The role of aspirin, statins, colchicine, and IL-1 inhibitors in prevention of cardiovascular events: a systematic integrative review.

CONTEXT: Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed. Drugs that work by reducing platelet aggregation, blocking cholesterol formation (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors), and/or blocking inflammation pathways (mainly interleukin-1b [IL-1b]) have been linked to preventing adverse CVEs, including acetylsalicylic acid (ASA, aspirin), statins, colchicine, and IL-1 inhibitors (interleukin-1 receptor antagonists). This systematic review aims to provide insight into utilizing these four agents for the primary and/or secondary prevention of CVD. OBJECTIVES: In this systematic review, we opted to review the efficacy of aspirin, statins, colchicine, and IL-1 inhibitors in the primary and secondary prevention of CVE to provide clinical practitioners with evidence-based practice approaches and determine any unmet needs in their utilization. METHODS: Between October 1 and 12, 2021, a search was conducted and completed on five databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Biomedical Reference Collection: Comprehensive. A total of 13 researchers (V.A., A.H., S.B., V.G., D.C., C.C., C.B., C.A., S.K., J.H., A.K., S.F., and S.E.) were involved in the search and screening of the articles. Search terms included "aspirin, statins, colchicine, IL-1 inhibitors, and primary, secondary, myocardial infarction (MI)." Inclusion criteria included clinical study design, English language articles, all genders older than 50 years old, and established patient history of CVD, including MI. In addition, articles were excluded if they were animal models, in vitro studies, pharmacokinetic studies, systematic reviews, literature reviews, and studies exploring therapies other than those listed in the inclusion criteria. First, five individuals independently sorted through abstracts or articles based on the inclusion and exclusion criteria. Then, a team of 13 individuals sorted through full-text articles of selected abstracts based on the same criteria. A separate researcher resolved conflicts between the team. RESULTS: A total of 725 articles were identified from all databases, from which 256 duplicated articles were removed. Thus, a total of 469 articles abstracts were screened, of which 425 articles either did not meet the inclusion criteria or met the exclusion criteria. A total of 42 articles were retrieved and assessed for full-text review, from which 15 articles were retrieved for analysis. CONCLUSIONS: Statins may prevent primary CVEs based on their role in preventing cholesterol formation. Aspirin, canakinumab, and colchicine may be helpful in the secondary prevention of CVEs due to their blocking of various steps in the inflammation pathway leading to CVD. Future research should primarily focus on the use of canakinumab and colchicine in preventing CVD due to the limited number of studies on these drugs.

Component Separation: A Case Report of Hybrid and Synthetic Absorbable Mesh Use for Complex Large Ventral Hernia Reparation.

Ventral abdominal hernias are a common abdominal wall defect in the United States. We present a 50-year-old Caucasian male with a large (>18 cm) abdominal wall defect. An extensive complex abdominal wall reconstruction with advanced bilateral fascial flaps/component separation and repair of the abdominal wall defect was planned to restore the appropriate abdominal wall anatomic contour. The use of double mesh in large abdominal wall defects is still a relatively new documented technique. Only two case series detail the same technique used on this patient, with no articles on using a hybrid mesh with a synthetic absorbable mesh. This case uses an underlay and onlay mesh technique, with a hybrid mesh, Tela Biologics (Malvern, PA, USA), under the muscle, in this case, intraperitoneal bridging the gap. The anterior rectus sheath was reinforced with intercepted 0-Ethibond sutures (Ethicon/J&J, Bridgewater, NJ, USA) and then reinforced with a synthetic absorbable mesh (PhasixTM, Becton Dickinson, Franklin Lakes, NJ). The outcome with this patient shows more research should be conducted on considering long-term results with the types of mesh and the question of whether there are additional benefits when using two different types of mesh and their placement in the sandwich technique.

Oral Microbiome as a Tool of Systemic Disease on Cleft Patients: A New Landscape.

The oral cavity microbiome comprises benign and pathogenic bacteria, with more than 700 species identified. However, the current literature regarding resident bacterial flora in the oropharyngeal cavities in cleft lip/palate (CLP) patients still needs to be completed. This review aims to evaluate the role of the oral microbiome of cleft patients as an indicator in systemic diseases for which cleft patients might be at higher risk in the short or long term. A literature review was performed in July 2020 using Biomedical Reference Collection Comprehensive, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, Dentistry & Oral Sciences Source via Elton B. Stephens Company/Online Database (EBSCO), Turning Research into Practice (TRIP), and PubMed. The keywords used were "oral, bacteria, microbiome, biota, flora, cleft, palate." The resulting 466 articles were deduplicated using Endnote. The total amount of articles' abstracts without duplicates was filtered using a set criterion. The title and abstract filter criteria included 1) cleft lip (CL) and/or cleft palate (CP) patients, 2) changes in the oral microbiome in CL and/or CP patients, 3) male and female patients 0-21 years old, and 4) English language. The full-text filter criteria included 1) CL and/or CP patients vs. non-cleft control patients, 2) oral bacteria, 3) nonprocedural measurements of microorganisms, and 4) case-control studies. A Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow chart was created using the EndNote data results. The final five articles of the systematic search indicated that the oral cavity of cleft lip and/or palate patients resulted in 1) contradicting levels of Streptococcus mitis and Streptococcus salivarius; 2) lower levels of Streptococcus gordonii, Bordetella dentium, Fusobacterium nucleatum, Veillonella parvula, Bacillus and Lautropia when compared to the control group; 3) higher levels of Staphylococcus epidermidis and Methicillin-sensitive Staphylococcus aureus compared to the control group; 4) presence of Enterobacter cloacae 36.6%, Klebsiella pneumoni 53.3%, and Klebsiella oxytoca 76.6% vs. absence in the control non-cleft group. Patients with CL and/or CP are at higher risk for caries, periodontal diseases, and upper and lower respiratory infections. The results from this review indicate that relative levels of certain bacteria may be associated with these issues. The lower levels of S. mitis, S. salivarius, S. gordini, and F. nucleatum in the oral cavity of cleft patients could be linked as a possible cause of the higher incidence of tooth decay, gingivitis and periodontal disease as high levels of these bacteria are associated with oral disease. Further, the higher incidence of sinusitis in cleft patients might be linked to low levels of S. salivarius in the oral profile of these patients. Likewise, E. cloacae, K. oxycota, and K. pneumoni have been linked with pneumonia and bronchiolitis, both of which are increased in cleft patients. The oral bacterial dysbiosis of cleft patients observed in this review may play a vital function in the oral microbiome's diversity, which could play a role in disease progression and disease markers. The pattern seen in cleft patients potentially demonstrates how structural abnormalities can lead to the onset of severe infection.

Glucocorticoid use in rheumatoid arthritis patients and the onset of pneumonia: a systematic review and meta-analysis.

CONTEXT: Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood. OBJECTIVES: The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework. METHODS: On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity. RESULTS: A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002). CONCLUSIONS: Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.

Comorbidities and Symptomatology of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-Related Myocarditis and SARS-CoV-2 Vaccine-Related Myocarditis: A Review.

Myocarditis is an inflammatory disease of the heart muscle, with manifestations that include myocardial infarction, arrhythmia, and even sudden death. The primary etiology of myocarditis is a viral infection, with studies demonstrating that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to myocarditis. This enzyme is involved in many body tissues, including the gastrointestinal system and the cardiac system. This enzyme is responsible for converting angiotensin I to angiotensin II in the renin-angiotensin system of our body. This review aims to characterize the symptomatology and comorbidities of males, females, and pediatric patients who developed the SARS-CoV-2-related myocarditis (SARS-CoV-2RM) or the SARS-CoV-2 vaccine-related myocarditis (SARS-CoV-2VRM). From July 10 to July 20, 2021, a PubMed database search for "SARS CoV-2 Related Myocarditis" was conducted. From July 21 to July 30, 2021, the search for "SARS CoV-2 Vaccine Related Myocarditis" was conducted. The search completed was specific for title/abstract fields using keywords "Covid-19" AND "Myocarditis" AND "Vaccine" and specifying "Males" or "Females", respectively. Inclusion criteria included articles discussing comorbidities and symptomatology. Exclusion criteria included autopsy/postmortem reports, letters to the editor, retrospective studies, and observational studies. In the end, 49 articles were found and included in this review. We found that 27 of 40 pediatric patients with SARS-CoV-2RM presented with gastrointestinal symptoms, and 12 of 40 pediatric patients had no comorbidities. In female cases, eight of 12 patients with SARS-CoV-2RM presented with noncardiac symptoms, and only four of 12 had comorbidities such as asthma, diabetes, and obesity. In male patients with SARS-CoV-2RM, 10 of 12 presented with respiratory and/or cardiac symptoms, and seven of 12 had cardiac and/or diabetic comorbidities. Furthermore, 22 of 31 male patients with SARS-CoV-2VRM presented with chest pain with no previous comorbidities; four of six females with SARS-CoV-2VRM presented with chest pain, and three of six females had no comorbidities; and seven of 11 pediatric patients with SARS-CoV-2VRM had no comorbidities, but 11 of 11 pediatric patients presented with chest pain. In conclusion, males, females, and pediatric patients with previous SARS-CoV-2VRM showed mostly chest pain with no comorbidities. Males presenting with SARS-CoV-2RM showed mostly respiratory and cardiac symptoms with cardiac and diabetic comorbidities. Females with SARS-CoV-2RM described various symptoms from flu-like, respiratory, to cardiac and had no previous comorbidities. The bulk of pediatric patients with SARS-CoV-2RM mainly presented with GI symptoms and no past comorbidities. More studies are needed to determine the clinical presentation and risk factors that lead to SARS-CoV-2RM and SARS-CoV-2VRM.

Microbiome in Rheumatoid Arthritis and Celiac Disease: A Friend or Foe.

Rheumatoid arthritis (RA) and celiac disease (CD) are both autoimmune diseases with increasing global prevalence. These two diseases have been connected based on similar HLA mutations, serological markers, rheumatological, and gastrointestinal manifestations. In this review, we discuss the role of the oral and gut microbiome in the development and progression of RA and CD. Here, we highlight similar microbial dysbiosis and how these alterations in composition can lead to worsening disease severity in both CD and RA. Additionally, we analyze the role of probiotics in regulating the microbiome and improving symptoms associated with RA and CD.