Platelet Glycoprotein IIIa PlA1/PlA2 Polymorphism Modulates the Risk of Myocardial Infarction in Non-Diabetics.

Background: Genetic polymorphisms of platelet glycoprotein IIIa (GPIIIa gene) have been investigated intensively in several thrombotic diseases, but their role in cardiovascular diseases remains controversial. This study aimed to investigate the association between platelet glycoprotein IIIa PlA1/PlA2 polymorphism and susceptibility to myocardial infarction in non-diabetics. Methods: A total of 200 participants were recruited for the study, 100 non-diabetic patients with myocardial infarction and 100 apparently healthy volunteers as a control group. GPIIIa PlA1/PlA2 polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The distribution of GPIIIa PlA1/PlA2 polymorphic genotypes among the study groups was significantly different (P value = 0.00). The PlA1/PlA2 and PlA2/PlA2 genotypes were more frequent in the patients with myocardial infarction while the genotype PlA1/PlA1 was more prevalent in the control group. There was a statistically significant association between the PlA1/PlA1 genotype and reduced risk of both ST-segment elevation myocardial infarction (odds ratio (OR) = 0.19; 95% confidence interval (CI): 0.09 - 0.34, P value = 0.00) and non-ST-segment elevation myocardial infarction (OR = 0.21; 95% CI: 0.09 - 0.45, P value = 0.00). The genotype PlA1/PlA2 was found to be associated with an increased risk of both types of myocardial infarction (OR = 6.0; 95% CI: 2.61 - 13.8, P value = 0.00 for ST-segment elevation myocardial infarction and OR = 6.65; 95% CI: 2.69 - 16.45, P value = 0.00 for non- ST-segment elevation myocardial infarction. In the patients carrying the PlA1/PlA2 genotype, the risk of ST-segment elevation myocardial infarction was increased to about 14 folds in the presence of family history (OR: 13.57, 95% CI: 1.42 - 130.03, P value = 0.02), and the risk of non-ST-segment elevation myocardial infarction increased to about 18 folds in the smokers carrying the genotype PlA2/PlA2 (OR: 17.63, 95% CI: 0.96 - 324.70, P value = 0.05). Conclusions: The GPIII PlA1/PlA1 genotype is associated with a reduced risk of ST-segment elevation and non-ST-segment elevation myocardial infarction, while PlA1/PlA2 is associated with an increased risk of both types of myocardial infarction.

COVID-19 Vaccine as a Potential Triggering Factor for Anti-Glomerular Basement Membrane (GBM) Disease: A Case Report and Literature Review.

Coronavirus 2019 (COVID-19) is considered one of the most significant medical pandemics of this century, with high morbidity and mortality associated with the pandemic. The virus was recognized initially as a cause of pneumonia, but subsequent studies showed significant association with gastrointestinal, neurological, and autoimmune diseases. By 2020, several vaccines became available for use, significantly reducing the infection rate. A good safety profile supported most of the studies related to vaccines. However, this area is still under study, and some reports linked the COVID-19 vaccine to the development of thrombocytopenia, thrombosis, Guillain-Barre syndrome, autoimmune diseases, and myocarditis. These side effects need to be reported to VAERS (Vaccine Adverse Event Reporting System). The exact etiology of anti-glomerular basement (Anti-GBM) disease remains unknown, but the disease is thought to be triggered by environmental factors in genetically predisposed individuals. It is considered one of the serious diseases that could lead to permanent kidney impairment if not treated early and adequately. That's why a great effort is being made by health care practitioners to figure out and avoid the risk and triggering factors. Few previously published papers linked the COVID-19 vaccine and the development of anti-GBM disease, which raised concerns about digging more into this area. Herein, we are reporting a case of a patient who developed rapidly progressive glomerulonephritis (RPGN) due to anti-glomerular basement membrane (GBM) antibody disease two days after receiving the second dose of the COVID-19 vaccine.

COVID-19 infection presented as Guillain-Barre Syndrome: Report of two new cases and review of 116 reported cases and case series.

BACKGROUND: /Aims: Corona virus disease 2019 (COVID 19) is a pandemic infectious disease of 2020, which often presents with respiratory and gastrointestinal symptoms. The behavior of the virus and its full clinical picture has not been fully studied yet. Many case reports and case series have been running in order to elaborate different presentations and associations. Pulmonary and gastrointestinal features of COVID-19 infection are well outlined; however, neurological manifestations are less defined. CASE PRESENTATION: We report two adult cases of COVID-19 infection presented with acute Guillain-Barre Syndrome (GBS), and a literature review on the causal association between COVID-19 and GBS. CONCLUSION: Our two case reports in addition to literature review of 116 published cases may help offer insight into the clinical course of COVID-19 infection. Our two COVID-19 patients presented with neurological manifestations of GBS which were not preceded with any respiratory, gastrointestinal or other systemic infection. This leads us to raise the possibility of establish direct causal association between COVID-19 infection and GBS. Physicians should have high clinical suspicions when encounter GBS patient during the current COVID-19 pandemic and consider co-existence of COVID-19 infection that may warrant SARS-CoV-2 testing, isolation precautions, and specific treatment for Covid-19 infection.

Case of Resistance to Thyroid Hormones With a Relatively Rare Mutation in Thyroid Hormones Receptor.

Normal thyroid hormone level is essential to maintain the normal physiologic function of the human body. Disturbances of these hormone levels have variable clinical manifestations ranging from asymptomatic to severe illness. Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced intracellular action of T3, the active thyroid hormone. It is a rare autosomal dominant condition and occurs mostly due to heterogeneous mutations in the thyroid hormone receptor. Other causes of RTH include thyroid hormone cell membrane transport defect and thyroid hormone metabolism defect. Affected individuals present with symptoms of both increased and decreased thyroid hormone action, depending on the tissue's predominant receptor isoform expression, the magnitude of hormonal resistance, and the effectiveness of compensatory mechanisms. Here, we share our experience in diagnosing a case of RTH confirmed with a genetic test and found to have sequence variant mutation that is not well described in the literature previously due to the absence of genetic conclusive evidence.

Eltrombopag Dose Adjustment During Infection-Induced Thrombocytosis in a Patient With Chronic Idiopathic Thrombocytopenic Purpura.

Idiopathic thrombocytopenic purpura (ITP) is an immune disorder in which antibodies attack platelets, leading to platelet destruction and increased bleeding risk. Standard treatment is to maintain a platelet count sufficient to mitigate the bleeding risk. First-line therapies include steroids and IV immunoglobulins, and second-line therapy includes thrombopoietin receptor agonists like eltrombopag in combination with other medications (e.g., rituximab) to reduce immune attack. Eltrombopag is a nonpeptide oral thrombopoietin (TPO)-receptor agonist that increases platelet counts by binding to and activating the human TPO receptor. While using eltrombopag, the target platelet count range is usually between 50,000/mm³ and 200,000/mm³, so the dose should be adjusted accordingly. However, this dose adjustment is based on platelet count increments in response to eltrombopag administration. Adjusting the dose when the platelet count is elevated due to a different factor can be challenging. Data are not yet available on whether stopping the treatment or reducing the dose will harm the patient or result in an acute drop in platelet count and increased bleeding. We present the case of a 60-year-old woman with ITP on a stable eltrombopag regimen who completed an eltrombopag-free period after developing infection-induced thrombocytosis.

Eltrombopag and its beneficial role in management of ulcerative Colitis associated with ITP as an upfront therapy case report.

Eltrombopag can be used safely as upfront medication in the management of ulcerative colitis as well as ITP, and it showed a beneficial effect in both disorders.

Steroid-Refractory Chronic Idiopathic Thrombocytopenic Purpura Responding to Combination Therapy With Eltrombopag and Rituximab.

