Non-negligible ultrasonographic findings in sarcoid myositis: A case series and literature review.

Sarcoid myositis is a rare and often debilitating extrapulmonary manifestation of sarcoidosis that can be difficult to recognize without a prior sarcoidosis diagnosis. Sarcoidosis with muscle nodules or masses as the first symptom is the least common form, occurring in approximately 0.5%-2.3% of cases. This article presents four middle-aged female patients who initially sought medical attention for a lower limb mass. Ultrasound examinations revealed consistent characteristic changes indicative of myositis. All patients underwent ultrasound-guided muscle biopsy and were diagnosed with sarcoidosis. Therefore, ultrasonography plays a pivotal role as the primary diagnostic tool for the early detection of sarcoid myositis.

Optical noise-resistant nonreciprocal phonon blockade in a spinning optomechanical resonator.

A scheme of nonreciprocal conventional phonon blockade (PB) is proposed in a spinning optomechanical resonator coupled with a two-level atom. The coherent coupling between the atom and breathing mode is mediated by the optical mode with a large detuning. Due to the Fizeau shift caused by the spinning resonator, the PB can be implemented in a nonreciprocal way. Specifically, when the spinning resonator is driven from one direction, the single-phonon (1PB) and two-phonon blockade (2PB) can be achieved by adjusting both the amplitude and frequency of the mechanical drive field, while phonon-induced tunneling (PIT) occurs when the spinning resonator is driven from the opposite direction. The PB effects are insensitive to cavity decay because of the adiabatic elimination of the optical mode, thus making the scheme more robust to the optical noise and still feasible even in a low-Q cavity. Our scheme provides a flexible method for engineering a unidirectional phonon source with external control, which is expected to be used as a chiral quantum device in quantum computing networks.

Hemorrhagic shock after contrast-enhanced ultrasound-guided liver biopsy: A case report of primary hepatic angiosarcoma.

Primary hepatic angiosarcoma (PHA) is a rare, highly aggressive malignancy. There is no specificity in clinical manifestations, laboratory examinations and imaging examinations. The definitive diagnosis of PHA depends on pathological analysis. The gold standard method to obtain specimens is percutaneous transhepatic biopsy under the guidance of contrast-enhanced ultrasound (CEUS). However, CEUS-guided biopsy for PHA is controversial. If a biopsy is necessary, a comprehensive preoperative evaluation is essential. In addition, CEUS has an auxiliary value in diagnosing PHA. In this case, we present an elderly woman who underwent CEUS-guided liver mass biopsy. The patient developed hemorrhagic shock after biopsy.

Reliability of Sonography-based Volume Computer Aided Diagnosis in the Normal Fetal Heart.

OBJECTIVES: To explore the inter- and intra-observer reliability of Sonography-based Volume Computer Aided Diagnosis (SonoVCAD) in the display of 8 diagnostic planes of fetal echocardiography and to evaluate its efficiency. METHODS: Three-dimensional volume data sets of the 56 normal singleton fetuses were acquired from a 4-chamber view by using a volume probe. After processing the data sets by using SonoVCAD, 8 cardiac diagnostic planes were displayed automatically. Three doctors with different experiences of performing fetal echocardiography evaluated each diagnostic plane and the success rates of 8 diagnostic planes were calculated. Inter-observer and intra-observer reliabilities were estimated by Cohen's kappa statistics. RESULTS: A total of 276 volume data sets acquired from the 56 normal fetuses were used for SonoVCAD analysis and display. The success rate of each diagnostic section was more than 90%, ranging from 90.6% to 99.6%. Among 276 volumes, 81.5% (225/276) of volumes were able to generate all 8 diagnostic views successfully. Moderate to substantial agreement (kappa, 0.509-0.794) was found between 2 less experienced operators. Moderate to near-perfect agreement (kappa, 0.439-0.933) was found between an expert and 2 less experienced sonographers. Intra-observer reliability was substantial to near-perfect (kappa, 0.602-0.903). The efficiency of SonoVCAD was assessed. The expert spent less time than 2 less experienced examiners (P < 0.001) but no significant difference was found between 2 less experienced examiners (P = 0.176). Besides, SonoVCAD consumed significantly less time than 2-dimensional ultrasound (P < 0.001). CONCLUSIONS: SonoVCAD can significantly improve the success rates of 8 diagnostic planes in fetal echocardiography with low operator dependency, good reproducibility and high efficiency.

Novel foetal echocardiographic image processing software (5D Heart) improves the display of key diagnostic elements in foetal echocardiography.

BACKGROUND: To evaluate the clinical value of foetal intelligent navigation echocardiography (5D Heart) for the display of key diagnostic elements in basic sections. METHODS: 3D volume datasets of 182 normal singleton foetuses were acquired with a four chamber view by using a volume probe. After processing the datasets by using 5D Heart, eight cardiac diagnostic planes were demonstrated, and the image qualities of the key diagnostic elements were graded by 3 doctors with different experiences in performing foetal echocardiography. RESULTS: A total of 231 volume datasets acquired from the 182 normal foetuses were used for 5D Heart analysis and display. The success rate of 8 standard diagnostic views was 88.2%, and the success rate of each diagnostic view was 55.8-99.2% and 70.7-99.0% for the random four chamber view as the initial section and for the apical four chamber view as the initial section, respectively. The success rate of each diagnostic element in the 8 diagnostic sections obtained by 5D Heart was 58.9%~ 100%. Excellent agreement was found between experienced sonographers and less-experienced sonographers (kappa> 0.769). Inter- and intra-observer agreement were substantial to near-perfect, kappa values ranging from 0.612 to 1.000 (Cohen's kappa). CONCLUSIONS: 5D Heart can significantly improve the image quality of key diagnostic elements in foetal echocardiography with low operator dependency and good reproducibility.

Two-dimensional tissue tracking: a novel echocardiographic technique to measure left atrial volume: comparison with biplane area length method and real time three-dimensional echocardiography.

Enlargement of the left atrium is an independent predictor of adverse cardiovascular outcomes, and an accurate, convenient imaging modality is necessary for clinical practice. The objectives of this study were to evaluate the feasibility of a novel imaging technique, two-dimensional tissue tracking (2DTT), for assessment of left atrial (LA) volume and function and to compare its correlation and agreement with biplane area length (AL) method and real time three-dimensional echocardiography (RT3DE). A total of 105 patients prospectively underwent 2DTT, AL and RT3DE. The LA volume index (LAVI) and emptying fraction were measured. In addition, intra- and inter-observer agreement were calculated by using the intraclass correlation coefficient. There were no significant differences in LAVI and emptying fraction measured by 2DTT in comparison with those made by AL or RT3DE, furthermore Bland-Altman analysis showed that 2DTT had significantly better agreement for LAVI and emptying fraction with AL and RT3DE. 2DTT also exhibited smaller intra- and inter-observer variability as compared with AL or RT3DE. Furthermore, the time to measure LA volume and acquire time-volume curve was significantly less by 2DTT than that by RT3DE (U = 49.00, P < 0.001). These observations suggest that the 2DTT could provide valuable information which is consistent with the standard AL and RT3DE measurements for LAVI and function with potentially lower intra- and inter-observer variability.

Enhanced intensity on preoperative double contrast-enhanced sonography as a useful indicator of lymph node metastasis in patients with gastric cancer.

