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Abstract Introduction Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or “treat-and-extend” (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. Methods We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. Results From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p

Background: Independent use of artificial intelligence with computer-aided detection (CADe) and Endocuff Vision (ECV) has demonstrated enhanced adenoma detection rates (ADRs). Objective: Our pilot study aimed to define the necessary participant number for future randomized controlled trials (RCTs) by comparing the ADR of combined CADe + ECV against CADe alone and standard colonoscopy. Design: This single-center pilot study retrospectively analyzed a prospectively maintained database, where patients underwent screening colonoscopies sequentially by standard method, CADe alone, and then CADe + ECV. Method: The allocation of the technique depended on the study period. Patients were randomly selected from the cohort to form three groups of 30 patients, with stratification based on factors influencing the ADR. The primary endpoint was the ADR. Results: From April to June 2021, 244 patients underwent screening colonoscopy. 198 were eligible, and after randomization, 90 patients were included across three groups (colonoscopy n = 30, CADe n = 30, CADe + ECV = 30). The ADR was higher in the CADe + ECV group compared to the CADe and colonoscopy groups: 60% versus 40%, and 30%, respectively ( p = 0.03). The number of polyps ⩽3 mm detected was greater in the CADe + ECV group ( n = 23) versus CADe ( n = 7) and colonoscopy ( n = 12) groups, respectively ( p = 0.03). CADe + ECV identified more polyps in the cecum/right colon ( n = 26) compared to CADe ( n = 18) and colonoscopy ( n = 12) groups ( p = 0.04), and in the left colon/sigmoid ( n = 14) compared to CADe ( n = 5) and colonoscopy ( n = 2) ( p = 0.02). Conclusion: These findings underscore the synergic potential of combining CADe with ECV to enhance ADR and enable us to perform sample size calculations for future RCTs. Registration: Clinical Trials number: NCT05080088. Registration 06/06/2021.

BackgroundThe relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.MethodsIn this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.ResultsBecause of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).ConclusionsPRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.

Abstract Introduction Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME). We investigated the effect of initial glycosylated hemoglobin (HbA1c) level and glomerular filtration rate (GFR) on treatment outcomes in patients with DME receiving anti-VEGF injections in routine clinical practice. Methods A retrospective analysis of data from the prospective, multi-center, observational Fight Retinal Blindness! registry was performed. A total of 178 eyes with DME treated with anti-VEGF agents (ranibizumab or aflibercept) from 1 January 2010 to 31 March 2019 were enrolled in the analysis, with the long study period to allow for up to 24 months of follow-up. Data for eyes were tracked in the Fight Retinal Blindness! registry, and clinical parameters were collected by using local software. Changes in visual (best-corrected visual acuity [BCVA], in letters) and anatomic outcomes (central subfield thickness [CST], in microns) between subgroups of patients according to baseline HbA1c level (≤ 7% vs. > 7%) and GFR (> vs. ≤ 60 ml/min/m2 at 24 months were assessed. Results The multivariate adjusted mean improvement in BCVA at 24 months of treatment was + 5.2 and + 6.8 letters in subgroups with baseline HbA1c level ≤ 7% and > 7%, respectively (p = 0.541), and + 6.9 and + 6.4 letters in subgroups with GFR > 60 and 7%, respectively (p = 0.505), and − 85 and − 115 µm in subgroups with baseline GFR > 60 and ≤ 60 ml/min/1.73 m2, respectively (p = 0.130). Conclusion These results seem to indicate that visual and anatomical improvement in patients receiving intravitreal VEGF inhibitors for DME are independent of baseline HbA1c level and GFR, leading to the conclusion that high HbA1c levels or low GFR should not dictate injection timing in routine clinical practice. This study offers valuable insights for ophthalmologists, enabling a personalized treatment approach and optimizing DME patient outcomes.

