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.

B lymphocytopenia and Bregs in a not-to-die murine sepsis model.

Sepsis is a leading cause of mortality in intensive care units due to multi-organ failure caused by dysregulated immune reactions. In this study, kinetic changes in the immune system were analyzed for 72 h in cecal ligation and puncture (CLP)-induced septic mice while preventing animal death by keeping body temperature. Increase of myeloid cells and decrease of B cells in circulation at 6 h after CLP were markedly observed. At the same time point, interleukin (IL)-10 expressing CD5+ regulatory B cells (Bregs) appeared. IL-10 and programmed death-ligand 1 (PD-L1) mRNA as well as IL-1ß, IL-6 and interferon γ (IFNγ) mRNA was increased in the spleen at 6 h. A gradual decrease in Bcl-2 and abrupt increase of Bim expression in the spleen at the late phase were also found. These results showed that B lymphocytopenia with the appearance of Bregs is the earliest event, likely leading to immunoparalysis in sepsis.

Adverse events associated with continuous interscalene block administered using the catheter-over-needle method: a retrospective analysis.

BACKGROUND: Continuous interscalene block is widely used for pain management in shoulder surgery. However, continuous interscalene block performed using the catheter-through-needle method is reportedly associated with adverse events such as pericatheter leakage of the local anesthetic, phrenic nerve paralysis, and hoarseness. Because we expected that the catheter-over-needle method would reduce these adverse events, we examined cases in which continuous interscalene block was performed using the catheter-over-needle method to determine what adverse events occurred and when. METHODS: We retrospectively reviewed the anesthesia and medical records of adult patients who underwent catheter insertion to receive a continuous interscalene block performed using the catheter-over-needle method at our hospital from July 2015 to July 2017. RESULTS: During the surveillance period, 122 adult patients underwent catheter insertion to receive a continuous interscalene block administered using the catheter-over-needle method. No case of pericatheter local anesthetic leakage was observed. Adverse events, such as dyspnea, hoarseness, insufficient anesthetic effect, dizziness, cough reflex during drinking, or ptosis, were observed in 42 patients (34.4%; 95% confidence interval 26-42.7). Most of the adverse events occurred on postoperative day 2. The median time between surgery and the onset of adverse events was 28.5 h. CONCLUSIONS: The catheter-over-needle method may prevent the pericatheter leakage of the local anesthetic. However, adverse events occurred in more than one-third of the patients. During continuous interscalene block, patients must be carefully observed for adverse events, especially on postoperative day 2. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry on August 13th, 2019 ( UMIN000037673 ).

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.

Prediction of the service life of surgical instruments from the surgical instrument management system log using radio frequency identification.

BACKGROUND: Bar code- or radio frequency identification (RFID)-based medical instrument management systems have gradually been introduced in the field of surgical medicine for the individual management and identification of instruments. We hypothesized that individual management of instruments using RFID tags can provide previously unavailable information, particularly the precise service life of an instrument. Such information can be used to prevent medical accidents caused by surgical instrument failure. This study aimed to predict the precise service life of instruments by analyzing the data available in instrument management systems. METHODS: We evaluated the repair history of instruments and the usage count until failure and then analyzed the data by the following three methods: the distribution of the instrument usage count was determined, an instrument failure probability model was generated through logistic regression analysis, and survival analysis was performed to predict instrument failure. RESULTS: The usage count followed a normal distribution. Analysis showed that instruments were not used uniformly during surgery. In addition, the Kaplan-Meier curves plotted for five types of instruments showed significant differences in the cumulative survival rate of different instruments. CONCLUSIONS: The usage history of instruments obtained with RFID tags or bar codes can be used to predict the probability of instrument failure. This prediction is significant for determining the service life of an instrument. Implementation of the developed model in instrument management systems can help prevent accidents due to instrument failure. Knowledge of the instrument service life will also help in developing a purchase plan for instruments to minimize wastage.

Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea.

Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1ß (IL-1ß), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor ß1 (TGFß1), interleukin-6 (IL-6), and tumor necrosis factor α at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGFß1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.

Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model.

CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died after 45 d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45+ cells, including natural killer cells and CD8+ lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.

Lower limb perfusion during robotic-assisted laparoscopic radical prostatectomy evaluated by near-infrared spectroscopy: an observational prospective study.

BACKGROUND: Decreased perfusion in the lower extremities is one of the several adverse effects of placing patients in a lithotomy or Trendelenburg position during surgery. This study aimed to evaluate the effects of patient positioning in lower limb perfusion patients undergoing robotic-assisted laparoscopic radical prostatectomy (RARP) using near-infrared spectroscopy (NIRS). METHODS: This observation study comprised 30 consenting males with American Society of Anaesthesiologists physical status classes I and II (age range, ≥20 to < 80 years). Regional saturation of oxygen measurements was obtained using an INVOS™ oximeter (Somanetics, Troy, MI, USA). A NIRS sensor was positioned on the surface of the skin at the mid-diaphyseal region of the calf muscles (the gastrocnemius and soleus), over the posterior compartment, in the right lower leg. Regional saturation of oxygen (rSO2) was sampled during the following time points: before and 5 min after induction of anaesthesia (T0,T1); 5 min after establishment of pneumoperitoneum in a 0° lithotomy position (T2); 5 min after a 25° Trendelenburg position (T3); 30, 60, 90 and 120 min after pneumoperitoneum in a Trendelenburg position (T4, T5, T6 and T7, respectively); after desufflation in a supine position (T8); and after tracheal extubation (T9). RESULTS: Lower limb perfusion evaluated by NIRS was increased after induction of anaesthesia and maintained during steep Trendelenburg positions in RARP patients with no risk for lower limb compartment syndrome (LLCS) (T0:65 ± 7.2%, T1:69 ± 6.1%, T2:70±:6.1%, T3:68 ± 6.7%, T4:66 ± 7.5%, T5:67 ± 6.9%, T6:68 ± 7.2%, T8:73 ± 7.2%, T9:71 ± 7.9%, respectively). CONCLUSIONS: Lower limb perfusion evaluated by NIRS was maintained during the RARP procedure. Correct patient positioning and careful assessment of risk factors such as vascular morbidity could be important for the prevention of LLCS during RARP.

Effects of hypnotic bromovalerylurea on microglial BV2 cells.

An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level.

[Refractory Hypotension Induced by Continuous Phonation during Spinal Anesthesia in a Patient Suffering from Severe Aortic Stenosis.]

An 85-year-old man suffering from severe aortic ste- nosis underwent transurethral resection of the prostate (TUR-P) under spinal anesthesia producing analgesia below T7. TUR-P was performed uneventfully with repeated injections of phenylephrine 0.05 to 0.1 mg which kept systolic blood pressure around 100 mmHg. Refractory hypotension occurred in the intensive care unit two hours after spinal anesthesia when the patient continued to speak ; systolic blood pressure fell to 60 mmHg from 100 mmHg, and discontinuance of speak- ing restored the blood pressure, although injections of phenylephrine had no effect Four episodes of hypoten- sion occurred before the movement of lower extremi- ties was restored, 5.5 hours after spinal anesthesia. Refractory hypotension might have been the result of a decrease in venous return caused by increased intra- thoracic pressure during speaking, and sympatholysis and decreased abdominal compression by spinal anes- thesia combined with complicating cardiac dysfunction.

Suppression of peritoneal thickening by histamine in a mouse model of peritoneal scraping.

BACKGROUND: Inflammatory reactions play an important role in peritoneal sclerosis in patients on peritoneal dialysis. Since histamine affects inflammatory reactions and immune responses, we investigated effects of intraperitoneal administration of histamine on peritonitis induced by mechanical scraping in mice. METHODS: After anesthesia, the right peritoneum was scraped 90 times over 1 min, and bilateral peritonea were observed by light microscopy after 7 days. RESULTS: Thickness of the peritoneal membrane on the right side was 174 ± 77 µm (mean ± SD, n = 8), while that on the left side was 24 ± 19 µm. Intraperitoneal administration of histamine (0.3 or 1.0 mmol/L, 0.5 mL each) twice daily for 7 days after scraping decreased thickness of the right peritoneum to 42 and 43 % of that in saline-injected animals, respectively (P < 0.01), although histamine (0.1 mmol/L) did not affect it. Promethazine (5 nmol, twice daily for 7 days), a histamine H1 receptor antagonist, abolished the amelioration caused by histamine (1.0 mmol/L). Neither ranitidine (15 nmol), a histamine H2 receptor antagonist, nor thioperamide (7.5 nmol), a histamine H3/H4 receptor antagonist, affected the outcome in histamine-treated mice. CONCLUSION: These findings indicate that histamine H1 action partly prevents the development of peritoneal fibrosis caused by mechanical scraping.

[Efficacy and safety of sugammadex (Org 25969) in reversing moderate neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 98 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional doses of rocuronium or vecuronium for maintenance of moderate block. At T2 reappearance sugammadex 0-4.0 mg . kg-1 was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 82.1 min in the placebo group to 1.8 min in the 4.0 mg . kg-1 sugammadex group. For the vecuronium-induced neuromuscular block, it decreased from 83.2 min in the placebo group to 2.1 min in the sugammadex 4.0 mg . kg-1 group. Plasma concentrations of sugammadex were approximately dose proportional over the dose range of 0.5 to 4.0 mg . kg-1 and independent of the neuromuscular blocking agents used. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients.

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.

[The looks of Gendai Kamada].

We realized the looks of Gendai Kamada. At first, we found in a figure, in "Seishu Hanaoka and His Surgery" by Syuzo Kure, that the portrait described as that of Gendai is his father's. And we discovered the illustrations that illustrate the looks of Gendai in "Gekakihaizufu", which was a textbook of clinical anesthesia and surgery, printed in 1840. Using these illustrations, we realized the looks of Gendai Kamada.

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.