Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

Nanoparticle albumin bound-paclitaxel for treatment of advanced non-small cell lung cancer: an evaluation of the clinical evidence

Introduction: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel).

Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology).

Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents.     

Treatment of oral manifestations of toxic epidermal necrolysis with low‐level laser therapy in a pediatric patient

Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life.     

Intraoperative Patterns of Gastric Microperfusion During Laparoscopic Roux-en-Y Gastric Bypass

Introduction

Visible light spectroscopy (VLS) represents a sensitive, non-invasive method to quantify tissue oxygen levels and detect hypoxemia. The aim of this study was to assess the microperfusion patterns of the gastric pouch during laparoscopic Roux-en-Y gastric bypass (LRYGB) using the VLS technique.

Methods

Twenty patients were enrolled. Tissue oxygenation (StO2%) measurements were performed at three different localizations of the gastric wall, prior and after the creation of the gastric pouch, and after the creation of the gastro-jejunostomy.

Results

Prior to the creation of the gastric pouch, the lowest StO2% levels were observed at the level of the distal esophagus with a median StO2% of 43 (IQR 40.8–49.5). After the creation of the gastric pouch and after the creation of the gastro-jejunostomy, the lowest StO2% levels were recorded at the level of the His angle with median values of 29% (IQR 20–38.5) and 34.5% (IQR 19–39), respectively. The highest mean StO2 reduction was recorded at the level of the His angle after the creation of the gastric pouch, and it was 18.3% (SD ± 18.1%, p < 0.001). A reduction of StO2% was recorded at all localizations after the formation of the gastro-jejunostomy compared to the beginning of the operation, but the mean differences of the StO2% levels were statistically significant only at the resection line of the pouch and at the His angle (p = 0.044 and p < 0.001, respectively).

Conclusion

Gastric pouch demonstrates reduction of StO2% during LRYGB. VLS is a useful technique to assess microperfusion patterns of the stomach during LRYGB.

Graphical abstract