Feasibility and Accuracy of Measuring Carotid Plaque Volume (Burden) With Contrast-Enhanced Tomographic 3D Ultrasound and Ultrasound Image Fusion.

BACKGROUND: Stenosis severity has been the indication for carotid endarterectomy (CEA) for 4 decades, but the annual stroke risk in asymptomatic carotid stenosis >70% is under 2%. Atherosclerotic volume has emerged as a risk factor for future stroke, but needs to be measured noninvasively. Tomographic ultrasound (tUS) is a novel technology that assembles 3D images in seconds. We evaluated accuracy of measuring Carotid Plaque Volume (CPV) with tUS in patients undergoing CEA. METHOD: Consecutive patients were imaged immediately before CEA by tUS and contrast-enhanced tUS (CEtUS). CPV was measured using tUS, CEtUS, and a fused images incorporating both tUS and CEtUS by trained vascular scientists. Precise volume of the endarterectomy specimen was measured using Archimedes technique. RESULTS: Mean ± sd (range) CPV in 129 endarterectomy specimens was 0.75 ± 0.43 cm3 (0.10-2.47 cm3). Mean ± sd CPV measured by tUS (n = 114) was 0.87 ± 0.51 cm3, CEtUS (n = 104) was 0.75 ± 0.45 cm3 and with fusion (n = 95) was 0.83 ± 0.49 cm3. Differences between specimen volume and CPV measured by tUS (0.13 ± 0.24 cm3), CEtUS (-0.01 ± 0.21 cm3) or fusion (-0.08 ± 0.20) were clinically insignificant. Intra-/interobserver differences were minimal. CONCLUSIONS: tUS accurately measures CPV with excellent intra-/interobserver agreement. CEtUS improves accuracy if precise CPV measurement is needed for research but tUS alone would be sufficient for population screening.

Maintenance therapy with a poly(ADP-ribose) polymerase inhibitor in patients with newly diagnosed advanced epithelial ovarian cancer: individual patient data and trial-level meta-analysis.

BACKGROUND: We synthesize the efficacy and toxicity of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with newly diagnosed advanced ovarian cancer. PATIENTS AND METHODS: We manually extracted individual patient data (IPD) for progression-free survival (PFS) from published survival curves of randomized controlled trials (RCTs) that compared PARPi versus placebo as maintenance therapy in first-line treatment, for whole study populations and subgroups, based on BRCA1/BRCA2 mutation (germline and/or somatic) and homologous recombination deficiency (HRD) status, using WebPlotDigitizer software. The respective PFS curves for each study and combined population were reconstructed from extracted IPD. The primary outcome was PFS in combined whole population and subgroups. RESULTS: In IPD analysis of combined population from three RCTs, with 2296 patients and 1287 events, PFS was significantly longer in PARPi versus placebo [median 20.4 (95% confidence interval (CI) 18.6-21.9) versus 14.9 (95% CI 13.9-16.5) months, respectively; hazard ratio (HR) 0.67, 95% CI 0.60-0.75; P < 0.001]. In IPD subgroup analyses from four eligible RCTs (2687 patients and 1485 events), median PFS was significantly longer in PARPi versus placebo arm, in the BRCA-mutated (45.7 versus 17.7 months, respectively; HR 0.38, 95% CI 0.32-0.46; P < 0.001), HRD-positive including BRCA-mutated (34.7 versus 17.9 months, respectively; HR 0.45, 95% CI 0.38-0.54; P < 0.001), and HRD positive excluding BRCA-mutated (22.3 versus 13.1 months, respectively; HR 0.47, 95% CI 0.34-0.65; P < 0.001) subgroups, but not in the HRD-negative (15.0 versus 11.3 months, respectively; HR 0.90, 95% CI 0.76-1.05; P = 0.75) subgroup. Results of trial-level meta-analysis were concordant with IPD analysis in whole population and subgroups. CONCLUSIONS: Among newly diagnosed ovarian cancer patients, PARPi maintenance therapy significantly improves PFS in those with germline and/or somatic BRCA mutation and/or HRD-positive tumor but not in those with HRD-negative tumor.

"Randomised controlled trial of scalp cooling for the prevention of chemotherapy induced alopecia".

BACKGROUND: Randomized controlled trials (RCT) of scalp cooling (SC) to prevent chemotherapy induced alopecia (CIA) did not evaluate its effect on hair regrowth (HR) and was conducted in a predominantly taxane (T) treated population. We conducted an RCT of SC in a setting of anthracycline (A) and taxane chemotherapy (CT) and assessed its effect on CIA and HR. METHODS: Non-metastatic breast cancer women undergoing (neo) adjuvant CT were randomized to receive SC using the Paxman scalp cooling system during every cycle of CT, or no SC. The primary end point (PEP) was successful hair preservation (HP) assessed clinically and by review of photographs after CT. HR was assessed at 6 and 12 weeks. RESULTS: 51 patients were randomized to SC (34) or control arm (17) in a 2:1 ratio. Twenty-five (49%) patients received A followed by T and the two arms were balanced with respect to this factor. HP rate was significantly higher in SC arm compared to control arm (56.3% vs 0%, P = 0.000004). HR was higher in SC arm compared to control at 6 weeks (89% vs 12%; P < 0.001) and 12 weeks (100% vs 59%, P = 0.0003). Loss of hair at PEP evaluation, which was a quality of life measure, was significantly lower in SC versus control arm (45% vs 82%, P = 0.016). There were no grade 3-4 cold related adverse effects. CONCLUSIONS: Women with breast cancer receiving A or T chemotherapy receiving SC were significantly more likely to have less than 50% hair loss after CT, superior hair regrowth and improvement in patient reported outcomes, with acceptable tolerance. It merits wider usage.

Organic zinc and copper supplementation on antioxidant protective mechanism and their correlation with sperm functional characteristics in goats.

Trace minerals feeding had significant effects on sperm production and fertility with better absorption and proper utilization within the body for optimum reproductive function. Several studies have shown that more influenced trace elements in the diets of animals are copper (Cu) and zinc (Zn). Bucks showing deficiency of this mineral might affect the quality of semen production which in turn would affect the fertility. This experiment was thus designed to test the effects of organic Cu and Zn supplementation on antioxidants enzyme activities and sperm functional attributes in fresh semen of bucks. Forty bucks (n = 40, Aged 5 months) were assigned to ten groups of four animals in each group, supplemented (for a period of 8 months) with different levels of organic Zn: 20 mg (T2), 40 mg (T3) and 60 mg (T4), organic Cu: 12.5 mg (T5), 25 mg (T6), 37.5 mg (T7) and combined organic Zn and Cu: 20 + 12.5 mg (T8), 40 + 25 mg (T9), 60 + 37.5 mg (T10), respectively, per kg dry matter and no additional mineral diet (control; T1). One hundred and sixty semen samples were collected through electro-ejaculator and analysed for sperm quantity, quality, acrosome intactness and plasma membrane integrity and correlated with the catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase enzyme activities in seminal plasma. The results indicated organic Cu and zinc supplemented bucks produced more sperm cells, had higher sperm concentrations, maintained higher (p < .01) sperm livability, plasma membrane and acrosome integrities, more motility and velocity. The increased antioxidant enzyme activities, reduced oxidative stress and lowered lipid peroxidation were positively correlated (p < .05) with the sperm functional attributes. In conclusion, organic Cu and Zn supplement to male goats showed protective roles against oxidative damage and maintained better fresh semen characteristics.

Response of in ovo administration of zinc on egg hatchability and immune response of commercial broiler chicken.

An experiment was conducted to determine the effect of in ovo administration of different forms of zinc with respect to hatchability and performance of commercial broiler chicken. In trial 1, the fertile eggs on day 18 were divided into six treatment groups: Group I as control without any supplementation of zinc, group II to IV were supplemented with 0.5 mg zinc per egg as zinc sulphate, zinc methionine or nano zinc, respectively, and Group V with nano zinc at 0.25 mg zinc per egg. Sixth group received 0.5 ml citric acid per egg as sham control. The results of the first trial indicated that in ovo administration of nano zinc at both levels and zinc methionine resulted in complete failure of hatchability. A second trial to validate the result of trial 1 consisted of Group I control (no administration). Group II and Group III were supplemented with zinc sulphate and zinc methionine, respectively, at 0.5 mg zinc per egg. Group IV and Group V were supplemented with nano zinc at 0.04 and 0.08 mg per egg. In the second trial, again there was a similar pattern for zinc sulphate and zinc methionine. Administration of Zn by nano form had around 80% hatchability on fertile eggs in comparison with the unadministered control eggs (92%). There was no difference (p > .05) in body weight gain, feed intake and FCR. No difference (p > .05) was observed between treatments for cell-mediated immune response and humoral immune response. Nano Zn-administered group showed a non-significant downregulation of MUC2 gene. It could be concluded that in ovo administration of higher levels of zinc has to be with caution for the developing embryo of commercial broiler chicken.

Three-dimensional Ultrasound in the Management of Abdominal Aortic Aneurysms: A Topical Review.

Three-dimensional (3D) ultrasound is an evolving modality that may have numerous applications in the management of abdominal aortic aneurysms. Many vascular specialists will not be familiar with the different ways in which 3D vascular ultrasound data can be acquired nor how potential applications are being explored by researchers. Most of the current literature consists of small series and single-centre experience, although clinical themes such as measurement of abdominal aortic aneurysm volume and surveillance following endovascular repair are emerging. The aim of this topical review is to introduce clinicians to the current concepts of 3D ultrasound, review the current literature, and highlight avenues for further research in this new and exciting field of vascular imaging.

Everolimus in heavily pretreated metastatic breast cancer: Is real world experience different?

BACKGROUND: Drugs targeting mammalian target of rapamycin signaling pathway have been recently approved for treatment of hormone receptor (HR) positive metastatic breast cancer (MBC). However, there is lack of real world data from India on the use of this therapeutic strategy. MATERIALS AND METHODS: A retrospective analysis of MBC patients who had recurrence or progression while receiving aromatase inhibitors (AI's) and further treated with everolimus and either tamoxifen/AI/fulvestrant between March 2012 and June 2014, was undertaken. RESULTS: There were 41 patients with median age 55 years, 73% with visceral metastasis, and 73% with ≥2 sites of metastases. Thirty (73%) patients had received 3 prior lines of therapy including AI (100%), tamoxifen (94%), fulvestrant (39%), and chemotherapy (100%) while the remaining had received <3 lines of prior therapy. The commonest Grade 3/4 adverse events were stomatitis (19%), hyperglycemia (new/worsening, 17%), fatigue (14.5%), nonneutropenic infections (14%), anemia (12%) and pneumonitis (7%). Everolimus dose reductions were required in 31% patients. There were 30% partial responses, 38% prolonged disease stabilizations and 32% disease progression as best responses to everolimus. The median progression-free survival was 22 weeks (5 months). CONCLUSIONS: Everolimus based treatment has meaningful activity in heavily pretreated patients with HR-positive MBC but is associated with considerable toxicity and requirement for dose adjustment.

Eribulin in heavily pretreated metastatic breast cancer: A tertiary care center experience from India.

INTRODUCTION: Heavily pretreated metastatic breast cancer (MBC) remains a major therapeutic challenge with limited treatment options this. Eribulin, an anti-microtubule agent, has been recently approved for this indication. There are sparse data from the Asian region for eribulin and merits exploration. MATERIALS AND METHODS: This was a single institution retrospective analysis of MBC patients treated with eribulin from 2013 to 2014. These patients had received at least 2 lines of prior therapy for metastatic disease. Patients received standard doses of eribulin and were monitored for toxicity and responses. RESULTS: Eighteen patients were included in this analysis. They had received a median of 6 lines of therapy previously (including adjuvant treatment) and had significant visceral involvement (median 3 organs). A median of 4 cycles of eribulin was delivered. There were no complete responses; partial responses were seen in 33% (6/18), stable disease status in 28% (5/18) patients, and progressive disease on eribulin in 39% (7/18) patients. The median progression-free survival was 15 weeks (3.5 months), and median overall survival was 27 weeks (6.2 months). Significant Grade 3/4 toxicities seen included peripheral neuropathy in 28% (5/18) and neutropenia in 28% (5/18) of patients while dose reductions were required in 22% (4/18) of patients. CONCLUSION: Eribulin offers a viable, well-tolerated regimen that provides meaningful clinical benefit in Indian patients with MBC.

