Inhibitors of the sodium‐glucose co‐transporter‐2 (SGLT‐2) are a novel class of glucose‐lowering agents that show promising results. However, the use of canagliflozin has been associated with an ...increased risk of lower‐limb amputation. Whether this risk concerns other SGLT‐2 inhibitors is unclear, and our objective was to address this issue. We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase). Among the 8 293 886 reports available between January 2013 and December 2017, we identified 79 reports of lower‐limb amputation that were associated with SGLT‐2 inhibitors. Among all blood glucose lowering drugs, the proportional reporting ratio (PRR) was increased only for SGLT‐2 inhibitors (5.55 4.23, 7.29). While we observed an expected signal for canagliflozin (7.09 5.25, 9.57), the PRR was also high for empagliflozin (4.96 2.89, 8.50) and, for toe amputations only, for dapagliflozin (2.62 1.33, 5.14). In conclusion, our results reveal a positive disproportionality signal for canagliflozin, and also for empagliflozin, and, for toe amputations only, for dapagliflozin. However, our analysis relies on a limited number of cases and is exposed to the biases inherent to pharmacovigilance studies. Further prospective data are therefore needed to better characterize the risk of amputations with different SGLT‐2 inhibitors.
Several noninvasive techniques have been developed using laser light interaction in the skin to explore the skin's microcirculation. Combined with laser Doppler or LSCI, reactivity tests are used to ...explore skin endothelial and neurovascular function in humans, including PORH, LTH, PIV, and iontophoresis of vasodilators. Recent advances in our comprehension of the physiological pathways underlying these reactivity tests have been possible through topical or intradermal delivery of drugs that produce elevated local concentrations. Skin microvascular function has also been proposed as a prognostic biomarker or for evaluating the effect of drugs. Comprehension of the physiological pathways, together with recent technological improvements in microcirculation imaging, has provided reliable and reproducible tools to study skin microcirculation.
Peripheral microvascular dysfunction has been described in many physiological and pathological conditions. Owing to its accessibility, the cutaneous microcirculation provides a unique index of ...microvascular function. Skin microvascular function has therefore been proposed as a prognostic marker or for evaluating the effect of drugs on the microcirculation. Various reactivity tests, coupled with techniques measuring skin blood flux, are used to non-invasively explore both endothelial and neurovascular microvascular functioning in humans. We review the advantages and limitations of the main reactivity tests, including post-occlusive reactive hyperemia, local thermal hyperemia, pressure-induced vasodilation, and iontophoresis of vasodilators, combined with measurement techniques such as laser Doppler and laser speckle contrast imaging. Recent advances in our comprehension of the physiological pathways underlying these reactivity tests, as well as technological developments in microcirculation imaging, have provided reliable and reproducible tools for studying the microcirculation.
Background
The vagus nerve has anti‐inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti‐inflammatory pathway in a ...pilot study in Crohn's disease patients. The main objectives addressed the questions of long‐term safety, tolerability, and anti‐inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months.
Methods
Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed‐up.
Key Results
After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C‐reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more “healthy profile”: Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorβ1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta‐hydroxybutyrate. VNS was well tolerated.
Conclusion & Inferences
Vagus nerve stimulation appears as an innovative and well‐tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double‐blinded control study.
Please cite this paper as: Roustit and Cracowski (2012). Non‐invasive Assessment of Skin Microvascular Function in Humans: An Insight Into Methods. Microcirculation 19(1), 47–64.
For more than two ...decades, methods for the non‐invasive exploration of cutaneous microcirculation have been mainly based on optical microscopy and laser Doppler techniques. In this review, we discuss the advantages and drawbacks of these techniques. Although optical microscopy‐derived techniques, such as nailfold videocapillaroscopy, have found clinical applications, they mainly provide morphological information about the microvessels. Laser Doppler techniques coupled with reactivity tests are widespread in the field of microvascular function research, but many technical issues need to be taken into account when performing these tests. Post‐occlusive reactive hyperemia and local thermal hyperemia have been shown to be reliable tests, although their underlying mechanisms are not yet fully understood. Acetylcholine and sodium nitroprusside iontophoresis, despite their wide use as specific tests of endothelium‐dependent and ‐independent function, respectively, show limitations. The influence of the skin site, recording conditions, and the way of expressing data are also reviewed. Finally, we focus on promising tools such as laser speckle contrast imaging.
Iontophoresis is a method of non‐invasive transdermal drug delivery based on the transfer of charged molecules using a low‐intensity electric current. Both local and systemic administration are ...possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing iontophoresis, we detail the current applications of iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma‐related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of iontophoresis.
The objective of this study is to examine the potential association between drug use and adverse event reporting in France. A number of drug users and cases reported were extracted from the French ...Health Care Insurance database (Open Medic) and the French pharmacovigilance database. We performed two separate mixed‐effect models (with a drug used or reporting rate as dependent variables) with a random intercept for drug classes. We selected 62 drugs from 10 drug classes, for which 177 364 cases were reported in the French pharmacovigilance database in 2020. The results showed a strong association between drug users and the number of reported cases in France among each drug class (P < 0.01). Within a drug class, the number of reported cases is, therefore, a proxy for the exposure to a given drug in the population. This finding could be useful to approximate and compare drug exposure from pharmacovigilance databases.
PDF
