A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators-

We report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators. Two years later, her pulmonary vascular resistance (PVR) was improved but still not at the level where VSD closure was possible. To control the increased PA flow resulting from intensive PAH treatment and to reduce the risk of hemoptysis, we performed pulmonary artery banding (PAB). As the risk of hemoptysis decreased, a prostacyclin analog was introduced, and the dose was increased. More than 1 year after PAB, active vasoactivity testing became positive, suggesting that the pulmonary vascular lesion was now “reversible”. We performed VSD closure and atrial septal defect creation even though her PVR was still high. After the operation, her exercise capacity was remarkably improved. We suggest that stepwise surgical repair with pulmonary vasodilators is an important treatment option for select patients with VSD with severe PAH.Learning objectiveAdvances in pulmonary arterial hypertension (PAH) treatment have led to the use of a “treat-and-repair” strategy to close the intracardiac shunt after PAH treatment in select patients with adult congenital heart disease. In our case, ventricular septal defect (VSD) closure was achieved with stepwise surgical repair and a combination of pulmonary vasodilators, even though long-standing severe PAH with persistent hemoptysis remained. Even after a long period of exposure to high blood flow, this strategy may reduce pulmonary vascular resistance and permit eventual closure of the VSD

WHATS-3: An Improved Flow-Through Multi-bottle Fluid Sampler for Deep-Sea Geofluid Research

Deep-sea geofluid systems, such as hydrothermal vents and cold seeps, are key to understanding subseafloor environments of Earth. Fluid chemistry, especially, provides crucial information toward elucidating the physical, chemical, and biological processes that occur in these ecosystems. To accurately assess fluid and gas properties of deep-sea geofluids, well-designed pressure-tight fluid samplers are indispensable and as such they are important assets of deep-sea geofluid research. Here, the development of a new flow-through, pressure-tight fluid sampler capable of four independent sampling events (two subsamples for liquid and gas analyses from each) is reported. This new sampler, named WHATS-3, is a new addition to the WHATS-series samplers and a major upgrade from the previous WHATS-2 sampler with improvements in sample number, valve operational time, physical robustness, and ease of maintenance. Routine laboratory-based pressure tests proved that it is suitable for operation up to 35 MPa pressure. Successful field tests of the new sampler were also carried out in five hydrothermal fields, two in Indian Ocean, and three in Okinawa Trough (max. depth 3,300 m). Relations of Mg and major ion species demonstrated bimodal mixing trends between a hydrothermal fluid and seawater, confirming the high quality of fluids sampled. The newly developed WHATS-3 sampler is well-balanced in sampling capability, field usability, and maintenance feasibility, and can serve as one of the best geofluid samplers available at present to conduct efficient research of deep-sea geofluid systems

A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial)

Introduction: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol. Methods/Design: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response. Discussion: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab. Trial registration: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150

Left atrial extension of metastatic lung tumor via pulmonary vein: report on the first case of Ewing sarcoma

Extension of metastatic lung tumors into the left atrium via pulmonary veins is rare. Here, we report the first case of Ewing sarcoma exhibiting such extension. A 31-year-old man with pulmonary metastasis from Ewing sarcoma presented with a mass in the left lung, extending to the left atrium through the left inferior pulmonary vein. As the patient was considered to be at risk of tumor embolism, the mass was excised surgically

Changes of Driver Behavior by Rear-end Collision Prevention Support System in Poor Visibility

Changes of driver behavior by the rear-end collision prevention support system with road-to-vehicle communication, was evaluated on a public road. From a viewpoint of safety, “normative behavior” which the system certainly requires to a driver was defined as “deceleration behavior in a poor visibility section”, and it was compared between with-system and without-system conditions. As a result, behavioral changes of gas pedal release or speed decrease were observed in a part of participants. By analysis of driver’s individual characteristics, the result of behavioral changes could be interpreted as being due to driver’s situation awareness for the risk of “invisible objects”

