Using hemoglobin vesicles to treat operative hemorrhagic shock after pneu- monectomy in dog models: an experimental study.

Hemoglobin vesicles (HbVs), considered as red blood cell substitutes, are liposomes encapsulating purified hemoglobin, with a phospholipid bilayer membrane (diameter: 250 nm; P50, 28 Torr). In this study, we aimed to investigate HbV function during hemorrhagic shock in lung resection and analyze the details of oxygen delivery. Left pneumonectomy was performed in dogs under mechanical ventilation, followed by rapid exsanguination of approximately 30% of the total circulating blood volume, which led to shock, reducing the mean arterial pressure (MAP) by approximately 60% of baseline. Subsequently, either 5% human serum albumin (HSA) or HbVs suspended in 5% HSA were infused for resuscitation. The MAP only recovered to 75% of baseline after HSA administration, but fully recovered (100%) after HbV administration, with significant differences between the groups (P < 0.005). Oxygen delivery was restored in the HbV group and was significantly higher than that in the HSA group (P < 0.0001). The infusion of HbVs dispersed in a 5% HSA solution compensated for the rapid loss of approximately 30% of the total circulating blood volume in a dog pneumonectomy model, even with impaired lung function. Thus, HbVs can be used for resuscitation from hemorrhagic shock during thoracic surgery.

Poly(2-ethyl-2-oxazoline)-Conjugated Hemoglobins as a Red Blood Cell Substitute.

Hemoglobin wrapped covalently with poly(2-ethyl-2-oxazoline)s (POx-Hb) is characterized physicochemically and physiologically as an artificial O2 carrier for use as a red blood cell (RBC) substitute. The POx-Hb is generated by linkage of porcine Hb surface-lysines to a sulfhydryl terminus of the POx derivative, with the average binding number of the polymers ascertained as 6. The POx-Hb shows moderately higher colloid osmotic activity and O2 affinity than the naked Hb. Human adult HbA conjugated with POx also possesses equivalent features and O2 binding properties. The POx-Hb solution exhibits good hemocompatibility, with no influence on the functions of platelets, granulocytes, and monocytes. Its circulation half-life in rats is 14 times longer than that of naked Hb. Hemorrhagic shock in rats is relieved sufficiently by infusion of the POx-Hb solution, as revealed by improvements of circulatory parameters. Serum biochemistry tests and histopathological observations indicate no acute toxicity or abnormality in the related organs. All results indicate that POx-Hb represents an attractive alternative for RBCs and a useful O2 therapeutic reagent in transfusion medicine.

Polyoxazoline-conjugated porcine serum albumin as an artificial plasma expander for dogs.

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs. The aqueous POx-PSA solution showed moderately high colloid osmotic pressure and good blood cell compatibility. Actually, lyophilized powder stored for 1 year can regenerate into a homogeneous solution. The circulation half-life of POx-PSA in rats was 2.1-fold longer than that of naked PSA. Rats produced neither anti-PSA IgG antibody nor anti-POx IgG antibody, which suggests excellent immunological stealth properties of POx-PSA. Complete resuscitation of hemorrhagic shock in rats was achieved soon after injection of POx-PSA solution. Serum biochemistry tests and histopathological observations indicated no abnormality in the related organs. When POx-PSA was administered to dogs intravenously, (i) no serum biochemical or hematological alteration was observed, also (ii) no overt deterioration of animal health was observed. These results indicate that POx-PSA has potential as an artificial plasma expander for dogs.

Zinc Substituted Myoglobin-Albumin Fusion Protein: A Photosensitizer for Cancer Therapy.

Myoglobin combined with human serum albumin (Mb-HSA) can be produced using yeast Pichia pastoris as a host strain, with secretion into the culture medium. This Mb-HSA fusion protein possesses identical O2 binding affinity to that of naked Mb. The Mb unit is reconstituted with a zinc(II) protoporphyrin IX, yielding (zinc substituted Mb)-HSA, ZnMb-HSA. The photophysical property and singlet O2 generation ability of ZnMb-HSA are equivalent to those of ZnMb. In vitro cell experiments revealed that ZnMb-HSA acts as a superior photosensitizer for photodynamic cancer therapy. It is noteworthy that ZnMb-HSA shows long circulation lifetime in vivo.

Core-Shell Structured Hemoglobin Nanoparticles as Artificial O2 Carriers.

