Differentiation of histopathological growth patterns of colorectal liver metastases by MRI features.

BACKGROUND: It is necessary to develop an accurate non-invasive method to determine the histopathological growth pattern (HGP) of colorectal liver metastasis (CRLM) before surgery. The present study aimed to identify various HGPs of CRLM by magnetic resonance imaging (MRI) features. METHODS: This retrospective study included 53 chemo-naïve patients with CRLM between December 2013 and September 2019. The HGPs of CRLM were assessed according to the international consensus guidelines, and were classified as either replacement HGP (rHGP) or non-rHGP. The MRI features of CRLM were retrospectively reviewed in consensus by two radiologists. The differences of MRI features between rHGP and non-rHGP tumors were compared by using Chi-square test and Student's t-test. The Spearman or Pearson correlation analysis was performed to determine the correlation between different MRI features. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic ability. RESULTS: Of the 53 chemo-naïve patients (mean age, 60.11±9.85 years; age range, 38-86 years), 12 were diagnosed as rHGP, while 41 were diagnosed as non-rHGP. Rim enhancement were more common in rHGP than in non-rHGP (P<0.001). Besides, the diameter difference (ΔD) between the precontrast and postcontrast images of rHGP was significantly larger than that of the non-rHGP (P=0.001). The rim width was correlated with ΔD, but not correlated with tumor size. The non-rHGP colorectal liver metastases were prone to be washed out in the delayed phases (P=0.043). The area under the curve (AUC) for the differentiation of rHGP and non-rHGP by using rim enhancement and ΔD was 0.828 (95% CI: 0.708-0.949). CONCLUSIONS: The MRI features of CRLM are characteristic and could help to differentiate rHGP and non-rHGP.

DLX5 gene regulates the Notch signaling pathway to promote glomerulosclerosis and interstitial fibrosis in uremic rats.

Uremia largely results from the accumulation of organic waste products normally cleared by the kidneys, which commonly accompanies kidney failure and chronic kidney disease. However, genetic investigations in a uremia remain largely unclear. This study aimed to determine the expression patterns of distal-less homeobox 5 (DLX5) in uremia rat model and further to study its effects on glomerulosclerosis and interstitial fibrosis. Uremic expression chip was applied to screen differentially expressed genes in uremia. Next, we used small interfering RNA-mediated RNA interference to specifically silence DLX5 in experimental uremic rats to understand the regulatory mechanism of DLX5. To understand effect of Notch1 signaling pathway in uremia, we also treated experimental uremic rats with γ-secretase inhibitor (GSI), an inhibitor of Notch1 signaling pathway. The expression of fibronectin (FN), laminin (LN), transforming growth factor-ß1 (TGF-ß1), Hes1, Hes5, and Jagged2 was determined. The semiquantitative assessment was applied to verify the effects of DLX5 on glomerulosclerosis. In the uremic expression chip, we found that DLX5 was upregulated in uremia samples, and considered to regulate the Notch signaling pathway. We found that small interfering RNA-mediated DLX5 inhibition or Notch1 signaling pathway inhibitory treatment relieved and delayed the kidney injury and glomerulosclerosis in uremia. Meanwhile, inhibition of DLX5 or Nothch1 signaling pathway reduced expression of FN, LN, Nothch1, TGF-ß1, Hes1, Hes5, and Jagged2. Intriguingly, we discovered that Notch1 signaling pathway was inhibited after silencing DLX5. In conclusion, these findings highlight that DLX5 regulates Notch signaling, which may, in turn, promote complications of uremia such as kidney fibrosis, providing a novel therapeutic target for treating uremia.

Colony-stimulating factor 1 receptor inhibition prevents against lipopolysaccharide -induced osteoporosis by inhibiting osteoclast formation.

