Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Methods: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Results: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Conclusion: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anticytokine randomized trials will be key.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O 2 /O 3 ) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case–control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU—Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O 3 -autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O 2 /O 3 mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O 3 -autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O 3 -treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O 2 /O 3 gaseous mixture. O 2 /O 3 therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].

Background Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. Methods The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). Results A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p= 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1] , [2] , [3] the O3-AHT arm; p= 0.018). No adverse events related O3-AHT treatment was observed. Conclusion In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

This paper reports the beneficial effects of ozone autohemotherapy (OHT) in 2 patients afflicted with painful, intractable leg ulcers. One patient had diabetes mellitus type II (DM), the other had vasculitis. Both patients had seen multiple specialists, including a dermatologist, an internist, and a vascular surgeon, but their clinical course continued to worsen. When the pain became intolerable, the patients came to our pain clinic. Chemical lumbar sympathectomy as well as epidural blockade with bupivacaine and morphine were moderately effective in reducing their pain but had no effect on the ulcers. Only after OHT treatments were performed for several months was satisfactory healing observed.

[250 words] Objective Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Results In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8+/-10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Conclusion Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.

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BACKGROUND: Pharmacological treatments for critical processes in patients need to be initiated as rapidly as possible; for this reason, it is a standard of care to prepare the main anesthesia and emergency drugs in advance. As a result, 20%–50% of the prepared drugs remain unused and are then discarded. Decreasing waste by optimizing drug use is an attractive strategy for meeting both cost containment and environmental sustainability. The primary end point of this study was to measure the actual amount of drug wastage in the operating rooms (ORs) and intensive care units (ICUs) of a Regional Health Service (RHS). The secondary end point was to analyze and estimate the economic implications of this waste for the Health Service and to suggest possible measures to reduce it. METHODS: This prospective observational multicenter study was conducted across 12 hospitals, all of which belong to the same RHS in the north-east of Italy. Data collection took place in March 2018 and included patients admitted to ICUs, emergency areas, and ORs of the participating hospitals. Data concerning drug preparation and administration were collected for all consecutive patients, independent of case types and of whether operations were scheduled or unscheduled. Drug wastage was defined as follows: drugs prepared in ready-to-use syringes but not administered at all and discarded untouched. We then estimated the costs of wasted drugs for a 1-year period using the data from this study and the yearly regional pharmacy orders of drugs provided to the ORs and ICUs. We also performed a sensitivity analysis to validate the robustness of our assumptions and qualitative conclusions. RESULTS: We collected data for a total of 13,078 prepared drug syringes. Drug wastage varied from 7.8% (Urapidil, an alpha-1 antagonist antihypertensive) to 85.7% (epinephrine) of prepared syringes, with an overall mean wastage rate of 38%. The estimated yearly waste was 139,531 syringes, for a total estimated financial cost of €78,060 ($92,569), and an additional quantity of medical waste amounting to 4968 kg per year. The total provider time dedicated to the preparation of unused drugs was predicted to be 1512 working hours per year. CONCLUSIONS: The overall extent of drug wastage in ORs and ICUs is concerning. Interventions aimed at minimizing waste-related costs and improving the environmental sustainability of our practice are paramount. Effort should be put into designing a more efficient workflow that reduces this waste while providing for the emergency availability of these medications in the OR and ICU.

The incidence of out-of-hospital cardiac arrest and survival rate lies within the known range. A wider database is necessary to achieve a better knowledge of out-of-hospital cardiac arrest and to drive future investments in the healthcare system.