This paper describes the synthesis and O2 binding properties of core-shell structured hemoglobin (Hb) nanoparticles (NPs), artificial O2 carriers of five types, as designed for use as red blood cell (RBC) substitutes. Human adult Hbs were polymerized using α-succinimidyl-ω-maleimide and dithiothreitol in spheroidal shapes to create parent particles. Subsequent covalent wrapping of the sphere with human serum albumin (HSA) yielded 100 nm-diameter Hb nanoparticles (HbNPs). The HbNP showed higher O2 affinity than that of RBC, but NPs prepared under a N2 atmosphere exhibited low O2 affinity. Entirely synthetic particles comprising recombinant human adult Hb and recombinant HSA were also fabricated. Using a recombinant Hb (rHb) variant in which Leu-ß28 of the heme pocket had been replaced with Phe, we found somewhat low O2 affinity of rHb(ßL28F)NP. Particles made of stroma-free Hb (SFHb) containing natural antioxidant enzyme catalase (SFHbNP) formed a very stable O2 complex, even in aqueous H2O2 solution. The SFHbNP showed good blood compatibility and did not affect the blood cell component functionality. The circulation half-life of SFHbNP in rats was considerably longer than that of naked Hb. All results indicate these Hb-based NPs as useful alternative materials for RBC and as a useful O2 therapeutic reagent in diverse medical scenarios.

A case of cerebral infarction due to aplastic or twig-like middle cerebral artery after lung cancer surgery.

Aplastic/twig-like middle cerebral artery is a rare vascular abnormality. We report a case of postoperative cerebral infarction caused by this disease. The patient is a male in his 40s. A 9-cm tumour was revealed to have invaded the superior vena cava from his right lung. He underwent right upper and middle bilobectomy. Due to the vascular invasion, the intraoperative bleeding exceeded 2 litres. Mechanical ventilation was required for postoperative pneumonia. After extubation, he was unable to write and was found to have cerebral infiltration in the left middle cerebral artery region. The cause of the cerebral infarction was investigated, but no thrombus in the left atrium or arteriosclerosis was found. No atrial fibrillation was observed during or after the surgery. Magnetic resonance angiography of the brain revealed an aplastic/twig-like middle cerebral artery.

Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hemoglobin vesicles (HbVs), liposomes containing concentrated hemoglobin extracted from outdated human red blood cells (RBC), are artificial oxygen carriers with a small particle size. To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC. Isogenic mice were used as donors and recipients in a parallel trachea transplant model. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 mL of HbV solution (Hb concentration, 10 g/dL) was administered via the tail vein. The recipients were euthanized 1, 4, 6, and 8 h after surgery (n = 5 in each group). The tracheas were harvested, and tracheal subepithelial capillaries (SEC) reperfusion was histologically evaluated. A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 and 8 h later. Our findings suggest that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBCs after transplantation and contribute to the oxygenation of transplanted tissues.

Hemoglobin-albumin clusters as an artificial O2 carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats.

A bovine hemoglobin (HbBv) or human adult hemoglobin (HbA) wrapped covalently by human serum albumins (HSAs), hemoglobin-albumin clusters (HbBv-HSA3 and HbA-HSA3 ), are artificial O2 carriers used as a red blood cell substitute. This article describes the physicochemical properties of the HbBv-HSA3 and HbA-HSA3 solutions, and their abilities to restore the systemic condition after resuscitation from hemorrhagic shock in anesthetized rats. The HbBv-HSA3 and HbA-HSA3 , which have high colloid osmotic activity, showed equivalent solution characteristics and O2 binding parameters. Shock was induced by 50% blood withdrawal. Rats exhibited hypotension and significant metabolic acidosis. After 15 min, the rats were administered shed autologous blood (SAB), HbBv-HSA3 , HbA-HSA3 , or Ringer's lactate (RL) solution. Survival rates, circulation parameters, hematological parameters, and blood gas parameters were monitored during the hemorrhagic shock and for 6 h after administration. All rats in the SAB, HbBv-HSA3 , and HbA-HSA3 groups survived for 6 h. The HbBv-HSA3 and HbA-HSA3 groups restored mean arterial pressure after the resuscitation. No remarkable difference was observed in the time courses of blood gas parameters in any resuscitated group except for the RL group. Serum biochemical tests showed increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the HbBv-HSA3 and HbA-HSA3 groups compared to the SAB group. Therefore, we observed other rats awakened after resuscitation with HbA-HSA3 for 7 days. The blood cell count, AST, and ALT recovered to the baseline values by 7 days. All the results implied that HbBv-HSA3 and HbA-HSA3 clusters provide restoration from hemorrhagic shock as an alternative material for SAB transfusion.

