Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

Detection of carbon dioxide embolism by transesophageal echocardiography during transanal/perineal endoscopic surgery: a pilot study.

The transanal/perineal (ta/tp) endoscopic approach has been widely used for anorectal surgery in recent years, but carbon dioxide embolism is a possible lethal complication. The frequency of this complication in this approach is not known. In this study, we investigated the frequency of intraoperative (including occult) carbon dioxide embolism using transesophageal echocardiography. Patients who underwent surgery via the ta/tp approach and consented to participate were included. Intraoperative transesophageal echocardiography was used to observe the right ventricular system in a four-chamber view. Changes in end-tidal carbon dioxide (EtCO2), oxygen saturation (SpO2), and blood pressure were taken from anesthesia records. Median maximum insufflation pressure during the ta/tp approach was 13.5 (12-18) mmHg. One patient (4.8%) was observed to have a bubble in the right atrium on intraoperative transesophageal echocardiography, with a decrease in EtCO2 from 39 to 35 mmHg but no obvious change in SpO2 or blood pressure. By lowering the insufflation pressure from 15 to 10 mmHg and controlling bleeding from the veins around the prostate, the gas rapidly disappeared and the operation could be continued. Among all patients, the range of variation in intraoperative EtCO2 was 5-22 mmHg, and an intraoperative decrease in EtCO2 of > 3 mmHg within 5 min was observed in 19 patients (median 5 mmHg in 1-10 times).Clinicians should be aware of carbon dioxide embolism as a rare but potentially lethal complication of anorectal surgery, especially when using the ta/tp approach.

Postoperative Noninvasive Hemoglobin Monitoring Is Useful to Prevent Unnoticed Postoperative Anemia and Inappropriate Blood Transfusion in Patients Undergoing Total Hip or Knee Arthroplasty: A Randomized Controlled Trial.

INTRODUCTION: Postoperative nadir hemoglobin (Hb) is related to a longer length of stay for geriatric patients undergoing orthopedic surgery. We investigated whether postoperative pulse Hb (SpHb) measurement is useful for avoiding anemia and inappropriate blood transfusion after total hip arthroplasty and total knee arthroplasty. MATERIAL AND METHODS: This prospective randomized controlled study included 150 patients randomly assigned to receive blood transfusion, either guided by SpHb monitoring (SpHb group) or based on the surgeons' experience (control group). The target laboratory Hb value was set to >8 g/dL at postoperative day 1 (POD1). The primary endpoints were the product of total time and degree of SpHb <8 g/dL (area under SpHb 8 g/dL) during the period up to POD1 and the incidence of laboratory Hb <8 g/dL at POD1. The secondary endpoints were the amount of blood transfusion and inappropriate blood transfusion, which was defined as allogeneic blood transfusion unnecessary in a case of SpHb >12 g/dL or delayed transfusion in a case of SpHb <8 g/dL. RESULTS: The area under SpHb 8 g/dL was 37.6 ± 44.1 g/dL-min (5 patients) in the control group and none in the SpHb group (P = .0281). There was 1 patient with Hb <8 g/dL at POD1 in the control group. There was no difference in laboratory Hb levels and the amount of blood transfusion. Forty-one patients (19 in the control group and 22 in the SpHb group) received an allogeneic blood transfusion. Among these patients, 7 in the control group and none in the SpHb group received inappropriate blood transfusion (P = .0022). DISCUSSION: The SpHb monitoring could reduce unnoticed anemia, which may prevent complications and be useful in avoiding unnecessary and excessive blood transfusion. CONCLUSION: Postoperative SpHb monitoring decreased the incidence of transient, unnoticed anemia during the period up to POD1 and inappropriate blood transfusion.

Cerebral hemorrhagic infarction was diagnosed subsequently after high-amplitude slow waves detected on processed electroencephalogram during sedation: a case report.

BACKGROUND: Continuous electroencephalogram (EEG) monitoring is useful for assessing the level of sedation and detecting non-convulsive epileptic seizures and cerebral ischemia in the intensive care unit. This report describes a case of cerebral hemorrhagic infarction diagnosed after the detection of high-amplitude slow waves on processed EEG during sedation. CASE PRESENTATION: A 68-year-old man who underwent cardiac surgery was sedated in the intensive care unit following an invasive procedure. High-amplitude slow waves appeared on processed EEG monitoring before the detection of anisocoria. Computed tomography revealed a cerebral hemorrhagic infarction. CONCLUSIONS: In the management of critically ill patients, continuous EEG monitoring with forehead electrodes may be useful in the early detection of brain lesions.

