Melanoma in older patients: declining gap in survival between younger and older patients with melanoma

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older peopl

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Role of Rydberg states in the photochemical dynamics of ethylene

We use the ab initio multiple spawning method with potential energy surfaces and nonadiabatic coupling vectors computed from multistate multireference perturbation theory (MSPT2) to follow the dynamics of ethylene after photoexcitation. We introduce an analytic formulation for the nonadiabatic coupling vector in the context of MSPT2 calculations. We explicitly include the low-lying 3s Rydberg state which has been neglected in previous ab initio molecular dynamics studies of this process. We find that although the 3s Rydberg state lies below the optically bright \u3c0\u3c0* state, little population gets trapped on this state. Instead, the 3s Rydberg state is largely a spectator in the photodynamics, with little effect on the quenching mechanism or excited state lifetime. We predict the time-resolved photoelectron spectrum for ethylene and point out the signature of Rydberg state involvement that should be easily observed. \ua9 2011 American Chemical Society.Peer reviewed: YesNRC publication: Ye

Risk factors for second primary melanoma among Dutch patients with melanoma

BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified surveillance. OBJECTIVES: To identify risk factors for a second primary cutaneous melanoma. METHODS: Possible risk factors for a second primary melanoma were assessed in 1127 patients with cutaneous melanoma who were diagnosed between 2003 and 2011 and completed a baseline questionnaire. Additional data were extracted from the Netherlands Cancer Registry and medical files. RESULTS: Fifty-three patients were diagnosed with a second melanoma during a median follow-up time of 6.3 years. The 5-year cumulative risk was 3.7% and the conditional cumulative risk was 4.6% in years 5-10 after diagnosis. In multivariable analyses, the risk of a second melanoma increased with older age at diagnosis [hazard ratio (HR) 1.03 per year; 95% confidence interval (CI) 1.00-1.06], a high naevus density (HR 7.16, 95% CI 2.89-17.75) and working outside for > 10 years (HR 2.88, 95% CI 1.38-6.03). Patients with invasive melanoma (> 1 mm) had a decreased risk compared with patients with melanoma in situ (HR 0.35, 95% CI 0.13-0.93). CONCLUSIONS: Besides phenotypic characteristics, cumulative sun exposure seemed to increase the risk of a second melanoma. Patients with melanoma in situ may need to be offered follow-up, which is currently not advised. As the risk of a second melanoma did not decline in years 5-10 after diagnosis, a subgroup of patients may need a longer follow-up than is currently advised

Photodissociation dynamics of Cyclopropenylidene, c-C3H2

In this joint experimental and theoretical study we characterize the complete dynamical "life cycle" associated with the photoexcitation of the singlet carbene cyclopropenylidene to the lowest lying optically bright excited electronic state: from the initial creation of an excited-state wavepacket to the ultimate fragmentation of the molecule on the vibrationally hot ground electronic state. Cyclopropenylidene is prepared in this work using an improved synthetic pathway for the preparation of the precursor quadricyclane, thereby greatly simplifying the assignment of the molecular origin of the measured photofragments. The excitation process and subsequent non-adiabatic dynamics have been previously investigated employing time-resolved photoelectron spectroscopy and are now complemented with high-level ab initio trajectory simulations that elucidate the specific vibronic relaxation pathways. Lastly, the fragmentation channels accessed by the molecule following internal conversion are probed using velocity map imaging (VMI) so that the identity of the fragmentation products and their corresponding energy distributions can be definitively assigned.Peer reviewed: YesNRC publication: Ye

A quantum molecular movie polyad predissociation dynamics in the VUV excited 3p sigma Rydberg state of nitrogen dioxide

The optical formation of coherent superposition states, a wavepacket, can allow the study of zeroth order states, the evolution of which exhibit structural and electronic changes as a function of time this leads to the notion of a molecular movie. Intramolecular vibrational energy redistribution, due to anharmonic coupling between modes, is the molecular movie considered here. There is no guarantee, however, that the formed superposition will behave semi classically e.g. Gaussian wavepacket dynamics or even as an intuitively useful zeroth order state. Here we present time resolved photoelectron spectroscopy TRPES studies of an electronically excited triatomic molecule wherein the vibrational dynamics must be treated quantum mechanically and the simple picture of population flow between coupled normal modes fails. Specifically, we report on vibronic wavepacket dynamics in the zeroth order 3p amp; 963;2 amp; 931;u Rydberg state of NO2. This wavepacket exemplifies two general features of excited state dynamics in polyatomic molecules anharmonic multimodal vibrational coupling forming polyads ; nonadiabatic coupling between nuclear and electronic coordinates, leading to predissociation. The latter suggests that the polyad vibrational states in the zeroth order 3p Rydberg manifold are quasi bound and best understood to be scattering resonances. We observed a rapid dephasing of an initially prepared bright valence state into the relatively long lived 3p Rydberg state whose multimodal vibrational dynamics and decay we monitor as a function of time. Our quantum simulations, based on an effective spectroscopic Hamiltonian, describe the essential features of the multimodal Fermi resonance driven vibrational dynamics in the 3p state. We also present evidence of polyad specificity in the state dependent predissociation rates, leading to free atomic and molecular fragments. We emphasize that a quantum molecular movie is required to visualize wavepacket dynamics in the 3p amp; 963;2 amp; 931;u Rydberg state of NO

Rare vulvar malignancies; incidence, treatment and survival in the Netherlands

OBJECTIVE: To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. METHODS: All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch Cancer Registry (n=6436). Standardized incidence rates, estimated annual percentage change (EAPC) and 5-year relative survival rates were calculated for basal cell carcinomas (BCCs) and melanomas. Patients with vulvar melanomas were matched to women with cutaneous melanomas on period of diagnosis, age, Breslow thickness, tumour ulceration, lymph node status and distant metastases. Differences in survival were evaluated using Kaplan-Meier curves and the log rank test. RESULTS: 489 women were diagnosed with a BCC and 350 with a melanoma of the vulva. The EAPC in incidence for melanomas was 0.2% and 1.1% for BCCs. Eighty-six percent of patients with BCC underwent surgical treatment in 1989-2006 and 95% in 2005-2012. Forty-five percent with BCC and 79% with melanoma were treated in a referral centre. Five-year relative survival for BCCs was 100% and for melanomas survival increased from 37% (95%CI 28-47%) in 1989-1999 to 45% (95%CI: 37-54%) in 2000-2012. Five years after diagnosis survival of women with vulvar melanoma was 15% lower compared to matched cutaneous melanoma patients (p=0.002). CONCLUSION: No trends in age-adjusted incidence have been observed but more patients with BCC received surgical treatment over time. Having had vulvar BCC did not affect life expectancy. Well-known prognostic factors explained most of the differences in survival between cutaneous and vulvar melanoma patients, however a difference of 15% remained unexplained