Deep Immune Phenotyping and Single-Cell Transcriptomics Allow Identification of Circulating TRM-Like Cells Which Correlate With Liver-Stage Immunity and Vaccine-Induced Protection From Malaria.

Protection from liver-stage malaria requires high numbers of CD8+ T cells to find and kill Plasmodium-infected cells. A new malaria vaccine strategy, prime-target vaccination, involves sequential viral-vectored vaccination by intramuscular and intravenous routes to target cellular immunity to the liver. Liver tissue-resident memory (TRM) CD8+ T cells have been shown to be necessary and sufficient for protection against rodent malaria by this vaccine regimen. Ultimately, to most faithfully assess immunotherapeutic responses by these local, specialised, hepatic T cells, periodic liver sampling is necessary, however this is not feasible at large scales in human trials. Here, as part of a phase I/II P. falciparum challenge study of prime-target vaccination, we performed deep immune phenotyping, single-cell RNA-sequencing and kinetics of hepatic fine needle aspirates and peripheral blood samples to study liver CD8+ TRM cells and circulating counterparts. We found that while these peripheral 'TRM-like' cells differed to TRM cells in terms of previously described characteristics, they are similar phenotypically and indistinguishable in terms of key T cell residency transcriptional signatures. By exploring the heterogeneity among liver CD8+ TRM cells at single cell resolution we found two main subpopulations that each share expression profiles with blood T cells. Lastly, our work points towards the potential for using TRM-like cells as a correlate of protection by liver-stage malaria vaccines and, in particular, those adopting a prime-target approach. A simple and reproducible correlate of protection would be particularly valuable in trials of liver-stage malaria vaccines as they progress to phase III, large-scale testing in African infants. We provide a blueprint for understanding and monitoring liver TRM cells induced by a prime-target malaria vaccine approach.

Clinical Performance Status and Technical Factors Affecting Outcomes from Percutaneous Transhepatic Biliary Interventions; A Multicentre, Prospective, Observational Cohort Study.

PURPOSE: The purpose of this study was to evaluate the predictive value of a 'Modified Karnofsky Scoring System' on outcomes and provide real-world data regarding the UK practice of biliary interventions. MATERIALS AND METHODS: A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure. RESULTS: A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky 'high risk' group the 7 day mortality was 9.7% versus 0% for the 'low risk' group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) CONCLUSION: Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.

Pain Management Protocols During Uterine Fibroid Embolisation: A Systematic Review of the Evidence.

BACKGROUND: Uterine fibroid embolisation (UFE) is an effective treatment for fibroids. There are varying analgesia protocols published to control procedure associated pain. We aimed to assess what protocols are most effective in controlling post-procedural pain. MATERIALS AND METHODS: A systematic review of the Embase and Medline databases was conducted according to PRISMA guidelines. Studies regarding analgesia protocols post-uterine fibroid embolisation with Visual Analogue Scale or Numerical Rating Scale pain scores were included. The mean maximal pain scores of patients post-procedure were evaluated. ANOVA and t tests were performed. RESULTS: We identified 26 studies (total 3353 patients), with a mean procedural success rate of > 87%. We stratified protocols into four groups. Mean pain scores were: opioids ± NSAIDs ± acetaminophen (4.84, SD = 1.56); opioids ± NSAIDs ± acetaminophen + nerve block (4.7, SD = 1.37); opioids ± NSAIDs ± acetaminophen + intrauterine artery drug administration (4.09, SD = 0.60); and opioids ± NSAIDs ± acetaminophen + other (5.30, SD = 1.13) without significant difference between groups (p = 0.71). Similarly, there was no difference (p = 0.057) between groups for time to discharge or side effects. CONCLUSIONS: There is no evidence to suggest that there is any superiority of one protocol above another in the published literature. Appropriate use of opioids ± NSAIDs ± acetaminophen alone appears to be sufficient to control pain post-UFE. However, due to large heterogeneity of the literature no firm conclusions can be reached, and further research is warranted. LEVEL OF EVIDENCE: Level 1, Systematic review.

Typical and atypical benign liver lesions: A review.

Focal liver lesions are routinely encountered by clinical radiologists and represent a wide spectrum of pathology. Majority of these lesions are likely to be benign in nature, especially in the absence of chronic liver disease or primary cancer. A radiologist must be aware of common and uncommon imaging features of benign lesions across the various imaging modalities. This review discusses pathognomonic imaging features of common benign focal liver lesions seen on ultrasound, computed tomography and magnetic resonance, and adds to existing knowledge with the recent updates to have emerged in this area.