OBJECTIVES: The aim of this study was to investigate the predictive value of enhanced intensity on double contrast-enhanced sonography in assessing lymph node metastasis of gastric cancer. METHODS: A total of 357 patients with gastric cancer were enrolled in this study. Double contrast-enhanced sonography, in which an oral ultrasound contrast agent is combined with an intravenous contrast agent, was performed preoperatively, and the data were analyzed quantitatively. The predictive ability of enhanced intensity, a quantitative double contrast-enhanced sonographic measure, for lymph node metastasis was evaluated retrospectively. RESULTS: Compared to negative lymph node metastasis cases, the presence of thicker lesions, deeper invasion, poorer differentiation, and higher enhanced intensity were found in positive cases (P< .05). An enhanced intensity cutoff value of 16.91 dB was the best point for balancing the sensitivity and specificity (71.50% and 79.30%, respectively) for prediction of lymph node metastasis, with the highest Youden index of 0.508. The area under the receiver operating characteristic curve was 0.828 (P < .001; 95% confidence interval, 0.786-0.870). In cases in which the lesions were hyperenhanced (enhanced intensity >16.91 dB), the lesions were significantly thicker and had deeper invasion, poorer differentiation, and more positive metastasis findings compared to non-hyperenhanced cases (enhanced intensity ≤16.91 dB; P < .05). On logistic regression analysis, the enhanced intensity of primary tumors and the invasion depth were significantly associated with lymph node metastasis. CONCLUSIONS: Double contrast-enhanced sonography with quantitative analysis may be considered a novel alternative imaging modality for noninvasive preoperative evaluation of lymph node metastasis with good reliability.

Predictors of Gleason Grading Group Upgrading in Low-Risk Prostate Cancer Patients From Transperineal Biopsy After Radical Prostatectomy.

RATIONALE AND OBJECTIVES: To investigate the predictors of Gleason Grading Group (GGG) upgrading in low-risk prostate cancer (Gleason score=3 + 3) from transperineal biopsy after radical prostatectomy (RP). MATERIALS AND METHODS: The clinical data of 160 patients who underwent transperineal biopsy and RP from January 2017 to December 2022 were retrospectively analyzed. First, univariate and multivariate logistic regression analysis were used to obtain independent predictors of postoperative GGG upgrading. Then receiver operating characteristic curve was used to evaluate the diagnostic efficacy of predictors. Finally, Linear-by-Linear Association test was used to analyze the risk trends of patients in different predictor groups in the postoperative GGG. RESULTS: In this study, there were 81 cases (50.6%) in the GGG concordance group and 79 cases (49.4%) in the GGG upgrading group. Univariate analysis showed age, free/total prostate-specific antigen (f/tPSA), proportion of positive biopsies, positive target of magnetic-resonance imaging (MRI) and positive target of contrast-enhanced ultrasound had significant effects on GGG upgrading (all P < .05). In multivariate logistic regression analysis, age (odds ratio [OR]=1.066, 95%CI=1.007-1.127, P = .027), f/tPSA (OR=0.001, 95%CI=0-0.146, P = .001) and positive target of MRI (OR=3.005, 95%CI=1.353-76.674, P = .007) were independent predictors. The prediction model (area under curve=0.751 P < .001) had higher predictive efficacy than all independent predictors. The proportion of patients in exposed group of different GGG increased with the level of GGG, but decreased in nonexposed group, and the linear trend was significantly different (all P < .001). CONCLUSION: Age, f/tPSA, and positive target of MRI were independent predictors of postoperative GGG upgrading. The predictive model constructed had the best diagnostic efficacy.

Designing a Trifoliate Flap for Isolated Congenital Alar Rim Defect in Pediatric Patients.

Isolated congenital alar rim defects are extremely rare, and there has been no standard technique for the reconstruction of remarkable aesthetic deformity. Herein, we introduce a trifoliate flap for the correction of isolated congenital alar rim defects in pediatric patients. Fifteen cases undergoing nasal alar sulcus rotation flap surgery were analyzed retrospectively. This rotation flap including 3 triangles was a modified flap based on prior studies. Clinical medical notes and photographs were reviewed. Patients' (or their parents) reported satisfactions with aesthetic outcome were also evaluated during the post-operative follow-up period. In all patients, the isolated congenital alar rim defects were successfully reconstructed. The rotation flap survived and the wound healed primarily. The follow-up period ranged from 6 to 22 months (average 11 months). There were no incidents of flap loss, step-off deformities, nasal obstruction, or alar retraction. At follow-up of post-operative 3 months, pale red scars were observed in the operative area in few patients (2/15). However, these scars gradually became invisible at post-operative 6 months. All patients (or their parents) were satisfied with the aesthetic outcome of this operation. This newly designed trifoliate flap can be an alternative method for the reconstruction of isolated congenital alar rim defects in pediatric patients. The scars of this procedure can be unobvious with fine surgical suture.

Contexte: Les anomalies congénitales isolées du pourtour de l'aile du nez sont extrêmement rares et il n'existe aucune technique de référence pour la reconstruction de cette difformité esthétique notable. Nous présentons ici un volet trifolié pour la correction des anomalies congénitales du pourtour de l'aile du nez chez des patients pédiatriques. Méthodes: Quinze cas de patients subissant une chirurgie avec rotation de lambeau de sillon de l'aile du nez ont été analysés rétrospectivement. Ce lambeau de rotation comportant trois triangles était une version modifiée d'un lambeau utilisé dans des études précédentes. Les notes médicales cliniques et les photographies ont été analysées. La satisfaction exprimée par les patients (ou leurs parents) à propos du résultat esthétique a été également évaluée au cours de la période de suivi postopératoire. Résultats: L'anomalie congénitale isolée du pourtour de l'aile du nez a été réparée avec succès chez tous les patients. Le lambeau de rotation a survécu et la plaie a guéri d'emblée: la durée de la période de suivi allait de 6 mois à 22 mois (moyenne: 11 mois). Il n'y a pas eu d'incidents de perte du lambeau, de difformité en marche d'escalier, d'obstruction nasale ou de rétraction de l'aile du nez. Au suivi postopératoire de 3 mois, des cicatrices rouge pâle ont été observées dans la zone opératoire de quelques patients (2/15). Cependant, ces cicatrices sont devenues progressivement invisibles à la visite postopératoire de 6 mois. Tous les patients (ou leurs parents) ont été satisfaits du résultat esthétique de cette opération. Conclusion: Ce lambeau trifolié nouvellement conçu peut être une méthode de substitution pour la reconstruction des anomalies congénitales isolées du pourtour de l'aile du nez chez des patients pédiatriques. Les cicatrices secondaires à cette opération peuvent être non évidentes avec une suture chirurgicale fine.

Preoperative Value of Contrast-Enhanced Ultrasound in Totally Laparoscopic Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Liver Tumors: A Preliminary Study.

ABSTRACT: The clinical data of 15 cases that planned to receive totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy were retrospectively collected. Before the stage 1 operation, the size and number of the tumors in future liver remnant (FLR) and the presence of cancer embolus in the portal vein were assessed using contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). Before the stage 2 operation, CEUS was performed to assess the presence of traffic blood flow between the diseased liver and FLR after round-the-liver ligation. Before the stage 1 operation, 5 cases with tumors in FLR were found by CEUS and 6 cases were found by CECT ( P > 0.05). Similarly, CEUS found 5 cases with cancer thrombus in portal vein, and CECT found 7 cases ( P = 0.500). The consistency between the 2 modalities was good (κ = 0.857, P < 0.05, κ = 0.727, P < 0.05, respectively). Before the stage 2 operation, CEUS confirmed that there were 7 cases without traffic blood flow between the diseased liver and FLR, and 3 cases with residual traffic blood flow. The daily growth rate of FLR in the group without traffic blood flow (mean rank = 7.00) was higher than that in the group with traffic blood flow (2.00) significantly ( P < 0.05). Contrast-enhanced ultrasound is a promising application in the preoperative evaluation of totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy.

Diagnostic performance of artificial intelligence-based computer-aided diagnosis system in longitudinal and transverse ultrasonic views for differentiating thyroid nodules.

