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.

Perioperative Anaphylaxis in Japanese Secondary Care Institutions: Incidence, Causes, and the Imperative for Improved Diagnostic Practices.

Background This research investigates the incidence, suspected causes, and diagnostic procedures for perioperative anaphylaxis (POA), a potentially severe complication, in secondary care hospitals across Japan. Methodology We surveyed Saiseikai hospitals and gathered data on surgical procedures, POA occurrences, potential triggers, and diagnostic methods. Results Among 70,523 surgeries, seven were associated with POA, resulting in an approximate incidence rate of 0.01%. Rocuronium was the most commonly suspected trigger, followed by sugammadex, latex, and angiography contrast agents. Despite the importance of skin tests as the most basic and crucial diagnostic method, they were conducted in only three instances. No in vitro tests for drug identification were conducted, and in four cases, the cause was determined merely based on the timing of drug administration, indicating significant diagnostic limitations. Conclusions The study underscores the critical situation in Japan regarding insufficient diagnostic practices and difficulties in identifying triggering drugs rather than the consistent prevalence of POA in secondary care facilities. The findings emphasize the need for improved diagnostic proficiency and more rigorous drug identification practices to ensure prompt and accurate POA diagnosis. It is essential to conduct further research and interventions to increase patient safety during the perioperative period in secondary care settings.

Pediatric Neurogenic Pulmonary Edema After Brain Tumor Removal Complicated with Severe Myocardial Injury: A Case Report.

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.

Efficacy of high-frequency spinal cord stimulation for fibromyalgia syndrome in two cases: case reports.

BACKGROUND: Reports on the effectiveness of spinal cord stimulation (SCS) for the alleviation of fibromyalgia syndrome (FMS) pain are scarce. We report two cases of effective high-frequency SCS at 1000 Hz against upper- and lower-limb pain in patients with FMS. CASE PRESENTATION: Two women with widespread pain were diagnosed with FMS and the pain gradually worsened. A 1-week SCS trial was conducted in each patient. In both cases, the patients complained of unpleasant sensations during 10-Hz SCS. However, the pain was alleviated after 1000-Hz stimulation without irritation. Therefore, leads and a generator were implanted, after which they felt almost no pain. Moreover, the dose of the oral medication could be reduced and the patients returned to their daily lives. CONCLUSION: SCS at 1000 Hz may effectively treat pain associated with FMS. Therefore, performing an SCS trial for patients with FMS with intractable pain might be worthwhile.

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.

Anti-inflammatory effects of dopamine on microglia and a D1 receptor agonist ameliorates neuroinflammation of the brain in a rat delirium model.

Microglia play a central role in neuroinflammatory processes by releasing proinflammatory mediators. This process is tightly regulated along with neuronal activities, and neurotransmitters may link neuronal activities to the microglia. In this study, we showed that primary cultured rat microglia express the dopamine (DA) D1 receptor (D1R) and D4R, but not D2R, D3R, or D5R. In response to a D1R-specific agonist SKF-81297 (SKF), the cultured microglia exhibited increased intracellular cAMP levels. DA and SKF suppressed lipopolysaccharide (LPS)-induced expression of interleukin-1ß (IL-1ß) and tumor necrosis α (TNFα) in cultured microglia. Microglia in the normal mature rat prefrontal cortex (PFC) were sorted and significant expression of D1R, D2R, and D4R was observed. A delirium model was established by administering LPS intraperitoneally to mature male Wistar rats. The model also displayed sleep-wake disturbances as revealed by electroencephalogram and electromyogram recordings as well as increased expression of IL-1ß and TNFα in the PFC. DA levels were increased in the PFC 21 h after LPS administration. Increased cytokine expression was observed in sorted microglia from the PFC of the delirium model; however, TNFα, but not IL-1ß expression, was abruptly decreased 21 h after LPS administration in the delirium model, whereas DA levels were increased. A D1R antagonist SCH23390 partially abolished the TNFα expression change. This suggests that endogenous DA may play a role in suppressing neuroinflammation. Administration of the DA precursor L-DOPA or SKF to the delirium model rats inhibited the expression of IL-1ß and TNFα. The simultaneous administration of clozapine, a D4R antagonist, strengthened the suppressive effects of L-DOPA. These results suggest that D1R mediates the suppressive effects of LPS-induced neuroinflammation, in which microglia may play an important role. Agonists for D1R may be effective for treating delirium.

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.

Enhanced recovery from fulminant myocarditis by treatment with the combined use of the Impella left ventricular assist device with extracorporeal membrane oxygenation: a case series.

BACKGROUND: We experienced two adult cases of fulminant myocarditis with severe cardiogenic shock where Impella left ventricular assist device [left ventricle (LV)-Impella] was concomitantly used with venoarterial extracorporeal membrane oxygenation (V-A ECMO). CASE PRESENTATION: A 67-year-old man and a 49-year-old man with fulminant myocarditis were transferred to our hospital with mechanical support of V-A ECMO and IABP. Impella 5.0 and Impella CP were implanted 21 h and 17 h after establishing V-A ECMO for each case. Within 1 week, the patients' LV function progressively improved. Then the Impellas were withdrawn after discontinuing V-A ECMO. They were discharged from the intensive care unit within the following 8 days. CONCLUSIONS: The optimal introducing timing of LV-Impella is not currently precise. However, this case report suggests that the initiation of LV-Impella within at least 24 h after establishing V-A ECMO may be acceptable for the recovery of cardiac function.

