Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.

Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history.

The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others.This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases.The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM.TGFβ plays a crucial role in pancreatic β cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC.NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes.In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC.On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients.In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the physiological direction?

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

Although certain risk factors have been associated with increased morbidity and mortality in patients admitted with Coronavirus Disease 2019 (COVID-19), the impact of cardiac injury and high-sensitivity troponin-I (hs-cTnI) concentrations are not well described. In this large retrospective longitudinal cohort study, we analyzed the cases of 1,044 consecutively admitted patients with COVID-19 from March 9 until April 15. Cardiac injury was defined by hs-cTnI concentration >99th percentile. Patient characteristics, laboratory data, and outcomes were described in patients with cardiac injury and different hs-cTnI cutoffs. The primary outcome was mortality, and the secondary outcomes were length of stay, need for intensive care unit care or mechanical ventilation, and their different composites. The final analyzed cohort included 1,020 patients. The median age was 63 years, 511 (50% patients were female, and 403 (40% were white. 390 (38%) patients had cardiac injury on presentation. These patients were older (median age 70 years), had a higher cardiovascular disease burden, in addition to higher serum concentrations of inflammatory markers. They also exhibited an increased risk for our primary and secondary outcomes, with the risk increasing with higher hs-cTnI concentrations. Peak hs-cTnI concentrations continued to be significantly associated with mortality after a multivariate regression controlling for comorbid conditions, inflammatory markers, acute kidney injury, and acute respiratory distress syndrome. Within the same multivariate regression model, presenting hs-cTnI concentrations were not significantly associated with outcomes, and undetectable hs-cTnI concentrations on presentation did not completely rule out the risk for mechanical ventilation or death. In conclusion, cardiac injury was common in patients admitted with COVID-19. The extent of cardiac injury and peak hs-cTnI concentrations were associated with worse outcomes.

Inflammatory bowel disease is a chronic inflammatory condition that encompasses Crohn’s disease and ulcerative colitis. Inflammatory bowel disease is not exclusive to the gastrointestinal system, as it has been identified to be associated with extraintestinal manifestations that encompass every other organ system in the human body. This review article will comprehensively review the current knowledge on extraintestinal manifestations of inflammatory bowel disease. In addition, it will discuss the recommendations for screening and surveillance for extraintestinal manifestations in these patients since early appropriate diagnosis is imperative in preventing morbidity and cancer development.

Introduction: The purpose of this study was to assess the impact of anxiety and depression on immediate inhospital outcomes and complications after total joint arthroplasty of the hip (total hip arthroplasty [THA]) and knee (total knee arthroplasty [TKA]) using a large national registry. Methods: Data from the National Inpatient Sample was used to identify all patients undergoing TKA and THA between 2006 and 2015. Patients were divided in four groups based on a concomitant diagnosis of depression, anxiety, depression plus anxiety, and neither depression nor anxiety (control group). Propensity score analysis was performed to determine whether these psychiatric comorbidities were risk factors for inhospital economic, disposition, and complication outcomes. Results: A total of 5,901,057 TKAs and 2,838,742 THAs were performed in our study period. The relative percentage of patients with anxiety and depression undergoing these procedures markedly increased over time. All three psychiatric comorbidity groups were markedly associated with an increased risk of postoperative anemia and were markedly associated with other inhospital complications compared with the control group. Notable associations were also found between the study groups and total charges, length of stay, and disposition. Discussion: Anxiety and depression are major risk factors for inhospital complications and are markedly associated with economic and disposition outcomes after TKA and THA. The relative proportion of patients with anxiety and depression undergoing these procedures is rapidly increasing. It is critical for clinicians to remain aware of these risk factors, and attention should be directed on the development of standardized perioperative optimization protocols and medication management for these patients. Level of Evidence: Level III, retrospective study

Human Papillomavirus (HPV) vaccination decreases the risk for cervical cancer. However, the uptake of HPV vaccine remains low when compared with other recommended vaccines. This study evaluates the knowledge and attitudes towards HPV infection and vaccination, and the readiness for the uptake of HPV vaccine amongst female students attending Oakland University (OU) in Michigan, United States. This is a cross-sectional study targeting a randomized sample of a 1000 female OU students using an online questionnaire. The data were statistically analyzed using SPSS software. A total of 192 female students, with the mean age of 24 years completed the survey. The majority of participants had previous sexual experience with occasional use of contraceptives (78.1%), were non-smokers (92.7%), and non-alcohol drinkers (54.2%). The participants had a mean knowledge score of 53.0% with a standard error of 2.3% translating to a moderately informed population. The majority agreed that HPV is life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects would not deter them from vaccination (63%). Although two thirds (67%) believed that, based on sexual practices in the United States, female college students in Michigan have a higher chance of contracting HPV, about 50% did not believe they themselves were at risk. Higher knowledge correlated with increased recommendation for the vaccine (correlation-factor 0.20, p = 0.005). Results suggested that the best predictor for improvement of vaccination was the awareness level and health education. This indicates a need for an educational intervention to raise awareness, increase HPV vaccine uptake, and decrease the incidence of cervical cancer.