[A new era for glucagon-like peptide-1 receptor agonists]. / Une nouvelle ère pour les agonistes des récepteurs du glucagon-like peptide-1.

Glucagon-like peptide-1 (GLP-1) receptor agonists have a privileged place in the management of type 2 diabetes (T2D). They not only improve glucose control without inducing hypoglycaemia and trigger weight loss, but also protect against atherosclerotic cardiovascular disease. Increasing the dose of three of them (liraglutide, semaglutide, dulaglutide) allows better glycaemic results and of potential interest a greater weight reduction. Liraglutide at a daily dose of 3.0 mg and semaglutide at a weekly dose of 2.4 mg received the indication for the therapy of obesity. A recent innovation consists in the development of dual unimolecular agonists that target GLP-1 and GIP («glucose-dependent insulinotropic polypeptide¼) receptors (tirzepatide) or GLP-1 and glucagon receptors (cotadutide). Tirzepatide, in the SURPASS programme, showed impressive reductions in glycated haemoglobin level and body weight, greater than those observed with dulaglutide or semaglutide. Tirzepatide received the indication of the treatment of T2D and is currently tested in obesity (SURMOUNT programme). Interestingly, triagonists GIP/GLP-1/glucagon are currently developed for the management of T2D and obesity, with also perspectives for treating metabolic-associated fatty liver disease.

Les agonistes du glucagon-like peptide-1 (GLP-1) ont une place de choix dans la prise en charge des patients avec un diabète de type 2 (DT2). Non seulement ils améliorent le contrôle glycémique sans provoquer des hypoglycémies et font perdre du poids, mais ils protègent également contre les maladies cardiovasculaires athéromateuses. Une augmentation de la posologie de trois d'entre eux (liraglutide, sémaglutide, dulaglutide) a permis de meilleurs résultats glycémiques et surtout une plus grande perte pondérale. Le liraglutide, à la dose de 3,0 mg/jour, et le sémaglutide, à la dose de 2,4 mg/semaine, ont d'ailleurs reçu l'indication pour le traitement de l'obésité. Une innovation récente consiste dans le développement d'agonistes unimoléculaires doubles ciblant les récepteurs du GLP-1 et du GIP («glucose-dependent insulinotropic polypeptide¼) (tirzépatide) ou les récepteurs du GLP-1 et du glucagon (cotadutide). Le tirzépatide, dans le programme SURPASS, a montré des réductions importantes du taux d'hémoglobine glyquée et du poids corporel, supérieures à celles observées avec le dulaglutide ou le sémaglutide. Il a reçu l'indication du traitement du DT2 et est actuellement testé dans l'obésité (programme SURMOUNT). Des triagonistes GIP/GLP-1/glucagon sont également développés pour le traitement du DT2 et de l'obésité, avec des perspectives également dans la stéatopathie hépatique.

Plasma pharmacokinetics of bedaquiline administered by nasogastric tube in an intensive care unit.

We present the case of a 21-year-old man admitted to the intensive care unit with multi-organ failure due to multidrug-resistant tuberculosis (TB). TB treatment initially comprised moxifloxacin, ethambutol, linezolid and amikacin administered intravenously. Due to suspected moxifloxacin-induced liver injury, we stopped all fluoroquinolones and switched to bedaquiline (BDQ), which is only available in tablets for oral administration. Since our patient had to be fed through a nasogastric tube (NGT), BDQ was administered after being crushed and dissolved in water; drug pharmacokinetics were studied using repeated blood sampling. Therapeutic drug monitoring showed that BDQ was detectable in blood plasma with a trough concentration above the supposed efficacy threshold, suggesting that this molecule could be administered through NGT.

[Input of genetic analyses in the differential diagnosis of kidney cysts]. / Diagnostic différentiel des kystes rénaux : importance de l'approche génétique.

The incidental finding of renal cysts is a common clinical situation given their high prevalence (~ 50 % after the age of 50) and the continuous improvement of abdomen imaging. Diagnosis is central to appropriately dictate the management of the patient. During the diagnostic work-up, it is important to consider (i) the aspect of the cysts, (ii) their number, (iii) and their location, as well as (iv) the age of the patient and his/her personal and familial medical history, (v) the presence of extra-renal manifestations, (vi) and the renal function (including the urinary sediment). Starting from an atypical clinical case characterized by a rapidly evolving chronic kidney disease associated with bilateral renal cysts, we review the classical diagnostic work-up of kidney cysts. As a conclusion, we propose a diagnostic algorithm including both acquired and hereditary nephropathies.

La découverte, souvent fortuite, de kystes rénaux est une situation clinique fréquente vu leur prévalence élevée (~ 50 % dès l'âge de 50 ans) et les progrès de l'imagerie abdominale. Un diagnostic étiologique conditionnera la prise en charge et le pronostic du patient. Lors de la démarche diagnostique, il est important de considérer (i) l'aspect des kystes, (ii) leur nombre et (iii) leur localisation, ainsi que (iv) l'âge du patient et ses antécédents personnels et familiaux, (v) la présence de manifestations extrarénales et (vi) la fonction rénale et le sédiment urinaire. A partir d'un cas clinique inhabituel présentant une insuffisance rénale chronique rapidement progressive associée à des kystes rénaux, nous revoyons la mise au point classique des kystes rénaux. En guise de conclusion, nous proposons un algorithme diagnostique incluant les néphropathies acquises et héréditaires.

Sedation and analgesia in interventional radiology: Where do we stand, where are we heading and why does it matter?

The aims of this review were to describe the rationale and the techniques of sedation in interventional radiology, and to compile the safety and efficacy results available so far in the literature. A systematic MEDLINE/PubMed literature search was performed. Preliminary results from several studies demonstrated the feasibility, the efficacy and the safety of using sedative techniques in interventional radiology. Beyond pharmacological sedation and clinical hypnosis, digital sedation could reduce the anxiety and pain associated with interventional radiology procedures.

[Place of biomarkers in the management of pulmonary infections]. / Place des biomarqueurs dans la prise en charge des infections pulmonaires.

INTRODUCTION: The management of acute lower respiratory tract infections and, in particular, the decision whether or not to commence antibiotic therapy, still remains difficult in the absence of reliable clinical or radiological criteria allowing confident distinction between bacterial and viral infections. Numerous biomarkers have been developed to help the clinician in his/her diagnostic and therapeutic approach, but the role and significance of each has not been clearly defined. BACKGROUND: Though procalcitonin (PCT) or C-reactive protein (CRP) seem equal in helping the clinician to decide whether to commence antibiotic therapy or not during the course of an exacerbation of asthma or chronic obstructive pulmonary disease (COPD), PCT is currently the most useful biomarker to distinguish sepsis from other causes of inflammation and to determine the bacterial or viral origin of a pneumonia. OUTLOOK: The ability of PCT to reduce the global exposure to antibiotics remains uncertain and the results of randomised trials are contradictory. CONCLUSIONS: Prescription algorithms involving PCT may be used without increased risk for patients even though clinical signs of severity remain important. Changes in PCT also have a prognostic value in identifying those patients with unfavourable outcome.

[Mediastinal fat necrosis]. / Nécrose de la graisse médiastinale.

Epicardial fat necrosis is a rare cause of benign chest pain. Its physiopathological mechanism is unknown. Diagnosis is easily performed through radiological investigations that show a round opacity of fat density limited by a dense pseudo-capsule in the anterior mediastinum, close to the heart.

[Respiratory manifestations of Marfan's syndrome]. / Manifestations respiratoires du syndrome de Marfan.

Marfan's syndrome is a rare genetic disorder caused by a mutation of the gene FBN1, coding for the protein fibrillin-1. Cardiovascular, musculoskeletal and ophthalmic manifestations are the most commonly observed, but minor diagnostic criteria also include pulmonary manifestations. Pneumothorax, frequently relapsing, affects 5 to 11% of patients. Rib cage abnormalities (pectus excavatum or pectus carinatum) and apical blebs may contribute to their occurrence. Treatment does not require any specific procedure but there is an increased risk of recurrence. Pectus excavatum affects up to 60% of the patients, without any functional impairment in most cases. Surgery may be required (using the Nuss procedure) in case of cardiovascular or psychological symptoms. Marfan's syndrome is frequently associated with obstructive sleep apnoea, which may itself contribute to aortic dilatation. Some studies suggest a potential role of craniofacial abnormalities in the pathogenesis of sleep apnea in these patients. Pulmonologists should consider Marfan's syndrome when treating patients for recurrent spontaneous pneumothorax or rib cage abnormalities, since early detection of cardiac abnormalities improves the prognosis significantly.

Correlation between MRI and biopsies under second look ultrasound.

The term "second look" lesions in MRI refers to lesions detected by MRI that were not initially seen on mammography or ultrasound. The objectives of our study were to analyse the displacement of targets between MRI and ultrasound; to define discriminating BIRADS morphological criteria to predict benign or malignant character and better establish the indications of second look ultrasound and biopsy; and to analyse the agreement between ultrasound and MRI in terms of morphological criteria. A retrospective and monocentric review was performed of the records of consecutive patients with breast abnormalities (mass or non-mass) initially detected by MRI that were not initially seen on mammography or ultrasound. All patients with abnormalities found during the performance of second look ultrasound and biopsied were included in the study. All lesions were documented using the BIRADS lexicon for MRI and ultrasound. Of 100 included patients, 108 lesions were detected by MRI, found via second look ultrasound and biopsied between January 2008 and 2010. All of the included patients were followed-up for a variable period, from 2 to 5 years. Eighty-two upon 108 biopsied lesions (76%) were benign and 26/108 lesions (24%) were malignant. This study confirmed the switch from procubitus to decubitus essentially displaces the tumour in the antero-posterior direction. It showed that the risk factors were not reliable criteria for establishing an indication for second look ultrasound. This study also showed that circumscribed contours and a progressive enhancement curve (type I) for masses on MRI had the strongest negative predictive value of greater than 0.85. In ultrasound, the round or oval shape, circumscribed contours and the parallel orientation to the skin favoured benignity with a NPV of greater than 0.85. For masses, the study showed that the agreement in interpretation of the benign versus suspicious morphological criteria between the MRI and the ultrasound was very weak for the shape (Kappa=0.09) and weak for the contours (Kappa=0.23). Finally, the MRI overestimated the size of the targets compared to ultrasound (Student t-test, p=0.0001). The performance of second look ultrasound has to be performed after the detection of an abdnormality on MRI even for lesion classified BIRADS 3. The biopsy indications must be wide with insertion of a clip and a control MRI. Only this control allows to stop the investigation if the biopsied lesion is benign.

[Pneumocystis pneumonia in a patient treated with pemetrexed for non small cell lung cancer]. / Pneumocystose chez un patient traité par pemetrexed pour adénocarcinome pulmonaire.

INTRODUCTION: Pneumocystis pneumonia is a life-threatening infection in patients undergoing chemotherapy for solid malignancies. CASE REPORT: A 49-year-old man developed gradually increasing dyspnoea while receiving pemetrexed as a third line treatment for an adenocarcinoma of the lung. The diagnosis of pneumocystis pneumonia was based on ground-glass opacities on the thoracic CT scan and alveolar lavage revealing occasional cysts of Pneumocystis jiroveci in the context of recent lymphopenia developing during chemotherapy. Treatment with cotrimoxazole for three weeks was only partially successful due to progression of the tumour. CONCLUSIONS: Pneumocystis pneumonia should be considered in cancer patients receiving antifolate drugs and presenting with increasing dyspnoea. It is important to identify a high-risk population among patients undergoing chemotherapy because of the significant morbidity and mortality and in order to administer effective prophylactic agents.

[Blood gas and acid-base changes and rhythmologic tolerance of acetate and bicarbonate hemodialysis using a standard dialyser with high sodium and control of ultrafiltration]. / Modifications gazométriques et acido-basiques et tolérance rythmologique durant les hémodialyses acétate et bicarbonate sur dialyseur standard avec sodium élevé et maîtrise de l'ultrafiltration.

In order to demonstrate a possible superiority of bicarbonate dialysis (HDB) over acetate dialysis (HDA) in conditions of standard dialysis (4 hours on a 1 m2 cuprophan dialyser) but with a bath rich in sodium (143 mEq/l) and control of ultrafiltration, we have compared 2 sequences of 3 runs of HDA and HDB with these conditions in 8 patients as regards their acido-basic and cardiologic parameters (continuous monitoring of ECG by Holter, regular measurement of blood pressure). Acid base balance study in AHD led to the distinction of 2 groups according to wether their plasma bicarbonate increased or decreased during the run. Rythmological tolerance was the same in BHD and AHD, wether all patients or both groups were considered. Heart rate was however slightly but significantly higher during AHD than during BHD, in the patients whose plasma bicarbonate decreased. In conclusion, the benefit of HDB is not remarkable when HDA is performed not only in standard conditions but also with a bath rich in sodium and with control of ultrafiltration.