Enteric-type thymic adenocarcinoma: a case report and literature review focusing on prognosis based on histological subtypes.

Thymic adenocarcinoma is a rare disease and enteric-type thymic adenocarcinoma is even more rarely found. We report a resected case of a non-mucinous, enteric-type thymic adenocarcinoma in a 53-year-old woman. The operation was performed by median sternotomy, and the tumor was stage II in the Masaoka classification. Six months after the operation, recurrence-free follow-up is currently underway. Knowledge of enteric-type thymic adenocarcinoma can prevent misdiagnosis of metastatic tumors. We also determined the prognosis of enteric-type thymic adenocarcinoma based on histological subtypes through our literature review.

Bioinspired carbon monoxide delivery using artificial blood attenuates the progression of obliterative bronchiolitis via suppression of macrophage activation by IL-17A.

Carbon monoxide (CO) is expected to attenuate the progression of obliterative bronchiolitis (OB), which is a serious complication after lung transplantation. However, issues in terms of feasible exogenous CO supply, such as continuousness and safety, remain unsolved. Here, we applied nano red blood cells, namely hemoglobin vesicles (Hb-V), as a CO cargo based on the biomimetic concept and investigated the therapeutic potential of CO-loaded Hb-V on OB in orthotopic tracheal transplant model mice. The CO-loaded Hb-V was comprised of negatively charged liposomes encapsulating carbonylhemoglobin with a size of ca. 220 nm. The results of histological evaluation showed that allograft luminal occlusion and fibrosis were significantly ameliorated by treatment with CO-loaded Hb-V compared to treatment with saline, cyclosporine, and Hb-V. The therapeutic effects of CO-loaded Hb-V on OB were due to the suppression of M1 macrophage activation in tracheal allografts, resulting from decreased IL-17A production. Furthermore, the expression of TNF-α and TGF-ß in tracheal allografts was decreased by CO-loaded Hb-V treatment but not saline and Hb-V treatment, indicating that CO liberated from CO-loaded Hb-V inhibits epithelial-mesenchymal transition. These findings suggest that CO-loaded Hb-V exerts strong therapeutic efficacy against OB via the regulation of macrophage activation by IL-17A and TGF-ß-driven epithelial-mesenchymal transition.

A desmoplastic fibroblastoma that developed in the anterior mediastinum: a case report.

BACKGROUND: Desmoplastic fibroblastoma (also known as collagenous fibroma) is a benign, slowly growing soft-tissue tumor. Most desmoplastic fibroblastomas develop in the limbs, neck, or trunk. A mediastinal origin is quite rare. CASE PRESENTATION: A 32-year-old Asian female was referred to us for the diagnosis and treatment of an anterior mediastinal tumor. The tumor was 80 mm in the largest diameter and was located on the pericardium. No invasion was evident. She underwent resection of the tumor via video-assisted thoracoscopic resection. The tumor was totally encapsulated, and its pedicle was on the pericardium. The resected specimen was very rigid, making it difficult to remove from the intercostal space. Histologically, the tumor was composed of a paucicellular dense collagenous tissue. Mitosis was rarely observed, and cellular atypia was not evident, suggesting that the tumor was benign. We diagnosed the tumor as a desmoplastic fibroblastoma by morphology and immunohistochemistry. CONCLUSIONS: Desmoplastic fibroblastoma of the mediastinum is an extremely rare disease. Preoperative diagnosis is difficult. Early surgical resection is suitable for diagnosis and treatment planning.

A surgical Case of Synchronous Multiple Primary Lung Cancers with Small Cell Carcinoma and Squamous Cell Carcinoma.

The incidence of synchronous multiple primary lung cancers has increased in recent years, however, there are few reports of cases involving small cell carcinoma. A 72-year-old man was referred to our department because of an abnormal shadow on chest radiography. He was receiving treatment for pulmonary fibrosis, emphysema, rheumatoid arthritis, and prostate cancer. Computed tomography revealed two lung nodules in the left lower lobe. A definitive diagnosis was unable to be made based on transbronchial lung biopsy. Positron emission tomography demonstrated abnormal fluorodeoxyglucose uptake in the two lung nodules and lung cancer (cT3N0M0) was suspected. Thoracoscopic partial resection of the left lower lobe was performed. As primary lung cancer was diagnosed using the frozen specimen, we performed left lower lobectomy with lymph node dissection. Pathological examination of the S9 and S6 tumors revealed combined small cell carcinoma and squamous cell carcinoma, respectively. Both tumors were separated and diagnosed as synchronous multiple primary lung cancers. No lymph node metastasis was found. We report a rare case of synchronous multiple primary lung cancers, including small cell carcinoma.

Myxofibrosarcoma that Developed Rapidly in the Breast of an Elderly Man and Recurred Early after Surgery: A Case Report.

BACKGROUND: Myxofibrosarcoma is a rare disease occurring subcutaneously in the limbs. We report a case of a rapidly growing myxofibrosarcoma in the breast of an elderly man that recurred early after surgery. CASE PRESENTATION: A 73-year-old man presented with a breast mass. Physical findings showed a large tumor in the right breast, and malignancy was suspected on ultrasonography. Computed tomography (CT) revealed tumor invasion into the pectoralis major and pectoralis minor muscles. Positron emission tomography/CT showed no abnormality in other organs. Needle biopsy results excluded breast cancer but did not provide a definitive diagnosis. However, the tumor grew rapidly before further results were available, so emergency mastectomy was performed. The final pathological diagnosis was high-grade myxofibrosarcoma. Postoperative radiotherapy was started because of remnant tumor. The wound became worsened and swollen, and needle biopsy 10 days after the start of therapy indicated recurrence. Radical resection and thoracoplasty were performed. Postoperative pathological specimens showed no residual tumor. Radical radiation therapy was resumed. The patient has shown no recurrence after an year. CONCLUSIONS: It is important to consult a soft tissue oncologist for tumors in the breast and perform appropriate examination and treatment if soft tissue tumors cannot be ruled out.

Postintubation tracheal stenosis 35 years after neonatal resuscitation.

INTRODUCTION: Postintubation tracheal stenosis involves granulation or cicatrization of the tracheal epithelium. It is progressive and can become life-threatening within a few months after extubation. PRESENTATION OF CASE: We here report a case of tracheal stenosis with a delayed manifestation, presenting 35 years after endotracheal intubation for neonatal resuscitation. A female patient complained of dyspnea during pregnancy. Bronchoscopy revealed 75% constriction of the tracheal lumen by cicatrization, from the 2nd to 4th tracheal rings. After child-birth, the scar tissue was ablated using argon plasma coagulation. DISCUSSION: The patient had no significant medical history, such as severe airway infection or cervical/chest trauma, which might have caused the circumferential cicatricial tracheal stenosis, other than the endotracheal intubation she had undergone for neonatal resuscitation. Therefore, we considered this to reflect postintubation tracheal stenosis with delayed manifestation. CONCLUSION: Delayed postintubation tracheal stenosis should be taken into consideration, when a patient suffers from suffocating tracheal stenosis.

Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model.

BACKGROUND: Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P50=28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors. METHODS: Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ~30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P50 HbV, P50=9 Torr), normal HbV suspended in 5% albumin (HbV, P50=28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated. RESULTS: Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO2 in the low-P50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P50 HbV as well as rat RBCs. CONCLUSIONS: The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.

The Incidence of Hemorrhagic Complications Was Lower With the Guide Sheath Than With the Conventional Forceps Biopsy Method: Results of Bronchoscopy in the 2016 Nationwide Survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: The Japan Society for Respiratory Endoscopy performed a nationwide survey to evaluate the current status and complications of bronchoscopy. Data on deaths due to bronchoscopy, complications after bronchoscopy, and particularly, complications of forceps biopsy were surveyed. METHODS: The survey form was mailed to 532 facilities accredited by the society. The numbers of procedures, complications, and deaths were investigated. RESULTS: The response rate was 79.1% (421 facilities). Deaths attributable to diagnostic bronchoscopy occurred in 11 (0.011%) of 98,497 cases.In regards to forceps biopsy, the guide sheath method was applied in 23,916 cases and the conventional method in 31,419 cases was done with conventional method. Complications of forceps biopsy developed in 1019 cases in total, with an incidence rate of 1.84%. The most frequent complication was pneumothorax (0.70%), followed by pneumonia/pleurisy (0.46%) and hemorrhage (0.45%). The incidence of hemorrhagic complication was significantly lower in the guide sheath group than in the non-guide sheath group (0.29% vs. 0.58%; P<0.001). The overall incidence of complications (1.63% vs. 2.00%; P=0.002) and the mortality rate (0% vs. 0.02%; P=0.04) were significantly lower in the guide sheath group. CONCLUSION: The incidence of hemorrhagic complications in forceps biopsy of peripheral pulmonary lesions was lower when the guide sheath method was applied. It is necessary to increase the awareness for safety control in diagnostic bronchoscopy for new procedures.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Congenital cystic adenomatoid malformation in adults: Report of a case presenting with a recurrent pneumothorax and a literature review of 60 cases.

Congenital cystic adenomatoid malformation (CCAM) is a congenital pulmonary cystic disease that is mostly detected and diagnosed prenatally or during the neonatal period, while rarely being observed in adults. Here, we report an adult case of CCAM that was diagnosed following surgery for a recurrent pneumothorax. We further review 60 case reports on adult CCAM that have been previously published. The patient was a 29-year-old woman with a severe left pneumothorax. Her computed tomography scan showed the presence of multiple pulmonary cysts at the base of the left lower lobe. Since she had experienced a left pneumothorax twice previously, surgery was indicated. A wedge lung resection of the pulmonary cysts was performed thoracoscopically. The postoperative pathological diagnosis was type I CCAM. From the review, 7 adult CCAM patients (11.7%) out of 61, including the patient in the present case, presented with pneumothorax, while 21 patients (35%) presented with infection. Thirty-nine foci of CCAM (65%) were located in lower lobes. Moreover, malignancies were associated in 8 cases (13.3%). We propose that if multicystic lung lesions are found in pneumothorax patients, particularly in lower lobes, CCAM should be considered during the differential diagnosis, even in adults.

Current status of diagnostic and therapeutic bronchoscopy in Japan: 2016 national survey of bronchoscopy.

BACKGROUND: The safety management committee of the Japan Society for Respiratory Endoscopy (JSRE) conducted national surveys to clarify the state of diagnostic and therapeutic bronchoscopy in 2016. METHODS: Questionnaire forms were mailed to 532 JSRE-accredited facilities throughout Japan. We surveyed the actual condition of clinical practice and cases of bronchoscopy during 2016. RESULTS: Four hundred and thirty-three facilities responded giving a response rate of 81.4%; 67.6% held more than 400 beds. The average number of board accredited senior Fellows and Fellows per facility was 1.9 and 3.2, respectively. Diagnostic bronchoscopy was performed in a hospitalized setting in 74.6% of all facilities. The radial type ultrasound probe was operated in 51.7% of all facilities. The number of facilities has markedly increased compared with that reported in the 2010 survey (19.6%). The bronchoscopic navigation system had been in operation in 41.7% of all facilities. Antithrombotic drugs were adjusted before biopsy in 96.8% of all facilities. For intravenous sedation, midazolam was the first choice in 76.9% of all facilities. Endobronchial ultrasound guided transbronchial lymph node needle aspiration (EBUS-TBNA) has become popular over the decade (19.6% in 2010 to 68.1% in 2016). The mean number of the board accredited senior Fellows and board accredited Fellows increased in comparison with that in 2010. As a new technique, radial type ultrasound-guided peripheral approach has become popular. CONCLUSIONS: Through this survey, the advanced safety of bronchoscopic examination has been secured in many facilities. A continuous monitoring of bronchoscopic practices with respect to safety management is recommended.

Hemoglobin-albumin cluster: physiological responses after exchange transfusion into rats and blood circulation persistence in dogs.

A core-shell protein cluster comprising hemoglobin and human serum albumins, hemoglobin-albumin cluster (Hb-HSA3), was designed and synthesized for use as an artificial O2 carrier and red blood cell (RBC) substitute. For initial preclinical safety evaluation of the Hb-HSA3 solution, we observed blood compatibility in vitro, physiological responses after exchange transfusion into rats and blood circulation lifetime in dogs. Dilution of human whole blood with Hb-HSA3 showed an appropriate decrease in blood cell number, proportional to the mixing volume ratio. Time courses in the circulation parameters and blood gas parameters after 20% exchange transfusion with Hb-HSA3 in anesthetized rats were almost identical to those observed in a sham group (without infusion) and an HSA group (with HSA administration) for 6 h. Serum biochemical tests of the withdrawn blood indicated safety of the protein cluster. Furthermore, fluorescent Hb-HSA3 was infused into beagle dogs to assess blood retention. Fluorescence measurements of the blood samples enabled us to ascertain the cluster half-life within the intravascular space. Histopathologic inspections of the vital organs imply no abnormality in tissues. All these results indicate sufficient initial preclinical safety of Hb-HSA3 as an alternative material for use in RBC transfusion.