[The Internal medicine articles that struck us the most in 2021]. / Année 2021 mise en perspective par les internistes hospitaliers.

The year 2021 has seen many breakthroughs in general internal medicine, despite the ongoing COVID-19 pandemic, with multiple implications in our daily clinical practice. From shorter antibiotic treatment duration in community-acquired pneumonia, to new indications for colchicine treatment, without forgetting better targets of hemoglobin for transfusion, questioning of the interest of high dose vitamin D substitution when preventing falls in older patients and finally disappointing hopes for new indications of albumin substitution in cirrhosis, the literature is full of new evidence. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles, chosen, summarized, and commented for you.

L'année 2021, malgré la pandémie de Covid-19, a vu de nombreux progrès en médecine interne générale, avec de multiples implications pour notre pratique quotidienne. D'une durée diminuée d'antibiothérapie pour le traitement de la pneumonie communautaire à de nouvelles indications au traitement de colchicine, en passant par des précisions sur les cibles de transfusion érythrocytaire, ainsi qu'une remise en question de l'intérêt de la vitamine D à haute dose dans la prévention des chutes chez la personne âgée, et pour finir des espoirs déçus de nouvelle indication à la substitution d'albumine dans la cirrhose, les nouveautés abondent dans la littérature. Chaque année, les cheffes et chefs de clinique du Service de médecine interne du CHUV se réunissent pour partager leurs lectures : voici une sélection de dix articles choisis, revus et commentés pour vous.

Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya® (EVG/COBI/FTC/TAF) and simvastatin; a case report.

BACKGROUND: Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction. CASE PRESENTATION: We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated. CONCLUSION: Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.

Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1ß, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.

Phytochelatins and monothiols in salt marsh plants and their relation with metal tolerance.

Phytochelatins (PCs) and monothiols and their relation with trace element concentrations were studied in three plant species from two Portuguese salt marshes. Belowground tissues showed always higher element concentrations, while enhanced values of monothiols were found in aboveground biomass. Glutathione was usually the most abundant monothiol. The concentration of total PCs was higher in leaves or stems than in roots of Halimione portulacoides and Sarcocornia perennis, while in Spartina maritima the highest concentrations were reported in large roots. PC2 was synthesized by all tissues and species and was higher in large roots of S. maritima. PC4 and PC5 were in high levels in small roots of S. maritima. PC2 was positively correlated with As, Zn and Pb. Although being the first evidence of PCs and monothiols in these species under natural conditions, our results do not point to a simple relationship with elements concentrations, suggesting a complex mechanism involved.

Elemental mapping inventory of the fish Liza aurata brain: a biomarker of metal pollution vulnerability.

The elemental distributions in optic tectum of brains of wild Liza aurata a teleost fish captured in polluted and reference coastal areas were assessed quantitatively by nuclear microscopy providing insights into brain vulnerability to metal pollution. Elemental maps enabled us to visualize optic tectum layers and identify cellular arrangements. Whereas Cl, K and Ca contents identify meninges, the Ca, Fe and Zn concentrations distinguish the underneath grey matter, white matter and inner cellular layers. Exposed animals showed significantly decreased P concentrations and increased contents of Cu, Zn and Ni in all brain structures. These changes highlight homeostasis modification, altered permeability of the blood-brain barrier and suggest risk for neurological toxicity. Our study initiated for the first time an inventory of physiological measures containing images and elemental compositions of brain regions of fish exposed to different environmental conditions. This will help defining total and local brain vulnerability to metals and pollution levels.

Imaging of intracellular metal partitioning in marine diatoms exposed to metal pollution: consequences to cellular toxicity and metal fate in the environment.

This study investigates the metal content and compartmentalization changes in whole cells of diatom Coscinodiscus eccentricus exposed to metal overload, examining consequences to cellular toxicity, tolerance mechanisms, and metal fate in the environment. Cells exposed to Ni, Cu and Zn were analysed using nuclear microprobe techniques. Particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS), and scanning transmission ion microscopy (STIM) were used simultaneously to obtain high-resolution imaging of morphological and quantitative elemental distribution data. Elemental partitioning within cell compartments, such as cell wall, cytoplasm and major organelles, was assessed. Diatoms clearly responded to excess metal levels, by changing cytoplasm morphology, concentrating added metals, and altering Fe transport mechanisms. Different metal accumulation patterns indicated high susceptibility to Cu, retained in the cytoplasm, and detoxification capability for Ni and Zn, mobilized to the vacuole. Iron and Zn were accumulated in the siliceous wall. Different metal distributions within the cell imply distinct environmental fates, Cu and Ni remain available with potential for biomagnification through the food web, whereas Fe and Zn are deposited at the bottom through frustule sedimentation.