Tuning the Selectivity of Catalytic Nitrile Hydrogenation with Phase-Controlled Co Nanoparticles Prepared by Hydrosilane-Assisted Method.

Cobalt (Co) is a promising candidate to replace noble metals in the hydrogenation process, which is widely employed in the chemical industry. Although the catalytic performance for this reaction has been considered to be significantly dependent on the Co crystal phase, no satisfactory systematic studies have been conducted, because it is difficult to synthesize metal nanoparticles that have different crystalline structures with similar sizes. Here we report a new method for the synthesis of cobalt nanoparticles using hydrosilane as a reducing agent (hydrosilane-assisted method). This new method uses 1,3-butanediol and propylene glycol to successfully prepare fcc and hcp cobalt nanoparticles, respectively. These two types of Co nanoparticles have similar sizes and surface areas. The hcp Co nanoparticles exhibit higher catalytic performance than fcc nanoparticles for the hydrogenation of benzonitrile under mild conditions. The present hcp Co catalyst is also effective for highly selective benzyl amine production from benzonitrile without ammonia addition, whereas many catalytic systems require ammonia addition for selective benzyl amine production. Mechanistic studies revealed that the fast formation of the primary amine and the prevention of condensation and secondary amine hydrogenation promote selective benzonitrile hydrogenation for benzylamine over hcp Co nanoparticles.

A multi-institutional prospective observational study to compare postoperative quality of life of patients who undergo total or proximal gastrectomy for early gastric cancer (CCOG1602).

BACKGROUND: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach. However, advantages of PG in postoperative quality of life (QOL) over total gastrectomy (TG) has not fully proven. METHODS: We conducted a multi-institutional prospective observational study (CCOG1602) of patients who undergo TG or PG for cStage I gastric cancer. We used the PGSAS-37 and EORTC-QLQ-C30 to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. RESULTS: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (p = 0.056, Cohen's d 0.656) during postoperative year 1% and 15.0% and 10.8% for TG and PG (p = 0.068, Cohen's d 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (p < 0.001, Cohen's d -1.085) and total symptom score (p = 0.050, Cohen's d -0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 detected no difference between the groups at any time point during 3-year postoperative period. CONCLUSIONS: This prospective study demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.

Thirty-year outcomes of low-intensity anticoagulation for mechanical aortic valve.

The long-term safety, efficacy, and outcomes of low-intensity anticoagulation for mechanical heart valves remain unclear. This study aimed to evaluate the long-term outcomes of low-intensity anticoagulation therapy after aortic valve replacement (AVR) with a mechanical prosthesis. This retrospective cohort study consulted medical records and conducted a questionnaire to investigate 519 patients who underwent single AVR with the St. Jude Medical bileaflet valve and were in sinus rhythm. All patients were followed up with an international normalized ratio (INR) target of 1.6-2.5, and their INR values were checked throughout the follow-up period. The survival rate, incidence of major adverse cardiac and cerebrovascular events (MACCE), and risk factors for cardiac death and MACCE were investigated. The total follow-up was 9793 patient-years, and the follow-up periods were 19.9 (standard deviation [SD]: 7.9) years. The mean INR was 2.03 (SD: 0.54). Survival rates from cardiac death were 93.6% in 20 years and 85.2% in 30 years. Advanced age ≥ 70 years was the only significant risk factor for cardiac death and MACCE, and the INR < 2.0 was not significant risk factor for MACCE including thromboembolism or bleeding events. Low-intensity anticoagulation with an INR of 1.6-2.5 for patients with sinus rhythm after AVR with a bileaflet mechanical valve is safe and effective, even over 30 years.

The long-term quality of life after distal and pylorus-preserving gastrectomy for stage I gastric cancer: A prospective multi-institutional study (CCOG1601).

