Functionality of immune cells in COVID-19 infection: development of cell-based therapeutics.

Introduction: In late December 2019, a sudden severe respiratory illness of unknown origin was reported in China. In early January 2020, the cause of COVID-19 infection was announced a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Examination of the SARS-CoV-2 genome sequence revealed a close resemblance to the previously reported SARS-CoV and coronavirus Middle East respiratory syndrome (MERS-CoV). However, initial testing of drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. One of the key strategies to fight the virus is to look at how the immune system works against the virus, which has led to a better understanding of the disease and the development of new therapies and vaccine designs. Methods: This review discussed the innate and acquired immune system responses and how immune cells function against the virus to shed light on the human body's defense strategies. Results: Although immune responses have been revealed critical to eradicating infections caused by coronaviruses, dysregulated immune responses can lead to immune pathologies thoroughly investigated. Also, the benefit of mesenchymal stem cells, NK cells, Treg cells, specific T cells, and platelet lysates have been submitted as promising solutions to prevent the effects of infection in patients with COVID-19. Conclusion: It has been concluded that none of the above has undoubtedly been approved for the treatment or prevention of COVID-19, but clinical trials are underway better to understand the efficacy and safety of these cellular therapies.

Molecular and phylogenetic analysis of E. vermicularis in appendectomy specimens from Iran.

Human infection with Enterobius vermicularis occurs worldwide, particularly in children. The role of E. vermicularis in appendicitis is neglected. This study was designed to investigate genotypes of E. vermicularis detected from appendectomy specimens in the human population from Iran and clarify the intra-species variation of the parasite. Seventy appendectomies for acute clinical appendicitis isolates from Azerbaijan and North Khorasan of Iran were used in the present study. The genetic information of Tehran and Hamedan regions was also obtained from GenBank for comparison and analysis. The nucleotide sequence of cytochrome c oxidase subunit 1 (cox1) gene was analyzed to perform genetic differentiation, haplotype network analysis, and population structure. Phylogenetic analysis of all the isolates were included in type B haplogroup. The number of haplotypes in all geographical locations of Iran is not much. Network analysis of sequences for regions such as Thailand, Iran, Denmark, and Poland show three classified subtypes B1, B2, and B3 in the B haplogroup. It seems that the haplotypes of E. vermicularis detected from appendectomy are B type, and divided into three subtypes. Further research using another genetic marker is required to elucidate the genetic variation of the parasites in detail.

Three cases of brain hydatidosis in North Khorasan, Iran.

Cystic hydatidosis is a serious public health problem in Iran. Although cysts can develop in almost all organs and the brain cysts are very rare. Here, we present 3 confirmed cases of brain hydatidosis and the patients who underwent successful surgery. Pathological examinations demonstrated the presence of cystic hydatidosis.

Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart.

Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.

Clinico-Hematological Findings of Acute Pediatric Visceral Leishmaniasis Referred to the Northeast of Iran during 2005-2015.

BACKGROUND: To characterize the epidemiological, clinical, hematological and biochemical features of 33 cases hospitalized with pediatric visceral leishmaniasis (PVL) in North Khorasan Province of Iran from 2005 to 2015. METHODS: The serological, hematological and biochemical tests were employed in 33 children between 8 months to 6 yr with a final diagnosis of acute visceral leishmaniasis (VL). The diagnosis of VL was established by microscopic demonstration of Leishmania spp. amastigotes inactive bone marrow aspiration (BMA). RESULTS: The most common presenting features were anemia (82.5%), fever (75%), and hepatosplenomegaly (45.4%). Various hematological parameters showed that most patients were suffering from moderate to severe microcytic hypochromic anemia (78.8% had RBC count less than 4 million cells/ul, 67.7% Hb less than 8 fl). 66.7% of them were leukopenic (WBC: less than 5× 10 3 /µL) and 24.2% had decreased platelet counts. Pancytopenia was observed in 18.2% of cases. MCV, MCH, and MCHC levels were below the reference range in 88%, 90% and 85.1% of the patients respectively. Moreover, aspartate transaminase (AST) and alanine transaminase (ALT) levels were increased in 53.33% and 6.66% of the patients respectively. 92.9% of cases were C-reactive protein (CRP) positive. Bone marrow was found hyper-cellular in all of them, and myeloid to erythroid ratio (M/E) was more than 4 in 39.1% of cases. Plasma cells slightly were increased in 60% of patients and megakaryocytes were decreased in thrombocytopenic patients. CONCLUSION: Bone marrow/splenic aspiration still remains the gold standard test despite its risk and pain for patients.

Survival analysis of patients with hip fracture, Shiraz, Iran.

This study aimed to determine factors affecting the survival of patients with hip fracture in Shiraz, Iran. Alzheimer's disease, hypertension, and cardiovascular diseases were risk factors, while female gender and living with family members or in nursing homes were protective factors against mortality following hip fracture. PURPOSE: Hip fractures are the most common orthopedic fractures in elderly. This study aimed to determine the factors affecting the survival of patients with hip fracture in Shiraz. METHODS: This historical cohort study was conducted in Shiraz, Iran. All patients with hip fracture who were admitted to any of the hospitals providing orthopedic services in Shiraz, from September 1, 2011, to August 30, 2012, were included in the study. The log rank test, Kaplan-Meier methods, and the univariate and multivariate Cox regression model were used for data analysis. RESULTS: A total of 631 patients were enrolled, of these, 264 (41.8%) were male. The mean age of patients was 74.9 ± 11.5. The patients' survival rate after the 1st, 2nd, 3rd, 4th, and 5th year were 81.1%, 73.7%, 69.4%, 64.8%, and 60.2%, respectively. After adjusting data for age, Alzheimer's disease (HR = 4.9, 95% CI 1.4-7.3, P = 0.023), hypertension (HR = 2.27, 95% CI 1.3-3.8, P = 0.003), and cardiovascular diseases (HR = 2.02, 95% CI 1.04-3.09, P = 0.039) remained as risk factors for mortality in patients with hip fracture. However, female patients (HR = 0.46, 95% CI 0.27-0.8, P = 0.006) and those who lived with family members or in nursing homes (HR = 0.43, 95% CI 0.19-0.92, P = 0.03) were protective factors. CONCLUSION: This study showed that women are more likely to have hip fractures, but mortality among men is more observable. Alzheimer's disease, hypertension, and cardiovascular diseases were considered as risk factors, while patients who were female and those who lived with the family member or in nursing homes had better survival.

Factors affecting recovery during the first 6 months after hip fracture, using the decision tree model.

Pelvic fractures are one of the most common orthopedic problems that can reduce the quality of life in the elderly. In this prospective study, we found that osteoporosis, depression, and socioeconomic status were the most important factors associated with patients' recovery during the first 6 months after pelvic fracture. PURPOSE: Hip fractures are one of the most common orthopedic problems that can reduce the quality of life in the elderly. Considering that, we aimed to provide a comprehensive assessment of the factors affecting recovery during the first 6 months after hip fracture. METHODS: All patients with hip fracture admitted to any of the orthopedic hospitals during July 10, 2011 to July 9, 2012 in Shiraz, Iran were included in this prospective cohort study. Patients' demographic data and also information regarding their performance and mobility after hip fracture was collected in two interviews at intervals of 6 months. All analyses were done in R software and mostly by party packages and PCAmixdata package. Tree and forest models of conditional inference were used to evaluate the factors affecting the recovery after hip fracture. RESULTS: Two hundred sixty-six out of 514 patients (51.75%) with hip fracture recovered completely after a 6-month follow-up period. Osteoporosis, new-onset depression after hip fracture, and socioeconomic status (SES) were the most important predictors of patients' mobility status 6 months after hip fracture. In identifying predictor variables, the conditional inference forest method provided a more appropriate fit for the data than the conditional inference tree. CONCLUSIONS: Awareness of the factors that affect patients' recovery can be helpful in improving the patients' health, as well as improving care services, thereby increasing the success of treatment. Osteoporosis, new-onset depression after hip fracture, and SES were the most important factors associated with patients' recovery. Therefore, focusing on these variables is essential.

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling.

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

Is There Any Benefit of Neuromonitoring During Descending and Thoracoabdominal Aortic Aneurysm Repair?

OBJECTIVE: Paraplegia remains the most feared and a devastating complication after descending and thoracoabdominal aneurysm operative repair (DTA and TAAAR). Neuromonitoring, particularly use of motor-evoked potentials (MEPs), for this surgery has gained popularity. However, ambiguity remains regarding its use and benefit. We systematically reviewed the literature to assess the benefit and applicability of neuromonitoring in DTA and TAAAR. METHODS: Electronic searches were performed on 4 major databases from inception until February 2014 to identify relevant studies. Eligibility decisions, method quality, data extraction, and analysis were performed according to predefined clinical criteria and end points. RESULTS: Among the studies matching our inclusion criteria, 1297 patients had MEP monitoring during DTA and TAAAR. In-hospital mortality was low (6.9% ± 3.6). Immediate neurological deficit was low (3.5% ± 2.6). In one third of patients (30.4% ± 14.2), the MEPs dropped below threshold, which were 30.4% and 29.4% with threshold levels of 75% and 50%, respectively. A range of surgical techniques were applied after reduction in MEPs. Most patients whose MEPs dropped and remained below threshold had immediate permanent neurological deficit (92.0% ± 23.6). Somatosensory-evoked potentials were reported in one third of papers with little association between loss of somatosensory-evoked potentials and permanent neurological deficit (16.7% ± 28.9%). CONCLUSIONS: We demonstrate that MEPs are useful at predicting paraplegia in patients who lose their MEPs and do not regain them intraoperatively. To date, there is no consensus regarding the applicability and use of MEPs. Current evidence does not mandate or support MEP use.

Setting up and utilizing a service for measuring perioperative transcranial motor evoked potentials during thoracoabdominal aortic surgery and thoracic endovascular repair.

OBJECTIVES: Paraplegia is a complication that may occur following surgery or endovascular stenting of thoracic and thoracoabdominal aortic pathology. Measuring transcranial motor evoked potentials (tcMEPs) has been shown to provide a reliable measure of spinal cord function during such procedures allowing interventions to protect cord function. In the spirit of sharing experience and eliminating the learning curve for others, this manuscript describes our experience of setting up a service for tcMEP monitoring as well as the documents and algorithms for measuring, recording and acting on the patient data, the so-called 'MEP Pathway'. METHODS: Recording and interpretation of tcMEP during thoracoabdominal aortic intervention requires training of staff and close team working in the operating theatre and postoperative intensive care unit. Providing consistent, reliable, specific and sensitive information on spinal cord function and its safe and effective use to alter patient outcomes requires a protocol. The MEP pathway was developed by medical and paramedical staff at our institution based on clinical experience and literature reviews over a 1-year period (2012-2013). RESULTS: The tcMEP pathway comprises six documents that guide staff in: (a) assessing suitability of patients, (b) setting up hardware, (c) preparing algorithms for management, (d) documenting intervention (left heart bypass, cardiopulmonary bypass or endovascular stenting) as well as (e) documenting postoperative intensive care processes. CONCLUSIONS: The tcMEP pathway acts as a guide for safe introduction and use of tcMEPs in thoracoabdominal aortic interventions. tcMEP-led guidance of intraoperative and postoperative management in thoracic aortic surgery is an important adjunct in caring for this patient group.

Novel application of acetazolamide to reduce cerebrospinal fluid production in patients undergoing thoracoabdominal aortic surgery.

OBJECTIVES: Paraplegia is a rare but devastating complication, which may follow thoracoabdominal aortic surgery. Many adjuncts have been developed to reduce this risk including cerebrospinal fluid (CSF) drainage. Acetazolamide (carbonic anhydrase inhibitor) is a drug used to counteract mountain sickness and one of its effects is to reduce CSF production. Here, we report its first postoperative application in thoracoabdominal surgery with the aim of reducing cerebrospinal cord perfusion pressure and reducing risk of paraplegia. METHODS: We retrospectively reviewed 6 patients who have been treated with this drug between 2011 and 2012 who were undergoing thoracoabdominal aortic surgery. Our indications were decided to include: (i) patients in whom a spinal drain could not be positioned; (ii) patients with blood-stained CSF; (iii) patients in whom the volume of CSF drained was outside guidelines; (iv) patients in whom CSF pressure was elevated; (v) patients with excessive vasopressor usage and (vi) patients with postoperative neurological dysfunction as measured by motor-evoked potentials or clinical examination. All were given 500 mg intravenous acetazolamide, not more than eight hourly, for a duration dependent on response. RESULTS: In the 6 patients, 2 received a single dose of the drug and responded by an immediate drop in intracranial pressure (ICP) pressure. Of the 4 who received multiple doses of the drug, 1 had an immediate decline in ICP after each of the first six doses, while 3 had no discernable response. CONCLUSIONS: This is the first report of the efficacy of acetazolamide in reducing CSF production and lowering ICP during thoracoabdominal aortic surgery. We believe that its use will be beneficial in the 6 patient groups described. Our experience suggests there are 'responders' and 'non-responders', the characteristics of whom are yet to be defined. Its efficacy in reducing not just CSF volume and ICP but also clinically relevant morbidity such as paraplegia, is the subject of a planned randomized controlled trial. This report serves to raise awareness of the possible efficacy of this drug when normal management strategies are limited or exhausted.