Lipopolysaccharide (LPS) can induce bone loss by stimulating osteoclast formation. Colony-stimulating factor 1 receptor (CSF 1R) inhibitors have great potential for the treatment of rheumatoid arthritis and tumor-related bone erosion. However, its role in LPS-induced bone loss is still not clarified. In this study, we observed the effects of CSF 1R inhibitor, PLX3397, on LPS-induced bone damage in an animal model. The models were established by LPS administration in male Sprague-Dawley rats. PLX3397 (30 mg/kg body weight) was given by oral gavage. MicroCT analysis, biomechanical properties, biomarker assay, histological examination, and mRNA expression of osteoclast differentiation-related genes (Traf6, Fra1, c-fos and NFATc1) were performed on the 8th week. LPS induced bone loss was shown as the decrease in bone volume fraction and trabecular number and increase in trabecular separation (p < 0.05). LPS exposure also markedly decreased the bone biomechanical properties. PLX3397 significantly abolished the LPS-induced bone microstructure damage (p < 0.05) and loss of biomechanical properties. PLX3397 also inhibited the increases of serum tartrate-resistant acid phosphatase 5b level enhanced by LPS (p < 0.05). PLX3397 attenuated the high expression of Traf6, Fra1, c-fos and NFATc1 stimulated by LPS. Our data demonstrated that PLX3397, a type of CSF 1R inhibitor, can suppress LPS-induced bone loss via the inhibition osteoclast formation.

Efficacy of different hemodialysis methods on dendritic cell marker CD40 and CD80 and platelet activation marker CD62P and P10 in patients with chronic renal failure.

BACKGROUND: Chronic renal failure (CRF) has become a major public health concern, which increases the risk of stroke and systemic thromboembolism. Therefore, therapeutic strategies are in urgent requirement. This study was conducted for investigating efficacy of hemodialysis (HD), hemodiafiltration (HDF), and hemoperfusion (HP) in patients with CRF and the correlation with the presence of complications following HD therapy. METHODS: The therapeutic effect, living quality, biochemical indicators, and dry weight were detected before and after the treatment regimens. Flow cytometry was conducted to detect expressions of dendritic cell markers (CD40 and CD80) and platelet activation markers (CD62P and P10), and the relationship between their expression and therapeutic effect as well as the association of these expressions with complications was analyzed. RESULTS: After HD therapy, patients presented with decreased serum creatinine, serum phosphorus, triglyceride, parathyroid hormone, and ß2 -MG expression; increased hemoglobin, plasma albumin expressions, and dry weight; and enhanced therapeutic effect and living quality. CD62P and P10 expressions decreased, while CD40 and CD80 expressions increased following HD therapy. The therapeutic effect improved in patients with low expressions of CD40 and CD80 and high expressions of CD62P and P10 following HP treatment and complications were lower after treatment of HDF and HP. CONCLUSION: The aforementioned results indicated that CRF patients treated with HP exhibited higher expression of CD40 and CD80 and lower expression of CD62P and P10, suggesting that HP is conferred to have better efficacy than HDF and HD. Therefore, HP may be a promising clinical regimen for treatment of CRF patients.

Effects of microRNA-370 on mesangial cell proliferation and extracellular matrix accumulation by binding to canopy 1 in a rat model of diabetic nephropathy.

As one major diabetic complication, diabetic nephropathy (DN) has been reported to be associated with various kinds of microRNA (miRNA). Thus, we conducted this study to explore the potential of miR-370 in a rat model of DN through investigation of mesangial cell proliferation and extracellular matrix (ECM). A total of 40 healthy adult male Sprague-Dawley rats were enrolled and assigned into normal (n = 10) and DN ( n = 30, DN rat model) groups. Dual-luciferase reporter assay was performed for the targeting relationship between miR-370 and canopy 1 (CNPY1). Mesangial cells were collected and transfected with prepared mimic, inhibitor or small interfering RNA (siRNA) for analyzing the effect of miR-370 on DN mice with the help of expression and cell biological processes detection. CNPY1 was confirmed as a target gene of miR-370. DN mice had increased expression of miR-370, fibronectin, type I collagen (Col I), type IV collagen (Col IV), and plasminogen activator inhibitor-1 (PAI-1) but reduced CNPY1 expression. Cells transfected with miR-370 mimic and siRNA-CNPY1 had increased expression of fibronectin, Col I, Col IV, and PAI-1 but decreased CNPY1 expression. The miR-370 mimic and siRNA-CNPY1 groups showed increased cell proliferation, as well as elevated ECM accumulation and declined cell apoptosis rate as compared with the blank and negative control groups, with reverse trends observed in the miR-370 inhibitor group. Our study concludes that overexpression of miR-370 promotes mesangial cell proliferation and ECM accumulation by suppressing CNPY1 in a rat model of DN.

Gastrin-releasing peptide receptor gene silencing inhibits the development of the epithelial-mesenchymal transition and formation of a calcium oxalate crystal in renal tubular epithelial cells in mice with kidney stones via the PI3K/Akt signaling pathway.

Between 1% and 15% of people are globally affected by kidney stones, and this disease has become more common since the 1970s. Therefore, this study aims to investigate the effects of gastrin-releasing peptide receptor (GRPR) gene silencing via the PI3K/Akt signaling pathway on the development of the epithelial-mesenchymal transition (EMT) and formation of a calcium oxalate crystal in renal tubular epithelial cells (TECs) of kidney stones. A total of 70 clean and healthy C57BL/6J mice were assigned into the normal ( n = 10) and kidney stones groups ( n = 60). The underlying regulatory mechanisms of GRPR were analyzed in concert with the treatment of shGRPR-1, LY294002, and shGRPR-1 + LY294002 in TECs isolated from mice with kidney stones. A series of experiments were conducted for the measurement of urinary oxalate and urinary calcium, the renal calcium salt deposition, the positive rate of GRPR, the expressions of renal TECs related genes and calcium oxalate regulation related genes, and the growth of calcium crystals induced by cells. After treatment of shGRPR-1 and shGRPR-1 + LY294002, levels of urinary oxalate and urinary calcium in the serum, as well as positive rate of GRPR, became relatively low, levels of E-cadherin enhanced, whereas levels of Akt, PI3K, GRPR, extents of PI3K and Akt phosphorylation, α-SMA, Vimentin and FSP-1, OPN, MCP-1, and CD44 decreased and a number of crystals reduced. Taken together, we conclude that GRPR gene silencing suppresses the development of the EMT and formation of the calcium oxalate crystal in renal TECs of kidney stones through the inactivation of the PI3K/Akt signaling pathway.

Beraprost Sodium, a Stable Analogue of PGI2, Inhibits the Renin-Angiotensin System in the Renal Tissues of Rats with Chronic Renal Failure.

BACKGROUND/AIMS: Chronic renal failure (CRF) is a prolonged kidney condition characterized by decreased kidney function that can eventually develop into total kidney failure. The renin-angiotensin system (RAS) helps to regulate the balance between human bodily fluids and electrolytes. The aim of the present study was to investigate the effects of a prostacyclin analogue (beraprost sodium [BPS]) on the expression of key factors associated with local RAS activities in the renal tissues of rats with CRF. METHODS: After a CRF rat model was successfully established, the levels of BUN, SCr, phosphorus, and calcium were detected by an automatic biochemistry analyzer. Furthermore, the activities of malondialdehyde (MDA) and superoxide dismutase (SOD) in rat renal tissues were measured using a colorimetric method, while the activity of angiotensin-converting enzyme (ACE) was determined by ultraviolet (UV) spectrophotometry. In situ hybridization was employed to determine the expression of angiotensin II type 1 receptor (AT). Finally, the positive expression rates of cells expressing important apoptotic proteins (Bax and Bcl-2) were determined, and the protein and mRNA levels of phosphatidylinositol 3-kinase (AKT) and key factors involved in the RAS (AT1, AT2, angiotensin ACE and angiotensinogen [AGT]) were evaluated by RT-qPCR and western blot analysis. RESULTS: Initial observations revealed that treatment with BPS decreased the levels of BUN, SCr and phosphorus but increased calcium levels in the renal tissues of CRF rats. Additionally, BPS reduced the levels of MDA while increasing the levels of SOD, ACE activity, and AT1 expression in the renal tissues of CRF rats. BPS inhibited glomerular hypertension and hyperfiltration; increased the mRNA and protein levels of AKT and AT2; and decreased the mRNA and protein levels of AT1, AGT, and ACE in the renal tissues of CRF rats. CONCLUSION: The results of this study demonstrate that BPS, a PGI2 analogue, inhibits the expression of key factors involved in the local RAS, resulting in a delay in the occurrence and development of CRF. The key findings of the present study ultimately highlight the potential of this PGI2 analogue as a promising therapeutic strategy for treating CRF.

Research and application of transnasal transesophageal echocardiography probe.

The intubation of conventional transesophageal echocardiography (TEE) probes into patients causes serious esophagus irritation, and thus the use of TEE probes in pediatric practice is limited. In this study, we aimed at the development of a special probe which could be inserted through the nasopharyngeal cavity into the esophagus to obtain the same high-quality echocardiography images as those obtained by conventional TEE and improve patients' experience. During the examination, the patients felt relaxed for a longer time and cooperated with the sonographers in the process of cardiac catheterization conducted in the surgery room or the intensive care unit (ICU), resulting in improved accuracy of the diagnosis and timely administration of appropriate treatment. Two years ago, Prof. Xin-fang WANG put theories into practice by inserting the probe through the nasal cavity and pharynx into the esophagus of volunteers to successfully detect the heart and great vessels at the retrocardiac space. Later, Prof. Ming-xing XIE performed the transnasal TEE examination in 12 atrial septal defect (ASD) patients and proved the safety and reliability of this method, which could become a new way for clinical diagnosis and treatment.

Relationship between the abnormal diastolic vortex structure and impaired left ventricle filling in patients with hyperthyroidism.

Intraventricular hydrodynamics plays an important role in evaluating cardiac function. Relationship between diastolic vortex and left ventricular (LV) filling is still rarely elucidated. The aim of this study was to evaluate the evolution of vortex during diastole in hyperthyroidism (HT) and explore the alteration of hydromechanics characteristics with sensitive indexes.Forty-three patients diagnosed with HT were classified into 2 groups according to whether myocardial damage existed: simple hyperthyroid group (HT1, n = 21) and thyrotoxic cardiomyopathy (HT2, n = 22). Twenty-seven age- and gender-matched healthy volunteers were enrolled as the control group. Offline vector flow mapping (VFM model) was used to analyze the LV diastolic blood flow patterns and fluid dynamics. Hemodynamic parameters, vortex area (A), circulation (C), and intraventricular pressure gradient (ΔP), in different diastolic phases (early, mid, and late) were calculated and analyzed.HT2, with a lower E/A ratio and left ventricular ejection fraction (LVEF), had a larger left atrium diameter (LAD) compared with those of the control group and HT1 (P < .05). Compared with the control group, the vortex size and strength, intraventricular pressure gradient during early and mid-diastole were higher in HT1 and lower in HT2 (P < .05). And in late diastole, the vortex size and strength, intraventricular pressure gradient of HT2 became higher than those of the control group (P < .05). Good correlation could be found between CE and E/A (P < .05), CM and ΔPM (P < .01), CL and FT3 (P < .05).VFM is proven practical for detecting the relationship between the changes of left ventricular diastolic vortex and the abnormal left ventricular filling.

Research and Application of Transnasal Transesophageal Echocardiography Probe / 华中科技大学学报（医学）（英德文版）

The intubation of conventional transesophageal echocardiography (TEE) probes into patients causes serious esophagus irritation,and thus the use of TEE probes in pediatric practice is limited.In this study,we aimed at the development of a special probe which could be inserted through the nasopharyngeal cavity into the esophagus to obtain the same high-quality echocardiography images as those obtained by conventional TEE and improve patients' experience.During the examination,the patients felt relaxed for a longer time and cooperated with the sonographers in the process of cardiac catheterization conducted in the surgery room or the intensive care unit (ICU),resulting in improved accuracy of the diagnosis and timely administration of appropriate treatment.Two years ago,Prof.Xin-fang WANG put theories into practice by inserting the probe through the nasal cavity and pharynx into the esophagus of volunteers to successfully detect the heart and great vessels at the retrocardiac space.Later,Prof.Ming-xing XIE performed the transnasal TEE examination in 12 atrial septal defect (ASD) patients and proved the safety and reliability of this method,which could become a new way for clinical diagnosis and treatment.

(±)-Sinensilactam A, a pair of rare hybrid metabolites with Smad3 phosphorylation inhibition from Ganoderma sinensis.

(+)- and (-)-Sinensilactam A (1), novel hybrid metabolites possessing a unique 2H-pyrrolo[2,1-b][1,3]oxazin-6(7H)-one ring system, were isolated from the fruit bodies of Ganoderma sinensis. The structures of these substances and absolute configurations at their stereocenters were assigned using spectroscopic and computational methods along with X-ray crystallographic analysis. A plausible pathway for the biosynthesis of 1 is proposed. (-)-1 was found to be a Smad3 phosphorylation inhibitor in TGF-ß1 induced human renal proximal tubular cells.

Two new compounds from Ganoderma lucidum.

Two pairs of new enantiomers, lucidulactones A and B (1 and 2), and two known compounds were isolated from Ganoderma lucidum. Their structures were determined by means of spectroscopic methods. The chiral HPLC was used to separate the ( - )- and (+)-antipodes of the new compounds.

Echocardiographic diagnosis of sinus of Valsalva aneurysm: a 17-year (1995-2012) experience of 212 surgically treated patients from one single medical center in China.

OBJECTIVE: To evaluate the value of echocardiography in the diagnosis of different pathological patterns of sinus of Valsalva aneurysms (SVAs). METHODS: Echocardiographic features and surgical findings of 212 consecutive patients with SVAs treated in the last 17 years (1995-2012) at the Union Hospital of Huazhong University of Science and Technology were compared and analyzed retrospectively. RESULTS: 212 Chinese patients with SVAs underwent surgical repairs from January 1995 to May 2012 in our hospital. The aneurysms originated from the right, non-, multiple and left coronary sinus in 77.8%, 19.3%, 2.4% and 0.5%, respectively. 71.7% were ruptured, most commonly into the right ventricle (67.9%) followed by the right atrium (27.4%). Other rare entry sites of rupture included the left atrium, the left ventricle, the interatrial septum, the interventricular septum and the pulmonary artery (0.5%-1.9%). 164 SVAs arising from the right coronary sinus were classified by the Sakakibara method: 47.6% type I, 33.5% type II, 6.1% type IIIv and 12.8% type IIIa. 41 aneurysms of the non-coronary sinus were classified by the Guo method: 61.0% type I, 34.1% type IIa and 4.9% type IIv. The three most common associated cardiovascular lesions were ventricular septal defect (VSD) (53.3%), stenosis of right ventricular outflow tract (RVOTS) (7.5%) and aortic valvular malformations (5.2%). Compared with surgical results, the sensitivity, specificity and accuracy of echocardiographic diagnosis of SVAs were 93.9%, 99.9% and 99.8%, respectively. Of the 13 SVAs that were missed on echocardiography, 77% were small aneurysms of the right coronary sinus extending into the right ventricle across a VSD. Of the 199 cases diagnosed by echocardiography prior to surgery, the diagnostic accuracy of aneurismal origination, termination and whether ruptured or not was 99.0%, 99.0% and 97.5%, respectively. Echocardiography also diagnosed accurately all of the complications of the SVAs with the exception of aneurismal vegetations. The sensitivity, specificity and accuracy of echocardiography in diagnosing the associated cardiovascular lesions were 89.2%, 99.9% and 99.0%, respectively. The most common misdiagnosis and misdiagnosed associated lesions were the RVOTS and the types of VSD, respectively. CONCLUSIONS: Echocardiography has a specific value in the diagnosis of different pathological patterns of the SVAs with distinguishing ultrasonic features. To the best of our knowledge, this is the largest series of patients with SVAs surgically treated in a single medical center.

Coronary sinus septal defect (unroofed coronary sinus): echocardiographic diagnosis and surgical treatment.

OBJECTIVE: To explore the value of transthoracic and right heart contrast echocardiography in the diagnosis of coronary sinus septal defect (CSSD), also known as unroofed coronary sinus. METHODS: The echocardiographic characteristics of 20 patients with CSSD who underwent surgery in our hospital between October 1999 and June 2012 were reviewed retrospectively, including results of 9 cases studied by contrast echocardiography, and compared with surgical results. RESULTS: Of the coronary sinuses in these 20 patients, 40% were totally unroofed, 35% partially unroofed in mid-portion, 20% partially unroofed in terminal portion, and 5% mixed type (mid- and terminal portions). Of these 20 patients, 65% were associated with other types of atrial septal defects, and 65% had a persistent left superior vena cava. The diagnostic accuracy of echocardiography for the CSSD was 65%. In patients whose diagnoses were confirmed by echocardiography, the accuracy for the types of CSSD was 84.6%. All of the first 6 cases studied before 2002 were either undiagnosed or misdiagnosed, and 78.6% of the last 14 cases studied were diagnosed accurately. Of 9 patients who underwent contrast echocardiography, 8 were correctly diagnosed, including 5 type II and 3 Raghib syndromes. 1 case of type IIIa was misdiagnosed as Raghib syndrome. CONCLUSIONS: The combination of transthoracic and contrast echocardiography can diagnose and classify CSSD accurately in most cases and should be the first choice for diagnosing CSSD.

Can the tumor deposits be counted as metastatic lymph nodes in the UICC TNM staging system for colorectal cancer?

OBJECTIVE: The 7th edition of AJCC staging manual implicitly states that only T1 and T2 lesions that lack regional lymph node metastasis but have tumor deposit(s) will be classified in addition as N1c, though it is not consistent in that pN1c is also an option for pT3/T4a tumors in the staging table. Nevertheless, in this TNM classification, how to classify tumor deposits (TDs) in colorectal cancer patients with lymph node metastasis (LNM) and TDs simultaneously is still not clear. The aim of this study is to investigate the possibility of counting TDs as metastatic lymph nodes in TNM classification and to identify its prognostic value for colorectal cancer patients. METHODS AND RESULTS: In this retrospective study, 513 cases of colorectal cancer with LNM were reviewed. We proposed a novel pN (npN) category in which TDs were counted as metastatic lymph nodes in the TNM classification. Cancer-specific survival according to the npN or pN category was analyzed using Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to identify significant prognostic factors. Harrell's C statistic was used to test the predictive capacity of the prognostic models. The results revealed that the TD was a significant prognostic factor in colorectal cancer. Univariate and multivariate analyses uniformly indicated that the npN category was significantly correlated with prognosis. The results of Harrell's C statistical analysis demonstrated that the npN category exhibited a superior predictive capacity compared to the pN category of the 7th edition TNM classification. Moreover, we also found no significant prognostic differences in patients with or without TD in the same npN categories. CONCLUSIONS: The counting of TDs as metastatic lymph nodes in the TNM classification system is potentially superior to the classification in the 7th edition of the TNM staging system to assess prognosis and survival for colorectal cancer patients.

Evaluation of left atrial function in patients with coronary artery disease by two-dimensional strain and strain rate imaging.

