The mesh controversy [version 1; referees: 2 approved]

Pelvic organ prolapse and stress urinary incontinence are common conditions for which approximately 11% of women will undergo surgical intervention in their lifetime. The use of vaginal mesh for pelvic organ prolapse and stress urinary incontinence rose rapidly in the early 2000s as over 100 mesh products were introduced into the clinical armamentarium with little regulatory oversight for their use. US Food and Drug Administration Public Health Notifications in 2008 and 2011, as well as reclassification of transvaginal mesh for prolapse to class III in early 2016, were a response to debilitating complications associated with transvaginal mesh placement in many women. The midurethral sling has not been subject to the same reclassification and continues to be endorsed as the “gold standard” for surgical management of stress urinary incontinence by subspecialty societies. However, litigators have not differentiated between mesh for prolapse and mesh for incontinence. As such, all mesh, including that placed for stress urinary incontinence, faces continued controversy amidst an uncertain future. In this article, we review the background of the mesh controversy, recent developments, and the anticipated role of mesh in surgery for prolapse and stress urinary incontinence going forward

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy