Immune checkpoint inhibition: a future guided by radiology.

The limitation of the function of antitumour immune cells is a common hallmark of cancers that enables their survival. As such, the potential of immune checkpoint inhibition (ICI) acts as a paradigm shift in the treatment of a range of cancers but has not yet been fully capitalised. Combining minimally and non-invasive locoregional therapies offered by radiologists with ICI is now an active field of research with the aim of furthering therapeutic capabilities in medical oncology. In parallel to this impending advancement, the "imaging toolbox" available to radiologists is also growing, enabling more refined tumour characterisation as well as greater accuracy in evaluating responses to therapy. Options range from metabolite labelling to cellular localisation to immune checkpoint screening. It is foreseeable that these novel imaging techniques will be integrated into personalised treatment algorithms. This growth in the field must include updating the current standardised imaging criteria to ensure they are fit for purpose. Such criteria is crucial to both appropriately guide clinical decision-making regarding next steps of treatment, but also provide reliable prognosis. Quantitative approaches to these novel imaging techniques are also already being investigated to further optimise personalised therapeutic decision-making. The therapeutic potential of specific ICIs and locoregional therapies could be determined before administration thus limiting unnecessary side-effects whilst maintaining efficacy. Several radiological aspects of oncological care are advancing simultaneously. Therefore, it is essential that each development is assessed for clinical use and optimised to ensure the best treatment decisions are being offered to the patient. In this review, we discuss state of the art advances in novel functional imaging techniques in the field of immuno-oncology both pre-clinically and clinically.

Giant duodenal diverticulum masquerading as a sealed perforation.

Giant duodenal diverticula are large outpouchings involving all layers of the duodenal wall. Whilst often an incidental finding, giant duodenal diverticula can present with diverticulitis or biliary obstruction. We report a case of a giant duodenal diverticulum that was initially misdiagnosed as a localised duodenal perforation on CT. Additional ultrasound and fluoroscopic imaging demonstrated the final diagnosis of acute cholecystitis. The clinical course of this patient highlights the challenge of recognising a giant duodenal diverticulum and the limitations of solely relying on CT in the context of an acute abdominal presentation.

Short-Term Outcomes of Pediatric Keratoprosthesis With the Near-Complete Conjunctival Flap.

PURPOSE: The Boston keratoprosthesis (KPro) has been used for certain indications in pediatric patients with congenital corneal opacities. Here, we describe the use of a near-complete conjunctival flap at the time of Boston type 1 KPro surgery in pediatric patients, with the goal of improving pediatric KPro outcomes. METHODS: We performed a retrospective chart review of 21 eyes from 16 patients who received their first KPro before the age of 18 years at a tertiary care center in Rochester, NY. Surgeries were performed between 2011 and 2017 (3 years before and after the incorporation of a conjunctival flap, which began in 2014 as part of the pediatric KPro procedure). Patients who had a minimum 1-year postoperative follow-up, or had corneal melts within 1 year of KPro implantation, were included in our study. The main outcome measure in this study was a comparison of the number of complications that required surgical intervention, including retroprosthetic membrane, corneal melt, retinal detachment, and endophthalmitis, in eyes that received KPro implantation without a conjunctival flap compared with eyes that received KPro implantation with a conjunctival flap. Change in the visual acuity up to 1 year postoperatively was also measured. RESULTS: Ten eyes received KPro with no conjunctival flap, and 11 eyes received KPro with a near-complete conjunctival flap. After 1-year postoperative follow-up, eyes receiving a KPro with a conjunctival flap had fewer KPro-related complications requiring surgical intervention (5 vs. 16, P = 0.0002). Corneal melt was seen in 2 of 11 (18%) eyes in the conjunctival flap group and 5 of 10 (50%) eyes in the nonflap group (P = 0.12). No eyes developed endophthalmitis in the flap group, whereas 1 of 10 (10%) eyes developed endophthalmitis in the nonflap group. Visual acuity at 1-year follow-up improved in 9 of 11 (82%) eyes in the flap group compared with 5 of 10 (50%) eyes in the nonflap group (P = 0.3). CONCLUSIONS: Implementation of a conjunctival flap in pediatric KPro may help decrease the short-term postoperative complications requiring surgical procedures and may lead to improved visual acuity after 1 year. Further investigation, including longer-term follow-up, is needed to better understand how the described technique affects surgical outcomes in children.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Outcome of ambulatory video-EEG monitoring in a ˜10,000 patient nationwide cohort.

PURPOSE: We evaluate outcome of in-home diagnostic ambulatory video-EEG monitoring (AVEM) performed on a nationwide cohort of patients over one calendar year, and we compare our findings with outcomes of inpatient adult and pediatric VEM performed during the same year at two academic epilepsy centers. METHODS: This is a retrospective cohort study. We obtained AVEM outcome data from an independent ambulatory-EEG testing facility. Inpatient VEM data from a 4-bed adult epilepsy center and an 8-bed pediatric epilepsy center were also included. Primary outcome measure was composite percentage of VEM records with epileptiform activity on EEG tracings or at least one video-recorded pushbutton event. We assessed patient-reported symptoms documented in AVEM event diaries. RESULTS: Of 9221 AVEM recordings performed across 28 states, 62.5% attained primary outcome. At least one patient-activated pushbutton event was captured on video in 54% of AVEM recordings (53.6% in adults, 56.1% in children). Epileptiform activity was reported in 1657 (18.0%) AVEM recordings (1473 [88.9%] only interictal, 9 [0.5%] only ictal, 175 [10.6%] both interictal and ictal). Most common patient-reported symptomatology during AVEM pushbutton events was behavioral/autonomic/emotional in adults and children. Compared to AVEM, inpatient VEM captured more confirmed representative events in adult and pediatric samples. CONCLUSIONS: AVEM is useful for non-urgent diagnostic evaluation of events.

Association of Intraocular Pressure With Human Immunodeficiency Virus.

PURPOSE: Prior studies have shown an association between human immunodeficiency virus (HIV) and reduced intraocular pressures (IOP). The purpose of this study was to determine if patients with HIV on highly active antiretroviral therapy (HAART) had any difference in their IOP compared with patients without HIV or with HIV who are not on HAART. DESIGN: Retrospective cross-sectional study. METHODS: We included 400 patients from our academic eye center between 2000 and 2016. Group 1 (G1) consisted of patients with HIV on HAART (n = 176), Group 2 (G2) consisted of patients with HIV who were not on HAART (n = 48), and Group 3 (G3) consisted of controls without HIV (n = 176). An analysis of variance (ANOVA) was performed to compare mean IOP values. Multivariate linear and logistic regression models were performed to assess factors impacting IOP. Difference in IOP was the primary outcome being measured. RESULTS: The mean IOPs in mm Hg were 13.7 ± 5.1 (G1), 13.1 ± 3.6 (G2), and 17.3 ± 3.8 (G3), P < .01. In regression modeling, having a CD4 count ≤700 cells/mm3 contributed to a 2.1 mm Hg decrease in IOP. Patients with HIV were 7 times more likely to have an IOP ≤10 mm Hg, and patients with a CD4 count ≤700 cells/mm3 were 13 times more likely to have an IOP ≤10 mm Hg. CONCLUSIONS: Absolute CD4 counts may play a role in IOP fluctuations. This association was found in patients with HIV regardless of whether patients were on HAART.

The Monocular Duke of Urbino.

Federico da Montefeltro (1422-1482), the Duke of Urbino, was a well-known historical figure during the Italian Renaissance. He is the subject of a famous painting by Piero della Francesca (1416-1492), which displays the Duke from the left and highlights his oddly shaped nose. The Duke is known to have lost his right eye due to an injury sustained during a jousting tournament, which is why the painting portrays him from the left. Some historians teach that the Duke subsequently underwent nasal surgery to remove tissue from the bridge of his nose in order to expand his visual field in an attempt to compensate for the lost eye. In theory, removal of a piece of the nose may have expanded the nasal visual field, especially the "eye motion visual field" that encompasses eye movements. In addition, removing part of the nose may have reduced some of the effects of ocular parallax. Finally, shifting of the visual egocenter may have occurred, although this seems likely unrelated to the proposed nasal surgery. Whether or not the Duke actually underwent the surgery cannot be proven, but it seems unlikely that this would have substantially improved his visual function.

