Insights into the interaction between time and reward prediction on the activity of striatal tonically active neurons: A pilot study in rhesus monkeys.

Prior studies have documented the role of the striatum and its dopaminergic input in time processing, but the contribution of local striatal cholinergic innervation has not been specifically investigated. To address this issue, we recorded the activity of tonically active neurons (TANs), thought to be cholinergic interneurons in the striatum, in two male macaques performing self-initiated movements after specified intervals in the seconds range have elapsed. The behavioral data showed that movement timing was adjusted according to the temporal requirements. About one-third of all recorded TANs displayed brief depressions in firing in response to the cue that indicates the interval duration, and the strength of these modulations was, in some instances, related to the timing of movement. The rewarding outcome of actions also impacted TAN activity, as reflected by stronger responses to the cue paralleled by weaker responses to reward when monkeys performed correctly timed movements over consecutive trials. It therefore appears that TAN responses may act as a start signal for keeping track of time and reward prediction could be incorporated in this signaling function. We conclude that the role of the striatal cholinergic TAN system in time processing is embedded in predicting rewarding outcomes during timing behavior.

[Prevalence of Bell's phenomenon and changes after surgery for aponeurotic ptosis]. / Prévalence du réflexe de Charles Bell et évolution postopératoire dans la chirurgie du ptosis aponévrotique.

BACKGROUND: Ptosis surgery is common in oculoplastics, and its most threatening complication is corneal ulceration. Several factors have been associated with postoperative corneal disorders, such as the strength of the orbicularis muscle, the type of surgery performed, and the Bell's phenomenon reflex (BPR). The goal of this study was to investigate the prevalence of physiological BPR, absence of BPR, and presence of inverse BP in patients undergoing surgery for aponeurotic ptosis. The changes in the BPR during the postoperative course as well as the occurrence of corneal complications were also studied. MATERIALS AND METHODS: A retrospective study was conducted at the University Hospital of Nice from January 2018 to December 2023. Patients operated on for aponeurotic ptosis were included. Patients with myogenic or neurogenic ptosis or with missing data were excluded. Data were recorded preoperatively and one month postoperatively and included: eyelid height, orbicularis muscle strength, prevalence of BPR, lack of BPR, inverse BPR, and postoperative corneal ulcer. RESULTS: Ninety-eight eyelids of 57 patients were included over the study period. Preoperatively, the prevalence of physiological BPR, no BPR, and inverse BPR were 71.4%, 18.4%, and 10.2%, respectively. At one month postoperatively, 30.6% of patients experienced a change in BPR (p=0.004). The postoperative prevalence of BPR, no BPR, and inverse BPR were 77.5%, 17.4%, and 5.1%, respectively. The rate of postoperative corneal ulcers was 1.02%. CONCLUSION: Among patients operated on for aponeurotic ptosis, the prevalence of physiological BPR was 71.4% preoperatively. Approximately one-third of patients experienced a change in BPR one month postoperatively with a postoperative physiological BPR prevalence of 77.5%. The rate of corneal complications was low.

Is Floppy Eyelid Syndrome predictive of Intraoperative Floppy Iris Syndrome? A prospective and translational study.

INTRODUCTION: Intraoperative floppy iris syndrome (IFIS) is defined as an excessive billowing of the iris during cataract surgery. Floppy eyelid syndrome is defined as an excessive hyperlaxity of the eyelids. Based in our daily experience, we suspected FES to be associated with IFIS. This association has been investigated. The goal of the study was to explore whether FES was predictive of IFIS. MATERIAL AND METHODS: We conducted a prospective observational single-center study at the University Hospital of Nice. IFIS and FES were investigated in patients undergoing cataract surgery from November 2019 to May 2021. In addition, tarsus and iris samples were harvested in 2 fresh cadavers, and Verhoeff staining was used to identify elastin fibers. RESULTS: We included 452 eyes (n=312 patients, 50.9% male) with a mean age of 71.7years (±11.4). IFIS was diagnosed in 88 (19.5%) patients, including 20 (4.4%) grade 1, 34 (7.5%) grade 2, and 33 (7.3%) grade 3. FES was diagnosed in 35 (7.7%) patients. PEX was found in 23 (5.1%) patients. On multivariate analysis, FES (P<0.001), pseudo exfoliation (P=0.017), intracameral dilatation (P<0.004), senior surgeons (P=0.009) and α1-ARA (P<0.001) were associated with IFIS. Elastin fibers were identified in small amounts in the tarsus samples but not in the iris samples. CONCLUSION: FES is predictive of IFIS. Surgeons should be aware of this association to prevent intraoperative complications.

Basic action protocol for the outpatient management of chronic heart failure of the Spanish Society of Internal Medicine.

Chronic heart failure (CHF) represents a challenge for the healthy system due to its high prevalence, high burden of morbidity and mortality, and high consumption of health resources. To address this problem, it is necessary to develop efficient management strategies that include both hospital care and outpatient care. The primary objective is to stabilize the patient and prevent decompensation, with the consequent improvement in quality of life, reduction in hospital admissions and emergency department care, and, consequently, reduction in healthcare costs. In this context, the heart failure and atrial fibrilation working group of the Spanish Society of Internal Medicine has developed a protocol for the management of outpatient CHF, that addresses, from the perspective of Internal medicine, all the problems suffered by the patient with CHF. This protocol aims to optimize pharmacological treatment, control cardiovascular risk factors and various comorbidities, educate the patient and their environment about the disease, promote adherence to treatment and stablish follow-up adapted to their condition.

Cardiac amyloidosis worsens prognosis in patients with heart failure: findings from the PREVAMIC study.

BACKGROUND AND OBJECTIVES: Cardiac amyloidosis (CA) is a common pathology in elderly patients that usually presents as heart failure (HF). However, it is not clear whether CA associated with HF has a worse prognosis compared with HF due to other etiologies. MATERIAL AND METHODS: Prospective, observational cohort study that recruited patients ≥65 years of age with HF in 30 Spanish centers. The cohort was divided according to whether the patients had AC or not. Patients were followed for 1 year. RESULTS: A total of 484 patients were included in the analysis. The population was elderly (median 86 years) and 49% were women CA was present in 23.8 % of the included patients. In the CA group, there was a lower prevalence of diabetes mellitus and valvular disease. At one year of follow-up, mortality was significantly more frequent in patients with CA compared to those without (33.0 vs.14.9%, p < 0.001). However, there were no differences between both groups in visits to the emergency room or readmissions. In the multivariate analysis, the variables that were shown to predict all-cause mortality at one year of follow-up were chronic kidney disease (HR 1.75 (1.01-3.05) p 0.045), NT-proBNP levels (HR 2.51 (1.46-4.30) p < 0.001), confusion (HR 2.05 (1.01-4.17), p 0.048), and the presence of CA (HR 1.77 (1.11-2.84), p 0.017). CONCLUSION: The presence of CA in elderly patients with HF is related to a worse prognosis at one year of follow-up. Early diagnosis of the pathology and multidisciplinary management can help improve patient outcomes.

The RICA-2 registry: design and baseline characteristics of the first 1,000 patients.

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a syndrome of epidemic proportions and one of the main reasons for hospital admission. Patient registries provide real-world clinical practice information which is complementary to clinical trials. RICA-2 is a registry of the Spanish Society of Internal Medicine. Its main goal is to know the clinical and epidemiological characteristics and prognostic factors of patients with HF treated in Internal Medicine Departments. The objective of this study is to present the design of the RICA-2, the baseline characteristics of the first 1000 patients included and their comparison with those of the historical cohort of the RICA registry. METHODS: Observational, multicentre and prospective study of patients with HF with the following inclusion criteria: age equal to or greater than 18 years old, diagnosis of HF according to the European Guidelines, indistinct inclusion in decompensation or stable phase, of patients with de novo HF or chronic HF, regardless of left ventricular ejection fraction, aetiology and comorbidities. RESULTS: RICA-2 patients have advanced age (83 years old) and 51% are women. The comorbidity burden is higher than in the RICA registry (5 points in the Charlson comorbidity index), with predominating chronic decompensated HF (74%), hypertensive aetiology (39%) and preserved ejection fraction (52%). Most patients are pre-frail or vulnerable and are at risk of malnutrition. CONCLUSION: The RICA-2 represents a contemporary cohort of patients that will provide us with clinical, epidemiological and prognostic information on patients with acute and chronic HF treated in Internal Medicine.

Clinical features, diagnosis, treatment, and course of ocular sarcoidosis with or without uveitis: A retrospective, comparative study.

OBJECTIVE: To evaluate and compare characteristics, diagnosis, treatment, visual prognosis, and course between ocular sarcoidosis with or without uveitis in a population in Southern France. METHODS: We retrospectively analyzed data from patients with ocular sarcoidosis in a tertiary eye care center in Nice from January 2003 to December 2021. The inclusion criterion was biopsy-proven ocular sarcoidosis according to IWOS criteria as the first clinical manifestation of sarcoidosis. RESULTS: A total of 25 patients were included. Twenty patients had uveitis (70% panuveitis, 20% intermediate uveitis, and 10% anterior uveitis) and five patients had non-uveitic ocular sarcoidosis (one patient with dacryoadenitis, one patient with orbital granuloma, two patients with palpebral granuloma, and one patient with episcleritis). Only the cases with uveitis had bilateral involvement (85% of cases). There was no significant difference in ethnicity, biopsy diagnosis, systemic manifestations, or treatment between the two groups. Final visual outcomes remained good for both groups, with 96% of patients with BCVA>20/50, with no significant difference. Patients with non-uveitic sarcoidosis experienced less recurrence on treatment (P=0.042) and more remission (P=0.038) than patients with uveitis. Eighty percent of patients with uveitis had at least three suggestive clinical intraocular signs meeting IWOS criteria. CONCLUSION: In this population in Southern France, uveitis was the most common presentation of ocular sarcoidosis. The type of ocular sarcoidosis does not appear to be correlated with the type of systemic manifestations, use of systemic therapy, or visual prognosis, but patients with non-uveitic ocular sarcoidosis appear to have a better course with fewer recurrences on treatment and more remission than patients with uveitic ocular sarcoidosis.

[Contribution of technological aids to the extraction of orbital foreign bodies]. / Apport des aides technologiques dans l'extraction des corps étrangers orbitaires.

BACKGROUND: Removal of orbital foreign bodies is a surgical challenge. The purpose of this study is to report our experience in the removal of orbital foreign bodies and to evaluate the usefulness of various technological aids in their removal. MATERIALS AND METHODS: We conducted a single-center retrospective study at Nice University Hospital (France) from January 2017 to December 2023. All patients undergoing surgery for an orbital foreign body during the study period were included. Data recorded included the nature of the orbital foreign body, its size, location, surgical route, outcome (success, partial success, failure), and technological aids used (intraoperative navigation, intraoperative imaging scope, orbital magnet). Concurrently, we designed a dedicated orbital magnet, which was tested in the anatomy laboratory and in two of our patients. RESULTS: Six patients, all young men, were included during the study period. Removal was successful, partially successful, or unsuccessful in one-third of cases, respectively. Failure was associated with orbital foreign bodies located in the intraconal or posterior orbital space. Preoperatively, the use of a "low-artifact" scanner allowed us to better determine the exact size and shape of the orbital foreign body. Intraoperative navigation was not accurate enough, due to the mobility of the orbital bodies within the orbital fat. In our experience, intraoperative scope imaging was more accurate. The use of a dedicated orbital magnet was successfully tested in the anatomy laboratory and allowed the removal of a small orbital foreign body in one of our patients. Intraoperative surgical videos are provided. CONCLUSION: Vegetal orbital foreign bodies must be systematically removed. Removal of non-vegetal orbital foreign bodies should be considered on a case-by-case basis based on their size, best assessed using a "low artifact" scanner, their location, and their intrinsic ferromagnetism. Intraoperative navigation does not appear useful, while intraoperative scope imaging does. A dedicated orbital magnet might be helpful in removing ferromagnetic orbital foreign bodies. However, an orbital magnet may be ineffective in removing intraorbital bullets, since they are made primarily of an alloy of copper and lead.

Sex differences in clinical characteristics and outcomes in the CLOROTIC (combining loop with thiazide diuretics for decompensated heart failure) trial.

AIMS: The addition of hydrochlorothiazide (HCTZ) to furosemide improved the diuretic response in patients with acute heart failure (AHF) in the CLOROTIC trial. Our aim was to evaluate if there were differences in clinical characteristics and outcomes according to sex. METHODS: This is a post-hoc analysis of the CLOROTIC trial, including 230 patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The primary and secondary outcomes included changes in weight and patient-reported dyspnoea 72 and 96 h after randomization, metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. The influence of sex on primary, secondary and safety outcomes was evaluated. RESULTS: One hundred and eleven (48%) women were included in the study. Women were older and had higher values of left ventricular ejection fraction. Men had more ischemic cardiomyopathy and chronic obstructive pulmonary disease and higher values of natriuretic peptides. The addition of HCTZ to furosemide was associated to a greatest weight loss at 72/96 h, better metrics of diuretic response and higher 24-h diuresis compared to placebo without significant differences according to sex (all p-values for interaction were not significant). Worsening renal function occurred more frequently in women (OR [95%CI]: 8.68 [3.41-24.63]) than men (OR [95%CI]: 2.5 [0.99-4.87]), p = 0.027. There were no differences in mortality or rehospitalizations at 30/90 days. CONCLUSION: Adding HCTZ to intravenous furosemide is an effective strategy to improve diuretic response in AHF with no difference according to sex, but worsening renal function was more frequent in women. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36.

Can 18F-FDG PET/CT findings be used to predict orbital tumor histology?

PURPOSE: To investigate whether 18F-FDG PET/CT might be useful to predict the histology of various orbital tumors based on the maximum standard uptake value (SUVmax) and the OMSUV (orbital max SUV)/MLSUV (mean liver SUV) ratio. PATIENTS AND METHODS: A retrospective single-center study was conducted between May 2019 and December 2020. Patients with an orbital mass who underwent preoperative 18F-FDG PET/CT followed by an orbital biopsy were included. Tumor histology was classified as follows: orbital inflammation, solid tumor, low-grade lymphoid tumor, and high-grade lymphoid tumor. Orbital tumors were also classified as indolent or aggressive. Data recorded included the orbital SUVmax, OMSUV/MLSUV ratio and additional extra-orbital SUV sites. RESULTS: Forty-five patients (24 men) were included. There were 15 (33.3%), 14 (31.1%), 9 (20%), and 7 (15.5%) cases of orbital inflammation, solid tumor, low-grade lymphoid tumor, and high-grade lymphoid tumor, respectively. No correlation was found between the OMSUV/MLSUV ratio and orbital SUVmax and tumor histology (Z = -0.77, Z = -0.6, Z = -1.6, and Z = 0.94, all P > 0.05, respectively). No correlation was found between the OMSUV/MLSUV ratio (Z = -1.42, P > 0.05) and orbital SUVmax (Z = -0.82, P > 0.05) and tumor aggressiveness (indolent versus aggressive). Subgroup analyses showed that SUVmax was predictive of lymphoma aggressiveness (P = 0.05) and was able to distinguish orbital cancers (all lymphomas+solid tumors) from benign tumors (P = 0.02). CONCLUSION: 18F-FDG PET/CT could not be used to predict the underlying orbital tumor histology. However, more aggressive tumors, especially high-grade lymphomas and cancers, tended to have a higher orbital SUVmax compared to indolent lesions.

Intraoperative iStent versus postoperative selective laser trabeculoplasty in early glaucoma patients undergoing cataract surgery: A retrospective comparative study.

PURPOSE: To compare the efficacy and safety of iStent inject® versus 360° selective laser trabeculoplasty (SLT) in patients with early glaucoma undergoing cataract surgery. METHODS: A retrospective non-randomized study was conducted in 73 eyes divided into two groups: cataract surgery+intraoperative iStent (n=40) versus cataract surgery+postoperative SLT at one month (n=33). The primary endpoint was intraocular pressure (IOP) lowering≥20% between baseline and 6 months postoperatively. The secondary endpoints were IOP lowering at 1, 6 and 12 months, and the mean number of IOP-lowering medications at 6 and 12 months. RESULTS: The mean baseline IOP was 19.1 mmHg with no significant difference between groups. The mean baseline number of IOP-lowering medications was higher in the iStent group (n=1.95) compared to the SLT group (n=1.53; P=0.04). At 6 months, 18 (60%) patients in the SLT group and 20 (51%) patients in the iStent group achieved IOP lowering≥20% with no significant difference between groups (P=0.431). At 6 months, no difference in the mean number of IOP-lowering medications was found between groups (-0.92 and -0.89 in the iStent and SLT groups, respectively). Similar results were found at 12 months. CONCLUSION: These results suggest similar safety and efficacy of intraoperative iStent and postoperative 360° SLT in lowering IOP and reducing glaucoma eye drops in early glaucoma patients undergoing cataract surgery. Treatment choice should be based on the ophthalmologist's experience and on the cost-benefit ratio.

[Current status of French oculoplastics in France and in Europe]. / État des lieux de l'oculoplastie française en France et en Europe.

INTRODUCTION: In 2023, oculoplastics in France is experiencing a paradox with an imbalance between demand and supply of trainees. The goal of this study is to establish a factual overview of oculoplastics in France, with its limitations, and make proposals to optimize this sector. METHODS: An observational study was conducted by compiling epidemiological data related to oculoplastics. This included full-time hospital practitioners (HPs) in French university hospitals (FUH), data from the distributed computerized system for health assessment (SIDES), the specialized cross-disciplinary training (FST) in oculoplastics, the interuniversity diploma (DIU) in oculoplastics, the French University Ophthalmologists College (COUF), and the French Society of Reconstructive and Aesthetic Ophthalmology (SOPREF). RESULTS: Of the 32 FUH, only 11 full-time HPs (among them 5 academic) are specialized in oculoplastics. Several "priority" regions are underrepresented in oculoplastic surgeons. The number of ophthalmology residency coordinators and residents participating in the oculoplastics FST are decreasing over time and favoring other subspecialties. On the SIDES platform dedicated to residents, 26 (11.5%) of the 226 courses are devoted to oculoplastics. The role of women in oculoplastics is also discussed. CONCLUSION: Despite offering quality theoretical training, the future of French oculoplastics is clouded by a lack of practical training. Corrective measures include increasing oculoplastic surgeons in the FUH, developing private practice fellowships, prioritizing residents from "priority" regions for the oculoplastics DIU, optimizing the inter-CHU network, creating innovative teaching resources, and organizing specific congresses for the residents.

Executive summary of the 2023 update on the consensus regarding basic conduct during hospital admission for patients with acute heart failure.

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge.