Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk ...factors for severe outcomes among adults hospitalized with COVID-19.
We analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.
The data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios aRRs, 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).
In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the ...incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous melanoma has a median survival time of less than 1 year. Surgical removal, radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies have been utilized in the treatment of melanoma. Current treatment strategies and the results of recent clinical trials are also discussed in this article.
Abstract
Background
Data on risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors ...independently associated with COVID-19–associated hospitalizations.
Methods
Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March–23 June 2020 were identified from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization.
Results
Among 5416 adults, hospitalization rates (all reported as aRR 95% confidence interval) were higher among those with ≥3 underlying conditions (vs without) (5.0 3.9–6.3), severe obesity (4.4 3.4–5.7), chronic kidney disease (4.0 3.0–5.2), diabetes (3.2 2.5–4.1), obesity (2.9 2.3–3.5), hypertension (2.8 2.3–3.4), and asthma (1.4 1.1–1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45–64 years (vs 18–44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites).
Conclusions
Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
Severe obesity, chronic kidney disease, diabetes, obesity, hypertension, asthma, age ≥45 years, male sex, and non-Hispanic black and other race/ethnicity are associated with increased risk of coronavirus disease 2019–associated hospitalizations.
Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we ...document the state-wide uptake of co-testing with HPV and cytology in women aged 30–64 years as recommended by national and international bodies.
Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21–64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology.
A total of 1,704,055 cervical screening tests from 681,440 women aged 21–64 years in the state of New Mexico were identified. The proportion of screening tests which were co-tests rose from 5.6% in 2008 to 84.3% in 2019 among women aged 30–64 years with a marked change from the near exclusive use of the Hybrid Capture II HPV test, (a signal amplified test method) to the use of target amplified HPV tests. The largest increases were seen between 2013 and 2015, reflecting the introduction and adoption of new clinical guidelines. Increases in co-testing were also seen in younger women.
Co-testing is now well established in women aged 30–64 years, but smaller increases have also been seen at younger ages, although this is not currently recommended. The impact of co-testing on cervical disease outcomes and number of colposcopies and biopsies in routine population settings remain important, especially in young women.
•Cervical cancer screening by co-testing increased from 5.6% in 2008 to 84.3% in 2019 among women ages 30–64 years.•Smaller increases in co-test usage were observed in women of younger ages, although not currently recommended.•The median screening interval increased from 15 to 39 months as screening guideline recommendations were adopted.•The near exclusive use of the Hybrid Capture II HPV test has changed to the use of target amplified HPV tests.
Lower Anogenital Squamous Terminology (LAST) standardization recommended p16
immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 ...(CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs).
To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.
A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.
Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (
≤ .001) and within each HPV risk group (
≤ .001 except for low-risk HPV
< .010). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (
< .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (
< .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL
cytology, or to be diagnosed as CIN3
by the EP (
.001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (
< .001).
p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.
Identification of positive staining is often qualitative and subjective. This is particularly troublesome in pigmented melanoma lesions, because melanin is difficult to distinguish from the brown ...stain resulting from immunohistochemistry (IHC) using horse radish peroxidase developed with 3,3'-Diaminobenzidine (HRP-DAB). We sought to identify and quantify positive staining, particularly in melanoma lesions. We visualized G-protein coupled estrogen receptor (GPER) expression developed with HRP-DAB and counterstained with Azure B (stains melanin) in melanoma tissue sections (n = 3). Matched sections (n = 3), along with 22 unmatched sections, were stained only with Azure B as a control. Breast tissue (n = 1) was used as a positive HRP-DAB control. Images of the stained tissues were generated using a Nuance Spectral Imaging Camera. Analysis of the images was performed using the Nuance Spectral Imaging software and SlideBook. Data was analyzed using a Kruskal-Wallis one way analysis of variance (ANOVA). We showed that a pigmented melanoma tissue doubly stained with anti-GPER HRP-DAB and Azure B can be unmixed using spectra derived from a matched, Azure B-only section, and an anti-GPER HRP-DAB control. We unmixed each of the melanoma lesions using each of the Azure B spectra, evaluated the mean intensity of positive staining, and examined the distribution of the mean intensities (P = .73; Kruskal-Wallis). These results suggest that this method does not require a matched Azure B-only stained control tissue for every melanoma lesion, allowing precious tissues to be conserved for other studies. Importantly, this quantification method reduces the subjectivity of protein expression analysis, and provides a valuable tool for accurate evaluation, particularly for pigmented tissues.
