Safety and Effectiveness of Acceleration Training as Cardiac Rehabilitation Immediately After Open Heart Surgery　- A Pilot Study.

BACKGROUND: We examined the safety and efficacy of acceleration training (AT) in patients immediately after cardiac surgery.Methods and Results: This randomized controlled study included patients who underwent open-heart surgery using cardiopulmonary bypass. Of these patients, 31 received regular cardiac rehabilitation (CR) and 39 received AT in addition to regular CR (AT group). AT was provided using a vibration platform (Power Plate®Pro7TMand Power plate®personal; Performance Health System, Chicago, IL, USA). The AT group performed 5 static resistance training sessions: squats, wide stance squats, toe stands, banded squats, and front lunges. Each vibration session lasted 30 s. We evaluated the short physical performance battery, anterior mid-thigh thickness, maximum voluntary isometric contraction of the knee extensors, and serum intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations as indicators of endothelial function. The observation period was during hospitalization and lasted approximately 20 days. No adverse events occurred during AT. Ultrasound revealed a significantly lower reduction in muscle mass at discharge in the AT group. No significant differences were observed in ICAM-1 and VCAM-1 concentrations between the 2 groups preoperatively, postoperatively, or at discharge. CONCLUSIONS: AT is considered safe and effective for patients immediately after open-heart surgery. AT, along with regular CR, may prevent skeletal muscle mass loss, muscle weakness, and physical function loss immediately after open-heart surgery.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/µL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/µL), with an average treatment effect of 98/µL (95% confidence interval [CI], 2-270/µL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/µL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/µL), with an average treatment effect (ATE) of 79/µL (95% CI, 19-171/µL); these EDEV levels remained elevated until day 5. CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

Loss of p16 Immunoexpression and Deletions of CDKN2A in the Progression of Extramammary Paget Disease: An Immunohistochemical and Genetic Study of 24 Invasive/Metastatic Cases.

ABSTRACT: Information regarding the genetic alterations in extramammary Paget disease (EMPD) is scarce. This study investigated the significance of CDKN2A and MTAP alterations in EMPD progression using immunohistochemistry and panel DNA sequencing. In total, 24 invasive/metastatic EMPD cases were included in this study. The immunoexpression of p16 and MTAP in the primary in situ, primary invasive, and metastatic tumor components was evaluated. Panel DNA sequencing was performed for metastatic tumor components in 5 of the 24 cases. Immunoexpression of p16 in the in situ tumor component was at least partially preserved in all 19 tested cases (100%). By contrast, the invasive tumor component was diffusely or partially lost in 18 (81.8%) of 22 tested cases. Regarding the foci of lymph node metastasis, 13 (81.2%) of the 16 patients showed a significant loss of p16 expression. Loss of MTAP immunoexpression was observed less frequently compared with the loss of p16 expression. CDKN2A homozygous deletions were confirmed in all 5 tested cases by sequencing, whereas MTAP deletions were detected in only 2 cases. In conclusion, p16 expression loss and CDKN2A deletions can be frequently seen in invasive/metastatic cases of EMPD.

Simulation to determine the approach of transcatheter aortic valve implantation in patients undergoing hemodialysis.

PURPOSE: The present study investigated potential access vessels in patients receiving hemodialysis who underwent surgical aortic valve replacement and determined which approaches were most suitable for performing transcatheter aortic valve implantation. METHODS: Consecutive patients undergoing hemodialysis with aortic valve stenosis who underwent surgical aortic valve replacement were included. Preoperative computed tomography data were analyzed to assess the vessel diameter and calcification. Simulations were conducted to determine the feasibility of inserting the 14-F eSheath of Sapien 3 via transfemoral, trans-cervical, trans-subclavian, and direct aorta approaches. RESULTS: A total of 72 patients were included in this study. The access route was characterized by severe calcification of the common iliac artery. The transfemoral approach was feasible in 77.8% of the cases, but the rate decreased to 33% when the calculations were based on the maximum sheath extension diameter. The trans-cervical, trans-subclavian, and direct aortic approaches were suitable for many patients. Lower extremity artery disease was identified as a risk factor for the unsuitability of the transfemoral approach. CONCLUSIONS: Common iliac artery calcification in patients undergoing hemodialysis restricts the use of the transfemoral approach. Therefore, some patients require alternative approaches.

[Resumption of Enfortumab Vedotin Supported by Diagnosis of a Late- Onset Immune-Related Adverse Event in Metastatic Urothelial Carcinoma : A Case Report].

A 71-year-old man presented with exertional dyspnea. Chest radiography revealed multiple pulmonary nodules, and contrast-enhanced computed tomography showed findings suspicious of right renal pelvic cancer. Percutaneous lung tumor biopsy revealed a histological diagnosis of urothelial carcinoma, and right renal pelvic cancer cT3N2M1 was diagnosed. Favorable response was shown during primary chemotherapy with gemcitabine and cisplatin but resulted in tumor progression after four cycles. The patient was switched to a second-line treatment, pembrolizumab, which resulted in rapid tumor growth. Hyper-progression was suspected, and the patient was promptly switched to a third-line treatment, enfortumab vedotin. The tumor shrank significantly. After three treatment cycles, an adverse event of enteritis was observed. A biopsy of the intestinal mucosa led to a histopathologic diagnosis of late-onset immune-related adverse event; therefore, enfortumab vedotin could be continued.

A protocol-based treatment for ruptured abdominal aortic aneurysm contributed to improving aorta-related mortality: a retrospective cohort study.

BACKGROUND: Recent guidelines state that improving the survival rate of patients with ruptured abdominal aortic aneurysm (rAAA) requires a protocol or algorithm for the emergency management of these patients. We aimed to investigate whether introducing a protocol treatment for rAAA improves clinical outcomes compared with the pre-protocol strategy. METHODS: At our institution, 92 patients treated for rAAA between June 2008 and August 2022 were retrospectively analyzed. In 2014, the protocol-based treatment was introduced comprising a transfer algorithm to shorten the time to proximal control, use of an endovascular occlusion balloon, strict indications for endovascular aortic aneurysm repair (EVAR) or open surgical repair, and perioperative care, including for abdominal compartment syndrome (ACS). Clinical outcomes were compared between the protocol and pre-protocol group, including operative status, all-cause mortality, and rAAA-related death at 30-day, in-hospital, and 1-year postoperative follow-ups. RESULTS: Overall, 52 and 40 patients received the protocol-based and pre-protocol treatments, respectively. EVAR was more frequently performed in the protocol group. The rate of achieving time to proximal control was significantly faster, and the transfusion volume was lower in the protocol group. ACS occurred more frequently in the protocol group with a higher EVAR. No difference was found in all-cause mortality between the two groups. The protocol group exhibited fewer rAAA-related deaths than the pre-protocol group during the following time points: 30 days (9.6% vs. 22.5%), during the hospital stay (11.5% vs. 30.0%), and 1 year (14.5% vs. 31.5%). CONCLUSIONS: The protocol-based treatment improved the survival rate of patients with rAAA.

Accuracy of Cardiac Output Measured by Fourth-Generation FloTrac and LiDCOrapid, and Their Characteristics Regarding Systemic Vascular Resistance in Patients Undergoing Cardiac Surgery.

OBJECTIVES: The clinical use of less-invasive devices that calculate the cardiac output from arterial pressure waveform is increasing. The authors aimed to evaluate the accuracy and characteristics of the systemic vascular resistance index (SVRI) of the cardiac index measured by 2 less-invasive devices, fourth-generation FloTrac (CIFT) and LiDCOrapid (CILR), compared with the intermittent thermodilution technique, using a pulmonary artery catheter (CITD). DESIGN: This was a prospective observational study. SETTING: This study was conducted at a single university hospital. PARTICIPANTS: Twenty-nine adult patients undergoing elective cardiac surgery. INTERVENTIONS: Elective cardiac surgery was used as an intervention. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, CIFT, CILR, and CITD, were measured after the induction of general anesthesia, at the start of cardiopulmonary bypass, after completion of weaning from cardiopulmonary bypass, 30 minutes after weaning, and at sternal closure (135 measurements in total). The CIFT and CILR had moderate correlations with CITD (r = 0.62 and 0.58, respectively). Compared with CITD, CIFT, and CILR had a bias of -0.73 and -0.61 L/min/m2, limit of agreement of -2.14-to-0.68 L/min/m2 and -2.42-to-1.20 L/min/m2, and percentage error of 39.9% and 51.2%, respectively. Subgroup analysis for evaluating SVRI characteristics showed that the percentage errors of CIFT and CILR were 33.9% and 54.5% in low SVRI (<1,200 dyne×s/cm5/m), 37.6% and 47.9% in moderate SVRI (1,200-1,800 dyne×s/cm5/m), 49.3% and 50.6% in high SVRI (>1,800 dyne·s/cm5/m2), respectively. CONCLUSIONS: The accuracy of CIFT or CILR was not clinically acceptable for cardiac surgery. Fourth-generation FloTrac was unreliable in high SVRI. LiDCOrapid was inaccurate across a broad range of SVRI, and minimally affected by SVRI.

