The Effect of the Different Waves of COVID-19 Pandemic on the Outcome of Diabetic Foot Ulcers

Objective: Diabetic foot ulcers (DFUs) are complications of diabetes mellitus. COVID-19 pandemic has massively impacted human health. We studied effect of COVID-19 on outcome of DFUs. Method(s): We recruited 483 people with DFU from June 2020-April 2022 (pandemic group) together with a matched group of 227 people with DFU from March 2019-March 2020 (pre-pandemic group). Matching was done with respect to glycemic control (Average HbA1c in pandemic group 9.15%;pre-pandemic group 8.92%), and renal status. Primary endpoint was outcome of ulcers- healed or undergone amputation. Primary outcome was further sub analyzed in the 3 waves of COVID-19 Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data with site, nature and Wegner's grading of DFUs were collected. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ABI. Standardized treatment protocol including glycemic control, infection control, debridement, dressing, offloading was provided. All patients were monitored for >6 months. Result(s): In pandemic cohort of 483 patients 323(66.9%) patients had healed ulcers, 70(14.5%) had minor amputation, 11(2,2%) had major amputation, 29(6%) lost to follow up, 22(4.6%) had not healed and 28 are in follow up (5.8%). Rate of healing of DFU in pandemic group was higher (66.9%) than control group (53.5%). Similarly, rate of amputation in pandemic group was less (16.7%) than pre-pandemic group (23.4%). Among healed ulcers in pandemic group, non-infected neuropathic ulcers healed better (77.8%;199/256) than other types (54.6%;124/227) [p< 0.00001]. Similarly, rate of amputation (major/minor) in ischemic and neuroischemic ulcers in pandemic group was more (32.3%;11/34) than other types (15.6%;70/449) [p= 0.011]. Rate of healing of foot ulcers in 1st wave was 65.4% (53/81), 2nd wave 75.2% (158/210), 3rd wave 58.3% (112/192). Neuropathic ulcers though less prevalent in first two waves (49.8%;145/291) than 3rd wave (57.8%;111/192) healing rate was more in first two (79.3%;115/145 vs 75.6%;84/111). [p=0.488 (statistically not significant]. Ischemic and neuroischemic ulcers were more in 3rd wave (7.8%;15/192) than first two waves (6.5%;19/291) and undergone more amputation (46.7%;7/15 vs 15.7%;3/19). [p=0.58 (statistically not significant;due to small sample size]. Discussion/Conclusion: COVID-19 pandemic (mainly first two waves) accounted for travel restrictions contributing to better healing of neuropathic ulcers whereas ischemic and neuroischemic ulcers worsened and underwent more amputation as patients could not seek intervention. Conversely, in third wave withdrawal of COVID restrictions lead to worsening of DFUs leading to less healing and more amputation.Copyright © 2023

Promoting improved healing: Lessons learned from the fetus

Background: It has long been known that the fetal response to skin injury is regenerative, with a lack of abnormal collagen deposition or scar, and restoration of normal dermal architecture. This response is associated with minimal inflammation.We have shown that the decreased inflammation is due to decreased production of pro-inflammatory cytokine production compared to the adult response. In addition, we have shown fetal tendon and the fetal heart can heal by regeneration, with restoration of structure and function, and is also associated with decreased proinflammatory cytokine production and decreased inflammation. We hypothesized that strategies targeting inflammation and associated oxidative stress could be used in adult diseases. We have identified diabetic wounds, acute lung injury, and colitis where inflammation and oxidative stress plays a central role in the pathogenesis the disease. Material(s) and Method(s): We have developed a novel strategy using nanotechnology to target inflammation and oxidative stress. We have conjugated novel cerium oxide nanoparticles, which act as potent scavengers of reactive oxygen species, to the anti-inflammatory microRNA miR146a, which suppresses the NFkB pathway and the production of the pro-inflammatory cytokines IL-6 and IL-8. Result(s): In diabetic wounds, impaired healing is associated with chronic inflammation and oxidative stress. We have demonstrated, in both small and large diabetic animals models, that CNP-miR146a can decrease inflammation and oxidative stress and correct the diabetic wound healing impairment and promote regeneration, similar to rates of healing in non-diabetic animals. We have also examined other disease states where inflammation and oxidative stress is pathogenic. Following acute lung injury, inflammation and oxidative stress leads to the development of adult respiratory distress syndrome or ARDS, the number one cause of mortality with COVID-19, and is associated with a 30-50% mortality. Inflammation and oxidative stress play a central role in the pathogenesis of ARDS. We have shown in models of acute lung injury, including bleomycin, LPS, MRSA, ventilator induced lung injury (VILI) and mustard gas, that CNP-miR146a decreases inflammation and oxidative stress, promotes regeneration and restoration of function, and decreased mortality. Finally, pathogenic inflammation plays a central role in the development of colitis or inflammatory bowel disease. We have shown that CNP-miR146a enemas can prevent progression of disease, restore weight gain, and lacks the adverse effects of systemic immunosuppression. Conclusion(s): We have used our understanding of the mechanisms of fetal regeneration following injury, which progresses with minimal inflammation and oxidative stress, to develop strategies targeting these processes to promote regeneration in adult disease.

Wound complications in patients with acute lower limb venous thrombosis associated with COVID-19

The course of the reparative process in surgical pathology directly depends on hemomicrocirculation, nutrition and oxygen supply in tissues, as well as the activity of lipid peroxidation processes. A novel coronavirus infection can slow down the reparative process and potentiate the development of wound complications. Aim - to study the features of the tissue healing process in patients with deep vein thrombosis of the lower extremities against the background of a new coronavirus infection. Material and methods. 130 patients were monitored: group 1 - 48 patients with acute thrombosis of the veins of the lower extremities, group 2 - 82 patients with acute deep vein thrombosis of the lower extremities, combined with coronavirus infection. Patients underwent thrombectomy followed by plication. On the 2nd, 4th and 7th days, a comprehensive study of the state of the tissues of the area of surgical intervention was carried out to determine the nature and rate of healing, the development of wound complications. Results. In a quantitative analysis of the developed complications on the side of the wound after surgery, it turned out that their number in patients with coronavirus infection was more than 7 times higher (p<0.001). A feature of the wound process as a whole was prolonged lymphorrhea. Cytological signs of impaired tissue healing in the wound area were established. So, in group 2 two days after the operation the number of neutrophilic leukocytes in the wound exudate was 48.2% more than in the group 1, by day 7th - 69.5% more. Weak dynamics of the regenerative-degenerative index was noted. The number of tissue polyblasts in patients of group 2, was 4.2-100.2% lower than those of group 1 at all stages of observation, and lymphoid polyblasts - 47.0-159.1% higher. Patients with coronavirus infection have more significant microcirculatory disorders. According to thromboelastography data, in patients of group 2, an imbalance in the blood coagulation system was registered with a predominance of thrombosis. Conclusion. In patients with acute deep vein thrombosis of the lower limb against the background of coronavirus infection, the wound healing process, which underlies the development of wound complications, slows down. One of the factors that reduce the rate of tissue healing are microcirculation disorders against the background of pronounced disorders in the hemostasis system. The most significant changes in the microenvironment of regenerating structures occur in the first 2-4 days after surgery.

Monoclonal Antibodies Anti-Covid-19: Analysis Of Efficacy And Safety Data In The Early Months Of Use

Introduction. In addition to the vaccination, other options for treating COVID-19 have been made available;such options include the monoclonal antibody (MAbs) combinations Casirivimab/Imdevimab and Bamlanivamab/Etesevimab, which have shown to reduce the chances of hospitalisation in patients at risk of severe forms of disease. The aim of this work is to define data on the use of monoclonal therapy at the hospital where our U.O.C. Pharmacy is located and also to provide a first analysis on the efficacy and safety of the treatments. Methods and materials. The period under consideration runs from March 20th to August 15th 2021. Clinical data were extracted from AIFA web records and processed using Microsoft Excel. For patients whose treatment was closed, it has been calculated: follow-up period, degree of healing, rates of negativization, average overall negativization time and for subgroups of patients identified according to specific clinical parameters. Finally, a total percentage by type of adverse reaction was established. Results. 91 treatments with one of the two MAbs combinations have been activated. The average age of patients was between 59 and 72 years. The most common symptom was fever (83,52% of patients), while the most frequently encountered risk factor was Cardio-cerebrovascular disease (59,34%). Patient files have been closed for 86 patients, 84 of which recovered and 2 deceased. Negativization rates at 7, 14, 21, 28 and 35 days were 2.60%, 27.27%, 44.16%, 74.03% and 77.92% respectively. The average time of negativization was 22.33 days;in patients treated within 3 days of onset symptom, the average time was of 18,09 days, while in those treated after 3 days it was 26.00. Only 9.09% of patients involved in the treatment experienced one or more adverse reactions to the infusion. Conclusions. The results of this work show that correctly used anti-Covid-19 MAbs are an important therapeutic resource against the new infectious agent. As observed during the experimental phase, monoclonal antibodies prove their beneficial effect when used in the early stages of infection.

Dynamical analysis for the impact of asymptomatic infective and infection delay on disease transmission

The influence of asymptomatic patients on disease transmission has attracted more and more attention, but the mechanism of some factors affecting disease transmission needs to be studied urgently. Considering the self-healing rate of asymptomatic patients, the cure rate of symptomatic patients, the transformation rate from asymptomatic to symptomatic and the infection delay, a type of infectious disease dynamics model SIsIaS with asymptomatic infection and infection delay is established in this paper. It is found that both the infection delay and the difference size between the cure rate and the self-healing rate not only affect the minimum value of the total number of patients in the persistent state of the disease, but also lead to disease extinction to be controlled by the proportion of symptomatic patients in patients. Moreover, the infection delay can lead to local Hopf bifurcation of periodic solutions. By using the normal form and center manifold theory the direction of Hopf bifurcations and the stability of bifurcated periodic solutions are discussed. At last, sensitivity analysis shows that the infection delay can change the correlation of the proportion of symptomatic patients in patients and the transformation rate to the total number of patients. (C) 2022 International Association for Mathematics and Computers in Simulation (IMACS). Published by Elsevier B.V. All rights reserved.