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Aims Cardiac resynchronization therapy (CRT) is highly effective in dilated cardiomyopathy (DCM) patients with impaired left ventricular ejection fraction (LVEF) and left bundle block branch. In cardiac amyloidosis (CA) patients, left ventricular dysfunction and conduction defects are common, but the potential of CRT to improve cardiac remodelling and survival in this particular setting remains undefined. We investigated cardiovascular outcomes in CA patients after CRT implantation in terms of CRT echocardiographic response and major cardiovascular events (MACEs). Methods and results Our retrospective study included 47 CA patients implanted with CRT devices from January 2012 to February 2020, in nine French university hospitals (77 ± 6 years old, baseline LVEF 30 ± 8%) compared with propensity‐matched (1:1 for age, LVEF at implantation, and CRT indication) DCM patients with a CRT device. CA patients had lower rates of CRT response (absolute delta LVEF ≥ 10%) compared with DCM patients (36% vs. 70%, P = 0.002). After multivariate Cox analysis, CA was independently associated with MACE (hospitalization for heart failure/cardiovascular death) [hazard ratio (HR) 3.73, 95% confidence interval (CI) 1.85–7.54, P

Purpose To evaluate early predictive factors of visual loss in patients treated with anti–vascular endothelial growth factor (VEGF) injections under an as-needed regimen for neovascular age-related macular degeneration (AMD). Design Post hoc analysis from the randomized controlled trial Groupe d’Evaluation Francais Avastin versus Lucentis (GEFAL). Participants A total of 393 patients with neovascular AMD. Methods The present analysis is based on 1-year data from patients included in the study. Patients were separately categorized according to the best-corrected visual acuity (BCVA) change at 3 months and 1 year into 3 trajectories: (1) patients with no vision loss ≥5 letters at 3 months and 1 year (absence of loss ≥5 letters); (2) patients with no vision loss ≥5 letters at 3 months but loss ≥5 letters at 1 year (secondary loss ≥5 letters); and (3) patients with vision loss ≥5 letters at 3 months and 1 year (initial loss ≥5 letters). Main Outcome Measures The following factors were evaluated at baseline and 3 months: age, sex, BCVA, presence of fluid, central macular thickness, angiographic choroidal neovascularization (CNV) subtype, CNV area measured in disc area on fluorescein angiography, and number of intravitreal injections. Results An absence of loss ≥5 letters was found in 225 patients (57.3%), a secondary loss ≥5 letters after 3 months was found in 109 patients (27.7%), and an initial loss ≥5 letters was found in 59 patients (15%). Baseline characteristics were comparable among the 3 groups except for the total CNV area, which was larger in the initial and secondary loss groups (P = 0.0412). At 3 months, a significant association was found between presence of subretinal fluid (SRF) (P = 0.0318) and vision loss ≥5 letters, and an even stronger significant association between the presence of intraretinal fluid (IRF) (P = 0.0066) and vision loss ≥5 letters. Conclusions In the present study, we found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters despite anti-VEGF injection. The presence of fluid, both SRF and IRF, at 3 months was found in patients with poorer trajectories.

1) Objective Pulmonary optical endomicroscopy (POE) is an imaging technology in real time. It allows to examine pulmonary alveoli at a microscopic level. Acquired in clinical settings, a POE image sequence can have as much as 25% of the sequence being uninformative frames (i.e. pure-noise and motion artifacts). For future data analysis, these uninformative frames must be first removed from the sequence. Therefore, the objective of our work is to develop an automatic detection method of uninformative images in endomicroscopy images. 2) Material and methods We propose to take the detection problem as a classification one. Considering advantages of deep learning methods, a classifier based on CNN (Convolutional Neural Network) is designed with a new loss function based on Havrda-Charvat entropy which is a parametrical generalization of the Shannon entropy. We propose to use this formula to get a better hold on all sorts of data since it provides a model more stable than the Shannon entropy. 3) Results Our method is tested on one POE dataset including 3895 distinct images and is showing better results than using Shannon entropy and behaves better with regard to the problem of overfitting. We obtain 70% of accuracy with Shannon entropy versus 77 to 79% with Havrda-Charvat. 4) Conclusion We can conclude that Havrda-Charvat entropy is better suited for restricted and or noisy datasets due to its generalized nature. It is also more suitable for classification in endomicroscopy datasets.

