Physiology and pathology of the C3 amplification cycle: A retrospective.

The C3 "Tickover" hypothesis, a mechanism whereby the host maintains constant surveillance of potential invading pathogens, targeting them for elimination through amplified C3b generation and C3-dependent effector mechanisms, was proposed by the late Professor Peter Lachmann in 1973. This unique insight came from a combined understanding of the complement system as it was then defined and the nature of the disease process in rare complement deficiencies and complement-driven diseases. In this review, I give a personal perspective of how understanding of "Tickover" has developed in the subsequent 50 years, culminating in the introduction into the clinic of therapeutic agents designed to combat amplification-driven disease.

Automated Segmentation of Lymph Nodes on Neck CT Scans Using Deep Learning.

Early and accurate detection of cervical lymph nodes is essential for the optimal management and staging of patients with head and neck malignancies. Pilot studies have demonstrated the potential for radiomic and artificial intelligence (AI) approaches in increasing diagnostic accuracy for the detection and classification of lymph nodes, but implementation of many of these approaches in real-world clinical settings would necessitate an automated lymph node segmentation pipeline as a first step. In this study, we aim to develop a non-invasive deep learning (DL) algorithm for detecting and automatically segmenting cervical lymph nodes in 25,119 CT slices from 221 normal neck contrast-enhanced CT scans from patients without head and neck cancer. We focused on the most challenging task of segmentation of small lymph nodes, evaluated multiple architectures, and employed U-Net and our adapted spatial context network to detect and segment small lymph nodes measuring 5-10 mm. The developed algorithm achieved a Dice score of 0.8084, indicating its effectiveness in detecting and segmenting cervical lymph nodes despite their small size. A segmentation framework successful in this task could represent an essential initial block for future algorithms aiming to evaluate small objects such as lymph nodes in different body parts, including small lymph nodes looking normal to the naked human eye but harboring early nodal metastases.

Assessment of tracer delay effect in whole-brain computed tomography perfusion: results for selected regions of interest in middle cerebral artery acute ischemic strokes.

OBJECTIVE: The objective of this study was to compare the variability of computed tomography perfusion (CTP) results in identical data sets of middle cerebral artery (MCA) acute ischemic stroke (AIS) generated by standard singular value decomposition (sSVD) deconvolution and tracer delay-insensitive singular value decomposition (SVD+) algorithm analyses. METHODS: Whole-brain 320-detector-row CTP data sets from 9 unilateral MCA AIS cases and 9 controls were retrospectively analyzed. Computed tomography perfusion values for the combined core/penumbra, contralateral hemispheres and arterial territories were measured and compared with literature values. Simple linear regression models are provided to predict corresponding SVD+ value and sSVD CTP values. RESULTS: In the core/penumbra, sSVD generated lower cerebral blood flow (CBF) values, higher mean transit time (MTT) values, and a broader range of CBF and MTT values as compared with SVD+. Mean transit time value differences between the core/penumbra and contralateral hemispheres were statistically significant using sSVD, whereas those of SVD+ were not. Goodness of fit between algorithms for the core/penumbra was lower for CBF (0.483) and MTT (0.494), as compared with time to peak (0.891) and cerebral blood volume (0.997). CONCLUSIONS: In this study using identical source data for patients with MCA AIS, use of either sSVD or SVD+ analyses created statistically significant differences in the CTP value results. Tracer delay-sensitive and -insensitive algorithms impact CTP results in AIS and controls, highlighting the need to pursue additional studies that assess the variability, accuracy, and clinical implications of CTP results generated when using heterogeneous deconvolution algorithms.

Assessment of the tracer delay effect in whole-brain computed tomography perfusion: results in patients without known neuroanatomic abnormalities.

OBJECTIVE: Whole-brain computed tomography perfusion (CTP) data sets generated by tracer delay-insensitive singular value decomposition plus (SVD+) and standard singular value decomposition (sSVD) deconvolution algorithms were evaluated to quantify relatedness and discrepancies in CTP results. METHODS: Twenty females with symmetrical hemispheric CTP maps indicative of brain tissue without apparent abnormalities were studied. Tissue-specific CTP values were analyzed. RESULTS: Standard SVD values were higher than SVD+ for cerebral blood flow. Other CTP values had minimal differences across brain regions. All simple linear regression models were statistically significant (P < 0.05) except for cerebral blood flow in white matter (P = 0.06). Cerebral blood volume had a good model fit, and mean transit time, a poor fit. CONCLUSIONS: Corresponding fitted CTP values for sSVD and SVD+ based on regression equations for brain-tissue types are presented. Additional research is required to compare SVD+ and sSVD in disease states when significant hemodynamic brain alterations are present.

Pattern of brexucabtagene autoleucel-related neurotoxicity on magnetic resonance imaging of the brain in a patient with relapsed/refractory B-cell acute lymphoblastic leukemia and prior leptomeningeal disease.

Immune effector cell-associated neurotoxicity syndrome (ICANS) secondary to chimeric antigen receptor T-cell therapy is common in adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL), but imaging findings during neurologic toxicity and their meaning have yet to be systematically described in this patient population. Brexucabtagene autoleucel (brexu-cel) is a CD19-directed autologous T-cell immunotherapy for the treatment of adult patients with R/R B-cell ALL that can enter the central nervous system. We present a case of an adult patient with R/R B-cell ALL and prior leptomeningeal disease who developed neurologic toxicity and new findings on magnetic resonance imaging of the brain while receiving brexu-cel. We interpret the patient's neuroimaging studies within clinical context to differentiate ICANS from active treatment of residual leukemia.

Medical imaging and multimodal artificial intelligence models for streamlining and enhancing cancer care: opportunities and challenges.

INTRODUCTION: Artificial intelligence (AI) has the potential to transform oncologic care. There have been significant developments in AI applications in medical imaging and increasing interest in multimodal models. These are likely to enable improved oncologic care through more precise diagnosis, increasingly in a more personalized and less invasive manner. In this review, we provide an overview of the current state and challenges that clinicians, administrative personnel and policy makers need to be aware of and mitigate for the technology to reach its full potential. AREAS COVERED: The article provides a brief targeted overview of AI, a high-level review of the current state and future potential AI applications in diagnostic radiology and to a lesser extent digital pathology, focusing on oncologic applications. This is followed by a discussion of emerging approaches, including multimodal models. The article concludes with a discussion of technical, regulatory challenges and infrastructure needs for AI to realize its full potential. EXPERT OPINION: There is a large volume of promising research, and steadily increasing commercially available tools using AI. For the most advanced and promising precision diagnostic applications of AI to be used clinically, robust and comprehensive quality monitoring systems and informatics platforms will likely be required.

Applications of Artificial Intelligence in the Radiology Roundtrip: Process Streamlining, Workflow Optimization, and Beyond.

There are many impactful applications of artificial intelligence (AI) in the electronic radiology roundtrip and the patient's journey through the healthcare system that go beyond diagnostic applications. These tools have the potential to improve quality and safety, optimize workflow, increase efficiency, and increase patient satisfaction. In this article, we review the role of AI for process improvement and workflow enhancement which includes applications beginning from the time of order entry, scan acquisition, applications supporting the image interpretation task, and applications supporting tasks after image interpretation such as result communication. These non-diagnostic workflow and process optimization tasks are an important part of the arsenal of potential AI tools that can streamline day to day clinical practice and patient care.

Introduction to Radiomics and Artificial Intelligence: A Primer for Radiologists.

Health informatics and artificial intelligence (AI) are expected to transform the healthcare enterprise and the future practice of radiology. There is an increasing body of literature on radiomics and deep learning/AI applications in medical imaging. There are also a steadily increasing number of FDA cleared AI applications in radiology. It is therefore essential for radiologists to have a basic understanding of these approaches, whether in academia or private practice. In this article, we will provide an overview of the field and familiarize the readers with the fundamental concepts behind these approaches.

Endovascular intervention for acute stroke due to infective endocarditis: case report.

The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option.

GCS 15: when mild TBI isn't so mild.

OBJECTIVE: The present study characterizes patients with the mildest of mild traumatic brain injury (TBI), as defined by a Glasgow coma score (GCS) of 15. METHODS: This is an IRB approved observational cohort study of adult patients who presented to the emergency department of a Level-1 trauma center, with the primary diagnosis of TBI and a GCS score of 15 on arrival. Data collected included demographic variables such as age, gender, race, mechanisms of injury, signs and symptoms including associated vomiting, seizures, loss of consciousness (LOC), alteration of consciousness (AOC), and post-traumatic amnesia (PTA).Pre- hospital GCS, Emergency Department (ED) GCS, and results of brain CT scans were also collected as well as patient centered outcomes including hospital or intensive care unit (ICU) admission, neurosurgical intervention, and in hospital death. Data were stored in REDCap (Research Electronic Data Capture), a secure, web- based application. Descriptive and inferential analysis was done using JMP 14.0 for the Mac. RESULTS: Univariate predictors of hospital admission included LOC, AOC, and PTA, all p < 0.0001. Patients admitted to ICU were significantly more likely to be on an antiplatelet or anticoagulant (P < 0.0001), have experienced PTA (p = 0.0025), LOC (p < 0.0001), or have an abnormal brain CT (p < 0.0001). Patients who died in the hospital were significantly more likely to be on an antiplatelet or anticoagulant (P = 0.0005. All who died in the hospital had intracranial hemorrhage on ED head CT, despite having presented to the ED with GCS of 15. Patients were also significantly more likely to have had vomiting (p < 0.0001). Patients who underwent neurosurgical intervention were significantly more likely to be male (P = 0.0203), to be on an antiplatelet or anticoagulant (P = < 0.0001) likely to have suffered their TBI from a fall (P = 0.0349), and experienced vomiting afterwards (P = 0.0193). CONCLUSIONS: This study underscores: 1) the importance of neuroimaging in all patients with TBI, including those with a GCS 15. Fully 10% of our cohort was not imaged. Extrapolating, these would represent 2.5% bleeds, and 1.47% fractures. 2) The limitations of GCS in classifying TBI, as patients with even the mildest of mild TBI have a high frequency of gross CT abnormalities.

The Francis Crick Institute.

The Francis Crick Institute Laboratory, opened in 2016, is supported by the Medical Research Council, Cancer Research UK, the Wellcome Trust, and University College London, King's College London and Imperial College London. The emphasis on research training and early independence of gifted scientists in a multidisciplinary environment provides unique opportunities for UK medical science, including clinical and translational research.

Orbital hemangioma requiring enucleation in a premature infant.

A preterm male infant developed a rapidly growing, treatment-resistant orbital hemangioma. Despite aggressive management, the patient required enucleation of his right eye and image-guided ethanol sclerosis to limit tumor progression intracranially.

The value of neurocognitive testing for acute outcomes after mild traumatic brain injury.

BACKGROUND: Traditionally, neurocognitive testing is performed weeks to months after head injury and is mostly performed on patients who continue to have symptoms or difficulties. In this study, we sought to determine whether these tests, when administered acutely, could assist in predicting short-term outcomes after acute traumatic brain injury (TBI). METHODS: This is an IRB-approved prospective study of adult patients who came to the emergency department of our Level-1 trauma center with TBI. Patients were enrolled prospectively after providing written informed consent and underwent three separate neurocognitive tests: the Galveston Orientation Amnesia Test (GOAT) the Rivermead Post-Concussion Survey Questionnaire (RPCSQ) and the Mini Mental Status Examination (MMSE). RESULTS: A lower GOAT score was significantly associated with hospitalization (P = 0.0212) and the development of post-concussion syndrome (P = 0.0081) at late follow-up. A higher RPCSQ score was significantly associated with hospital admission (P = 0.0098), re-admission within 30 days of discharge (P = 0.0431) and evidence of post-concussion syndrome (PCS) at early follow-up (P = 0.0004). A higher MMSE score was significantly associated with not being admitted to the hospital (P = 0.0002) and not returning to the emergency department (ED) within 72 hours of discharge (P = 0.0078). Lower MMSE was also significantly associated with bleeding or a fracture on the brain CT (P = 0.0431). CONCLUSIONS: While neurocognitive testing is not commonly performed in the ED in the setting of acute head injury, it is both feasible and appears to have value in predicting hospital admission and PCS. These data are especially important in terms of helping patients understand what to expect, thus, aiding in their recovery.

Return of visual function after bilateral visual loss following flow diversion embolization of a giant ophthalmic aneurysm due to both reduction in mass effect and reduction in aneurysm pulsation.

Large and giant paraclinoid aneurysms are challenging to treat by either surgical or endovascular means. Visual dysfunction secondary to optic nerve compression and its relationship with aneurysm size, pulsation and thrombosis is poorly understood. We present a patient with a giant paraclinoid aneurysm resulting in bilateral visual loss that worsened following placement of a Pipeline Embolization Device and adjunctive coiling. Visual worsening occurred in conjunction with aneurysm thrombosis, increase in maximal aneurysm diameter and new adjacent edema. Her visual function spontaneously improved in a delayed fashion to better than pre-procedure, in conjunction with reduced aneurysmal mass effect, size and pulsation artifact on MRI. This report documents detailed ophthalmologic and MRI evidence for the role of thrombosis, aneurysm mass effect and aneurysm pulsation as causative etiologies for both cranial nerve dysfunction and delayed resolution following flow diversion treatment of large cerebral aneurysms.

TBI ADAPTER: traumatic brain injury assessment diagnosis advocacy prevention and treatment from the emergency room--a prospective observational study.

There is no standard treatment algorithm for patients who present to the emergency department (ED) with acute traumatic brain injury (TBI). This is in part because of the heterogeneity of the injury pattern and the patient profile, and the lack of evidence-based guidelines, especially for mild TBI in adults. As TBI is seen more and more frequently in the ED, a standardized assessment would be beneficial in terms of efficiency. The authors present their ED approach to mild TBI evaluation in the ED, along with results to date. These data represent a prospective observational cohort study, where each patient provided individual, written informed consent.

Understanding Why Patients Return to the Emergency Department after Mild Traumatic Brain Injury within 72 Hours.

INTRODUCTION: Although there are approximately 1.1 million case presentations of mild traumatic brain injury (mTBI) in the emergency department (ED) each year, little data is available to clinicians to identify patients who are at risk for poor outcomes, including 72-hour ED return after discharge. An understanding of patients at risk for ED return visits during the hyperacute phase following head injury would allow ED providers to develop clinical interventions that reduce its occurrence and improve outcomes. METHODS: This institutional review board-approved consecutive cohort study collected injury and outcome variables on adults with the purpose of identifying positive predictors for 72-hour ED return visits in mTBI patients. RESULTS: Of 2,787 mTBI patients, 145 (5%) returned unexpectedly to the ED within 72 hours of hospital discharge. Positive predictors for ED return visits included being male (p=0.0298), being black (p=0.0456), having a lower prehospital Glasgow Coma Score (p=0.0335), suffering the injury due to a motor vehicle collision (p=0.0065), or having a bleed on head computed tomography (CT) (p=0.0334). ED return visits were not significantly associated with age, fracture on head CT, or symptomology following head trauma. Patients with return visits most commonly reported post-concussion syndrome (43.1%), pain (18.7%), and recall for further clinical evaluation (14.6%) as the reason for return. Of the 124 patients who returned to the ED within 72 hours, one out of five were admitted to the hospital for further care, with five requiring intensive care unit stays and four undergoing neurosurgery. CONCLUSION: Approximately 5% of adult patients who present to the ED for mTBI will return within 72 hours of discharge for further care. Clinicians should identify at-risk individuals during their initial visits and attempt to provide anticipatory guidance when possible.

A red eye and then a really red eye.

A 90-year-old woman presented with a 4-week history of a presumed infectious conjunctivitis resistant to topical antibiotic medications. Examination revealed tortuous, dilated conjunctival vessels in the right eye, retinal hemorrhages, and an orbital bruit suggestive of a carotid-cavernous sinus fistula (CCF). While awaiting a magnetic resonance imaging study, she returned to the clinic the next day with a painful, swollen right eye and an intraocular pressure of 69 mm Hg. A cerebral arteriogram confirmed a direct CCF. Because of the tortuosity of the systemic vascular anatomy, a right carotid artery cut-down with balloon occlusion was performed with successful closure of the fistula and prompt resolution of the orbital congestion. This case illustrates the spectrum of subtle to conspicuous ocular manifestations that can be seen in patients with CCF and its potential to present as an emergency. CCF should be included in the differential diagnosis of an "atypical" red eye. Recognition of arteriolized conjunctival vessels and auscultation of an orbital bruit raises the possibility of a CCF, requiring prompt diagnostic studies.

Adult patient doses in interventional neuroradiology.

We investigated radiation doses to 149 adult patients who underwent interventional neuroradiologic procedures, consisting of 132 patients who had diagnostic imaging examinations and 17 patients who had therapeutic procedures. The interventional procedures were carried out on a biplane system capable of performing fluoroscopy and digital subtraction angiography (DSA). The x-ray imaging system was interfaced to a patient dosimetry system, which computed surface (skin) doses based on the selected radiographic technique factors in each of the radiographic and fluoroscopic imaging modes. For each patient, an assessment was made of the maximum surface dose received during the procedure, which predicts the possibility of inducing deterministic effects. Knowledge of the surface doses, beam quality and x-ray cross sectional area permitted the computation of the total energy imparted to each patient. Energy imparted values were converted to effective dose, which provides an estimate of the stochastic radiation risk to the patient. The median surface dose for the frontal plane during diagnostic imaging examinations was 1.3 Gy, with a maximum surface dose of 5.1 Gy. The median surface dose for the frontal plane during therapeutic procedures was 2.8 Gy with a maximum surface dose of 5.0 Gy. Ratios of the lateral to frontal median surface doses were 0.47 for diagnostic examinations and 0.68 for interventional procedures. The median energy imparted was 1.8 J during fluoroscopy, and 4.3 J during radiography, showing that on average, 66% of the patient exposure comes from radiographic imaging (DSA). For diagnostic examinations, the median patient effective dose was 33 mSv, with a maximum of 152 mSv. For therapeutic procedures, the median patient effective dose was 74 mSv, with a maximum of 156 mSv. In interventional neuroradiology, surface doses could induce deterministic effects, and the corresponding effective doses are noticeably higher than those normally encountered in diagnostic radiology.