Single coronary artery diagnosed in the perinatal period: A case report

Objective: Having a single coronary artery (SCA) is a rare congenital anomaly in which a single artery arises from the aorta. Although most cases of SCA are asymptomatic and incidental, its effects during the perinatal period remain unknown. Herein, we report a case of pregnant woman with suspected SCA, based on transthoracic echocardiography (TTE) findings. Case report: A 33-year-old multiparous woman presented with preterm premature rupture of the membrane at 29 weeks gestation. The patient’s preoperative electrocardiogram (ECG) showed slight ST changes. TTE showed dilated right coronary artery and hypoplastic left coronary artery. Cesarean section was performed at 30 weeks of gestation due to non-reassuring fetal status. Although poor oxygenation was observed postoperatively, the patient was managed appropriately. She was diagnosed with SCA based on coronary computed tomographic angiography findings one month after delivery. Conclusion: Pregnant women with SCA require careful perinatal care

The glycerol-3-phosphate acyltransferase PLAT2 functions in the generation of DHA-rich glycerolipids in Aurantiochytrium limacinum F26-b.

Thraustochytrids possess docosahexaenoic acid (DHA, 22:6n-3) as acyl chain(s) of triacylglycerol (TG) and phosphatidylcholine (PC), some of which contain multiple DHAs. However, little is known about how these DHA-rich glycerolipids are produced in thraustochytrids. In this study, we identified PLAT2 in Aurantiochytrium limacinum F26-b as a glycerol-3-phosphate (G3P) acyltransferase (GPAT) by heterologous expression of the gene in budding yeast. Subsequently, we found that GPAT activity was reduced by disruption of the PLAT2 gene in A. limacinum, resulting in a decrease in DHA-containing lysophosphatidic acid (LPA 22:6). Conversely, overexpression of PLAT2 increased both GPAT activity and LPA 22:6. These results indicate that PLAT2 is a GPAT that transfers DHA to G3P in vivo as well as in vitro. Overexpression of the PLAT2 gene increased the production of a two DHA-containing diacylglycerol (DG 44:12), followed by an increase in the three DHA-containing TG (TG 66:18), two-DHA-containing TG (TG 60:12), and two DHA-containing PC (PC 44:12). However, overexpression of PLAT2 did not increase DHA-free DG (DG32:0), which was preferentially converted to three 16:0-containing TG (TG 48:0) but not two 16:0-containing PC (PC 32:0). Collectively, we revealed that DHA-rich glycerolipids are produced from a precursor, LPA 22:6, which is generated by incorporating DHA to G3P by PLAT2 in the A. limacinum

Possibility of inhibiting arthritis and joint destruction by SSEA-3 positive cells derived from synovial tissue in rheumatoid arthritis

Aim: Joint destruction progresses irreversibly once they occur in rheumatoid arthritis (RA), even with the recent development of anti-rheumatic drugs. Cells positive for stage-specific embryonic antigen-3 (SSEA-3), a marker of human embryonic stem cell, act as stem cells in the blood. The aim of this study is to investigate the effectiveness of SSEA-3 positive cells for the treatment for RA. Methods: Synovial tissues were harvested at the time of joint surgery in RA patients. Cultured synovial cells were sorted by anti-SSEA-3 antibody using flow cytometry and were analyzed in in vitro. To investigate inhibitory effects on arthritis by SSEA-3 positive cells, collagen antibody-induced arthritis (CAIA) mice were used and transplanted with labeled cells intravenously. Results: Presence of SSEA-3 positive cells was confirmed with approximately 1% in RA synovial cells. SSEA-3 positive cells were negative for CD34 and positive for CD44, CD90 and CD105. Multipotency of SSEA-3 positive cells was higher than that of SSEA-3 negative cells. Arthritis of the group transplanted with SSEA-3 positive cells in CAIA mice decreased over time. Conclusions: SSEA-3 positive cells derived from RA synovial tissue might have the inhibitory effect on arthritis and would be one of cell source for new RA treatment