OBJECTIVE To evaluate the impact of implementing cell-free DNA (cfDNA) testing on gestational age (GA) at termination of pregnancy in a French perinatal network. METHODS We conducted a retrospective study. All women having undergone a termination of pregnancy between 1 January 2012 and 31 December 2017 were included. We compared the periods before and after the introduction of second-line cfDNA testing, which started on 1 January 2015. Throughout the study period, the invasive procedures were foetal karyotyping and chromosomal microarray analysis. The primary study outcome was GA at termination. The secondary outcomes were GA at termination for trisomy 21 and the frequency and GA at the time of invasive procedures. RESULTS During the 6-year study period, 840 women underwent termination. The median GA at termination before and after the implementation of cfDNA testing was 19.4 and 19.0 weeks, respectively (p = 0.38). Although the frequency of termination for trisomy 21 increased significantly from 23% to 32% (p

Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.

A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.

Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries and is threatening worldwide tomato production. Various strategies have been developed and implemented to manage this pest. Here, we present a timely review on the up-to-date development and practical implementation of integrated pest management (IPM) programs for tomato crops across different world regions infested by T. absoluta. While insecticide resistance is a growing concern, biological control via releasing or conserving arthropod natural enemies and sex pheromone-based biotechnical control are the most successful management practices. Agronomic control-related research is an emerging area where the soil fertilization and/or irrigation, as well as breeding of resistant cultivars, has the potential to enhance IPM effectiveness. Grower survey responses in the native areas (i.e., South America), early-invaded areas (i.e., first report between 2006 and 2012) and newly invaded areas (i.e., first report after 2012) showed that the control programs evolved along with the areas and time since invasion. Growers in the early-invaded areas shifted more rapidly from chemical control to biological control compared to those from the native area. In all concerned regions, the pest control failure risk following chemical insecticide applications and the high cost associated with either biological or biotechnical control methods have been the greatest concerns for growers. The information gathered from the native and/or early-invaded areas may help achieve a more effective management in newly invaded areas. Lastly, researchers are expected to break the bottlenecks of some key issues that would enable lowering application cost of novel biorational alternative management options.

PURPOSE Patients with locally advanced grade 2-3 extremity/truncal soft tissue sarcomas (STS) are at high risk of recurrence. The objective of this study was to assess the efficacy and feasibility of neoadjuvant concurrent chemoradiotherapy (cCRT) in selected grade 2-3 patients with limb or trunk wall STS, and to compare this schedule to a sequential approach combining neoadjuvant chemotherapy and adjuvant radiotherapy. METHODS We retrospectively included patients who underwent neoadjuvant cCRT at two comprehensive cancer centers from 1992-2016. We then compared these results to those of patients treated with preoperative chemotherapy and postoperative radiotherapy from a third comprehensive cancer center with a propensity score matched analysis. RESULTS A total of 53 patients were treated by neoadjuvant cCRT; 58 patients could be matched with 29 patients in each treatment group after propensity score matching. Disease-free survival and overall survival at 5 years were 54.9 and 63.5%, respectively with neoadjuvant cCRT, with no significant difference when compared to the sequential treatment group. R0 resection rate was higher (90.9 vs 44.8%, p

Introduction The use of direct oral anticoagulants (DOAC) is increasing. Specific concentrations are available and have been proven to be reliable and reproducible in optimising patient care. This retrospective, monocentric study aimed to describe the indications and consequences of monitoring DOAC plasma levels on patient care. Materials and methods We collected data of patients hospitalised at the Bordeaux University Hospital between January 2017 and December 2018. These included demographics, indications, type, dose of DOAC, standard coagulation tests, creatinine clearance and DOAC plasma concentration using specifically calibrated rivaroxaban and apixaban anti-Xa and dabigatran anti-IIa assays. The date of last DOAC intake, the time between intake and plasma level measurement were also collected and analysed. Results A total of 2197 DOAC assays in 1488 patients were obtained in various clinical situations: urgent or elective procedures, context of acute renal failure, suspicion or occurrence of ischemic strokes, intra-cranial and other bleeding sites. Interpretation of these assays led physicians to maintain, postpone or cancel invasive and high haemorrhagic risk procedures in 757, 261 and 56 cases respectively. The remaining 1123 assays were associated with no significant modification of patient care. DOAC plasma concentration was ≤30 ng ml-1 (sensitivity 85.4%, specificity 73.6%, positive predictive value 71.1%, negative predictive value 86.7%, AUC 0.81) after a last intake of at least 2 days. Conclusions Our study is, to date, the largest report of real-life measurement of specific DOAC plasma level at a single institution. Patient care was not modified in more than half of the assays.

