Successful bronchial artery embolization using hydrogel coils for hemoptysis during extracorporeal membrane oxygenation

A 58-year-old woman with bronchiectasis presented with massive hemoptysis and severe respiratory failure, which required long-term extracorporeal membrane oxygenation with continuous heparin infusion. Bronchial artery embolization using hydrogel coils, which provide a greater volume occlusion than bare platinum coils, was performed; hemoptysis stopped and she fully recovered. No recanalization was observed on follow-up computed tomography angiography 2 months postbronchial artery embolization, and there had been no recurrence of bleeding at the time of this report (at least 6 months). Although continuous anticoagulation during extracorporeal membrane oxygenation might hinder complete vessel occlusion by metallic coils or induce early recanalization (because the homeostatic mechanism of coils depends on the patient''s coagulability), our experience showed that bronchial artery embolization using hydrogel coils was effective and safe. Additionally, this case presents a successful example of anticoagulation management for patients with hemoptysis on extracorporeal membrane oxygenation who undergo bronchial artery embolization using coils.     

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.     

Vesicular nucleotide transporter is a molecular target of eicosapentaenoic acid for neuropathic and inflammatory pain treatment

Eicosapentaenoic acid (EPA), an omega-3 (ω-3) polyunsaturated fatty acid, is an essential nutrient that exhibits antiinflammatory, neuroprotective, and cardiovascular-protective activities. Although EPA is used as a nutrient-based pharmaceutical agent or dietary supplement, its molecular target(s) is debatable. Here, we showed that EPA and its metabolites strongly and reversibly inhibit vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and release of adenosine triphosphate (ATP) in purinergic chemical transmission. In vitro analysis showed that EPA inhibits human VNUT-mediated ATP uptake at a half-maximal inhibitory concentration (IC₅₀) of 67 nM, acting as an allosteric modulator through competition with Cl⁻. EPA impaired vesicular ATP release from neurons without affecting the vesicular release of other neurotransmitters. In vivo, VNUT^−/− mice showed a delay in the onset of neuropathic pain and resistance to both neuropathic and inflammatory pain. EPA potently attenuated neuropathic and inflammatory pain in wild-type mice but not in VNUT^−/− mice without affecting the basal nociception. The analgesic effect of EPA was canceled by the intrathecal injection of purinoceptor agonists and was stronger than that of existing drugs used for neuropathic pain treatment, with few side effects. Neuropathic pain impaired insulin sensitivity in previous studies, which was improved by EPA in the wild-type mice but not in the VNUT^−/− mice. Our results showed that VNUT is a molecular target of EPA that attenuates neuropathic and inflammatory pain and insulin resistance. EPA may represent a unique nutrient-based treatment and prevention strategy for neurological, immunological, and metabolic diseases by targeting purinergic chemical transmission.

Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are essential nutrients that contain multiple double bonds. PUFAs can be classified into ω-3 and ω-6 depending on the position of the bonds. As humans cannot produce PUFAs, they must be acquired from the diet to maintain homeostasis. Omega-3 PUFAs, such as eicosapentaenoic acid (EPA), are abundantly present in fish and linseed oil and exhibit antiinflammatory, neuroprotective, and cardiovascular-protective activities via the competitive inhibition of cyclooxygenase (COX)-2 in eicosanoid production (1–3). Danish and Greenland Inuit epidemiological studies have reported that EPA reduces the risk of death after myocardial infarction (4, 5), and other studies have reported its influence on analgesia, neuroinflammatory disease (Parkinson’s disease, Alzheimer’s disease, and depression) improvement, platelet aggregation inhibition, decrease in blood triglyceride and glucose levels, and improved insulin resistance (1, 6–11). Omega-3 fatty acid supplementation in COVID-19 patients showed a beneficial effect in managing the cytokine storm (12). Conversely, omega-6 fatty acids, such as arachidonic acid, produce inflammatory eicosanoids and play central roles in the initial stage of inflammatory responses (13). Although arachidonic acid has also been reported to produce antiinflammatory metabolites, omega-6 PUFA-derived linoleate diols have a harmful effect and are biomarkers for severe COVID-19 infection (14). An omega-6 PUFA-enriched Western-style diet, which abundantly contains linoleate, causes neuropathy and chronic pain, but an omega-3 PUFA-enriched diet attenuates these pathological conditions (15).All therapeutic effects of EPA cannot be explained by COX-2 inhibition alone (16). Typically, COX-2 inhibitors (nonsteroidal antiinflammatory druga [NSAIDs]) are effective for inflammatory pain but ineffective for neuropathic pain (16). However, EPA significantly attenuates both inflammatory and neuropathic pain, which strongly suggests another important molecular target of EPA related to neuropathy (7, 8). Although chronic pain is coincidentally caused by inflammation and neuropathy, there is no therapeutic drug with few side effects to attenuate both inflammatory and neuropathic pain (17–20). In this situation, EPA may affect the key signaling molecule(s) in neurological, metabolic, and immunological functions.Purinergic chemical transmission is involved in neurological, metabolic, and immunological disruptions and functions, including neuropathic and inflammatory pain, depression, inflammation, increase in blood triglyceride and glucose levels, insulin resistance, and blood coagulation (21, 22). The released adenosine triphosphate (ATP) and degraded adenosine diphosphate (ADP) or adenosine binds to many types of purinoceptors that are intricately involved in biological and pathological processes. In pain perception, ATP and ADP bind to P2X and P2Y receptors and thereby exacerbate neuropathic and inflammatory pain (23). Adenosine binds to P1 receptors and thereby attenuates neuropathic and inflammatory pain (24). However, a vesicular nucleotide transporter (VNUT/SLC17A9) is localized in the secretory vesicles of neuronal, endocrine, and immune cells. It plays an essential role in vesicular ATP storage in a Δψ- and Cl^–-dependent manner in the purinergic chemical transmission, which leads to vesicular ATP release (25, 26). Thus, VNUT is a key molecule in the initiation of purinergic signaling for neurological, metabolic, and immunological disruptions and functions. Interestingly, the observed effects of the VNUT inhibitor and phenotypes of VNUT^−/− mice were consistent with the above-mentioned therapeutic effects of EPA (27–31). Therefore, we hypothesized that VNUT serves as a molecular target of EPA to attenuate neuropathic and inflammatory pain.Here, we demonstrated that a low concentration of EPA and its metabolites, but not docosahexaenoic acid (DHA), are potent and selective physiological inhibitors of vesicular ATP release via the blockade of purinergic chemical transmission, which improved neuropathic and inflammatory pain and insulin resistance. Furthermore, EPA is more effective for neuropathic and inflammatory pain and has fewer side effects than existing drugs.     

Hemangiopericytoma on the intradural thoracic spinal cord: a case report

Hemangiopericytoma develops from many organs. In the central nervous system, most tumors arise in the intracranial portion, and tumors originating from the spinal cord are rare. Its clinical course and neurological characteristics have not been disclosed. We present a case of a 51-year-old woman with gradually progressing paraparesis. Magnetic resonance (MR) images of the thoracic spine demonstrated an intradural tumor at the 6 and 7 thoracic vertebral body level. The patient underwent total excision of the tumor. The histological diagnosis was hemangiopericytoma. MR images after the operation showed no residual tumor and the patient was followed up without adjuvant therapy. However, 5 years later, the patient complained of back pain and gait disturbance again, and MR images showed a recurrence of the tumor. We resected the tumor under motor evoked potential (MEP) monitoring and removed the extradural part of the tumor, but the part of the tumor which had infiltrated the spinal cord was left due to the lowering of MEP amplitude. The operation resulted in partial resection. Spinal intradural hemangiopericytoma is very rare, and only 15 cases including the present case have been reported. This paper will discuss the clinical characteristics and treatment for this tumor.     

Pulmonary Metastasis From Breast Cancer With an 18-Year Disease-Free Interval: Implication of the Role of Surgery

The appearance of pulmonary metastasis more than 15 years after primary treatment for breast cancer is rare. We herein report the case of a breast cancer patient with solitary pulmonary metastasis, after an 18-year disease-free period, treated with resection. A 66-year-old Japanese woman was found to exhibit an abnormal shadow on a chest X-ray. She had undergone a left mastectomy for breast cancer 18 years previously. The nodule was suspected to be either metastatic or primary lung cancer, and thus thoracoscopic surgery was performed. The histologic diagnosis was metastasis from breast cancer. Pulmonary resection in breast cancer recurrence is an important diagnostic tool that allows for a differential diagnosis with primary lung cancer. The clinical implication of surgery for a solitary pulmonary metastasis from breast cancer is discussed in this report.     

