Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort.

Background: Despite numerous observations of neuropsychological deficits immediately following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, little is known about what happens to these deficits over time and whether they are affected by changes in fatigue and any psychiatric symptoms. We aimed to assess the prevalence of neuropsychological deficits at 6-9 months and again at 12-15 months after coronavirus disease 2019 (COVID-19) and to explore whether it was associated with changes in fatigue and psychiatric symptoms. Methods: We administered a series of neuropsychological tests and psychiatric questionnaires to 95 patients (mean age = 57.12 years, standard deviation (SD) = 10.68; 35.79% women) 222 (time point 1 (T1)) and 441 (time point 2 (T2)) days on average after infection. Patients were categorised according to the severity of their respiratory COVID-19 symptoms in the acute phase: mild (no hospitalisation), moderate (conventional hospitalisation), and severe (hospitalisation in intensive care unit (ICU) plus mechanical ventilation). We ran Monte-Carlo simulation methods at each time point to generate a simulated population and then compared the cumulative percentages of cognitive disorders displayed by the three patient subgroups with the estimated normative data. We calculated generalised estimating equations for the whole sample to assess the longitudinal associations between cumulative neuropsychological deficits, fatigue, and psychiatric data (anxiety, depressive symptoms, posttraumatic stress disorder, and apathy). Results: Most participants (>50%) exhibited a decrease in their neuropsychological impairments, while approximately 25% showed an escalation in these cognitive deficits. At T2, patients in the mild subgroup remained free of accumulated neuropsychological impairments. Patients with moderate severity of symptoms displayed a decrease in the magnitude of cumulative deficits in perceptual and attentional functions, a persistence of executive, memory and logical reasoning deficits, and the emergence of language deficits. In patients with severe symptoms, perceptual deficits emerged and executive deficits increased, while attentional and memory deficits remained unchanged. Changes in executive functions were significantly associated with changes in depressive symptoms, but the generalised estimating equations failed to reveal any other significant effect. Conclusion: While most cumulative neuropsychological deficits observed at T1 persisted and even worsened over time in the subgroups of patients with moderate and severe symptoms, a significant proportion of patients, mainly in the mild subgroup, exhibited improved performances. However, we identified heterogeneous neuropsychological profiles both cross-sectionally and over time, suggesting that there may be distinct patient phenotypes. Predictors of these detrimental dynamics have yet to be identified.

[Selected novelties for hospital based internal medicine]. / Nouveautés en médecine interne hospitalière.

In this selective overview of articles, we describe new concepts, therapeutic measures and pharmacological agents that may modify current practice in clinical internal medicine. Novelties for the management of cardiovascular disease, such as heart failure, hypoxemic respiratory failure, nosocomial pneumonia and certain allergies are discussed.

À travers quelques articles et études choisis, cet article décrit de nouveaux concepts, mesures thérapeutiques et agents pharmacologiques pouvant modifier les pratiques courantes en médecine interne. Des notions concernant la gestion de maladies cardiovasculaires telles que l'insuffisance cardiaque, les décompensations respiratoires hypoxémiques, les pneumonies nosocomiales et la gestion d'allergies y figurent au premier plan.

[Treatment of pleural space infections]. / Prise en charge des infections de l'espace pleural.

Pleural space infections occur in approximately 10% of patients hospitalized for pneumonia and their incidence is increasing with an aging population. Pulmonary ultrasound is a good bedside diagnostic tool able to reduce complications associated with thoracocentesis and drainage. The RAPID score is being increasingly validated as a predictor for mortality but has not yet been proven useful to guide the treatment strategy and needs incorporation into prospective studies. Awaiting studies on outcome prediction and the comparison of an early surgical strategy versus drainage with intrapleural enzyme therapy, this article presents a summary of current knowledge of this complication.

Les infections de l'espace pleural surviennent chez environ 10 % des patients hospitalisés pour une pneumonie. Leur incidence est en augmentation, en parallèle du vieillissement de la population. L'échographie pleuropulmonaire est un outil diagnostique sensible, directement accessible au lit du malade et permettant de diminuer les complications du drainage grâce au guidage. Le score RAPID a été validé pour prédire la mortalité liée à l'infection de l'espace pleural mais son utilité pour sélectionner la meilleure stratégie thérapeutique reste encore à démontrer. Dans l'attente des résultats d'une étude prospective randomisée comparant une prise en charge chirurgicale précoce au drainage avec fibrinolyse, cet article présente l'état des connaissances concernant le traitement de cette affection.

[Diagnosis of asthma: new developments in general internal medicine]. / Diagnostic de l'asthme : nouveautés pour la médecine interne générale.

Asthma, a chronic inflammatory lung disease affecting about 10 % of the population, involves both the general internist and the pulmonologist. The risk of over and underdiagnosis generates significant health costs and evitable clinical consequences. Improved screening through dedicated anamneses and questionnaires, as well as use of fractional exhaled nitric oxide (FeNO) may improve the diagnosis of asthma in general internal medicine.

L'asthme, maladie pulmonaire inflammatoire chronique affectant environ 10 % de la population, implique autant la médecine interne générale (MIG) que la pneumologie. Les risques de sous- et surdiagnostic engendrent d'importants coûts et conséquences cliniques évitables. Améliorer le dépistage lors de l'anamnèse avec l'utilisation de questionnaires dédiés et lors des examens fonctionnels par l'utilisation de la mesure de la fraction exhalée de l'oxyde nitrique pourrait être la clé d'un meilleur diagnostic de l'asthme en MIG.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

Validation of sham treatment in hyperbaric medicine: a randomised trial.

INTRODUCTION: This study aimed to determine the lowest possible atmospheric pressure in the 111-152 kPa (1.1-1.5 atmospheres absolute [atm abs]) range that would require the patients to equalise their ears, allowing an effective sham for a 203 kPa (2.0 atm abs) hyperbaric exposure. METHODS: We performed a randomised controlled study on 60 volunteers divided into 3 groups (compression to 111, 132 and 152 kPa (1.1, 1.3, 1.5 atm abs) to determine the minimum pressure to obtain blinding. Secondly, we applied additional blinding strategies (faster compression with ventilation during the fictitious compression time, heating at compression, cooling at decompression) on 25 new volunteers in order to enhance blinding. RESULTS: The number of participants who did not believe they had been compressed to 203 kPa was significantly higher in the 111 kPa compressed arm than in the other two arms (11/18 vs 5/19 and 4/18 respectively; P = 0.049 and P = 0.041, Fisher's exact test). There was no difference between compressions to 132 and 152 kPa. By applying additional blinding strategies, the number of participants who believed they had been compressed to 203 kPa increased to 86.5 %. CONCLUSIONS: A compression to 132 kPa, (1.3 atm abs, 3 metres of seawater equivalent) combined with the additional blinding strategies of forced ventilation, enclosure heating and compression in five minutes, simulates a therapeutic compression table and can be used as a hyperbaric placebo.

[Advances in hospital based internal medicine]. / Nouveautés en médecine interne hospitalière.

Hospital based internal medicine has been strongly solicited for over two years with the SARS-CoV-2 epidemic. This epidemic continues to evolve and represents a strain for public health. Numerous studies have addressed issues concerning this epidemic, and multiple novelties concerning other frequent pathologies have also been published. Management strategies of cardiovascular, pulmonary, gastro-intestinal and metabolic diseases are discussed.

La médecine interne hospitalière a été fortement sollicitée depuis 2 ans avec l'épidémie de SARS-CoV-2. Celle-ci continue d'évoluer et reste une épreuve pour la santé publique. Une pléthore d'études a tenté de résoudre les multiples défis que représente cette épidémie, mais de multiples nouveautés concernant d'autres pathologies fréquentes sont également apparues. La prise en charge des maladies cardiovasculaires, pulmonaires, gastro-intestinales et métaboliques est évoquée.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

[Diabetes and pancreatic cancer - When diabetes indicates a pancreatic cancer]. / Diabète et cancer du pancréas - Quand le diabète est annonciateur de cancer pancréatique.

