Accuracy of clinical staging for T2N0 oesophageal cancer: systematic review and meta-analysis

Oesophageal cancer is the sixth commonest cause of overall cancer mortality. Clinical staging utilizes multiple imaging modalities to guide treatment and prognostication. T2N0 oesophageal cancer is a treatment threshold for neoadjuvant therapy. Data on accuracy of current clinical staging tests for this disease subgroup are conflicting. We performed a meta-analysis of all primary studies comparing clinical staging accuracy using multiple imaging modalities (index test) to histopathological staging following oesophagectomy (reference standard) in T2N0 oesophageal cancer. Patients that underwent neoadjuvant therapy were excluded. Electronic databases (MEDLINE, Embase, Cochrane Library) were searched up to September 2019. The primary outcome was diagnostic accuracy of combined T&N clinical staging. Publication date, first recruitment date, number of centers, sample size and geographical location main histological subtype were evaluated as potential sources of heterogeneity. The search strategy identified 1,199 studies. Twenty studies containing 5,213 patients met the inclusion criteria. Combined T&N staging accuracy was 19% (95% CI, 15–24); T staging accuracy was 29% (95% CI, 24–35); percentage of patients with T downstaging was 41% (95% CI, 33–50); percentage of patients with T upstaging was 28% (95% CI, 24–32) and percentage of patients with N upstaging was 34% (95% CI, 30–39). Significant sources of heterogeneity included the number of centers, sample size and study region. T2N0 oesophageal cancer staging remains inaccurate. A significant proportion of patients were downstaged (could have received endotherapy) or upstaged (should have received neoadjuvant chemotherapy). These findings were largely unchanged over the past two decades highlighting an urgent need for more accurate staging tests for this subgroup of patients

Effects of seasonal variations on sediment-plume streaks from dredging operations

When mixtures of aggregates and water dredged from the seabed are discharged at the surface into the adjacent water from a barge, coarse sediments sink immediately and fine sediments are suspended forming a plume. Recently, elongated plumes of fine sediment were observed by satellites near a dredging location on the continental shelf. Such plume streaks were longer in certain conditions with seasonality than expected or reported previously. Therefore, the present work studied the appearance of sediment plume with field measurements and numerical simulations and explains the seasonally varying restoring force and thicknesses of the surface mixed layer resulting from the vertical density distribution near the surface, along with mixing by hydrodynamic process. The resulting mixtures, after vertical restoring and mixing with the surroundings, determine the horizontal transport of suspended sediments. A numerical model successfully reproduced and explained the results from field measurements and satellite images along with the seasonal variations

Intra-Operative Assessment of Cancer with X-Ray Phase Contrast Computed Tomography

X-ray Phase-Contrast Computed Tomography (PC-CT) increases contrast in weakly attenuating samples, such as soft tissues. In Edge-Illumination (EI) PC-CT, phase effects are accessed from amplitude modulation of the x-ray beam using alternating transmitting and attenuating masks placed prior to the sample and detector. A large field of view PC-CT scanner using this technique was applied to two areas of cancer assessment, namely excised breast and esophageal tissue. For the breast tissue, Wide Local Excisions (WLEs) were studied intra-operatively using PC-CT for the evaluation of tumor removal in breast conservation surgery. Images were acquired in 10 minutes without compromising on image quality, showing this can be used in a clinical setting. Longer, higher resolution PC-CT images were also taken, with analysis showing previously undetected thinning of tumor strands. This would allow a second use of the system for “virtual histopathology”, outside of surgery. For the esophagus samples, tissues were taken from esophagectomy surgery, where the lower part of the esophagus is removed, and the stomach relocated. For the assessment of ongoing therapy, accurate staging of tumors in the removed esophagus is essential, with the current gold standard provided by histopathology. PCCT images were acquired on several samples and compare well with histopathology, with both modalities showing similar features. Examples are shown where staging of tumor penetration is possible with PC-CT images alone, which is hoped will be an important step in performing the imaging and staging intra-operatively

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

How COVID-19 has changed the unselected medical take: an observational study

INTRODUCTION: COVID-19 has had a profound effect on the NHS. Little information has been published as to how the unselected medical take has been affected. METHODS: We retrospectively reviewed patients who were referred to general medicine during March 2020. We compared clinical outcomes of patients with and without COVID-19. RESULTS: 814 patients were included, comprising 777 unique patients. On average, 26 patients were admitted per day. 38% of admitted patients were suspected of COVID-19, with greater numbers of COVID-19 patients in the second half compared to the first half of the month (p<0.001). Logistic regression analyses showed suspected COVID-19 was an independent predictor for inpatient mortality (odds ratio [OR] = 6.09, p<0.001) and 30-day mortality (OR = 4.66, p<0.001). CONCLUSIONS: COVID-19 patients had worse clinical outcomes and increased healthcare use compared to non-COVID-19 patients. Our study highlights some of the challenges in healthcare provision faced during this pandemic

Carotid Stenting for Radiation-Induced Extracranial Carotid Artery Occlusive Disease: Efficacy and Midterm Outcomes

Purpose: To investigate the immediate and midterm results of carotid stenting for severe radiation-induced extracranial carotid artery disease. Methods: Between April 1998 and May 2002, 16 patients (15 men; mean age 64±8 years, range 48-72) presented with 18 severe radiation-induced carotid stenoses in the internal carotid artery (n=3), common carotid artery (n=7), and both vessels (n=8). Thirteen (76%) patients were symptomatic; the mean degree of carotid stenosis was 85%±10% (range 70%-95%). An independent neurological specialist assessed perioperative neurological complications before and after treatment. The patients were followed prospectively for at least 12 months by clinical examination and serial duplex ultrasound scanning. Restenosis was defined as a diameter reduction >50%. Results: Of 18 stent procedures attempted (2 staged), 1 was abandoned owing to failure to pass the guidewire across a tight lesion (94% technical success by intent to treat). In the 17 successfully completed procedures, 17 Wallstents and 4 SMART stents were deployed with satisfactory anatomical results. One postoperative stroke occurred as a result of thromboembolism to the ipsilateral middle cerebral artery and led to hospital death (5.9% combined stroke and death rate). One transient ischemic attack occurred (11.6% neurological event rate). With a median 30-month follow-up (range 5-55), 3 (17.6%) recurrent stenoses (>50%) were detected on duplex scan; 1 repeat angioplasty was performed. No new neurological event has been detected. Conclusions: Carotid stenting may be performed in patients with irradiation-induced carotid stenosis with acceptable risks and midterm durability.link_to_subscribed_fulltex