Third-Generation Hydroxyethyl Starch Causes Dose-Dependent Coagulopathy in Patients Undergoing Off-Pump Coronary Artery Bypass with Continuation of Preoperative Aspirin.

BACKGROUND: We aimed to evaluate the effect of third-generation hydroxyethyl starch (6% HES 130/0.4) on hemostasis and perioperative blood loss in patients undergoing off-pump coronary artery bypass (OPCAB) with continuation of preoperative aspirin. METHODS: Forty-nine consecutive patients, who underwent OPCAB at a single institution between November 1, 2014 and March 31, 2016, were included. Coagulation tests, including thromboelastometry and clinical data of all patients, retrospectively were collected from anesthesia and medical records. RESULTS: The total amount of intraoperative crystalloid and HES was 2057.5 ± 771.6 mL (N = 32) and 1090.6 ± 645.0 mL (N = 32), respectively. In the coagulation pathway, the change ratio of fibrinogen concentration, prothrombin time, and fibrinogen thromboelastometry-maximum clot firmness (FIBTEM-MCF) significantly correlated with HES (P < 0.001, P = 0.00131, and P < 0.001, respectively), but not with crystalloid. In the coagulation pathway concerning interaction with platelets, the change ratio of platelet count, extrinsic thromboelastometry-clotting formation time (EXTEM-CFT), and EXTEM-MCF significantly were correlated with HES (P < 0.001, P < 0.001, and P < 0.001, respectively), but not with crystalloid. At chest closure, the hematocrit decreased in a dose-dependent manner with HES (P < 0.001), but not with crystalloid administration. There was an association between the change ratio of hematocrit and EXTEM-MCF (P = 0.00122). However, intra-postoperative blood loss was not correlated with HES 130/0.4 or crystalloid administration. CONCLUSION: We found that 6% HES 130/0.4 prolonged coagulation testing in a dose-dependent manner due to hemodilution but did not increase blood loss in patients undergoing OPCAB with continuation of preoperative aspirin.

Anesthetic management of multiple acyl-coenzyme A dehydrogenase deficiency in a series of surgeries under general anesthesia: a case report.

BACKGROUND: Glutaric acidemia is a type of multiple acyl-coenzyme A dehydrogenase deficiency, an inborn error in fatty acid metabolism. In patients with glutaric acidemia, during the perioperative period, prolonged fasting, stress, and pain have been identified as risk factors for the induction of metabolic derangement. This report describes the surgical and anesthetic management of a patient with glutaric acidemia. CASE PRESENTATION: A 56-year-old male patient with glutaric acidemia type 2 underwent a series of surgeries. During the initial off-pump coronary artery bypass surgery, the patient developed renal failure due to rhabdomyolysis upon receiving glucose at 2 mg/kg/min. However, in the second laparoscopic cholecystectomy, rhabdomyolysis was avoided by administering glucose at 4 mg/kg/min. CONCLUSIONS: To avoid catabolism in patients with glutaric acidemia, appropriate glucose administration is important, depending on the surgical risk.

Preoperative elevated E/e' (≥ 15) with preserved ejection fraction is associated with the development of postoperative heart failure in intermediate-risk non-cardiac surgical patients.

PURPOSE: Left ventricular diastolic dysfunction is an independent risk factor for adverse cardiovascular morbidities and mortalities in cardiovascular and high-risk surgical patients. However, there were only a few investigations among intermediate-risk surgical patients. This study aimed to investigate postoperative heart failure (HF) in intermediate-risk surgical patients who had preoperative diastolic dysfunction with preserved ejection fraction (EF). METHODS: Consecutive patients underwent intermediate-risk surgery between January 2016 and December 2018 were retrospectively evaluated. Patients with preserved EF were divided into three groups using one of the parameters of diastolic function: the ratio of early diastolic filling velocity to the peak diastolic velocity of mitral medial annulus (E/e') ≥ 15, E/e' between 8 and 15, and E/e' < 8. Postoperative HF was defined as clinical symptoms and radiological evidence and low SpO2 less than 93%. The primary outcome was the incidence of postoperative HF and its relation to preoperative E/e'. Chi-squared test, unpaired t test with Welch's correction, and multivariate logistic regression were used for analysis. RESULTS: In total, 965 patients were included in the final analysis. Postoperative HF developed in 36/965 (3.7%) patients with preserved EF. The incidence of postoperative HF was stratified according to the E/e', and the rates of HF occurrence in patients with E/e' < 8, 8-15, and ≥ 15 were 1.8%, 2.7%, and 15%, respectively (P < 0.01). CONCLUSION: Preoperative elevated E/e' (≥ 15) was associated with the development of postoperative HF in intermediate-risk surgical patients with preserved EF.