Diabetes and pancreatic cancer have an intricate relationship where each is a risk factor for developing the other. In case of type 2 diabetes, there is an increased probability of developing pancreatic cancer. Similarly, the onset of diabetes often precedes the diagnosis of pancreatic cancer. Since hyperglycemia is secondary to tumor involvement of the exocrine pancreas, diabetes is considered pancreatogenic. In the current classification, it is part of the entities belonging to type 3c diabetes. The pathophysiology is specific, characterized by a high glycemic variability and a tendency to weight loss. Early identification of inaugural type 3c diabetes would reduce diagnostic delays and could optimize oncologic management. In the absence of specific markers, the challenge for the clinician is indisputable.

Diabète et cancer du pancréas entretiennent une relation intriquée où chacun constitue un risque de développer l'autre. En cas de diabète de type 2, le risque de cancer augmente. La survenue d'un diabète précède aussi souvent le diagnostic de cancer du pancréas. L'hyperglycémie étant secondaire à l'atteinte tumorale du pancréas exocrine, ce diabète est considéré comme pancréatogénique. Dans la dénomination actuelle, il fait partie des entités appartenant au diabète de type 3c. La pathophysiologie est spécifique, caractérisée par une forte variabilité glycémique et une tendance à la perte de poids. Distinguer précocement les diabètes inauguraux de type 3c permettrait de réduire les délais diagnostiques et d'optimiser la prise en charge oncologique. En l'absence de marqueurs spécifiques, le challenge est indiscutable pour le clinicien.

[Healing communication: Therapeutic communication in internal medicine]. / La « communication thérapeutique ¼ en médecine interne.

Caregiver-patient communication is a central element of the therapeutic relationship and a powerful placebo. While poorly adapted communication can have harmful effects, adequate communication offers many benefits for the patient and the caregiver. Therapeutic communication (TC), a set of strategies inspired by clinical hypnosis, is easy to learn and apply. In addition to reinforcing an empathetic attitude, TC appears to be effective in various clinical situations, particularly for its effects on pain and anxiety. In order to better understand the interest of CT in internal medicine, we have conducted a literature review on its efficacy during different medical procedures.

La communication soignant-e/soigné-e est un élément central de la relation thérapeutique et un puissant placebo dont il serait dommage de se priver. Mal adaptée, elle peut avoir des effets néfastes, efficace, elle offre de nombreux bénéfices pour les patient-e-s et soignant-e-s. La communication thérapeutique (CT), un ensemble de stratégies inspirées de l'hypnose clinique, est facile à apprendre et à appliquer. En plus de renforcer une attitude empathique, la CT semble efficace dans diverses situations cliniques, notamment pour ses effets sur la douleur et l'anxiété. Dans le but de mieux comprendre l'intérêt de la CT en médecine interne, nous avons effectué une revue de littérature démontrant son utilisation lors de gestes techniques auxquels les patient-e-s sont fréquemment confronté-e-s.

[VEXAS syndrome : when do we have to consider it ?] / Syndrome VEXAS : quand y penser ?

VEXAS syndrome was recently discovered in patients who developed late in adulthood an inflammatory syndrome with fever, cytopenias, dysplastic bone marrow, cutaneous and pulmonary neutrophilic inflammation, arthritis, chondritis, or vasculitis. It is the result of an inactivating somatic mutation affecting methionine codon 41 of the UBA1 gene which encodes an ubiquitin activating enzyme (E1). Systemic corticosteroids generally reduce symptoms, while other immunosuppressive drugs only have limited long-term effects. Azacitidine is a promising treatment, but further studies are warranted. Here, we describe 2 new cases including one associated with pyoderma gangrenosum and cryoglobulinemia.

Le syndrome VEXAS (Vacuoles, E1 Enzyme, X-Linked, Auto- Inflammatory, Somatic Syndrome) a été récemment découvert chez des patients développant tardivement à l'âge adulte un syndrome inflammatoire associé à de la fièvre, des cytopénies, une moelle osseuse dysplasique, une inflammation neutrophilique cutanée et pulmonaire, des arthrites, des chondrites ou des vasculites. Il est le résultat d'une mutation somatique inactivatrice affectant le codon méthionine 41 du gène UBA1 qui encode une enzyme E1 activant l'ubiquitine. Les corticostéroïdes systémiques permettent généralement de diminuer les symptômes alors que les autres immunosuppresseurs ont un effet limité à long terme. L'azacitidine est l'un des traitements ayant démontré une efficacité, cependant de nouvelles études sont souhaitables. Nous décrivons ici 2 cas dont l'un est associé à un pyoderma gangrenosum et une cryoglobulinémie.

Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?

Lack of awareness of cognitive impairment (i.e. anosognosia) could be a key factor for distinguishing between neuropsychological post-COVID-19 condition phenotypes. In this context, the 2-fold aim of the present study was to (i) establish the prevalence of anosognosia for memory impairment, according to the severity of the infection in the acute phase and (ii) determine whether anosognosic patients with post-COVID syndrome have a different cognitive and psychiatric profile from nosognosic patients, with associated differences in brain functional connectivity. A battery of neuropsychological, psychiatric, olfactory, dyspnoea, fatigue and quality-of-life tests was administered 227.07 ± 42.69 days post-SARS-CoV-2 infection to 102 patients (mean age: 56.35 years, 65 men, no history of neurological, psychiatric, neuro-oncological or neurodevelopmental disorder prior to infection) who had experienced either a mild (not hospitalized; n = 45), moderate (conventional hospitalization; n = 34) or severe (hospitalization with intensive care unit stay and mechanical ventilation; n = 23) presentation in the acute phase. Patients were first divided into two groups according to the presence or absence of anosognosia for memory deficits (26 anosognosic patients and 76 nosognosic patients). Of these, 49 patients underwent an MRI. Structural images were visually analysed, and statistical intergroup analyses were then performed on behavioural and functional connectivity measures. Only 15.6% of patients who presented mild disease displayed anosognosia for memory dysfunction, compared with 32.4% of patients with moderate presentation and 34.8% of patients with severe disease. Compared with nosognosic patients, those with anosognosia for memory dysfunction performed significantly more poorly on objective cognitive and olfactory measures. By contrast, they gave significantly more positive subjective assessments of their quality of life, psychiatric status and fatigue. Interestingly, the proportion of patients exhibiting a lack of consciousness of olfactory deficits was significantly higher in the anosognosic group. Functional connectivity analyses revealed a significant decrease in connectivity, in the anosognosic group as compared with the nosognosic group, within and between the following networks: the left default mode, the bilateral somatosensory motor, the right executive control, the right salient ventral attention and the bilateral dorsal attention networks, as well as the right Lobules IV and V of the cerebellum. Lack of awareness of cognitive disorders and, to a broader extent, impairment of the self-monitoring brain system, may be a key factor for distinguishing between the clinical phenotypes of post-COVID syndrome with neuropsychological deficits.

[Latest progress in internal medicine]. / Avancées récentes en médecine interne.

Internal medicine continues de evolve as a result of further insight and evidence for the efficacy of given interventions. Although numerous studies have addressed issues concerning the SARS-COV-2 epidemic, multiple novelties concerning other frequent pathologies have also been presented. Management strategies of cardiovascular disease, infectious diseases and venous thromboembolism are particularly concerned.

La médecine interne continue d'évoluer au fur et à mesure de nouvelles évidences d'efficacité par rapport aux diverses interventions. Une pléthore d'études a tenté de résoudre les multiples défis que représente l'épidémie au SARS-CoV-2, mais de multiples nouveautés concernant d'autres pathologies fréquentes sont également apparues. La prise en charge des maladies cardiovasculaires, de maladies infectieuses et la maladie thromboembolique sont particulièrement concernées.