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Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO 2 :FiO 2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.

Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP [PAI < 1] and normal PP [PAI ≥ 1]) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP.

Background Camptocormia, a postural deformity seen in Parkinson’s disease (PD), complicates general anesthesia, especially airway management, owing to severe spinal flexion in advanced stages. Case presentation We report the anesthetic management of a 76-year-old man with PD who developed severe long-seated forward flexion with the face buried between the knees, from camptocormia and multiple spinal surgeries. Removal of the exposed spinal implants was necessary, and general anesthesia was planned. Anesthesia was administered in the right lateral position from induction to awakening. Video laryngoscopy enabled successful intubation, and remimazolam with flumazenil ensured good recovery without complications. Conclusions This case demonstrates the feasibility of managing the airway and administering anesthesia in the right lateral position in patients with PD with severe long-seated forward flexion. Video-laryngoscopy and remimazolam with flumazenil offer advantages in such cases, although further studies are required to validate their broader applications.

 Peripheral perfusion monitoring is crucial for the management of critically ill patients because abnormal peripheral perfusion is associated with a poor prognosis. The peripheral perfusion index (PPI), derived from pulse oximetry, quantifies peripheral perfusion but varies across fingers. A pulse oximeter probe may cause burns when worn at the same site. Therefore, changing the site has been recommended. However, changes in PPI values owing to probe replacement reduce the reliability of clinical and research applications. No two fingers with equivalent PPI values have been identified yet. This study assessed the interfinger differences in PPI by measuring the five fingers simultaneously and identified the two fingers with the least fluctuation in values.  A total of 30 healthy volunteers were included in this single-center prospective exploratory study. For PPI measurements, the pulse amplitude index (PAI) was measured using a pulse oximeter on a bedside monitor (Life Scope PT; Nihon Kohden Corp., Tokyo, Japan). The tape-type disposable pulse oximeter probes were attached to each of the five fingertips of the dominant hand, and measurements were conducted in three rooms with different temperatures (16°C, 22°C, and 28°C) to induce thermoregulatory responses and capture a wide range of PAI values. The primary endpoint was the PAI in pairs of two fingers each (a total of 10 pairs). Paired t-tests with Bonferroni correction were used to compare finger pairs, with statistical significance defined as < 0.005. The combination with the least difference in PAI was the index-ring finger combination (0.07% ± 1.89%, = 0.74), followed by the middle-ring finger (0.45% ± 1.93%, = 0.03) and index-middle finger combinations (0.52% ± 2.05%, = 0.02). All other finger combinations showed statistically significant differences ( < 0.001).  PPI values measured using the pulse oximeter showed the smallest interfinger difference between the index and ring fingers. If changing the finger to which the probe is attached during clinical or research use is needed, it may be possible to consistently measure the PPI values by alternately attaching the probe to the index and ring fingers.

Background The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock. Methods This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed. Results Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson’s r  = 0.490 [95% confidence interval: 0.263–0.666]; P  < 0.001 and r  = 0.479 [95% confidence interval: 0.240–0.664]; P  < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1–24.7]; P  = 0.007 and estimate, 26.9 [95% confidence interval: 11.0–42.7]; P  = 0.001, respectively) adjusting for severity score and renal function. Conclusions Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.

Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition. Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl). The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

Background The current study was carried out to determine whether fasudil hydrochloride (fasudil), a Rho-kinase inhibitor, has myocardial postconditioning (PostC) activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP) channels. Methods Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg) or high-dose (0.5 mg/kg) fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD), an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR). Results Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively) compared with that in the control (42 ± 7%). Under hyperglycemia, low-dose fasudil (40 ± 11%) and diazoxide (44 ± 14%) could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%). 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%). Conclusion Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

Background The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP). Methods Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Results Under normoglycemia, both 30 μg/kg milrinone (29 ± 12%) and 10 μg/kg levosimendan (33 ± 13%) reduced infarct size compared with that in the control (58 ± 7%). Under hyperglycemia, milrinone (34 ± 13%) reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9%) reduced infarct size compared with that in the hyperglycemic control (58 ± 13%). All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Conclusion Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.

Background Prolonged heart rate-corrected QT (QTc) interval is frequently observed in subarachnoid hemorrhage (SAH). This study was conducted to determine the relationship between QTc interval and neurological outcome during the acute posthemorrhagic period after aneurysmal SAH. Methods We studied 71 patients undergoing surgery who were admitted within 24 h after the onset of aneurysmal SAH. Standard 12-lead electrocardiography was performed on admission (T1) and at 1 and 7 days after operation (T2 and T3). QT intervals were corrected by heart rate according to the Fridericia formula. The Glasgow Coma Scale (GCS) score was calculated over the period T1–T3. Neurological outcome was assessed using the Glasgow Outcome Scale at hospital discharge. Results Among the 71 patients, 31 had an unfavorable neurological outcome. Although QTc interval prolongation improved in patients with a good outcome, QTc interval prolongation continued in patients with an unfavorable outcome. The areas under the receiver–operator characteristic curves showed that the QTc and GCS score at T3, and the Hunt and Hess grade were significant predictors of an unfavorable neurological outcome. The threshold value, sensitivity, and specificity for the QTc at T3 were 448 ms, 73% [95% confidence interval (CI), 68–78], and 93% (95% CI, 90–96), respectively. Conclusion This study confirms that QTc interval prolongation continues in the SAH patients with an unfavorable outcome but that QTc interval prolongation improves in patients with a good outcome, suggesting that a QTc interval of more than 448 ms at 7 days after operation is a predictor of neurological outcome after SAH.

We sought to evaluate the levels of intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, as a predictor of 28-day mortality and bowel ischemia in septic shock patients. In this preliminary prospective observational study, 57 adult septic shock patients under mechanical ventilation were enrolled. Serum I-FABP levels and prognostic biomarkers were recorded upon intensive care unit (ICU) admission. The overall 28-day mortality rate of participants was 23% (13/57). Non-survivors displayed significantly higher lactate (p=0.009), I-FABP (p=0.012), and N-terminal pro-B-type natriuretic peptide (p=0.039) levels compared to survivors. Only I-FABP was associated with 28-day mortality (odds ratio, 1.036; 95% confidence interval, 1.003–1.069; p=0.031) in a multiple logistic regression analysis adjusted for the Acute Physiology and Chronic Health Evaluation II score. When divided into low and high I-FABP groups based on the optimum cut-off value of 19.0ng/mL for predicting 28-day mortality, high-I-FABP patients had a significantly higher incidence of non-occlusive mesenteric ischemia (NOMI) (2% [1/43] vs 29% [4/14]; p=0.011). I-FABP level at ICU admission can serve as a predictor of 28-day mortality in septic shock patients and is associated with the incidence of NOMI. •We studied intestinal fatty acid-binding protein and mortality in septic shock.•I-FABP level was a predictor of 28-day mortality in septic shock patients.•Predictive ability of ICU baseline I-FABP in septic shock patients was evaluated.