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.

Perioperative management of emergent cesarean section in a patient with peripartum cardiomyopathy and orthopnea: a case report.

Perioperative management of pregnant women with heart failure is difficult. Management of anesthesia in pregnant women is especially difficult because all of the currently available choices present challenges. We report a patient with peripartum cardiomyopathy (PPCM) who required an emergent cesarean section and discuss the possible tactics for managing anesthesia. A 40-year-old primipara with severe cardiac and respiratory failure required an emergent cesarean section at 39+1 gestational weeks. Her left ventricular ejection fraction was between 10% and 15%, and she had orthopnea. General anesthesia was planned after inserting sheaths for percutaneous cardiopulmonary support from the femoral artery and vein. However, when the patient was asked to lie down on the operation bed, she panicked and resisted because of labor pain and dyspnea. Therefore, anesthesia was induced instead of the initial plan. Finally, we successfully managed the anesthesia and delivered the newborn. There are no alternatives to general anesthesia in patients with PPCM presenting with orthopnea. Anesthesia induction in the supine position is impossible in such patients owing to dyspnea. Anesthesia should be started with light sedation in the sitting position, and ketamine or low-dose remifentanil may be an option to maintain maternal hemodynamics and prevent neonatal asphyxia.

Treatment and prognosis of patients with both cancer and impaired decision-patient with both cancer and dementia making as a symptom of dementia.

AIM: In our aging society, the number of patients with both cancer and dementia has recently been increasing. One of the major clinical questions is whether patients with dementia could receive appropriate cancer treatment. The purpose of this study is to know the prognosis of patients with both cancer and impaired decision-making as a symptom of dementia, and to discuss the proper cancer treatment of the patients with dementia. METHODS: Patients newly diagnosed with both cancer and impaired decision-making as a symptom of dementia at Ehime University Hospital between January 2010 and December 2016 were reviewed. The data of patients with cancer were retrospectively analyzed using an electronic medical record system. RESULTS: In total, 9354 cases were diagnosed with cancer in the Ehime University Hospital over 7 years, and only 105 (1.1%) cases with impaired decision-making as a symptom of dementia were recorded by medical professionals, probably due to poor attention to the cognitive functions of patients with cancer. Analysis of the cancer prognosis of these patients showed that a better prognosis was seen in patients with any therapeutic interventions than in those with no treatment for the cancer itself. However, the prognosis of patients was not significantly different between standard and non-standard treatments. CONCLUSIONS: This study suggests that the poor interest of medical professionals in the cognitive function of patients with cancer at the time of diagnosis of cancer and the lack of any guidelines for patients with both cancer and dementia are major problems in our aging society. Geriatr Gerontol Int 2021; 21: 1105-1110.

Independent Predicting Factors for Subcutaneous Emphysema Associated with Robotic-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Single-Center Study.

OBJECTIVES: Subcutaneous emphysema (SCE) is a complication associated with laparoscopic surgery. Severe SCE complicated by excessive hypercarbia may afford detrimental effects in surgical patients with cardiac dysfunction. Robotic-assisted laparoscopic radical prostatectomy (RALP) has several predisposing factors that contribute to SCE. The main purpose of our single-center retrospective study was to determine the preoperative and intraoperative predicting factors for SCE associated with RALP and to determine the actual incidence of SCE. METHODS: In total, 229 adult male patients underwent standardized RALP for prostate cancer over the period of 1 May 2016 to 31 October 2018 at the Ehime University Hospital. We reviewed electronic clinical records for individual characteristics including age, body weight, height, coexisting disorders, preoperative ASA physical status, and the length of postoperative hospital stay. We also reviewed surgical and anesthetic records for the operation time, anesthetic method, and the partial pressure of end-tidal CO2 (PetCO2) during RALP. To determine the presence of SCE, we examined supine chest X-rays obtained after the completion of surgery. RESULTS: We found 55 cases (24.0%) of SCE. Multiple logistic regression analysis showed that a BMI < 25 kg/m2 (OR: 3.0, 95% CI: 1.25-7.26) and a maximum value of PetCO2 of 46 mmHg or greater (OR: 23.3, 95% CI: 8.22-66.1) were independent predicting factors for SCE. CONCLUSION: These two predicting factors may be helpful to recognize the occurrence of SCE. Anesthesiologists should protect against SCE progression with the earlier detection of SCE for safe anesthetic management in patients undergoing RALP.

Takotsubo Cardiomyopathy Induced by Very Low-Dose Epinephrine Contained in Local Anesthetics: A Case Report.

BACKGROUND Takotsubo cardiomyopathy is a reversible left ventricular dysfunction triggered by emotional or physical stress. Perioperatively, takotsubo cardiomyopathy is sometimes induced by various psychological factors, such as stress from surgery, and non-psychological factors, such as epinephrine misinjection. This report describes a case of takotsubo cardiomyopathy induced by the administration of very low-dose epinephrine contained in a local anesthetic. CASE REPORT A 78-year-old woman with mycosis in the maxillary sinus was scheduled to undergo endoscopic sinus surgery. After the submucosal injection of 3 mL of local anesthetic (lidocaine, 0.5%; epinephrine, 1: 200 000) immediately before the incision, her heart rate and blood pressure reached 135 beats per min and 254/185 mmHg, respectively, inducing ventricular tachycardia. After receiving 50 mg of lidocaine, her cardiac rhythm resumed a normal sinus rhythm, without cardioversion. As her hemodynamics stabilized, the surgical procedure began as planned. Postoperative electrocardiography, echocardiography, and coronary arteriography demonstrated takotsubo cardiomyopathy. Subsequently, her cardiac movement gradually improved, and she was discharged from the hospital on postoperative day 9. CONCLUSIONS To the best of our knowledge, this is the first reported case in which a very small amount of epinephrine (0.015 mg) induced takotsubo cardiomyopathy. Therefore, epinephrine should be used cautiously, especially in the nasal mucosa, vaginal mucosa, and uterus, where blood flow is relatively high. If unexpected hemodynamic alterations and ST-segment abnormalities occur after epinephrine administration, asymptomatic takotsubo cardiomyopathy should be considered.

Disseminated intravascular coagulation as a complication of bursitis: angiogenesis and repetitive bleeding as potential factors for disseminated intravascular coagulation: a case report.

BACKGROUND: Malignant tumors, such as acute leukemia and solid cancers, frequently cause disseminated intravascular coagulation. However, cases of disseminated intravascular coagulation as a complication of bursitis were not reported previously. CASE PRESENTATION: A 72-year-old Japanese woman was scheduled to undergo resection of a rapidly growing subcutaneous tumor-like lesion on her left back. Preoperative blood tests suggested disseminated intravascular coagulation. The resected lesion was cystic tumor containing a hematoma. After the operation, the patient completely recovered from disseminated intravascular coagulation, indicating that disseminated intravascular coagulation in this case was caused by the tumor. Pathological examination of the resected tumor revealed considerable fibrin deposition and angiogenesis on the cyst wall, which was presumably a response to inflammation and indicated presence of repetitive intratumoral bleeding, subsequently leading to a diagnosis of chronic hemorrhagic bursitis. CONCLUSIONS: Clinicians should note that, despite being benign, soft-tissue tumors accompanied by inflammation with angiogenesis and repetitive intratumoral bleeding can cause disseminated intravascular coagulation, albeit rarely.

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems.

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.

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.

A case report of thrombotic complete obstruction of the ascending aorta as a complication of Venoarterial extracorporeal membrane oxygenation support: steps to prevent thrombosis.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis. CASE PRESENTATION: A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated; therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation. CONCLUSIONS: To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.

A novel MRGPRX2-targeting antagonistic DNA aptamer inhibits histamine release and prevents mast cell-mediated anaphylaxis.

Anaphylaxis during general anaesthesia is a significant clinical challenge for anaesthesiologists. Approximately 50% of perioperative anaphylaxis cases lack the presence of specific IgE antibodies. Mas-related G-protein coupled receptor X2 (MRGPRX2) in humans and its mouse orthologue Mas-related G-protein coupled receptor B2 (Mrgprb2) are crucial receptors in non-IgE-dependent histamine release. Anaesthetics such as rocuronium and atracurium cause perioperative anaphylaxis by activating histamine release via the Mrgprb2 pathway. We hypothesized that antagonistic DNA aptamers that target MRGPRX2 can prevent perioperative anaphylaxis. Selection of a DNA aptamer that specifically binds MRGPRX2 was achieved by using our modified Systematic Evolution of Ligands by Exponential enrichment (SELEX) approach. Our SELEX process used MRGPRX2-proteoliposomes synthesised by a wheat germ cell-free system as templates. The activity of the selected aptamer to inhibit histamine release from MRGPRX2-activated mast cells and in an anaphylaxis rat model transplanted with this cell line was examined. Our selection process identified aptamer-X35 with the sequence 5'-ATGACCATGACCCTCCACACTGTAGGCACCACGGGTCCCTGGCAGTTAAAAGTACGTTTGTCAGACTGTGGCAGGGAAACA-3'. In silico 2D modelling of aptamer-X35 revealed a structure with a small loop and a long stem. Aptamer-X35 inhibited histamine release from mast cells by 70%. Subcutaneous injection of 30 nmol of aptamer-X35 inhibited the anaphylactic reaction in the rat anaphylaxis model. This study demonstrated that aptamer-X35 selected by the modified SELEX approach reduced histamine release by inhibiting the MRGPRX2 pathway. Overall, our findings establish aptamer-X35 as a potential therapeutic candidate against perioperative anaphylaxis.