Preoperative Left Ventricular Diastolic Dysfunction Is Associated with Pulmonary Edema after Carotid Endarterectomy.

This retrospective study was aimed to investigate the association between preoperative left ventricular (LV) cardiac function and the incidence of postoperative pulmonary edema (PE) in patients undergoing carotid endarterectomy (CEA). Most patients undergoing CEA for carotid artery stenosis have concomitant heart diseases, leading to hemodynamic instability that can cause postoperative cardiac complications such as cardiac heart failure. LV diastolic function has recently been recognized as an independent predictor of adverse cardiac events in patients undergoing cardiovascular surgery. We analyzed clinical data from the anesthetic and medical records of 149 consecutive patients who underwent CEA at our university hospital between March 2012 and March 2018. LV systolic and diastolic function were evaluated by ejection fraction and the ratio of LV early diastolic filling velocity to the peak velocity of mitral medial annulus (E/e'). Postoperative PE was diagnosed based on chest X-ray and arterial gas analysis by two independent physicians. Postoperative PE was developed in four patients (2.8%). Patients with postoperative PE were not related to preoperative low ventricular ejection fraction, but had a significantly higher E/e' ratio than those without PE (P = 0.01). Furthermore, there was an increasing trend of PE according to the E/e' category. Preoperative LV diastolic function evaluated by E/e' was associated with the development of postoperative PE in patients who underwent CEA. The results suggest that the evaluation of LV diastolic dysfunction could be possibly useful to predict PE in patients undergoing CEA.

Risk Vessels of Retropharyngeal Hematoma During Stellate Ganglion Block.

BACKGROUND AND OBJECTIVE: Bleeding into the retropharyngeal space is a potential complication in stellate ganglion block (SGB). Retropharyngeal hematoma formation is considered to be due to damage of small arteries in the region, although only scanty details of the region are available. The aim of this study was to map the risk blood vessels in the retropharyngeal space to avoid accidental damage during SGB. METHODS: Contrast-enhanced 3-dimensional computed tomography images performed on 80 patients were reanalyzed retrospectively to construct detailed map of cervical blood vessels that are prone to damage and bleeding during SGB. RESULTS: Of the 160 bilateral necks, 6 (3.8%) and 82 (51.3%) small arteries were identified in the medial portions of the ventral surface of the transverse processes of the sixth and seventh cervical vertebrae, respectively. In particular, 5 of the 6 small arteries detected in the medial portion of the ventral surface of the transverse process of the sixth cervical vertebra were the inferior thyroid artery (ITA). Of the 160 vertebral arteries, 2 arteries were missing, 4 (2.5%) entered the transverse foramen of the fifth cervical vertebra, whereas 1 artery (0.6%) entered the transverse foramen of the fourth cervical vertebra. CONCLUSIONS: Three-dimensional computed tomography identified the ITA in the medial portion of the ventral surface of the transverse process of the sixth cervical vertebra. The risk vessels of retropharyngeal hematoma during SGB could include the ITA.

Association between Preoperative Cardiac Left Ventricular Dysfunction and Perioperative Intraaortic Balloon Pump in Patients Undergoing Off-Pump Coronary Artery Bypass Surgery.

BACKGROUND: Prophylactic use of intraaortic balloon pump (IABP) reduces hospital mortality in patients with left ventricular (LV) systolic dysfunction undergoing coronary artery bypass surgery (CABG); however, its association in patients with LV diastolic dysfunction is unclear. This retrospective study investigated the association between preoperative LV function and perioperative use of IABP in patients undergoing off-pump CABG (OPCAB) at a university hospital. METHODS: 100 consecutive patients who underwent OPCAB between January 1, 2011 and August 31, 2014 were studied. Preoperative LV function was categorized into four groups based on LV systolic and diastolic function determined with preoperative transthoracic echocardiography. The use of IABP was reviewed from medical records. The Mann-Whitney test, Pearson chi-square test, or Fisher exact test were used. RESULTS: Patients were categorized into the following groups: normal LV function (n = 43), isolated LV systolic dysfunction (n = 13), isolated LV diastolic dysfunction (n = 21), and combined LV systolic and diastolic dysfunction (n = 14). Intraoperative IABP use was significantly more frequent in patients with isolated LV systolic dysfunction, isolated LV diastolic dysfunction, and combined LV systolic and diastolic dysfunction than in those with normal LV function (P < .05). Furthermore, IABP was used more frequently in patients who developed combined LV systolic and diastolic dysfunction postoperatively (P < .05). Conclusion: Not only the presence of preoperative systolic dysfunction but also LV diastolic dysfunction in the presence of normal LV systolic function were associated with increased use of IABP during and after OPCAB.

Neurally Mediated Syncope During Cesarean Delivery: A Case Report.

A 28-year-old woman with preeclampsia at 32 weeks of gestation underwent a cesarean delivery under spinal anesthesia. Administration of nitroglycerin at 200 µg to relax uterine smooth muscles and the application of fundal pressure led to severe bradycardia and loss of consciousness, followed by cardiac arrest. Delivery was completed immediately and recovery was achieved 10 seconds later following cardiopulmonary resuscitation. Neurally mediated syncope was considered the cause of cardiac arrest. Anesthetists should be aware of the potential risk during cesarean delivery following the administration of nitroglycerin, fundal pressure, regional anesthesia, and hypovolemia because of preeclampsia.

Clinical implication of blood glucose monitoring in general dental offices: the Ehime Dental Diabetes Study.

OBJECTIVE: We examined whether general dentists can contribute to the detection of patients with undiagnosed diabetes and prediabetes by monitoring blood glucose in dental clinics. RESEARCH DESIGN AND METHODS: A total of 716 patients who visited clinics for dental treatment were enrolled and classified into 3 groups (mild, moderate, and severe) according to Kornman's criteria for periodontitis. The correlations between the casual blood glucose level, presence or absence of the history of diabetes, and/or severity of periodontitis were evaluated. RESULTS: 68 patients (9.5%) had hyperglycemia (blood glucose ≥200 mg/dL). Of these patients, 20 (29.4%) did not have a history of diabetes. Blood glucose tended to be higher with greater periodontitis severity. Of the 3 groups, the severe periodontitis group had the highest proportion of patients with hyperglycemia (p<0.0001). CONCLUSIONS: Patients with dental problems could be screened for diabetes, especially undiagnosed diabetes. General dentists could function as practitioners to screen for diabetes. TRIAL REGISTRATION NUMBER: UMIN-CTR 000014877.

Spontaneous recovery of paraplegia caused by spinal epidural hematoma after removal of epidural catheter.

We report a patient who developed paraplegia caused by a spinal epidural hematoma after removal of an epidural catheter, which resolved spontaneously. A 60-year-old woman underwent thoracoscopic partial resection of the left lung under general anesthesia combined with epidural anesthesia. She neither was coagulopathic nor had received anticoagulants. Paraplegia occurred 40 minutes after removal of the epidural catheter on the first postoperative day. Magnetic resonance images revealed a spinal epidural hematoma. Surgery was not required as the paraplegia gradually improved until, within 1 hour, it had completely resolved. Hypoesthesia had completely resolved by the third postoperative day.

[Anesthetic management of total hysterectomy in a patient with pulmonary thromboembolism].

We report anesthetic management of a 38-year-old woman with pulmonary thromboembolism for total hysterectomy. She had been taking oral contraceptives for adenomyosis of the uterus. She had thrombi in the arteries from pulmonary trunk to bilateral main pulmonary arteries. Thrombolytic and anticoagulant therapies did not decrease the thrombi. Removal of the swollen uterus suspected to be the origin of the thrombi, rather than thromboembolectomy, was scheduled. Cannulation for percutaneous cardiopulmonary support was set up just in case of hemodynamic derangement, before the surgery. Cardiac contraction was evaluated with transesophageal echocardiography during the surgery. There was no untoward perioperative event. Pulmonary thromboembolectomy was not done because the postoperative CT revealed shrinkage of the pulmonary thrombi after anticoagulation treatment.

Recovery of train-of-four ratio to 0.70 and 0.90 is delayed in type 2 diabetes with vecuronium-induced neuromuscular block.

