Anti-IL6 treatment of serious COVID-19 disease: A monocentric retrospective experience

COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention.     

Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs

Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the metabolic tumor suppressor AMPK when thymidine and hypoxanthine were present in the extracellular milieu. Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways.     

Combined use of super‐oxidised solution with negative pressure for the treatment of pressure ulcers: case report

A 61‐year‐old patient was affected by flaccid paraplegia for 20 years because of post‐traumatic medullar injury caused by an accidental fall, with stage IV sacral pressure ulcer for 3 years. The patient later developed stage IV sacral pressure ulcer. After 6 months, a new granulation tissue formation appeared in the wound and a reduction of its diameter was observed (length 20 cm, width 15 cm, depth 5 cm). We therefore treated the wound with PRP (platelet rich plasma) intra‐lesion and peri‐lesional injections. The wounds were covered with three‐dimensional polymerised hyaluronic acid medicated biologic dressing. After the surgery, a moderate reduction in diameter and the depth was observed. Super‐oxidised solution (SOS‐Dermacyn) was applied to control infection locally together with negative pressure to control the exudate and the local bacteremia, to avoid infectious complications without application of systematic antibiotic therapy.     

Silver nanoparticles inhaled during pregnancy reach and affect the placenta and the foetus

Recently, interest for the potential impact of consumer-relevant engineered nanoparticles on pregnancy has dramatically increased. This study investigates whether inhaled silver nanoparticles (AgNPs) reach and cross mouse placental barrier and induce adverse effects. Apart from their relevance for the growing use in consumer products and biomedical applications, AgNPs are selected since they can be unequivocally identified in tissues. Pregnant mouse females are exposed during the first 15 days of gestation by nose-only inhalation to a freshly produced aerosol of 18–20?nm AgNPs for either 1 or 4?h, at a particle number concentration of 3.80?×?107 part./cm^?3 and at a mass concentration of 640?μg/m³. AgNPs are identified and quantitated in maternal tissues, placentas and foetuses by transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy and single-particle inductively coupled plasma mass spectrometry. Inhalation of AgNPs results in increased number of resorbed foetuses associated with reduced oestrogen plasma levels, in the 4?h/day exposed mothers. Increased expression of pregnancy-relevant inflammatory cytokines is also detected in the placentas of both groups. These results prove that NPs are able to reach and cross the mouse placenta and suggest that precaution should be taken with respect to acute exposure to nanoparticles during pregnancy.