (P = .0005) were independent factors for thoracic procedure time in the conventional minimally invasive esophagectomy group. Moreover, thoracic cavity-to-cage ratio at the tracheal bifurcation level (P = .0331) was the only independent factor for thoracic procedure time in the robot-assisted minimally invasive esophagectomy group. CONCLUSION: Thoracic cavity-to-cage ratio could be a predictor of technical difficulties in both conventional minimally invasive esophagectomy and robot-assisted minimally invasive esophagectomy.

Laparoscopic creation of a retrosternal route for gastric conduit reconstruction.

BACKGROUND: Retrosternal reconstruction is associated with a lower risk of mediastinitis, gastro-tracheal fistula, and hiatal hernia. Historically, traumatic manual creation of the retrosternal tunnel has been performed using one's fist. We report a novel and atraumatic laparoscopic procedure to create the retrosternal route. METHODS: We have laparoscopically created the retrosternal route in 25 thoracoscopic, mediastinoscopic, or robot-assisted minimally invasive esophagectomies since August 2019. Specifically, a peritoneal incision is started at the dorsal side of the xiphoid process. Through a 12-mm port inserted slightly to the right of and superior to the umbilical camera port, we dissect loose connective tissues from the caudal to the cranial side using behind the sternum and inside the internal thoracic vessels as landmarks. The time required to create the route was calculated. Then, the cumulative sum (CUSUM) method and the simple moving average of five cases were used to evaluate the learning curve of this novel procedure. Operative outcomes were analyzed according to the learning curve results and also compared with 25 cases of postmediastinal reconstruction counterparts. RESULTS: Twenty-five patients were divided into the early group (six patients) and late group (19 patients) based on the peak of the CUSUM chart. The time required for route creation was 28.5 min (median) in the early and 15 min in the late group, indicating a significant difference (P = 0.038). The overall incidence of pleural injury was 20% (5 of 25 patients), with no significant difference between the groups. There was no significant difference in the incidence of perioperative complications. Also, there were no significant differences in perioperative complications or gastric conduit functions 1 year after surgery between the retrosternal and the postmediastinal reconstruction. CONCLUSION: Laparoscopic creation of a retrosternal route for gastric conduit reconstruction is safe and feasible and has a short learning curve.

Albumin-Derived NLR Score is a Novel Prognostic Marker for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Multidisciplinary treatment for esophageal squamous cell carcinoma (ESCC) has improved outcomes, but the prognosis for ESCC remains poor. Nutritional and inflammatory indicators are reported to be associated with cancer prognosis. The combination of albumin and the derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score was established to measure the immune system and nutritional status. The authors hypothesized that the Alb-dNLR score could be a new reliable prognostic factor for ESCC patients. METHODS: The study evaluated 269 patients who underwent esophagectomy between April 2010 and March 2018, including 185 patients who received neoadjuvant chemotherapy. The Alb-dNLR score was calculated using serum albumin and the dNLR. The dNLR was calculated as neutrophils to (leukocyte-neutrophil count). The cutoff values of the albumin and dNLR for overall survival (OS) were determined using the receiver operating characteristic curve. Patients were divided into "high" and "low" groups according to the Alb-dNLR score. RESULTS: A high Alb-dNLR score was found in 61 cases (22.7%). The 5-year OS was 34% in the high Alb-dNLR group and 66.2% in the low Alb-dNLR group (p < 0.0001). The 5-year cause-specific survival (CSS) was 51.5% in the high Alb-dNLR group and 74.7% in the low Alb-dNLR group (p < 0.0001). Multivariate analyses demonstrated that the Alb-dNLR score was an independent prognostic factor for OS (hazard ratio [HR], 2.198; 95% confidence interval [CI], 1.460-3.263; p = 0.0002) and CSS (HR, 1.733; 95% CI, 1.035-2.835; p = 0.0371). CONCLUSIONS: The Alb-dNLR score is an extremely useful, easy-to-use parameter to predict OS and CSS for ESCC patients.

Distinguishing between isomeric neoxanthin and violaxanthin esters in yellow flower petals using liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry and tandem mass spectrometry.

RATIONALE: Liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry (LC/PDA-APCI-MS) is used for the analysis of various carotenoid pigments in plants. Among them, it is difficult to distinguish between the isomeric violaxanthin/neoxanthin esters. METHODS: The yellow pigments of tomato petals were extracted with acetone, and the extracts were kept at -30°C to allow the contaminating triacylglycerols to settle out physically. The supernatants were analyzed using LC/PDA-APCI-MS with a high-resolution orbitrap mass spectrometer for their exact masses. The expected carotenoid esters were calculated with the combination of carotenoids and fatty acids, and they were matched with the experimental exact masses. The fatty acid structures in the carotenoid esters were also identified using collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). The isomeric violaxanthin/neoxanthin esters were distinguished using CID MS/MS from their in-source dehydrated product ions as pseudoprecursor ions. RESULTS: The in-source dehydrated ions [M - H2 O + H]+ of neoxanthin diesters predominated over their protonated molecules [M + H]+ in LC/MS. By contrast, the protonated molecules of violaxanthin diesters predominated. The 92 u loss product ions [M - H2 O - C7 H8 + H]+ were observed from the dehydrated violaxanthin diesters, but they were not generated from the dehydrated neoxanthin diesters in the CID MS/MS of their dehydrated pseudoprecursor ion [M - H2 O + H]+ . CONCLUSIONS: The allene allyl carbocation in neoxanthin diesters was generated from dehydration after preferential protonation at the hydroxy group. The epoxide group of violaxanthin diesters opens easily after protonation; however, the dehydration did not proceed at this stage. The 92 u loss of C7 H8 was explained by an intramolecular [2 + 2] cycloaddition, which proceeded preferentially in dehydrated violaxanthin diesters because the carbocations in the dehydrated species were conjugated to the polyene and those double bonds were depolarized during CID MS/MS. Therefore, the isomeric neoxanthin/violaxanthin diesters were distinguished using LC/PDA-APCI-MS and MS/MS. This method was a practical and useful method of profiling the carotenoid esters of the yellow petals.

Incidence of Recurrent Laryngeal Nerve Palsy in Robot-Assisted Versus Conventional Minimally Invasive McKeown Esophagectomy in Prone Position: A Propensity Score-Matched Study.

BACKGROUND: Esophagectomy with lymphadenectomy is the principal treatment for localized esophageal cancer. Conventional minimally invasive esophagectomy (C-MIE) in prone position has spread worldwide as it is less invasive. However, its efficacy remains controversial. Robot-assisted MIE (RAMIE) can have more advantages than C-MIE. Therefore, the current study aimed to validate whether RAMIE is associated with lower incidence of left recurrent laryngeal nerve (RLN) palsy compared with C-MIE in prone position. PATIENTS AND METHODS: In total, 404 patients with esophageal carcinoma underwent MIE (353 C-MIEs and 51 RAMIEs) in prone position at Kobe University between 2010 and 2020. Then, propensity score matching was performed, and results showed that 51 patients should be included in each group. Thereafter, the perioperative outcomes between the two groups were compared. RESULTS: The RAMIE group had a significantly longer operative time than the C-MIE group (P < 0.0001). However, the number of lymph nodes resected along the left RLN was similar in both groups. Moreover, the incidence of left RLN palsy was significantly lower in the RAMIE group than in the C-MIE [Clavien-Dindo classification grade II; 0 (0%) versus 32 (9%), P = 0.022 in entire cohort, and 0 (0%) versus 5 (10%), P = 0.022 in matched cohort. Esophagectomy Complications Consensus Group definitions type I; 8 (16%) versus 101 (29%), P = 0.041 in entire cohort and 8 (16%) versus 18 (35%) in matched cohort, P = 0.023]. CONCLUSION: RAMIE is superior to C-MIE in prone position in decreasing the incidence of left RLN palsy.

[Brain Metastasis and Leptomeningeal Carcinomatosis after Surgery for Esophageal Cancer-A Case Report].

A 70-year-old man had undergone thoracoscopic esophagectomy following neoadjuvant chemotherapy for thoracic esophageal squamous cell carcinoma 3 years before presentation. He was undergoing whole-brain irradiation following surgery for a solitary brain metastatic tumor. The chief complaint was left leg pain during irradiation. FDG-PET/CT and MRI revealed metastases in bilateral cauda equina S1 nerve roots. Cerebrospinal fluid examination also revealed malignant cells. He received chemotherapy with 2 courses of 5-fluorouracil and cisplatin following 30 Gy of spinal irradiation. To control neurological symptoms, 4 courses of intrathecal chemotherapy with methotrexate, cytarabine, and betamethasone were performed. However, he gradually weakened and died 8 months after brain metastasis and 7 months after leptomeningeal carcinomatosis. The multidisciplinary treatment using irradiation and systemic and intrathecal chemotherapies could improve the survival of patients with leptomeningeal carcinomatosis of esophageal squamous cell carcinoma.

(+)-Sesamin-oxidising CYP92B14 shapes specialised lignan metabolism in sesame.

Sesamum spp. (sesame) are known to accumulate a variety of lignans in a lineage-specific manner. In cultivated sesame (Sesamum indicum), (+)-sesamin, (+)-sesamolin and (+)-sesaminol triglucoside are the three major lignans found richly in the seeds. A recent study demonstrated that SiCYP92B14 is a pivotal enzyme that allocates the substrate (+)-sesamin to two products, (+)-sesamolin and (+)-sesaminol, through multiple reaction schemes including oxidative rearrangement of α-oxy-substituted aryl groups (ORA). In contrast, it remains unclear whether (+)-sesamin in wild sesame undergoes oxidation reactions as in S. indicum and how, if at all, the ratio of the co-products is tailored at the molecular level. Here, we functionally characterised SrCYP92B14 as a SiCYP92B14 orthologue from a wild sesame, Sesamum radiatum, in which we revealed accumulation of the (+)-sesaminol derivatives (+)-sesangolin and its novel structural isomer (+)-7´-episesantalin. Intriguingly, SrCYP92B14 predominantly produced (+)-sesaminol either through ORA or direct oxidation on the aromatic ring, while a relatively low but detectable level of (+)-sesamolin was produced. Amino acid substitution analysis suggested that residues in the putative distal helix and the neighbouring heme propionate of CYP92B14 affect the ratios of its co-products. These data collectively show that the bimodal oxidation mechanism of (+)-sesamin might be widespread across Sesamum spp., and that CYP92B14 is likely to be a key enzyme in shaping the ratio of (+)-sesaminol- and (+)-sesamolin-derived lignans from the biochemical and evolutionary perspectives.

Author Correction: Identification of a binding protein for sesamin and characterization of its roles in plant growth.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.