CONTEXT: The recovery profile of train-of-four ratio to more than 0.70 in patients with diabetes mellitus has not been well investigated. OBJECTIVE: Our primary objective was to evaluate the spontaneous recovery profile of neuromuscular block by vecuronium until train-of-four ratio more than 0.90 in patients with type 2 diabetes mellitus compared with controls, using first dorsal interosseous electromyography. DESIGN: Single-centre prospective case-control study. SETTING: The operating theatres of Fukuoka University Hospital. PATIENTS: Fourteen adults with type 2 diabetes mellitus (diabetes mellitus group) and 14 control patients (control group) were included in this study. INTERVENTION: Evoked responses to train-of-four stimuli were measured by electromyography at the first dorsal interosseous muscle. General anaesthesia was induced with propofol, fentanyl and remifentanil. Vecuronium (0.1  mg kg) was administered to all patients. Anaesthesia was maintained with propofol, fentanyl and remifentanil. The neuromuscular block was assessed until spontaneous recovery to train-of-four ratio more than 0.90. MAIN OUTCOME MEASURES: Recovery times to train-of-four ratio 0.70 and 0.90. RESULTS: Recovery times to train-of-four ratio 0.70 and 0.90 were significantly longer in the diabetes mellitus group than the control group (P = 0.041 and P = 0.027, respectively). The time from train-of-four ratio 0.25 to 0.90 was also significantly longer in the diabetes mellitus group than the control group (P = 0.029). In five of 14 patients in the diabetes mellitus group, the time from train-of-four ratio 0.25 to 0.90 was longer than 60  min, which is longer than the duration of action of neostigmine. The time from train-of-four ratio 0.25 to 0.90 was longer than 60  min in only one of 14 in the control group. CONCLUSION: Recovery times to train-of-four ratio 0.70 and 0.90 were delayed in patients with type 2 diabetes mellitus. Neuromuscular block by vecuronium should be carefully monitored in patients with type 2 diabetes mellitus until recovery of train-of-four ratio to a safe level is confirmed.

Effect of CCL2 antisense oligodeoxynucleotides on bacterial translocation and subsequent sepsis in severely burned mice orally infected with Enterococcus faecalis.

Severely burned mice are susceptible to sepsis stemming from Enterococcus faecalis translocation due to the impaired generation of M1 macrophages (M1MΦs) in local translocation sites. In our previous studies, CCL2 has been characterized as a major effector molecule on the burn-associated generation of M2MΦs, an inhibitor cell type for resident MΦ conversion into M1MΦs. In this study, we tried to protect burned mice orally infected with E. faecalis utilizing CCL2 antisense oligodeoxynucleotides (ODNs). We show that M2MΦs in mesenteric lymph nodes (MLNs) were not demonstrated in burned mice treated with CCL2 antisense ODNs. M1MΦs were not induced by heat-killed E. faecalis from resident MΦs transwell-cultured with mesenteric lymph node macrophages (MLN-MΦs) from burned mice, while M1MΦs were induced by the same antigen from resident MΦs transwell-cultured with MΦs which were isolated from burned mice treated with CCL2 antisense ODNs. Bacterial growth in MLNs was shown in burned mice orally infected with a lethal dose of E. faecalis. However, after the same infection, sepsis did not develop in burned mice treated with CCL2 antisense ODNs. These results indicate that bacterial translocation and subsequent sepsis are controlled in burned mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing CCL2 antisense ODNs.

M2b monocytes predominated in peripheral blood of severely burned patients.

Severely burned patients were shown to be carriers of M2 monocytes, and all of the monocytes isolated from peripheral blood of severely burned patients (19 of 19 patients) were demonstrated as M2b monocytes (IL-12(-)IL-10(+)CCL1(+) monocytes). Low levels of M2a (IL-12(-)IL-10(+)CCL17(+) monocytes) and M2c monocytes (IL-12(-)IL-10(+)CXCL13(+) monocytes) were demonstrated in peripheral blood of severely burned patients (M2a, 2 of 19 patients; M2c, 5 of 19 patients). M2b, M2a, and M2c monocytes were not detected in peripheral blood of healthy donors. However, M2b monocytes appeared when healthy donor monocytes were cultured in media supplemented with burn patient serum (15%). CCL2 was detected in sera of all burn patients, and M2b monocytes were not generated from healthy donor monocytes cultured with media containing 15% burn patient sera that were previously treated with anti-CCL2 mAb. In addition, M2b monocytes were generated from healthy donor monocytes in cultures supplemented with rCCL2. These results indicate that M2b monocytes are predominant in peripheral blood of severely burned patients who are carriers of CCL2 that functions to stimulate monocyte conversion from resident monocytes to M2b monocytes.

Enterococcus faecalis translocation in mice with severe burn injury: a pathogenic role of CCL2 and alternatively activated macrophages (M2aMphi and M2cMphi).

Here, we investigated a role of CCL2 on the increased susceptibility of severely burned mice to Enterococcus faecalis translocation. After inoculation of Mphi from MLMphi of normal mice, 80% of the SCIDbgMN mice orally infected with the lethal dose of E. faecalis survived, and all mice inoculated with MLMphi from thermally injured mice died. At this time, SCIDbgMN mice inoculated with MLMphi from thermally injured CCL2(-/-) mice were shown to be resistant (90% survival). M1Mphi were not induced by E. faecalis antigen in cultures of MLMphi from thermally injured wild-type mice, and MLMphi from thermally injured CCL2(-/-) mice converted to M1Mphi after the antigen stimulation. MLMphi from wild-type mice 2 days postburn injury possessed M2a- and M2cMphi properties, and those from mice 7-21 days postburn injury carried M2bMphi properties. However, MLMphi from thermally injured CCL2(-/-) mice did not show any typical properties for M2a- or M2cMphi. CCL17 and CXCL13 (biomarkers for M2a- and M2cMphi), but not CCL1 (a biomarker of M2bMphi), were produced by MLMphi from thermally injured CCL2(-/-) mice treated with rCCL2. These results indicate that CCL2 converts resident MLMphi to M2a- and M2cMphi, detected early after burn injury, and decreases host antibacterial innate immunity against sepsis stemming from oral E. faecalis infection.

Gr-1(+)CD11b(+) cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice.

Using a mouse model of thermal injury, we studied why antimicrobial peptides are not produced at the burn-site tissues and how this defect contributes to the increased susceptibility to Pseudomonas aeruginosa burn-wound infection. Logarithmic growth of P. aeruginosa was demonstrated locally (at the burn site) and systemically (in circulation) in thermally injured mice exposed to 10(2) CFU/mouse of the pathogen beneath the burn wound. However, neither systemic nor local growth of the pathogen was observed in sham burn mice when they were infected intradermally with 10(6) CFU/mouse P. aeruginosa. Murine beta-defensins (MBDs) were detected in the skin homogenates of sham burn mice. However, the amounts of MBDs were reduced greatly in the same tissue homogenates from thermally injured mice. Gr-1(+)CD11b(+) cells, with an ability to suppress antimicrobial peptide production by skin keratinocytes, were isolated from tissues surrounding the burn areas, and these cells were not obtained from skin tissues of sham burn mice. After intradermal inoculation of Gr-1(+)CD11b(+) cells, which were isolated from burn-site tissues, the production of antimicrobial peptides around the cell-inoculation site of sham burn mice decreased. Also, like thermally injured mice, these mice were shown to be susceptible to P. aeruginosa intradermal infection. These results indicate that sepsis stemming from P. aeruginosa burn-wound infection is accelerated by burn-induced Gr-1(+)CD11b(+) cells with abilities to suppress antimicrobial peptide production by epidermal keratinocytes.

Role of polymorphonuclear neutrophils on infectious complications stemming from Enterococcus faecalis oral infection in thermally injured mice.

Thermally injured mice are susceptible to Enterococcus faecalis translocation. In this study, the role of polymorphonuclear neutrophils (PMN) on the development of sepsis stemming from E. faecalis translocation was studied in SCID-beige (SCIDbg) mice depleted of PMN (SCIDbgN mice) or macrophages (Mphi) and PMN (SCIDbgMN mice). Sepsis was not developed in SCIDbgN mice orally infected with E. faecalis, while the orally infected pathogen spread systemically in the same mice inoculated with PMN from thermally injured mice (TI-PMN). SCIDbgMN mice were shown to be greatly susceptible to sepsis caused by E. faecalis translocation, while orally infected E. faecalis did not spread into sepsis in the same mice that were previously inoculated with Mphi from unburned SCIDbg mice (resident Mphi). In contrast, orally infected E. faecalis spread systemically in SCIDbgMN mice inoculated with resident Mphi and TI-PMN, while all SCIDbgMN mice inoculated in combination with resident Mphi and PMN from unburned SCIDbg mice survived after the infection. After cultivation with TI-PMN in a dual-chamber transwell, resident Mphi converted to alternatively activated Mphi, which are inhibitory on the generation of classically activated Mphi (typical effector cells in host antibacterial innate immunities). TI-PMN were characterized as immunosuppressive PMN (PMN-II) with abilities to produce cc-chemokine ligand-2 and IL-10. These results indicate that PMN-II appearing in response to burn injury impair host antibacterial resistance against sepsis stemming from E. faecalis translocation through the conversion of resident Mphi to alternatively activated Mphi.