Intestinal MAdCAM-1 imaging as biomarker for prognostic in murine models of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Recent evidence suggests that lymphocyte trafficking in the intestines could play a key role in its etiology. Nevertheless, it is not clear how intestinal tissue is involved in the disease onset nor its evolution. In the present study, we aimed to evaluate intestinal inflammation dynamic throughout the disease course and its potential impact on disease progression. METHODS: We used tissue immunophenotyping (immunohistofluorescence and flow cytometry) and a recently described molecular magnetic resonance imaging (MRI) method targeting mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to assess intestinal inflammation in vivo in two distinct animal models of MS (Experimental Autoimmune Encephalomyelitis - EAE) at several time points of disease progression. RESULTS: We report a positive correlation between disease severity and MAdCAM-1 MRI signal in two EAE models. Moreover, high MAdCAM-1 MRI signal during the asymptomatic phase is associated with a delayed disease onset in progressive EAE and to a lower risk of conversion to a secondary-progressive form in relapsing-remitting EAE. During disease evolution, in line with a bi-directional immune communication between the gut and the central nervous system, we observed a decrease in T-CD4+ and B lymphocytes in the ileum concomitantly with their increase in the spinal cord. CONCLUSION: Altogether, these data unveil a crosstalk between intestinal and central inflammation in EAE and support the use of molecular MRI of intestinal MAdCAM-1 as a new biomarker for prognostic in MS patients.

MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes.

The trafficking of autoreactive leucocytes across the blood-brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood-brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood-brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood-brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of TH1 and TH17 lymphocytes across the blood-brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4+ T lymphocytes that cross the blood-brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4+ T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis.

Impact of Peripheral Hydrogen Bond on Electronic Properties of the Primary Acceptor Chlorophyll in the Reaction Center of Photosystem I.

Photosystem I (PS I) is a photosynthetic pigment-protein complex that absorbs light and uses the absorbed energy to initiate electron transfer. Electron transfer has been shown to occur concurrently along two (A- and B-) branches of reaction center (RC) cofactors. The electron transfer chain originates from a special pair of chlorophyll a molecules (P700), followed by two chlorophylls and one phylloquinone in each branch (denoted as A-1, A0, A1, respectively), converging in a single iron-sulfur complex Fx. While there is a consensus that the ultimate electron donor-acceptor pair is P700+A0-, the involvement of A-1 in electron transfer, as well as the mechanism of the very first step in the charge separation sequence, has been under debate. To resolve this question, multiple groups have targeted electron transfer cofactors by site-directed mutations. In this work, the peripheral hydrogen bonds to keto groups of A0 chlorophylls have been disrupted by mutagenesis. Four mutants were generated: PsaA-Y692F; PsaB-Y667F; PsaB-Y667A; and a double mutant PsaA-Y692F/PsaB-Y667F. Contrary to expectations, but in agreement with density functional theory modeling, the removal of the hydrogen bond by Tyr → Phe substitution was found to have a negligible effect on redox potentials and optical absorption spectra of respective chlorophylls. In contrast, Tyr → Ala substitution was shown to have a fatal effect on the PS I function. It is thus inferred that PsaA-Y692 and PsaB-Y667 residues have primarily structural significance, and their ability to coordinate respective chlorophylls in electron transfer via hydrogen bond plays a minor role.

Incidence of Retinal Detachment, Macular Edema, and Ocular Hypertension after Neodymium:Yttrium-Aluminum-Garnet Capsulotomy: A Population-Based Nationwide Study-The French YAG 2 Study.

PURPOSE: To estimate the incidence and assess the risk factors associated with 3 adverse events (AEs) after neodymium:yttrium-aluminum-garnet posterior capsulotomy (Nd:YAG-caps): ocular hypertension (OHT), macular edema (ME), and retinal detachment (RD). DESIGN: Observational cohort study using a nationwide claims database. PARTICIPANTS: Adults who underwent Nd:YAG-caps between 2014 and 2017, with no ocular disease history in the year before. METHODS: Patients who underwent Nd:YAG-caps were identified using data from the French national representative sample and followed up for 12 months postprocedure. The time to AE was assessed using the Kaplan-Meier method. Factors associated with AE were assessed using Cox models. MAIN OUTCOME MEASURES: Neodymium:YAG-caps epidemiology, patients' characteristics, proportion of patients with AE, and hazard ratios (HRs) associated with variables identified as factors associated with AEs. RESULTS: During the study period, 6210 patients received Nd:YAG-caps (7958 procedures). The mean age (± standard deviation) at Nd:YAG-caps was 75.0 (± 10.3) years. The 3-month and 12-month overall AE rates (≥ 1 AE of interest) were 8.6% and 13.3%, respectively. Among patients with ≥ 1 AE of interest, 68.4% of AEs occurred within 3 months post-Nd:YAG-caps. Three-month rates were ≈5% for OHT and ME. Retinal detachment remained ≤ 0.5% over follow-up. Cox models showed that patients with Nd:YAG-caps performed within 1 year after cataract surgery had a higher risk of AEs than those with later Nd:YAG-caps (hazard ratio [HR], 1.314 [1.034-1.669], P = 0.0256), notably ME (HR, 1.500 [1.087-2.070], P = 0.0137). Diabetic patients were more at risk of OHT (HR, 1.233 [1.005-1.513], P = 0.0448) and ME (HR, 1.810 [1.446-2.266], P < 0.0001) than nondiabetic patients. Patients with Nd:YAG-caps performed between 1 and 2 years after cataract surgery were more at risk of OHT than patients with later Nd:YAG-caps (HR, 1.429 [1.185-1.723], P = 0.0002). CONCLUSIONS: According to a national claims database, OHT and ME were the most frequent AEs of interest post-Nd:YAG-caps, mainly observed within 3 months postprocedure, highlighting the need for a close follow-up during this period or a delayed capsulotomy. Diabetes and an early Nd:YAG-caps after cataract surgery were among the main drivers for AE occurrence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Incidence of Nd:YAG laser capsulotomy following cataract surgery: a population-based nation-wide study - FreYAG1 study.

RATIONALE: Nd:YAG (neodymium:yttrium-aluminum-garnet) capsulotomy (Nd:YAG-caps) is the gold standard for the treatment of PCO (Posterior Capsule Opacification). There is a lack of real-world data about Nd:YAG-caps use. PURPOSE: This study's objectives were to estimate Nd:YAG-caps incidence in France, to describe the patient characteristics, and to analyze the time between surgeries and capsulotomies. SETTING: The study was based on data extracted from the EGB database, a 1/97th sample representative of the French population. DESIGN: observational, retrospective, cohort study using national claims data. METHODS: French adult patients who underwent Nd:YAG-caps between 2014 and 2017 were selected. Main outcomes were the number of patients and procedures performed and the risk factors associated with early Nd:YAG-caps. RESULTS: During the study period, Nd:YAG-caps were performed in 8,425 patients accounting for 10,774 procedures. The extrapolation to the French population led to estimate that 253.103 patients had Nd:YAG-caps, representing 312.103 procedures in 2017. The mean age at Nd:YAG-caps was 75.1 (± 10.2) years. About 36% of patients presented at least one ocular comorbidity. Nd:YAG-caps was performed within 2 years after surgery in 33.0% of patients and within one year in 9.8% of patients. Patients with Nd:YAG-caps within the first year (OR CI95 0.721 [0.673-0.772]) or in the first two years (OR CI95 0.721 [0.673-0.772]) were younger than patients with later Nd:YAG-caps and had a more frequent history of treated ocular diseases (OR 1.516 and 1.178, respectively). CONCLUSIONS: This study brought new real-world and large-scale data regarding Nd:YAG-caps use and gave an updated insight into the patients' characteristics.

A scoping review of intensive longitudinal methods in informal caregivers of people with dementia.

BACKGROUND: The daily life of informal caregivers assisting individuals with dementia widely varies throughout the day and week. As an answer, an increasing number of researchers have used intensive longitudinal methods (ILMs) such as diary studies, experience sampling methods, or ecological momentary assessment. OBJECTIVES AND METHODS: The present scoping review aims at synthesizing the use of ILMs in informal dementia caregivers to clarify what is currently done and how, as well as what remains unaddressed. RESULTS: The screening process identified 48 studies from 22 different datasets. Synthesis of these studies showed the diversity of devices and uses of ILMs in informal care, including the exploration of associations between variables or accompanying an intervention. ILMs showed the important variability of caregiving phenomena, as well as the important association of momentary stress and well-being. Gaps were nevertheless identified, such as transparency in the construction of the tool or the absence of focus on emotions and dyads. CONCLUSIONS: For now, this field of research remains in its infancy and does not seem to have reached its full potential as it has in other fields. Nevertheless, it appears that ILMs are promising tools for informal dementia caregivers as they contribute to understanding the complexity of their daily life, with changing resources and challenges. Future directions include focusing more on (emotion) regulation, temporal lags, and the use of ILMs in interventional designs. TRIAL REGISTRATION: The present review was registered on OSF (osf.io/b2qr4).

Awareness dimensions and associated factors in Alzheimer's disease.

OBJECTIVES: We recently reported the major role depression and apathy in awareness among Alzheimer patients, using the stage of the disease as an exposure factor and exploring different assessment methods. Using the same patient data, we aimed here to explore the different dimensions of awareness assessed by different sub-scales in awareness scales. METHOD: Sixty-one Alzheimer patients were examined using four awareness scales relating to three assessment methods: (a) patient-caregiver discrepancy; (b) clinical rating; and (c) prediction of performance discrepancy. Global cognition, executive functioning, autonomy, depression and apathy were also assessed. Multivariate logistic models were performed using disease stage as an exposure factor for awareness scales and sub-scales. Correlations across the different factors and patient and caregiver awareness ratings were computed. RESULTS: The patient-caregiver discrepancy and clinical rating methods (a, b) both identified the factors associated with awareness in the overall scales and the sub-scales as being depression and/or apathy. Depression correlated with patient self-ratings while apathy correlated with caregiver ratings. The prediction of performance discrepancy method (c) identified different factors in the overall scale, executive factors in three sub-scales involving executive domains and the memory factor in a sub-scale involving the mnesic domain. DISCUSSION: The awareness scales using a referential based on a human rating (a, b) suggest that awareness is unidimensional, with depression impacting self-reports and apathy influencing caregiver/clinical reports. Scales based on a test rating (c) appear to be more closely associated with the dimensions assessed. This highlights the role of the reference system for awareness assessment in Alzheimer's disease.

Conflict-related environmental damages on health: lessons learned from the past wars and ongoing Russian invasion of Ukraine.

On 24 February 2022, Russian military forces invaded Ukraine. The fighting has already caused unimaginable conditions and millions of people were forced to flee their homes. For decades, conflicts have been linked to environmental pollution, exposure to radioactivity and heavy metals as well as infectious diseases. The invasion may cause specific environmental risks, like the release of radioactive substances from nuclear power plants and contaminated soils. Because international collaboration is one of the most effective ways to address environmental problems, it is critical to establish scientific bodies within a global framework to identify concrete actions and tangible measures to provide immediate assistance to citizens. This commentary discusses the above issues from lessons learned from the past wars and the way forward in the Russian invasion of Ukraine.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Utility of Core-Shell Nanomaterials in the Catalytic Transformations of Renewable Substrates.

In recent years, core-shell nano-catalysts have received increasing attention due to their tunable properties and broad applications in catalysis. Control of the two components of these materials allows their catalytic properties to be tuned to various sustainable processes in synthetic and energy-related applications. This Concept article describes recent state-of-the-art core-shell materials and their application as heterogeneous catalysts for a range of sustainable catalytic transformations, focusing on two important classes of renewable substrates, CO2 and biomass. In the discussion, emphasis is directed to the role of the constituent parts of the core-shell structure and how they can be manipulated to enhance activity.

Cerebral and Limb Tissue Oxygenation During Peripheral Venoarterial Extracorporeal Life Support.

Femoral access in extracorporeal life support (ECLS) has been associated with regional variations in arterial oxygen saturation, potentially predisposing the patient to ischemic tissue damage. Current monitoring techniques, however, are limited to intermittent bedside evaluation of capillary refill among other factors. The aim of this study was to assess whether cerebral and limb regional tissue oxygen saturation (rSO2) values reflect changes in various patient-related parameters during venoarterial ECLS (VA-ECLS). This retrospective observational study included adults assisted by femorofemoral VA-ECLS. Bifrontal cerebral and bilateral limb tissue oximetry was performed for the entire duration of support. Hemodynamic data were analyzed parallel to cerebral and limb rSO2. A total of 23 patients were included with a median ECLS duration of 5 [1-20] days. Cardiac arrhythmias were observed in 12 patients, which was associated with a decreased mean rSO2 from 61%±11% to 51%±10% during atrial fibrillation and 67%±9% to 58%±10% during ventricular fibrillation (P<0.001 for both). A presumably sudden increase in cardiac output due to myocardial recovery (n=8) resulted in a significant decrease in mean cerebral rSO2 from 73%±7% to 54%±6% and from 69%±9% to 53%±8% for the left and right cerebral hemisphere, respectively (P=0.012 for both hemispheres). Also, right radial artery partial gas pressure for oxygen decreased from 15.6±2.8 to 8.3±1.9 kPa (P=0.028). No differences were found in cerebral desaturation episodes between patients with and without neurologic complications. In six patients, limb rSO2 increased from on average 29.3±2.7 to 64.0±5.1 following insertion of a distal cannula in the femoral artery (P=0.027). Likewise, restoration of flow in a clotted distal cannula inserted in the femoral artery was necessary in four cases and resulted in increased limb rSO2 from 31.3±0.8 to 79.5±9.0; P=0.068. Non-invasive tissue oximetry adequately reflects events influencing cerebral and limb perfusion and can aid in monitoring tissue perfusion in patients assisted by ECLS.

Adalimumab in Patients with Active Noninfectious Uveitis.

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Indirect CO2 Methanation: Hydrogenolysis of Cyclic Carbonates Catalyzed by Ru-Modified Zeolite Produces Methane and Diols.

We report a ruthenium-modified zeolite which efficiently transforms propylene carbonate to propylene glycol and methane, under solvent-free conditions. The catalyst achieved high product selectivity and no significant ageing effect was observed after multiple cycles. The resulting liquid product (water-containing glycol) can be directly used as anti-freeze solution and the gas phase can directly be used as an energy carrier in the form of H2 -enriched methane. This process efficiently bridges energy storage and an important chemical synthesis under sustainable (CO2 consuming) conditions.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

TOPIC: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. CLINICAL RELEVANCE: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. METHODS: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. RESULTS: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. CONCLUSIONS: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Perioperative Transcutaneous Tibial Nerve Stimulation to Reduce Postoperative Ileus After Colorectal Resection: A Pilot Study.

BACKGROUND: Postoperative ileus involves an inflammatory pathway characterized by an increase of inflammation mediators in the colon wall; this could probably be prevented by sacral nerve neuromodulation. The posterior tibial nerve can be stimulated electrically to mimic neuromodulation. OBJECTIVE: The aims of this study were to assess the efficacy of transcutaneous posterior tibial nerve stimulation in reducing the delay in GI motility recovery, to assess the safety of posterior tibial nerve stimulation in a perioperative setting, and to assess the efficacy of posterior tibial nerve stimulation in reducing the occurrence of postoperative ileus. DESIGN: This was a preliminary randomized controlled study. SETTINGS: This study was conducted in 1 academic hospital in France. PATIENTS: Forty patients undergoing an elective colectomy were included and randomly assigned into 2 groups, posterior tibial nerve stimulation or placebo, according to the side of colectomy and the surgical access size. INTERVENTION: Perioperative posterior tibial nerve stimulation or placebo was performed 3 times per day according to the randomly assigned group. MAIN OUTCOME MEASURES: Delay in GI motility recovery (passage of stool and tolerance of solid food) was measured. RESULTS: Of the 40 patients included, 34 were included in the final analysis, in which 2 patients in the placebo group were allocated the incorrect device. The 6 other patients were secondarily excluded because of protocol deviation. In the intention-to-treat analysis, the mean delay in GI motility recovery was 3.6 and 3.11 days (in the placebo and tibial nerve stimulation groups; p = 0.60). Occurrence of postoperative ileus was not significantly higher in the placebo group (35.3% vs 17.6%; p = 0.42). In the per-protocol analysis, we observed the same trends except for the occurrence of postoperative ileus, which was significantly higher in the placebo group (p = 0.045). Tolerance to posterior tibial nerve stimulation was good, and all of the patients completed the protocol. LIMITATIONS: The amplitude of stimulation is set according to patient sensation, so some patients could have been aware of their group. In addition there were some inherent limitations because of the preliminary nature of the study and several deviations from the protocol. CONCLUSIONS: Posterior tibial nerve stimulation was safe in a perioperative setting and had a potential effect on GI motility recovery. The results of this study will be useful for sample size calculations in a larger prospective randomized trial. See Video Abstract at http://links.lww.com/DCR/A708.

Cancer-associated retinopathy preceding the diagnosis of cancer.

BACKGROUND: The early diagnosis of cancer is of crucial importance and a key prognostic factor. Cancer-associated retinopathy (CAR) can be symptomatic prior to other manifestations directly related to malignant tumors. The aim of this study was to show that, in selected cases, ophthalmic findings are consistent enough with the diagnosis of CAR to trigger investigations aimed at detecting a previously unknown malignancy. METHODS: This was a monocentric retrospective case series performed in a tertiary referral center. Patients with a diagnosis of CAR were included. Diagnosis was based on the clinical presentation, the visual field and electroretinogram alterations. The clinical presentation, visual field testing and electroretinographic results were analyzed as well as the malignancies identified following the diagnosis of CAR. Follow-up data was collected. RESULTS: Four patients (two men, two women, median age 65.5 years) were included. All patients presented with posterior segment inflammation at initial presentation as well as advanced visual field loss and an extinguished electroretinogram. The best corrected decimal visual acuity was 0.8 or better in both eyes of three patients and decreased to 0.3 OD and O.2 OS in one patient due to a bilateral macular edema. No patient had a previously known history of cancer. Once the diagnosis of CAR was made, investigations aimed at identifying a malignant tumors subsequently led to the diagnosis of two cases of small cell lung tumors, of one prostate carcinoma and of a uterine sarcoma. The treatment of CAR included plasmapheresis, systemic corticosteroids, azathioprine, cyclosporine and periocular or intraocular corticosteroid injections. In all cases the intraocular inflammation resolved, but pigment mottling, diffuse retinal atrophy, optic disc pallor and arterial narrowing were among manifestations observed during the follow-up of the patients. CONCLUSION: In selected patients, findings suggestive of CAR can be useful for the early detection of a cancer.

Untreated Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): a case series.

BACKGROUND: Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare inflammatory eye disease that affects the Retinal Pigment Epithelium and outer retina. The purpose of this study was to describe its presentations, as well as its prognosis in a series of untreated patients. METHODS: Records of patients seen in the department of Ophthalmology at Cochin University Hospital, Paris, between April 2002 and June 2015 were retrospectively studied. Patients were included if they presented with the typical findings of APMPPE characterized by whitish or yellowish bilateral placoid lesions, a typical pattern of early hypofluorescence and late hyperfluorescence on fluorescein angiography. Only untreated patients who had been followed for at least 1 month were included. RESULTS: Out of 22 patients' records with a diagnosis of APMPPE, 10 patients (9 women, 1 man), with a mean age of 24.5 ± 4.2 years, fulfilled the study criteria with a diagnosis of typical untreated APMPPE. Prodromal symptoms were reported in 7/10 patients. Macular lesions were observed in 18/20 eyes. Sub-retinal fluid was seen at presentation in 3 eyes. Initial mean BCVA was 0.56 ± 0.81 LogMAR [- 0.10 to 2.30]. In 9 out of 10 cases, the time interval between manifestations in the first affected eye and the fellow eye was less than 3 days. After 1 month, BCVA had improved to 0.05 ± 0.089 LogMAR [0-0.3], with a decimal BCVA ≥0.8 in 17/20 eyes. CONCLUSIONS: In these 10 cases of untreated APMPPE, a favorable outcome was observed.

Deletions Overlapping VCAN Exon 8 Are New Molecular Defects for Wagner Disease.

Wagner disease is a rare nonsyndromic autosomal-dominant vitreoretinopathy, associated with splice mutations specifically targeting VCAN exon 8. We report the extensive genetic analysis of two Wagner probands, previously found negative for disease-associated splice mutations. Next-generation sequencing (NGS), quantitative real-time PCR, and long-range PCR identified two deletions (3.4 and 10.5 kb) removing at least one exon-intron boundary of exon 8, and both correlating with an imbalance of VCAN mRNA isoforms. We showed that the 10.5-kb deletion occurred de novo, causing somatic mosaicism in the proband's mother who had an unusually mild asymmetrical phenotype. Therefore, exon 8 deletions are novel VCAN genetic defects responsible for Wagner disease, and VCAN mosaic mutations may be involved in the pathogenesis of Wagner disease with attenuated phenotype. NGS is then an effective screening tool for genetic diagnosis of Wagner disease, improving the chance of identifying all disease-causative variants as well as mosaic mutations in VCAN.