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Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

TGF-β is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-β blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-β type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer. This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA–IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0–2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/m2 over 24 h daily 7 days per week during radiotherapy or oral capecitabine 825 mg/m2 twice per day 5 days per week during radiotherapy; radiotherapy consisted of 50·4–54·0 Gy in 28–30 fractions). 5–9 weeks later, patients underwent response assessment. Patients with a complete response could opt for non-operative management and proceed to modified FOLFOX6 (intravenous leucovorin 400 mg/m2 on day 1, intravenous fluorouracil 400 mg/m2 on day 1 then 2400 mg/m2 over 46 h, and intravenous oxaliplatin 85 mg/m2 on day 1 delivered every 2 weeks for eight cycles) or CAPEOX (intravenous oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks for four cycles). Patients with less than complete response underwent surgical resection. The primary endpoint was complete response rate, which was a composite of pathological complete response in patients who proceeded to surgery, or clinical complete response maintained at 1 year after last therapy in patients with non-operative management. Safety was a coprimary endpoint. Both endpoints were assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02688712, and is active but not recruiting. Between Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred. The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials. Eli Lilly via ExIST program, The Providence Foundation.

Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing.

Background Cellulite is a common aesthetic condition of the skin, predominantly affecting more than 90% of postpubertal females. Energy‐based devices (EBDs) have demonstrated efficacy in treating a variety of dermatologic concerns. A controlled thermal injury to the dermis can stimulate remodeling of the extracellular matrix (ECM), leading to skin tightening, an effect that may improve the dimpled appearance of cellulite. Objective To assess the efficacy and safety of synchronous parallel ultrasound using a high‐density handpiece for improving cellulite appearance. Materials and Methods Sixty subjects, aged 23–65, were enrolled in a prospective, open‐label, non‐randomized, multicenter study. Subjects underwent two treatment sessions using a novel ultrasonic system equipped with a new high‐density handpiece, applied on either one side or both sides of the thighs and/or buttocks. The follow‐up period extended up to 3 months after the second treatment. Clinical improvements were evaluated by three blinded physicians based on baseline and follow‐up photographs, using the Cellulite Severity Scale (CSS), Global Aesthetic Improvement Scale (GAIS), and Laxity Scale (LS). Satisfaction questionnaires were completed by subjects. Treatment discomfort was rated immediately after treatment using the Numerical Scale Response (NSR). Results Sixty subjects, with a mean age of 47, were enrolled in the study. GAIS results showed improvement in 91% of the treated areas, CSS score improved by 69%, while LS score improved by 53%. Most subjects (73%) reported satisfaction. Mean pain score was 4.26 ± 2.33. No serious adverse events were reported. Conclusion The novel ultrasound system was found to be effective and safe for improving cellulite appearance.

Pulmonary blastoma is a rare lung cancer classified into three subtypes: classic biphasic pulmonary blastoma (CBPB), well-differentiated fetal adenocarcinoma (WDFA), and pleuropulmonary blastoma (PPB) of childhood. Compared to the other subtypes, CPPB is an aggressive tumor with an overall five-year survival of 16% across all stages. We present two cases of biopsy-proven metastatic CBPB, who have been disease-free for over 10 years since treatment completion. Both patients were treated with surgery to the primary tumor followed by an adjuvant cisplatin-based chemotherapy for four cycles and thoracic radiation. One patient relapsed shortly after the completion of thoracic radiation with brain metastases and underwent craniotomy, gamma knife radiosurgery (GKRS), and whole brain radiation therapy. The other patient presented with synchronous pelvic metastases and underwent metastasectomy after the completion of chemotherapy but before the initiation of thoracic radiation. We review the literature regarding surgical, chemotherapeutic, and radiation treatment for patients with metastatic pulmonary blastoma. Based on our experience and review of the existing case reports, aggressive tri-modality treatment including surgery, chemotherapy with a cisplatin backbone, and a definitive treatment of oligometastatic lesions amenable to local therapy including resection or radiosurgery is reasonable to consider for medically fit patients with CBPB.

Surgical resection remains the cornerstone of therapy for early-stage disease and offers the best chance for cure. Local and distant failure rates, however, remain unacceptably high with surgery alone. Radiation and systemic chemotherapy have been used to reduce recurrences in early-stage disease. Neoadjuvant and adjuvant strategies both offer sound theoretical benefit, but evidence supporting this has been lacking. The publication of a meta-analysis in 1995 triggered a reevaluation of adjuvant chemotherapy. Four randomized trials reported in the last 2 years support the use of adjuvant platinum-based chemotherapy. This article reviews the history of clinical trials evaluating neoadjuvant and adjuvant therapy in non-small-cell lung cancer. Adjuvant chemotherapy improves 5-year survival rates by approximately 5%-15% compared with surgery alone. Surgical resection followed by adjuvant chemotherapy is the standard of care treatment for patients with completely resected stage I, II, and IIIA non-small-cell lung cancer.