Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2.

BACKGROUND: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. OBJECTIVE: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). METHODS: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. RESULTS: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. CONCLUSIONS: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.

Risk Factors and Outcome of Acute Kidney Injury after Congenital Heart Surgery: A Prospective Observational Study.

BACKGROUNDS AND AIMS: Acute kidney injury (AKI) is a frequent event after congenital heart surgery with increased mortality and morbidity. We investigated frequency, risk factors, and associated morbidity and mortality of AKI after pediatric cardiac surgery at a single institution. METHODS: Children undergoing congenital heart surgery from March 2013 to February 2016 were assessed for development of AKI based on modified pediatric Risk, Injury, Failure, Loss, and End-stage renal disease criteria. They were also investigated for predictive risk factors, associated mortality, and morbidity including duration of mechanical ventilation, Intensive Care Unit (ICU), and hospital length of stay. RESULTS: Five hundred and nineteen patients were recruited during the study period including 259 (49.9%) males and 260 (50.1%) females. AKI was seen in 150 (28.9%) patients including 101 (67.3%), 42 (28%), and 7 (4.7%) cases with risk, injury, and failure stages, respectively. Patients with AKI had longer ventilation time (P = 0.002), ICU (P = 0.05), and hospital (P = 0.56) stay. Mortality was seen in 31 (2.7%) and 44 (11.9%) patients with and without AKI, respectively (P = 0.01). After multivariable logistic regression, there was an association between AKI and preoperative abnormal levels of creatinine (adjusted odds ratio [aOR] = 0.47, 95% confidence interval [CI] 0.22-1.01; P = 0.05), presence of cyanotic heart disease (aOR = 1.97, 95% CI = 1.15-3.2; P = 0.01), duration of surgery (aOR = 1.05/10 min, 95% CI = 1.01-1.08; P = 0.007), and elevated lactate level (aOR = 1.14, 95% CI = 1.03-1.3; P = 0.01). CONCLUSION: The presence of cyanotic heart disease, duration of surgery, elevated postoperative lactate level, and likely preoperative creatinine level were independent risk factors for the development of AKI after congenital heart surgery.

Evaluation of the effect of empagliflozin on prevention of atrial fibrillation after coronary artery bypass grafting: a double-blind, randomized, placebo-controlled trial.

This study is aimed at evaluating the effect of empagliflozin in preventing atrial fibrillation after coronary artery bypass grafting (CABG). Eighty-two patients who fulfilled the inclusion criteria were allocated to the empagliflozin group (n = 43) or placebo group (n = 39). In two groups, patients received empagliflozin or placebo tablets 3 days before surgery and on the first three postoperative days (for 6 days) in addition to the standard regimen during hospitalization. During the first 3 days after surgery, types of arrhythmias after cardiac surgery, including supraventricular arrhythmias, especially postoperative atrial fibrillation (POAF), ventricular arrhythmias, and heart blocks, were assessed by electrocardiogram monitoring. C-reactive protein (CRP) levels were evaluated pre-operatively and postoperative on the third day. The incidence of POAF in the treatment group was lower compared to the control group; however, this reduction was statistically non-significant (p = 0.09). The frequency of ventricular tachycardia was reduced significantly in the treatment group versus patients in the control (p = 0.02). Also, a significant reduction in the frequency of premature ventricular contractions (PVCs) was seen in the treatment group in comparison with the control group (p = 0.001). After the intervention, CRP levels were significantly less in the empagliflozin group compared to the control group in the third postoperative day (p = 0.04). The prophylactic use of empagliflozin effectively reduced the incidence of ventricular arrhythmia in patients undergoing CABG surgery.

Sustainability inspired fabrication of next generation neurostimulation and cardiac rhythm management electrodes via reactive hierarchical surface restructuring.