Objective: To evaluate the diagnostic performance of different ultrasound sections of thyroid nodule (TN) using computer-aided diagnosis system based on artificial intelligence (AI-CADS) in predicting thyroid malignancy. Materials and methods: This is a retrospective study. From January 2019 to July 2019, patients with preoperative thyroid ultrasound data and postoperative pathological results were enrolled, which were divided into two groups: lower risk group (ACR TI-RADS 1, 2 and 3) and higher risk group (ACR TI-RADS 4 and 5). The malignant risk scores (MRS) of TNs were obtained from longitudinal and transverse sections using AI-CADS. The diagnostic performance of AI-CADS and the consistency of each US characteristic were evaluated between these sections. The receiver operating characteristic (ROC) curve and the Cohen κ-statistic were performed. Results: A total of 203 patients (45.61 ± 11.59 years, 163 female) with 221 TNs were enrolled. The area under the ROC curve (AUC) of criterion 3 [0.86 (95%CI: 0.80~0.91)] was lower than criterion 1 [0.94 (95%CI: 0.90~ 0.99)], 2 [0.93 (95%CI: 0.89~0.97)] and 4 [0.94 (95%CI: 0.90, 0.99)] significantly (P<0.001, P=0.01, P<0.001, respectively). In the higher risk group, the MRS of transverse section was higher than longitudinal section (P<0.001), and the agreement of extrathyroidal extension and shape was moderate and fair (κ =0.48, 0.31 respectively). The diagnostic agreement of other ultrasonic features was substantial or almost perfect (κ >0.60). Conclusion: The diagnostic performance of computer-aided diagnosis system based on artificial intelligence (AI-CADS) in longitudinal and transverse ultrasonic views for differentiating thyroid nodules (TN) was different, which was higher in the transverse section. It was more dependent on the section for the AI-CADS diagnosis of suspected malignant TNs.

Comparison of S-Detect and thyroid imaging reporting and data system classifications in the diagnosis of cytologically indeterminate thyroid nodules.

Purpose: The aim of this study was to investigate the value of S-Detect for predicting the malignant risk of cytologically indeterminate thyroid nodules (CITNs). Methods: The preoperative prediction of 159 CITNs (Bethesda III, IV and V) were performed using S-Detect, Thyroid Imaging Reporting and Data System of American College of Radiology (ACR TI-RADS) and Chinese TI-RADS (C-TIRADS). First, Linear-by-Linear Association test and chi-square test were used to analyze the malignant risk of CITNs. McNemar's test and receiver operating characteristic curve were used to compare the diagnostic efficacy of S-Detect and the two TI-RADS classifications for CITNs. In addition, the McNemar's test was used to compare the diagnostic accuracy of the above three methods for different pathological types of nodules. Results: The maximum diameter of the benign nodules was significantly larger than that of malignant nodules [0.88(0.57-1.42) vs 0.57(0.46-0.81), P=0.002]. The risk of malignant CITNs in Bethesda system and the two TI-RADS classifications increased with grade (all P for trend<0.001). In all the enrolled CITNs, the diagnostic results of S-Detect were significantly different from those of ACR TI-RADS and C-TIRADS, respectively (P=0.021 and P=0.007). The sensitivity and accuracy of S-Detect [95.9%(90.1%-98.5%) and 88.1%(81.7%-92.5%)] were higher than those of ACR TI-RADS [87.6%(80.1%-92.7%) and 81.8%(74.7%-87.3%)] (P=0.006 and P=0.021) and C-TIRADS [84.3%(76.3%-90.0%) and 78.6%(71.3%-84.5%)] (P=0.001 and P=0.001). Moreover, the negative predictive value and the area under curve value of S-Detect [82.8% (63.5%-93.5%) and 0.795%(0.724%-0.855%)] was higher than that of C-TIRADS [54.8%(38.8%-69.8%) and 0.724%(0.648%-0.792%] (P=0.024 and P=0.035). However, the specificity and positive predictive value of S-Detect were similar to those of ACR TI-RADS (P=1.000 and P=0.154) and C-TIRADS (P=1.000 and P=0.072). There was no significant difference in all the evaluated indicators between ACR TI-RADS and C-TIRADS (all P>0.05). The diagnostic accuracy of S-Detect (97.4%) for papillary thyroid carcinoma (PTC) was higher than that of ACR TI-RADS (90.4%) and C-TIRADS (87.8%) (P=0.021 and P=0.003). Conclusion: The diagnostic performance of S-Detect in differentiating CITNs was similar to ACR TI-RADS and superior to C-TIRADS, especially for PTC.

Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant.

PhaP or phasin is an amphiphilic protein located on surfaces of microbial storage polyhydroxyalkanoates granules. This study aimed to explore amphiphilic properties of PhaP for possible application as a protein surfactant. Following agents were used to conduct this study as controls including bovine serum albumin, sodium dodecyl sulfate (SDS), Tween 20, sodium oleate, a commercial liquefied detergent together with the same amount of PhaP. Among all these tested control surfactants, PhaP showed the strongest effect to form emulsions with lubricating oil, diesel, and soybean oil, respectively. PhaP emulsion stability study compared with SDS revealed that PhaP had a stronger capability to maintain a very stable emulsion layer after 30 days while SDS lost half and two-thirds of its capacity after 2 and 30 days, respectively. When PhaP was more than 200 µg/ml in the water, all liquids started to exhibit stable emulsion layers. Similar to SDS, PhaP significantly reduced the water contact angles of water on a hydrophobic film of biaxially oriented polypropylene. PhaP was thermally very stable, it showed ability to form emulsion and to bind to the surface of polyhydroxybutyrate nanoparticles after a 60- min heating process at 95 °C. It is therefore concluded that PhaP is a protein with thermally stable property for application as natural and environmentally friendly surfactant for food, cosmetic, and pharmaceutical usages.

Microbial production of polyhydroxyalkanoate block copolymer by recombinant Pseudomonas putida.

Polyhydroxyalkanoate (PHA) synthesis genes phaPCJ(Ac) cloned from Aeromonas caviae were transformed into Pseudomonas putida KTOY06ΔC, a mutant of P. putida KT2442, resulting in the ability of the recombinant P. putida KTOY06ΔC (phaPCJ(A.c)) to produce a short-chain-length and medium-chain-length PHA block copolymer consisting of poly-3-hydroxybutyrate (PHB) as one block and random copolymer of 3-hydroxyvalerate (3HV) and 3-hydroxyheptanoate (3HHp) as another block. The novel block polymer was studied by differential scanning calorimetry (DSC), nuclear magnetic resonance, and rheology measurements. DSC studies showed the polymer to possess two glass transition temperatures (T(g)), one melting temperature (T(m)) and one cool crystallization temperature (T(c)). Rheology studies clearly indicated a polymer chain re-arrangement in the copolymer; these studies confirmed the polymer to be a block copolymer, with over 70 mol% homopolymer (PHB) of 3-hydroxybutyrate (3HB) as one block and around 30 mol% random copolymers of 3HV and 3HHp as the second block. The block copolymer was shown to have the highest tensile strength and Young's modulus compared with a random copolymer with similar ratio and a blend of homopolymers PHB and PHVHHp with similar ratio. Compared with other commercially available PHA including PHB, PHBV, PHBHHx, and P3HB4HB, the short-chain- and medium-chain-length block copolymer PHB-b-PHVHHp showed differences in terms of mechanical properties and should draw more attentions from the PHA research community.

Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction.

