Recent Evolution in the Management of Lymph Node Metastases in Melanoma

Introduction. Based upon two large randomized international clinical trials (German Dermatologic Cooperative Oncology Group (DeCOG-SLT) and Multicenter Selective Lymphadenectomy Trial II (MSLT-II)) which were published in 2016 and 2017, respectively, active surveillance has been demonstrated to have equivalent survival outcomes to completion lymphadenectomy (CLND) for a subset of patients who have microscopic lymph node disease. In this study, we examined the changes in national practice patterns regarding the utilization of CLND after positive sentinel lymph node biopsy (SLNB). Methods. Using the National Cancer Database, we examined CLND utilization in SLN-positive patients diagnosed with melanoma between 2012 and 2016. A hierarchal logistical regression model with hospital-level random intercepts was constructed to examine the factors associated with SLNB followed by observation vs. SLNB with CLND. Results. Of the 148,982 patients identified, 43% (n = 63,358) underwent SLNB, and 10.3% (n = 6,551) had a SLNB with microscopic disease. CLND was performed for 57% (n = 2,817) of these patients. Patients were more likely to undergo CLND if they were < 55 years of age (OR, 0.687;  p = <0.0001), ages 56 - 65 (OR, 0.886; p = 0.0237), Charlson Deyo Score = 0 (OR, 0.859; p = 0.0437), or were diagnosed with melanoma in 2012 (OR, 0.794, p = <0.0001). Conclusions. We found the utilization of CLND among patients with microscopic nodal melanoma to be significantly lower in 2016 compared to 2012. Younger age, lack of comorbidities, and primary tumor location on the trunk or head/neck were associated with higher utilization of CLND

Gene expression differs in susceptible and resistant amphibians exposed to Batrachochytrium dendrobatidis.

Chytridiomycosis, the disease caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has devastated global amphibian biodiversity. Nevertheless, some hosts avoid disease after Bd exposure even as others experience near-complete extirpation. It remains unclear whether the amphibian adaptive immune system plays a role in Bd defence. Here, we describe gene expression in two host species-one susceptible to chytridiomycosis and one resistant-following exposure to two Bd isolates that differ in virulence. Susceptible wood frogs (Rana sylvatica) had high infection loads and mortality when exposed to the more virulent Bd isolate but lower infection loads and no fatal disease when exposed to the less virulent isolate. Resistant American bullfrogs (R. catesbeiana) had high survival across treatments and rapidly cleared Bd infection or avoided infection entirely. We found widespread upregulation of adaptive immune genes and downregulation of important metabolic and cellular maintenance components in wood frogs after Bd exposure, whereas American bullfrogs showed little gene expression change and no evidence of an adaptive immune response. Wood frog responses suggest that adaptive immune defences may be ineffective against virulent Bd isolates that can cause rapid physiological dysfunction. By contrast, American bullfrogs exhibited robust resistance to Bd that is likely attributable, at least in part, to their continued upkeep of metabolic and skin integrity pathways as well as greater antimicrobial peptide expression compared to wood frogs, regardless of exposure. Greater understanding of these defences will ultimately help conservationists manage chytridiomycosis

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Disruption of placental ACKR3 effects embryo, and offspring, growth and hematopoietic development

ACKR3 scavenges and degrades the stem cell recruiting chemokine CXCL12 which is essential for proper embryonic, and in particular hematopoietic development. Here we demonstrate strong expression of ACKR3 on trophoblasts. Using a maternally-administered pharmacological blocker, and Cre-mediated genetic approaches, we demonstrate that trophoblast ACKR3 is essential for preventing movement of CXCL12 from the mother to the embryo with elevated plasma CXCL12 levels being detected in embryos from ACKR3-blocker treated mothers. Mice born to mothers treated with the blocker are lighter and shorter than those born to vehicle-treated mothers and, in addition, display profound anaemia associated with a markedly reduced bone marrow hematopoietic stem cell population. Importantly, whilst the hematopoietic abnormalities are corrected as mice age, our studies reveal a postnatal window during which offspring of ACKR3 blocker treated mice are unable to mount effective inflammatory responses to inflammatory/infectious stimuli. Overall, these data demonstrate that ACKR3 is essential for preventing CXCL12 transfer from mother to embryo and for ensuring properly regulated CXCL12 control over the development of the hematopoietic system