Over the last two decades, platinum group metals (PGMs) and their alloys have dominated as the materials of choice for electrodes in long-term implantable neurostimulation and cardiac rhythm management devices due to their superior conductivity, mechanical and chemical stability, biocompatibility, corrosion resistance, radiopacity, and electrochemical performance. Despite these benefits, PGM manufacturing processes are extremely costly, complex, and challenging with potential health hazards. Additionally, the volatility in PGM prices and their high supply risk, combined with their scarce concentration of approximately 0.01 ppm in the earth's upper crust and limited mining geographical areas, underscores their classification as critical raw materials, thus, their effective recovery or substitution worldwide is of paramount importance. Since postmortem recovery from deceased patients and/or refining of PGMs that are used in the manufacturing of the electrodes and microelectrode arrays is extremely rare, challenging, and highly costly, therefore, substitution of PGM-based electrodes with other biocompatible materials that can yield electrochemical performance values equal or greater than PGMs is the only viable and sustainable solution to reduce and ultimately substitute the use of PGMs in long-term implantable neurostimulation and cardiac rhythm management devices. In this article, we demonstrate for the first time how the novel technique of "reactive hierarchical surface restructuring" can be utilized on titanium-that is widely used in many non-stimulation medical device and implant applications-to manufacture biocompatible, low-cost, sustainable, and high-performing neurostimulation and cardiac rhythm management electrodes. We have shown how the surface of titanium electrodes with extremely poor electrochemical performance undergoes compositional and topographical transformations that result in electrodes with outstanding electrochemical performance.

Gas-assisted femtosecond pulsed laser machining: A high-throughput alternative to focused ion beam for creating large, high-resolution cross sections.

Cross sectioning is a critical sample preparation technique used in a wide range of applications, that enables investigation of buried layers and subsurface features or defects. State-of-the-art cross-sectioning methods, each have their own pros and cons, but generally suffer from a tradeoff between throughput and accuracy. Mechanical methods are fast but lack accuracy. On the other hand, ion-based methods, such as focused ion beam (FIB), offer high resolutions but are slow. Lasers, which can potentially improve this tradeoff, face multiple challenges that include creation of heat affected zones (HAZs), undesirably large spot size as well as material redeposition. In this work, we utilized, for the first time, a femtosecond pulsed laser, which has been shown to cause minimal to zero HAZ, for rapid creation of large cross sections that are comparable with FIB cross sections in quality. The laser was integrated with a targeted CO2 gas delivery system for redeposition control and beam tail curtailing, and a hard mask for top surface protection and further shrinkage of the effective spot size. The performance of the proposed system is showcased through real world examples that compare the throughput and quality resulted from the laser and FIB cross sectioning techniques.

Development of antibacterial neural stimulation electrodes via hierarchical surface restructuring and atomic layer deposition.

Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus-two common types of bacteria responsible for implant infections.

Comparison of Adhesion and Proliferation of Human Gingival Fibroblasts on Acellular Dermal Matrix with and without Low Level Diode Laser Irradiation, an in vitro Study.

Statement of the Problem: In recent years, regeneration of periodontal soft tissues in the reconstruction of periodontal defects and the finding of suitable membranes and graft materials for the placement of autogenous grafts have been of great interest in various studies. In this regard, the proliferation and adhesion of regenerative cells are two linchpins of the complete regenerative process. Purpose: This study aimed to evaluate the effects of low-level laser beams on the attachment and the proliferation of human gingival fibroblasts in the presence of acellular dermal matrix (ADM). Materials and Method: All the experiments were conducted compared to tissue culture plate in four groups as follows: (1) Fibroblast+ADM+laser, (2) Fibroblast+ADM+ no laser, (3) Fibroblast + laser radiation, and (4) Fibroblast+ no laser. In this experimental study, the primary attachment was evaluated by passing 8h from seeding of 5×105 gingival fibroblasts with or without a single dose (15.6 J/cm2) of laser radiation. Cell proliferation rate was also examined at 24, 48, and 72 hours after cell culture, following exposure to 5.2 J/cm2 of laser at each day of examination. Thereafter, fibroblasts were incubated under the normal culture condition (at 37°C, 5% CO2) in high glucose Dulbecco's Modified Eagle's medium (DMEM) medium supplemented with 10% fetal bovine serum, 1% glutamax, and 1% penicillin/streptomycin. Subsequently, the cellular viability was assessed on each time point using MTS calorimetric assay. The obtained data were statistically analyzed by applying ANOVA and Tukey tests. Results: There was a significant difference among the means of these four groups in terms of the proliferation of fibroblasts at 24, 48 and 72 hours (p< 0.001). Moreover, there was no significant difference among the means of two groups in terms of fibroblastic attachment in 8 hours (p< 0.2). The fibroblast group has shown the highest proliferation rate among all groups after laser radiation. Conclusion: It was indicated that the laser radiation increases the fibroblast cell proliferation. Accordingly, although this increase was higher in the fibroblast group alone compared to the fibroblasts cultured on acellular dermal matrix, the laser radiation did not significantly increase the attachment of fibroblast cells to acellular dermal matrix.

Oropharyngeal Decontamination for Prevention of VAP in Patients Admitted to Intensive Care Units: A Systematic Review.

Introduction: Oropharyngeal colonization with pathogenic organisms contributes to the development of ventilator-associated pneumonia (VAP) in intensive care units (ICUs). Oral hygiene care (OHC) is a very effective method for reducing the risk of VAP in these patients. This study aimed to evaluate recent OHC strategies to decrease VAP. Methods: Randomized clinical trials (RCTs) published in the PubMed, Scopus, Embase, Cochrane Library, and Web of Science databases from inception to September 10, 2020 were reviewed to compare the effects of selective oropharyngeal decontamination (SOD) on the incidence of VAP in adult patients requiring mechanical ventilation. Results: Out of a total of 1098 articles reviewed, 17 eligible studies were included for final analysis. The results showed that the use of chlorhexidine for oropharyngeal decontamination reduces the incidence of VAP. However, it had a small effect on gram-negative resistant bacteria. Also, it was observed that the combined use of colistin and chlorhexidine was more effective than chlorhexidine alone in preventing VAP. The results of studies on the use of toothbrushes to reduce the incidence of pneumonia are unclear since they used chlorhexidine at the same time. However, tooth brushing is one of the best ways to maintain oral hygiene. Using povidoneiodine, Nanosil, and non-absorbable topical antibiotics reduced the incidence of VAP, while Iseganan did not show a significant effect in this regard. Conclusion: The prophylactic use of topical bactericidal agents in critically-ill patients is effective in reducing the incidence of VAP. However, the use of non-absorbable topical antibiotics is more effective than other methods in oropharyngeal decontamination.

Educational challenges of family caregivers of vegetative state patients for home care preparedness: A qualitative content analysis.

BACKGROUND: Patients with a vegetative state (VS) are completely dependent on caregivers in all physical aspects of their lives. Caring for such patients comes with a great deal of difficulty for family caregivers. As a result, family caregivers must be fully trained and prepared for this role. The present qualitative study was conducted to investigate the educational challenges faced by family caregivers of VS patients for home care preparedness. MATERIALS AND METHODS: The present qualitative study was conducted through the conventional content analysis method from August 2020 to September 2021 in two provinces of Iran (Sistan and Baluchestan Province; and Razavi Khorasan Province). Fourteen family caregivers of patients in a VS were included in the study. Semi-structured and in-depth interviews were employed to collect data. The Graneheim and Lundman method was utilized to conduct the data analysis using MAXQDA2020 software. Data collection continued until data saturation and the identification of main categories. RESULTS: As indicated by the data analysis, three categories of "unmet educational needs," "confused caregiver," and "searching for practical knowledge" which included 19 sub-categories described the experiences of family caregivers of patients in a VS concerning challenges they went through in preparation for patient care at home. Participants' experiences revealed that despite the inadequacy of educations provided by health-care providers on knowledge and skills required by family caregivers, they were committed to caring for the patient and trying to acquire the required knowledge. CONCLUSION: Results indicated that inadequate education and the lack of family caregivers' contribution to caring for the patient in the VS during their stay in the hospital impedes their acquisition of adequate knowledge and skill to care for patients at home. Therefore, healthcare system policymakers should be planning to eliminate the educational barriers faced by family caregivers and expand the educational activities of hospitals' homecare centers to provide educational support of family caregivers after the patient's discharge.

Femtosecond laser hierarchical surface restructuring for next generation neural interfacing electrodes and microelectrode arrays.

Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve stimulation, as well as sensing and recording electrical signals to and from neural tissue. To improve specificity, functionality, and performance of these devices, the electrodes and microelectrode arrays-that are the basis of most emerging devices-must be further miniaturized and must possess exceptional electrochemical performance and charge exchange characteristics with neural tissue. In this report, we show for the first time that the electrochemical performance of femtosecond-laser hierarchically-restructured electrodes can be tuned to yield unprecedented performance values that significantly exceed those reported in the literature, e.g. charge storage capacity and specific capacitance were shown to have improved by two orders of magnitude and over 700-fold, respectively, compared to un-restructured electrodes. Additionally, correlation amongst laser parameters, electrochemical performance and surface parameters of the electrodes was established, and while performance metrics exhibit a relatively consistent increasing behavior with laser parameters, surface parameters tend to follow a less predictable trend negating a direct relationship between these surface parameters and performance. To answer the question of what drives such performance and tunability, and whether the widely adopted reasoning of increased surface area and roughening of the electrodes are the key contributors to the observed increase in performance, cross-sectional analysis of the electrodes using focused ion beam shows, for the first time, the existence of subsurface features that may have contributed to the observed electrochemical performance enhancements. This report is the first time that such performance enhancement and tunability are reported for femtosecond-laser hierarchically-restructured electrodes for neural interfacing applications.

Evaluation of the effect of crocin on prevention of atrial fibrillation after coronary artery bypass grafting or heart valve replacement: A double-blind, randomized, placebo-controlled trial.

Objective: The aim of this study was to evaluate the effect of crocin on the prevention of atrial fibrillation after coronary artery bypass grafting (CABG) and heart valve replacement. Materials and Methods: 100 patients who were scheduled for CABG or heart valve replacement surgeries were randomly assigned into two groups of treatment and placebo. In the treatment group, patients received crocin tablets from three days prior to surgery and on the first three postoperative days (for a total of six days). During the first three days after surgery, postoperative atrial fibrillation (POAF) was assessed by electrocardiogram monitoring. Prooxidant-antioxidant balance (PAB) and c-reactive protein (CRP) levels were also assessed. Results: POAF developed in 7 patients in the treatment group versus 18 patients in the control (p=0.02). PAB levels were significantly lower in the crocin group (p<0.001), while differences in CRP levels were insignificant (p=0.39). Conclusion: It seems that prophylactic use of crocin is effective in reducing the incidence of POAF in patients undergoing heart surgeries.

Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome.

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.

On the stability of mg nanograins to coarsening after repeated melting.

Herein we report on the extraordinary thermal stability of approximately 35 nm Mg-nanograins that constitute the matrix of a Ti(2)AlC-Mg composite that has previously been shown to have excellent mechanical properties. The microstructure is so stable that heating the composite three times to 700 degrees C, which is 50 degrees C over the melting point of Mg, not only resulted in the repeated melting of the Mg, but surprisingly and within the resolution of our differential scanning calorimeter, did not lead to any coarsening. The reduction in the Mg melting point due to the nanograins was approximately 50 degrees C. X-ray diffraction and neutron spectroscopy results suggest that thin, amorphous, and/or poorly crystallized rutile, anatase, and/or magnesia layers separate the Mg nanograins and prevent them from coarsening. Clearly that layer is thin enough, and thus mechanically robust enough, to survive the melting and solidification stresses encountered during cycling. Annealing in hydrogen at 250 degrees C for 20 h, also did not seem to alter the grain size significantly.

The use of remifentanil in general anesthesia for cesarean section in a parturient with severe mitral stenosis and pulmonary edema.

Valvular heart diseases have adverse effects on hemodynamic condition in the parturients during pregnancy. Cesarean section with an opioid based general anesthesia has been used to alleviate these deleterious effects. We hereby describe the effective application of remifentanil, for cesarean section under general anesthesia, in a 30 yr. old primigravida suffering of severe multivalvular heart disease and pulmonary hypertension presenting with pulmonary edema who was in active labor and without neonatal respiratory depression.

The Application of a Reduced Dye Used in Orthopedics as a Novel Treatment against Coronavirus (COVID-19): A Suggested Therapeutic Protocol.

The severe acute respiratory syndrome caused by COVID-19 is now a global catastrophic event. Currently there is no approved drug or vaccine for the disease. Methylene blue (MB, oxidized form, blue color) has been used in many different areas of clinical medicine, ranging from malaria to orthopedics. Leucomethylene Blue (reduced form of MB, colorless) may be applied for the treatment of COVID-19 according to the scientific evidences. In severe patients, there is a cytokine storm (hyperinflammation) and high oxidative stress (OS). Inflammation and OS has a mutual correlation and exacerbate each other. In human body, MB first induces OS through absorbing electron (like a free radical) from other molecules, if the body could counteract to this OS, then reduced MB decreases OS through other mechanisms. Reduced MB could prevent inflammation, propagation of the virus RNA, and also improves hypoxia through reducing methemoglobin. Therefore, to avoid the increment of OS, we suggest using Leucomethylene Blue through the following protocol: The IV cocktail contains 50 mg MB (1mg/kg, 50-kg weight), 1000-2000 mg vitamin C, 500-1000 mg N-Acetylcysteine (or glutathione or cysteine or α-lipoic acid) and 10-20 gr urea (optional) in 100 ml dextrose 5%. Before the injection, the cocktail should be kept in a dark place for 1-2 hour to become fade or colorless.

Application of electrospun polycaprolactone fibers embedding lignin nanoparticle for peripheral nerve regeneration: In vitro and in vivo study.

Lignin displays attractive properties in peripheral nerve applications. Here, aligned polycaprolactone (PCL) fibers with various percentages of lignin nanoparticles were fabricated using the electrospinning method. The morphologies, contact angles, mechanical properties, in vitro degradation, and water uptake of the PCL/lignin fibers were characterized. Cell viability and adhesion of PC12 and human adipose-derived stem cells (hADSCs) were studied employing MTT assay and SEM, respectively. SEM, immunocytochemistry, and Real-Time PCR were utilized to characterize neural differentiation and neurite length of PC12 and hADSCs. To further study on lignin effect on nerve regeneration, in vivo studies were performed. The results indicated that all nanocomposite fibers were smooth and bead-free. With increasing the lignin content, the water contact angle decreased while in vitro degradation, water uptake, and Young's modulus increased compared to the PCL fibers. Cell viability, and differentiation along with neurite length extension were promoted by increasing lignin content. The neural markers expression for differentiated cells were upregulated by the increase of lignin percent. In vivo investigation also demonstrates that sample groups incorporating 15% lignin nanoparticles showed better regeneration among others. Therefore, PCL with 15% of lignin nanoparticles shows great potential to be applied for nerve regeneration.

Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial.

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.

Ocular Manifestations of Hospitalized Patients with COVID-19 in Northeast of Iran.

PURPOSE: To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the Northeast of Iran. METHODS: In a cross-sectional, observational study all consecutive patients with confirmed COVID-19 diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular examinations (external and slit) were randomly performed for the patients who were admitted to the Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum chemistry results were collected. RESULTS: A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23-96 years) and almost equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and 22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyperemia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at least one ocular manifestation had significantly higher blood urea levels at the time of admission compared to those with no obvious ocular involvement (median: 41.5, IQR: 28-66.3 vs. median: 33, IQR: 23.8-51.8, P = .023). Moreover, a significant difference was observed in the total white blood cell count, lymphocyte percent, neutrophil count, Erythrocyte Sedimentation Rate (ESR), and blood urea level between patients with positive and negative Polymerase Chain Reaction (PCR) for SARS-CoV-2 virus. None of the patients reported ocular symptoms prior to systemic involvement. The proportion of patients with at least one ocular manifestation was significantly higher in those admitted in the ICU compared to the non-ICU wards. wards. While conjunctival hyperemia was the most prevalent ocular finding in all patients, chemosis was the most common ocular manifestation in ICU admitted patients. CONCLUSION: Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it seems important to involve ophthalmologist in the diagnosis and management of these patients.

The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children.

BACKGROUND: Postoperative pain in children is common after adenotonsillectomy. Rectal acetaminophen has been used effectively for postoperative pain management in small children. The aim of this randomized double blind study was to evaluate the prophylactic effect of rectal acetaminophen on postoperative pain management and opioid requirements in children undergoing adenotonsillectomy. MATERIALS AND METHODS: 104 children, 7 to 15 yr, ASA I or II scheduled for elective adenotonsillectomy were recruited for the study. Patients were randomized to receive either rectal acetaminophen 40 mg/kg or nothing after induction of standard anesthesia. The postoperative pain was assessed using visual analog scale (VAS) every 2 hours for the first 6 hours. The need for rescue analgesic, intravenous pethedine of 0.5 mg/kg, was recorded at 24 hours after surgery. RESULTS: Pain scores were significantly lower in acetaminophen group at different times (p<0.001) and needed less rescue analgesic (p<0.001). CONCLUSION: We conclude that prophylactic rectal acetaminophen is effective in reducing pain after adenotonsillectomy and postoperative analgesic requirement.