Idiopathic thrombocytopenic purpura (ITP) is a disease in which the immune system attacks platelets and decreases their number, which increases the patient's risk of bleeding. ITP is diagnosed by exclusion and usually manifests as acute disease. It is self-limiting in pediatric patients, while it tends to be a chronic disease in adults. Treatment of ITP focuses on maintaining a sufficient platelet count to decrease the risk of bleeding rather than normalize the platelet count. Most patients respond to first-line treatments, such as steroids and intravenous immunoglobulin (IVIG). However, some cases can become steroid-dependent or unresponsive to first-line therapy, in which case, second-line therapy is required to control symptoms or the platelet count. Second-line therapy includes either rituximab or a thrombopoietin receptor agonist (eltrombopag, romiplostim). In a few cases, when second-line therapy alone is insufficient to control the disease, a combination of therapies is required to control the symptoms and platelet count. Here, we present a case of a 41-year-old man with refractory ITP who did not respond to first-line treatment with either steroids or IVIG or a combination of the two, and also did not respond to eltrombopag alone and required a combination of eltrombopag and rituximab to control his disease.

Left Anterior Descending Artery Bridging and Atypical Chest Pain in a Young Woman.

Cardiac-related chest pain is a frequent cause of morbidity and mortality and should be carefully assessed due to its burden on patient health. Its etiology can sometimes prove challenging to discover because of atypical presentations or rare causes of chest pain like myocardial bridging (MB). MB requires a high index of suspicion to be diagnosed. MB is a rare congenital anomaly that occurs due to the passage of a segment of a coronary artery inside the myocardium, causing chest pain due to compression during systole. MB usually has no clinical significance in most cases. However, when severe bridging occurs in the major coronary arteries, patients can experience myocardial ischemia, coronary thrombosis, myocardial infarction, and stress cardiomyopathy, leading to arrhythmias and sudden death. We present the case of a young woman who presented with atypical (rather than ischemic) chest pain due to MB.

A Case of Fulminant Liver Failure in a 24-Year-Old Man with Coinfection with Hepatitis B Virus and SARS-CoV-2.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a newly emerging disease that is still not fully characterized. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that can be transmitted easily from human to human mainly by the respiratory route. Currently, there is no specific treatment for COVID-19 or a vaccine for prevention. The disease has various degrees of severity. It often presents with nonspecific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Severe disease is associated with hemophagocytic syndrome and cytokine storm due to altered immune response. Patients with severe disease are more likely to have increased liver enzymes. The disease can affect the liver through various mechanisms. CASE REPORT We report an unusual case of SARS-CoV-2 infection in a 24-year-old man with no previous medical illness, who presented with mild respiratory involvement. He had no serious lung injury during the disease course. However, he experienced acute fulminant hepatitis B infection and cytokine release syndrome that led to multiorgan failure and death. CONCLUSIONS It is uncommon for SARS-CoV-2 infection with mild respiratory symptoms to result in severe systemic disease and organ failure. We report an unusual case of acute hepatitis B infection with concomitant SARS-CoV-2 leading to fulminant hepatitis, multiorgan failure, and death.

The Relationship Between Sickle Cell Disease and Sudden Onset Sensorineural Deafness.

Sickle cell anemia (SCA) is a hereditary hemoglobin (Hb) disorder associated with a very specific molecular lesion, which is the exchange of glutamic acid for valine in the sixth residue of the Hb beta chain, originating the S Hb. It is characterized by intermittent episodes of vascular occlusion and end-organ damage. Progressive organ damage may affect any organ with brain, eyes, pulmonary, hepatobiliary, spleen, genitourinary, and the musculoskeletal systems being the most commonly involved and reported. Other complications of the disease that have not been well described or studied include cranio-orbital syndromes, oropharyngeal syndromes, periodontal disease, and otologic syndromes. Considering the vaso-occlusive nature of sickle cell disease (SCD), the potential for auditory damage is not unexpected. However, the incidence of subjective hearing impairment among SCA is very low and and little is known about the relationship between SCA and hearing loss. Here we report a 43-year-old female with SCA who presented with sudden bilateral hearing loss and generalized body ache and admitted as a case of sensorineural deafness with vascular crisis; she received IV fluid and analgesia and improved after five days from the therapy.

Cutaneous Lesions as the Sole Presentation of Tuberous Sclerosis.

Tuberous sclerosis complex (TSC) is a rare genetic, neurocutaneous condition characterized by hamartomas in different organs, including the brain, skin, heart, kidney, and lungs. Fibromas are the typical presentation, but rare symptoms may present as well. We present the case of a 26-year-old woman who presented to our clinic with long-standing cutaneous manifestations of TSC and lacked the typical neurological and intellectual signs of the condition.

Low-Dose Eltrombopag in a Patient with Chronic Idiopathic Thrombocytopenic Purpura Post Sleeve Gastrectomy.

Idiopathic thrombocytopenic purpura (ITP) is a disease in which the immune system attacks platelets and causes decrease in its number exposing the patient to risk of bleeding. It is diagnosed by exclusion. Eltrombopag is a thrombopoietin receptor agonist which is used as second-line treatment for patients with ITP. The usual starting dose is 25 mg daily and maintenance dose is 75 mg daily. Little is known about the dose of eltrombopag in patients with sleeve gastrectomy since reduction in the amount of functioning gastrointestinal tract after gastric bypass surgery leads to decreased time to drug absorption and reduced drug bioavailability. Here we are reporting a 46-year-old female with ITP and sleeve gastrectomy who responded to low-dose eltrombopag 25 mg every other day, which is equivalent to 12.5 mg daily, and maintained adequate platelet counts on this dose.

Iron Deficiency Anemia-Induced Neutropenia in Adult Female.

Iron deficiency anemia is a common cause of anemia that develops when body stores of an iron drop too low to support normal red blood cell (RBC) production. Inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in the urine may be the cause. Iron is a key part of red blood cells. Without iron, the blood cannot carry oxygen effectively. Our body normally gets iron through the diet. It also reuses iron from old red blood cells. A little is known about the association between iron deficiency anemia and neutropenia. Here we report a 44-year-old female who presented with iron deficiency anemia and found to have neutropenia recovered after she received intravenous (IV) iron therapy. However, she did not develop any serious infections during the neutropenia and responded to iron therapy.

Treatment-Free Remission in Chronic Idiopathic Thrombocytopenic Purpura.

Idiopathic thrombocytopenic purpura (ITP) is a disease in which the immune system attacks platelets and causes a decrease in their number, exposing the patient to bleeding risk. It is a diagnosis by exclusion. ITP usually presents as acute disease and is self-limiting in pediatric patients, while it tends to be chronic in adults. Eltrombopag is a thrombopoietin receptor agonist used as a second-line treatment for ITP. This drug is approved for use in adults as second-line therapy, but little is known about its use in the pediatric patient population. We report the case of a 14-year-old girl with chronic steroid-dependent ITP who responded well to eltrombopag and maintained treatment-free remission after stopping the drug.

Herbal medicine as an auspicious therapeutic approach for the eradication of Helicobacter pylori infection: A concise review.

Helicobacter pylori (H. pylori) causes gastric mucosa inflammation and gastric cancer mostly via several virulence factors. Induction of proinflammatory pathways plays a crucial role in chronic inflammation, gastric carcinoma, and H. pylori pathogenesis. Herbal medicines (HMs) are nontoxic, inexpensive, and mostly anti-inflammatory reminding meticulous emphasis on the elimination of H. pylori and gastric cancer. Several HM has exerted paramount anti-H. pylori traits. In addition, they exert anti-inflammatory effects through several cellular circuits such as inhibition of 5'-adenosine monophosphate-activated protein kinase, nuclear factor-κB, and activator protein-1 pathway activation leading to the inhibition of proinflammatory cytokines (interleukin 1α [IL-1α], IL-1ß, IL-6, IL-8, IL-12, interferon γ, and tumor necrosis factor-α) expression. Furthermore, they inhibit nitrous oxide release and COX-2 and iNOS activity. The apoptosis induction in Th1 and Th17-polarized lymphocytes and M2-macrophagic polarization and STAT6 activation has also been exhibited. Thus, their exact consumable amount has not been revealed, and clinical trials are needed to achieve optimal concentration and their pharmacokinetics. In the aspect of bioavailability, solubility, absorption, and metabolism of herbal compounds, nanocarriers such as poly lactideco-glycolide-based loading and related formulations are helpful. Noticeably, combined therapies accompanied by probiotics can also be examined for better clearance of gastric mucosa. In addition, downregulation of inflammatory microRNAs (miRNAs) by HMs and upregulation of those anti-inflammatory miRNAs is proposed to protect the gastric mucosa. Thus there is anticipation that in near future HM-based formulations and proper delivery systems are possibly applicable against gastric cancer or other ailments because of H. pylori.

Seasonal behavior and forecasting trends of tuberculosis incidence in Holy Kerbala, Iraq.

Background: Pulmonary tuberculosis (PTB) remains major public health problem over the world. Cities witnessing religious event throughout of the year like Kerbala/Iraq require great efforts to minimize the incidence of deadly communicable diseases like TB. The aim of this study is to model the monthly incidence rates of PTB cases in Kerbala/Iraq. Methods: This is a retrospective study in which records of confirmed PTB patients whom they referred to the chest and respiratory illnesses center of Holy Kerbala governorate were obtained. Monthly registered new smear-positive PTB cases from January 2010 to December 2016 were analyzed. Seasonal autoregressive integrated moving average (SARIMA), SARIMA-exponential smoothing method (ETS), SARIMA-neural network autoregressive, and SARIMA-adaptive neuro-fuzzy inference system (SARIMA-ANFIS) were used for forecasting monthly incidence rate of TB in Kerbala, Iraq. Mean absolute percentage error, root mean square error, and mean absolute square error were used to compare the models, and Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to selected best model. Results: The trend of PTB incidence showed a seasonal characteristic, with peaks in spring and winter. Predicted estimates using all models proposed to forecast the number of PTB cases from 2016 to 2018 showed that the PTB cases indicated marginal decrease trends and best forecasted in SARIMA-ANFIS model (the lower AIC and BIC values, 712.69 and 731.05, respectively). Conclusion: Seasonal characteristic of PTB incidence was observed with peaks during spring and winter. Forecasting of PTB incidence between the period 2016 and 2018 showed marginal decrease trends, and the best forecasting model was SARIMA-ANFIS model.

Epidemiology of multidrug-resistant, extensively drug resistant, and totally drug resistant tuberculosis in Middle East countries.

The 2015 represent the deadline for the global tuberculosis (TB) targets set through the Millennium Development Goals (MDG). From 2016 and onward, new goals were set to end the global TB epidemic via implementing new campaign entitled "the End TB Strategy". The major hurdle to end TB epidemic in several parts of the world is the emergence and spread of drug resistant Mycobacterium tuberculosis (MTB) strains. The better understanding of the actual global burden of drug resistant tuberculosis would feed into better implementing the End TB Strategy. In this article we summarize the current knowledge on the patterns of drug resistance tuberculosis cases in the Middle East countries. These countries are served by the Eastern Mediterranean Regional Office (EMRO), one out of six regional offices of World Health Organization. Middle East countries are characterized by geographic vicinity and population's interaction. However, they are dissimilar in several aspects such as economy and health infrastructures. Regarding economy, countries in this region are ranging from wealthy to very poor. Prevalence of tuberculosis and patterns drug resistance tuberculosis cases are also following variable trends within countries of this region. In almost all Middle East countries, there is under-reporting of drug-resistance tuberculosis cases. There are shortages in the infrastructures and facilities for detecting the pattern of drug-resistance tuberculosis. For instance, sixout of 14 countries have neither in-country capacity nor a linkage with a partner laboratory for second-line drug susceptibility testing and only 4 countries have registered site performing Xpert MTB/RIF.

Snapshot of the genetic diversity of Mycobacterium tuberculosis isolates in Iraq.

UNLABELLED: This study explored the genetic diversity of Mycobacterium tuberculosis isolates in Iraq by spoligotyping and 15-locus-based mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) methods. Initially, 270 isolates from 134 patients were collected and then 134 non-duplicating isolates (1 isolate/patient) were subjected to the study analyses, 70 isolates were found to be multidrug resistant (MDR) upon testing by proportion method on Löwenstein-Jensen medium. Spoligotyping yielded 39 patterns; 111/134 (82.2%) isolates being grouped in 16 clusters vs. 23/134 (17.2%) isolates being unique. SIT1144/T1 represented the largest cluster (n=20, 14.9%), followed by SIT25/CAS1_Delhi (n=19, 14.2), SIT22/CAS1_Delhi (n=12, 9%); the other clusters ranged from 2 to 8 isolates. The SIT1144 is not reported in neighboring countries and only 4 isolates were reported worldwide (2 in USA, 1 in Venezuela, and 1 in Greece). This study reported 4 isolates belonging to SIT41/Turkey family, and thus it seems that this family is not exclusive to Turkey as previously thought. CAS lineage was predominant in this study (42.5%), followed by ill-defined T (29.9%). Highly diverse MIRU-VNTR genotypes were displayed; 100 distinct MIRU-VNTR genotypes were detected (8 clusters with 2-8 strains/cluster and 92 unique). The clustering rate was 18.03%. The discriminatory efficiency of MIRU-VNTR was high (Hunter-Gaston discriminatory index [HGDI]=0.992); it was higher than that of spoligotyping (HGDI; 0.930). However, the highest discriminatory power was provided by spoligotyping and MIRUs together. Owing to the low clustering rate by MIRU-VNTR, these results suggest that drug-resistance TB in Iraq is due to acquired resistance as opposed to transmission. CONCLUSION: Iraq is specific in having its own most predominant lineage (SIT1144/T1) which is not found among neighboring countries. The 15-locus MIRU-VNTR can be useful in discriminating M. tuberculosis isolates in Iraq.

Application of a new design of cryo-jaw and its biomechanical evaluation in rat achilles tendon in vitro / 生物医学工程学杂志

This study was aimed to design a new, accurate and easy-to-use water bath cryo-jaw, and try to solve the problems met in small animals achilles tendon mechanical testing. The muscle-tendon-bony units were fixed in the clamps. SD rats achilles tendon were randomly divided into group A and B. Group A was tested by the newly designed water bath cryo-jaw, while group B was treated by non-water bath cryo-jaw. The mechanical tests revealed that non of the samples of the newly-designed water bath cryo-jaw in group A slipped and fell off, and the achilles tendons were in a physiologically active state, but one of the group B samples slipped and fell off, and the others had the frozen phenomenon obviously. The maximum stress, fracture displacement and Young's modulus of the rats in group A were significantly different compared to those in group B (P < 0.05). In conclusion, the new water bath cryo-jaw has more advantages than traditional ones. It exhibits a good simulation in vivo in the environmental conditions for testing the mechanical properties of the achilles tendon.

First experience with using simple polymerase chain reaction-based methods as an alternative to phenotypic drug susceptibility testing for Myobacterium tuberculosis in Iraq.

CONTEXT: In Iraq, the time-consuming, phenotypic drug susceptibility testing (DST) on agar is the sole method available for detecting drug resistance in Myobacterium tuberculosis (TB). Furthermore, only single laboratory across Iraq is performing it on wide scale. AIMS: To explore utility of rapid, polymerase chain reaction (PCR)-based systems in detection of drug resistance in under the Iraqi settings. SETTINGS AND DESIGN: Cross-sectional study. A total of 79 nonduplicated isolates were included in this study. Multiplex allele-specific PCR was used to detect mutations at positions 531, 526, and 516 of the rpoB gene. Two simplex PCR systems were used to detect mutations in katG3 15 gene and inhAP-15. STATISTICAL ANALYSIS USED: Chi-square and crosstabs by SPSS v. 20. RESULTS: On DST, out of 69 isolates, 55 isolates were found multidrug-resistant (MDR)-TB; six isolates were susceptible to both rifampin (RIF) and isoniazid (INH); two isolates were resistant to RIF but not to INH; and six isolates were resistant to INH but not RIF. RIF and INH resistance mutations were detected in 50 (90.9%), and 43 (78.2%) MDR cases, respectively. Combine resistance mutations to RIF and INH were detected in 40 MDR cases (72.7%). The most frequently mutated codon was the codon 531 in rpoB gene, mutated in 42 isolates. inhAP-15 and katG315 codons were found mutated in 23 and 25 MDR cases (54.8% and 58.1%), respectively. Among 57 RIF-resistant isolates, 52 (91.2%) were harboring mutations resistance to RIF. CONCLUSIONS: These PCR-based methods are potential diagnostic and/or screening tools to detect drug-resistance TB in Iraqi settings.