Antithrombotic treatment for acute extracranial carotid artery dissections: a meta-analysis.

INTRODUCTION: Carotid artery dissection is a leading cause of stroke in younger patients, with an associated prevalence of 2.6-3.0 per 100,000 population. This meta-analysis aims to determine whether in patients managed medically, treatment with anticoagulants or antiplatelet agents was associated with a better outcome with respect to mortality, ischaemic stroke, and major bleeding episodes. PATIENTS AND METHODS: A comprehensive search strategy was employed of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to March 2015), and EMBASE (January 1980 to March 2015) databases. Primary outcomes were death (all causes) or disability. Secondary outcomes were ischaemic stroke, symptomatic intracranial haemorrhage, and major extracranial haemorrhage during the reported follow-up period. RESULTS: No completed randomized trials were found. Comparing antiplatelets with anticoagulants across 38 studies (1,398 patients), there were no significant differences in the odds of death (effects size, ES, -0.007, p = .871), nor in the death and disability comparison or across any secondary outcomes. CONCLUSION: There were no randomised trials comparing either anticoagulants or antiplatelets with control, thus there is no level 1 evidence to support their routine use for the treatment of carotid artery dissection. Also, there were no randomised trials that directly compared anticoagulants with antiplatelet drugs, and the reported non-randomised studies did not show any evidence of a significant difference between the two.

Sunitinib in patients with imatinib-resistant gastrointestinal stromal tumor: A single center experience study.

AIM: The outcome of patients with advanced gastrointestinal stromal tumor (GIST) has improved with the use of imatinib. Despite high response rates with this drug resistance eventually develops in nearly all patients. We present an analysis of prospectively collected data on sunitinib efficacy and safety in patients with imatinib-resistant GIST. SUBJECTS AND METHODS: Between November 2006 and October 2007, patients with GIST were accrued in an approved sunitinib patient access protocol. Key eligibility criteria included tumor resistance to imatinib and/or patient intolerance to this drug. Patients received sunitinib at a starting dose of 50 mg once daily for 4 weeks in a 6 week cycle, with standardized dose modification titrated to toxicity. Patients were continued on sunitinib until disease progression or unacceptable toxicity. The endpoints were safety, overall survival (OS) and objective response rate (ORR). RESULTS: Fifteen patients, all of whom had imatinib resistance and none intolerance, with median age of 48 (26-69) years, were treated on the protocol. The most common sites of primary disease were small intestine (40%), stomach (26.7%) and retroperitoneal (26.7%). A median of 10 (1-47) cycles of sunitinib were delivered, 9 (60%) patients required dose reductions due to toxicity whereas dose delay of > 2 weeks was required in only one (6.7%) patient. There were no toxicity-related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand-foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow-up of 81 months in surviving patients, the median progression-free and overall survivals were 15.5 and 18.7 months, respectively. CONCLUSIONS: Sunitinib appears to be an effective and well-tolerated treatment for Indian patients with imatinib-resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy.

Solitary rectal ulcer syndrome: clinical, endoscopic, histological and anorectal manometry findings in north Indian patients.

BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a chronic, benign defecation disorder often related to excessive straining. SRUS is diagnosed on the basis of clinical symptoms, endoscopic and histological findings. METHODS: All patients diagnosed with SRUS by colonoscopy and confirmed by histopathology from October 2012 to August 2014 in the Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, India, were included in the study. Out of 92 patients, thirty-four patients underwent anorectal manometry. Twenty age-matched healthy volunteers were also studied with anorectal manometry to serve as controls. RESULTS: Mean age of the group was 41 ± 19 years with age range of 10-82 years; males were 58 (63%) with male to female ratio of 1.7:1. Bleeding per rectum was present in 83%, constipation in 46.7%, abdominal pain in 27.2%, and diarrhea in 25% of the patients. On endoscopy, ulcerative lesions were seen in 83% patients of whom solitary and multiple lesions were present in 44% and 39%, respectively. Polypoidal lesions were reported in 17.4% whilst rectal polyps and erythematous mucosa were found in 5.4% and 2.2%, respectively. Histological examination revealed fibromuscular obliteration in 100% of patients, surface ulceration in 70.6% and crypt distortion in 20.65% of patients. Anal relaxation and balloon expulsion test was significantly abnormal in SRUS patients compared to healthy controls (53% vs. 20%, p < 0.01). CONCLUSION: Rectal bleeding was the most common symptom and ulcerative lesions the most common endoscopic finding. Fecal evaluation disorder was more prevalent inpatients with SRUS.

Multilocus analysis of hormonal, neurotransmitter, inflammatory pathways and genome-wide associated variants in migraine susceptibility.

BACKGROUND AND PURPOSE: Migraine pathophysiology involves a complex interplay of processes wherein the hormonal, neurotransmitter and inflammatory pathways interact to influence the migraine phenotype. However, all studies pertaining to the role of genetic variants in migraine have been restricted to a specific pathway and none of the studies has looked into inter-pathway genetic analysis. Our aim was to combine all the genetic variants from our previously reported studies to conduct higher order gene-gene interaction analysis using different multi-analytical approaches. METHODS: The study group included 324 migraine patients and 134 healthy controls. The study included 20 polymorphisms from hormonal, neurotransmitter, inflammatory and genome-wide associated variants from our published reports. Univariate and multivariate analyses were carried out by logistic regression. Classification and regression tree (CART) analysis was performed to build a decision tree via recursive partitioning. The high order genetic interactions associated with migraine risk were analyzed using multifactor dimensionality reduction (MDR). RESULTS: Univariate analysis revealed significant associations of polymorphisms in CYP19A1, ESR1, TNFA and PRDM16 genes with migraine susceptibility. Multiple regression analysis found significant results for four markers in CYP19A1, TNFA, ESR1 and LRP1 genes. In CART, the most prominent splitting variable was CYP19A1 polymorphism followed by TNFA, ESR1 and PRDM16 markers. The MDR analysis identified markers of CYP19A1, CYP19A1- TNFA, CYP19A1- ESR1- TNFA and CYP19A1- ESR1- TRPM8- PRDM16 as best models for one, two, three and four factors, respectively. CONCLUSIONS: The present study suggests interactions amongst hormonal, inflammatory and genome-wide associated variants but not with neurotransmitter pathway variants in migraine susceptibility.

3D contrast enhanced ultrasound for detecting endoleak following endovascular aneurysm repair (EVAR).

OBJECTIVE: CT angiography (CTA) for endovascular aneurysm repair (EVAR) surveillance involves irradiation and nephrotoxic X-ray contrast agents. Three-dimensional contrast enhanced ultrasound (3D CEUS) is a novel imaging technique that may be more sensitive to blood flow detection than CTA or 2D CEUS. 3D CEUS utilises positional information from magnetic field emitters to assemble all ultrasound reflections into a high-definition image. We compared 3D CEUS with CTA for the detection of endoleak and aneurysm expansion following EVAR. METHODS: 3D CEUS (Curefab), 2D CEUS (Philips IU22), and CTA were compared in 30-paired images from 23 patients. Sensitivity, specificity, positive, and negative predictive value were calculated for 2D and 3D CEUS against CTA as the 'gold standard'. Pearson correlation was used to compare aneurysm sac diameter. Data were analysed using SPSS version 19.0. RESULTS: 30 paired 3D CEUS and CTA images were analysed from 23 patients. Endoleaks were detected in 17 images with CTA, 18 on 2D CEUS, and 18 on 3D CEUS. The sensitivity, specificity, positive, and negative predictive values of 3D CEUS to detect endoleak were 100%, 92%, 94%, and 100%, respectively. There was excellent correlation (r=0.935; p≤.0001) between CTA and 3D CEUS for AAA sac diameter. Only 3D CEUS detected the inflow and outflow arteries in all 18 scans with endoleak. 2D CEUS detected the inflow in 16 (88.8%) and CTA on 12 (66.6%) of the images. CONCLUSION: 3D CEUS may be more sensitive to endoleak following EVAR than either 2D CEUS or CTA.

Leptomeningeal metastasis in solid tumors with a special focus on lung cancer.

Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer.