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•Subclinical hemolysis after TAVI has occasionally been documented.•Decompensated hemolytic anemia requiring specific treatment has been rare.•The incidence of hemolytic anemia after TAVI using S3UR was not negligible.•PVL ≥ mild was associated with an increased risk of hemolytic anemia. Decompensated hemolytic anemia after transcatheter aortic valve implantation (TAVI) requiring specific treatment is rarely encountered in actual clinical practice. Nevertheless, there have been several cases of clinically relevant hemolytic anemia following implantation of the recently launched SAPIEN 3 Ultra RESILIA (S3UR). This study aimed to elucidate the clinical features of hemolytic anemia following S3UR implantation. Patients who underwent TAVI using S3UR from the end of March 2023 to November 2023 were enrolled from the Japanese multicenter OCEAN (Optimized CathEter vAlvular iNtervention)–TAVI registry. Hemolytic anemia was defined as (1) a drop in hemoglobin level by >2.0 g/dL within 3 months after the index TAVI procedure and (2) the diagnosis of mechanical hemolysis as the cause of anemia made by the attending physician and hematologist based on the presence of any 2 of the following criteria: (1) serum lactate dehydrogenase level >220 IU/L; (2) haptoglobin level <0.5 g/L; and (3) reticulocyte count ≥2%. Of the 1,070 patients, 18 (1.7%) patients developed hemolytic anemia after TAVI. These patients had a significantly lower prosthesis oversizing relative to native annulus (−3.7% [−5.9% to 0.1%] vs 7.5% [0.6% to 14.0%], p <0.001) and a higher prevalence of paravalvular leakage (PVL) ≥mild (mild PVL: 61.1% vs 12.4%; moderate-to-severe PVL: 16.7% vs 0.2%; p <0.001) than those without hemolytic anemia. PVL ≥mild was associated with a higher incidence of hemolytic anemia particularly in patients with oversizing of <−5% (33.3% vs 1.3%, p <0.001) and in those with −5%≤ oversizing <10% (8.3% vs 0.7%, p <0.001). In conclusion, the incidence of decompensated hemolytic anemia after S3UR implantation was not negligible, and the results of the present study support the importance of selecting a prosthesis size with a sufficient oversizing relative to native annulus to minimize residual PVL ≥mild leading to hemolytic anemia after TAVI. [Display omitted]

Phosphoenolpyruvate (PEP) is an intermediate metabolite of the glycolytic pathway and an in vivo high-energy phosphate compound. We have examined the protective effects of PEP on ischemia–reperfusion lung injury in isolated rabbits lungs perfused with a physiological salt solution. The lungs were divided into three treatment groups: (1) ischemia–reperfusion (IR), (2) ischemia–reperfusion with PEP treatment (PEP-IR), in which 1 mM PEP was pre-administered into the perfusate during the stable period, and (3) ventilation–perfusion continued without interruption (Cont). In the IR and PEP-IR groups, ventilation–perfusion was discontinued for about 60 min after a 30-min stable period and then restarted. The capillary filtration coefficients (Kfc) and pyruvate concentration in the perfusate were determined immediately before ischemia and 30 and 60 min after reperfusion. The left lungs were dried at the end of the experiment to calculate the tissue wet-to-dry weight ratio (W/D). The Kfc values after reperfusion were significantly higher in the IR group than in the other two groups. Pyruvate concentrations were significantly higher at three time-points in the PEP-IR group than in the other two groups. The W/D was significantly higher in the IR group than in the other two groups. Based on these results, we conclude that the administration of PEP prior to lung ischemia alleviates lung ischemia–reperfusion injury.

Background Isoflurane and sevoflurane protect lungs with ischemia–reperfusion (IR) injury. We examined the influence of desflurane on IR lung injury using isolated rabbit lungs perfused with a physiological salt solution. Methods The isolated lungs were divided into three groups: IR, desflurane-treated ischemia–reperfusion (DES-IR), and ventilation/perfusion-continued control (Cont) groups (n = 6 per group). In the DES-IR group, inhalation of desflurane at 1 minimum alveolar concentration (MAC) was conducted in a stable 30-min phase. In the IR and DES-IR groups, ventilation/perfusion was stopped for 75 min after the stable phase. Subsequently, they were resumed. Each lung was placed on a balance, and weighed. Weight changes were measured serially throughout this experiment. The coefficient of filtration (K fc ) was determined immediately before ischemia and 60 min after reperfusion. Furthermore, bronchoalveolar lavage fluid (BALF) was collected from the right bronchus at the completion of the experiment. After the completion of the experiment, the left lung was dried, and the lung wet-to-dry weight ratio (W/D) was calculated. Results The K fc values at 60 min after perfusion were 0.40 ± 0.13 ml/min/mmHg/100 g in the DES-IR group, 0.26 ± 0.07 ml/min/mmHg/100 g in the IR group, and 0.22 ± 0.08 (mean ± SD) ml/mmHg/100 g in the Cont group. In the DES-IR group, the K fc at 60 min after the start of reperfusion was significantly higher than in the other groups. In the DES-IR group, W/D was significantly higher than in the Cont group. In the DES-IR group, the BALF concentrations of nitric oxide metabolites were significantly higher than in the other groups. In the DES-IR group, the total amount of vascular endothelial growth factor in BALF was significantly higher than in the Cont group. Conclusions The pre-inhalation of desflurane at 1 MAC exacerbates pulmonary IR injury in isolated/perfused rabbit lungs.

PurposeTo investigate the effects of the intraoperative administration of Ringer’s solution with 1% glucose on the metabolism of glucose, lipid and muscle protein during surgery.MethodsThirty-one adult patients, American Society of Anesthesiologists physical status I or II, undergoing elective otorhinolaryngeal, head and neck surgeries were randomly assigned to one of two patient groups: those receiving acetated Ringer’s solution with 1% glucose (Group G) or those receiving acetated Ringer’s solution without glucose (Group R) throughout the surgical procedure. Plasma glucose was measured at anesthetic induction (T0), artery 1 h (T1), 2 h (T2), 3 h after anesthetic induction (T3) and at the end of surgery (T4). Plasma ketone bodies, insulin and 3-methylhistidine were measured at T0 and T4.ResultsThe intravenous infusion for patients in Group G and R was 6.1 ± 0.8 and 6.3 ± 1.7 ml/kg/h, respectively, with Group G patients receiving a dose of 4.1 g/h glucose. Plasma glucose levels were significantly higher in Group G than in Group R patients at T1, T2, T3 and T4; however, plasma glucose remained <150 mg/dl in both groups. The plasma concentration of ketone bodies was significantly higher (P < 0.05) in Group R than in Group G patients at T4. Changes in plasma 3-methylhistidine concentration was significantly lower in Group G than in Group R patients. These results indicate that acetated Ringer’s solution with 1% glucose decreased protein catabolism without hyperglycemia among the Group G patients.ConclusionThe infusion of a small dose of glucose (1%) during minor otorhinolaryngeal, head and neck surgeries may suppress protein catabolism without hyperglycemia and hypoglycemia.

PurposeWe conducted a randomized, double-blinded study to test our hypothesis that caudal blockade as preemptive analgesia for low back surgery might accelerate time to walking exercise following surgery and reduce postoperative analgesics, thereby attaining faster recovery of cognitive function.MethodsOur study included 51 elderly patients >70 years with American Society of Anesthesiologists (ASA) physical status 1–3, who underwent lumbosacral surgery under general anesthesia. After anesthetic induction and tracheal intubation, patients in the study group (group B) were injected with simple 0.5% bupivacaine [10 ml × height (m)] as a caudal block 15 min before surgical incision, whereas patients in the control group (group C) received normal saline. After surgery, patients had access to intravenous patient-administered analgesia (IV PCA), fentanyl, for postoperative pain relief. We assessed Mini-Mental State Examination (MMSE) scores before and after the surgery, values of visual analog scale (VAS) for postoperative analgesic status, fentanyl consumption during and for 3 days after surgery, and time to begin walking exercise after surgery.ResultsVAS value of group B patients was significantly lower than those in group C throughout the postoperative 48-h period (p < 0.005), and group B patients began walking exercise significantly earlier than those in group C [mean ± standard deviation (SD) 70.2 (14.3) in group C, and 61.9 (7.6) in group B; p = 0.0133]. Cognitive function level was higher in group B than in group C patients 24 h after operation.ConclusionsCaudal blockade as preemptive analgesia shortened the time to start walking exercise after surgery and accelerated recovery of postoperative cognitive function.

Data concerning the clinical effect of the latest-generation self-expandable transcatheter heart valve (Evolut FX) remain limited. We aimed to assess the in-hospital outcomes of 3 bioprosthetic valves (Evolut EPO, PRO+, and FX). We analyzed data from a Japanese multicenter registry involving 634 consecutive patients who underwent transcatheter aortic valve replacement with Evolut FX up until October 2023. Patients who underwent transcatheter aortic valve replacement with Evolut EPO between 2018 and 2020 (n = 1,128), and those with Evolut EPO+ between 2020 and 2023 (n = 1,696) served as the control groups. The exclusion criteria comprised patients on dialysis with a history of infective endocarditis or with insufficient data. Unmatched comparisons among the 3 valves were conducted, followed by a propensity score–matched comparison between Evolut EPO+ and FX. In the unmatched cohort, among the Evolut EPO, PRO+, and FX groups, all vascular complications (7.8% vs 5.2% vs 4.5%, respectively, p <0.01) and new pacemaker implantation rates (11.2% vs 6.1% vs 7.7%, respectively, p <0.01) differed significantly. In the propensity score–matched analysis, the rate of all bleeding events was significantly higher in the Evolut EPO+ group (11.0%) than in the FX group (7.0%) (p = 0.02), whereas all vascular complications (4.6% vs 4.6%, respectively, p = 1.00) and new pacemaker implantation (5.9% vs 7.6%, respectively, p = 0.28) rates were comparable. The incidence of stroke in the FX group was approximately half that of the EP+ group (3.7% vs 1.9%, p = 0.095), without statistical significance. In conclusion, compared with the Evolut EPO+, Evolut FX was associated with a lower incidence of in-hospital bleeding complications and may reduce the incidence of in-hospital stroke.

BackgroundCoaptation gap (CG) is one of the challenging anatomies of mitral transcatheter edge-to-edge repair (TEER), but its impact on patient outcomes is unclear. This study aimed to evaluate the impact of CG on procedural and clinical outcomes in patients with functional mitral regurgitation (MR).MethodsData from 2140 patients undergoing TEER for functional MR were analysed, focusing on the presence of CG, which is a missing leaflet coaptation between the anterior and posterior leaflets during systole. The primary outcome was a composite of death, heart failure hospitalisation and mitral valve reintervention.ResultsOf the 2140 patients, 219 (10%) had CG and 1921 (90%) did not, as assessed by baseline transoesophageal echocardiography. In patients with CG, baseline MR grade and New York Heart Association (NYHA) functional class were more severe, and long/wide clip types were used more frequently. Post-TEER, patients with CG had significantly lower achievement of MR grade ≤2+ (93%) and ≤1+ (65%) compared with patients without CG (97%, p<0.01; 82%, p<0.01, respectively). NYHA functional class at 1 year was similar in both groups. The cumulative incidence of the primary outcome was comparable between CG and non-CG groups (51% vs 53% at 3 years, p=0.71). While residual MR grade 2+ was associated with the higher primary outcome incidence compared with ≤1+ in patients without CG (p<0.01), no significant difference was found in patients with CG (p=0.51).ConclusionCG was associated with less MR reduction but with no clear difference in adverse clinical outcomes after TEER. Similar outcomes between residual MR grade 2+ and ≤1+ in CG patients highlight the importance of procedural endpoint in anatomically challenging cases.Trial registration numberUMIN000023653.

Background Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. Methods In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. Results Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0–1 ( P  = 0.026), non-peritoneal metastasis ( P  = 0.021), PD-L1 TPS ≥ 1 ( P  = 0.012), CPS ≥ 5 ( P  = 0.007) or ≥ 10 ( P  < 0.001) or MMR deficiency ( P  < 0.001). The HPD rate was significantly higher in patients with PS 2–3 ( P  = 0.026), liver metastasis ( P  < 0.001) and CPS < 10 ( P  = 0.048). Multivariate analysis revealed that CPS ( P  = 0.001) and MMR ( P  = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis ( P  < 0.001), peritoneal metastasis ( P  = 0.004) and CRP ( P  < 0.001). Conclusions PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. Clinical trial registration UMIN000032164.

BackgroundBody weight loss (BWL) after gastrectomy is associated with not only a deteriorated quality of life but also a poor prognosis. Oral nutritional supplements (ONS) may be used to minimize BWL, which is observed in the first 3 months after gastrectomy and becomes stable thereafter, although the results of several randomized trials remain controversial.MethodsWe performed a multicenter, open-label randomized controlled trial including 1003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the ONS group or the control group. In the former, 400 ml (400 kcal) per day for 12 weeks as enteral nutrition was planned, and the actual intake amount was recorded daily by patients themselves. The primary endpoint was BWL 1 year after gastrectomy.ResultsBWL data were available in 880 patients (ONS 437, control 443). BWL at 3 months was significantly lower in the ONS group than in the control group (7.1 ± 5.6% and 8.5 ± 5.8%, p = 0.0011). However, the difference gradually declined after 6 months and was not significant 1 year after surgery (9.3 ± 8.2% and 9.8 ± 8.7%, p = 0.37). In the ONS group, 50.4% of patients took more than 200 ml/day of ONS (average 301 ml) and showed significantly less BWL (8.2 ± 7.2%) at 1 year than the control (p = 0.0204).ConclusionThe administration of ONS for 12 weeks after gastrectomy did not improve BWL at 1 year. However, the improvement in BWL remained until 1 year after surgery in patients who took more than 200 kcal/day of ONS.

The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting. Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.