Worsening Right Ventricular Function during Cardiac Surgery Is a Strong Predictor of Postoperative Acute Kidney Injury: A Prospective Observational Study.

This prospective, observational study was conducted in a university hospital to verify that intraoperative worsening of right ventricular function causes cardiac surgery-associated acute kidney injury. Adult patients undergoing cardiac surgery under mid-sternal incision with cardiopulmonary bypass were included. Echocardiographic right and left ventricular function parameters were measured before and after bypass and compared using the Wilcoxon signed-rank test. Perioperative serum creatinine values at baseline and within the first 48 hours postoperatively were measured for the diagnosis of acute kidney injury. Spearman rank-order correlation (ρ) and receiver operating characteristic analysis were used to reveal relationships. Thirty-four patients were evaluated. Right ventricular ejection fraction (56.2 ± 7.0 vs. 51.6 ± 7.2%; P = 0.0002), right ventricular fractional area change (49.1 ± 6.4 vs. 46.6 ± 5.3%; P = 0.0201; mean ± standard deviation), and left ventricular ejection fraction (57.4 ± 6.1 vs. 51.7 ± 6.2%; P < 0.0001) were significantly decreased. Central venous pressure was significantly increased (7.2 ± 3.5 vs. 9.7 ± 3.7; P = 0.0001). Serum creatinine values increased from 0.82 [0.70-1.08] to 0.99 [0.82-1.54] mg/dL (P < 0.0001; median [interquartile range]). Changes in right ventricular ejection fraction, fractional area change, and right ventricular strain during cardiovascular surgery were significantly correlated with changes in serum creatinine values. Fractional area change exhibited the strongest correlation (ρ = -0.61, P < 0.0001). Change in fractional area change showed an area under the curve of 0.902 and a cutoff value of -2.1, which predicted acute kidney injury with 92% sensitivity, 73% specificity, and 79% accuracy. The functions of both ventricles were decreased after cardiopulmonary bypass. Worsening right ventricular function was independently correlated with postoperative renal dysfunction, and fractional area change was the strongest predictor of cardiac surgery-associated acute kidney injury.

Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system.

Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt-/-), oxytocin receptor-deficient (Oxtr-/-), and oxytocin receptor-Venus (OxtrVenus/+) mice lines. Response thresholds in Oxtr-/- mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds in Oxt-/- mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions in OxtrVenus/+ mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger in Oxtr-/- mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions. Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.

Neonatal Fc receptor induces intravenous immunoglobulin growth suppression in Langerhans cell histiocytosis.

The neonatal Fc receptor (FcRn) plays a role in trafficking IgG and albumin and is thought to mediate intravenous immunoglobulin (IVIG) therapy for certain diseases. IVIG can be used for the treatment of human Langerhans cell histiocytosis (LCH); however, the mechanism remains unclear. The expression and function of FcRn protein have not been studied in LCH, though the expression of FcRn messenger RNA (mRNA) have been reported. In this report, we confirmed the expression of FcRn in 26 of 30 pathological cases (86.7%) diagnosed immunohistochemically as LCH. The expression was independent of age, gender, location, multi- or single-system, and the status of BRAFV600E immunostaining. We also confirmed the expression of FcRn mRNA and protein in the human LCH-like cell line, ELD-1. FcRn suppressed albumin consumption and growth of IVIG preparation-treated ELD-1 cells, but not of IVIG preparation-untreated or FcRn-knockdown ELD-1 cells. In addition, FITC-conjugated albumin was taken into Rab11-positive recycle vesicles in mock ELD-1 cells but not in FcRn-knockdown ELD-1 cells. IVIG preparation prolonged this status in mock ELD-1 cells. Therefore, ELD-1 recycled albumin via FcRn and albumin was not used for metabolism. Our results increase our understanding of the molecular mechanism of IVIG treatment of LCH.