PURPOSE: While regarded as function-preserving gastrectomy, few prospective longitudinal clinical trials have addressed the postoperative quality of life (QOL) after pylorus-preserving gastrectomy (PPG). We prospectively compared chronological changes in postoperative body weight and the QOL between PPG and distal gastrectomy (DG) for pathological Stage I gastric cancer (GC). METHODS: We conducted a multi-institutional prospective study (CCOG1601) to evaluate patients who underwent DG and PPG. The QOL was examined using the European Organization for Research and Treatment of Cancer Quality of life questionnaire-C30 (EORTC QLQ-C30) and the Post-Gastrectomy Syndrome Assessment Scale-37 (PGSAS-37). A total of 295 patients were enrolled from 15 institutions, and propensity score matching was performed to adjust for the essential variables for comparison analyses. RESULTS: After propensity score matching, 25 pairs of patients were identified. In the first postoperative month, DG achieved a superior nausea and vomiting score (EORTC QLQ-C30) and meal-related distress, indigestion, and dumping scores (PGSAS-37). No significant differences were noted between DG and PPG in the long-term QOL. Postoperative body weight loss was similar in both groups. CONCLUSIONS: This prospective observational study failed to demonstrate the superiority of PPG over DG in terms of postoperative body weight changes and the QOL.

Low-Temperature Ammonia Synthesis on Iron Catalyst with an Electron Donor.

Haber-Bosch process produces ammonia to provide food for over 5 billion people; however, it is currently required to be produced without the use of fossil fuels to reduce global CO2 emissions by 3% or more. It is indispensable to devise heterogeneous catalysts for the synthesis of ammonia below 100-150 °C to minimize the energy consumption of the process. In this paper, we report metallic iron particles with an electron-donating material as a catalyst for ammonia synthesis. Metallic iron particles combined with a mixture of BaO and BaH2 species in an appropriate manner could catalyze ammonia synthesis even at 100 °C. The iron catalyst revealed that iron can exhibit a high turnover frequency (∼12 s-1), which is over an order of magnitude higher than those of other transition metals used in highly active catalysts for ammonia synthesis. This can be attributed to the intrinsic nature of iron to desorb adsorbed hydrogen atoms as hydrogen molecules at low temperatures.

The Impact of Nutritional Support on Survival Outcomes in Patients with Advanced Gastric Adenocarcinoma Treated with Chemotherapy.

Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC). This study elucidated the effect of nutritional support (NS) on survival outcomes among patients with AGC undergoing chemotherapy. We retrospectively evaluated new AGC cases at our institute between January 2015 and January 2021. Inclusion criteria were unresectable or recurrent chemotherapy-treated gastric adenocarcinoma, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) and overall survival (OS) were evaluated, and univariate and multivariate analyses identified prognostic factors. A total of 103 eligible patients were separated into groups: 69 patients (67%) into NS and 34 (33%) into routine care (RC). The median follow-up time was 11.0 mo, (0.5-92). NS was offered to patients with poorer PS (p = 0.03), Glasgow prognostic score (GPS) positivity (p = 0.001), and high neutrophil-to-lymphocyte ratios (cut-off ≤ 3, p = 0.02). Median OS and TTF in the RC and NS groups were 11.6 and 10.4 mo, (p = 0.99) and 4.2 and 5.5 mo, (p = 0.07), respectively. Multivariate analyses identified NS (hazard ratio [HR] = 0.53, p = 0.01) and GPS positivity for TTF, and low body mass index (HR = 2.03, p = 0.007) and GPS positivity (HR = 2.25, p = 0.001) for OS as significant prognostic factors. Thus, NS with chemotherapy is a potentially effective intervention for AGC.

[Mobile Thrombus in the Ascending Aorta Detected Incidentally in the Patient with Fever before Surgery for Esophageal Cancer:Report of a Case].

A mobile thrombus in the ascending aorta is extremely rare. A 57-year-old man was referred to our hospital with suspected esophageal cancer. Following thorough evaluation, he was diagnosed with esophageal cancer( UtMt type0-Ⅱa T1b, Mt type0-Ⅱc T1a N0M0 cStageⅠ) and tongue cancer in situ. He was administered preoperative chemotherapy comprising fluorouracil and cisplatin. The patient developed fever on day four of the first course of the chemotherapy. Contrast-enhanced chest and abdominal computed tomography revealed a mobile thrombus in the ascending aorta with bilateral partial renal infarction. We initiated intravenous unfractionated heparin and oral warfarin as anticoagulant therapy. The thrombus did not disappear despite ten-day treatment;therefore, he underwent aortic thrombectomy under hypothermic circulatory arrest with retrograde cerebral perfusion. Intraoperatively, we detected a pedunculated mobile thrombus attached to the aorta. His postoperative course was uneventful and he was treated at discharge with warfarin. He underwent video-assisted thoracoscopic esophagectomy postoperatively and was discharged without any complication. Currently, he showed no recurrent thrombus or cancer.

