Multi-modal trained artificial intelligence solution to triage chest X-ray for COVID-19 using pristine ground-truth, versus radiologists.

The front-line imaging modalities computed tomography (CT) and X-ray play important roles for triaging COVID patients. Thoracic CT has been accepted to have higher sensitivity than a chest X-ray for COVID diagnosis. Considering the limited access to resources (both hardware and trained personnel) and issues related to decontamination, CT may not be ideal for triaging suspected subjects. Artificial intelligence (AI) assisted X-ray based application for triaging and monitoring require experienced radiologists to identify COVID patients in a timely manner with the additional ability to delineate and quantify the disease region is seen as a promising solution for widespread clinical use. Our proposed solution differs from existing solutions presented by industry and academic communities. We demonstrate a functional AI model to triage by classifying and segmenting a single chest X-ray image, while the AI model is trained using both X-ray and CT data. We report on how such a multi-modal training process improves the solution compared to single modality (X-ray only) training. The multi-modal solution increases the AUC (area under the receiver operating characteristic curve) from 0.89 to 0.93 for a binary classification between COVID-19 and non-COVID-19 cases. It also positively impacts the Dice coefficient (0.59 to 0.62) for localizing the COVID-19 pathology. To compare the performance of experienced readers to the AI model, a reader study is also conducted. The AI model showed good consistency with respect to radiologists. The DICE score between two radiologists on the COVID group was 0.53 while the AI had a DICE value of 0.52 and 0.55 when compared to the segmentation done by the two radiologists separately. From a classification perspective, the AUCs of two readers was 0.87 and 0.81 while the AUC of the AI is 0.93 based on the reader study dataset. We also conducted a generalization study by comparing our method to the-state-art methods on independent datasets. The results show better performance from the proposed method. Leveraging multi-modal information for the development benefits the single-modal inferencing.

In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems.

The usage of flavored electronic nicotine delivery systems (ENDS) is popular, specifically in the teen and young adult age-groups. The possible cardiac toxicity of the flavoring aspect of ENDS is largely unknown. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor," an aerosolized mixture of nicotine and/or flavors. We report our investigation into the cardiotoxic effects of flavored e-liquids. E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry, were more toxic in HL-1 cardiomyocytes than fruit-flavored e-vapor. Exposure of human induced pluripotent stem cell-derived cardiomyocytes to cinnamaldehyde or vanillin-flavored e-vapor affected the beating frequency and prolonged the field potential duration of these cells more than fruit-flavored e-vapor. In addition, vanillin aldehyde-flavored e-vapor reduced the human ether-à-go-go-related gene (hERG)-encoded potassium current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde-flavored e-vapor for 10 wk caused increased sympathetic predominance in heart rate variability measurements. In vivo inducible ventricular tachycardia was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the vanillin aldehyde-flavored e-vapor-exposed mice than in controls. We conclude that the widely popular flavored ENDS are not harm free, and they have a potential for cardiac harm. More studies are needed to further assess their cardiac safety profile and long-term health effects.NEW & NOTEWORTHY The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.

Cellular and physiological approaches to evaluate the chelating effect of Chlorella on metal ion stressed lymphocytes.

Chlorella is a green alga consumed as dietary food supplement in pulverized form. In addition to its high nutritional value, it is reported as an excellent detoxifying agent. The pulverized Chlorella is partially soluble in water and insoluble portion has been reported for removal of mercury, cadmium and radioactive strontium from body. Chlorella contains a variety of metal-binding functional groups such as carboxyl, amino, phosphoryl, hydroxyl and carbonyl groups, which has high affinity towards various metal ions. The present study was envisaged to evaluate the chelating effect of water soluble fraction of Chlorella powder (AqCH) on metal ions. Fura-2 fluorescence ratio (F340/F380) was measured by fluorescence spectrometer (FS) after the exposure of chloride salt of metals viz., strontium, cobalt, barium, cesium, thallium and mercury to lymphocytes. Pretreatment of AqCH (0.1-20 mg mL-1) was given to evaluate the attenuating effect on fura-2 fluorescence ratio induced by metal ions. The intracellular levels of these metal ions were analyzed by atomic absorption spectrophotometer (AAS) and fluorescence microscopy (FM). Pretreatment with AqCH significantly attenuated the metal induced fluorescence ratio in dose-dependent manner. The results of AAS and FM were found in coherence with fura-2 fluorescence ratio which emphasized that AqCH significantly prevented the metal ions internalization. The present study suggests AqCH chelates with these metal ions and prevents its interaction with cells thereby reducing the intracellular mobilization of Ca2+.

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas.

The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc-(EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/µmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 µM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERß and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy.

Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells.

BACKGROUND: Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. METHODS: We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. RESULTS: MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. CONCLUSIONS: These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage.

Comparative evaluation of brain neurometabolites and DTI indices following whole body and cranial irradiation: a magnetic resonance imaging and spectroscopy study.

Understanding early differential response of brain during whole body radiation or cranial radiation exposure is of significant importance for better injury management during accidental or intentional exposure to ionizing radiation. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) following whole body and cranial radiation exposure of 8 Gy in mice using a 7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5 and 10 post irradiation. A significant decrease in fractional anisotropy (FA) values was found in hippocampus, thalamic and hypothalamic regions (p < 0.05) in both whole body and cranial irradiated groups compared with controls, suggesting radiation induced reactive astrogliosis or neuroinflammatory response. In animals exposed to whole body radiation, FA was significantly decreased in some additional brain regions such as sensory motor cortex and corpus callosum in comparison with cranial irradiation groups and controls. Changes in FA were observed till day 10 post irradiation in both the groups. However, MRS study from hippocampus revealed changes only in the whole body radiation dose group. Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02) and taurine (tau, p = 0.03) to total creatine were observed, and these metabolic alterations persisted till day 10 post irradiation. To the best of our knowledge this study has for the first time documented a comparative account of microstructural and metabolic aspects of whole body and cranial radiation induced early brain injury using in vivo MRI. Overall our findings suggest differential response at microstructure and metabolite levels following cranial or whole body radiation exposure.

Dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose reduces endotoxemia-induced inflammation and oxidative stress: Implications in PAMP-associated acute and chronic pathology.

Pathogen-associated molecular patterns (PAMPs) like bacterial cell wall components and viral nucleic acids are known ligands of innate inflammatory receptors that trigger multiple inflammatory pathways that may result in acute inflammation and oxidative stress-driven tissue and organ toxicity. When dysregulated, this inflammation may lead to acute toxicity and multiorgan failure. Inflammatory events are often driven by high energy demands and macromolecular biosynthesis. Therefore, we proposed that targeting the metabolism of lipopolysaccharide (LPS)-driven inflammatory events, using an energy restriction approach, can be an effective strategy to prevent the acute or chronic detrimental effects of accidental or seasonal bacterial and other pathogenic exposures. In the present study, we investigated the potential of energy restriction mimetic agent (ERMA) 2-deoxy-D-glucose (2-DG) in targeting the metabolism of inflammatory events during LPS-elicited acute inflammatory response. Mice fed with 2-DG as a dietary component in drinking water showed reduced LPS-driven inflammatory processes. Dietary 2-DG reduced LPS-induced lung endothelial damage and oxidative stress by strengthening the antioxidant defense system and limiting the activation and expression of inflammatory proteins, viz., P-Stat-3, NfκΒ, and MAP kinases. This was accompanied by decreased TNF, IL-1ß, and IL-6 levels in peripheral blood and bronchoalveolar lavage fluid (BALF). 2-DG also reduced the infiltration of PMNCs (polymorphonuclear cells) in inflamed tissues. Altered glycolysis and improved mitochondrial activity in 2-DG-treated RAW 264.7 macrophage cells suggested possible impairment of macrophage metabolism and, therefore, activation in macrophages. Taken together, the present study suggests that inclusion of glycolytic inhibitor 2-DG as a part of the diet can be helpful in preventing the severity and poor prognosis associated with inflammatory events during bacterial and other pathogenic exposures.

A Unique Presentation of Spontaneous Pneumomediastinum Following COVID-19 Infection.

Pneumomediastinum is a rare, life-threatening condition in which air leaks into the mediastinum. Usually, it results from a traumatic event that leads to the escape of air from the airway, lungs, or bowel into the chest cavity. Patients with underlying lung pathology or a history of invasive mechanical ventilation have an increased risk of developing a pneumomediastinum. A spontaneous pneumomediastinum (SPM) occurs in the absence of these risk factors. Patients with coronavirus disease 2019 (COVID-19) pneumonia tend to have a higher risk of developing an SPM, however, this is usually linked to mechanical ventilator use. Although rare, cases of healthy young patients with no history of underlying lung pathology or mechanical ventilator use developing an SPM are increasingly being reported. In efforts to bring more attention to this complication, we present the case of an SPM in a 40-year-old female patient with COVID-19 pneumonia and highlight the importance of close follow-up.

Pixantrone confers radiosensitization in KRAS mutated cancer cells by suppression of radiation-induced prosurvival pathways.

Radioresistance towards radiation therapy has generated the need for the development of radiosensitizers as a potential drug. KRAS mutation brings radioresistance in tumor cells. The present work proves sensitization of cancer cells towards radiotherapy through inhibition of KRAS activation. Acquiring a drug repurposing approach, the in-silico screening revealed that pixantrone, an antineoplastic drug, possesses a high affinity towards KRAS G12C and G12D subtypes. The SPR study suggests that maximum affinity of pixantrone was observed with KRAS G12C>WT>G12D and G12S. Pixantrone potentially inhibited the KRAS activation in stable transfectants G12C and G12D cell lines and radiosensitized distinct KRAS mutant subtype cells. The combination of pixantrone with radiation causes enhanced dsDNA breaks along with enhanced ATM expression, and increased late apoptosis. The preclinical studies on NCr-fox1nu xenograft mice showed potent inhibition of tumor progression and prolonged survival of mcie due to the radiosensitizing effect of pixantrone. Radiation-induced activation of key effector proteins of RAS downstream pathways, like MAPK and PI3K/Akt/mTOR pathways, were downregulated in tumor cells upon combination treatment. Interestingly, a robust upregulation of senescence marker p21 was observed in the tumor cells in combination treatment. These findings reveal a convergence between KRAS signaling, pixantrone treatment, and radiation conferring tumor cell death.

Head and neck surgery during COVID-19.

Thirty-two Head and Neck cancer patients were operated by surgical team of the Indian Institute of Head and Neck Oncology (IIHNO) in a period ranging from May 2020 to the first week of December 2020. Surgical procedures ranged from surgery for tongue cancer, resection of cancers of the oral mucosa/cheek (with or without reconstruction), as well as surgery for paranasal cancers and thyroid cancers, with an average duration of 3 h for the procedures. This article reviews this experience during the peak of covid pandemic regarding the approaches adopted by the team of the IIHNO, a flagship project of the Indore Cancer Foundation, a public charitable trust.

Amifostine analog, DRDE-30, alleviates radiation induced lung damage by attenuating inflammation and fibrosis.

BACKGROUND: Radiotherapy of thoracic neoplasms and accidental radiation exposure often results in pneumonitis and fibrosis of lungs. Here, we investigated the potential of amifostine analogs: DRDE-07, DRDE-30, and DRDE-35, in alleviating radiation-induced lung damage. METHODS: C57BL/6 mice were exposed to 13.5 Gy thoracic irradiation, 30 min after intraperitoneal administration of the analogs, and assessed for modulation of the pathological response at 12 and 24 weeks. KEY FINDINGS: DRDE-07, DRDE-30 and DRDE-35 increased the survival of irradiated mice from 20% to 30%, 80% and 70% respectively. Reduced parenchymal opacity (X-ray CT) in the lungs of DRDE-30 pre-treated mice corroborated well with the significant decrease in Ashcroft score (p < 0.01). Two-fold increase in SOD and catalase activities (p < 0.05), coupled with a 50% increase in GSH content and a 60% decrease in MDA content (p < 0.05) suggested restoration of the antioxidant defence system. A 20% to 40% decrease in radiation-induced apoptotic and mitotic death in the lung tissue (micronuclei: p < 0.01), resulted in attenuated lung and vascular permeability (FITC-Dextran leakage) by 50% (p < 0.01), and a commensurate reduction (~50%) in leukocyte infiltration in the injured tissue (p < 0.05). DRDE-30 abrogated the activation of pro-inflammatory NF-κB and p38/MAPK signaling cascades, suppressing the release of pro-inflammatory cytokines (IL-1ß: p < 0.05; TNF-α: p < 0.05; IL-6: p < 0.05) and up-regulation of CAMs on the endothelial cell surface. Reduction in hydroxyproline content (p < 0.01) and collagen suggested inhibition of lung fibrosis which was associated with attenuation of TGF-ß/Smad pathway-mediated-EMT. CONCLUSION: DRDE-30 could be a potential prophylactic agent against radiation-induced lung injury.

PTEN inhibitor bpV(HOpic) confers protection against ionizing radiation.

Exposure to Ionizing radiation (IR) poses a severe threat to human health. Therefore, there is an urgent need to develop potent and safe radioprotective agents for radio-nuclear emergencies. Phosphatidylinositol-3-kinase (PI3K) mediates its cytoprotective signaling against IR by phosphorylating membrane phospholipids to phosphatidylinositol 3,4,5 triphosphate, PIP3, that serve as a docking site for AKT. Phosphatase and Tensin Homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating PIP3, thus suppressing PI3K/AKT signaling that could prevent IR induced cytotoxicity. The current study was undertaken to investigate the radioprotective potential of PTEN inhibitor (PTENi), bpV(HOpic). The cell cytotoxicity, proliferation index, and clonogenic survival assays were performed for assessing the radioprotective potential of bpV(HOpic). A safe dose of bpV(HOpic) was shown to be radioprotective in three radiosensitive tissue origin cells. Further, bpV(HOpic) significantly reduced the IR-induced apoptosis and associated pro-death signaling. A faster and better DNA repair kinetics was also observed in bpV(HOpic) pretreated cells exposed to IR. Additionally, bpV(HOpic) decreased the IR-induced oxidative stress and significantly enhanced the antioxidant defense mechanism in cells. The radioprotective effect of bpV(HOpic) was found to be AKT dependant and primarily regulated by the enhanced glycolysis and associated signaling. Furthermore, this in-vitro observation was verified in-vivo, where administration of bpV(HOpic) in C57BL/6 mice resulted in AKT activation and conferred survival advantage against IR-induced mortality. These results imply that bpV(HOpic) ameliorates IR-induced oxidative stress and cell death by inducing AKT signaling mediated antioxidant defense system and DNA repair pathways, thus strengthening its potential to be used as a radiation countermeasure.

Prochlorperazine enhances radiosensitivity of non-small cell lung carcinoma by stabilizing GDP-bound mutant KRAS conformation.

Lung cancer is considered as leading cancer with the highest mortality. The KRAS-oncogenic mutations are dominant in lung carcinoma leading to poor prognosis and radioresistance, which is a major impediment to radiotherapy. Thus, KRAS mutant inhibitors that synergistically sensitize tumours to radiation are urgently needed. In pursuance of the search for a novel radiosensitizer, high-throughput screening of FDA-approved drugs was performed at active site of K-Ras. Prochlorperazine (PCZ), an antipsychotic drug, showed good binding affinity with KRAS-mutant proteins. PCZ binds to the GTP-binding pocket of KRAS-mutant protein and inhibits its constitutive activation by stabilizing the GDP-bound conformation of K-Ras mutants by 9 kcal/mol compared to WT. PCZ alongwith radiation decreased the clonogenic survival of KRAS-mutant NSCLC but not KRAS-WT cells. The combination treatment activates p-ATM, p53, and p21 proteins, leading to cell cycle arrest. PCZ with increasing radiation caused a linear increase in γH2AX foci, suggesting enhanced DSBs-associated apoptosis in radioresistant A549 cells. Pharmacokinetics study showed Cmax = 526 ng/ml at 30min, 4.6h half-life in plasma, and highest accumulation in tumours. PCZ and 10Gy irradiation synergistically radiosensitize mice xenografts via downregulation of Ras/Raf/MEK/ERK pathway. Our efforts have led to the discovery of PCZ as a lead compound. In preclinical analyses, treatment with PCZ alone and in combination with radiation led to regression of KRAS-G12S tumours.

Mild mitochondrial uncoupling protects from ionizing radiation induced cell death by attenuating oxidative stress and mitochondrial damage.

Ionizing radiation (IR) induced mitochondrial dysfunction is associated with enhanced radiation stimulated metabolic oxidative stress that interacts randomly with intracellular bio-macromolecules causing lethal cellular injury and cell death. Since mild mitochondrial uncoupling emerged as a valuable therapeutic approach by regulating oxidative stress in most prevalent human diseases including ageing, ischemic reperfusion injury, and neurodegeneration with comparable features of IR inflicted mitochondrial damage. Therefore, we explored whether mitochondrial uncoupling could also protect from IR induced cytotoxic insult. Our results showed that DNP, BHT, FCCP, and BAM15 are safe to cells at different concentrations range depending on their respective mitochondrial uncoupling potential. Pre-incubation of murine fibroblast (NIH/3T3) cells with the safe concentration of these uncouplers followed by gamma (γ)-radiation showed significant cell growth recovery, reduced ROS generation, and apoptosis, compared to IR treatment alone. We observed that DNP pre-treatment increased the surviving fraction of IR exposed HEK-293, Raw 264.7 and NIH/3T3 cells. Additionally, DNP pre-treatment followed by IR leads to reduced total and mitochondrial oxidative stress (mos), regulated calcium (Ca2+) homeostasis, and mitochondrial bioenergetics in NIH/3T3 cells. It also significantly reduced macromolecular oxidation, correlated with the regulated ROS generation and antioxidant defence system. Moreover, DNP facilitated DNA repair kinetics evidenced by reducing the number of γ-H2AX foci formation and fragmented nuclei with time. DNP pre-incubation restrained the radiation induced pro-apoptotic factors and inhibits apoptosis. Our findings raise the possibility that mild mitochondrial uncoupling with DNP could be a potential therapeutic approach for radiation induced cytotoxic insult associated with an altered mitochondrial function.

Unravelling the Role of HSP70 as the Unexplored Molecular Target in Age-Related Macular Degeneration.

The motive behind writing this paper was to highlight the relationship between heat shock protein 70 (HSP70) and age-related macular degeneration (AMD) to explore the potential role of HSP70 as a molecular target in AMD therapy. We performed a comprehensive literature search in various databases and finally found 43 relevant studies related to our objective. In our research, we found that in AMD, oxidative stress causes increased inflammation and excessive apoptosis due to the accumulation of aberrant proteins in retinal pigment epithelium (RPE) cells. The long-lasting overstimulation of the defence system leads to RPE degeneration and results in visual impairment or vision loss. However, after thorough research, it was found that HSP70's role as an immunomodulator, the guardian of the proteolytic pathway and regulator of apoptosis makes it a potential therapeutic target in AMD.

How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed functional gastrointestinal (GI) disorders. It affects both men and women. Enteric serotonin (5HT) is responsible for gut motility, secretion, visceral hypersensitivity, and inflammation. The serotonin reuptake transporter (SERT) maintains serotonin levels by regulating its reuptake. An increase in SERT expression causes a decrease in serotonin, which leads to IBS-C (irritable bowel syndrome, constipation-predominant), whereas a decrease in SERT transcription causes an increase in serotonin, which leads to IBS-D (irritable bowel syndrome, diarrhea-predominant). Some factors can alter SERT transcription, such as certain bacteria, inflammation, growth factor, and glucagon-like peptide-1. This shows that 5HT and SERT both have an important role in IBS pathophysiology so that it would be a better subject to target for the treatment aspect of IBS. 5HT3 receptor antagonists are advisable for IBS-D to block the excessive activity of serotonin at the 5HT3 receptor and reduce gut motility. For IBS-C, we prescribe 5HT4 receptor agonists, which promote gut motility. Also, the latest treatment approach, antidepressant drugs TCAs (tricyclic antidepressants) and SSRIs (selective serotonin reuptake inhibitors), are helpful by modulating serotonin levels in the gut. In this literature review, we found that serotonin is one of the main pathophysiological factors for IBS, and we can treat IBS by targeting serotonin function on gut motility.

Correction: How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome.

[This corrects the article DOI: 10.7759/cureus.9871.].

Antigenic Variability a Potential Factor in Assessing Relationship Between Guillain Barré Syndrome and Influenza Vaccine - Up to Date Literature Review.

Guillain-Barré syndrome (GBS) is a possible serious adverse event of the influenza vaccine but it is yet to be proven. The objective of our traditional literature review is to assess the potential relationship between GBS and influenza vaccine. A traditional literature review has been carried out by selecting 26 articles from PubMed published between 2011 and 2020. Twenty-six articles met the selection criteria (eight observational studies, four systematic literature review, three meta-analyses, two case-control, two retrospective cohort, and seven case series). Selected studies were focused on monitoring the safety of influenza vaccines, the relative safety of pandemic and seasonal influenza vaccines, influenza vaccine a potential etiology of GBS, and pathogenesis of post-vaccination GBS. Few studies have shown a higher incidence of GBS with a pandemic influenza vaccine compared to the seasonal influenza vaccine, while several studies have concluded a small increase in the possibility of GBS following any type of influenza vaccine. There were some studies that estimated no association possibly due to the presence of confounding factors such as influenza-like illness, low power of the study, and reporting bias in post-vaccination surveillance programs. GSB should be taken into consideration as one of the less common but serious side effects of the influenza vaccine but it should not adversely affect the acceptance of the influenza vaccination program. Continuous monitoring of influenza vaccine safety should be performed regularly.

Resection and Stump Stabilization in Giant Cell Tumor Distal Ulna: A Case Report.

INTRODUCTION: Giant cell tumors (GCTs) of distal ulna are extremely rare accounting for 0.45%-3.2% of all the cases of GCTs. These are locally aggressive and have a higher rate of recurrence of up to 40% with conservative modality of treatment. Proximity to carpus and diminished range of motion makes their treatment a challenge. CASE REPORT: A 27-year-old male presented to us with swelling right distal ulna. X-ray and MRI were suggestive of GCT. The diagnosis was confirmed by core needle biopsy. The patient was managed by wide resection ulna with extensor carpi ulnaris tenodesis. CONCLUSION: GCT ulna although very rare in presentation is a possible diagnosis. Wide resection of ulna is a viable treatment option to achieve disease free status. Extensor carpi ulnaris tenodesis helps stabilization of ulnar stump.

Understanding the Fight Against Resistance: Hospital-Acquired Methicillin-Resistant Staphylococcus Aureus vs. Community-Acquired Methicillin-Resistant Staphylococcus Aureus.

Since the identification of Staphylococcus (S.) aureus, penicillin was exclusively used to combat its disastrous toxic effects. Shortly thereafter, resistant strains arose, which were no longer susceptible to penicillin or methicillin treatments. These strands were later identified as methicillin-resistant Staphylococcus aureus (MRSA). Two particular MRSA strands that are discussed below are the hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) strands and the community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strands. Despite arising from a single bacterium, S. aureus, each of these two strands possesses quite different resistance and virulence factors. These differences contribute to the type of population in which they affect, their ability to resist traditional treatment approaches, and their overall morbidity and mortality rates. We explore these differences by reviewing several review articles published on various reputable scientific online databases. Findings include sources from studies conducted in the United States, China, Nepal, and Uganda, ranging from 2006 to 2019. These resistance and virulence factors, the Staphylococcal cassette cartridge mecA resistance gene (SCCmec) and the Panton-Valentine Leukocidin toxin gene (PVL), were identified and isolated in each of these studies in order to appreciate similarities and differences in how they impact human beings.