Intermediate Results of the Research for Percutaneous and Surgical Treatment for Left Anterior Descending Artery Chronic Total Occlusion

Objective: Is to find out which revascularization methods have less of risk factors and complications after the surgery and long-term period. Method(s): From January 2018 to December 2019 were operated 134 patients with LAD CTO. 48 of them underwent MIDCAB: 36 (75%) males and 12 (25%) females;aged 58.7 +/-8.7;7 (14.6%) with previous diabetes;10 (20.8%) with previous PCI of LAD with drug-eluting stent. In the PCI group there were 86 patients: 52 (60.5%) males and 34 (39.5%) females;aged 64.8 +/-8.3;23 (26.7%) with previous diabetes. Result(s): Hospital mortality was 0 (0%) in MIDCAB unlike 1 (1.2%) in PCI. Myocardial infarction was 0 (0%) in both the groups. In MIDCAB the number of conversions to onpump and sternotomy was 0 (0%), there were 6 (12.5%) pleuritis with pleural puncture and 3 (6.2%) with long wound-aches. The hospitalization period was 10.7+/-2.9 days for MIDCAB and 9.9 +/-3.9 days for PCI. In the PCI group 2.0 +/-1.0 drug-eluting stents were used. In-hospital costs were higher for PCI 3809 unlike 3258 for MIDCAB. After one year in MIDCAB group died 2 (4.2%) patients, from noncardiac causes. In PCI group died 3 (3.5%) patients, all from cardiac causes. Because of pandemic COVID-19 were checked only 48 patients by angiography and general clinical examination: 25 after MIDCAB and 23 after PCI. 5 patients have a graft failure, caused by surgical mistakes. 4 patients have stents restenosis and 1 has LAD's reocclusion. Conclusion(s): Both methods of revascularization for LAD CTO are demonstrated similar results. EuroSCORE II (P = 0.008) and glomerular filtrating rate (P = 0.004) are significant potential risk factors for mortality in both groups, age is potential risk factor for graft failure (P = 0.05). Dyslipidemia is significant risk factor for LAD restenosis in PCI group (P = 0.02). MIDCAB is associated with lower incidence of revascularization repeat and in-hospital mortality in the literature data and it costs lower than PCI for LAD CTO as our study has shown.

Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Non-Hodgkin's lymphoma complicated with human coronavirus HKU1 pneumonia: A case report and literature review.

Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.

Acute or chronic? Failing left ventricle in a 34 year old

Submission content Introduction: An unusual case of a very young patient without previously known cardiac disease presenting with severe left ventricular failure, detected by a point of care echocardiogram. Main Body: A 34 year old previously well man was brought to hospital after seeing his general practitioner with one month of progressive shortness of breath on exertion. This began around the time the patient received his second covid-19 vaccination. He was sleeping in a chair as he was unable to lie flat. Abnormal observations led the GP to call an ambulance. In the emergency department, the patient required oxygen 5L/min to maintain SpO2 >94%, but he was not in respiratory distress at rest. Blood pressure was 92/53mmHg, mean 67mmHg. Point of care testing for COVID-19 was negative. He was alert, with warm peripheries. Lactate was 1.0mmol/L and he was producing more than 0.5ml/kg/hr of urine. There was no ankle swelling. ECG showed sinus tachycardia. He underwent CT pulmonary angiography which demonstrated no pulmonary embolus, but there was bilateral pulmonary edema. Troponin was 17ng/l, BNP was 2700pg/ml. Furosemide 40mg was given intravenously by the general medical team. Critical care outreach asked for an urgent intensivist review given the highly unusual diagnosis of pulmonary edema in a man of this age. An immediate FUSIC Heart scan identified a dilated left ventricle with end diastolic diameter 7cm and severe global systolic impairment. The right ventricle was not severely impaired, with TAPSE 18mm. There was no significant pericardial effusion. Multiple B lines and trace pulmonary effusions were identified at the lung bases. The patient was urgently discussed with the regional cardiac unit in case of further deterioration, basic images were shared via a cloud system. A potential diagnosis of vaccination-associated myocarditis was considered,1 but in view of the low troponin, the presentation was felt most likely to represent decompensated chronic dilated cardiomyopathy. The patient disclosed a family history of early cardiac death in males. Aggressive diuresis was commenced. The patient was admitted to a monitored bed given the potential risk of arrhythmia or further haemodynamic deterioration. Advice was given that in the event of worsening hypotension, fluids should not be administered but the cardiac centre should be contacted immediately. Formal echocardiography confirmed the POCUS findings, with ejection fraction <35%. He was initiated on ACE inhibitors and beta adrenergic blockade. His symptoms improved and he was able to return home and to work, and is currently undergoing further investigations to establish the etiology of his condition. Conclusion(s): Early echocardiography provided early evidence of a cardiac cause for the patient's presentation and highlighted the severity of the underlying pathology. This directed early aggressive diuresis and safety-netting by virtue of discussion with a tertiary cardiac centre whilst it was established whether this was an acute or decompensated chronic pathology. Ultrasound findings: PLAX, PSAX and A4Ch views demonstrating a severely dilated (7cm end diastolic diameter) left ventricle with global severe systolic impairment.

Long-term support of COVID-19 patients with veno-venous extracorporeal membrane oxygenation: Complications, predictors of mortality and long-term outcome

Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.

The Impact of Dialysis Sessions on Blood Levels of D-dimer among Chronic Kidney Disease Patients Infected with COVID-19

Coronavirus disease-19 (COVID-19) pandemic is a real challenge to our communities worldwide, exerting a high socioeconomic impact. The disease is associated with a great deal of co-agulation cascade disorder, with a considerable increase in D-dimer concentration in blood. Objec-tives: To assess the impact of dialysis session frequency on blood levels of D-dimer among CKD patients infected with COVID-19. Patients and Methods: The study included 40 CKD patients (22 males and 18 females) infected with COVID-19, who attended the Artificial Kidney Unit at Al Hussein Teaching Hospital, Thi-Qar, Iraq for regular dialysis. They were divided into two groups;Group I: 20 CKD patients who had COVID-19. They underwent one hemodialysis session per week. The second group, which included 20 CKD patients infected with COVID-19 underwent three dialysis sessions per week. Plasma levels of D-dimer were measured one day before the start of the study and one day after three weeks in both groups. Result(s): The results of the present study re-vealed that CKD patients infected with COVID-19 who underwent three dialysis session per week (Group II) had a significant drop in blood D-dimer level at the end of three weeks in comparison to the initial values. Furthermore, the decrease in blood D-dimer level was significantly higher among CKD patients with COVID-19 who underwent three dialysis sessions per week (Group II) in comparison to COVID-19 infected CKD patients who underwent single dialysis sessions per week (Group I). Conclusion(s): CKD patients with COVID-19 have an elevated blood level of D-dimer. Increasing the frequency of hemodialysis plays an essential role in lowering the serum D-dimer level among these patients.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Characterization of Adaptive Immune Responses to SARS-CoV-2 Updated Bivalent Booster

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

COVID-19 in tobacco users.

Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Acute myocardial infarction and coronavirus infection (COVID-19).

The aim of the study is to describe a case of COVID-19 and myocardial infarction in an elderly patient. Material and methods. The analysis of medical documentation (outpatient card of the patient, medical history, postmortem report) was carried out. Studied macro- and micropreparations (staining with hematoxylin and eosin). Results. A 67-year-old patient, from 23.04.2020 to 26.04.2020, was hospitalized with a diagnosis of suspected coronavirus infection (COVID-19). On the background of the treatment, the patient's biological death occurred (26.04.2020). The sectional study revealed signs of bilateral total hemorrhagic pneumonia. The signs of acute transmural myocardial infarction of the anterior wall of the left ventricle were determined. Posthumously, SARS-CoV-2 RNA was detected in the lung tissue by nucleic acid amplification. In the described clinical case, a patient with concomitant cardiovascular diseases, such as arterial hypertension, coronary heart disease, developed complications against the background of COVID-19: hemorrhagic pneumonia and myocardial infarction with a fatal outcome.Copyright © Infectious Diseases: News, Opinions, Training.

Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

Findings from the ECHO Cohorts Regarding the Effects of the COVID-19 Pandemic

Background: Studies suggest perinatal infection with SARSCoV- 2 can induce adverse birth outcomes, but studies published to date have substantial limitations. Most have identified cases based upon their presentation for clinical care, and very few have examined pandemic-related stress which may also impact adverse birth outcomes. Objective(s): To evaluate the relationships between SARSCoV- 2 infection in pregnancy and pandemic-related stress with birth outcomes. Study Design: We conducted an observational study of 211 mother-newborn dyads in three urban cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program. Serology for SARS-CoV-2 was assessed in a convenience sample of prenatal maternal, cord serum or dried blood spots from births occurring between January 2020-September 2021. Specimens were assessed for IgG, IgM, and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. A Pandemic-related Traumatic Stress (PTS) scale was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Acute Stress Disorder criteria. Result(s): 36% were positive for at least one antibody type, chiefly IgG. Self-report of infection was not significantly correlated with combined serology. There were no differences in gestational age (GA), birth weight, preterm birth (PTB), or low birth weight (LBW) among seropositive mothers. However, IgM seropositive mothers had children with lower BW (434g, 95% CI: 116- 752), BW Z score-for-GA (0.73 SD, 95% CI 0.10-1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22-62.4). Associations with LBW sustained in sensitivity analyses limited to pre-vaccine samples, and PTS symptoms were not associated with birth outcomes. The addition of PTS did not substantially change associations with BW, although associations with PTB attenuated to near-significance. Conclusion(s): We identified decreased birth weight and increased prematurity in mothers IgM seropositive to SARS-CoV-2, independent of PTS. Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy.

Dried Blood Spot Analyses for the Diagnosis of Anti-cytokine Autoantibodies

Background: High-titer neutralizing anti-cytokine autoantibodies have been shown to be involved in several acquired diseases, including pulmonary alveolar proteinosis, cryptococcal meningitis, and disseminated/extrapulmonary Nocardia infections (anti-GM-CSF autoantibodies), disseminated mycobacterial disease (anti-IFN-gamma autoantibodies), and some cases of severe COVID-19 infection (anti-type 1 interferons). Currently, patient blood samples are shipped via courier and require temperaturecontrolled conditions for transfer. This method is expensive and requires patients to have access to medical personnel to draw the blood. However, the well-established technique of collecting blood on a paper card as a dried blood spot (DBS) for diagnosis offers a point of care alternative which can be performed with a simple finger prick. This method is less invasive, cheaper, and allows for easy transport of patient samples. Method(s): 30 uL of whole blood from patients was blotted on filter paper and stored at 4C until use. The filter paper was hole punched and each punched spot was eluted with 150 uL of a 0.05% Tween PBS solution at room temperature overnight. The eluate was screened for anti-cytokine autoantibodies using a particle-based approach. Patient plasma was also screened in conjunction for comparison. Result(s): We confirmed the presence of autoantibodies in the DBS eluate from 4 previously diagnosed patients with anti-GM-CSF autoantibodies and 2 patients with anti-IFN-gamma autoantibodies. Functional studies showed the DBS eluate from a patient with anti-GM-CSF autoantibodies was able to block GM-CSF-induced STAT-5 phosphorylation in normal PBMC. As a proof of concept and to increase the number of patients evaluated, we also confirmed the presence of anti-cytokine autoantibodies using dried plasma eluate from 9 patients with known anti-GM-CSF autoantibodies and 9 patients with anti-IFN-gamma autoantibodies. Levels detected in DBS analyses were comparable to the levels found in plasma from the same patients not subjected to blotting and elution. Temperature studies showed that the autoantibodies were detected at similar levels when stored at 4C, 25C, and 40C for a week. Conclusion(s): The diagnosis of pathogenic anti-cytokine autoantibodies should be considered in the context of unusual or adult-onset infections, and screening for this diagnosis can be performed with dried blood spot testing.Copyright © 2023 Elsevier Inc.

Preoperative COVID-19 RT-PCR Testing of Asymptomatic Patients for Ophthalmic Surgery: Experience from Two Tertiary Referral Centers

Purpose: The aim of this study was to evaluate how prevalent asymptomatic SARS-CoV-2 virus infection (COVID-19) is among patients undergoing ophthalmic surgery at two tertiary referral hospitals. Material(s) and Method(s): This retrospective study included patients without COVID-19 symptoms who underwent preoperative screening using reverse transcription-polymerase chain reaction (RT-PCR) before ophthalmic surgery at the Kocaeli University and Gaziantep University departments of ophthalmology [between September 1, 2020, and December 15, 2020 (group 1);between March 1, 2021, and May 30, 2021 (group 2)]. Patients scheduled for surgery and followed up in the retina, glaucoma, pediatric ophthalmology and strabismus, cataract and refractive surgery, and cornea departments were examined. Result(s): RT-PCR was positive for SARS-CoV-2 in 12 (1.4%) of 840 patients in group 1 and 7 (1.1%) out of 600 patients in group 2. None of the patients were symptomatic of COVID-19. The majority of the patients were scheduled for retina or cataract and refractive surgery in both groups (group 1;retina: 29.2%, cataract and refractive: 57.0%, group-2;retina: 31.3%, cataract and refractive: 54.5%). SARS-CoV-2 RT-PCR testing was positive for seven patients in group 1 (7/245, 2.9%) and five patients in group 2 (5/188, 2.6%) who were scheduled for retinal surgery. Conclusion(s): The necessity, availability, and practicality of COVID-19 RT-PCR testing prior to ophthalmic surgeries varies depending on the protocols of each institution. COVID-19 RT-PCR testing is suggested especially before vitreoretinal surgeries and general anesthesia procedures, because of the difficulty in managing postoperative complications.Copyright © 2023 Gazi Eye Foundation. All rights reserved.

Increases in expression of carbohydrate sulfotransferases CHST11 and CHST15 and decline in N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB) require phospho-p38-MAPK following exposure to SARS-CoV-2 spike protein receptor binding domain in human a

Objective: Immunohistochemistry of post-mortem lung tissue from Covid-19 patients with diffuse alveolar damage demonstrated marked increases in chondroitin sulfate and CHST15 and decline in N-acetylgalactosamine-4-sulfatase. Studies were undertaken to identify the mechanisms involved in these effects. Method(s): Human primary small airway epithelial cells (PCS 301-010;ATCC) were cultured and exposed to the SARSCoV- 2 spike protein receptor binding domain (SPRBD;AA: Lys310-Leu560;Amsbio). Expression of the spike protein receptor, angiotensin converting enzyme 2 (ACE2), was enhanced by treatment with Interferon-beta. Promoter activation, DNA-binding, RNA silencing, QPCR, Western blots, ELISAs, and specific enzyme inhibitors were used to elucidate the underlying molecular mechanisms. Result(s): Treatment of the cultured cells by the SPRBD led to increased CHST15 and CHST11 expression and decline in ARSB expression. Sulfotransferase activity, total chondroitin sulfate, and sulfated glycosaminoglycan (GAG) content were increased. Phospho-T180/T182-p38-MAPK and phospho- S423/S425-Smad3 were required for the activation of the CHST15 and CHST11 promoters. Inhibition by SB203580, a phospho-p38 MAPK inhibitor, and by SIS3, a Smad3 inhibitor, blocked the CHST15 and CHST11 promoter activation. SB203580 reversed the SPRBD-induced decline in ARSB expression, but SIS3 had no effect on ARSB expression or promoter activation. Phospho-p38 MAPK was shown to reduce retinoblastoma protein (RB) S807/S811 phosphorylation and increase RB S249/T252 phosphorylation. E2F-DNA binding declined following exposure to SPRBD, and SB203580 reversed this effect. This indicates a mechanism by which SPRBD, phospho-p38 MAPK, E2F, and RB can regulate ARSB expression and thereby impact on chondroitin 4-sulfate and dermatan sulfate and molecules that bind to these sulfated GAGs, including Interleukin-8, bone morphogenetic protein-4, galectin-3 and SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2). Conclusion(s): The enzyme ARSB is required for the degradation of chondroitin 4-sulfate and dermatan sulfate, and accumulation of these sulfated GAGs can contribute to lung pathophysiology, as evident in Covid-19. Some effects of the SPRBD may be attributable to unopposed Angiotensin II, when Ang1-7 counter effects are diminished due to binding of ACE2 with the SARS-CoV-2 spike protein and reduced production of Ang1-7. Aberrant cell signaling and activation of the phospho-p38 MAPK and Smad3 pathways increase CHST15 and CHST11 production, which can contribute to increased chondroitin sulfate in infected cells. Decline in ARSB may occur as a consequence of effects of phospho-p38 MAPK on RB phosphorylation and E2F1 availability. Decline in ARSB and the resulting impaired degradation of sulfated GAGs have profound consequences on cellular metabolic, signaling, and transcriptional events. Funding is VA Merit Award.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Adverse Effects of Covid-19 Vaccine, an Observational Studymainly Focusing on the Cutaneous Reactions in Both Genders

Objective: COVID-19 caused a deleterious impact on the health care system globally.The roll out of vaccines seems to be the only effective way to curtail the spread of disease.The purpose of this study is to assess the dermatological adverse effect of post COVID-19vaccination on a gender basis. Methodology: This was an observational,cross-sectional,questionnaire-based survey conducted in Pakistan.The sample comprises 518 participants. The questionnaire was self-designed. The trial lasted six months, from August 1, 2022, until January 31, 2023. We used a non-probability sampling technique.Dermatological adverse effects like burning pain, redness, rashes, and lymphadenopathy at the injection site were recorded.Fever was also noted. All the participants have received booster shots or double doses of any one of CCOVID-19 vaccines, such as AstraZeneca, Pfizer, Sinovac, Sinopharm,Pakvac, etc. A p-value of less than 0.05 was considered statistically significant.Qualitative data was reported as frequency and percentage, and quantitativedata was reported as standard deviation and mean. Result(s): The study included 518 subjects, of whom 262 were males and 256 were females. The mean age of male is 42.70+/-14.05 years and female is 39.04+/-14.6years with a significant difference observed between them (p=0.004). The most common complaint among dermatological adverse effects after first was pain. 106(40.5%) male and 132(51.6%) female reported painwith a significant difference observed between them (p=0.011) followed by swelling which was reported by 92(35.1%) males and 120(46.9%) females with a significant difference observed between them (p=0.006).Burning was reported in 92(35.1%) male and 148(57.8%) female with a significant difference observed between them(p<0.001). Fever was also quite commonly reported in both male 116(44.3%) and female 178(69.5%) with significantdifference observed between them (p<0.001),Likewise post 2nd dose of vaccination, pain was most commonly noted in 90(34.4%) male and female 124(48.4%) female with significant difference observed between them (p=0.001). Moreover, burning was reported by 80(30.5%) malesand 132(51.6%) females with a significant difference observed between them (p<0.001). rashes were reported by76(29.0%) males and 100(39.1%) females with a significant difference observed between them (p=0.016), lymphadenopathy was also significantly associated with genders, (p<0.001). Conclusion(s): This study concluded that the burning pain,redness,rashes,and lymphadenopathywere the most prevalent side effects in male and female post 1st and 2ndCOVID-19 vaccination.Furthermore fever was also reported in majority of subjects.In addition to this higher percentage of side effects were recorded in females as comparedto males.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Metodo LAMP como alternativa diagnostica para la deteccion del virus SARS-CoV-2

Summary Introduction: The SARS-CoV-2 coronavirus, that causes the COVID-19 disease, has become a global public health problem that requires the implementation of rapid and sensitive diagnostic tests. Aim(s): To evaluate and compare the sensitivity of LAMP assay to a standard method and use RT-LAMP for the diagnosis of SARS-CoV-2 in clinical samples from Colombian patients. Method(s): A descriptive and cross-sectional study was conducted. A total of 25 nasopharyngeal swab samples including negative and positive samples for SARS-CoV-2 were analyzed, through the RT-LAMP method compared to the RT-qPCR assay. Result(s): LAMP method detected ~18 copies of the N gene, in 30 min, evidenced a detection limit similar to the standard method, in a shorter time and a concordance in RT-LAMP of 100% with the results. Conclusion(s): RT-LAMP is a sensitive, specific, and rapid method that can be used as a diagnostic aid of COVID-19 disease.Copyright © 2021. All Rights Reserved.

Association of SARS-COV-2 viral RNAemia, IL- 6 gene polymorphism, serum IL-6 and peripheral blood lymphocytes and monocytes with disease severity in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.

Septic cavernous sinus thrombosis in a patient with COVID-19.

The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Using Absorbable Suture For Traumatic Wound Closure To Avoid Additional Hospital Visit For Suture Removal During The Covid 19 Pandemic: A Randomized Controlled Trial

Introduction: The COVID-19 pandemic worldwide forced governments to undertake intervention measures to encourage social distancing. Meanwhile, traumatic skin lacerations require multiple hospital visits for dressing, changings, and suture removal since they are usually repaired with non-absorbable sutures. In a matter of fact, these visits can be avoided by using absorbable sutures instead. However, absorbable sutures carry the theoretical risk of wound infection. In this study, our aim was to determine whether absorbable sutures are better than non-absorbable sutures in repairing lacerations during the COVID-19 pandemic. The first and second objectives were to assess the rate of infection and the number of postoperative hospital visits. Method(s): A sample of 469 patients with traumatic skin lacerations were analysed during the COVID-19 pandemic in April-July 2020. In the control group, wounds were repaired using non-absorbable sutures, while rapid-onset absorbable sutures were used in the treatment group. By conducting a phone call follow-up after 21 days, several parameters regarding infection signs and hospital visits were compared between both groups. Result(s): No statistically significant difference was observed between both groups regarding wound infection (p-value= 0.623). Using absorbable sutures resulted in fewer postoperative hospital visits than non-absorbable sutures (p-value= 0.001). This study is limited because the assessment of wound infection was subjective to the patient by a phone call follow-up. Conclusion(s): Using absorbable sutures to close traumatic skin lacerations is safe. They should be considered during a pandemic to reduce hospital visits for suture removal, which will subsequently enhance social distancing and relieve hospital load.

Covid-19: Is the placenta a safe space

Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.