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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated vaccine development. The BNT162b2 messenger RNA (mRNA) vaccine is being administered worldwide. The purpose of this case series is to report a possible association between the BNT162b2 mRNA vaccine and Central serous chorioretinopathy (CSC). Although rare, CSC has been reported following the administration of anthrax, influenza and smallpox vaccines.Four individuals who developed CSC following the BNT162b2 mRNA vaccine were examined in our institution using multimodal imaging of the retina, and their demographic data were analyzed and compared to all the similar cases published to date.Four patients (3 males, 1 female) between the ages of 35 and 65 presented with acute CSC (n=3) and relapsed CSC (n=1) within the first week following the administration of the BNT162b2 mRNA vaccine. Three individuals demonstrated hyper-reflective foci in the outer segments of the retina.The timing of the BNT162b2 mRNA vaccine administration relative to the development of CSC suggests a possible causal relationship. Further research is necessary to explore this possible association.

OBJECTIVES: To identify predictors of infant sleep arrangement and examine the directionality of the relationships between maternal depressive symptoms, infant sleep problems, and bedsharing. DESIGN: Secondary analysis of longitudinal data from the Mothers and Others: Family-Based Obesity Prevention for Infants and Toddlers randomized trial. SETTING: Central North Carolina, USA. PARTICIPANTS: Four-hundred and twenty-eight predominantly low-income, non-Hispanic Black mother-infant pairs. MEASUREMENTS: Data were collected at 28 weeks pregnancy and 1, 3, 6, 9, 12, and 15 months postpartum. Maternal depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale and infant sleep variables were measured using the Brief Infant Sleep Questionnaire. RESULTS: The prevalence of reported bedsharing increased from 16.7% at 1 month to 35.6% at 15 months postpartum. Bedsharing was associated with shortened breastfeeding duration and maternal perception of an infant sleep problem. Concurrently, maternal perception of an infant sleep problem, but not presence of maternal depressive symptoms, was associated with an increased likelihood of bedsharing. Longitudinally, neither maternal perception of an infant sleep problem nor presence of maternal depressive symptoms predicted bedsharing. Bedsharing predicted an increased likelihood of maternal perception of an infant sleep problem and presence of maternal depressive symptoms. CONCLUSION: Prevalence of bedsharing increased over time and was predictive of maternal depressive symptoms. Providers should discuss the conflicting infant sleep recommendations with their patients and provide safe-sleep guidelines for mothers who intend to bedshare.

This study compared pain and anxiety levels in individuals receiving intravitreal injections (IVIs) using a speculum-free injection technique, the lid splinting eyelid retraction technique, or using a speculum.This was a prospective study of individuals receiving IVI at a single tertiary care medical center who responded to a questionnaire and visual analog scale (VAS) between December 2019 and January 2020. In one group, a speculum was used prior to injection, whereas in the other group, a speculum-free injection technique was used.A total of 108 individuals were included in this study: 54 received IVI with the speculum-free lid splinting eyelid retraction technique and 54 received IVI with a speculum. A correlation between pain and anxiety was demonstrated in the control group (p-value 0.01); however, in the speculum-free group, this correlation was lower and not significant. When comparing pain and anxiety between the study groups, lower median pain (Mood's: Z = 5.378, p-value 0.001) and lower anxiety (Mood's: Z = 2.108, p-value = 0.035) scores were demonstrated in the speculum-free group than in the control group. The distribution of pain scores was significantly different between the study groups (Kolmogorov-Smirnov: D = 0.518, p-value 0.001), and trending differences in anxiety between the groups were observed (Kolmogorov-Smirnov: D = 0.259, p-value = 0.053).The lid splinting eyelid retraction technique, a speculum-free technique, was associated with less anxiety and pain in patients than the use of a speculum. As IVI often involves repeated treatment, identifying modifiable factors that may relieve anxiety and pain is of utmost importance.

To study the distribution of ocular biometric parameters using a swept-source optical coherence tomography (SS-OCT) biometer in adult candidates for cataract surgery.A retrospective cross-sectional study.This is a single-center analysis of consecutive eyes measured with the IOLMaster 700 SS-OCT biometer at a large tertiary medical center between February 2018 and June 2020.Three thousand eight hundred thirty-six eyes of 3836 patients were included in the study. The mean ± SD age was 72.3 ± 12.8 years and 53% were female. The mean biometric values were as follows: total corneal power (44.17 ± 1.70 diopters [D]), total corneal astigmatism (TCA; 1.11 ± 0.87 D), mean posterior keratometry (-5.87 ± 0.26 D), posterior corneal astigmatism (-0.26 ± 0.15 D), axial length (AL; 23.95 ± 1.66 mm), anterior chamber depth (ACD; 3.18 ± 0.42 mm), lens thickness (LT; 4.49 ± 0.47 mm), white-to-white distance (WTW; 11.92 ± 0.44 mm), central corneal thickness (CCT; 0.54 ± 0.04 mm), angle alpha (0.49 ± 0.17 mm), and angle kappa (0.34 ± 0.17 mm). There were sex-related differences in all biometric parameters save for LT (P = .440), angle kappa (P = .216), and corneal astigmatism (P = .103). Biometric parameters demonstrated correlations between AL, WTW distance, ACD, and LT (P.001). Age correlated with all parameters (P.001) except CCT and posterior keratometry. Angle alpha and angle kappa magnitudes also correlated (P.001). The prevalence of patients with TCA ≥0.75 D, 1.0 D, and 1.5 D were 59.1%, 43.4%, and 22.6%, respectively.Age significantly correlated with most of the biometric parameters and significant differences between sexes were noted. In addition, the high prevalence of TCA and relatively large angle alpha and angle kappa magnitudes were noted among subjects. These data can be relevant in planning local and national health economics.

Es werden die Ergebnisse von Tiefenmessungen und von Horizontalmessungen in Meereshohe diskutiert. Einige Eigenarten, wie Intensitatsabnahme mit der 2,6 ten Potenz der Tiefe, starker Abfall der Intensitat bei dunnen und Wiederanstieg der Intensitat bei dickeren zwischengelegten Bleischichten, sowie grosere Intensitat in grosen Tiefen aus geneigten Eichtungen konnen erklart werden, wenn die Strahlung in grosen Tiefen bzw. in Meereshohe aus Horizontalrichtung aus Neutrinos oder Neutronen besteht, die aus dem Zerfall der Mesonen entstehen.

Background Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early‐ and intermediate‐stage HCC. Materials and Methods Twenty‐four patients with modified Child‐Pugh class A early‐ and intermediate‐stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR‐blockade, time to progression (TTP), and overall survival (OS). Results Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3–4 adverse events, most frequently (on‐target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF‐A, VEGF‐D, and placental growth factor increased significantly, whereas sTie‐2 decreased, consistent with VEGFR‐blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer‐specific survival was not reached. Conclusion Already after a short 4‐week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. Implications for Practice Orthotopic liver transplantation may cure early and intermediate‐stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing., Considering the scarcity of liver donors and expected waiting time to liver transplantation, there is an unmet need for effective neoadjuvant downsizing strategies. This article reports on the safety and efficacy of neoadjuvant dovitinib in patients with hepatocellular carcinoma eligible for locoregional treatment.

To investigate music selection as a treatment for anxiety during Intravitreal injections (IVI) for individuals of varying cultures.106 individuals were enrolled in this randomized controlled study. Individuals were randomized into one to three categories: (1) a control group in which the IVI procedure was performed without music (n = 35), (2) an experimental group in which the music was selected by the physician (n = 36), (3) an experimental group in which the music was selected by the patient (n = 35). After the procedure, all patients responded to a questionnaire regarding their level of experienced anxiety, pain and discomfort (grade 0-10). The primary outcome was anxiety level during the procedure.The experimental group in which patients selected music had higher number of patients with low anxiety score compared to the other groups (anxiety score4 in 19,18 and 27 patients, respectively,Music selection may be an effective way to reduce anxiety levels during IVI. Preference for music during future injections is higher in patients who were exposed to music during IVI and may be influenced by culture.