BACKGROUND: Chronic alcoholism leads to the onset and progression of alcoholic cardiomyopathy through toxic mechanisms of ethanol and its metabolite, acetaldehyde. This study examined the impact of altered acetaldehyde metabolism through systemic transgenic overexpression of aldehyde dehydrogenase-2 (ALDH2) on chronic alcohol ingestion-induced myocardial damage. METHODS AND RESULTS: ALDH2 transgenic mice were produced with the chicken beta-actin promoter. Wild-type FVB and ALDH2 mice were placed on a 4% alcohol diet or a control diet for 14 weeks. Myocardial and cardiomyocyte contraction, intracellular Ca(2+) handling, histology (hematoxylin and eosin, Masson trichrome), protein damage, and apoptosis were determined. Western blot was used to monitor the expression of NADPH oxidase, calcineurin, apoptosis-stimulated kinase (ASK-1), glycogen synthase kinase-3beta (GSK-3beta), GATA4, and cAMP-response element binding (CREB) protein. ALDH2 reduced the chronic alcohol ingestion-induced elevation in plasma and tissue acetaldehyde levels. Chronic alcohol consumption led to cardiac hypertrophy, reduced fractional shortening, cell shortening, and impaired intracellular Ca(2+) homeostasis, the effect of which was alleviated by ALDH2. In addition, the ALDH2 transgene significantly attenuated chronic alcohol intake-induced myocardial fibrosis, protein carbonyl formation, apoptosis, enhanced NADPH oxidase p47(phox) and calcineurin expression, as well as phosphorylation of ASK-1, GSK-3beta, GATA4, and CREB. CONCLUSIONS: The present results suggest that transgenic overexpression of ALDH2 effectively antagonizes chronic alcohol intake-elicited myocardial hypertrophy and contractile defect through a mechanism that is associated, at least in part, with phosphorylation of ASK-1, GSK-3beta, GATA4, and CREB. These data strongly support the notion that acetaldehyde may be an essential contributor to the chronic development of alcoholic cardiomyopathy.

Characterization of variant diphtheria toxin-interleukin-3 fusion protein, DTIL3K116W, for phase I clinical trials.

We have produced clinical grade of DTIL3K116W, a variant diphtheria toxin-interleukin-3 fusion protein, for treatment of acute myeloid leukemia. The product was filter sterilized, aseptically vialed, and stored at -80 degrees C. It was characterized by Coomassie-stained SDS-PAGE, endotoxin assay, cytotoxicity assay, sterility, mass spectroscopy, receptor binding affinity, ADP-ribosylation, inhibition of normal human CFU-GM, disulfide bond analysis, immunoblots, stability, size exclusion chromatography-HPLC, sequencing, and immunohistochemistry. Vialed product was sterile in 0.25 M NaCl/5 mM Tris, pH 7.9, and had a protein concentration of 1.08 mg/ml. Purity by SDS-PAGE was >99%. Aggregates by HPLC were <1%. Endotoxin levels were 0.296EU/mg. Peptide mapping and mass spectroscopy confirmed its composition and molecular weight. The vialed drug kept reactivity with anti-IL3 and DT antibodies. Potency study revealed a 48-h EC(50) of 0.5 pM on TF1/H-ras cell. Its binding properties were confirmed by competitive experiments showing IC(50) of 1.4 nM. ADP-ribosylation activity was equivalent to DTGM-CSF. Drug did not react with tested frozen human tissue sections by immunohistochemistry. There was no evidence of loss of solubility, proteolysis aggregation, or loss of potency over 6 months at -80 degrees C. Further, the drug was stable at 4 and 25 degrees C in the plastic syringe and administration tubing for 48 h.

A rare case report: tricuspid valve prolapse due to spontaneous chordae rupture in a congenitally corrected transposition of the great arteries patient.

BACKGROUND: Congenitally corrected transposition of great arteries (CCTGA) is caused by atrioventricular and ventriculoarterial discordance. Cases of CCTGA with spontaneous chordae rupture of tricuspid valve have not been reported before. CASE PRESENTATION: Here we diagnosed a 38-year-old man, who was found CCTGA 14 years ago, as spontaneous chordae rupture by real-time three dimentional transesophageal echocardiography (RT-3D-TEE). The present case is the first report to describe a CCTGA patient combine with spontaneous chordae rupture in tricuspid valve. After tricuspid valve replacement, the patient was uneventful after 6 years' follow-up. CONCLUSION: We reported a rare case with spontaneous chordae rupture of tricuspid valve in a CCTGA patient and explored its etiology here. RT-3D-TEE is an important supplement to 2-dimentional transthoracic echocardiography and can provide more accurate detections in tricuspid valve diseases in CCTGA.