Factors affecting successful isolation of human corneal endothelial cells for clinical use.

Corneal transplantation is a common transplant procedure used to improve visual acuity by replacing the opaque or distorted host tissue with clear healthy donor tissue. However, its clinical utility is limited due to a lack of donor supply of high-quality corneas. Bioengineered neocorneas, created using an expandable population of human donor-derived corneal endothelial cells (HCECs), could address this shortage. Thus, the objective of this study was to evaluate HCEC sourcing with various isolation methods, including enzymatic digestion, culture medium components, and adhesive proteins. HCECs were obtained from corneas obtained from various aged donors after endothelial keratoplasty. Under a dissection microscope, the Descemet's membrane, including the attached corneal endothelium, was stripped from the stroma, and the cells were isolated and expanded by explant culture or by enzymatic digestion with enzymes such as collagenase II, dispase, or trypsin. In order to improve the initial cell attachment, tissue culture plates were coated with collagen IV, fibronectin, or fibronectin-collagen combination coating mix (FNC) before cell plating. We were able to successfully obtain HCECs from 32% (86/269) of donor corneas. Donor age and isolation method influenced the characteristics of the resulting in vitro HCEC culture. Under all conditions tested, FNC-coated plates showed higher quality cultures than the other coatings tested. These results suggest that donor age and HCEC isolation methodology are the two factors that most directly affect the quality of the resulting HCEC culture in vitro. These factors should guide the methodological development for the clinical expansion of HCECs for the generation of bioengineered neocorneas.

In vitro evaluation of the interactions between human corneal endothelial cells and extracellular matrix proteins.

The corneal endothelium is the innermost cell layer of the cornea and rests on Descemet's membrane consisting of various extracellular matrix (ECM) proteins which can directly affect the cellular behaviors such as cell adhesion, proliferation, polarity, morphogenesis and function. The objective of this study was to investigate the interactions between the ECM environment and human corneal endothelial cells (HCECs), with the ultimate goal to improve cell proliferation and function in vitro. To evaluate the interaction of HCECs with ECM proteins, cells were seeded on ECM-coated tissue culture dishes, including collagen type I (COL I), collagen type IV (COL IV), fibronectin (FN), FNC coating mix (FNC) and laminin (LM). Cell adhesion and proliferation of HCECs on each substratum and expression of CEC markers were studied. The results showed that HCECs plated on the COL I, COL IV, FN and FNC-coated plates had enhanced cell adhesion initially; the number for COL I, COL IV, FN and FNC was significantly higher than the control (P < 0.05). In addition, cells grown on ECM protein-coated dishes showed more compact cellular morphology and CEC marker expression compared to cells seeded on uncoated dishes. Collectively, our results suggest that an adequate ECM protein combination can provide a long-term culture environment for HCECs for corneal endothelium transplantation.

Electrocardiographic spatial QRS-T angle and incident cardiovascular disease in HIV-infected patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] study).

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.

Effects of a family-implemented treatment on the repetitive behaviors of children with autism.

The restricted and repetitive behaviors of children with autism can interfere with family functioning as well as learning and socialization opportunities for the child. To date, neither pharmacological nor comprehensive behavioral treatments have been found to be consistently effective at significantly reducing children's engagement in repetitive behaviors. We developed Family-Implemented Treatment for Behavioral Inflexibility (FITBI) to target the full variety of repetitive behaviors found in autism. For the current study, a therapist and parents of five children with autism (mean age = 48 months) co-implemented FITBI in a clinic setting over a 12-week treatment period. Using single case design methodology, significant reductions in repetitive behaviors were found for all participants and maintenance of treatment effects for 4 of 5 participants.