Suppressive effect of the anesthetic propofol on the T cell function and T cell-dependent immune responses.

General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.

Incidence and characteristics of early elevation of cardiac troponin I after intrathoracic surgery: A single-center retrospective observational study.

The early elevation of cardiac troponins within 24 hours after noncardiac surgery is reportedly associated with increased postoperative morbidities. Several predisposing factors, including the frequent occurrence of hypoxia and increased pulmonary arterial pressure, may likely contribute to this elevation, especially after intrathoracic surgery. Therefore, this retrospective study aimed to elucidate the incidence and characteristics of the early elevation of cardiac troponin I after intrathoracic surgery. This study included 320 patients who underwent intrathoracic surgery between January 1, 2018, and June 30, 2021. Specific perioperative variables were retrospectively collected from their electrical clinical records. The serum concentration of high-sensitivity cardiac troponin I (hs cTnI) was measured twice immediately after the intensive care unit arrival and on the following day. We grouped these patients into two: the early elevation of hs cTnI (EECT) group (hs cTnI value > 26.2 ng/L by at least 1 measurement) and the non-early elevation (non-EECT) group. Patient characteristics were then compared between these groups. The hs cTnI level elevated within 24 hours postoperatively in 103 patients (32.2%). In univariate analysis, intraoperative variables, including the duration of unilateral ventilation (199.2 minutes, P = .0025) and surgery (210.6 minutes, P = .0012), estimated blood loss volume (406.7 mL, P = .0022), percentage of stored red blood cell (RBC) transfusion (10.7%, P = .0059), and percentage of lobectomy or combination of other lung resection types (88.3%, P = .00188), were significantly higher in the EECT group than in the non-EECT group. In the log-rank test, prolonged hospitalization was more prevalent in the EECT group (P = .0485). Furthermore, multivariate analysis revealed 3 independent risk factors for the early elevation of hs cTnI: coexisting chronic renal failure (odds ratio [OR], 3.25), lobectomy or combined resections (OR, 2.65), and stored RBC transfusion (OR, 3.41). The early elevation of hs cTnI commonly occurs after intrathoracic surgery, with an incidence of 32.2%. Its 3 independent risk factors are coexisting chronic renal failure, lung resection type, and stored RBC transfusion.

Hemodynamic deterioration due to increased anterior and posterior cardiac compression during posterior spinal fusion for scoliosis with pectus excavatum.

Hemodynamics may deteriorate during the perioperative period when performing posterior spinal fusion in patients with pectus excavatum and scoliosis. A 13-year-old teenager diagnosed with Marfan syndrome had thoracic scoliosis and pectus excavatum. Thoracic scoliosis was convex to the right, and a right ventricular inflow tract stenosis was observed due to compression induced by the depressed sternum. The patient underwent T3-L4 posterior spinal fusion surgery for scoliosis. Deterioration of hemodynamics was observed when the patient was placed in the prone position or when the thoracic spine was corrected to the left front. Postoperative computed tomography examination showed that the mediastinal space was narrowed due to the corrected thoracic spine. Special attention should be paid in the following cases: (1) severe pectus excavatum, (2) right ventricular inflow tract compression due to depressed sternum on the left side, (3) correction of the thoracic spine on the left front, (4) long-term surgery, and (5) risk of massive bleeding. In some cases, pectus excavatum surgery should be prioritized.

Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response.

Glucocorticoids (GCs), immunosuppressive, and anti-inflammatory agents have various effects on T cells. However, the long-term influence of GCs on the T cell-mediated immune response remain to be elucidated. We demonstrated that the administration of GC during the TCR-mediated activation phase induced long-lasting suppression of glycolysis, even after the withdrawal of GC. The acquisition of the effector functions was inhibited, while the expression of PD-1 was increased in CD8 T cells activated in the presence of GC. Furthermore, adoptive transfer experiments revealed that GC-treated CD8 T cells reduced memory T cell formation and anti-tumor activity. These findings reveal that GCs have long-lasting influence on the T cell-mediated immune response via modulation of T cell metabolism.

T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses.

Although the important roles of glycolysis in T cells have been demonstrated, the regulatory mechanism of glycolysis in activated T cells has not been fully elucidated. Furthermore, the influences of glycolytic failure on the T cell-dependent immune response in vivo remain unclear. We therefore assessed the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. The helper T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine acts as a metabolic hub in activated T cells, since the TCR-dependent increase in intracellular glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation and differentiation.

Hemolytic reaction in the washed salvaged blood of a patient with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: In patients with paroxysmal nocturnal hemoglobinuria (PNH), the membrane-attack complex (MAC) formed on red blood cells (RBCs) causes hemolysis due to the patient's own activated complement system by an infection, inflammation, or surgical stress. The efficacy of transfusion therapy for patients with PNH has been documented, but no studies have focused on the perioperative use of salvaged autologous blood in patients with PNH. CASE PRESENTATION: A 71-year-old man underwent total hip replacement surgery. An autologous blood salvage device was put in place due to the large bleeding volume and the existence of an irregular antibody. The potassium concentration in the transfer bag of salvaged RBCs after the wash process was high at 6.2 mmol/L, although the washing generally removes > 90% of the potassium from the blood. This may have been caused by continued hemolysis even after the wash process. Once activated, the complement in patients with PNH forms the MAC on the RBCs, and the hemolytic reaction may not be stopped even with RBC washing. CONCLUSIONS: Packed RBCs, instead of salvaged autologous RBCs, should be used for transfusions in patients with PNH. The use of salvaged autologous RBCs in patients with PNH should be limited to critical situations, such as massive bleeding. Physicians should note that the hemolytic reaction may be present inside the transfer bag even after the wash process.

Influence of Nutritional Management and Rehabilitation on Physical Outcome in Japanese Intensive Care Unit Patients: A Multicenter Observational Study.

BACKGROUND: There is lack of evidence regarding nutritional management among intensive care unit (ICU) patients in a population with relatively low body mass index. Therefore, we conducted an observational study to assess the nutritional management in Japanese ICUs. Also, we investigated the impact of nutritional management and rehabilitation on physical outcome. METHODS: The study population comprised 389 consecutive patients who received mechanical ventilation for at least 24 h and those admitted to the ICU for > 72 h in 13 hospitals. The primary outcomes were caloric and protein intake in ICU on days 3 and 7, and at ICU discharge. The secondary outcome was the impact of nutritional management and rehabilitation on physical status at ICU discharge. We defined good physical status as more than end sitting and poor physical status as bed rest and sitting. We divided the participants into 2 groups, namely, the good physical status group (Good group) and poor physical status group (Poor group) for analysis of the secondary outcome. Data were expressed as median (interquartile range). RESULTS: The median amount of caloric intake on days 3 and 7, and at ICU discharge via enteral and parenteral routes were 8.4 (3.1-15.6), 14.9 (7.5-22.0), and 11.2 (2.5-19.1) kcal/kg/day, respectively. The median amount of protein intake on days 3 and 7, and at ICU discharge were 0.2 (0-0.5), 0.4 (0.1-0.8), and 0.3 (0-0.7) g/kg/day, respectively. The amount of caloric intake on day 3 in the Poor group was significantly higher than that of the Good group (10.1 [5.8, 16.2] vs. 5.2 [1.9, 12.4] kcal/kg/day, p < 0.001). The proportion of patients who were received rehabilitation in ICU in the Good group was significantly higher than that of the Poor group (92 vs. 63%, p < 0.001). The multivariate analysis revealed that caloric intake on day 3 and rehabilitation in ICU were considered independent factors that affect physical status (OR 1.19; 95% CI 1.05-1.34; p = 0.005 and OR 0.07; 95% CI 0.01-0.34; p = 0.001). CONCLUSIONS: The caloric and protein intakes in Japanese ICUs were 15 kcal/kg/day and 0.4 g/kg/day, respectively. In addition, critically ill patients might benefit from low caloric intake (less than 10 kcal/kg/day) until day 3 and rehabilitation during ICU stay.

Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage.

Carbon monoxide (CO) causes not only acute fatal poisoning but also may cause a delayed neurologic syndrome called delayed encephalopathy (DE), which occasionally occurs after an interval of several days to several weeks post-exposure. However, the mechanisms of DE have not been fully elucidated. This study aimed to clarify the pathophysiology of CO-induced DE and its distinctive features compared with hypoxemic hypoxia. Rats were randomly assigned to three groups; the air group, the CO group (exposed to CO), and the low O2 group (exposed to low concentration of O2). Impairment of memory function was observed only in the CO group. The hippocampus tissues were collected and analyzed for assessment of CO-induced changes and microglial reaction. Demyelination was observed only in the CO group and it was more severe and persisted longer than that observed in the low O2 group. Moreover, in the CO group, decreased in microglial cell numbers were observed using flow cytometry, and microglia with detached branches were observed were observed using immunohistochemistry. Conversely, microglial cells with shortened branches and enlarged somata were observed in the low O2 group. Furthermore, mRNAs encoding several neurotrophic factors expressed by microglia were decreased in the CO group but were increased in the low O2 group. Thus, CO-induced DE displayed distinctive pathological features from those of simple hypoxic insults: prolonged demyelination accompanying a significant decrease in microglial cells. Decreased neurotrophic factor expression by microglial cells may be one of the causes of CO-induced DE.

Effect of dexmedetomidine on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy under total intravenous anesthesia: A randomized, double blinded placebo controlled clinical trial.

STUDY OBJECTIVE: To study the effects of intraoperative dexmedetomidine on the intraocular pressure (IOP) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) under propofol-remifentanil anesthesia. DESIGN: Double-blind, randomized controlled trial. SETTING: Operating room. PATIENTS: Forty consenting male patients aged ≥20 to <80 years with American Society of Anesthesiologists physical status classes I and II. INTERVENTIONS: The patients were randomly assigned to either dexmedetomidine (DEX) (n = 20) or control (n = 20) group. Anesthesia was induced and maintained using propofol, remifentanil, and rocuronium. In the dexmedetomidine group, dexmedetomidine was administered at 0.4 µg/kg/h immediately after anesthesia induction until the end of the surgery, whereas normal saline was administered as placebo in the control group. MEASUREMENTS: IOP was measured using a rebound tonometer. Time points of measuring IOP were as follows: T1: before anesthesia induction, T2: 5 min after intubation, T3: 60 min after placing patient in the Trendelenburg position, T4: 120 min after placing patient in the Trendelenburg position, T5: 180 min after placing patient in the Trendelenburg position, T6: 5 min after placing patient in a horizontal position, T7: 5 min after extubation, and T8: 30 min after extubation. MAIN RESULTS: A linear mixed model analysis demonstrated a significant intergroup difference in IOP over time and during pneumoperitoneum in the steep Trendelenburg position. IOP at T5 was significantly lower in the dexmedetomidine group than in the control group even after post-hoc analysis in the steep Trendelenburg position periods with Bonferroni correction. CONCLUSIONS: Dexmedetomidine combined with propofol decreases IOP in the steep Trendelenburg position during RALRP.

Real-time ultrasound-guided infraorbital nerve block to treat trigeminal neuralgia using a high concentration of tetracaine dissolved in bupivacaine.

Background Trigeminal neuralgia is a neuropathic disorder characterized by episodes of intense pain in the face. Drug therapy is the first choice of treatment. However, in cases where drug therapy are contraindicated due to side effects, patients can get pain relief from lengthy neurosurgical procedures. Alternatively, a peripheral trigeminal nerve block can be easily performed in an outpatient setting. Therefore it is a useful treatment option for the acute paroxysmal period of TN in patients who cannot use drug therapy. We performed real-time ultrasound guidance for infraorbital nerve blocks in TN patients using a high concentration of tetracaine dissolved in bupivacaine. In this report, we examine the efficacy of our methods. Patients As approved by the Institutional Review Board, the medical records in our hospital were queried retrospectively. Six patients with TN at the V2 area matched the study criteria. All patients could not continue drug therapy with carbamazepine due to side effects and they received an ultrasound-guided infraorbital nerve block with a high concentration of tetracaine dissolved in bupivacaine. Methods The patient was placed in the supine position and the patient's face was sterilized and draped. An ultrasound system with a 6-13 MHz linear probe was used with a sterile cover. The probe was inserted into the horizontal plane of the cheek just beside the nose and was slid in the cranial direction to find the dimple of the infraorbital foramen. The 25G 25 mm needle was inserted from the caudal side just across from the probe using an out-of-plane approach. To lead the needle tip to the foramen, needle direction was corrected with real-time ultrasound guidance. After the test block with lidocaine (2%, 0.5 ml), a solution of tetracaine (20 mg) dissolved in bupivacaine (0.5%, 0.5 ml) was injected. During each injection, the spread of the agent around the nerve was confirmed using ultrasound images. Results Ten blocks were performed for six patients. Immediately after the procedure, all 10 blocks produced analgesia and relieved the pain. In the three blocks, pain was experienced in a new trigger point outside of the infraorbital nerve region (around the back teeth) within a week after the block and pain were relieved using other treatment. Two patients developed small hematomas in the cheek but they disappeared in a week. All patients did not complain about other side effects including paraesthesia, hyperpathia, dysaesthesia, or double vision. Hypoaesthesia to touch and pain in the infraorbital region were observed in all blocks after 2 weeks. Conclusions We performed real-time ultrasound-guided infraorbital nerve block for TN with a high concentration of tetracaine dissolved in bupivacaine. Our method achieved a high success rate and there were only minor and transient side effects. Implications Real-time ultrasound-guided infraorbital nerve block is one of the useful options to treat the acute paroxysmal period of TN at the infraorbital nerve area. Ultrasound-guided injections may become the standard practice for injecting peripheral trigeminal nerves. Using this high concentration of tetracaine as a neurolytic agent is effective and appears to have only minor side effects.