[Thoracic Endovascular Aortic Repair for Idiopathic Aortic Rupture].

Idiopathic aortic rupture is a rare but often fatal condition that requires urgent attention and repair. I have performed thoracic endovascular aortic repair ( TEVAR) in two cases of idiopathic aortic rupture and have achieved positive results. It can be difficult to identify the site of rupture in these cases. Therefore, it is necessary to lengthen treatment and to determine the potential for spinal cord ischemia and associated paralysis of the lower extremities. Given its association with a favorable postoperative recovery, TEVAR can be considered as a minimally-invasive option that can be used early to treat this condition, including those associated with hemodynamic instability and in patients who are at high risk for complications.

Magnetic anchor-guided endoscopic submucosal dissection for colorectal tumors (with video).

BACKGROUND: The feasibility of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) using a neodymium magnet for colorectal tumors has not been evaluated. The aim of this study was to clarify the feasibility of MAG-ESD for colorectal tumors. METHODS: This prospective trial was conducted at Yamashita Hospital. MAG-ESD was performed for 49 colorectal tumors. The magnetic anchor comprised an internal magnet attached to an endoclip with 3-0 silk. Both external and internal magnets were made using neodymium magnets. The feasibility of traction achieved using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time required for preparation and attachment of the magnetic anchor, procedure time, rate of retrieval of magnetic anchors, and adverse events were evaluated. RESULTS: MAG-ESDs were successfully performed for 48 colorectal tumors except for a rectal case in which the internal magnet stuck to the endoscope. En bloc resections and complete en bloc resections were achieved in all cases. Attaching the magnetic anchor required a median of 8 min (range 3-37 min). Median procedure time was 76 min (range 28-283 min) and the magnetic anchors were retrieved in all cases without adverse events. CONCLUSION: MAG-ESD is feasible and safe in the colon and may facilitate the treatment of all difficult lesions. (UMIN000024100).

Randomized Phase II Study of Consecutive-Day versus Alternate-Day Treatment with S-1 as Second-Line Chemotherapy in Advanced Pancreatic Cancer.

OBJECTIVE: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. METHODS: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. RESULTS: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). CONCLUSION: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy.

BACKGROUND: The incidence of mixed hepatitis C virus (HCV) genotype infection is variable, and a few reports exist regarding the efficacy of direct-acting antivirals (DAA) therapy for mixed genotype. We aimed to investigate the prevalence of mixed genotype and its impact on the virologic response to DAA therapy. METHODS: A total of 365 patients with chronic HCV infection who completed antiviral therapy were recruited. Nested polymerase chain reaction with universal and specific primers of genotypes 1b and 2 and direct sequencing were used for HCV genotyping. RESULTS: Direct sequencing with universal primers defined genotypes 1b (n = 230), 2a (n = 95), and 2b (n = 40). Direct sequencing of genotype 2 was performed in patients with genotype 1b, and direct sequencing of genotype 1b in patients with genotype 2. Four patients with genotype 1b underwent amplification for genotype 2, and direct sequencing identified genotypes 1b (n = 1), 2a (n = 1), and 2b (n = 2). None with genotype 2 underwent amplification for genotype 1b. Three cases were confirmed to have mixed genotype. CONCLUSIONS: Mixed genotype was rare, and hence the impact of mixed genotype on treatment outcome with DAA therapy is expected to be minimal.

Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy.

The optimal term of follow-up for patients who achieve sustained virological responses (SVR) is an important topic because of the widespread use of direct-acting antivirals (DAA), which achieve a high SVR rate. Investigations of long-term follow-up among patients with SVR after interferon (IFN) therapy have reported that approximately 80%-100% of patients maintained SVR. However, the long-term durability of SVR to DAA treatment is unknown. The aim of this study was to evaluate the incidence of late relapse in patients who achieved SVR with daclatasvir (DCV) and asunaprevir (ASV). Four hundred and thirteen patients infected with hepatitis C virus (HCV) genotype 1b who completed ASV and DCV treatment and achieved SVR were selected. Patients who were persistently negative for serum HCV RNA at 24 weeks after withdrawal of DCV and ASV were considered to have SVR24. Mean follow-up period was 21.5 months (range, 4.8-30.3 months) after SVR24. Four patients redeveloped HCV RNA in serum at 6, 12, 12 and 26 months, respectively, after achieving SVR24. Results of molecular analysis by phylogenetic tree of HCV nonstructural protein 3 and 5A regions from late relapse indicated that the same strain was present at pretreatment and late relapse. In conclusion, late relapse by the original HCV strain was confirmed by direct sequencing in 4 of 413 patients with SVR to ASV and DCV. Although a few patients may develop late relapse, SVR achieved with all oral DAA therapy is as durable as that with IFN therapy.