Early hemodynamic effects of olprinone hydrochloride after coronary artery bypass grafting

Our purpose was to evaluate the hemodynamic effects of olprinone hydrochloride early after coronary artery bypass grafting (CABG). Fifteen patients undergoing CABG were administered a constant infusion of 0.1 μg/kg/min of olprinone and continued for 4 hours. No bolus infusion of olprinone was administered before continuous infusion. Systolic systemic arterial pressure, systolic pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance were significantly decreased. There were no significant changes in heart rate, mean central venous pressure, mean left atrial pressure and left ventricular stroke work index. Cardiac index was significantly increased, but a correlation between cardiac index and mixed venous blood oxygen saturation was not found. Double product was significantly decreased, which described above suggest that olprinone achieved improvement of left cardiac function without more myocardial oxygen consumption. Severe transient hypotension (systolic arterial pressure <80 mmHg) after infusion of olprinone was observed in three patients. Olprinone administered soon after CABG surgery had beneficial effects in terms of improvement of hemodynamic status without more oxygen consumption and reduction of pulmonary vascular resistance. However transient hypotension was a serious clinical problem in patients after open heart surgery, especially in CABG patients who need suitable systolic arterial pressure to keep enough blood perfusion of arterial bypass grafts.     

The management of the difficult pediatric airway

BACKGROUND: We are faced sometimes with the difficult pediatric airway due to congenital abnormalities. However, there has been no systematic examination for the management of the difficult pediatric airway. METHODS: We retrospectively examined the incidence of difficult airway in 13,557 pediatric patients who had undergone general anesthesia with tracheal intubation. The difficulties of the intubation were classified into grade 1 to 4; grade 1: intubated one time, grade 2: two times, grade 3: three times or more, grade 4: changed to another way. We defined grade 3 and 4 as "difficult airway". RESULTS: Twenty-five patients (0.17%) are "difficult airway" among 13,557 patients in which 21 patients (0.15%) are classified as grade 3, and 4 patients (0.02%) are grade 4. The difficulties were significantly different among the syndromes (P< 0.001). The rate of the incidence in the difficulty is high in Treacher Collins syndrome, arthrogryposis multiprex congenita and first and second brachial arch syndrome, but few is in Pierre-Robin syndrome, Crouzon syndrome and Apert syndrome which are known to accompany difficult airway. CONCLUSIONS: We demonstrated that the incidence of difficult airway is different among the syndromes.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Atlantoaxial transarticular screw fixation and posterior fusion using ultra-high-molecular-weight polyethylene cable

This article attempts to evaluate the effectiveness of the ultra-high-molecular-weight polyethylene (UHMW-PE) cable system in atlantoaxial transarticular screw fixation and posterior fusion through the clinical results of 10 postoperative patients with atlantoaxial subluxation secondary to rheumatoid arthritis. Among them, one patient with only one screw placed owing to an anomalous vertebral artery had the correction loss of the 3-mm atlas-dens interval after surgery. Another patient had a second operation to remove the screw and cable after 2 years 11 months because a unilateral transarticular screw had come to protrude through the lateral mass of the atlas ventrally. All patients had achieved C1-C2 osseous fusion without any complications associated with this cable system. The UHMW-PE cable is a very useful material as sublaminar wiring in atlantoaxial transarticular screw fixation and posterior fusion.     

Cardiac anesthesia induction by low target plasma concentration setting of propofol using target-controlled infusion

BACKGROUND: Propofol-anesthesia administerd using target-controlled infusion (TCI) has been proposed for cardiac surgery. But, moderate target concentration of propofol during induction using TCI has not been studied in detail. METHODS: Thirty patients scheduled for cardiac surgery under cardiopulmonary bypass (CPB) and TCI propofol anesthesia were randomly divided into two groups to receive a computer-controlled infusion of propofol with target concentrations of 1.5 or 2.0 micro/g x ml(-1) [1.5 microg x ml(-1) group (n=15) and 2.0 microg x ml(-1) group (n=15)]. Mean arterial pressure (MAP), heart rate (HR) and bispectral index scale (BIS) values were recorded at 5 time points during induction of anesthesia. RESULTS: MAP was significantly lower in 2.0 microg x ml(-1) group compared with 1.5 microg x ml(-1) group. In both groups, a rise of BIS value did not occur during tracheal intubation. CONCLUSIONS: We have demonstrated that propofol TCI at a target concentration of 1.5 microg x ml(-1) is effective for hemodynamic stability during induction of anesthesia in patients for cardiac surgery under CPB.