Thibaud Soumagne, Florence Levesque, Julie Milot, Krystelle Godbout, Yves Lacasse, François Maltais Service de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaCorrespondence: Thibaud SoumagneService de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaEmail thibaud_soumagne@live.frIntroduction: Stenotrophomonas maltophilia is an emerging Gram-negative MDR bacteria. In patients with chronic obstructive pulmonary disease (COPD), it is mostly found in those with severe exacerbation of COPD requiring mechanical ventilation. The significance of S. maltophilia when detected in the sputum of ambulatory patients with COPD is uncertain.Objective: To access the prevalence and the risk factors of the presence of S. maltophilia in the sputum of ambulatory patients with COPD and to determine whether it was associated with prognosis.Methods: All consecutive unselected ambulatory patients with GOLD 2– 4 COPD were recruited between January 2017 and September 2019 from the COPD clinic of a tertiary care hospital. Presence of S. maltophilia was defined by a positive sputum culture for S. maltophilia. Demographics, COPD characteristics, comorbidities and known predisposing risk factors associated with S. maltophilia were collected from medical records.Results: S. maltophilia was detected in the sputum of 41/393 (10%) of study participants. Comorbidities, exacerbation, use of oral steroids and carbapenems in the previous year were risk factors for the presence of S. maltophilia. After adjusting on confounding factors associated with mortality including age, Charlson comorbidity index and FEV1, S. maltophilia was significantly associated with mortality (adjusted hazard ratio 2.3; 95% CI 1.1– 4.9).Conclusion: In the current study, we found that 10% of ambulatory patients with GOLD 2– 4 COPD had S. maltophilia detected in their sputum. In addition, S. maltophilia may represent a marker of overall morbidity in patients with COPD.Keywords: Stenotrophomonas maltophilia, pulmonary disease, chronic obstructive, risk factors, prognosis

Aims Cardiac amyloidosis (CA) has a poor prognosis which is aggravated by diagnostic delay. Amyloidosis extracardiac and cardiac events (AECE and ACE) may help improve CA diagnosis and typing. The aim of this study was to compare AECE and ACE between different CA types and assess their relationship with survival. Methods and results This retrospective cohort study conducted in France from June 2008 to May 2019, at the Henry Mondor Hospital. This cohort included 983 patients with CA. Mean age at inclusion was 73.1 ± 11.4 years, 726 (75.1%) were male and the mean body mass index was 24.5 ± 4.1 kg/m2. Among them, 321 had immunoglobulin light chain (AL) amyloidosis, 434 had wild‐type transthyretin (ATTRwt), and 212 had hereditary transthyretin (ATTRv). The first AECE and/or ACE occurred at a mean age of 63 ± 11 years for AL and ATTRv, and 70 ± 12 years for ATTRwt (P

SARS-Cov-2 infects the alveolar epithelial cells causing COVID-19 pneumonia of varying severity [1, 2]. Fifteen to 30% of patients develop acute respiratory distress syndrome (ARDS) requiring hospitalisation in intensive care units (ICU) and mechanical ventilation [2, 3]. At 3 months, there are persisting CT abnormalities in 17 to 91% of discharged COVID-19 patients [4–8], mainly consistent with an organising pneumonia pattern. These anomalies are more frequently reported in patients who were admitted to ICU [9]. Pulmonary fibrosis has been reported at autopsy of patients deceased from COVID-19 pneumonia, along with pulmonary microvascular thrombosis [10]. Fibrotic-like changes have also been reported at 6-month CT follow-up in COVID-19 survivors [11]. A proportion of survivors from the first SARS-Cov outbreak of 2003 had residual impairment of lung function and abnormal chest radiograph (CXR) findings at 6 months [12]. However, little is known about long-term changes on CT following severe SARS-Cov-2 pneumonia, or after ARDS in general, most descriptions being limited to CXR.

Introduction Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678). Methods At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH). Results Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3–4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p

Aims Several reports suggest that illicit drug use may be a major cause of acute myocardial infarction (AMI) independently of smoking habits and associated with a poorer prognosis. The aim of our study was to evaluate the impact of illicit drug use on (i) the risk of AMI and (ii) its prognosis. Methods and results This French longitudinal cohort study was based on the administrative hospital-discharge database from the entire population. First, we collected data for all patients admitted in hospital in 2013 with at least 5 years of follow-up to identify potential predictors of AMI. In a second phase, we collected data for all patients admitted with AMI from January 2010 to December 2018. We identified patients with a history of illicit drug use (cannabis, cocaine, or opioid). These patients were matched with patients without illicit drug use to assess their prognosis. In 2013, 3 381 472 patients were hospitalized with a mean follow-up of 4.7 ± 1.8 years. In multivariable analysis, among all drugs under evaluation, only cannabis use was significantly associated with a higher risk of AMI [HR 1.32 (95% CI 1.09–1.59), P = 0.004]. Between January 2010 and December 2018, we then identified 738 899 AMI patients. Among these patients, 3827 (0.5%) had a known history of illicit drug use. These patients were younger, most often male and had less comorbidities. After 1:1 propensity score matching, during a mean follow-up of 1.9 ± 2.3 years, there was no significant difference between patients without illicit drug use and patients with illicit drug use regarding all-cause death, cardiovascular death, stroke, or heart failure. Conclusion In a large and systematic nationwide analysis, cannabis use was an independent risk factor for the incidence of AMI. However, the prognosis of illicit drug users presenting with AMI was similar to patients without illicit drug use.

Background/aimRejection is the main cause of graft failure after penetrating keratoplasty (PK). Its prevention by repeated instillation of steroid eye-drops has not evolved in decades. Poor adherence and discontinuous nature of eye-drop treatment may explain some PK failures. In a rabbit model, we previously demonstrated that a subconjunctival dexamethasone implant was well tolerated and prevented rejection efficiently in the first 5–6 weeks. This clinical trial investigates its tolerance and safety after PK.MethodsSingle-centre, phase II non-randomised tolerance and safety pilot study (NCT02834260). Designed to analyse the risk of elevated intraocular pressure (IOP), discomfort and resorption time. Fourteen patients with a low rejection risk indication of PK were enrolled between January 2017 and August 2018. The implant was injected in the 12 o’clock position, 5 mm from the limbus, at the end of PK. A steroid eye-drop treatment was planned when implant resorption was complete. Patients were monitored regularly for 12 months: IOP (main outcome measure at 1 month), discomfort and redness scores, implant status, rejection episode and central corneal thickness by optical coherence tomography. An independent data safety monitoring committee verified safety aspects.ResultsNo increase in IOP or other adverse event related to the implant was observed. Average resorption time was 6 weeks. The switch to steroid eye-drops was uneventful. One patient, included despite preoperative corneal neovascularisation (unintended protocol deviation) experienced a rejection.ConclusionsThis is the first proof of concept that dropless immunosuppression is possible after low rejection risk PK.Trial registration numberNCT02834260.

Background: Clinical and microbiological guidelines recommend treating infections caused by Enterobacter spp. with cefepime or carbapenems. The main objective of this study was to assess the risk of clinical failure with third generation cephalosporin (3GC) therapy compared to other β-lactams for infections caused by Enterobacter spp. Our secondary objective was to evaluate the risk of emergence of resistance during therapy. Methods: We conducted a prospective observational study in seven French hospitals over an 18-month period including all patients with a pulmonary and/or bloodstream infection due to Enterobacter spp. susceptible to 3GC. Results: Seventy-four patients were included in our study. Among them, 26 (35%) received a 3GC as a first-line treatment, and clinical improvements were observed for 13/21 (62%) of them. Four (5%) cases of emergence of 3GC resistance were observed during therapy including one in the 3GC group. 3GC therapy can be safely used as first-line therapy especially for non-severe patients suffering from pulmonary or bloodstream infections due to Enterobacter spp. Conclusions: Emergence of 3GC resistance remains a rare event, and there is a lack of evidence of the benefit of last-line antibiotics therapies.

To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia.Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis.Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1.We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

To analyze the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) or steroid injection for the management of Irvine Gass syndrome. It is an interventional, retrospective, multicenter study. One hundred and thirty-two injections were given in 79 eyes of 72 patients with Irvine Gass syndrome. Patients were treated with at least one intravitreal injection of either anti-VEGF or steroid. Outcomes were measured at 12 months (± 1 week). [Ranibizumab (Lucentis; Genentech, South San Francisco, CA) (Razumab; Intas Pharmaceutical Ltd, Ahmedabad, India) Bevacizumab (Avastin; Genentech, South San Francisco, CA) or Aflibercept (Eylea; Regeneron, Tarrytown, NY)] or steroids [Dexamethasone implant (Ozurdex, Allergan Inc, Irvine, CA) or intravitreal triamcinolone)]. Intravitreal injections were initiated in (67.6%) of eyes within 14 weeks of diagnosis. Intravitreal dexamethasone implant was used as the initial intravitreal therapy in (73.4%) of eyes. More than fifty percent (54.5%) of the patients were switched from anti-VEGF to Intravitreal dexamethasone implant. Reduction in the mean CMT was 336.7 ± 191.7 and 160.1 ± 153.1 microns in eyes treated within four weeks and more than 14 weeks from diagnosis (p = 0.005). Mean ETDRS letter gain was 16.7 ± 12.9 and 5.2 ± 9.2 in eyes treated within 4 weeks and more than 14 weeks from diagnosis (p = 0.004). Three eyes injected with intravitreal dexamethasone implant reported an intraocular pressure spike of > 25 mmHg which was controlled with topical medications. No other ocular or systemic adverse events were observed. Study results suggest that physicians tend to introduce intravitreal therapy within 14 weeks of diagnosis. The most common therapy at initiation and for the switch is intravitreal dexamethasone implant. Patients treated early (within 4 weeks) respond better in terms of structure and function.

Gastrointestinal cancers occur in a total of eight different locations, each of them with a different standard of care. This article is not an exhaustive review of what has been published in 2020. We have concentrated on the thirteen phase III randomized studies that are practice-changing. All these studies are oral presentations which have been given in one of the four major oncology congresses, namely American Society of Clinical Oncology (ASCO), ASCO gastrointestinal (GI), European Society of Medical Oncology (ESMO) and ESMO-GI. We provide a concise view of these major trials and their main outcomes, and put these results into context.

The work described in this paper harnesses an open-source astrodynamics engine and visualization to quantify the performance of on-board optical navigation. It introduces the Hough Circles transfor...

Background: Device-related thrombus (DRT) has been considered an Achilles’ heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. Objectives: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. Methods: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. Results: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. Conclusions: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

This study intend to compare the long-term psychological impact (depression, post-traumatic stress disorder) on both partners between patients that underwent uterine artery embolization (UAE) for post-partum hemorrhage (PPH) and uneventful deliveries. Women who experienced severe PPH treated by UAE in our institution between 2003 and 2013 were identified in our obstetrical database. These cases were matched to controls with uneventful deliveries. Matching criteria were maternal age, parity, ethnicity, year of delivery, birthweight, gestational age and mode of delivery. Patients and their partners completed validated questionnaires measuring post-traumatic stress (TSQ), as well as depression symptoms (MINI). A total of 63 cases of PPH and 189 matched controls (1:3) participated in a study exploring gynecological and obstetrical outcomes. With a mean of 8 years post-index delivery, patients after PPH showed increased risk of depression (p = 0.015) and post-traumatic stress disorder (22.2% versus 4.8%, p

International audience; Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland–Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.

Background Acute heart failure (AHF) is a common serious condition that contributes to about 5% of all emergency hospital admissions in Europe. Hypothesis To assess the type and chronology of the first AHF symptoms before hospitalization and to examine the French healthcare system pathways before, during and after hospitalization. Material and Methods A retrospective observational study including patients hospitalized for AHF Results 793 patients were included, 59.0% were men, 45.6% identified heart failure (HF) as the main cause of hospitalization; 36.0% were unaware of their HF. Mean age was 72.9 ± 14.5 years. The symptoms occurring the most before hospitalization were dyspnea (64.7%) and lower limb edema (27.7%). Prior to hospitalization, 47% had already experienced symptoms for 15 days; 32% of them for 2 months. Referral to hospital was made by the emergency medical assistance service (SAMU, 41.6%), a general practitioner (GP, 22.3%), a cardiologist (19.5%), or the patient (16.6%). The modality of referral depended more on symptom acuteness than on type of symptoms. A sudden onset of AHF symptoms led to making an emergency call or to spontaneously attending an emergency room (ER), whereas cardiologists were consulted when symptoms had already been present for over 15 days. Cardiologists referred more patients to cardiology departments and fewer patients to the ER than general practitioners or the SAMU. Conclusion This study described the French healthcare system pathways before, during and after hospitalization AHF. AHF clinic network should be developed to provide adequate care for all HF patients and create awareness regarding AHF symptoms.

Background Pazopanib is a tyrosine kinase inhibitor given at the approved dose of 800 mg orally once daily (OD), but often requiring individual dose adjustment due to toxicity. Limited data is available to guide prescription in older patients especially the unfit according to geriatric assessment. Patients and methods VOTRAGE is a 3 + 3 dose-escalation, open-label phase I trial of continuous OD oral administration of pazopanib to evaluate safety, PK and PD data in unfit older patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD). PK data were compared with those obtained in younger adult patients in a population PK analysis. Results Eighteen patients with a median age of 82.5 years (range 75–91) were included in three dosing cohorts (400, 600, and 800 mg daily). Three dose-limiting toxicities (DLT) were observed in five patients at 800 mg and one DLT at 600 mg in six evaluable patients. MTD was defined as level 2 dose (600 mg). Individual oral clearance was not correlated with age. A relationship was observed between the occurrence of DLT and pazopanib plasma exposure. Decreased oral bioavailability of pazopanib when given with proton-pump inhibitors was confirmed in this group of patients. Conclusion We recommend performing geriatric assessment in patients older than 75 and starting pazopanib at 600 mg per day in unfit older patients. Therapeutic drug monitoring appears very helpful in this population.

BackgroundThe global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing the ongoing coronavirus disease 2019 (COVID-19) pandemic has raised serious concern for patients with chronic disease. A correlation has been identified between the severity of COVID-19 and a patient’s preexisting comorbidities. Although COVID-19 primarily involves the respiratory system, dysfunction in multiple organ systems is common, particularly in the cardiovascular, gastrointestinal, immune, renal, and nervous systems. Patients with amyloid transthyretin (ATTR) amyloidosis represent a population particularly vulnerable to COVID-19 morbidity due to the multisystem nature of ATTR amyloidosis.Main bodyATTR amyloidosis is a clinically heterogeneous progressive disease, resulting from the accumulation of amyloid fibrils in various organs and tissues. Amyloid deposition causes multisystem clinical manifestations, including cardiomyopathy and polyneuropathy, along with gastrointestinal symptoms and renal dysfunction. Given the potential for exacerbation of organ dysfunction, physicians note possible unique challenges in the management of patients with ATTR amyloidosis who develop multiorgan complications from COVID-19. While the interplay between COVID-19 and ATTR amyloidosis is still being evaluated, physicians should consider that the heightened susceptibility of patients with ATTR amyloidosis to multiorgan complications might increase their risk for poor outcomes with COVID-19.ConclusionPatients with ATTR amyloidosis are suspected to have a higher risk of morbidity and mortality due to age and underlying ATTR amyloidosis-related organ dysfunction. While further research is needed to characterize this risk and management implications, ATTR amyloidosis patients might require specialized management if they develop COVID-19. The risks of delaying diagnosis or interrupting treatment for patients with ATTR amyloidosis should be balanced with the risk of exposure in the health care setting. Both physicians and patients must adapt to a new construct for care during and possibly after the pandemic to ensure optimal health for patients with ATTR amyloidosis, minimizing treatment interruptions.

Introduction: The aim of the study was to estimate the phenotype of retinal vessels using central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), tortuosity, and fractal analysis in the unaffected contralateral eye of patients with central or branch retinal vein occlusion (CRVO or BRVO). Methods: Thirty-four patients suffering from CRVO, 15 suffering from BRVO, and 49 controlled matched subjects had a fundus image analyzed using the VAMPIRE software. The intraclass correlation coefficient and a Bland-Altman plot were done for the reproducibility study. Results: There was a lack of evidence of difference between the control group and the CRVO group for CRAE (p = 0.06), CRVE (p = 0.3), and arterio-venule ratio (AVR, p = 0.6). Contralateral eyes of CRVO exhibited a significantly higher arterial and minimum arterial tortuosity values (p = 0.012), as compared with control eyes. Contralateral eyes of patients with a history of BRVO had a significantly higher CRAE (p = 0.02), AVR (p = 0.006), and minimal arterial tortuosity (p = 0.05). Fractal analysis showed that contralateral eyes of BRVO had higher values of fractal parameters (D0a, p = 0.005). Conclusion: This study suggests that CVRO or BRVO is not triggered by the same retinal vascular phenotypes in the contralateral eye. The morphology of retinal vasculature may be associated with the occurrence of RVO, independently of known risk factors.

AimTo assess the relevance of therapeutic drug monitoring (TDM) of adalimumab (ADA) treatment for the control of intraocular inflammation and treatment adjustment in chronic non-infectious uveitis (CNIU).MethodsRetrospective study of CNIU patients treated with ADA and for whom at least one dosage of serum ADA level and an antibodies against ADA (AAA) serology were performed, between June 2003 and July 2019.ResultsA total of 44 ADA-treated patients benefited from a TDM. A total of 48/79 (61%) TDM were performed in responders, 11/79 (14%) in primary non-responders, and 20/79 (25%) in secondary non-responders. Responders had significantly higher ADA levels than non-responders (p=0.0004). AAA were detectable in six patients, they were primary non-responders (n=2), secondary non-responders (n=3) or responders (n=1). In the five non-responders and immunised patients, ADA was switched (to golimumab or methotrexate). Among non-responders, TDM led to an increased frequency of injections 12/31 (38%), increased dose 1/31 (3%) and switch of treatment 10/31 (32%) (one missing data). No modification of biotherapy was performed 7/31 (22%) and only local or oral corticotherapy was adjusted. In 24/31 cases of therapeutic adjustment in non-responders, an improvement was observed in 87% of cases. Among responders for whom the ADA level was above the efficacy threshold, the frequency of injections was decreased for 15/31 (48.4%) cases and no relapse was observed in 12/15 (80%) cases.ConclusionTDM of ADA treatment proved relevant to provide CNIU patients with a personalised and optimised treatment course (in terms of frequency and type of drug).

Dementia with Lewy bodies remains underdiagnosed in clinical practice mainly because of the low sensitivity of existing diagnostic criteria and a strong overlap with Alzheimer’s pathology that can mask the Lewy phenotype. The objective of this study was therefore to develop and validate a new clinical scale designed to detect signs of Lewy body disease, called LeSCoD for Lewy body Screening scale in Cognitive Disorders. 128 patients who fulfilled the clinical criteria of dementia with Lewy bodies (DLB; n = 32), Alzheimer’s disease (AD; n = 77) or both (n = 19) was prospectively enrolled. 18F-DOPA PET imaging and/or CSF biomarkers were available in some patients. LeSCoD scale was systematically administered and the potential correlation with 18F-DOPA PET imaging was evaluated in a subgroup of patients. LeSCoD scale showed robust internal and external validity. We determined a cut-off of 10 above which the sensitivity and specificity for Lewy body disease diagnosis were 86% and 95%, respectively. The LeSCoD scale correlated with striatal dopamine uptake in 18F-DOPA PET. LeSCoD scale is a simple and reliable tool for the evaluation of Lewy body disease in routine clinical practice, with a higher sensitivity and specificity than the existing criteria. It might be an alternative to the use of dopamine-specific imaging.

International audience; The aim of this study was to improve our knowledge on the chemical markers of Cognac aromas. We report results concerning the distribution and sensorial impact of 3-methyl-2,4-nonanedione (MND), a well-known compound in aged red wine, reminiscent of anise or "dried fruit", according to its concentration. We assayed first this diketone (solid-phase microextraction (SPME)-gas chromatography (GC)/mass spectrometry (MS), chemical ionization (CI)) in many Cognac samples followed by grappa, brandy, rum, whisky, vodka, and fruit spirits, and concentrations ranged from traces to 11.2 mu g/L. Highest concentrations were obtained in grappa and freshly distilled eaux-de-vie of Cognac samples. Exceeding its detection threshold (100 ng/L, 70 vol %), MND contributes to the anise descriptor of these spirits. Its concentration decreased over aging while being highly correlated with the total amount of fatty acid ethyl ester. In addition, we showed that MND was produced during distillation according to the oxidation state of the white wine as well as the amount of lees used.

Resume Introduction Les inhibiteurs des tyrosines kinases (TKI) sont actifs dans divers cancers metastatiques. Ils presentent une bonne tolerance generale avec des effets secondaires principalement hepatiques, et dermatologiques. Rarement, des effets secondaires ophtalmologiques peuvent survenir : anomalies des cils, paupieres, troubles de la surface oculaire avec secheresse oculaire voire erosions corneennes pouvant aller jusqu’a la perforation. Le Regorafenib est un nouvel inhibiteur de tyrosine kinase multi cibles oral qui inhibe de multiples proteines kinases, y compris celles impliquees dans l’angiogenese tumorale, l’oncogenese et le microenvironnement tumoral. Description du cas Nous decrivons, a notre connaissance, le premier cas d’ulceres bilateraux complique de perforation corneenne, chez un patient sous REGORAFENIB. Observation Patient de 20 ans, atteint de chondrosarcomes du bassin, de la mandibule et du thorax metastatiques a recu une chimiotherapie par REGORAFENIB. Quelques semaines apres l’instauration du traitement, il a presente une augmentation du syndrome sec oculaire associe a des ulceres corneens bilateraux compliques d’une perforation. Malgre l’arret de la chimiotherapie et un traitement medical et chirurgical maximal (greffes de membranes amniotiques iteratives et greffe de cornee), l’evolution a ete defavorable. Discussion Il s’agit du premier cas connu de perforation corneenne sous REGORAFENIB. La physiopathologie est multifactorielle. D’une part, cette chimiotherapie a pour cible l’angiogenese (VEGFR), l’oncogenese (KIT, RET, RAF1, BRAF) et le micro environnement tumoral (PDGFR, FGFR). D’autres part, d’autres facteurs declenchants se surajoutent, a savoir le syndrome sec oculaire mixte, l’hypovitaminose A (anorexie), la composante neurotrophique, ainsi que la toxicite de la chimiotherapie via les larmes. Conclusion Premier cas decrit de perforation corneenne sous REGORAFENIB, non regressive a l’arret de la chimiotherapie, et malgre les traitements medicaux et chirurgicaux. Une surveillance ophtalmologique est donc necessaire pour les patients sous chimiotherapie par inhibiteurs des tyrosines kinases, car des complications oculaires graves notamment corneennes peuvent survenir.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Flexible planar spacecraft, such as solar sails, phased antenna arrays and space solar power satellites vary their shape in flight and also may not have a known shape after deployment. To allow applications where spacecraft shapes are measured to allow the closed-loop correction of flight or payload parameters, this paper presents a method for measuring shapes with miniature sun sensors embedded within the structure. Two algorithms to reconstruct the shape of the structure from the two local angles to the sun are presented; the first one is geometry-based, whereas the second one uses a finite element model of the structure. Both algorithms are validated on a 1.3 m × 0.25 m structure with 14 novel miniature sun sensors with an accuracy of 0 . 5 ∘ , developed for the present research. The structure was reconstructed to an accuracy better than one millimeter by both algorithms, after undergoing bending and torsional deformations. While the geometrically based algorithm is fast and accurate for small deformations, the finite element based algorithm performs better overall, especially for larger deformations.

Short RP interval atrioventricular re-entrant tachycardias do not typically present as an incessant form. We present 2 cases of incessant atrioventricular re-entrant tachycardias leading to tachycardia-induced cardiomyopathy with severe heart failure presentation in middle-aged adults. Both underwent accessory pathway ablation and recovered normal left ventricle function before hospital discharge. (Level of Difficulty: Intermediate.), Graphical abstract

The introduction of biological or absorbable synthetic meshes has provided an alternative to conventional repair for incisional hernia. The ability to predict the development of complications after hernia surgery is important, as it guides surgical planning and patient management. This retrospective study assessed whether the postoperative C-reactive protein (CRP) level can predict complications after incisional hernia repair using biological mesh reinforcement. Patients who underwent incisional hernia repair surgery using biological meshes between February 2009 and February 2015 were screened for study inclusion. Patients included in the study were divided into two groups: those with and without postoperative complications. The two groups were analysed based on sex, surgical operation, length of intensive care unit stay (ICU), complications and mortality. Laboratory values, including white blood cell (WBC) count and CRP levels, were determined preoperatively and up to postoperative day (POD) 10. Postoperative complications requiring further management occurred in 32 of the 60 patients (53.3%). Among 47 patients, the mean CRP and WBC levels were 6.6 mg/L and 9.073 G/L in the group without complications vs. 141.0 mg/L, 16.704 G/L in the group with complications (p 100 mg/L vs. 46% in the group with CRP 100 mg/L) up to POD10 may serve as a predictor of postoperative complications in patients undergoing incisional hernia using biological meshes.

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial, tafamidis significantly reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is associated with a significant burden of disease; further analysis of patient-reported quality of life will provide additional data on the efficacy of tafamidis. In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial, 441 adult patients with ATTR-CM were randomized (2:1:2) to tafamidis 80 mg, tafamidis 20 mg, or placebo for 30 months, with pooled tafamidis (80 mg and 20 mg) compared with placebo. Change in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) domain scores, EQ-5D-3L scores, and patient global assessment, were prespecified exploratory end points. A greater proportion of patients improved KCCQ-OS score at month 30 with tafamidis (41.8%) versus placebo (21.4%). Tafamidis significantly reduced the decline in all 4 KCCQ-OS domains (p

Objectives Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt). Background ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt. Methods In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv. Results There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p Conclusions Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889 )

Biliary tract cancer; Colorectal cancer; Drug development Cáncer del tracto biliar; Cáncer colorrectal; Desarrollo de fármacos Càncer del tracte biliar; Càncer colorectal; Desenvolupament de fàrmacs Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice. Open Access funding provided by Université de Genève.

The detection of corneas operated on for refractive surgery [LASIK or photorefractive keratectomy (PRK)] will become a major concern for eye banks in the coming years because this surgery is often forgotten during the interview with the deceased's relatives. We present here 2 corneas operated on with PKR and stored successively in organ culture (OC) and in the active storage machine (ASM) that restores intraocular pressure, restores the cornea to its original shape, respects transparency and incorporates non-invasive controls. The 2 corneas of a 49-year-old donor operated 17 years earlier by PRK for -2 and -3 diopters myopia were stored in OC for 14 days and then placed in ASM for 48 h. Thickness map and OCT topography were performed under the 2 storage conditions, histology and electron microscopy were then performed. Traces of PRK remained unnoticed in OC while they were evident in ASM with central epithelial anomaly, central thinning and flattening of central keratometry shown by OCT. Histology and ultrastructure confirmed the absence of Bowman's membrane in the center. By placing the cornea under physiological conditions, and in particular by triggering its deswelling and by restoring its natural curvature, the ASM allows effective detection of subtle refractive surgery traces like those present after PRK.

To determine the effect of commonly used intravitreal agents on immediate and long-term IOP elevations and their association, if any, with glaucoma. Literature searches in PubMed and the Cochrane databased in January 2020 yielded 407 individual articles. Of these, 87 were selected for review based on our inclusion criteria. Based on the evidence provided, 20 were assigned level I, 27 level II, and 22 level III. Eight articles were rejected because of poor quality, insufficient clarity, or irrelevance based on standardized protocols set out by the American Academy of Ophthalmology. The studies that reported on short-term IOP elevation (i.e., between 0 and 60 min) showed that an immediate increase in IOP is seen in all patients who receive anti-VEGF agents or triamcinolone acetonide when measured between 0 and 30 min of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection of anti-VEGF agents, while the position of the implant vis-à-vis, the anterior chamber was important for steroid therapy. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. However, some studies demonstrated RNFL thinning in patients receiving chronic anti-VEGF therapy. Most, if not all, intravitreal agents cause ocular hypertension, both in the short term and long term. The functional consequences of these observations are not very clear.