The Expression of Insulin-Like Growth Factor 2 Messenger RNA-Binding Protein 3 in Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma.

Langerhans cell neoplasms, which include Langerhans cell histiocytosis and Langerhans cell sarcoma, are tumors that originate from dendritic cells. Langerhans cell sarcoma is defined as a high-grade neoplasm with overtly malignant cytological features and the Langerhans cell-like phenotype, and generally has a poorer prognosis and more aggressive phenotype than Langerhans cell histiocytosis. Insulin-like growth factor 2 messenger RNA-binding protein 3 (IGF2BP3 or IMP3) is an oncofetal protein that is expressed in various cancer types; its expression is often associated with a poor prognosis and aggressive phenotype. Here, we used immunohistochemistry to evaluate IGF2BP3 expression in Langerhans cell neoplasms. IGF2BP3 expression was scored as negative (< 1%) or positive (≥ 1%) by immunohistochemistry. All 4 patients with Langerhans cell sarcoma (100%) and 6 of 22 pediatric (age < 18 years) patients with Langerhans cell histiocytosis (27.3%) had positive results for IGF2BP3; however, 16 of 22 pediatric patients with Langerhans cell histiocytosis (72.7%) and all 15 adult (age ≥ 18 years) patients with Langerhans cell histiocytosis (100%) had a negative result. Among patients with Langerhans cell histiocytosis, IGF2BP3 expression was independent of sex, location, prognosis, and BRAF V600E staining results. Taken together, these results indicate that IGF2BP3 expression may be a helpful marker for distinguishing Langerhans cell sarcoma from Langerhans cell histiocytosis in adult patients.

[Right Coronary Ostial Aneurysm after Modified Bentall Procedure with Carrel Patch Technique in a Patient with Marfan Syndrome:Report of a Case].

A 58-year-old man with Marfan syndrome visited our clinic for a routine examination. He had undergone a modified Bentall procedure with Carrel patch technique for annuloaortic ectasia 15 years previously. Computed tomography revealed an aneurysm of 43×57 mm in diameter at the right coronary ostium. He underwent resection of the aneurysm and coronary reconstruction using Piehler technique. He was discharged on the 37th postoperative day when his renal function recovered. Although the modified Bentall procedure may improve the surgical outcome, long-term follow-up is important because of various postoperative anastomotic complications in patients with Marfan syndrome.

Sarcopenia assessed by the quantity and quality of skeletal muscle is a prognostic factor for patients undergoing cardiac surgery.

PURPOSE: Sarcopenia was assessed as a prognostic factor for patients undergoing cardiac surgery by evaluating the quantity and quality of skeletal muscle. METHODS: Sarcopenia was assessed by perioperative abdominal computed tomography using the total psoas muscle index (TPI) and intra-muscular adipose tissue content (IMAC). Patients were classified into high- (HT, n = 143) and low- (LT, n = 63) TPI groups and low- (LI, n = 122) and high- (HI, n = 84) IMAC groups. RESULTS: There were significantly more complications in the LT and HI groups than in the HT and LI groups. (HT 15.4% vs. LT 30.2%, P = 0.014) (LI 11.5% vs. HI 31.1%, P < 0.001). There were more respiratory complications in the LT group (HT 0% vs. LT 6.3%, P = 0.002) and more surgical site infections in the HI group than in the LI group (LI 0.8% vs. HI 7.1%, P = 0.014). A multivariable analysis showed that low TPI and high IMAC significantly predicted more major complications than other combinations (odds ratio [OR] 2.375; 95% confidence interval [CI] 1.152-5.783; P = 0.036, OR 3.973; 95% CI 1.737-9.088; P = 0.001). CONCLUSIONS: Sarcopenia is a risk factor for complications. The quantity and quality of muscle must be assessed to predict operative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000027077.

Increase in circulating ACE-positive endothelial microparticles during acute lung injury.

Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+ microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients.The numbers of EMPs and ACE+ EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry.ACE+ EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+ EMPs and ACE+ EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+ EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+ EMPs and ACE+ EMP/EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001).Therefore, circulating ACE+ EMPs may be a prognostic marker for the development of ARDS in the septic patients.

Lung-diffusing capacity for carbon monoxide predicts early complications after cardiac surgery.

PURPOSE: Preoperative pulmonary dysfunction has been associated with increased operative mortality and morbidity after cardiac surgery. This study aimed to determine whether values for the diffusing capacity of the lung for carbon monoxide (DLCO) could predict postoperative complications after cardiac surgery. METHODS: This study included 408 consecutive patients who underwent cardiac surgery between June 2008 and December 2015. DLCO was routinely determined in all patients. A reduced DLCO was clinically defined as %DLCO < 70%. %DLCO was calculated as DLCO divided by the predicted DLCO. The association between %DLCO and in-hospital mortality was assessed, and independent predictors of complications were identified by a logistic regression analysis. RESULTS: Among the 408 patients, 338 and 70 had %DLCO values of ≥ 70% and < 70%, respectively. Complications were associated with in-hospital mortality (P < 0.001), but not %DLCO (P = 0.275). A multivariate logistic regression analysis with propensity score matching identified reduced DLCO as an independent predictor of complications (OR, 3.270; 95%CI, 1.356-7.882; P = 0.008). CONCLUSIONS: %DLCO is a powerful predictor of postoperative complications. The preoperative DLCO values might provide information that can be used to accurately predict the prognosis after cardiac surgery. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000029985.

SLAM family member 8 is involved in oncogenic KIT-mediated signalling in human mastocytosis.

The signalling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8 knock-down significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8 knock-down HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS-RAF-ERK signalling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF-ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

Influences of environmental noise level and respiration rate on the accuracy of acoustic respiration rate monitoring.

We tested the hypothesis that the environmental noise generated by a forced-air warming system reduces the monitoring accuracy of acoustic respiration rate (RRa). Noise levels were adjusted to 45-55, 56-65, 66-75, and 76-85 dB. Healthy participants breathed at set respiration rates (RRset) of 6, 12, and 30/min. Under each noise level at each RRset, the respiration rates by manual counting (RRm) and RRa were recorded. Any appearance of the alarm display on the RRa monitor was also recorded. Each RRm of all participants agreed with each RRset at each noise level. At 45-55 dB noise, the RRa of 13, 17, and 17 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of 14, 17, and 16 participants at 56-65 dB noise, agreed with RRset of 6, 12, and 30/min, respectively. At 66-75 dB noise, the RRa of 9, 15, and 16 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of one, nine, and nine participants at 76-85 dB noise agreed with RRset of 6, 12, and 30/min, respectively, which was significantly less than the other noise levels (P < 0.05). Overall, 72.9% of alarm displays highlighted incorrect values of RRa. In a noisy situation involving the operation of a forced-air warming system, the acoustic respiration monitoring should be used carefully especially in patients with a low respiration rate.

Positive pressure ventilation in a patient with a right upper lobar bronchocutaneous fistula: right upper bronchus occlusion using the cuff of a left-sided double lumen endobronchial tube.

In patients with a bronchocutaneous fistula, positive pressure ventilation leads to air leakage and potential hypoxemia. A male patient with a right upper bronchocutaneous fistula was scheduled for esophageal reconstruction. His preoperative chest computed tomography image revealed aeration in the right middle and lower lobe, a large bulla in the left upper lobe, and pleural effusion and pneumonia in the left lower lobe. Therefore, left one-lung ventilation was considered to result in hypoxemia. Before anesthesia induction, the bronchocutaneous fistula was covered with gauze and film to prevent air leakage. After anesthesia induction, mask ventilation was performed with a peak positive pressure of 10 cmH2O. A left-sided double lumen endobronchial tube (DLT) was then inserted into the right main bronchus for occluding only the right superior bronchus, and two-lung ventilation was performed to minimize airway pressure and maintain oxygenation, which did not cause air leakage through the fistula. During anesthesia, no ventilation-related difficulty was faced. The method of inserting a left-sided DLT into the right main bronchus and occluding the right upper bronchus selectively by bronchial cuff is considered to be an option for mechanical ventilation in patients with a right upper bronchial fistula, as demonstrated in the present case.