Contrast-enhanced US-guided Interventions: Improving Success Rate and Avoiding Complications Using US Contrast Agents.

Ultrasonography (US) is an established modality for intervention. The introduction of microbubble US contrast agents (UCAs) has the potential to further improve US imaging for intervention. According to licensing, UCAs are currently approved for clinical use in restricted situations, but many additional indications have become accepted as having clinical value. The use of UCAs has been shown to be safe, and there is no risk of renal toxic effects, unlike with iodinated or gadolinium contrast medium. Broadly speaking, UCAs can be injected into the bloodstream (intravascular use) or instilled into almost any accessible body cavity (endocavitary use), either in isolation or synchronously. In microvascular applications, contrast-enhanced US (CEUS) enhances delineation of necrotic areas and the vascularized target to improve real-time targeting. The ability of CEUS to allow true assessment of vascularity has also been used in follow-up of devascularizing intervention. In macrovascular applications, real-time angiographic images can be obtained with CEUS without nephrotoxic effects or radiation. In endocavitary applications, CEUS can achieve imaging similar to that of iodinated contrast medium-based fluoroscopy; follow-up to intervention (eg, tubography and nephrostography) can be performed at the bedside, which may be advantageous. The use of UCAs is a natural progression in US-guided intervention. The aim of this article is to describe the indications, contraindications, and techniques of using UCAs as an adjunctive tool for US-guided interventional procedures to facilitate effective treatment, improve complication management, and increase the overall success of interventional procedures. Online supplemental material is available for this article. ©RSNA, 2016.

Recanalisation of Chronically Occluded Remote Superficial Femoral Artery Endarterectomy Through Angioplasty for Limb Salvage.

We report a novel application of balloon angioplasty to recanalise a chronically occluded remote endarterectomy superficial femoral artery. This patient previously had two occluded surgical bypass grafts in an attempt to revascularise the limb and presented with critical limb ischaemia and necrotic foot ulcerations. Following the angioplasty, the patient showed significant improvement in rest pain and healing of the ulcerations. This technique may be useful for limb salvage in patients where surgical options have been exhausted.

OUTBACK catheter for treatment of superficial femoral and iliac artery chronic total occlusion: Experience from two centers.

PURPOSE: The OUTBACK(®) catheter is a reentry device that enables reentry into a vessel lumen from the subintimal space during subintimal angioplasty. It is reserved for cases where reentry has not been possible using conventional wire and catheter techniques. We report a two-center experience in recanalization of the chronic total occlusions of the common iliac (CIA) and the superficial femoral artery (SFA) using the OUTBACK(®) catheter in cases where other techniques were unsuccessful. MATERIAL AND METHODS: All cases where recanalization was performed using the OUTBACK(®) reentry catheter between January 2010 to January 2015 were retrospectively identified and included in this study. 21 patients were identified. The indication for intervention in these cases included claudication and critical leg ischemia. In all cases, conventional recanalization could not be successfully achieved. RESULTS: The OUTBACK(®) catheter was used to recanalize 10 SFA occlusion and 9 CIA occlusions. In 19 patients (90%), reentry into true arterial lumen was successfully achieved. 17 patients had their recanalization through the transfemoral approach whereas 2 patients had a transpopliteal artery approach. In 2 patients, reentry into the true lumen could not be achieved using the OUTBACK(®) catheter due to patient's intolerability for the procedure and severe atherosclerotic calcified plaques. There was 100% patency of the vessel intervened on Duplex ultrasound at 24 months of follow up. 16 patients (84%) remained asymptomatic and 2 patients (10.5%) reported worsening of their symptoms due to the development of new lesions within the arterial system. CONCLUSION: The OUTBACK(®) catheter is an effective and safe technique for reentry into the vessel lumen when conventional techniques fail.

Acute aortic syndrome-pitfalls on gated and non-gated CT scan.

Acute aortic syndrome (AAS) is a life-threatening condition which includes aortic dissection (AD), penetrating aortic ulcer (PAU) and intramural hematoma (IMH). Multi-detector computed tomography (MDCT) plays a crucial role in the diagnosis of this condition and for further clinical follow-up. It is important for radiologists to be aware of common pitfalls in cardiac-gated and non-gated CT in diagnosing AAS. They should also be wary of common mimics of AAS which may make a significant difference towards management of these patients. In this review, we present from our practice some of the common pitfalls and mimics of AAS on MDCT.

Mimics of acute coronary syndrome on MDCT.

Acute coronary syndrome (ACS) encompasses a spectrum of unstable coronary artery disease ranging from transmural myocardial infarction to unstable angina. The immediate management of these patients is dictated by the presence/absence of ST segment changes on electrocardiogram. More and more patients with non-ST elevation ACS are bypassing traditional diagnostic pathways to undergo urgent coronary catheter angiography. A proportion of these patients will have normal coronary angiography and an alternative diagnosis is often sought with multi-detector computed tomography (MDCT). It is vital that clinicians and radiologists are aware of the usual and unusual mimics of ACS so they can modify their imaging technique and protocol accordingly. In this review, we present some true mimics of ACS on MDCT, from our practice, and suggest an imaging protocol that can be utilised universally.

The MPTP status during early reoxygenation is critical for cardioprotection.

BACKGROUND: Previous studies have revealed that the mitochondrial permeability transition pore (MPTP) plays a critical role in necrotic and apoptotic cell death. Given the opposed roles of the MPTP in cardioprotection (transient versus sustained opening) the primary aim of this study was to determine how two structurally different MPTP inhibitors (cyclosporine A and bongkrekic acid) administered for varying time regimes influenced ischemia/reperfusion (I/R)-induced injury in myocardial slices from rat left ventricle. A second objective was to explore how pharmacologic MPTP opening (using atractyloside) at different time points during I/R modulated myocardial injury. MATERIALS AND METHODS: Myocardial slices from rat left ventricle were subjected to 90 min ischemia/120 min reoxygenation at 37°C. MPTP inhibitors and openers were added at various time points during the experimental regime. Tissue injury was assessed by creatine kinase (CK) released and determination of cell necrosis and apoptosis. Myocardial caspase 3 activity was also determined. RESULTS: The results show that the status of MPTP can dramatically influence ischemic/reoxygenation induced injury and protection of the rat left ventricular myocardium. Importantly, the status of the MPTP during first 10 min of reoxygenation is of critical importance with both opening and closing of the pore being as protective as ischemic preconditioning. CONCLUSIONS: The present study has shown that both formation and inhibition of the MPTP can be exploited for therapeutic purposes and that there is a defined therapeutic window, with the first few minutes of reoxygenation being a crucial period to achieve cardioprotection.

Is There a Role of Double Reporting and CT Pelvis for Lung Cancer Staging?

BACKGROUND: Lung cancer is the most common cancer in the world. Staging of lung cancer involves CT of chest and abdomen. Subsequently these are discussed in MDT and if required PET imaging is arranged. We have performed a study to assess double reporting of the initial staging CT would identify in field metastasis and hence decrease the use of PET. METHODS: A refined search from the lung cancer database over 2 years of 980 patients was performed. Metastasis identified on PET (SUV > 2.5) was nominated as the gold standard, 219 patients had both PET and staging CT (chest and abdomen) with 38 patients having metastasis on both PET and CT. CT images were reviewed by two independent radiologist who were blinded to the report. Identified metastases were graded if identified. These were grade as 1- definite, 2- equivocal, 3- normal. Subsequently through a process of arbitration a combined decision about the in field metastasis was achieved. RESULTS: There were 21 metastasis which were within the field of chest and abdomen (in field metastasis). Only a half of these were identified by blinded observers. Following an arbitration there was no significant improvement in the pick up rate. There were 19 out of field metastasis in 15 patients out of this cohort. Majority of these (72%) were in the bony pelvis which would have been reported if a CT pelvis was performed as a part of staging. We estimate that one would have to perform 10 CT pelvises to save one PET-CT. CONCLUSION: Double reading of staging scan would not identify all infield metastasis. The increased contrast in PET images makes it easy to spot metastases. Hence there is no role for double reporting of staging CT in lung cancer management. Inclusion of pelvis in staging of lung cancer may be effective and would improve the detection of out of field metastases hence decreasing the use of PET.

Diagnosis of malignancy of prostate.

Minimal or complete lack of symptoms hinders early diagnosis of malignancy of prostate leading to undue morbidity and mortality. Therefore early detection is imperative, making use of simple and safe technique with least of expense. Five hundred consecutive patients, who reported with urinary complaints, were assessed by digital rectal examination, transabdominal suprapubic ultrasonography for prostatic volume/weight and serum assay of prostate specific antigen (PSA). Histopathological examination of prostatic biopsy of all the cases was also done. Benign prostatic hyperplasia was found in 83.6% of cases and 16.4% of the cases were of adenocarcinoma prostate of varying severity (mild, moderate and severe). It was found that volume/weight of gland and PSA levels were very good indicators of the probable diagnosis and grade of adenocarcinoma. Statistical tests taking various levels of PSA values in account also validated the results.