Transhydrogenase couples the redox (hydride-transfer) reaction between NAD(H) and NADP(H) to proton translocation across a membrane. The redox reaction is catalyzed at the interface between two components (dI and dIII) which protrude from the membrane. A complex formed from recombinant dI and dIII (the dI(2)dIII(1) complex) from Rhodospirillum rubrum transhydrogenase catalyzes fast single-turnover hydride transfer between bound nucleotides. In this report we describe three new crystal structures of the dI(2)dIII(1) complex in different nucleotide-bound forms. The structures reveal an asymmetry in nucleotide binding that complements results from solution studies and supports the notion that intact transhydrogenase functions by an alternating site mechanism. In one structure, the redox site is occupied by NADH (on dI) and NADPH (on dIII). The dihydronicotinamide rings take up positions which may approximate to the ground state for hydride transfer: the redox-active C4(N) atoms are separated by only 3.6 A, and the perceived reaction stereochemistry matches that observed experimentally. The NADH conformation is different in the two dI polypeptides of this form of the dI(2)dIII(1) complex. Comparisons between a number of X-ray structures show that a conformational change in the NADH is driven by relative movement of the two domains which comprise dI. It is suggested that an equivalent conformational change in the intact enzyme is important in gating the hydride-transfer reaction. The observed nucleotide conformational change in the dI(2)dIII(1) complex is accompanied by rearrangements in the orientation of local amino acid side chains which may be responsible for sealing the site from the solvent and polarizing hydride transfer.

Gastrectomy is the mainstay treatment for gastric cancer. To reduce the associated patient burden, minimally invasive gastrectomy was introduced in almost 30 years ago. The increase in the availability of surgical robotic systems led to the first robotic-assisted gastrectomy to be performed in 2002 in Japan. Robotic gastrectomy however, particularly in Europe, has not yet gained significant traction. Most reports to date are from Asia, predominantly containing observational studies. These cohorts are commonly different in the tumour stage, location (particularly with regards to gastroesophageal junctional tumours) and patient BMI compared to those encountered in Europe. To date, no randomised clinical trials have been performed comparing robotic gastrectomy to either laparoscopic or open equivalent. Cohort studies show that robotic gastrectomy is equal oncological outcomes in terms of survival and lymph node yield. Operative times in the robotic group are consistently longer compared to laparoscopic or open gastrectomy, although evidence is emerging that resectional surgical time is equal. The only reproducibly significant difference in favour of robot-assisted gastrectomy is a reduction in intraoperative blood loss and some studies show a reduction in the risk of pancreatic fistula formation.

Risk assessment is relevant to predict outcomes in patients with gastric cancer. This systematic review aimed to investigate the predictive value of low muscle mass for postoperative complications in gastric cancer patients. A systematic literature search was performed to identify all articles reporting on muscle mass as measured on computed tomography (CT) scans in patients with gastric cancer. After full text screening, 15 articles reporting on 4887 patients were included. Meta-analysis demonstrated that patients with low muscle mass had significantly higher odds of postoperative complications (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.55–2.83) and severe postoperative complications (Clavien–Dindo grade ≥III, OR: 1.73, 95% CI: 1.14–2.63). Moreover, patients with low muscle mass had a significantly higher overall mortality (hazard ratio (HR): 1.81, 95% CI: 1.52–2.14) and disease-specific mortality (HR: 1.58, 95% CI: 1.36–1.84). In conclusion, assessment of muscle mass on CT scans is a potential relevant clinical tool for risk prediction in gastric cancer patients. Considering the heterogeneity in definitions applied for low muscle mass on CT scans in the included studies, a universal cutoff value of CT-based low muscle mass is required for more reliable conclusions.