Effect of Sarcopenia on Pneumonia after Endoscopic Submucosal Resection in Patients Aged ≥65 Years: A Retrospective Study.

We aimed to investigate the association between sarcopenia and incidence of pneumonia after endoscopic submucosal dissection (ESD) in patients aged ≥65 years. Patients with (n = 1571) and without sarcopenia (n = 1718) who underwent ESD for gastric neoplasm were included. Propensity score matching (PSM) was performed between the groups (n = 785) at a 1:1 ratio. The primary endpoint was the effect of sarcopenia on the incidence of pneumonia after ESD. Among the included patients, 2.2% (n = 71) developed pneumonia after ESD. After PSM, the incidence rate of pneumonia was significantly higher in patients with sarcopenia than that in patients without sarcopenia (p = 0.024). Sarcopenia and age ≥73 years were significantly associated with the incidence of pneumonia (sarcopenia and age <73 years, odd ratio (OR) = 1.22 [95% confidence interval (CI): 0.46-3.22]; sarcopenia and age ≥73 years, OR = 3.92 [95% CI: 1.79-8.74]). Patients with sarcopenia had an increased risk of developing pneumonia after ESD, even after adjusting for other factors, resulting in a higher incidence of leukocytosis and a longer duration of post-ESD hospitalization. The combination of sarcopenia and age ≥73 years could be an effective predictive factor for screening high-risk groups for pneumonia after ESD.

Hyperammonemia induces microglial NLRP3 inflammasome activation via mitochondrial oxidative stress in hepatic encephalopathy.

BACKGROUND: The role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of hepatic encephalopathy (HE) is unclear. Mitochondrial reactive oxygen species (mtROS) is a signal for NLRP3 inflammasome activation. Therefore, we aimed to determine whether mtROS-dependent NLRP3 inflammasome activation is involved in HE, using in vivo and in vitro models. METHODS: Bile duct ligation (BDL) in C57/BL6 mice was used as an in vivo HE model. NLRP3 activation was assessed in the hippocampus. Immunofluorescence staining was performed to determine the cellular source of NLRP3 in the hippocampal tissue. For the in vitro experiment, BV-2 microglial cells were primed with lipopolysaccharide (LPS), followed by ammonia treatment. NLRP3 activation and mitochondrial dysfunction were measured. Mito-TEMPO was used to suppress mtROS production. RESULTS: BDL mice showed cognitive impairment with hyperammonemia. Both the priming and activation steps of NLRP3 inflammasome activation were processed in the hippocampus of BDL mice. Moreover, intracellular ROS levels increased in the hippocampus, and NLRP3 was mainly expressed in the microglia of the hippocampus. In LPS-primed BV-2 cells, ammonia treatment induced NLRP3 inflammasome activation and pyroptosis, with elevation of mtROS and altered mitochondrial membrane potential. Pretreatment with Mito-TEMPO suppressed mtROS production and the subsequent NLRP3 inflammasome activation and pyroptosis under LPS and ammonia treatment in BV-2 cells. CONCLUSIONS: Hyperammonemia in HE may be involved in mtROS overproduction and subsequent NLRP3 inflammasome activation. Further studies using NLRP3-specific inhibitor or NLRP3 knockout mice are needed to elucidate the important role of NLRP3 inflammasome in HE development.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

Effects of Perioperative Dexmedetomidine on Immunomodulation in Uterine Cancer Surgery: A Randomized, Controlled Trial.

OBJECTIVE: Dexmedetomidine has sympatholytic, anti-inflammatory, and analgesic effects and may exert anti-tumor effect by acting on α2A adrenoreceptor. We investigated whether perioperative dexmedetomidine preserves immune function in patients undergoing uterine cancer surgery. METHODS: One hundred patients were randomly assigned to the control or dexmedetomidine groups (50 patients each). Dexmedetomidine was infused at rates of 0.4 µg/kg/h intraoperatively and 0.15 µg/kg/h during the first 24 h postoperatively. The primary outcome was natural killer (NK) cell activity, which was measured preoperatively and 1, 3, and 5 days postoperatively. The inflammatory response was measured by interleukin-6, interferon-γ, and neutrophil/lymphocyte ratio, and pain scores and opioid consumption were assessed. Cancer recurrence or metastasis and death were evaluated 2 years postoperatively. RESULTS: NK cell activity decreased postoperatively in both groups and changes over time were not different between groups (P=0.496). Interferon-γ increased postoperatively in the dexmedetomidine group, whereas it maintained at the baseline value in the control group. Change in interferon-γ differed significantly between groups (P=0.003). Changes in interleukin-6 and neutrophil-lymphocyte ratio were comparable between groups. Both pain score with activity during the first 1 h and opioid consumption during the first 1-24 h postoperatively were lower in the dexmedetomidine group. Rates of cancer recurrence/metastasis (16.3% vs. 8.7%, P=0.227) and death within 2 years postoperatively (6.7% vs. 2.2%, P=0.318) were not different between groups. CONCLUSIONS: Perioperative dexmedetomidine had no favorable impacts on NK cell activity, inflammatory responses, or prognosis, whereas it increased interferon-γ and reduced early postoperative pain severity and opioid consumption in uterine cancer surgery patients.

Combination of Static Echocardiographic Indices for the Prediction of Fluid Responsiveness in Patients Undergoing Coronary Surgery: A Pilot Study.

We investigated the role of echocardiographic indices consisting of left ventricular end-diastolic area (LVEDA) in combination with Doppler-derived surrogates of diastolic compliance and filling (E/E', E'/S', E'/A'; early transmitral flow velocity (E), tissue Doppler-derived early (E') diastolic, late (A') diastolic, or peak systolic (S') velocity of the mitral annulus) in predicting fluid responsiveness in off-pump coronary surgery. Hemodynamic and echocardiographic variables were prospectively assessed under general anesthesia before and after a fluid challenge of 6 mL/kg during apnea at atmospheric pressure in 64 patients with LV ejection fraction ≥40%. Forty patients (63%) were fluid responders (≥15% increase in stroke volume index). E/E' and E'/S' could predict fluid responsiveness with area under the receiver operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.56-0.85; p = 0.006) and 0.68 (95% CI, 0.54-0.82; p = 0.017), respectively. The combination of LVEDA and E/E' showed incremental predictive ability for fluid responsiveness compared with LVEDA (AUROC, 0.60; p = 0.170) or pulse pressure variation (AUROC, 0.70; p = 0.002), yielding the highest AUROC of 0.78 (95% CI, 0.66-0.90; p < 0.001). The combined index of echocardiographic variables reflecting LV dimension (LVEDA) and diastolic compliance and filling (E/E') is a potentially useful predictor of fluid responsiveness.