Magnetic anchor-guided endoscopic submucosal dissection for gastric lesions (with video).

BACKGROUND AND AIMS: The feasibility of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) using a neodymium magnet for gastric lesions has not been clarified. The aim of study was to evaluate the feasibility of MAG-ESD using neodymium magnets while treating gastric lesions. METHODS: This prospective trial was conducted at the Yamashita Hospital. MAG-ESD was performed for 50 gastric lesions using an insulated-tip knife. The magnetic anchor consisted of an internal neodymium magnet attached to a hemoclip with 3-0 silk. The external and internal magnets were made from the neodymium magnet. The feasibility of traction using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time required for preparation and attaching the magnetic anchor, procedure time, rate of retrieval of the magnetic anchors, and adverse events were evaluated. RESULTS: Fifty patients (median lesion size, 20 mm [range, 5-100]) were enrolled. MAG-ESDs were successfully performed for all 50 gastric lesions. Adequate counter-traction was obtained using the external magnet. En bloc resections were achieved and complete en bloc resections confirmed in all cases without adverse events. Attaching the magnetic anchor required a median of 6 minutes (range, 2-14). The median procedure time was 49 minutes (range, 15-301), and the magnetic anchors could be retrieved in all cases. CONCLUSIONS: This study clearly demonstrated the feasibility of this MAG-ESD in the stomach. We hope this procedure will facilitate the resection of difficult lesions. (Clinical trial registration number: UMIN000024100.).

Comparison of direct sequencing and Invader assay for Y93H mutation and response to interferon-free therapy in hepatitis C virus genotype 1b.

BACKGROUND AND AIM: Virologic failure of interferon-free therapy has been associated with Y93H mutation in the non-structure 5A region in hepatitis C virus (HCV) genotype 1b, and screening is recommended. A simple assay based on Q-Invader technology was developed for Y93H mutant screening to reduce cost and effort. The present study sought to compare two methods of detection of Y93H mutation and to evaluate the effect of Y93H mutation on response to interferon-free therapy. METHODS: Y93H mutation was examined in 258 patients with HCV genotype 1b using both direct sequencing analysis and the polymerase chain reaction (PCR)-Invader assay. Daclatasvir and asunaprevir or ledipasvir and sofosbuvir therapy was administered to 205 patients whose sustained virological responses (SVR) were checked. RESULTS: Hepatitis C virus was detected in 232 of 258 patients by direct sequencing and in 236 of 258 patients by the PCR-Invader assay. Forty of 231 cases were defined as Y93 mutation by direct sequencing, and 46 of 236 cases were defined as Y93 mutation by the PCR-Invader assay. SVR of patients who were Y93H by direct sequencing, Y93H by the PCR-Invader assay, and Y93H by both methods was 62.5%, 82.4%, and 50%, respectively. CONCLUSIONS: The sensitivity of the PCR-Invader assay was similar to that of direct sequencing analysis; however, the PCR-Invader assay had a better ability to detect minor strains. Combination of the two assays would improve prediction of the response to daclatasvir and asunaprevir, but Y93H mutation had little effect on SVR in ledipasvir and sofosbuvir therapy.

Photoassist-phosphorylated TiO2 as a catalyst for direct formation of 5-(hydroxymethyl)furfural from glucose.

Photo-assisted phosphorylation of an anatase TiO2 catalyst was examined to improve its catalytic performance for the direct production of 5-(hydroxymethyl)furfural (HMF), a versatile chemical platform, from glucose. In phosphorylation based on simple esterification between phosphoric acid and surface OH groups on anatase TiO2 with water-tolerant Lewis acid sites, the density of phosphates immobilized on TiO2 is limited to 2 phosphates nm-2, which limits selective HMF production. Phosphorylation of the TiO2 surface under fluorescent light irradiation increases the surface phosphate density to 50%, which is higher than the conventional limit, thus preventing the adsorption of hydrophilic glucose molecules on TiO2 and resulting in a more selective HMF production over photoassist-phosphorylated TiO2.