Background Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable. Purpose To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue. Study type Prospective. Population Eight breast cancer patients. Field strength/sequence A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout. Assessment VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam. Statistical tests Intra-class correlation coefficient (ICC) for interobserver agreement. Results The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score. Data conclusion We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients. Evidence level 1 TECHNICAL EFFICACY: Stage 1.

Background: Ophthalmology practice entails many hours of physical inactivity, a potential long-term health hazard. This study aims to perform a pedometer-based evaluation of the physical activity (PA) levels of ophthalmologists at work. Methods: This is a prospective observational study. Ophthalmologists from a single tertiary medical center were monitored with electronic pedometers during six morning sessions in the ophthalmology clinics. Working hours and the number of patients seen per clinic session were retrieved. The age and body mass index (BMI) of participants were documented. Step number per working hour (SPH) was calculated for all participants. Comparisons between males and females, practicing ophthalmologists (attendings) and ophthalmology residents (residents), and sub-specialties were performed. Correlations between SPH and age, BMI, and patients seen per clinic session were computed. Findings: Pedometer readings for a total of 673 working hours were analyzed for 24 ophthalmologists, 17% female, 17 attendings, mean age 44.2 years (standard deviation ( SD = 9.8). The average number of SPH for all participants was 359.7 ( SD = 166.7). The mean PA level of residents was significantly higher than that of attendings (410.17 SPH vs. 338.95 SPH, respectively, p = .019). Oculoplastic surgeons demonstrated significantly higher step counts per hour than cornea specialists (439.90 SPH vs. 245.55 SPH, respectively, p = .002). A negative correlation was observed between SPH and the number of patients seen per clinic session ( ρ = −0.274, p = .001). Conclusions/Applications to Practice: Low number of SPH for ophthalmologists in this study indicates ophthalmology to be a highly sedentary medical occupation. PA levels of ophthalmologists in the workplace may indicate a personal health care challenge.

Early childhood is a critical time of development. Caregiver feeding style, including of child care providers, has been implicated in influencing children's food preferences and obesity. A better understanding of the determinants of child care providers' feeding styles is important as children increasingly receive daily care and nutrition in child care centers. Valid instruments to measure provider feeding styles specifically for infants are needed. This study's objective was to validate, for use with child care providers, the Infant Feeding Styles Questionnaire (IFSQ), an instrument originally designed for parents of infants and toddlers. Study data came from the Baby Nutrition and Physical Activity Self-Assessment for Child Care (Baby NAP SACC) study, a cluster randomized trial, designed to evaluate the efficacy of a six-month-long obesity prevention intervention in child care centers. The IFSQ was administered at baseline and follow-up to infant and toddler teacher participants (n = 244). Scores for baseline IFSQ teacher responses (n = 219) were calculated for the 13 sub-constructs across the five feeding styles. We tested reliability with Cronbach's alpha coefficients and performed confirmatory factor analysis to examine factor loadings and goodness of fit characteristics, modifying constructs to achieve best fit. Reliability coefficients ranged from 0.42 to 0.82 for all sub-constructs. Goodness of fit indices for the final model ranged from: root mean square error of approximation (RMSEA) 0.000-0.082; comparative fit index (CFI) 0.943-1.000; Tucker-Lewis index (TLI) 0.906-1.000; and standardized root mean squared error (SRMR) 0.006-0.130. In a sample of racially diverse infant and toddler child care teachers, final models of the laissez-faire, pressuring, and responsive constructs and the restrictive-diet quality sub-construct performed well. Overall model fit was poor for the indulgence construct, but good for solely its corresponding belief items.

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy. Effective therapy requires adherence to a schedule of iterative IVI as well as routine clinic appointments. The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in the reduction of attendance at scheduled clinic visits and IVI. In this study, we attempted to analyze the effect of COVID-19 on compliance with anti-VEGF therapy. A total of 636 eyes received injections during a 4-week period of the COVID-19 outbreak in the Retina Clinic. The number of clinic visits for IVI during 1 month from March 15 to April 14 of 2020 was compared to a similar time period in each of the last 4 years. The study demonstrates a decrease in clinic visits for IVI when compared with the same 4-week interval in the four previous years. Based on the trend of the previous 4 years, 10.2% of the year's total was expected for this time period. Using this model, the 636 reported number of injections for the March-April 2020 period was ~ 5%. This represents a decrease of ~ 50% of the expected IVI for this time period. The COVID-19 outbreak in Israel severely impacted compliance with anti-VEGF treatments.

Purpose: The Coronavirus disease 2019 (COVID-19) pandemic is an ongoing healthcare crisis that continues its worldwide spread. Ophthalmologists are at high risk of acquiring and transmitting the virus. Telemedicine platforms have evolved and may play an important role in attenuating this risk. For patients, these platforms provide the possibility of clinic consultation without the concerns of a clinic visit. We aimed to assess the utilization of telemedicine by oculoplastics specialists worldwide during the COVID-19 pandemic. Methods: A 13-item survey was distributed internationally to practicing oculoplastic surgeons. Collected data included demographics, clinical practice variables and perceptions regarding telemedicine. Significance of associations and single survey items was evaluated by Chi-squared and z-score of proportions tests, respectively. Results: The questionnaire was completed by 70 oculoplastic surgeons (54.3% male, mean age 47.3 years, median experience 10 years) from eight countries, practicing in various clinical settings (50.0% hospitals, 45.7% private clinics, 4.3% community clinics). Most respondents reported telemedicine to be an effective tool for oculoplastic consultations (67.1%, p = 0.004), while only 12.8% ( p < 0.00001) had incorporated this modality into clinical practice prior to the pandemic. Even though a vast majority (98.6%) of participants had limited outpatient activity, most (55.7%) felt unprotected from the virus. Telemedicine had been incorporated by 70.5% ( p = 0.001) of respondents during the COVID-19 pandemic, whereas most (57.1%) predicted continued use of the modality. Conclusion: Telemedicine can be effectively and rapidly incorporated into the clinical practice of oculoplastic surgeons during the COVID-19 pandemic. Further research into the most effective utilization of these platforms appears warranted.

Background and Aims The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn’s disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas. Methods A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn’s disease was performed at the Leiden University Medical Center in 2012–2014. All patients treated with bmMSCs [1 x 107 bmMSCs cohort 1, n = 5; 3 × 107 bmMSCs cohort 2, n = 5; 9 × 107 bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy. Results Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years. Conclusions Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years.

A 45-year-old woman, immediately after receiving a cosmetic treatment with intense focused ultrasound (IFUS) over the eyelids, developed an acute, progressive, severe cataract with a unique shape as an adverse effect of the IFUS esthetic treatment. At examination of the lens in the right eye, 4 drop-like dense lens opacities aligned consecutively in a horizontal line together with a posterior capsular opacity in a stellate-shaped fashion. It rapidly progressed into a dense posterior cataract, leaving the patient with an uncorrected distance visual acuity (UDVA), from 20/20 prior to the event, to 20/160 4 days later. Phacoemulsification and intraocular lens implantation were performed, restoring her UDVA to 20/25. Cosmetic and ophthalmic healthcare providers should be aware of the potentially damaging effect of IFUS.

The purpose of this study was to report the most severe documented ocular injury caused by Ecballium elaterium , an invasive and toxic herb characterized by an explosive seed dispersal.A 55-year-old man presented to the emergency department several hours after direct exposure to the contents of E. elaterium to his left eye. Clinical examinations, investigations, and imaging findings are reported.Medical and ocular histories were unremarkable. On presentation, the patient exhibited markedly decreased visual acuity, severe periorbital edema, conjunctival chemosis, and corneal edema. Although other signs gradually improved, corneal edema worsened despite rapid initiation of systemic and topical steroids and normal intraocular pressure. After 4 months of follow-up, the cornea cleared and visual acuity returned to normal; however, a significant decrease in endothelial cell count was observed.Ecballium elaterium may cause a severe corneal chemical burn, with subsequent long-standing corneal edema and endothelial decompensation. Specular microscopy is a modality of great importance in these cases.

Background MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review. Methods Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities. Results 23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2–74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5–19 mm). All tumors were resectable. Conclusion MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis.

PURPOSE: The aim of this report was to report 2 patients who presented with acute corneal graft rejection 2 weeks after receiving the BNT162b2 messenger RNA (mRNA) vaccine for severe acute respiratory syndrome coronavirus 2. METHODS: Case report. RESULTS: Two men, aged 73 and 56 years, with a history of penetrating keratoplasty due to keratoconus were noted to have acute corneal graft rejection 2 weeks after receiving a first dose of the BNT162b2 mRNA vaccine. Both patients were treated with hourly dexamethasone 0.1% and oral prednisone 60 mg per day with prompt resolution of keratoplasty rejection. CONCLUSIONS: The BNT162b2 mRNA vaccine may be have been associated with a low-risk corneal graft rejection that responded well to topical and systemic steroids. Treating physicians should be aware of this potential complication and patients should be advised to report any visual changes after vaccination.

Background The management of abdominal aortic aneurysm (AAA) is fully dictated by AAA size, but there are no uniform measurement guidelines, and systematic differences exist between ultrasound- and CT-based size estimation. The aim of this study was to devise a uniform ultrasound acquisition and measurement protocol, and to test whether harmonization of ultrasound and CT readings is feasible. Methods A literature review was undertaken to evaluate evidence for ultrasound-based measurement of AAA. A protocol for measuring AAA was then developed, and intraobserver and interobserver reproducibility was tested. Finally, agreement between ultrasound readings and CT-based AAA diameters was evaluated. This was an observational study of patients with a small AAA who participated in two pharmaceutical intervention trials. Results Based on a literature review, an ultrasound acquisition and reading protocol was devised. Evaluation of the protocol showed an intraobserver repeatability of 1.6 mm (2s.d.) and an interobserver intraclass correlation coefficient (ICC) of 0.97. Comparison of protocolled ultrasound readings and local CT readings indicated a good correlation (r = 0.81), but a systematic +4.1-mm difference for CT. Harmonized size readings for ultrasound imaging and CT increased the correlation (r = 0.91) and reduced the systematic difference to +1.8 mm by CT. Interobserver reproducibility of protocolized CT measurements showed an ICC of 0.94 for the inner-to-inner method and 0.96 for the outer-to-outer method. Conclusion The absence of harmonized size acquisition and reading guidelines results in overtreatment and undertreatment of patients with AAA. This can be avoided by the implementation of standardized ultrasound acquisition and a harmonized reading protocol for ultrasound- and CT-based readings., Absence of harmonized size acquisition and reading guidelines result in overtreatment and undertreatment of patients with an abdominal aortic aneurysm. This can be avoided by the implementation of standardized ultrasound acquisition and the proposed harmonized reading protocol for ultrasound- and CT-based readings. Reducing measurement errors

Imatges per ressonància magnètica; Neoplàsies rectals; Microambient tumoral Imagen de resonancia magnética; Neoplasias rectales; Microambiente tumoral Magnetic Resonance Imaging; Rectal neoplasms; Tumor Microenvironment Objective This study evaluated the correlation between intratumoural stroma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer. Methods This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation ( r s ). Results The ADC values between stroma-low and stroma-high tumours were not significantly different. Intra-class correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84–0.86 for single slice and 0.86–0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADC mean r s = -0.162 ( p= 0.38) and ADC min r s = 0.041 ( p= 0.82) for the single-slice and r s = -0.108 ( p= 0.55) and r s = 0.019 ( p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADC mean r s = -0.022 ( p= 0.86) and ADC min r s = 0.049 ( p= 0.69) for the single-slice and r s = -0.064 ( p= 0.59) and r s = -0.063 ( p= 0.61) for the whole-volume measurements. Conclusions Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer. This study received financial support from “ Genootschap Landgoed Keukenhof .” Author R.P.L.’s work is supported by a PCF-Young Investigator Award . The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Background: In CDKN2A/p16-Leiden mutation carriers with a 15-20% lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), MRI surveillance has been shown to successfully detect PDAC at an early stage, resulting in increased resectability and survival. The purpose of this study is to retrospectively assess the value of different MRI-techniques in detection of PDAC in a screening setting, including a T1- weighted turbo field echo (TFE) with inversion recovery. Methods: Since the start of the screening program in 2000, 218 CDKN2A/p16-Leiden mutation carriers have been enrolled. During an observation period from January 2012 until August 2017, MRI protocols consisted of axial and coronal T2-weighted turbo spin echo (TSE), fat suppressed T1-weighted gradient echo multiphase contrast-enhanced (MCE) magnetic resonance cholangiopancreaticography (MRCP) and T1-TFE sequences performed at 3.0T. Diffusion weighted imaging (DWI) was added in 2015. Three readers independently analysed current and past MRI examinations for the presence of lesions and other imaging findings in subjects with a PDAC detected during the observation period. Contrast ratios (CR) measured on T1-TFE and T1-MCE were compared with a paired t-test. Results: Nine PDAC were detected, of which 8 (89%) were resectable with an average size of 13.4 mm at pathology. Seven of 9 PDAC were seen by all three readers on both T1-TFE and MCE (8 of 9 by at least two readers). Increased enhancement was seen on the delayed phase of T1-MCE in 7 PDAC. Pancreatic duct dilatation was present in 3 subjects. No cystic lesions were associated with the cancers. In 6 of 8 subjects with an incident tumor, a lesion or indirect signs thereof were seen on previous examinations by one or more readers. In two patients a lesion was retrospectively detected only on T1-TFE of the previous examination. The CR of lesions on T1-TFE was 75% greater compared to unenhanced T1-MCE (P=0.0001) and 58% greater compared to the late-arterial phase T1-MCE (P=0.0004). Conclusions: The inversion recovery prepulse of T1-TFE increases contrast between normal and abnormal pancreatic tissue. Knowledge of imaging features and recognition of subtle changes in the pancreas could improve detection of early pancreatic cancer in a high-risk screening population.

Type-1 Gaucher disease (GD1) is considered to be non- neuronopathic however recent evidence of neurological involvement continues to accumulate. There is limited evidence of retinal abnormalities in GD1. The purpose of this study was to evaluate the retinal findings of patients with GD1. Thirty GD1 individuals and 30 healthy volunteers between the ages 40–75 years were prospectively enrolled. Macular and optic nerve optical coherence tomography (OCT) scans of both eyes of each patient were performed and thickness maps were compared between groups. Patients with a known neurodegenerative disease, glaucoma, high myopia and previous intraocular surgeries were excluded. It was shown that patients with GD1 presented with higher incidence of abnormal pRNFL OCT scan and showed significantly thinner areas of pRNFL and macular ganglion cell complex (GCC) when compared to a healthy control population. Changes in retinal thickness were not associated with GD1 genotype, treatment status, disease monitoring biomarker (lyso-Gb1) and severity score index (Zimran SSI). Further investigations are needed to determine whether these findings possess functional visual implications and if retinal thinning may serve as biomarker for the development of future neurodegenerative disease in this population.

Background: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy. Effective therapy requires adherence to a schedule of iterative IVI as well as routine clinic appointments. The ongoing Coronavirus disease 2019 (COVID-19) pandemic has resulted in the reduction of attendance at scheduled clinics visits and IVI. In this study we attempted to analyze the effect of COVID-19 on compliance with anti-VEGF therapy.Methods: A total of 636 eyes received injections during a four-week period of the COVID-19 outbreak in the Retina Clinic. The number of clinic visits for IVI during one month from March 15 to April 14 of 2020 was compared to the similar time period in each of the last four years.Results: The study demonstrates a decrease in clinic visits for IVI when compared with the same four-week interval in the four previous years. Based on the trend of the previous four years, 10.2% of the year’s total was expected for this time period. Using this model, the 636 reported number of injections for the March-April, 2020 period was ~ 5%. This represents a decrease of ~50% of the expected IVI for this time period.Conclusion: The COVID-19 outbreak in Israel severely impacted compliance with anti-VEGF treatments.

The coronavirus disease (COVID-19) pandemic has evolved into a formidable healthcare crisis. Ophthalmologists are at daily personal risk of acquiring and transmitting the virus. Implementation of official practical and protective guidelines can be challenging and is often absent. The purpose of this study was to describe the status of ophthalmology practice in Israel, at the early stages of the outbreak. A 17-item questionnaire was distributed to ophthalmologists practicing in Israel. Data was obtained regarding demographics and clinical and surgical practice during the pandemic. One hundred and sixty-seven ophthalmologists completed the survey from all regions of Israel. The survey was distributed during the early stages of the outbreak. At this time, no official government guidelines were in place. Most respondents reported no reduction of elective clinic visits and surgeries and no utilization of triage questionnaires. COVID-19 guidelines were reportedly promulgated to hospital ophthalmologists but not to community and private physicians. Personal protective equipment (PPE) measures were reportedly utilized; however, many respondents often acquired them individually. A majority of respondents advocated that healthcare institutions limit clinic and surgery services to emergency services. During the critical early stages of the COVID-19 outbreak in Israel, this study emphasizes the delay in development of emergency guidelines, necessary to protect patients and ophthalmologists from this highly transmissible disease.

Introduction Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.

Recent research suggests that the strategic use of violence may increase a group’s chance of gaining independence. We investigate this topic using comprehensive data on all secessionist movements between 1900 and 2006 and an original data set on the institutional and extrainstitutional methods that secessionists have used from 1946 to 2011. Our analysis yields several important findings. First, strategy depends on context. Not all secessionist movements are the same, and many have legal and/or institutional routes to independence that shape the methods that they employ. Second, no secessionist movement challenging a contiguous state has won its sovereignty without using institutional methods, either exclusively or in combination with extrainstitutional methods. Finally, we identify four successful combinations of secessionist methods and discuss how these movements develop in relation to their strategic setting. Overall, we find no evidence that violence helps a secessionist movement to gain independence.

Background: Approximately 15% of all breast cancers occur in women with a family history of breast cancer, but for whom no causative hereditary gene mutation has been found. Screening guidelines for women with familial risk of breast cancer differ between countries. We did a randomised controlled trial (FaMRIsc) to compare MRI screening with mammography in women with familial risk. Methods: In this multicentre, randomised, controlled trial done in 12 hospitals in the Netherlands, women were eligible to participate if they were aged 30–55 years and had a cumulative lifetime breast cancer risk of at least 20% because of a familial predisposition, but were BRCA1, BRCA2, and TP53 wild-type. Participants who were breast-feeding, pregnant, had a previous breast cancer screen, or had a previous a diagnosis of ductal carcinoma in situ were eligible, but those with a previously diagnosed invasive carcinoma were excluded. Participants were randomly allocated (1:1) to receive either annual MRI and clinical breast examination plus biennial mammography (MRI group) or annual mammography and clinical breast examination (mammography group). Randomisation was done via a web-based system and stratified by centre. Women who did not provide consent for randomisation could give consent for registration if they followed either the mammography group protocol or the MRI group protocol in a joint decision with their physician. Results from the registration group were only used in the analyses stratified by breast density. Primary outcomes were number, size, and nodal status of detected breast cancers. Analyses were done by intention to treat. This trial is registered with the Netherlands Trial Register, number NL2661. Findings: Between Jan 1, 2011, and Dec 31, 2017, 1355 women provided consent for randomisation and 231 for registration. 675 of 1355 women were randomly allocated to the MRI group and 680 to the mammography group. 218 of 231 women opting to be in a registration group were in the mammography registration group and 13 were in the MRI registration group. The mean number of screening rounds per woman was 4·3 (SD 1·76). More breast cancers were detected in the MRI group than in the mammography group (40 vs 15; p=0·0017). Invasive cancers (24 in the MRI group and eight in the mammography group) were smaller in the MRI group than in the mammography group (median size 9 mm [5–14] vs 17 mm [13–22]; p=0·010) and less frequently node positive (four [17%] of 24 vs five [63%] of eight; p=0·023). Tumour stages of the cancers detected at incident rounds were significantly earlier in the MRI group (12 [48%] of 25 in the MRI group vs one [7%] of 15 in the mammography group were stage T1a and T1b cancers; one (4%) of 25 in the MRI group and two (13%) of 15 in the mammography group were stage T2 or higher; p=0·035) and node-positive tumours were less frequent (two [11%] of 18 in the MRI group vs five [63%] of eight in the mammography group; p=0·014). All seven tumours stage T2 or higher were in the two highest breast density categories (breast imaging reporting and data system categories C and D; p=0·0077) One patient died from breast cancer during follow-up (mammography registration group). Interpretation: MRI screening detected cancers at an earlier stage than mammography. The lower number of late-stage cancers identified in incident rounds might reduce the use of adjuvant chemotherapy and decrease breast cancer-related mortality. However, the advantages of the MRI screening approach might be at the cost of more false-positive results, especially at high breast density. Funding: Dutch Government ZonMw, Dutch Cancer Society, A Sister's Hope, Pink Ribbon, Stichting Coolsingel, J&T Rijke Stichting.

Background Widespread abdominal imaging has led to a substantial increase in the detection of incidentalomas. Currently, an increasing number of centers offer surveillance of the pancreas to individuals at high risk (IARs) of pancreatic ductal adenocarcinoma (PDAC). Objective The aims of this study were to evaluate the frequency and type of incidental findings in a magnetic resonance imaging (MRI)-based surveillance program for IARs for PDAC, and to discuss the benefit of detecting these lesions. Methods The outcome of MRI screening was reviewed in 568 individuals from three long-term pancreas surveillance programs conducted at three large European expert centers. All MRIs were studied in detail for the presence of incidental lesions. Results The most common lesions were liver cysts, renal cysts and liver hemangioma, which together comprised 75% of all lesions. Only five (0.9%) patients underwent surgery for a benign lesion. Cancer was detected in 11 patients (1.9%); early detection of tumors was beneficial in at least five cases. Conclusion The present study demonstrates that extrapancreatic incidentaloma is a common finding in IARs for PDAC, but rarely requires additional treatment. CDKN2A-p16-Leiden mutation carriers were the only patient group found to harbor a substantial number of cancers, and detection resulted in benefit in several cases.

Objective Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. Methods IAR from non- CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. Results 253 IAR with a median age of 48 (25–81) years underwent screening with a median of 3 (1–11) screening visits during a median follow-up of 28 (1–152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p

BACKGROUND & AIMS: Patients with perianal fistulizing Crohn's disease have a poor prognosis because these lesions do not heal well. We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells (MSCs) to these patients from healthy donors in a double-blind, placebo-controlled study. METHODS: Twenty-one patients with refractory perianal fistulizing Crohn's disease were randomly assigned to groups given injections of 1 x 10(7) (n = 5, group 1), 3 x 10(7) (n = 5, group 2), or 9 x 10(7) (n = 5, group 3) MSCs, or placebo (solution with no cells, n = 6), into the wall of curettaged fistula, around the trimmed and closed internal opening. The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as absence of discharge and