This review was prompted by continued public and professional interest of necrotizing fasciitis as well as worldwide increases in the incidence of streptococcal invasive infections. Our objective was to outline the clinical course of necrotizing fasciitis and delineate factors relating to mortality among 163 diagnosed patients. Over 14 years patients diagnosed with necrotizing fasciitis were reviewed for patient history, comorbid conditions, and progression of clinical course. A logistic regression model was used to identify factors increasing mortality risk among necrotizing fasciitis patients. Nearly 17 per cent of the patients showed no identifiable antecedent trauma. Seventy-one per cent of tissue culture-positive patients (145) had multibacterial infections. Although no streptococcal species were recovered from one-third of these culture-positive patients there was an increase in mortality noted with β- Streptococcus infections. Ninety-six per cent of the patient deaths were correlated with variables organized into the following categories: 1) patient history (intravenous drug use and age 60 years), 2) comorbid conditions (cancer, renal disease, and congestive heart failure), 3) characteristics of clinical course (trunk involvement, positive blood cultures, peripheral vascular disease, and positive cultures for β -streptococcus or anaerobic bacteria), and 4) quantitative timeline of clinical course (time: injury to diagnosis, diagnosis to treatment). Mortality is correlated to patient history, comorbid conditions, and progression of clinical course. Necrotizing fasciitis can occur idiopathically and is generally a polymicrobial infection that sometimes occurs in the absence of streptococci. Clearly the mortality and morbidity associated with necrotizing fasciitis can be decreased with clinical awareness, early diagnosis, adequate surgical debridement, and intensive supportive care.

Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let‐7 (MIRLET7) family controls developmental timing and differentiation. Let‐7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let‐7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let‐7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let‐7 function as tumor suppressor and oncogene, considering let‐7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let‐7 family members, pointing to abnormal processes involved in carcinogenesis. Let‐7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let‐7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let‐7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival.

Background: The pathobiology of radiation-induced periprosthetic capsular formation and factors that may ameliorate its development have not been fully elucidated. The authors hypothesized that AlloDerm would diminish radiation-induced capsular formation. Methods: Two 5-ml implants were placed submuscularly in the backs of 41 rats. The right implant was wrapped with AlloDerm and the left remained bare. After 48 hours, 20 animals underwent irradiation to each implant, and 21 animals underwent no further treatment and served as controls. After 3 and 12 weeks, the capsules were harvested and submitted for tensile strength and histologic examination. Intraprosthetic pressures were measured in each implant at the time of surgery and when the animals were killed. Results: The intraprosthetic pressure decrease was uniform among all groups at 3 and 12 weeks. Between 3 and 12 weeks, capsular tensile strength increased in nonirradiated bare implants. There was considerable invasion of nonirradiated AlloDerm by inflammatory infiltrates at 3 weeks, and AlloDerm thickness decreased over time. Cellular invasion of AlloDerm was decreased with irradiation at both time points. Capsular tensile strength and thickness of the irradiated bare and AlloDerm capsules did not change between 3 and 12 weeks. Radiation increased inflammation of bare capsules at 12 weeks, but it was significantly reduced in irradiated AlloDerm capsules. The majority of irradiated bare capsules developed pseudoepithelium, whereas AlloDerm protected capsules from this transformation. Conclusion: AlloDerm decreases radiation-related inflammation and delays or diminishes pseudoepithelium formation and thus may slow progression of capsular formation, fibrosis, and contraction.