Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death.

As therapies, oncolytic viruses regress tumors and have the potential to induce antitumor immune responses that clear hard-to-treat and late-stage cancers. Despite this promise, clearance from the blood prevents treatment of internal solid tumors. To address this issue, we developed virus-delivering Salmonella (VDS) to carry oncolytic viruses into cancer cells. The VDS strain contains the PsseJ-lysE delivery circuit and has deletions in four homologous recombination genes (ΔrecB, ΔsbcB, ΔsbcCD, and ΔrecF) to preserve essential hairpins in the viral genome required for replication and infectivity. VDS delivered the genome for minute virus of mice (MVMp) to multiple cancers, including breast, pancreatic, and osteosarcoma. Viral delivery produced functional viral particles that are cytotoxic and infective to neighboring cells. The release of mature virions initiated new rounds of infection and amplified the infection. Using Salmonella for delivery will circumvent the limitations of oncolytic viruses and will provide a new therapy for many cancers.

Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies.

Many systemically administered cancer therapies exhibit dose-limiting toxicities that reduce their effectiveness. To increase efficacy, bacterial delivery platforms have been developed that improve safety and prolong treatment. Bacteria are a unique class of therapy that selectively colonizes most solid tumors. As delivery vehicles, bacteria have been genetically modified to express a range of therapies that match multiple cancer indications. In this review, we describe a modular "build-a-bug" method that focuses on five design characteristics: bacterial strain (chassis), therapeutic compound, delivery method, immune-modulating features, and genetic control circuits. We emphasize how fundamental research into gut microbe pathogenesis has created safe bacterial therapies, some of which have entered clinical trials. The genomes of gut microbes are fertile grounds for discovery of components to improve delivery and modulate host immune responses. Future work coupling these delivery vehicles with insights from gut microbes could lead to the next generation of microbial cancer therapy.

Spinal Dural Arteriovenous Fistula in a Young Male Associated with Craniospinal Leptomeningeal Spread of a Treated High-Grade Glioma.

Spinal dural arteriovenous fistulae (SDAVF) are most commonly idiopathic in origin but may occasionally be seen secondary to surgery, trauma, or inflammation. We report a case of 27-year-old male who came with features of a myelopathy. He was found to have an SDAVF associated with leptomeningeal spread (LMS) of a previously treated high-grade cerebral glioma. Hemorrhagic presentation of gliomas, as in this case, is due to upregulation of vascular endothelial growth factor, which has also been postulated to play a role in the development of SDAVFs. This may suggest a possible mechanism of induction of secondary SDAVFs associated with such tumors. While the coexistence of intracranial neoplasms with vascular malformations has been reported previously, this is the first case report of LMS of a high-grade glioma associated with an SDAVF.

Magnetic resonance imaging of the orbit, Part 1: Basic principles and radiological approach.

Magnetic resonance imaging (MRI) is an eloquent, noninvasive, cross-sectional imaging modality that offers superior tissue characterization of orbital pathologies. The ophthalmologist needs to be aware of the advantages of MRI and its step-wise interpretation in liaison with a radiologist to optimize patient outcomes. In this review, we discuss the basic principles of MRI, some of the commonly used sequences and protocols, the anatomy of the orbit on MRI, and an approach to radiological interpretation.

Magnetic resonance imaging of the orbit, Part 2: Characterization of orbital pathologies.

In this article we focus on a systematic approach to assess common orbital lesions on magnetic resonance imaging (MRI). The identification of the probable compartment or structure of origin helps narrow the differential diagnosis of a lesion. Analyzing the morphology, appearance, and signal intensity on various sequences, the pattern, and degree of contrast enhancement are key to characterize lesions on MRI. Imaging features suggesting cellularity and vascularity can also be determined to help plan for biopsy or surgery of these lesions. MRI can also distinguish active from chronic disease in certain pathologies and aids in selecting appropriate medical management. MRI may thus serve as a diagnostic tool and help in guiding therapeutic strategies and posttreatment follow-up.

Orbital infarction syndrome secondary to rhino-orbital mucormycosis in a case of COVID-19: Clinico-radiological features.

Orbital infarction syndrome is an uncommon pathology with devastating consequences. It is frequently secondary to atherothrombotic phenomena in the internal carotid artery. We report a case of a 66-year-old male with uncontrolled diabetes and use of systemic steroids for COVID-19, who presented with a sudden loss of vision in the left eye, with total ophthalmoplegia and diffuse opacification of the retina. On imaging, he was found to have features of rhino-orbital cellulitis with ischemia of the orbital tissue secondary to isolated ophthalmic artery obstruction (OAO) with a patent internal carotid artery. KOH mount of deep nasal swab was confirmatory of mucor. This is the first reported case of orbital infarction syndrome in the setting of COVID-19.

Republished: Primary intraventricular haemorrhage due to rupture of giant varix of the basal vein of Rosenthal in a patient with long-standing direct CCF: angiographic features and treatment considerations.

Direct carotid cavernous fistulae (CCF) are often detected early and treated promptly resulting in a paucity of literature regarding its long-term evolution. We present a case of high flow post-traumatic direct CCF that was neglected for over 6 years and presented with a rare manifestation of primary intraventricular haemorrhage. Occlusions of the primary venous outlets likely resulted in engorgement of the deep venous system. The segmental anatomy of the shunting basal vein is critical to the clinical presentation and may range from basal ganglia or brainstem oedema/infarctions to uniquely, as in our case, isolated intraventricular haemorrhage secondary to variceal rupture. Treatment in such chronic cases requires a consideration of cerebral hyperperfusion syndrome necessitating deconstructive techniques with subsequent anticoagulation to avoid accelerated thrombosis of the venous varices.

Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

BACKGROUND AND PURPOSE: The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE). MATERIAL AND METHODS: The hospital electronic database was searched using the search words "encephalitis," "autoimmune encephalitis" and "Rasmussen's encephalitis" for the period of 1 Jan 2015 to 31 Jan 2017. Clinically diagnosed cases of RE for which epilepsy protocol magnetic resonance imaging (MRI) with perfusion imaging (ASL) performed on a 3T scanner were retrieved. The diagnosis of RE was based on Bien's criteria (Bien et al., 2005). We obtained patient's demographic details, clinical features, electrophysiological studies, and follow-up data from electronic hospital records. RESULTS: We included nine patients with RE of whom seven patients showed increased perfusion, and two patients decreased perfusion. Among these patients, MRI changes of gyral hyperintensity without volume loss corresponded to regional ASL hyperperfusion in six patients and ASL hypoperfusion in one patient. Two patients who showed ASL hypoperfusion had corresponding atrophy on MRI. Eight patients of RE had epilepsia partialis continua (EPC) or daily seizures, and one patient was seizure-free post-surgery. Five patients showed a concordance of ASL hyperperfusion with clinical ictal onset zone. Among the seven patients with ASL hyperperfusion, the finding was concordant (complete or partial) with the electroencephalogram (EEG) ictal onset zone in six patients and with interictal epileptiform discharges (IED) in seven patients. CONCLUSION: Increased perfusion in ASL of the involved brain parenchyma in RE is a common MRI finding and may be due to either active inflammation of the brain involved or a seizure-related finding.

Comparison of sutured versus sutureless scleral-fixated intraocular lenses.

PURPOSE: To compare the intermediate-term anatomic and visual results of scleral-fixated intraocular lens (IOL) implantation using 4-point suture fixation or transscleral sutureless fixation. SETTING: Tertiary referral eye care center in South India. DESIGN: Retrospective case series. METHODS: Medical records of consecutive patients who had scleral-fixated IOL surgery from January 1, 2010, to March 31, 2014, with more than 1 year of follow-up were retrospectively analyzed. Indication for scleral-fixated IOL implantation was aphakia after cataract extraction or trauma. The surgical technique was based on individual surgeon preference. The uncorrected distance visual acuity (UDVA), previous surgery, type of trauma, surgical technique, and complications were analyzed. RESULTS: One hundred nine cases were analyzed. The mean follow-up was 18.9 months ± 8.7 (SD). The majority of eyes experienced an improvement in UDVA after surgery; 93 eyes (86%) had a Snellen equivalent corrected distance visual acuity of 6/12 or better. The baseline characteristics and final visual outcomes in the sutured scleral-fixated IOL group (n = 52) and sutureless scleral-fixated IOL group (n = 59) were comparable. Patients with previous trauma (n = 52) were predominantly men and were significantly younger than those in the cataract group. The visual and refractive outcomes were comparable between eyes with previous trauma and eyes with previous cataract surgery. Transient cystoid macular edema was the most common complication (12%); retinal detachment occurred in 5 cases (4.5%). CONCLUSIONS: Scleral-fixated IOLs provided excellent visual rehabilitation of aphakic eyes without capsular support. The sutured technique and sutureless technique appear to be equally good in eyes with aphakia after cataract surgery or trauma. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Metastatic Serratia endophthalmitis associated with extravasation injury in a preterm neonate.

The authors report a case of a preterm neonate who presented with lid edema, corneal edema, and an inflammatory membrane with whitish exudates in the pupillary area, suggestive of endophthalmitis. There was also a cutaneous ulcer with an eschar on the right wrist at the site of extravasation associated with previous intravenous catheter. Cultures from the ulcer and vitreous samples both grew Serratia marcescens with identical antibiotic sensitivity and resistance patterns. The ocular infection was rapidly progressive and did not respond to administered medical and surgical therapy leading to subsequent phthisis bulbi. Serratia can cause endophthalmitis refractory to antibiotics and despite aggressive and timely treatment can have an unfavorable outcome. This report aims at highlighting the possibility of metastatic infection from an extravasation injury with a potentially fatal outcome.

Idiopathic Macular Telangiectasia Type 1 with Ruptured Retinal Arterial Macroaneurysm Post Intravitreal Bevacizumab.

A 50-year-old Indian male presented with defective vision in the right eye for 6 months. He was diagnosed to have idiopathic macular telangiectasia (IMT) type 1 associated with diffuse macular edema and multiple retinal arterial macroaneurysms (RAM). Intravitreal bevacizumab was administered for the treatment of macular edema, following which there was a rupture of a preexisting RAM with multilevel retinal hemorrhages. The hemorrhage gradually resolved over time with foveal thinning noted at last visit. We report this case for the rare occurrence of IMT type 1 and also the possibly associated rupture of RAM post intravitreal bevacizumab injection.

Quantum dot self-assembly for protein detection with sub-picomolar sensitivity.

A novel approach to sensitive and rapid antigen detection is described. In the presence of a specific antigen, quantum dot-antibody conjugates rapidly self-assemble into agglomerates that are typically more than 1 order of magnitude larger than their individual components. The size distribution of the agglomerated colloids depends on, among other things, the relative concentration of quantum dot conjugates and antigen molecules. Quantum dot agglomerates mediated by antigen recognition were characterized by measuring their light scattering and fluorescence characteristics in an unmodified flow cytometer. Protein antigens angiopoietin-2 and mouse IgG were detected to sub-picomolar concentrations using this method. This simple technique enables the potential simultaneous detection of multiple antigenic biomarkers directly from physiological media and could be used for early detection and frequent screening of cancers and other diseases.