Ultrasound accuracy for brachial plexus pathology.

AIM: To determine (a) the accuracy of ultrasound in detecting brachial plexus pathology and (b) outline the advantages and limitations of ultrasound compared to MRI for imaging the brachial plexus. MATERIAL AND METHODS: cases with clinically suspected brachial plexus pathology were evaluated first by ultrasound, followed by MRI. Patients with prior brachial plexus imaging were excluded. The final diagnosis was based on a combination of ultrasound, MRI, clinical follow-up, and surgical findings. The accuracy of the ultrasound was assessed by comparing the ultrasound and the final diagnoses. The mean clinical follow-up time following ultrasound was 1.8 ± 1.4 years. RESULTS: Ninety-two (64%) of the 143 cases had normal brachial plexus ultrasound and MRI examinations. Fifty-one (36%) of 143 cases had brachial plexus pathology on MRI, comprising post-radiation fibrosis (n=25, 49%), nerve sheath tumor (n=11, 21%), traumatic injury (n=7, 14%), inflammatory polyneuropathy (n=4, 8%), malignant infiltration (n=2, 4%), desmoid fibromatosis (n=1,2%), and neuralgic amyotrophy (n=1, 2%). Overall diagnostic accuracy of ultrasound for brachial plexus pathology was 98% (140/143), with three discordant cases (neuralgic amyotrophy n=1, inflammatory neuropathy n=1, postradiation fibrosis n=1) regarded as normal on ultrasound assessment. Sensitivity, specificity, and positive and negative predictive value of ultrasound for identifying brachial plexus pathology were 94%, 100%, 100%, and 97%, respectively. CONCLUSION: Ultrasound identifies brachial plexus pathology with high accuracy and specificity, showing comparable diagnostic efficacy to MRI. Ultrasound can serve as an effective first-line imaging investigation for suspected brachial plexus pathology.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Ultrasound-guided lymph node sampling: accuracy of FNAC, end-cutting (Franseen), and side-cutting (Temno) needle biopsy techniques.

AIM: To compare technical success, diagnostic accuracy, and histological yield of fine-needle aspiration cytology (FNAC), side-cutting (Temno) needle biopsy, and end-cutting (Franseen) needle biopsy for ultrasound-guided sampling of groin and axillary lymph nodes. MATERIALS AND METHODS: A total of 270 abnormal groin and axillary nodes were sampled using one of the three techniques. Nodes with a maximum length of <2.5 cm underwent FNAC or Franseen biopsy, while nodes >2.5 cm underwent Temno biopsy. Mean size of nodes sampled by FNAC (21.2 mm) and Franseen (19.7 mm) were similar while nodes sampled by Temno were larger (34.4 mm, p<0.0001). RESULTS: Technical success rates of FNAC (82/93, 88%), Franseen (105/111, 95%), and Temno (59/66, 89%) biopsies were similar (p>0.05 for all). Lymphoid tissue yield by FNAC (mean total area 1.51 mm2) was less than that by Franseen (7.14 mm2, p=0.002) or Temno biopsy (19.44 mm2, p<0.0001). Diagnostic accuracy for malignancy was lower for FNAC (22/30, 73%) than Franseen (25/26, 96%, p=0.02) or Temno biopsy (32/32, 100%, p=0.002). For malignant nodes, determining the likely organ of origin was also lower for FNAC (7/30, 23%) than Franseen (19/26, 73%, p=0.0002) or Temno biopsy (29/32, 91%, p<0.0001), with a similar pattern observed in the identification of lymphoma. CONCLUSION: For similarly sized nodes, Franseen biopsy provided more lymphoid material, a higher diagnostic accuracy for malignancy including lymphoma, and better identification of the likely organ of origin than FNAC. Routine use of Franseen biopsy is advocated rather than FNAC for percutaneous sampling of lymph nodes not suitable for side-cutting needle biopsy.

Spin-Orbital-Angular-Momentum Coupled Bose-Einstein Condensates.

We demonstrate coupling between the atomic spin- and orbital-angular momentum (OAM) of the atom's center-of-mass motion in a Bose-Einstein condensate (BEC). The coupling is induced by Raman-dressing lasers with a Laguerre-Gaussian beam and creates coreless vortices in an F=1 ^{87}Rb spinor BEC. We observe correlations between spin and OAM in the dressed state and characterize the spin texture; the result is in good agreement with the theory. In the presence of the Raman field, our dressed state is stable for 0.1 s or longer, and it decays due to collision-induced relaxation. As we turn off the Raman beams, the vortex cores in the bare spin |m_{F}=1⟩ and |-1⟩ split. These spin-OAM coupled systems with the Raman-dressing approach have great potential for exploring new topological textures and quantum states.

Rotating Atomic Quantum Gases with Light-Induced Azimuthal Gauge Potentials and the Observation of the Hess-Fairbank Effect.

We demonstrate synthetic azimuthal gauge potentials for Bose-Einstein condensates from engineering atom-light couplings. The gauge potential is created by adiabatically loading the condensate into the lowest energy Raman-dressed state, achieving a coreless vortex state. The azimuthal gauge potentials act as effective rotations and are tunable by the Raman coupling and detuning. We characterize the spin textures of the dressed states, in agreements with the theory. The lowest energy dressed state is stable with a 4.5-s half-atom-number-fraction lifetime. In addition, we exploit the azimuthal gauge potential to demonstrate the Hess-Fairbank effect, the analogue of Meissner effect in superconductors. The atoms in the absolute ground state has a zero quasiangular momentum and transits into a polar-core vortex when the synthetic magnetic flux is tuned to exceed a critical value. Our demonstration serves as a paradigm to create topological excitations by tailoring atom-light interactions where both types of SO(3) vortices in the |⟨F[over →]⟩|=1 manifold, coreless vortices and polar-core vortices, are created in our experiment. The gauge field in the stationary Hamiltonian opens a path to investigating rotation properties of atomic superfluids under thermal equilibrium.

Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer.

BACKGROUND: NRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer, but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown. PATIENTS AND METHODS: Here, we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had lung adenocarcinoma and patient 2 cholangiocarcinoma. Whole-genome and transcriptome sequencing were carried out for these cases with select findings validated by fluorescence in situ hybridization. RESULTS: Both tumors were found to be positive for NRG1 gene fusions. In patient 1, an SDC4-NRG1 gene fusion was detected, similar gene fusions having been described in lung cancers previously. In patient 2, a novel ATP1B1-NRG1 gene fusion was detected. Cholangiocarcinoma is not a disease type in which NRG1 fusions had been described previously. Integrative genome analysis was used to assess the potential functional significance of the detected genomic events including the gene fusions, prioritizing therapeutic strategies targeting the HER-family of growth factor receptors. Both patients were treated with the pan HER-family kinase inhibitor afatinib and both displayed significant and durable response to treatment. Upon progression sites of disease were sequenced. The lack of obvious genomic events to describe the disease progression indicated that broad transcriptomic or epigenetic mechanisms could be attributed to the lack of prolonged response to afatinib. CONCLUSION: These observations lend further support to the use of pan HER-tyrosine kinase inhibitors for the treatment of NRG1 fusion-positive in both cancers of lung and hepatocellular origin and indicate more broadly that cancers found to be NRG1 fusion-positive may benefit from such a clinical approach regardless of their site of origin. CLINICAL TRIAL INFORMATION: Personalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution (NCT02155621).

Comparison of green pit viper and Agkistrodon halys antivenom in inhibition of coagulopathy due to Trimeresurus albolabris venom: an in-vitro study using human plasma.

INTRODUCTION: There are two antivenoms that may be administered in Hong Kong following a bite by Trimeresurus albolabris: the green pit viper antivenom from the Thai Red Cross Society in Thailand and the Agkistrodon halys antivenom from the Shanghai Institute of Biological Products in China. Both are recommended by the Central Coordinating Committee of Accident and Emergency Services of the Hospital Authority for treating patients with a bite by Trimeresurus albolabris. The choice of which antivenom to use is based on physician preference. This study aimed to compare the relative efficacy of the two antivenoms. METHODS: This in-vitro experimental study was carried out by a wildlife conservation organisation and a regional hospital in Hong Kong. Human plasma from 40 adult health care worker volunteers was collected. The Trimeresurus albolabris venom was added to human plasma and the mixture was assayed after incubation with each antivenom (green pit viper and Agkistrodon halys) using saline as a control. Fibrinogen level and clotting time in both antivenom groups were studied. RESULTS: The mean fibrinogen level was elevated from 0 g/L to 2.86 g/L and 1.11 g/L after the addition of green pit viper antivenom and Agkistrodon halys antivenom, respectively. When mean clotting time was measured, the value was 6.70 minutes in the control, prolonged to more than 360 minutes by green pit viper antivenom and to 19.06 minutes by Agkistrodon halys antivenom. CONCLUSIONS: Green pit viper antivenom was superior to Agkistrodon halys antivenom in neutralisation of the thrombin-like and hypofibrinogenaemic activities of Trimeresurus albolabris venom.

Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.

Personalized oncogenomics in the management of gastrointestinal carcinomas-early experiences from a pilot study.

BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. RESULTS: In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. SUMMARY: We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.

EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma.

BACKGROUND: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. RESULTS: We recruited 55 eligible participants from September 2010 to August 2012. DEMOGRAPHICS: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. CONCLUSIONS: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12609000643279.

Quantum critical spin-2 chain with emergent SU(3) symmetry.

We study the quantum critical phase of an SU(2) symmetric spin-2 chain obtained from spin-2 bosons in a one-dimensional lattice. We obtain the scaling of the finite-size energies and entanglement entropy by exact diagonalization and density-matrix renormalization group methods. From the numerical results of the energy spectra, central charge, and scaling dimension we identify the conformal field theory describing the whole critical phase to be the SU(3)_{1} Wess-Zumino-Witten model. We find that, while the Hamiltonian is only SU(2) invariant, in this critical phase there is an emergent SU(3) symmetry in the thermodynamic limit.

The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients with diffuse large B-cell lymphoma.

We performed a retrospective study to analyse the characteristics and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis B virus (HBV) infection and compare with those without HBV infection. The occurrence of hepatitis after withdrawal of prophylactic antiviral treatment on completion of chemotherapy was also assessed. The HBsAg-positive patients were given prophylactic antiviral treatment until 6 months after finishing chemotherapy. A total of 81 patients were recruited with 16 in the HBsAg-positive group and 65 in the HBsAg-negative group. The clinical characteristics were similar in both groups of patients. There was no significant difference in complete remission rate between the two groups (63% in HBsAg-positive group vs. 54% in HBsAg-negative group, P = 0.59). There was also no statistically significant difference in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg-positive patients (25%) had hepatitis after cessation of chemotherapy and prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after stopping lamivudine. In conclusion, HBV infection did not appear to affect the prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to consider prophylactic antiviral therapy to extend to at least one year on completion of chemotherapy.

Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle.

Autophagy has been shown to be responsive to physical exercise. However, the effects of prolonged habitual exercise on autophagy in cardiac muscle remain unknown. The present study aimed to examine whether long-term habitual exercise alters the basal autophagic signalling in cardiac muscle. Female Sprague-Dawley rats aged 2 months were randomly assigned to control and exercise groups. Animals in exercise group were kept in cages with free access exercise wheels to perform habitual exercise for 5 months. Animals in the control group were placed in cages without exercise wheels. Ventricular muscle tissues were harvested for analysis after 5 months. Phosphorylation statuses of upstream autophagic regulatory proteins and protein expressions of downstream autophagic facts remained unchanged in the cardiac muscle of exercise animals when compared to control animals. Intriguingly, the protein abundance of microtubule-associated protein-1 light chain -3 II (LC3-II), heat shock protein 72 (HSP72) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly increased in cardiac muscle of exercise rats relative to control rats. 5 months of habitual exercise causes the adaptive increase in LC3-II reserve without altering autophagic flux, which probably contributes to the elevation of cellular autophagic capacity and efficiency of cardiac muscle.

Exploring microRNA-mediated alteration of EGFR signaling pathway in non-small cell lung cancer using an mRNA:miRNA regression model supported by target prediction databases.

EGFR signaling pathway and microRNAs (miRNAs) are two important factors for development and treatment in non-small cell lung cancer (NSCLC). Microarray analysis enables the genome-wide expression profiling. However, the information from microarray data may not be fully deciphered through the existing approaches. In this study we present an mRNA:miRNA stepwise regression model supported by miRNA target prediction databases. This model is applied to explore the roles of miRNAs in the EGFR signaling pathway. The results show that miR-145 is positively associated with epidermal growth factor (EGF) in the pre-surgery NSCLC group and miR-199a-5p is positively associated with EGF in the post-surgery NSCLC group. Surprisingly, miR-495 is positively associated with protein tyrosine kinase 2 (PTK2) in both groups. The coefficient of determination (R(2)) and leave-one-out cross-validation (LOOCV) demonstrate good performance of our regression model, indicating that it can identify the miRNA roles as oncomirs and tumor suppressor mirs in NSCLC.

Age, tumour stage, and preoperative serum albumin level are independent predictors of mortality after radical cystectomy for treatment of bladder cancer in Hong Kong Chinese.

OBJECTIVES: To evaluate the association between patient age, other clinical factors and mortality following radical cystectomy for treatment of bladder cancer. DESIGN: Historical cohort study. SETTING: A urology unit in Hong Kong. PATIENTS: The outcomes of 117 patients who had radical cystectomies performed in one urological unit from 2003 to 2011 were reviewed. Demographic and perioperative data, including tumour stage, Charlson Comorbidity Index, and preoperative serum albumin levels were retrieved from computerised medical records. Risk factors for 30-day mortality, and cancer-specific, other-cause, and overall death rates at 5 years were calculated. The data were subsequently stratified and analysed according to age. RESULTS: Of the 117 patients, 83 (71%) were aged 75 years or below. The mean follow-up duration was 31 (standard deviation, 29) months. Age, tumour stage, and preoperative serum albumin level, but not the Charlson Comorbidity Index, were found to be predictors of survival following radical cystectomy. The overall 30-day mortality rate was 3% in the full sample, 1% in patients aged 75 years or below, and 10% in patients aged over 75 years. There was no significant difference in 5-year cancer-caused mortalities between patients aged 75 years or below and those aged over 75 years (33% vs 33%, P=0.956). In patients older than 75 years, the 5-year other-cause and overall mortality rates were 47% and 80%, respectively; such rates were higher than those for younger patients (13% and 46%, respectively). CONCLUSION: Age, tumour stage, and preoperative serum albumin level were predictors of survival after radical cystectomy. Non-cancer-related death played a crucial role in the overall mortality rate in elderly patients having radical cystectomy for bladder cancer.

Nanostructure and nanomechanics of cement: polydisperse colloidal packing.

Cement setting and cohesion are governed by the precipitation and growth of calcium-silicate-hydrate, through a complex evolution of microstructure. A colloidal model to describe nucleation, packing, and rigidity of calcium-silicate-hydrate aggregates is proposed. Polydispersity and particle size dependent cohesion strength combine to produce a spectrum of packing fractions and of corresponding elastic properties that can be tested against nanoindentation experiments. Implications regarding plastic deformations and reconciling current structural characterizations are discussed.

Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China.

OBJECTIVE: To examine the life expectancy, standardized mortality ratios (SMRs), and causes of death in 6 groups of patients from Hong Kong with different rheumatic diseases. METHODS: Patients with a diagnosis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic vasculitis (SV), or systemic sclerosis (SSc) registered in 37 public hospitals between 1999 and 2008 were identified in the hospital registry. SMRs were calculated by comparing the mortality rate in patients with each disease with that in the general population. Life expectancy was calculated by abridged life-table analysis, and the causes of death were compared. RESULTS: In 2008, data on 8,367 RA, 5,243 SLE, 2,154 AS, 1,636 SV, 778 PsA, and 449 SSc patients were available in our registry. The age- and sex-adjusted SMRs were highest for SLE (5.25 [95% confidence interval 4.79-5.70]), SSc (3.94 [95% confidence interval 3.20-4.68]), and SV (2.64 [95% confidence interval 2.36-2.93]). In female patients, the loss in life expectancy was greatest for SSc (34.1 years), SV (19.3 years), and SLE (19.7 years). In male patients, the loss in life expectancy was highest for SV (28.3 years), SLE (27 years), and SSc (16 years). There were 2,486 deaths during the study period (1999-2008), and the principal causes were infections (28%), cardiovascular complications (18%), cancer (16%), and disease activity (7%). Infection was the leading cause of death in SLE, RA, AS, and PsA, whereas deaths from disease-related activity and cardiovascular complications were most frequent in SSc. Cancer was the most common cause of death in SV. CONCLUSION: Our findings indicate that patients with SLE, RA, AS, PsA, SV, and SSc have increased mortality rates and reduced life expectancy. SLE has the highest adjusted SMR, and female SSc patients have the greatest loss in life expectancy. Infection is the leading cause of death, followed by cardiovascular complications and malignancies.