BACKGROUND: Left ventricular (LV) dysfunction in patients with coronary artery disease is shown by strain and strain rate imaging. However, left atrium (LA) function in patients with coronary artery disease (CAD) has not been assessed by this method. METHODS AND RESULTS: In 34 CAD patients, including 17 patients with enlarged LA (LA diameter ≤ 4.0 cm) and 17 with normal-size LA (LA diameter ≤ 4.0 cm), two-dimensional strain echocardiographic imaging (2DSE) was performed. Twenty healthy subjects as a control group were included. Both conventional parameters and strain parameters, such as LA peak systolic strain (LAs S/SR), preatrial contraction strain (LAa S), peak systolic (LAs SR), early diastolic strain rate (LAe SR) and late diastolic strain rate (LAa SR), were measured. Conventional parameters were abnormal in CAD patients with enlarged LA (ELA), but there were no significant differences between CAD with normal-size left atrium (NLA) and control groups. LAs S/SR and LAe SR were lower in patients than in normal controls, and were even lower in CAD-ELA group (P < 0.05). LAa S/SR were lower in CAD patients with ELA (P < 0.05), but without a significant difference between CAD-NLA and control groups. A significant correlation was observed between LAs S/SR and LA emptying fraction (r = 0.85, P < 0.05; r = 0.72, P < 0.05, respectively). LAa S/SR related well to LA ejection fraction (r = 0.68, P < 0.05; r = 0.61, P < 0.05, respectively). LAs SR was most accurate in identifying both CAD patients with NLA from controls and CAD patients from controls (area under the curve: 0.91; 0.95, respectively). CONCLUSIONS: LA diastolic dysfunction occurs prior to LA systolic dysfunction in CAD patients, and LAs SR is the most accurate index in identifying patients with CAD.

Echocardiographic characteristics of the criss-cross heart.

OBJECTIVE: To assess the ultrasonic characteristics of the criss-cross heart, and explore the value of echocardiography in the diagnosis of this rare congenital cardiac defect. METHODS: We reviewed the echocardiographic findings in 4 patients having criss-crossed atrioventricular connections at our hospital, and compared the findings with observations at surgery in 3 of the patients. RESULTS: In all 4 patients, there was usual atrial arrangement, right hand ventricular topology, and concordant atrioventricular connections. The inlet components of the ventricular mass, however, crossed such that the apical component of the morphologically right ventricle was situated anteriorly and superiorly, and extended to the left relative to the apex of the morphologically left ventricle. The ventriculo-arterial connections were concordant in 1 patient, double outlet from the morphologically right ventricle in 2, and discordant in the other. In all 4 patients, it proved impossible to obtain the standard 4-chamber view showing simultaneously all four chambers and both atrioventricular valves. A series of apical 4-chamber or subcostal coronal views, obtained by tilting the transducer from posterior to anterior, demonstrate initially the connection of the left-sided left atrium and the right-sided left ventricle through the mitral valve. More anterior angulation of the transducer then showed the right-sided right atrium to be connected to the left-sided right ventricle through the tricuspid valve, confirming the presence of twisted atrioventricular connections. Color Doppler imaging displayed the crossing of the atrioventricular connections without mixing of the streams. Short-axis views across the ventricular mass confirmed that the right ventricle was superior, anterior, and to the left of the left ventricle, and demonstrated the horizontal position of the ventricular septum. When viewed subcostally, the distance between the tricuspid valve and the orifice of the inferior vena cava was significantly increased relative to normal findings. The echocardiographic findings were confirmed during surgical interventions in 3 patients, apart from the failure to diagnose one instance of persistent patency of the left superior vena cava. CONCLUSIONS: The failure to obtain a characteristic 4-chamber view in any cut was diagnostic for recognition of the criss-crossed atrioventricular junctions. Transthoracic echocardiography provides definitive images of this rare arrangement, and accurately defines the associated cardiac abnormalities.