The Prognostic Relevance of Subcarinal Lymph Node Dissection in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The objective of this study was to evaluate the prognostic relevance of subcarinal lymph node dissection in patients with esophageal squamous cell carcinoma (ESCC) and to identify a subset of patients in whom subcarinal lymph node dissection can be omitted. METHODS: We retrospectively analyzed 342 consecutive patients with thoracic ESCC who underwent R0 subtotal esophagectomy. All patients underwent subcarinal lymph node dissection. The efficacy index (frequency of metastasis to a particular lymph node station multiplied by the 5-year disease-specific survival rate of patients with metastasis to the station) was calculated for the subcarinal lymph node station, and the prognostic impact of dissecting this station was estimated with reference to the main tumor location. Independent predictive factors for pathological subcarinal lymph node metastasis were analyzed using a proportional hazards model. RESULTS: The overall frequency of metastasis to the subcarinal lymph nodes was 7.0 % (2.4, 8.9, and 5.8 % in patients with upper, middle, and lower thoracic ESCC, respectively). The efficacy index for the middle thoracic esophagus was 2.9, and that for the upper and lower thoracic esophagus was 0.0. The 5-year disease-free survival rate was significantly lower in patients with pathological subcarinal lymph node metastasis than those without (23.1 vs. 67.5 %, respectively; log-rank p < 0.0001). In multivariate analysis, clinical T stage (T2-T4) was the independent predictive factor for pathological subcarinal lymph node metastasis (p = 0.021). CONCLUSIONS: Subcarinal lymph node dissection might have little value in patients with upper and lower thoracic ESCC and could be omitted, especially for superficial carcinoma.

Short-term outcomes after conventional transthoracic esophagectomy.

In our department, we have attempted to reduce the incidence of complications of conventional esophagectomy. The objective of this retrospective study was to report the short-term outcomes of esophagectomy. We reviewed 138 consecutive patients who had undergone subtotal esophagectomy by combined laparotomy via a 12-cm upper abdominal vertical incision combined with right anterior muscle-sparing thoracotomy from August 2010 to August 2014. Most of the cervical para-esophageal lymph node dissection was completed within the thoracic cavity. We performed three-field dissection in patients with tumors in the upper or middle third of the esophagus with clinical lymph node metastases in the superior mediastinum; the others underwent two-field dissection. We performed neck anastomoses in patients undergoing three-field dissection and thoracic anastomoses in those undergoing two-field dissection. Effective postoperative pain management was achieved with a combination of epidural anesthesia and paravertebral block. Postoperative rehabilitation was instituted for early ambulation and recovery. Enteral nutrition via a duodenal feeding tube was administered from postoperative day 2. Median hospital stay after surgery was 15 days (range, 10-129). Rates for both 30-day and in-hospital mortality were 0%. Morbidity rate for all Clavien-Dindo grades was 41.3%, whereas the morbidity rate for Clavien-Dindo grades III and IV was 7.2%. Anastomotic leakage developed in two patients (1.4%), recurrent laryngeal nerve palsy in 11 (8.0%), and pneumonia in nine (6.5%). Good short-term outcomes, especially regarding anastomotic leaks, were achieved by consistent improvements in surgical techniques, optimization of several operative procedures, and appropriate perioperative management.

[Myxoma Originating from the Tricuspid Annulus Requiring Annular Reconstruction and Valve Replacement;Report of a Case].

A 66-year-old woman who had had coughing and worsening dyspnea for 3 weeks was admitted to our hospital. Echocardiography showed a solid round mass (72×49 mm in diameter) attached to the tricuspid septal annulus with a short stalk. A right atrial myxoma was suspected and operation was performed under cardiopulmonary bypass after heart failure symptoms subsided. The tumor was extirpated along with the tricuspid valve annulus. We performed reconstruction of the tricuspid annulus, tricuspid valve replacement with a bioprosthetic valve and pacemaker implantation. The histopathologic diagnosis was myxoma. The postoperative course was uneventful, and no recurrence has been noted for 1 year after surgery.