Twisting of HeartMate II outflow graft 2.5 years after implantation-HM2 is still ongoing.

A 47-year-old woman with dilated cardiomyopathy underwent HeartMate II (HM2) implantation as a bridge-to-transplantation. Her postoperative course was good. However, 2.5 years after surgery, the outflow graft was found to be twisted and the graft and pump was exchanged. While HeartMate 3(HM3) twisting of the outflow graft is well documented, such malfunctions in HM2 are almost unknown. Although HM2 has since been discontinued, there are a significant number of patients using HM2 who are awaiting heart transplants or destination therapy. We caution that, even with HM2, the possibility of late-phase twisting requires vigilance.

Aortic valve area index values of Trifecta implants correlate with energy loss and increased valve stress.

Biological valves are becoming more frequently used in aortic valve replacement. While several reports have evaluated the performance of biological valves, echocardiography studies during exercise stress remain scarce. Furthermore, no current reports compare rate changes in the aortic valve area of biological valves under increased exercise load. Here, we performed exercise stress echocardiography in patients after AVR with Trifecta or Inspiris valves and compared the rates of change in aortic valve areas (AVA). In addition, hydrodynamic analysis at rest was conducted with four-dimensional flow magnetic resonance imaging (4D-flow MRI). Exercise stress echocardiography was performed in seven Trifecta and seven Inspiris patients who underwent AVR at our hospital while 4D flow MRI was performed in all but two Trifecta cases. Comparing the percentage change in AVA when loaded to 25 W versus at rest, Trifecta was greater than Inspiris (28.7 ± 36.0 vs - 0.8 ± 12.4%). The smaller AVA at rest was considered causative for this. Meanwhile, Trifecta systolic energy loss in the prosthetic valve segment on 4D-flow MRI (97.5 ± 35.9 vs 52.7 ± 25.3 mW) was higher than Inspiris. The opening of the Trifecta valve was considered to be restricted at rest and this may reflect the current reports of early valve degradation requiring reoperation. Taken together, we observed that the Trifecta design may promote faster wear due to higher valve stress.

Second-line immunosuppressant administration for steroid-refractory immune-related adverse events in patients with lung cancer.

BACKGROUND: Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases. METHODS: This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects. RESULTS: Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection. CONCLUSION: Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs.

Soluble interleukin-2 receptor as a predictive biomarker for poor efficacy of combination treatment with anti-PD-1/PD-L1 antibodies and chemotherapy in non-small cell lung cancer patients.

Soluble interleukin-2 receptor (sIL-2R) suppresses effector T-cells. Few studies have assessed serum sIL-2R in patients receiving immunotherapy. We evaluated the association between serum sIL-2R levels and the efficacy of anti-programmed cell death 1/ programmed death-ligand 1 (anti-PD-1/PD-L1) antibody combined with chemotherapy in non-small cell lung cancer (NSCLC) patients. We prospectively enrolled NSCLC patients who received anti-PD-1/PD-L1 antibody combined with platinum-based chemotherapy between 8/2019 and 8/2020 and measured their serum sIL-2R. The patients were divided into high and low sIL-2R groups based on the median of sIL-2R levels at pretreatment. Progression-free survival (PFS) and overall survival (OS) of patients in the high and low sIL-2R groups were compared. The Kaplan-Meier curves of PFS and OS were evaluated using the log-rank test. The multivariate analysis of PFS and OS was performed using the Cox proportional hazard models. Among 54 patients (median age 65, range 34-84), 39 were male and 43 had non-squamous cell carcinoma. The sIL-2R cut-off value was 533 U/mL. Median PFS was 5.1 months (95% CI, 1.8-7.5 months) and 10.1 months (95% CI, 8.3-not reached [NR] months) in the high and low sIL-2R groups (P = 0.007), respectively. Median OS was 10.3 months (95% CI, 4.0-NR months) and NR (95% CI, 10.3-NR months) in the high and low sIL-2R groups (P = 0.005), respectively. Multivariate Cox regression analysis showed that high sIL-2R was significantly associated with shorter PFS and OS. SIL-2R may be a biomarker for the poor efficacy of anti-PD-1/PD-L1 antibody combined with chemotherapy.

Surgery for spina bifida occulta: spinal lipoma and tethered spinal cord.

The technical evolution of the surgery for spina bifida occulta (SBO) over the course of a half-century was reviewed with special foci placed on the spinal lipoma and tethered spinal cord. Looking back through history, SBO had been included in spina bifida (SB). Since the first surgery for spinal lipoma in the mid-nineteenth century, SBO has come to be recognized as an independent pathology in the early twentieth century. A half-century ago, the only option available for SB diagnosis was the plain X-ray, and pioneers of the time persevered in the field of surgery. The classification of spinal lipoma was first described in the early 1970s, and the concept of tethered spinal cord (TSC) was proposed in 1976. Surgical management of spinal lipoma with partial resection was the most widely practiced approach and was indicated only for symptomatic patients. After understanding TSC and tethered cord syndrome (TCS), more aggressive approaches became preferred. A PubMed search suggested that there was a dramatic increase of publications on the topic beginning around 1980. There have been immense academic achievements and technical evolutions since then. From the authors' viewpoint, landmark achievements in this field are listed as follows: (1) establishment of the concept of TSC and the understanding of TCS; (2) unraveling the process of secondary and junctional neurulation; (3) introduction of modern intraoperative neurophysiological mapping and monitoring (IONM) for surgery of spinal lipomas, especially the introduction of bulbocavernosus reflex (BCR) monitoring; (4) introduction of radical resection as a surgical technique; and (5) proposal of a new classification system of spinal lipomas based on embryonic stage. Understanding the embryonic background seems critical because different embryonic stages bring different clinical features and of course different spinal lipomas. Surgical indications and selection of surgical technique should be judged based on the background embryonic stage of the spinal lipoma. As time flows forward, technology continues to advance. Further accumulation of clinical experience and research will open the new horizon in the management of spinal lipomas and other SBO in the next half-century.

Right Ventricular Outflow Tract Myxoma with Absent Pulmonary Valve.

Myxoma is the most common benign cardiac tumor. Absent pulmonary valves, often treated surgically in childhood, are associated with 3-6% of tetralogy of Fallot. It is unusual for absent pulmonary valves without other congenital heart diseases to be asymptomatic until adulthood. Here, we report the unique case of an 80-year-old female with right ventricular outflow tract myxoma and absent pulmonary valve that has, to our knowledge, never been reported. We successfully performed a simple mass resection and pulmonary valve implantation.

[Pediatric Hemispheric Glioma].

About one-third of pediatric low-grade glioma and a half of pediatric high-grade glioma occur in the cerebrum. Pediatric hemispheric glioma may harbor diagnostic and therapeutically targetable genetic abnormalities, including BRAF V600E, H3.3 G34R/V, FGFR1 alternation, MYB or MYBL1 alternation, and NTRK/ALK/ROS1/MET fusion. In addition, the efficacy of molecular-targeted agents, such as BRAF inhibitors, MEK inhibitors, and NTRK inhibitors, against pediatric glioma with the relevant mutations has been demonstrated in several clinical trials. Furthermore, checkpoint inhibitors are considered a choice of treatment for hypermutated glioma, which is typically observed in patients with constitutional mismatch repair deficiency syndrome. Cancer gene panel testing, approved for insurance coverage in Japan in 2019, has been beneficial to pediatric cancer patients. However, to promote the clinical application of the recent molecular understanding of pediatric neuro-oncology, some issues have to be addressed. Herein, we review the genetic profiles of pediatric hemispheric glioma and introduce the current medical situation of precision medicine for pediatric patients with glioma in Japan.

A high performance nanocomposite based bioanode for biofuel cell and biosensor application.

Herein, to improve the current density and sensitivity for biofuel cell and glucose sensing application, a bioanode based on redox polymer (PEI-Fc) binding polydopamine (PDA) coated MWCNTs (PEI-Fc/PDA/MWCNTs) nanocomposite and glucose oxidase (GOD) was fabricated. PDA/MWCNTs nanocomposite was prepared by spontaneous self-polymerization of dopamine on MWCNTs surface and the PEI-Fc/PDA/MWCNTs nanocomposite was prepared by a simple self-assembly method. The PEI-Fc/PDA/MWCNTs nanocomposite and the resulting bioanode were fully characterized. A maximum current density of 0.73 mA cm-2 at the resulting bioanode was obtained by linear sweep voltammetry (LSV) at the scan rate of 50 mV s-1 with 20 mM glucose concentration. Moreover, a linear range up to 4 mM, a high sensitivity of 57.2 µA mM-1 cm-2, a fast response time reaching 95% of the steady current (2 s) and a low limit of detection (0.024 mM) were achieved. The amperometric method demonstrated both the sensitivity and the stability of the bioanode for glucose-sensing was improved by the employed PDA layer. Finally, the biosensor was used for glucose detection in human serum samples showing good recoveries. This study proposed an excellent functional material prepared by a facile self-assembled method for applying in biofuel cells and second-generation biosensors.

Role of PAR1-Egr1 in the Initiation of Thoracic Aortic Aneurysm in Fbln4-Deficient Mice.

OBJECTIVE: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4SMKO), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4SMKO mice and generated double knockout mice (DKO, Fbln4SMKO; Egr1-/-). Aneurysms were prevented in DKO mice (42.8%) and Fbln4SMKO; Egr1+/- mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. CONCLUSIONS: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.

Rhabdoid tumor predisposition syndrome with renal tumor 10 years after brain tumor.

We report a case of rhabdoid tumor predisposition syndrome with a renal tumor developing 10 years after a brain tumor, which demonstrated an unexpectedly favorable outcome. A 2-year-old boy underwent gross total resection of a brain tumor located in the fourth ventricle, and received adjuvant chemotherapy and radiotherapy. At the age of 11 years, a renal tumor was found and nephrectomy was performed. He is currently alive without evidence of disease over 2 years without postoperative therapy. Histologically, rhabdoid cells were observed in both brain and renal tumors. Loss of SMARCB1 (also known as INI1) expression was found in the nucleus of both tumor cells. Genetic testing revealed pathogenic variants of SMARCB1 exon 5 in the renal tumor and SMARCB1 exon 9 in the brain tumor. In addition, heterozygous deletion of 22q11.21-q11.23 containing the SMARCB1 locus was shared by both tumors and this deletion was identified in normal peripheral blood. Considering the histopathological and genetic findings, our case was considered to be rhabdoid tumor predisposition syndrome with atypical teratoid/rhabdoid tumor and late-onset rhabdoid tumor of the kidney.

Electrochemical characteristics of a gold nanoparticle-modified controlled enzyme-electrode contact junction electrode.

Biodevices in which biomolecules such as enzymes and antibodies are immobilized on the surface of electrode materials are capable of converting chemical energy into electrical energy, and are expected to contribute to solving energy problems and developing medical measurements especially as biobatteries and biosensors. Device performance depends on the interface formed between the biomolecule layer and electrode material, and the interface is required to simultaneously achieve a highly efficient enzymatic reaction and electron transfer. However, when enzymes were immobilized on a material surface, the enzymes undergoes a structural change due to the interaction between the enzyme and the electrode surface, making it difficult to maximize the function of the enzyme molecule on the material surface. In this study, we postulate that the structural change of the enzyme would be reduced and the electrochemical performance improved by making the contact area between the enzyme and the electrode extremely small and adsorbing it as a point. Therefore, we aimed to develop a high-power biodevice that retains enzyme structure and activity by interposing gold nanoparticles (AuNPs) between the enzyme and the electrode. The enzymatic and electrochemical properties of pyrroloquinoline quinone-dependent glucose dehydrogenase adsorbed on AuNPs of 5-40 nm diameter were investigated. We found that the characteristics differed among the particles, and the enzyme adsorbed on 20 nm AuNPs showed the best electrochemical characteristics.

The effect of roller head pump on platelet deterioration during the simulated extracorporeal circulation.

Roller pumping results in hemolysis and adverse effects on coagulation, but there are few reports on the influence of roller heads on platelets. Here, we evaluate the interaction between roller pumping and platelet function using a simulated extracorporeal circuit incorporating a vinyl chloride tube and roller head pump with 30 min recirculation. Platelet aggregation, platelet count, microparticle, P-selectin, Phosphatidylserine (PS) exposure and Ricinus Communis Agglutinin 1 (RCA-1) were measured before, 5, 10, 20, and 30 min after the recirculation using 100 ml of fresh human blood that had obtained from healthy volunteers (n = 9). Platelet aggregation and platelet count gradually decreased but microparticles significantly increased after the recirculation (P < 0.05). P-selectin, PS exposure and RCA-1 were measured using flow cytometry. There were no significant differences in the P-selectin and PS exposure expression during recirculation. RCA-1, a platelet apoptosis markers, significantly increased 30 min after recirculation (P < 0.05). We thus conclude that roller pumping induced platelet apoptosis and caused decreases in platelet count and aggregation after the recirculation.

Highly Efficient Multi-Step Oxidation Bioanode Using Microfluidic Channels.

With the rapid decline of fossil fuels, various types of biofuel cells (BFCs) are being developed as an alternative energy source. BFCs based on multi-enzyme cascade reactions are utilized to extract more electrons from substrates. Thus, more power density is obtained from a single molucule of substrate. In the present study, a bioanode that could extract six electrons from a single molecule of L-proline via a three-enzyme cascade reaction was developed and investigated for its possible use in BFCs. These enzymes were immobilized on the electrode to ensure highly efficient electron transfer. Then, oriented immobilization of enzymes was achieved using two types of self-assembled monolayers (SAMs). In addition, a microfluidic system was incorporated to achieve efficient electron transfer. The microfluidic system, in which the electrodes were arranged in a tooth-shaped comb, allowed for substrates to be supplied continuously to the cascade, which resulted in smooth electron transfer. Finally, we developed a high-performance bioanode which resulted in the accumulation of higher current density compared to that of a gold disc electrode (205.8 µA cm-2: approximately 187 times higher). This presents an opportunity for using the bioanode to develop high-performance BFCs in the future.

Dissociated responses at initial computed tomography evaluation is a good prognostic factor in non-small cell lung cancer patients treated with anti-programmed cell death-1/ligand 1 inhibitors.

BACKGROUND: Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. METHODS: This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation. In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. Cases not classified as DR were defined as 'true PD'. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. RESULTS: The present study included 62 NSCLC patients aged 27-82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months, respectively; hazard ratio for death: 0.40; 95% confidence interval: 0.17-0.94). CONCLUSIONS: Patients with DR exhibited a relatively favorable prognosis.

Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans.

RATIONALE: Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated. OBJECTIVE: The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy. METHODS AND RESULTS: We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4SMKO; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved. CONCLUSIONS: Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.

Strategy to minimize radiation burden in infants and high-risk medulloblastoma using intrathecal methotrexate and high-dose chemotherapy: A prospective registry study in Japan.

BACKGROUND: Most childhood medulloblastoma (MB) cases are curable using multimodal treatment, including craniospinal irradiation (CSI). However, late effects are a serious problem for survivors. This prospective registry study evaluated Japanese patients to determine whether a reduced radiation dose was feasible. PATIENTS AND METHODS: Patients with MB were classified as an infant group (<3 years old) and a high-risk (HR) group (≥3 years old with metastasis). The HR group received intrathecal methotrexate (IT-MTX) and high-dose chemotherapy (HDC) using thiotepa and melphalan, as well as concomitant radiotherapy with a recommended CSI dose of 18 Gy and a total local dose of 50 Gy. Radiotherapy was only considered for infants if residual tumors were present after the HDC. RESULTS: Between 1997 and 2006, we identified 28 HR patients (M1: 9, M2/3: 19) and 17 infant patients (M0: 11, M1: 3, M2/3: 3). During the median follow-up of 9.4 years for the entire HR group, the 5-year progression-free survival (PFS) rate was 82.1 ± 7.2% and the 5-year overall survival (OS) rate was 85.7 ± 6.6%. Subanalyses of the patients who received the recommended treatment revealed that the 5-year PFS and OS rates were both 90.5 ± 6.4%. In the infant group, the 5-year PFS rate was 52.9 ± 12.1% and the 5-year OS rate was 51.8 ± 12.4%. There were no serious adverse events associated with the IT-MTX and HDC treatments. CONCLUSION: Intensified chemotherapy using HDC and IT-MTX might allow for a reduced prophylactic radiation dose in patients with MB with metastases. Further studies are needed to validate these findings.

Phase II study of reduced-dose craniospinal irradiation and combination chemotherapy for children with newly diagnosed medulloblastoma: A report from the Japanese Pediatric Brain Tumor Consortium.

BACKGROUND: Standard doses of craniospinal irradiation (CSI) are 23.4 Gy for patients with average-risk and 36 Gy for those with high-risk medulloblastoma (MB). We investigated whether intensified chemotherapy including intrathecal chemotherapy with simultaneous irradiation is able to reduce CSI dose to 18 Gy. METHODS: Newly diagnosed average-risk patients aged 3-11 years and high-risk patients aged 3-18 years were eligible. Patients with Stage M1-4 disease were classified as high-risk MB and the others, including M0 patients with >1.5 cm2 postoperative residual tumor, were classified as average-risk MB. Patients received chemotherapy consisting of cyclophosphamide, etoposide, cisplatin, and vincristine. Radiotherapy was started concomitantly with the second course of chemotherapy. Radiation doses were 50 Gy to the primary site and 18 Gy to the craniospinal axis. Average-risk patients received five courses of chemotherapy. High-risk patients received high-dose chemotherapy consisting of thiotepa and melphalan following four courses of chemotherapy. All patients received intrathecal methotrexate. RESULTS: From 2006 to 2014, 48 patients (35 average and 13 high risk) who met the eligibility/exclusion criteria were enrolled. The 3-year progression-free survival (PFS) and 3-year overall survival (OS) were 90.5% (standard error 5.2%) and 93.9% (4.2%), respectively, for average-risk patients, and 100% and 100%, respectively, for high-risk patients. There was no leukoencephalopathy or treatment-related deaths. Two patients experienced secondary cancer. CONCLUSIONS: These results suggest that CSI 18 Gy is adequate at least in a proportion of patients with MB treated with intensified chemotherapy including intrathecal methotrexate and simultaneous irradiation, though the results in high-risk patients were only exploratory.

Formation of one-dimensional arrays of nanoparticles using segmented polyurethane nanofibers prepared by electrospinning.

The number density and the arrangement of metal nanoparticles in composite materials have a significant effect on their performance and hence their suitability for use in sensors and devices. Forming one-dimensional arrays of metal nanoparticles is one way of controlling their number density and arrangement in the devices. In this study, we fabricated one-dimensional arrays of gold nanoparticles by adsorbing them on linearly distributed hard segments present on the surfaces of segmented polyurethane nanofibers, which were produced by electrospinning under a stretching force. The length of the one-dimensional array was approximately 500 nm. Furthermore, the interparticle distance was almost constant at approximately 14 nm. Thus, the proposed method is suitable for fabricating one-dimensional arrays of metal nanoparticles with high precision.

TEG improves anticoagulation management during cardiopulmonary bypass complicated by antiphospholipid syndrome.

BACKGROUND AND AIM: Cardiopulmonary bypass (CPB) in antiphospholipid syndrome (APS) patients carries a high risk of thrombosis and hemorrhage. However, optimal anticoagulation surveillance methods have not been established and heparin optimization has not yet been totally validated as reflective of anticoagulation status. METHODS AND RESULT: Here, a 45-year-old female with APS underwent mitral valvuloplasty due to infective endocarditis. We used a perioperative, in vitro, heparin-activated clotting time (ACT) titration line coupled with synergistic, intraoperative thromboelastography (TEG) to monitor coagulation activity. After the ACT target was reached, TEG monitored the suppression of both intrinsic and extrinsic coagulation activity throughout the surgery. CONCLUSION: TEG thus provided valuable temporal information on both intrinsic and extrinsic coagulation suppression validating heparin-ACT titration targets.

Successful treatment of metastatic cerebral recurrence of pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare pediatric tumor. The central nervous system (CNS) is the most common site of extrathoracic metastasis. The prognosis of PPB patients with CNS metastases is dismal: most patients die within one year after recurrence. Here, we describe two patients diagnosed with PPB who developed intracranial recurrences shortly after the end of their initial treatment and were successfully treated by gross total resection, radiotherapy, and chemotherapy. Both patients are in complete remission four and three years after recurrence. Although an optimal regimen remains to be determined, these cases demonstrate that PPB with CNS metastases is potentially curable.