Chloé Chamard,1,2 Jerome J Maller,3,4 Nicolas Menjot,5 Eloi Debourdeau,1 Virginie Nael,6 Karen Ritchie,2,7 Isabelle Carriere,2,* Vincent Daien1,2,8,* 1Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, F-34000, France; 2Institute for Neurosciences of Montpellier INM, University Montpellier, INSERM, Montpellier, F-34091, France; 3General Electric Healthcare, Melbourne, VIC, Australia; 4Monash Alfred Psychiatry Research Centre, Melbourne, VIC, Australia; 5Department of Neuroradiology, Gui de Chauliac Hospital, Montpellier, F-34000, France; 6Bordeaux Population Health Research Center, UMR 1219, University Bordeaux, INSERM, Bordeaux, F-33000, France; 7Department of Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; 8The Save Sight Institute, Sydney Medical School, the University of Sydney, Sydney, NSW, Australia*These authors contributed equally to this workCorrespondence: Chloé Chamard, Department of Ophthalmology, Gui de Chauliac Hospital, 80 avenue Augustin Fliche, Montpellier, F-34000, France, Tel +33 6 33 55 65 06, Email chloe.chamard@gmail.comPurpose: Visual impairment is a major cause of disability and impairment of cognitive function in older people. Brain structural changes associated with visual function impairment are not well understood. The objective of this study was to assess the association between visual function and cortical thickness in older adults.Methods: Participants were selected from the French population-based ESPRIT cohort of 2259 community-dwelling adults ≥ 65 years old enrolled between 1999 and 2001. We considered visual function and brain MRI images at the 12-year follow-up in participants who were right-handed and free of dementia and/or stroke, randomly selected from the whole cohort. High-resolution structural T1-weighted brain scans acquired with a 3-Tesla scanner. Regional reconstruction and segmentation involved using the FreeSurfer image-analysis suite.Results: A total of 215 participants were included (mean [SD] age 81.8 [3.7] years; 53.0% women): 30 (14.0%) had central vision loss and 185 (86.0%) normal central vision. Vision loss was associated with thinner cortical thickness in the right insula (within the lateral sulcus of the brain) as compared with the control group (mean thickness 2.38 [0.04] vs 2.50 [0.03] mm, 4.8% thinning, pcorrected= 0.04) after adjustment for age, sex, lifetime depression and cardiovascular disease.Conclusion: The present study describes a significant thinning of the right insular cortex in older adults with vision loss. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognitive processing. Reduced insula thickness associated with vision loss may increase cognitive burden in the ageing brain.Keywords: visual function, vision, cortical thickness, brain, morphometry, MRI

Background: Gastric per oral endoscopic esophageal myotomy (G-POEM) is a promising procedure to treat refractory gastroparesis. The safety profile of G-POEM is an important topic because gastroparesis is a functional pathology, with a procedure whose effectiveness is between 50 and 65% depending on the studies. Objectives: We present this retrospective multicenter study, with the aim of establishing a safety profile, focusing on serious adverse events (AEs). Design: This was a multicenter observational cohort study conducted in five French expert centers. Methods: All patients who underwent G-POEM for refractory gastroparesis between 2015 and 2021 were included for analysis. AEs were classified into per endoscopic, early postoperative, and late postoperative, up to 1 month. Their severity was assessed using Dindo–Clavien and American Society for Gastrointestinal Endoscopy classification. The primary objective was to evaluate the rate of G-POEM severe AEs. Secondary objectives were to document other postoperative AEs, and to identify predictive factors. Results: In all, 217 patients were included: 81 men and 136 women, mean age 52 ± 17 years. The average procedural time was 44 ± 14 min (12–78). The average hospital stay was 3.7 ± 2.3 days. The AEs rate classified as Clavien–Dindo ⩾3 was 0.4% (one delayed bleeding requiring blood transfusion and endoscopic management). There were no deaths or patients admitted to intensive care unit. The rates of mucosotomy and capnoperitoneum were 3.7 and 1.8%, respectively, without clinical consequences. Most patients (81.5%) did not experience any AE. Three cases of dumping syndrome occurred, quickly managed by dietary measures. Conclusion: Our study confirms the safety of G-POEM with less than 0.5% of serious AEs, medically managed. This outcome makes this a procedure to have a good benefit–risk ratio.

De nombreux patients atteints de cancer ont besoin de soins palliatifs et la grande majorité des personnes suivies en soins palliatifs sont atteintes de cancer. Dans le contexte de cancer, le risque de maladie thromboembolique veineuse (MTEV) est élevé, d'autant plus pendant la phase palliative avancée, lorsque la mobilité est limitée ou inexistante. Par ailleurs, les patients atteints de cancer et recevant des soins palliatifs présentent un risque hémorragique plus élevé que les autres patients. Dans ce contexte, la décision de traiter la MTEV ou de suspendre l'anticoagulation s'avère difficile à prendre et dépend largement du jugement du clinicien. Nous présentons dans cet article une proposition de consensus pour la prise en charge de la thrombose associée au cancer (TAC) chez les patients en soins palliatifs. Cette proposition s'appuie sur une revue systématique de la littérature scientifique récente. Chez les patients cancéreux en soins palliatifs avancés, le rapport bénéfice/risque de l'anticoagulation semble défavorable, avec un risque hémorragique plus élevé que le bénéfice associé à la prévention de la récidive des TAC, en l'absence de tout bénéfice sur la qualité de vie. Pour cette raison, nous recommandons que la décision de prescription des anticoagulants se fasse au cas par cas. Le choix de traiter ou pas, ainsi que le choix de l'anticoagulant prescrit, tiendront compte de l'espérance de vie et des préférences du patient, ainsi que de facteurs cliniques tels que le risque hémorragique estimé, le type de MTEV et le temps écoulé depuis le diagnostic de l'événement thromboembolique veineux. Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative care are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit/risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event. [ABSTRACT FROM AUTHOR]

La thrombose liée au cathéter (TLC) est une complication relativement fréquente et potentiellement fatale chez les patients atteints de cancer qui nécessitent la pose d'un cathéter central pour un traitement intraveineux. Malgré sa fréquence et son retentissement clinique, peu de données sont disponibles pour guider le diagnostic et le traitement de la TLC. Aucune étude diagnostique ni aucun essai clinique n'ont été menés chez des patients porteurs d'un cathéter veineux central (CVC) dans un contexte de cancer. De nombreuses questions concernant la prise en charge optimale de la TLC restent ainsi sans réponse. En raison de la rareté de données de haut niveau de preuve, les recommandations sont dérivées des études sur la thrombose veineuse profonde des membres supérieurs pour le diagnostic, et des membres inférieurs pour le traitement. Cet article aborde les questions du diagnostic et de la prise en charge de la TLC à travers une revue de la littérature disponible. Chez les patients symptomatiques, l'échographie veineuse est l'examen d'imagerie le plus approprié en première ligne pour le diagnostic de la TLC, étant non invasive et ayant une performance diagnostique élevée (ce qui n'est pas le cas chez les patients asymptomatiques). En l'absence d'essais cliniques comparatifs directs, nous suggérons de traiter les patients atteints de TLC avec une héparine de bas poids moléculaire (HBPM) à dose curative, ou un inhibiteur direct du facteur Xa par voie orale (DXI), avec ou sans dose de charge. Les anticoagulants doivent être administrés pendant une durée totale d'au moins 3 mois, dont au moins 1 mois après le retrait du cathéter. Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least 3 months, including at least 1 month after catheter removal following initiation of therapy. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate risk factors associated with keratoconus in a monocentric cross-sectional case-control study. Methods. This observational study occurred from June 2019 to February 2021 in a university hospital (France). The case group consisted of 195 patients with keratoconus in at least one eye who were followed up by a corneal specialist. The control group consisted of 195 patients without any evidence of keratoconus on slit-lamp examination and corneal topography, who were matched 1 : 1 to controls by age and sex. Data were collected by a self-completed paper questionnaire before the consultation, and a multivariate logistic regression was performed. Results. Multivariate analysis revealed significant associations of keratoconus with family history (odds ratio [OR] = 22.2, p

Dysphagia in children is a relatively frequent symptom in childhood, and the main causes are congenital and linked to ear–nose–throat etiologies. However, non-congenital esophageal dysphagia is less common, and the main cause in such cases is eosinophilic esophagitis (EoE). When there is no response to a well-conducted treatment, with normalization of histology, the diagnosis of EoE must then be reconsidered. Here, we present the case of a 10-year-old patient whose initial diagnosis of eosinophilic esophagitis delayed the diagnosis of type III achalasia.

Abstract Background The phase II AFUGEM GERCOR trial aimed to assess the efficacy of a first‐line therapy combining nab‐paclitaxel plus either gemcitabine (gemcitabine group) or simplified leucovorin and fluorouracil (sLV5FU2 group) in patients with previously untreated metastatic pancreatic cancer. Results of progression‐free survival at 4 months (primary endpoint) were in favor of the sLV5FU2 group. This paper presents health‐related quality of life (HRQoL) data as a secondary endpoint. Methods HRQoL was assessed using the EORTC QLQ‐C30 questionnaire at baseline and at each chemotherapy cycle until the end of treatment. The HRQoL deterioration‐free survival (QFS) was used as a modality of longitudinal analysis. QFS was defined as the time between randomization and the first definitive HRQoL score deterioration as compared to the baseline score, or death. Sensitivity analysis was performed excluding death as an event. Univariate Cox models were used to estimate hazard ratios (HRs) and 90% confidence intervals (CIs) of the treatment effect. Results Between 2013 and 2014, 114 patients were randomized in a 1:2 ratio (39 in the gemcitabine group and 75 in the sLV5FU2 group). Patients in the sLV5FU2 group seemed to present longer QFS than those of the gemcitabine group for 14 out of 15 dimensions, with HRs

Background: The use of low-molecular-weight heparin (LMWH) for long-term therapy of venous thromboembolism (VTE) in patients without cancer has not been consistently evaluated. Methods: We used the data in the RIETE registry to compare the 3-month outcomes (VTE recurrences, major bleeding or death) in non-cancer patients with VTE, according to long-term therapy with LMWH or vitamin K antagonists (VKAs). Results: As of March 2018, 14,582 non-cancer patients with VTE had received initial therapy with LMWH and then switched to VKAs, while 9151 were prescribed LMWH for initial and long-term therapy. Overall, 11,494 had initially presented with pulmonary embolism (PE) and 12,239 with isolated deep vein thrombosis (DVT). Among 11,494 patients initially presenting with PE, 84 had VTE recurrences, 204 major bleeding and 406 died. Among 12,239 patients with isolated DVT, 133 developed VTE recurrences, 137 bled and 289 died. On propensity score analysis, PE patients on long-term LMWH therapy were at increased risk for PE recurrences (OR: 3.30; 95%CI: 1.67–6.48), major bleeding (OR: 1.68; 95%CI: 1.21–2.32) or death (OR: 3.16; 95%CI: 2.43–4.09) compared with those receiving VKAs. In patients with DVT, those on long-term LMWH also were at increased risk for PE recurrences (OR: 2.31; 95%CI: 1.13–4.73), major bleeding (OR 2.28; 95%CI: 1.51–3.44) or death (OR: 2.32; 95%CI: 1.54–3.51). Conclusions: In the RIETE non-cancer patients with VTE, long-term therapy with VKAs was associated with a lower risk for recurrences, major bleeding or death.

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative cancer are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit-risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event. [ABSTRACT FROM AUTHOR]

[Display omitted] Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least three months, including at least one month after catheter removal following initiation of therapy. [ABSTRACT FROM AUTHOR]

The use of laparoscopic fundoplication (LF) to treat refractory GERD may induce refractory dysphagia (5%-10%). The management is complex, and peroral endoscopic myotomy (POEM) including valve incision is a new therapeutic option. This retrospective study involved patients with postfundoplication refractory dysphagia treated by POEM associated with complete wrap incision. Patients were evaluated with Eckardt and dysphagia scores. Study objectives were to evaluate clinical and technical outcomes, adverse events, and GERD recurrence. Twenty-six patients, with a mean age of 57.3 ± 15.6 years, were included. Mean follow-up was 25.3 ± 17.6 months. The technical and clinical success rates were 96% and 84.6%, respectively. Among failures, 1 patient underwent Lewis-Santy, 2 required dilations, and 1 was lost to follow-up. Three late recurrences occurred and were endoscopically managed. Five patients (19%) had GERD recurrence that was mainly improved by proton pump inhibitors. POEM with fundoplication is a serious therapeutic option for managing persistent dysphagia after LF, with a low risk of GERD recurrence. [ABSTRACT FROM AUTHOR]