The BRAF inhibitor vemurafenib is currently used for treating patients with BRAF V600E mutant melanoma. However, the responses to vemurafenib are generally partial and of relatively short duration. ...Recent evidence suggests that activation of the epidermal growth factor receptor (EGFR)/erbB signaling pathway may be responsible for the development of BRAF inhibitor resistance in melanoma patients. In this study, we characterized the erbB family of receptors and ligands in melanoma cell lines and examined whether targeting both BRAF and erbB provided enhanced antitumor activity in BRAF mutant melanoma. Variable levels of erbB2, erbB3, and truncated erbB4 were expressed in both BRAF wildtype and mutant melanoma cells with no significant differences between wildtype and mutant lines. EGFR was rarely expressed. Neuregulin 3 and neuregulin 4 were the major erbB ligands released by melanoma cells. Multi-erbB targeting with the irreversible tyrosine kinase inhibitor canertinib exerted a more effective growth inhibitory effect in both BRAF wildtype and mutant melanoma cells compared with the single-erbB or dual-erbB targeting inhibitors, gefitinib, erlotinib, and lapatinib. Canertinib inhibited both EGF-induced and neuregulin 1-induced erbB downstream signaling in both mutant and wildtype cell lines. However, canertinib induced apoptosis and sub-G1 arrest only in mutant cells. Canertinib statistically increased the antiproliferative effects of vemurafenib in the BRAF mutant melanoma cell lines while little or no enhanced effect was observed with the combination treatment in the wildtype cell lines. A combined inhibition strategy targeting BRAF together with multiple erbB family kinases is potentially beneficial for treating BRAF V600E mutant melanoma. Wildtype BRAF melanoma may also benefit from a multi-erbB kinase inhibitor.
Summary
Although ultraviolet radiation (UV) exposure from indoor tanning has been linked to an increased risk of melanoma, the role of DNA repair genes in this process is unknown. We evaluated the ...association of 92 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes with the risk of melanoma and indoor tanning among 929 patients with melanoma and 817 controls from the Minnesota Skin Health Study. Significant associations with melanoma risk were identified for SNPs in ERCC4, ERCC6, RFC1, XPC, MGMT, and FBRSL1 genes; with a cutoff of P < 0.05. ERCC6 and FBRSL1 gene variants and haplotypes interacted with indoor tanning. However, none of the 92 SNPs tested met the correction criteria for multiple comparisons. This study, based on an a priori interest in investigating the role of DNA repair capacity using variants in base excision and nucleotide excision repair, identified several genes that may play a role in resolving UV‐induced DNA damage.
Experiments were performed: (i) to investigate potential age- and gender-dependent differences in mutagenic responses in T cells following exposures of B6C3F1 mice and F344 rats by inhalation for 2 ...weeks to 0 or 1250
ppm butadiene (BD), and (ii) to determine if exposures for 2 weeks to 62.5
ppm BD produce a mutagenic effect in female rats. To evaluate the effect of age on mutagenic response, mutant manifestation curves for splenic T cells of female mice exposed at 8–9 weeks of age were defined by measuring
Hprt mutant frequencies (MFs) at multiple time points after BD exposure using a T cell cloning assay and comparing the resulting mutagenic potency estimate (calculated as the difference of areas under the mutant manifestation curves of treated versus control animals) to that reported for female mice exposed to BD in the same fashion beginning at 4–5 weeks of age. The shapes of the mutant T cell manifestation curves for spleens were different e.g., the maximum BD-induced MFs in older mice (8.0
±
1.0 S.D.
×
10
−6) and younger mice (17.8
±
6.1
×
10
−6) were observed at 8 and 5 weeks post-exposure, respectively, but the mutagenic burden was the same for both age groups. To assess the effect of gender on mutagenic response, female and male rodents were exposed to BD at 4–5 weeks of age and
Hprt MFs were measured when maximum MFs are expected to occur post-exposure. The resulting data demonstrated that the pattern for mutagenic susceptibility from high-level BD exposure is female mice
>
male mice
>
female rats
>
male rats. Exposures of female rats to 62.5
ppm BD caused a minor but significant mutagenic response compared with controls (
n
=
16/group;
P
=
0.03). These results help explain part of the differing outcomes/interpretations of data in earlier
Hprt mutation studies in BD-exposed rodents.
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