Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches-NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.

Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial?

OPINION STATEMENT: In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.

Transthoracic Computed Tomography-Guided Lung Nodule Biopsy: Comparison of Core Needle and Fine Needle Aspiration Techniques.

PURPOSE: To determine if there is a statistically significant difference in the computed tomography (CT)-guided trans-thoracic needle biopsy diagnostic rate, complication rate, and degree of pathologist confidence in diagnosis between core needle biopsy (CNB) and fine needle aspiration biopsy (FNAB). METHODS: A retrospective cohort design was used to compare the diagnostic biopsy rate, diagnostic confidence, and biopsy-related complications of pneumothorax, chest tube placement, pulmonary hemorrhage, hemoptysis, admission to hospital, and length of stay between 251 transthoracic needle biopsies obtained via CNB (126) or FNAB (125). Complication rates were assessed using imaging and clinical follow-up. Final diagnosis was confirmed via surgical pathology or clinical follow-up over a period of up to 10 years. RESULTS: CNB provided diagnostic samples in 91% and FNA in 80% of biopsies, which was statistically significant (P < .05). The sensitivities for CNB and FNAB were 89% (85 of 95) and 95% (84 of 88), respectively. The specificity of CNB was 100% (21 of 21) and for FNAB was 81% (2 of 11) with 2 false positives in the FNAB group. The differences in complication rate was not statistically significant for pneumothorax (50% vs 46%; determined by routine postbiopsy CT), chest tube (2% vs 4%), hemoptysis (4% vs 6%), and pulmonary hemorrhage (38% vs 47%) between FNAB and CNB, respectively. Seven patients requiring chest tube were admitted to hospital, 2 in the FNAB cohort for an average of 2.5 days and 5 in the CNB cohort for an average of 4.6 days. CONCLUSIONS: CNB provided more diagnostic samples with no statistical difference in complication rate.

Percutaneous autologous pancreatic islet cell transplantation for traumatic pancreatic injury.

CONTEXT: Traumatic pancreatic injury with pancreatic duct disruption is surgically managed with at least a partial pancreatectomy, often leading to poor blood glucose control and the subsequent development of diabetes mellitus. Autologous ß-islet cell transplantation may therefore help to preserve pancreatic endocrine function. CASE DESCRIPTION: We describe 3 patients with pancreatic duct disruption from traumatic pancreatic injury who were treated with a partial pancreatectomy followed by autologous ß-islet cell transplantation via a percutaneous transhepatic approach. Immediately after trauma, 2 of the 3 patients had difficulty with glucose control that resolved after autologous ß-islet cell transplantation. At follow-up, all patients remained normoglycemic. CONCLUSION: In patients requiring partial pancreatectomy after pancreatic trauma, percutaneous transhepatic autologous ß-islet cell transplantation should be considered to minimize the risk of development of diabetes mellitus.

Dynamic arterial and valsalva-augmented venous phase multidetector CT for orbital vascular lesions: a pictorial review*.

PURPOSE: To describe the value and purpose of a new method of dynamic arterial and Valsalva-augmented venous phase CT angiographic assessment of vascular orbital lesions. METHODS: Description of a dynamic arterial and Valsalva-augmented venous phase multidetector CT protocol currently being used at the institution of the authors for investigation of orbital vascular lesions. Research ethics approval was not required by the institution because this is a 1-case report, with a pictorial review of imaging findings in various representative orbital vascular lesions. RESULTS: One case of a distensible venous malformation depicts the clinical application of the imaging protocol. Key features of the malformation were demonstrated by arterial and venous phases of imaging. CONCLUSIONS: This technique is of value in diagnosis and management of vascular malformations of the orbit.

Renal hyperperfusion injury resulting in transient proteinuria post renal artery angioplasty for fibromuscular dysplasia.

Renovascular hypertension (RVH) can be treated utilizing medical, surgical or endovascular techniques. We present a case in which severe exacerbation of pre-existing proteinuria followed percutaneous transluminal angioplasty of a highly stenotic renal artery to relieve RVH caused by fibromuscular dysplasia. We propose that the worsening proteinuria post-angioplasty was caused by a transient renal hyperperfusion injury that overcame the glomerular autoregulatory mechanisms, thereby leading to raised intraglomerular pressures and loss of proteins through the glomerular filtration barrier until the vascular autoregulatory ability of the glomeruli was successfully re-established.

Lung nodules in children: video-assisted thoracoscopic surgical resection after computed tomography-guided localization using a microcoil.

BACKGROUND: Lung nodules that develop in children with cancer may represent metastatic disease or other conditions potentially requiring aggressive treatment. Thoracoscopic methods have been used for nodule resection; however, lesions deep in the lung parenchyma can be difficult to visualize. Fluoroscopic-guided thoracoscopic surgical resection after computed tomography (CT)-guided localization using microcoils has been described in the adult literature and has the potential to assist in the resection of deep pulmonary nodules in children. METHODS: Six patients (ages 6-15 years) with an undiagnosed pulmonary nodule were treated using a combined CT-guided microcoil localization/fluoroscopic video-assisted thoracoscopic surgical technique. Preoperatively, a platinum-fibered microcoil was deployed with the deep end of the coil placed either through or in the vicinity of the pulmonary nodule and the superficial end coiled on the pleural surface. The nodule and coil were then resected with endoscopic staplers guided by fluoroscopy and video-assisted thoracoscopic surgical. RESULTS: Computed tomography-guided microcoil localization and fluoroscopic-guided thoracoscopic resection were successful and critically influenced the management of all patients. Three patients were diagnosed with malignancy (2 metastatic diseases and 1 Hodgkin disease). A diagnosis of nonmalignant disease was made in 3 patients (granuloma, eosinophilic granuloma, and aspergilloma). CONCLUSION: In the pediatric population, we have successfully applied a previously described adult technique using CT-localized microcoils to direct fluoroscopic-guided thoracoscopic surgical resection of pulmonary nodules.