Biofilm-derived oxylipin 10-HOME-mediated immune response in women with breast implants.

This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.

Referring Provider Opinions of Pediatric Cardiology Evaluations Performed by Nurse Practitioners.

In the setting of physician shortages, nurse practitioner (NP) roles have evolved, with increasing independence across most healthcare settings. We sought to characterize referring clinician perceptions of NP-performed outpatient pediatric cardiology consultations. We electronically distributed to pediatric and family medicine physicians and NPs in Arkansas our 11-item survey assessing the acceptability of pediatric cardiology consultations being completed by an NP under varying circumstances. Circumstances included seven common referral indications, and the scale offered five answer choices ranging from "definitely unacceptable" to "definitely acceptable". A total of 292 of 1756 (16.6% response rate) referring clinicians responded to the survey. Overall, 57% of responses indicated that NP-completed pediatric cardiology evaluations were either definitely or probably unacceptable. Acceptability was varied by referral indication and referring clinician characteristics. Unacceptability of NP-completed pediatric cardiology evaluations was greatest among family medicine physicians (81%), pediatricians (66%), and clinicians working in solo or two-physician practices (77%) or community hospitals/clinics (71%). If NP evaluation of a murmur included required review with a cardiologist, the unacceptability rate dropped from 50 to 24% (p < 0.0001). Unacceptability was higher in physicians who do not work with NPs (69%) compared to those who do (60%) (pp < 0.0001). Many referring physicians were willing to send patients ≥ 100 miles to ensure evaluation by a pediatric cardiologist. Most referring physicians find pediatric cardiology evaluations performed by NPs to be unacceptable. Requisite review with a cardiologist improved acceptability of NP evaluations. Many referring physicians would send patients much farther to guarantee evaluation by a cardiologist.

Breast Implant-Associated Immunological Disorders.

Background: Breast implants are commonly placed postbreast cancer reconstruction, cosmetic augmentation, and gender-affirming surgery. Breast implant illness (BII) is a systemic complication associated with breast implants. Patients with BII may experience autoimmune symptoms including fatigue, difficulty concentrating, hair loss, weight change, and depression. BII is poorly understood, and the etiology is unknown. The purpose of this literature review is to characterize BII autoimmune disorders and determine possible causes for its etiology. Methods: The PubMed, Google Scholar, Embase, Web of Science, and OVID databases were interrogated from 2010 to 2020 using a query strategy including search term combinations of "implants," "breast implant illness," "autoimmune," and "systemic illness." Results: BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. A review of epidemiological studies in the past ten years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren's syndrome, rheumatoid arthritis, systemic sclerosis, chronic fatigue syndrome, and Raynaud's syndrome. Explantation resulted in alleviation of symptoms in over 50% of patients, strengthening the hypothesis linking breast implants to BII. Studies have shown that silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem. Conclusion: BII could be dependent on biofilm infection and the microenvironment around the implants. The true pathophysiology behind these complaints must be further investigated so that alternative treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.

Advantages of the Delayed-Immediate Microsurgical Breast Reconstruction: Extending the Choice.

BACKGROUND: Deep inferior epigastric perforator (DIEP) reconstruction can be performed in an immediate (at time of mastectomy), delayed-immediate (immediate tissue expander followed by staged DIEP), or delayed timing following mastectomy. Avoiding flap radiation is a known benefit of the delayed-immediate approach. The purpose of this study is to evaluate patients who chose DIEP flap as the reconstructive method during initial consultation and compared characteristics of surgery in relation to their final reconstructive choice. METHODS: Consecutive patients having breast reconstruction from 2017 to 2019 were divided into three groups: immediate DIEP after mastectomy (Group I); delayed-immediate DIEP with tissue expander first followed by DIEP (Group II); and patients who initially chose delayed-immediate DIEP but later decided on implants for the second stage of reconstruction (Group III). Exclusion criteria were patients that had delayed DIEP (no immediate reconstruction) or had initially chose implant-based reconstruction. RESULTS: The study included 59 patients. Unilateral free flaps in Group II had shorter operative times (318 minutes) compared with Group I unilateral free flaps (488 minutes) (p = 0.024). Eleven patients (30.6%) had prophylactic mastectomies in Group I compared with none in Group II (p = 0.004). Patients who had immediate tissue expansion frequently changed their mind from DIEP to implant for second stage reconstruction frequently (52.2%). CONCLUSION: Delayed-immediate DIEP reconstruction has several advantages over immediate DIEP flap including shorter free flap operative times. Patients commonly alter their preference for second stage reconstruction. A patient-centered advantage of delayed-immediate reconstruction is prolonging the time for patients to make their choice for the final reconstruction.

Substance Abuse-Related Soft Tissue Infections: A Uniquely Complicated Subset of a Common Problem.

We hypothesize that soft tissue infections (SSIs) related to intravenous drug usage (IVDU) are associated with a more complicated and costly course than those not associated with IVDU. For the period 2005-2018, ICD 9/ICD 10 billing codes were used to identify patients admitted with SSIs and their causes/complications and associated costs. IVDU-related infections were then compared with non-IVDU-related infections. t test was used to compare treatment costs and length of stay. Logistic regression analysis was used to assess the likelihood/risk of specific events in the IVDU versus non-IVDU populations. Of 47,281 patients admitted with SSIs, 1323 were associated with IVDU. IVDU-related patients tended to be younger (36.2 vs 49.3 years, P = 0.001). Both cost and length of stay were significantly greater in the IVDU group ($30,471 vs $16,020, P = 0.001; 5.7days vs 3.7days, P = 0.001). In addition, IVDU admissions were more likely to be associated with chronic blood-borne infections (hepatitis B/C, HIV, P = 0.001) and a significantly greater incidence of secondary infectious complications, including endocarditis (P = 0.001), bacteremia (P = 0.001), and osteomyelitis (P = 0.003). SSI admissions related to IVDU are a unique subgroup of patients. These patients not only have longer and more costly lengths of stay but are also at higher risk for secondary complications such as chronic blood-borne viral illness and secondary bacterial infectious complications, such as bacteremia, endocarditis, and osteomyelitis. Further prospective study of these findings is warranted as we continue to battle the growing problem of IVDU in the United States.

Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders.

Genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. Inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. The purpose of this paper is to help define these complex issues relevant to the use of genetic medicines and to describe the strategy we have used to confront these issues in a phase I trial of adeno-associated virus-mediated gene transfer to the central nervous system of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal lysosomal storage disease associated with progressive neurodegeneration and death by mid-childhood. Our approach to these challenges should provide a useful paradigm for investigators initiating other genetic medicine- based studies to treat inevitably fatal diseases.