Long-term follow-up of balloon-expandable valves according to the implantation strategy: insight from the DIRECTAVI trial.

BACKGROUND: Safety and feasibility of transcatheter aortic valve replacement (TAVR) without balloon aortic valvuloplasty (BAV) using the SAPIEN 3 balloon-expandable device has been previously demonstrated. The impact on long-term valve hemodynamic performances and outcomes remains however unknown. We evaluate long-term clinical and hemodynamic results according to the implant strategy (direct TAVR vs BAV pre-TAVR) in patients included in the DIRECTAVI randomized trial (NCT02729519). METHODS: Clinical and echocardiographic follow-up until January 2023 was performed for all patients included in the DIRECTAVI trial since 2016 (n = 228). The primary endpoint was incidence of moderate/severe hemodynamic valve deterioration (HVD), according to the Valve Academic Research defined Consortium-3 criteria (increase in mean gradient ≥10 mmHg resulting in a final mean gradient ≥20 mmHg, or new/worsening aortic regurgitation of 1 grade resulting in ≥ moderate aortic regurgitation). RESULTS: Median follow-up was 3.8 (2.2-4.7) years. Mean age at follow-up was 87 ± 6.7 years. No difference in incidence of HVD in the direct implantation group compared to the BAV group was found (incidence of 1.97 per 100 person-years and 1.45 per 100 person-years, respectively, P = 0.6). Prevalence of predicted prothesis-patient mismatch was low (n = 13 [11.4%] in the direct TAVR group vs n = 15 [13.2%] in BAV group) and similar between both groups (P = .7). Major outcomes including death, stroke, hospitalization for heart failure and pacemaker implantation were similar between both groups, (P = .4, P = .7, P = .3, and P = .3 respectively). CONCLUSION: Direct implantation of the balloon-expandable device in TAVR was not associated with an increased risk of moderate/severe HVD or major outcomes up to 6-year follow-up. These results guarantee wide use of direct balloon-expandable valve implantation, when feasible. CLINICAL TRIALS REGISTRATION NUMBER: NCT05140317.

Balloon predilation or direct valve implantation in TAVI for women: Insights from the DIRECTAVI study.

BACKGROUND: The randomized DIRECTAVI trial demonstrated safety and feasibility of transcatheter aortic valve implantation (TAVI) without balloon aortic valvuloplasty (BAV) using SAPIEN 3 balloon-expandable devices. However, the female population with smaller anatomy may have potential higher risk of residual gradient and/or mismatch. PURPOSE: We assessed the impact of BAV on the procedural success rate and clinical outcomes in the female population of the DIRECTAVI trial. METHODS: Between May 2016 and May 2018, 91 of the 250 patients included in the DIRECTAVI trial were women (38.6%), 45 of them (49.5%) were enrolled in the BAV group and 46 of them (50.5%) in the direct TAVI group. The primary endpoint was procedural success rate in women (Valve Academic Research Consortium-2 criteria). The secondary endpoint included evaluation of PPM and 1-month major adverse events according to the implantation stategy in women and comparison between men and women regarding major endpoints. RESULTS: The primary endpoint occurred in 29 women (64.4%) in the BAV group and in 34 women (73.9%) in the direct TAVI group (mean difference 9.47%; 95% confidence interval: 6.5%-25.4%; p = 0.045 for non-inferiority of the direct strategy). One-month major adverse events were similar between the 2 women groups. Procedural success was lower in women vs men (p = 0.01) due to higher incidence of moderate mismatches in women (p = 0.001) but with no significant difference regarding the implantation strategy (p = 0.4). CONCLUSION: Direct implantation of the balloon-expandable SAPIEN 3 valve was non-inferior to predilatation on procedural success in women. Incidence of moderate mismatch was higher in women but was not related to the implantation strategy.

Transcatheter aortic valve implantation in patients with uninterrupted vitamin K antagonists.

BACKGROUND: Bridging of vitamin K antagonist (VKA) with heparin is usually not promoted during interventional or surgical procedures related to increased risk of bleeding and thrombotic events but this strategy has not been evaluated during transcatheter aortic valve implantation (TAVI). PURPOSE: The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA. METHODS: From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (International Normalized Ratio [INR] between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI was performed according to current guidelines and a 50 U/kg bolus of heparin was injected at the beginning of the procedure for all patients. Vascular and bleeding complications were assessed using the Valve Academic Research Consortium 3 (VARC3) and the Bleeding Academic Research Consortium (BARC) definitions at a 30-day follow-up. RESULTS: A total of 88 patients were included with a median age of 84 years (81.8-87.0), 42% being female. The median society of thoracic surgeons score was 5.1 (4.1-7.5), the median CHADS2-VASc was 5.5 (5-6) and 60.2% had a chronic kidney failure. Median INR at the time of implantation was 2.1 (1.8-2.6). The main VKA indication was atrial fibrillation. Transfemoral access was used in 88.6% of the patients. Major bleeding (BARC ≥ 3b) occurred in five patients (5.7%) and major vascular complications occurred in seven patients (8.0%). At 1 month follow-up, major bleeding (BARC ≥ 3) or vascular complications occurred in 10 patients (11.4%). In patients with major bleeding peripheral arterial disease (RR = 10.95; 95% confidence interval (CI) 1.63-73.75; p = 0.014) and carotid access (RR = 8.56; 95% CI 1.19-1.51; p = 0.033) were more common. INR > 2.5 was significantly associated with vascular complications (RR = 7.14; 95% CI 1.29-39.63; p = 0.025). At 30 days, mortality and stroke rates were 2.3% and 4.5%, respectively. CONCLUSION: TAVI with uninterrupted VKA treatment seems feasible and safe with a low risk of major bleeding and vascular complications in this first single-center experience. Particular caution is advocated in high body mass index patients and to keep INR < 2.5.

Features and risk factors for new (secondary) permanent visual involvement in giant cell arteritis.

OBJECTIVES: New permanent visual loss (PVL) in treated patients with giant cell arteritis (GCA) is a rare but worrisome occurrence. In this study, we aimed to describe the frequency and main features of new PVL occurring after the beginning of glucocorticoid therapy in patients with newly diagnosed GCA. METHODS: We included in an inception cohort all consecutive patients newly diagnosed with GCA in the internal medicine department of a tertiary-care hospital between 1976 and May 2020. The study population comprised all the patients without bilateral PVL before treatment who were followed for at least one year. Only well-documented visual events that set after the initiation of glucocorticoid treatment were regarded as new PVL. RESULTS: Eleven out of 502 patients (2.2%) experienced a new PVL including 6 occurrences during the initial therapeutic phase and 5 during the tapering phase. Patients with new PVL during treatment had higher mean age, more often displayed temporal artery abnormalities on physical examination, and had higher mean platelet counts at GCA onset. There was a strong excess risk of contralateral recurrence during treatment in patients with unilateral loss at GCA onset compared with patients with uncomplicated GCA (10.5% vs 1.1%, OR=10.26, p<0.001). CONCLUSIONS: New PVL in treated GCA is a rare, but significant occurrence. Older patients and patients who already had unilateral PVL at diagnosis have higher risk of new ischaemic visual loss during treatment compared to the other patients. Close clinical, laboratory, and eye monitoring of these high-risk patients is of paramount importance.

Expression of nuclear and mitochondrial genes encoding ATP synthase is synchronized by disassembly of a multisynthetase complex.

In eukaryotic cells, oxidative phosphorylation involves multisubunit complexes of mixed genetic origin. Assembling these complexes requires an organelle-independent synchronizing system for the proper expression of nuclear and mitochondrial genes. Here we show that proper expression of the F1FO ATP synthase (complex V) depends on a cytosolic complex (AME) made of two aminoacyl-tRNA synthetases (cERS and cMRS) attached to an anchor protein, Arc1p. When yeast cells adapt to respiration the Snf1/4 glucose-sensing pathway inhibits ARC1 expression triggering simultaneous release of cERS and cMRS. Free cMRS and cERS relocate to the nucleus and mitochondria, respectively, to synchronize nuclear transcription and mitochondrial translation of ATP synthase genes. Strains releasing asynchronously the two aminoacyl-tRNA synthetases display aberrant expression of nuclear and mitochondrial genes encoding subunits of complex V resulting in severe defects of the oxidative phosphorylation mechanism. This work shows that the AME complex coordinates expression of enzymes that require intergenomic control.

Focus on cell therapy to treat corneal endothelial diseases.

The cornea is a multi-layered structure which allows fine refraction and provides both resistance to external insults and adequate transparency. The corneal endothelium ensures stromal hydration, failure of which, such as in Fuchs endothelial corneal dystrophy, after trauma or in aging, may lead to loss of corneal transparency and induce blindness. Currently, no efficient therapeutic alternatives exist except for corneal grafting. Thus corneal tissue engineering represents a valuable alternative approach, which may overcome cornea donor shortage. Several studies describe protocols to isolate, differentiate, and cultivate corneal endothelial cells (CEnCs) in vitro. Two main in vitro strategies can be described: expansion of eye-native cell populations, such as CEnCs, or the production and expansion of CEnCs from non-eye native cell populations, such as induced Pluripotent Stem Cells (iPSCs). The challenge with these cells is to obtain a monolayer of CEnCs on a biocompatible carrier, with a specific morphology (flat hexagonal cells), and with specific functions such as programmed cell cycle arrest. Another issue for this cell culture methodology is to define the adapted protocol (media, trophic factors, timeframe) that can mimic physiological development. Additionally, contamination by other cell types still represents a huge problem. Thus, purification methods, such as Fluorescence Activated Cell Sorting (FACS), Magnetic Ativated Cell Sorting (MACS) or Sedimentation Field Flow Fractionation (SdFFF) are useful. Animal models are also crucial to provide a translational approach for these therapies, integrating macro- and microenvironment influences, systemic hormonal or immune responses, and exogenous interactions. Non-eye native cell graft protocols are constantly improving both in efficacy and safety, with the aim of being the most suitable candidate for corneal therapies in future routine practice. The aim of this work is to review these different aspects with a special focus on issues facing CEnC culture in vitro, and to highlight animal graft models adapted to screen the efficacy of these different protocols.

School tobacco policies and adolescent smoking in six European cities in 2013 and 2016: A school-level longitudinal study.

Assessment of the effectiveness of school tobacco policies (STPs) in reducing adolescent smoking remains inconclusive. Previous studies took insufficient account of different dimensions of STPs, the different views of students and staff, and policy changes over time. This study assessed how a multidimensional STP, as perceived by students and staff, was associated with adolescent smoking over time in six European cities. The SILNE and SILNE-R surveys were conducted among students (n = 18,502) and staff (n = 438) in 38 schools in 2013 and 2016. Three dimensions (comprehensiveness, enforcement, and communication) were assessed and we calculated total STP scores. Multilevel logistic regressions estimated associations of STPs with adolescent smoking on and just outside school premises and with weekly smoking. Further analyses estimated associations between 2013 and 2016 STP changes and smoking outcomes in 2016, controlling for STP and smoking prevalence in 2013. On average, there were few increases in STP scores over time. Greater STP enforcement, as perceived by students, was associated with lower odds of weekly smoking (OR:0.93, 95%CI:0.89-0.97) and of smoking on school premises (OR:0.80, 95%CI:0.72-0.90). Higher total STP scores were associated with lower odds of smoking on school premises (OR:0.76, 95%CI:0.67-0.86), but not of smoking just outside premises or smoking weekly. Greater increases in STP scores over time were associated with lower odds of smoking on school premises in 2016 (OR:0.65, 95%CI:0.47-0.89). Well-enforced STPs may help reduce adolescent smoking at school. Schools should be supported in adopting comprehensive policies that also extend to the surroundings of their premises.

STIP1/HOP Regulates the Actin Cytoskeleton through Interactions with Actin and Changes in Actin-Binding Proteins Cofilin and Profilin.

Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.

Yeast mitochondrial Gln-tRNA(Gln) is generated by a GatFAB-mediated transamidation pathway involving Arc1p-controlled subcellular sorting of cytosolic GluRS.

It is impossible to predict which pathway, direct glutaminylation of tRNA(Gln) or tRNA-dependent transamidation of glutamyl-tRNA(Gln), generates mitochondrial glutaminyl-tRNA(Gln) for protein synthesis in a given species. The report that yeast mitochondria import both cytosolic glutaminyl-tRNA synthetase and tRNA(Gln) has challenged the widespread use of the transamidation pathway in organelles. Here we demonstrate that yeast mitochondrial glutaminyl-tRNA(Gln) is in fact generated by a transamidation pathway involving a novel type of trimeric tRNA-dependent amidotransferase (AdT). More surprising is the fact that cytosolic glutamyl-tRNA synthetase ((c)ERS) is imported into mitochondria, where it constitutes the mitochondrial nondiscriminating ERS that generates the mitochondrial mischarged glutamyl-tRNA(Gln) substrate for the AdT. We show that dual localization of (c)ERS is controlled by binding to Arc1p, a tRNA nuclear export cofactor that behaves as a cytosolic anchoring platform for (c)ERS. Expression of Arc1p is down-regulated when yeast cells are switched from fermentation to respiratory metabolism, thus allowing increased import of (c)ERS to satisfy a higher demand of mitochondrial glutaminyl-tRNA(Gln) for mitochondrial protein synthesis. This novel strategy that enables a single protein to be localized in both the cytosol and mitochondria provides a new paradigm for regulation of the dynamic subcellular distribution of proteins between membrane-separated compartments.

Individual and contextual determinants of perceived peer smoking prevalence among adolescents in six European cities.

BACKGROUND: Young people perceiving a high peer smoking prevalence are more likely to initiate smoking. It is unclear which factors contribute to perceived peer smoking prevalence and if these factors vary according to education. This study aimed to assess the determinants of perceived smoking prevalence and assessed its variation at school and country-level. METHODS: Data of 10,283 14-17-year-old students in 50 secondary schools in six European cities were derived from the 2013 SILNE survey. The outcome was the perceived smoking prevalence score among peers at school (0-10 scale, 10 represented 100% smoking prevalence). Multilevel linear regression models estimated the associations of factors with perceived prevalence score and variance at school and country-levels. Analyses were also stratified by academic achievement of the adolescent and parental education. RESULTS: Determinants of a higher perceived prevalence score were female sex, ever smoking, having friends who smoke, low academic achievement, low parental educational level, and higher actual prevalence of smoking in the school. The perceived prevalence score was not associated with school policies or with the availability of cigarettes near the school. Determinants were very similar across levels of academic achievement and parental education. Perceived prevalence scores substantially varied between schools and countries: 10% and 11% of total variance was related to schools and countries respectively. CONCLUSION: Across educational levels, perceptions of peer smoking are strongly determined by both individual characteristics and school and national contexts. Future studies should assess why perceived smoking prevalence varies between schools and countries and identify modifiable factors.

Dataset from the literature on the ingestive behaviour of grazing ruminants.

The dataset described in this paper was constructed from 90 publications available from bibliographic databases. It presents the values of various quantitative components of ingestive behaviour of grazing ruminants (bite weight, biting rate, intake rate, grazing time, etc.). These values were coded according to the experimental factors tested and described in the publications, of a temporal nature (season, year, grazing cycle) or linked to the sward management strategies (overall density bulk or of the stems, the stage regrowth or the fertilization) or other pasture management strategies (herbage allowance, pasture access time, stocking rate). Other essential factors were also coded, specifying the characteristics of the grass grazed (height of the grass, apparent density, forage species), the characteristics of the animals used (species, stage, age and body weight) or the measurement methods of behavioural components. This coding process aims to facilitate the identification of subsets of data of interest, and have been analysed for example to highlight the main components determining bite weight or the components linking bite weight to intake rate and daily intake (see reference).

Cytomegalovirus detected by qPCR in iris and ciliary body of immunocompetent corneal donors.

BACKGROUND: Cytomegalovirus (CMV) can cause a wide panel of ocular infections. The involvement of CMV as a cause of anterior uveitis in the immunocompetent patient is recent and remains poorly understood. OBJECTIVE: To investigate the presence of CMV in anterior uveal tissues of immunocompetent corneal donors. STUDY DESIGN: We collected aqueous humor, iris, and ciliary body from both eyes of 25 donors died at the Limoges University Hospital between January 2020 and July 2021. CMV serology was determined for all patients from post-mortem blood sample. Ocular tissues were split in 2 fragments for qPCR and 2 for histological analysis. CMV genomes copies were quantified by Multiplex qPCR after DNA extraction. RESULTS: 16 of 25 patients (64%) displayed positive CMV serology, with a median age of 67 years. Viremia was positive in 3 of 16 (19%) CMV-positive patients. No CMV DNA copies were found from the aqueous humor samples. CMV DNA was detected in iris and ciliary body of 28 of 32 eyes of seropositive donors, and 5 of 18 eyes of seronegative donors. The median viral copy number [IQR] was 2.41 × 102 [8.91 × 101 - 1.01 × 103] copies/1 × 106 cells in the CMV-positive group and 0.00 [0.00 - 3.54 × 102] copies/1 × 106 cells in the CMV-negative group (p<0.001). Histology and immunohistochemistry did not reveal any CMV lesions from any sample. CONCLUSION: CMV DNA was found in iris and ciliary body of immunocompetent seropositive patients, but also, although less frequently, from seronegative donors. These results highlight mechanisms of infection, latency and reactivation of CMV in ocular tissues.

Corneal Toxicity in Patients Treated by BELANTAMAB MAFODOTIN: How to Improve and Facilitate Patients Follow-Up Using Refractive Shift?

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

Identification of Low- versus High-Risk Acute Coronary Syndrome for a Selective ECG Monitoring Strategy.

BACKGROUND: While admission of patients with acute coronary syndromes (ACS) in cardiology intensive care unit (CICU) is usual, in-hospital major outcomes in lower risk patients may be evaluated after early coronary angiography according to the European guidelines. METHODS: Consecutive ACS patients were prospectively included after coronary angiography evaluation within 24 h and percutaneous coronary intervention (PCI), when required. Patients were classified as high- or low-risk according to hemodynamics, rhythmic state, ischemic and bleeding risks. Major in-hospital outcomes were assessed. RESULTS: From January to June 2021, 277 patients were enrolled (62.8% with ST-segment elevation myocardial infarction (STEMI) (n = 174); 37.2% with non-NSTEMI (NSTEMI) (n = 103). PCI was required for 260 patients (93.9%). Seventy-four patients (26.7%) were classified as low-risk (n = 47 NSTEMI; n= 27 STEMI) and 203 patients (73.3%) as high-risk of events. All patients were monitored in CICU. While 38 patients (18.7%) from the high-risk group reached the primary endpoint, mainly related to rhythmic or conduction disorder (n = 24, 11.8%) or unstable hemodynamics (n = 17; 8.4%), only 1 patient (1.3%) in the low-risk group had one major outcome (no fatal bleeding); p < 0.01. The negative predictive value of our patient stratification for the absence of major in-hospital outcome was 100% (CI95%: 100-100%) for STEMI and 97.9% [CI95%: 93.2-100%] for NSTEMI patients. CONCLUSIONS: Stratification of ACS patients after early coronary angiography and most of the time PCI, identify a population with very low risk of in-hospital events (1/4 of all ACS and 1/2 of NSTEMI) who may probably not require ECG monitoring and/or CICU admission. (NCT04378504).

Keratoconus and the Impact of Treatment on Patients' Quality of Life: A Qualitative Study.

INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

Dung removal increases under higher dung beetle functional diversity regardless of grazing intensification.

Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.

Myxofibrosarcoma of the orbit: case report and review of literature.

A 17-year-old man was referred with a 6-month history of painless left inferior eyelid edema. Ophthalmic examination was normal except for the presence of a reddish conjunctiva in the left eye medial canthus. MRI demonstrated a 20-mm well-defined extraconical mass between the medial and inferior rectus muscle without destruction of the medial orbital wall. A low-grade myxofibrosarcoma was diagnosed on orbital biopsy. The tumor was locally excised, but the patient categorically refused left exenteration or conformal radiotherapy. He accepted to have annual clinical and radiologic checkup. To date, 2 years later, he has been followed up with no evidence of tumor recurrence. Orbital localization of myxofibrosarcoma is extremely rare, with only 2 cases reported in the literature. The differential diagnosis could be difficult: here, a fibromyxoid sarcoma and a myxoid variant of dedifferentiated liposarcoma have been especially discussed in terms of their histopathologic features. Risk of metastasis is related to the tumor grade. Management of these tumors associates surgery with orbital exenteration or globe-sparing approaches and postsurgical adjuvant radiation therapy.

Ophthalmologic outcome of direct and indirect carotid cavernous fistulas.

Carotid cavernous fistulas (CCFs) can be classified as direct and indirect, depending on their flow rates and their etiology. Both forms can cause the same characteristic ophthalmological symptoms and signs. We analyzed these ocular characteristics and determined the prognostics factors associated with treatment outcome. Forty-seven patients with an angiographically confirmed diagnosis of CCF, a preoperative ophthalmic evaluation and at least one ophthalmic sign or symptom at the initial presentation were retrospectively evaluated. The patients were followed-up ophthalmically until the end of treatment, and the complications and the remaining ophthalmological signs and symptoms were then recorded. The patients' ages ranged from 13 to 89 years, with an average of 55.78 (±20.73) years, and a predominance of 28 female (57.8 %) patients. The patients with a direct CCF had a lower average age (p = 0.02). The most common symptoms were blurred vision in 17 (36.2 %) and proptosis in 37 (78.7 %) patients. Elevated intraocular pressure (IOP) was more prevalent in patients with an indirect CCF (p = 0.02). Thrill was more prevalent in patients with direct CCF (p = 0.01). The presence of an initial decrease of visual acuity at the first ophthalmic evaluation was significantly associated with the persistence of ocular symptoms after fistula treatment (odds ratio 3.33). In conclusion our study shows a slight difference in ophthalmic symptoms among patients with different types of fistula. Elevated IOP was significantly associated with indirect fistulas, whereas thrill was significantly associated with direct fistulas. The presence of an initial decrease of visual acuity was significantly associated with a worse ophthalmic prognosis.

Intraoperative findings during temporal artery biopsy: keys to optimise the diagnosis of giant cell arteritis.

The objective of this study was to describe the perioperative findings during temporal artery biopsy (TAB) and the characteristics associated with a diagnosis of giant cell arteritis (GCA). Perioperative findings were prospectively described by a single operator blinded to the clinical and laboratory characteristics of the patients on 40 consecutive TABs, of which 21 were positive (53%) for GCA. Patients with a TAB positive for GCA (TAB+) more frequently had abnormalities on palpation of the temporal artery than negative TAB (TAB-) patients (mainly pulse abolition (p=0.007), indurated artery (p=0.002), and painful artery (p=0.021)). The appearance of a big artery (p<0.001), a thickened artery (p<0.001), and an indurated artery at incision (p<0.001) was significantly associated with a positive TAB. A multivariate model identified a big artery, no local bleeding, and pain during artery traction as being associated with TAB positivity (sensitivity 71.4% and specificity 89.5%). The appearance of the temporal artery during TAB is important in predicting the positivity of the biopsy. Whether this should influence the optimal length of the TAB warrants a prospective study.