Treatment approaches in immunosuppressed patients with advanced cutaneous squamous cell carcinoma

Immunosuppression, both iatrogenic and disease-related, is associated with a greatly increased incidence of cutaneous SCC (cSCC) and with aggressive cSCC and worse disease outcomes. Consequently, rapid access to skin cancer services and prudent surgical choices, such as circumferential margin assessment, is essential when treating advanced cSCC in an immunosuppressed patient. For high-risk cancers and control of cSCC multiplicity, additional strategies should be actively considered within the multidisciplinary clinical care team. These include minimization or revision of immunosuppressive medications, systemic chemoprevention (including retinoids, nicotinamide, capecitabine) and adjuvant therapies such as radiotherapy. Unfortunately, there is a relative paucity of good evidence for many of these treatments in the immunosuppressed. Systemic treatments for metastatic cSCC are often contraindicated in organ transplant recipients, notably checkpoint inhibitor immunotherapy. There are also toxicity concerns with some conventional chemotherapies and EGFR inhibitors. Until recently, clinical trials have largely excluded immunosuppressed individuals. Development of more effective treatment for advanced cSCC in this high-risk group and prospective clinical trials are now research priorities.</p

Nanowires of Lead-Free Solder Alloy SnCuAg

Ternary Sn88Ag5Cu7, Sn93Ag4Cu3, Sn58Ag18Cu24, Sn78Ag16Cu6, Sn90Ag4Cu6, Sn87Ag4Cu9 alloy nanowires were produced at various values of deposition potential by dc electrodeposition on highly ordered porous anodic alumina oxide (AAO) templates. During the deposition process some parameters, such as ion content, deposition time, pH, and temperature of the solution, were kept constant. The diameter and length of regular Sn93Ag4Cu3 nanowires electrodeposited at −1 V were determined by scanning electron microscopy (SEM) to be approximately 200–250 nm and 7-8 μm, respectively. Differential scanning calorimetry (DSC) results indicate that the melting onset temperature of Sn93Ag4Cu3 nanowires is about 204°C

Effect of environmental and pharmaceutical exposures on fetal testis development and function:a systematic review of human experimental data

BACKGROUND: Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance.OBJECTIVE AND RATIONALE: The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis.SEARCH METHODS: For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including 'endocrine disruptor', 'human', 'fetal', 'testis', 'germ cells', 'testosterone' and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches.OUTCOMES: A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues.WIDER IMPLICATIONS: Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.</p

The relationship between team ability and home advantage in the English football league system

The existence of home advantage (HA) has been found in a variety of team sports including football. There is a paucity of research on the relationship between team ability and HA in domestic football leagues and the findings of previous studies are inconclusive. Using longitudinal data from the top four football divisions in England, this study investigates the influence of team ability on the HA of teams. The data collected for this study spans 24 seasons from 1995/96 to 2018/19 and includes 48,864 matches from the English Premier League (n=9,120), the Championship (n=13,248), League One (n=13,248) and League Two (n=13,248). Team ability was interpreted in two ways: (1) the division in which teams play; and, (2) their league table position within each division. For both the divisional and positional analysis, HA was calculated as the ratio of home points to total points achieved by teams in each season under review. Evidence of a statistically significant HA was found in all four divisions and for teams of all abilities within each division. Small but statistically significant differences in HA were observed between divisions and between high, moderate and low ability teams within divisions

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy