The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

Multi-omics correlates of insulin resistance and circadian parameters mapped directly from human serum.

While it is generally known that metabolic disorders and circadian dysfunction are intertwined, how the two systems affect each other is not well understood, nor are the genetic factors that might exacerbate this pathological interaction. Blood chemistry is profoundly changed in metabolic disorders, and we have previously shown that serum factors change cellular clock properties. To investigate if circulating factors altered in metabolic disorders have circadian modifying effects, and whether these effects are of genetic origin, we measured circadian rhythms in U2OS cell in the presence of serum collected from diabetic, obese or control subjects. We observed that circadian period lengthening in U2OS cells was associated with serum chemistry that is characteristic of insulin resistance. Characterizing the genetic variants that altered circadian period length by genome-wide association analysis, we found that one of the top variants mapped to the E3 ubiquitin ligase MARCH1 involved in insulin sensitivity. Confirming our data, the serum circadian modifying variants were also enriched in type 2 diabetes and chronotype variants identified in the UK Biobank cohort. Finally, to identify serum factors that might be involved in period lengthening, we performed detailed metabolomics and found that the circadian modifying variants are particularly associated with branched chain amino acids, whose levels are known to correlate with diabetes and insulin resistance. Overall, our multi-omics data showed comprehensively that systemic factors serve as a path through which metabolic disorders influence circadian system, and these can be examined in human populations directly by simple cellular assays in common cultured cells.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Population pharmacokinetic analysis of doravirine in real-world people with HIV.

AIMS: The pharmacokinetics of doravirine has been studied in clinical trials but not in real-world settings. Our study aims to characterize and identify factors influencing doravirine (a CYP3A4 substrate) pharmacokinetics in real-world people with HIV (PWH). METHODS: A total of 174 doravirine concentrations measured in 146 PWH followed up in the therapeutic drug monitoring (TDM) program at the University Hospital of Lausanne (Switzerland) between 2019 and 2023 were included in the analysis. Demographic data, clinical information and comedications were recorded during the routine SHCS visits (every 3-6 months). Population pharmacokinetic analysis and Monte Carlo simulations to investigate the clinical significance of the covariates retained in the final model were performed using NONMEM. RESULTS: A one-compartment model with first-order absorption and linear elimination best described doravirine pharmacokinetics. Potent CYP3A4 inhibitors and, to a lesser extent age, were the only tested covariates to significantly impact doravirine clearance (CL). Potent CYP3A4 inhibitors reduced CL by 50%, and a 30% decrease in CL was observed in an 80-year-old compared with a 55-year-old PWH. The effect of potent CYP3A4 inhibitors was prominent, explaining 59% of between-subject variability in CL. Model-based simulations predicted 2.8-fold and 1.6-fold increases in median steady-state trough and maximum doravirine concentrations, respectively, when a potent CYP3A4 inhibitor was co-administered. CONCLUSIONS: Our findings show that potent CYP3A4 inhibitors and age influence doravirine pharmacokinetics. However, given the good tolerability of doravirine, dosing adjustment of doravirine is probably not mandatory in those situations. TDM remains useful essentially in specific clinical situations, such as hepatic impairment, suspected nonadherence or pregnancy.

Women in acute forensic psychiatric care: comparison of clinical, sociodemographic, and detention-related characteristics in pretrial detention, sentence execution, and court-ordered treatment.

Compared to men inmates, women display decreased prevalence of severe mental disorder but increased occurrence of substance use disorders (SUD) and higher rates of previous contacts with mental health services. The group of women in detention is highly heterogeneous according to the status of incarceration (pre-trial detention (PTD), sentence execution (SE) and court ordered treatments (COT)). Studies focusing on the comparison of sociodemographic patterns, detention-related and clinical variables between these groups are still lacking. We explored these parameters in 136 women admitted for acute psychiatric care in the sole Geneva forensic unit during a nine year period (2014-2023). Sociodemographic and detention-related data included age, nationality, marital status, presence of children, education attainment, most frequently speaking language, social support, employment before conviction and type of offenses. Clinical variables included the main ICD-10 diagnosis, presence of concomitant SUD, type of personality disorders, presence of suicidal thoughts and attempts at admission, as well as number and mean duration of stays. PTD and SE women had at least 9 years of formal education in 38.9% and 30.3% of cases. Most women in PTD (77.7%), SE (56.6%) and COT (56.2%) groups were Swiss or European citizens. The level of French knowledge was excellent in most of the cases. 43.8% of COT women had at least one child and this percentage is even higher for PTD and SE cases. The employment rate before conviction was also quite high, mainly for PTD and SE (61.1% and 60.6%) and, in a lesser degree, for COT (43.8%) women. Significant social support was present in the vast majority of women without any significant group difference. The distribution of type of offenses did not differ between the three types of detention with a predominance of physical violence, and drug trafficking. The number of stays during the period of reference was significantly higher in COT compared to both SE and PTD women. History of previous inpatient care was also significantly more frequent in COT that SE and PTD women. Adjustment and affective disorders were more often found in SE and PTD cases, these diagnoses were absent in the COT group. In contrast, a main diagnosis of psychotic disorders was found in 62.5% of COT cases compared to only 21.2% in SE and 24.1% in PTD cases. The number of stays, history of inpatient care and diagnosis of psychosis were independent predictors of COT status. In conclusion, the present data reveal the good social integration and emotional support of women needing acute psychiatric care in prison independently of the type of detention. Clinically, women in PTD and SE display more often emotional distress whereas those in COT suffer from acute psychotic symptoms with previous history of psychiatric care and multiple inpatient stays.

Food for thought: Reinforced learning and recall of physical activity calorie equivalent (PACE) and numerical calorie content in an associative learning task.

Calorie overconsumption has been proposed as a critical contributing factor to rising obesity rates. To combat this health issue, governments and policymakers have suggested implementing numerical caloric content labels. Alternatively, physical activity calorie equivalent (PACE) labels are being proposed as an easier-to-understand metric, representing the amount of physical activity required to burn off calorie content. This study examined individuals' ability to correctly estimate either the numerical caloric content or the PACE values of food images in an associative learning task. Moreover, it assessed whether this knowledge was learned and retained over time. One hundred and ninety-one participants were instructed to estimate either the numerical caloric content or PACE values of thirty food images. To facilitate learning, feedback on the correct number of calories or PACE values was provided during the first session (Time 1). To assess retention, people re-estimated numerical caloric content or PACE values of the same food pictures three days later (Time 2) and seven days later (Time 3), where feedback was not provided. Results showed that participants in both groups improved their estimations using feedback, with people being consistently more accurate when estimating numerical calorie content. Yet, our results also suggest that participants consolidated their knowledge of PACE values over time. Finally, our findings show that hunger moderates individuals' estimation ability, where hungrier people are less accurate than satiated ones. The results contribute to our understanding of how consumers process, estimate, and learn PACE labels versus numerical caloric content, and provide valuable information for researchers and policymakers to develop and implement nutritional labels as a health strategy.

CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.

INTRODUCTION: As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia. METHODS: Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons. RESULTS: CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5-/- mice neurons. DISCUSSION: We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.

Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Exploring Twitter chatter to assess the type and availability of cannabis-related products in Thailand.

Cannabis-related tweets were collected between January and April 2022 to estimate the availability and characteristics of cannabis products advertised on Twitter amid the legalization of recreational cannabis in Thailand. The Twitter API was called using the tweepy Python library to collect cannabis-related tweets in the Thai language. A total of 185,558 unique tweets were collected over the duration of the data collection period based on 83 search terms. Twenty thousand random tweets were manually coded by four Thai native speakers to assess the volume and characteristics of tweets proposing cannabis. 72.6% of collected tweets from the 20,000 random samples were coded as relevant to the study. 54.6% of relevant tweets were advertising cannabis products, 29.8% were personal communications, and 15.6% were related to news or media content. Among the tweets that advertised cannabis products, 94.4% proposed cannabis flower, 2.4% cannabis edibles and 1.8% cannabis concentrates. Consumption of potent forms of cannabis such as cannabis edibles and concentrates increase the risk of harmful side-effects, especially in a population with limited knowledge about these products. Our findings call for additional monitoring efforts and for increasing the public awareness on potent cannabis products emerging in Thailand.

[Diabetic gastroparesis and type 1 diabetes]. / Gastroparésie diabétique et diabète de type 1.

Gastroparesis is a rare and late microvascular complication, but a significant one of diabetes. Defined by a slowing of gastric emptying, this condition manifests with nonspecific gastrointestinal symptoms, including nausea, vomiting, abdominal pain, postprandial fullness, and early satiety. Faced with such a clinical presentation, it is often challenging to diagnose gastroparesis. In this article, we discuss the diagnostic procedures, as well as therapeutic approaches and management of the disease.

La gastroparésie est une complication microvasculaire rare et tardive, mais conséquente, du diabète. Définie par un ralentissement de la vidange gastrique, cette pathologie se présente sous la forme de symptômes gastro-intestinaux aspécifiques incluant des nausées, des vomissements, des douleurs abdominales, une sensation de réplétion postprandiale et une satiété précoce. Face à une présentation clinique de ce type, il est souvent difficile de poser le diagnostic de gastroparésie. Dans cet article, nous évoquons donc les examens complémentaires permettant de poser le diagnostic, ainsi que les propositions thérapeutiques et la prise en charge de la maladie.

[Diabetology: what's new in 2023]. / Diabétologie: ce qui a changé en 2023.

Diabetology is a continuously evolving discipline, many molecules are developed and treatment recommendations change often according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to guide the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2023 novelties in the field of diabetes.

La diabétologie est une discipline en évolution continue, de nombreuses molécules sont développées et les recommandations de traitement changent fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures du style de vie qu'il faut toujours privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 ou un agoniste du récepteur du GLP-1 après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est de fournir une aide au médecin de premier recours dans le choix du traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2023 dans le domaine du diabète.

[Obstetrics and Gynecology. Management and screening for gestational diabetes : what's new in 2023]. / Gynécologie-obstétrique. Prise en charge et dépistage du diabète gestationnel : ce qui a changé en 2023.

Gestational diabetes (GDM) is becoming increasingly common as a result of the increase in overweight, obesity and maternal age among pregnant women. As a result, in order to provide early hygienic and dietary management, it is recommended that targeted screening be carried out in the first trimester of pregnancy, based on the identification of risk factors in women. In the absence of risk factors, screening for gestational diabetes should be carried out for all pregnant women between 24 and 28 weeks' gestation. During pregnancy, the safest pharmacological treatment remains insulin, and the term of delivery should take account of additional risk factors, insulin requirements, fœtal growth kinetics and the balance of GDM. In the longer term, gestational diabetes should be regarded as a metabolic and cardiovascular warning sign.

Dû à l'augmentation du surpoids, de l'obésité et de l'âge maternel chez les femmes enceintes, le diabète gestationnel (DG) est de plus en plus fréquent. De ce fait, afin d'offrir une prise en charge hygiénodiététique précoce, il est recommandé d'effectuer un dépistage ciblé au premier trimestre de la grossesse pour identifier les facteurs de risque. En leur absence, le dépistage du DG doit être réalisé chez toutes les femmes enceintes entre 24 et 28 SA. Au cours de la grossesse, le traitement pharmacologique le plus sécuritaire reste l'insuline et le terme d'accouchement doit tenir compte des facteurs de risque surajoutés, des besoins en insuline, de la cinétique de croissance fœtale et de l'équilibre du DG. À plus long terme, le DG doit être considéré comme une alerte métabolique et cardiovasculaire.

[Court-ordered inpatient psychiatric care in Switzerland. Length of stay and treatment outcome]. / Thérapies sous mandat pénal en Suisse. Population clinique, durées de séjour et destinations de sortie.

Mentally disordered offenders may be convicted to court-ordered psychiatric-psychotherapeutic inpatient care. Based on the concept of a forensic therapeutic community, the treatments of 204 inmates of a medium-security hospital, who presented with psychosis, personality disorders or substance-use disorders, have been assessed. After a median stay of 2.5 years, 56% of the offenders had been transferred to a sheltered educational housing or to an open low-security psychiatric ward. Length of stay was independent of psychiatric diagnosis, yet dependent on the nature of the offense. Having a cluster B personality disorder or a conviction for a sexual offense increased the risk of return to prison. Younger age and offenses without interpersonal violence increased the chances to enter sheltered educational housing.

Les auteurs d'infractions atteints d'un trouble mental sévère peuvent être soumis à un traitement psychiatrique-psychothérapeutique par ordonnance pénale. Basés sur le concept de la communauté thérapeutique forensique, les suivis de 204 détenus-patients atteints d'un trouble psychotique ou de la personnalité ou encore d'une dépendance aux substances ont été évalués. Après un séjour médian de 2,5 ans, 56 % ont été transférés dans un foyer socioéducatif ou une unité psychiatrique hors prison. La durée de séjour est indépendante du diagnostic psychiatrique mais dépend du type de délit. Un diagnostic de trouble de la personnalité cluster B ou une infraction sexuelle augmentent la probabilité de retourner en prison. Un jeune âge et un délit sans violence interpersonnelle favorisent une sortie en foyer.

[Pharmacovigilance. Withdrawal and rebound effects: not just with psychotropic drugs]. / Pharmacovigilance. Sevrage et effet rebond: pas seulement avec les psychotropes.

The list of drugs whose abrupt discontinuation is likely to induce withdrawal symptoms or a rebound in the pathology being treated is not limited to psychotropic drugs. It includes a number of somatic drugs (e.g. proton pump inhibitors, opioids, triptans, fingolimod, corticosteroids, antiepileptics, nootropics, antiparkinsonians, denosumab, beta-blockers, laxatives, nasal vasoconstrictors, etc.). This type of unintended effect, often underestimated, generally results from a drug-induced homeostatic imbalance that persists after the drug has been discontinued. Taking this risk into account right from the initial prescription should make it possible to prevent such complications, by encouraging intermittent use of the drug, or by applying a very gradual reduction in dosage when a regular treatment is stopped.

La liste des médicaments dont l'arrêt brusque est susceptible d'entraîner des symptômes de sevrage ou un rebond de la pathologie traitée ne se limite pas aux psychotropes, mais inclut un certain nombre de médicaments somatiques (inhibiteurs de la pompe à protons, opioïdes, triptans, fingolimod, corticostéroïdes, antiépileptiques, nootropes, antiparkinsoniens, dénosumab, bêtabloquants, laxatifs, vasoconstricteurs nasaux, etc.). Ce type d'effet indésirable, souvent méconnu, résulte en général d'un déséquilibre homéostatique causé par le médicament, persistant après son interruption. La prise en compte de ce risque dès la prescription initiale devrait permettre de prévenir ces complications, en privilégiant un recours intermittent au médicament ou en prévoyant une diminution très progressive des posologies au moment de mettre un terme à un traitement continu.

Enhanced temporal resolution of vision in action video game players.

Video game play has been suggested to improve visual and attention processing. Nevertheless, while action video game play is highly dynamic, there is scarce research on how information is temporally discriminated at the millisecond level. This cross-sectional study investigates whether temporal discrimination at the millisecond level in vision varies across action video game players (VGPs; N = 23) and non-video game players (NVGPs; N = 23). Participants discriminated synchronous from asynchronous onsets of two visual targets in virtual reality, while their EEG and oculomotor movements were recorded. Results show an increased sensitivity to short asynchronies (11, 33 and 66 ms) in VGPs compared with NVGPs, which was especially marked at the start of the task, suggesting better temporal discrimination abilities. Pre-targets oculomotor freezing - the inhibition of small fixational saccades - was associated with correct temporal discrimination, probably revealing attentional preparation. However, this parameter did not differ between groups. EEG and reconstruction analyses suggest that the enhancement of temporal discrimination in VGPs during temporal discrimination is related to parieto-occipital processing, and a reduction of alpha-band (8-14 Hz) power and inter-trial phase coherence. Overall, the study reveals an enhanced ability in action video game players to discriminate in time visual events in close temporal proximity combined with reduced alpha-band oscillatory activities. Consequently, playing action video games is associated with an improved temporal resolution of vision.

Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort.

BACKGROUND: Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs). METHODS: This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence. RESULTS: Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months). CONCLUSIONS: Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Tool use acquisition induces a multifunctional interference effect during object processing: evidence from the sensorimotor mu rhythm.

A fundamental characteristic of human development is acquiring and accumulating tool use knowledge through observation and sensorimotor experience. Recent studies showed that, in children and adults, different action possibilities to grasp-to-move and grasp-to-use objects generate a conflict that extinguishes neural motor resonance phenomena during visual object processing. In this study, a training protocol coupled with EEG recordings was administered in virtual reality to healthy adults to evaluate whether a similar conflict occurs between novel tool use knowledge. Participants perceived and manipulated two novel 3D tools trained beforehand with either single or double-usage. A weaker reduction of mu-band (10-13 Hz) power, accompanied by a reduced inter-trial phase coherence, was recorded during the perception of the tool associated with the double-usage. These effects started within the first 200 ms of visual object processing and were predominantly recorded over the left motor system. Furthermore, interacting with the double usage tool delayed grasp-to-reach movements. The results highlight a multifunctional interference effect, such as tool use acquisition reduces the neural motor resonance phenomenon and inhibits the activation of the motor system during subsequent object recognition. These results imply that learned tool use information guides sensorimotor processes of objects.

Determinants of clinical outcome and length of stay in acute care forensic psychiatry units.

Criminological and sociodemographic variables, such as previous criminal convictions, increased risk of violence, early onset of mental disorder, antisocial personality, psychosis and low social support, have all been related to longer length of stay (LoS) and poorer outcome in long stay forensic services. The factors impacting on LoS and clinical response in acute care specialized units are poorly documented. To address this issue, we examined the psychiatric records of all cases admitted between January 1st and December 31th 2020 in the sole acute ward for detained persons located in the central prison of the Geneva County, Switzerland. Information on judicial status included pre-trial versus sentence execution, previous incarcerations, and age of the first incarceration. Sociodemographic data included age, gender, marital status, and education attainment. Previous inpatient stays prior to incarceration were recorded. All of the ICD-10 clinical diagnoses were made by two independent, board-certified psychiatrists blind to the scope of the study. The standardized assessment was based on the HoNOS (Health of Nation Outcome Scales) at admission and discharge, HONOS-secure at admission, HCR-20 (Historical Clinical Risk 20) version 2, PCL-R (Psychopathy Checklist Revised), and SAPROF (Structured Assessment of Protective Factors). Stepwise forward multiple linear regression models predicting the LoS and delta HONOS respectively were built with the above mentioned parameters. The selected variables were then used in univariate and multivariable regression models. Higher HCR-scores (mainly on clinical items), and longer LoS were related to higher delta HONOS scores. In contrast, cases in pre-trial detention showed a worst clinical outcome. In multivariable models, all three variables remained independent predictors of the clinical outcome and explained 30.7% of its variance. Only education and diagnosis of borderline personality were related to the LoS and explained 12.6% of its variance in multivariable models. Our results suggest that the use of acute wards specialized in forensic psychiatry are mainly useful for patients with prior inpatient care experience, and higher violence risk during sentence execution. In contrast, they seem to be less performant for persons in pre-trial detention that could benefit from less restrictive clinical settings.

Role of Oxidative Stress and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify two main factors that play a crucial role in the pathophysiology of NAFLD: oxidative stress and the key role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.