Percutaneous popliteal approach for angioplasty of superficial femoral artery occlusions

Angioplasty using the percutaneous popliteal approach was utilized in 50 patients (PTS) to recanalize 59 occluded superficial femoral arteries which had been unsuccessfully canalized by using the antegrade approach because of either a flush origin occlusion or inability to maintain the guide wire in the true lumen. All PTS had claudication; 8 had rest pain; 3 had non-healing ulcers. The laser Probe was used in 17 cases and the Rotablator in 3 cases. Occlusion length varied between 1 and 40 cm: 7 lesions were less than 10 cm (group 1); 9 were between 10 and 20 cm (group 2); and 43 were greater than 20 cm (group 3). An angiographic success was obtained in 48/59 lesions (81%): 14/16 (87%) in groups 1 and 2 and 34/43 (79%) in group 3. Three PTS needed complementary common femoral endarterectomy and one required percutaneous aspiration of a thromboembolus. Complications included: arterial perforation and/or dissection (without clinical sequelae) in 11 and a popliteal hematoma in 1 PT. One patient with a severely ischemic leg underwent successful emergency vascular surgery, while another limb salvage patient required below-knee amputation. There was no worsening of limb ischemia from any popliteal approach attempt. At discharge, 39 patients (78%) whose outcome would have been unsuccessful with the traditional antegrade approach were clinically improved after utilizing the popliteal approach to achieve a successful angioplasty procedure.     

Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.     

On the Role of Ultrasonography and CT Scan in the Diagnosis of Acute Appendicitis

The purposes of this study were to revisit the utility of ultrasonography (USG) as a primary imaging modality in acute appendicitis (AA) and to establish the role of CT scan as a second-line/problem-solving modality. All cases of suspected AA were referred for urgent USG. USG was done with standard protocol for appendicitis. Limited computed tomographic (CT) scan [NCCT ± CECT (IV contrast only)] was done for the lower abdomen and pelvis where sonographic findings were equivocal. One hundred and twenty-one patients were referred for USG for suspected appendicitis. Eight-four patients underwent surgery for AA based on clinical as well as imaging findings, of whom 76 had appendicitis confirmed at histopathology. Three patients were misdiagnosed (3.6 %) on USG as appendicitis. Of 76 patients of appendicitis confirmed histopathologically, 63 (82.8 %) had features of appendicitis on USG and did not require any additional imaging modality. Of 121 patients, 12 (10 %) needed CT scan because of atypical features on USG. Of these 12 patients, seven had retrocecal appendicitis, and three high-up paracolic appendicitis. USG alone had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81, 88, 92.6, 71.6, and 83 %, respectively. When combined with CT scan in select cases, the sensitivity, specificity, PPV, NPV, and accuracy of combined USG + CT scan were 96 % (P?=?0.0014), 89 %, 93 %, 93.5 % (P?=?0.0001), and 93 % (P?=?0.0484), respectively. Twenty-eight (23 %) patients were given alternative diagnosis on USG. Dedicated appendiceal USG should be used as a primary imaging modality in diagnosing or excluding AA. Appendiceal CT can serve as a problem-solving modality.     

Surgical experience with diseases of the tricuspid valve. Cross-sectional and Doppler echocardiographic evaluation following DeVega's repair

Seventy-eight patients undergoing mitral valve surgery with or without replacement of the aortic valve also underwent procedures on the tricuspid valve over a period of 10 years. All patients were in functional class III or IV preoperatively. The procedures were performed in all patients with organic disease of the tricuspid valve (N = 44) and in those with moderate or severe functional tricuspid valvar regurgitation (N = 34). Seventy-one patients underwent DeVega's annuloplasty with or without commissurotomy. The overall mortality was 11.5%. 65 long-term survivors were followed up for a period of 6 months to 10 years (mean 5.3 years). Sixty-three patients were in functional class I or II at the last follow-up. Six patients had clinical evidence of mild to moderate tricuspid regurgitation. Regression of cardiomegaly (as judged by the chest radiograph and right ventricular hypertrophy seen in the electrocardiogram) was evident in most cases. Fifty-one of 54 patients evaluated by cross-sectional echocardiography were reported to have a functionally normal tricuspid valve. Doppler echocardiography in 28 patients showed no significant tricuspid regurgitation or stenosis in 26 patients. Eleven consecutive patients undergoing DeVega's annuloplasty were studied prospectively with pre- and postoperative Doppler echocardiography. Good correlation existed between right ventricular systolic pressures predicted by Doppler with those obtained preoperatively at cardiac catheterization. Postoperative Doppler echocardiography in these 11 patients showed complete restoration of competence of the tricuspid valve as well as normalisation of the right ventricular systolic pressure in 10 patients.     

Do Current Recommendations for Upper Instrumented Vertebra Predict Shoulder Imbalance? An Attempted Validation of Level Selection for Adolescent Idiopathic Scoliosis

Background

Shoulder balance for adolescent idiopathic scoliosis (AIS) patients is associated with patient satisfaction and self-image. However, few validated systems exist for selecting the upper instrumented vertebra (UIV) post-surgical shoulder balance.

Questions/Purposes

The purpose is to examine the existing UIV selection criteria and correlate with post-surgical shoulder balance in AIS patients.

Methods

Patients who underwent spinal fusion at age 10–18 years for AIS over a 6-year period were reviewed. All patients with a minimum of 1-year radiographic follow-up were included. Imbalance was determined to be radiographic shoulder height |RSH| ≥ 15 mm at latest follow-up. Three UIV selection methods were considered: Lenke, Ilharreborde, and Trobisch. A recommended UIV was determined using each method from pre-surgical radiographs. The recommended UIV for each method was compared to the actual UIV instrumented for all three methods; concordance between these levels was defined as “Correct” UIV selection, and discordance was defined as “Incorrect” selection.

Results

One hundred seventy-one patients were included with 2.3 ± 1.1 year follow-up. For all methods, “Correct” UIV selection resulted in more shoulder imbalance than “Incorrect” UIV selection. Overall shoulder imbalance incidence was improved from 31.0% (53/171) to 15.2% (26/171). New shoulder imbalance incidence for patients with previously level shoulders was 8.8%.

Conclusions

We could not identify a set of UIV selection criteria that accurately predicted post-surgical shoulder balance. Further validated measures are needed in this area. The complexity of proximal thoracic curve correction is underscored in a case example, where shoulder imbalance occurred despite “Correct” UIV selection by all methods.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9451-y) contains supplementary material, which is available to authorized users.     

Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation

Tank-binding kinase (TBK)1 plays a central role in innate immunity: it serves as an integrator of multiple signals induced by receptor-mediated pathogen detection and as a modulator of IFN levels. Efforts to better understand the biology of this key immunological factor have intensified recently as growing evidence implicates aberrant TBK1 activity in a variety of autoimmune diseases and cancers. Nevertheless, key molecular details of TBK1 regulation and substrate selection remain unanswered. Here, structures of phosphorylated and unphosphorylated human TBK1 kinase and ubiquitin-like domains, combined with biochemical studies, indicate a molecular mechanism of activation via transautophosphorylation. These TBK1 structures are consistent with the tripartite architecture observed recently for the related kinase IKKβ, but domain contributions toward target recognition appear to differ for the two enzymes. In particular, both TBK1 autoactivation and substrate specificity are likely driven by signal-dependent colocalization events.     

Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anti-cluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4(+) T-cell allostimulatory capacity. CD27(+) memory B cells and, more specifically, CD27(+) IgM(+) B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. CONCLUSION: Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population.