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Comparison of Melanocyte-Associated Immunohistochemical Markers in Acral Lentiginous Melanoma and Acral Benign Nevi

Am J Dermatopathol. 2023 Nov 1;45(11):748-752. doi: 10.1097/DAD.0000000000002555.

ABSTRACT

Acral lentiginous melanoma (ALM) is a relatively rare clinicopathologic subtype of cutaneous malignant melanoma, but it is the most common type of melanoma among Asians. Although the research to identify immunohistochemical (IHC) markers to differentiate nevi from melanoma is being conducted, specific markers for ALM are not well-known. Therefore, we aimed to analyze and compare the differences in the expression of melanocyte-associated IHC markers between ALM and acral benign nevi (ABN). Two independent groups of 53 and 19 paraffin-embedded specimens (from patients with pathologically confirmed ALM and ABN, respectively) were subjected to IHC staining for MART-1, preferentially expressed antigen in melanoma (PRAME), SOX10, HMB-45, Ki-67, and p16. We performed a quantitative analysis of PRAME, SOX10, KI-67, and p16 expression and gradient pattern analysis of HMB-45 expression for each specimen. The PRAME (60.1% and 28.5%, P < 0.05) and Ki-67 (7.8% and 3.5%, P < 0.05) expression levels were significantly higher in the ALM group than in the ABN group. The p16 expression was significantly lower (14.2% and 19.4%, P < 0.05), and the absence of HMB-45 gradient was more frequent in the ALM group than in the ABN group. However, no statistical significance was noted in SOX10 (54.8% and 44.7%). Receiver operating characteristic curves showed that PRAME had the highest area under the curve value. In summary, among various IHC markers, PRAME was the most valuable marker for the diagnosis of ALM; however, further large-scale studies are needed to validate these findings.

PMID:37856738 | DOI:10.1097/DAD.0000000000002555

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Situational analysis of nutritional status among 1899 children presenting with cleft lip and/or palate in Indonesia

J Glob Health. 2023 Oct 20;13:04127. doi: 10.7189/jogh.13.04127.

ABSTRACT

BACKGROUND: Given the increased risk of malnutrition in children with cleft lip and/or palate (CLP), determining their nutritional status is critical for preventing adverse surgical risks. However, no such disaggregated, national-level data are available in Indonesia. We aimed to determine the nutritional status of patients with clefts in Indonesia and to identify problems and solutions for malnutrition cases within the population.

METHODS: In this cross-sectional study, we considered records of individuals who underwent primary surgery for CLP in Smile Train-sponsored facilities in Indonesia between 1 January 2016 and 31 December 2021 (n = 18 480). We only included children under the age of five with an evaluation date prior to admission date and excluded subjects with invalid data values. We classified their nutritional status by z-scores according to the World Health Organization Child Growth Standard (2006). Malnutrition cases cover four indicators – stunting, wasting, underweight, and overweight. We compared the prevalence for malnutrition cases in children under the age of five using national health survey data.

RESULTS: We included 1899 records following data validation. The national prevalence of stunting (24.4%), wasting (12.5%), and overweight cases (12.9%) was high, while underweight cases (6.8%) were comparatively low. Statistical analyses showed significant differences in nutritional status based on length/height-for-age between girls and boys aged 0-5 months (P = 0.008) and 48-60 months (P = 0.001), and based on body mass index-for-age (P = 0.000) between girls and boys aged 0-5 months. Girls in different age groups exhibited a statistically significant difference in nutritional status based on length/height-for-age (P = 0.002) and weight-for-age (P = 0.017). Concurrent stunting and overweight were the most common forms of concurrent malnutrition (8.7%). We found a significant difference in the prevalence of underweight (P = 0.001) and overweight (P = 0.000) cases between children with CLP and those without CLP.

CONCLUSIONS: Our findings highlight the importance of nutritional interventions for children with orofacial clefts in Indonesia, and the importance of age and gender in their design and implementation. Further investigation is necessary to explore the risks of overweight and concurrent malnutrition among this population.

PMID:37856736 | DOI:10.7189/jogh.13.04127

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A Fast, Robust Method for Quantitative Assessment of Collagen Fibril Architecture from Transmission Electron Micrographs

Microsc Microanal. 2023 Oct 19:ozad116. doi: 10.1093/micmic/ozad116. Online ahead of print.

ABSTRACT

Collagen is the most abundant protein in mammals; it exhibits a hierarchical organization and provides structural support to a wide range of soft tissues, including blood vessels. The architecture of collagen fibrils dictates vascular stiffness and strength, and changes therein can contribute to disease progression. While transmission electron microscopy (TEM) is routinely used to examine collagen fibrils under normal and pathological conditions, computational tools that enable fast and minimally subjective quantitative assessment remain lacking. In the present study, we describe a novel semi-automated image processing and statistical modeling pipeline for segmenting individual collagen fibrils from TEM images and quantifying key metrics of interest, including fibril cross-sectional area and aspect ratio. For validation, we show first-of-their-kind illustrative results for adventitial collagen in the thoracic aorta from three different mouse models.

PMID:37856696 | DOI:10.1093/micmic/ozad116

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Factors Associated with In-Hospital Exclusive Breastfeeding Among a Racially and Ethnically Diverse Patient Population

Breastfeed Med. 2023 Oct;18(10):751-758. doi: 10.1089/bfm.2023.0115.

ABSTRACT

Objective: The aim of this study is to examine in-hospital exclusive breastfeeding (EBF) and its association with sociodemographic factors, medical factors, breastfeeding intentions, and health care system breastfeeding support. Materials and Methods: We conducted a retrospective cross-sectional study using medical records from 2015 to 2019 of healthy term infants without breastfeeding contraindications at a public teaching hospital serving a racially and ethnically diverse patient population. Using multivariable regression analysis, we examined the associations between in-hospital EBF and sociodemographic factors, medical factors, breastfeeding intentions, and health care system breastfeeding support (in-hospital breastfeeding education and lactation support). Results: The prevalence of in-hospital EBF was 29.0%. The statistically significant findings from our fully adjusted regression analysis include that there was a higher prevalence of in-hospital EBF among adult mothers (prevalence ratio [PR]: range 1.78-1.96), married mothers (PR: 1.35, 95% confidence interval [CI]: 1.23-1.44), and mothers who were White (PR: 1.41, 95% CI: 1.20-1.66, compared with Black). Factors associated with a lower prevalence of in-hospital EBF were maternal diabetes (PR: 0.82, 95% CI: 0.70-0.95), pre-eclampsia/eclampsia (PR: 0.82, 95% CI: 0.71-0.95), cesarean delivery (PR: 0.84, 95% CI: 0.77-0.92), neonatal hypoglycemia (PR: 0.46, 95% CI: 0.36-0.59), and intention in the prenatal period to formula feed only (PR: 0.15, 95% CI: 0.10-0.22). In-hospital lactation support was associated with higher prevalence of in-hospital EBF (PR: 1.24, 95% CI: 1.16-1.33). Conclusions: Prioritizing lactation support for Black mothers, adolescent mothers, those intending in the prenatal period to formula feed only, and mother-infant dyads with certain medical factors could improve in-hospital EBF.

PMID:37856663 | DOI:10.1089/bfm.2023.0115

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Polymorphisms associated with oral clefts as potential markers for oral pre and malignant disorders

Oral Dis. 2023 Oct 19. doi: 10.1111/odi.14779. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether genes in the Wnt pathway, which have been previously associated with both oral clefts and oral squamous cell carcinoma, are also associated with oral potentially malignant disorders (leukoplakia, erythroplakia and lichen planus).

MATERIALS AND METHODS: Case-control study: Dataset consisted of clinical information linked to DNA samples from affected subjects diagnosed with oral potential malignant disorders and oral cancer and their matched controls. Individual samples, clinical history, and potential risk factors were obtained through the Dental Registry and DNA Repository project of the School of Dental Medicine, University of Pittsburgh. The rs1533767 (WNT11), rs9879992 (GSK3B), and rs3923087 (AXIN2) were tested. After genomic DNA had been extracted, genotyping was performed blindly to clinical diagnosis status. Representation of genotypes and alleles in affected subjects in comparison to the unaffected individuals was determined using PLINK. Additional analysis was performed to investigate associations between environmental (socioeconomic/lifestyle) risk factors and the oral pathologies studied using STATA.

RESULTS: Two of the SNPs tested (rs9879992 in GSK3B and rs3923087 in AXIN2) were statistically, significantly associated with the pathologies studied (p = 0.039 and 0.038, respectively).

CONCLUSION: Single-nucleotide polymorphisms in genes in the Wnt pathway were associated with oral potentially malignant disorders.

PMID:37856649 | DOI:10.1111/odi.14779

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Building an alliance to map global supply networks

Science. 2023 Oct 20;382(6668):270-272. doi: 10.1126/science.adi7521. Epub 2023 Oct 19.

ABSTRACT

New firm-level data can inform policy-making.

PMID:37856603 | DOI:10.1126/science.adi7521

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The ongoing impact of the COVID-19 pandemic on physical activity and screen time among Canadian adults

Health Rep. 2023 Oct 18;34(10):13-23. doi: 10.25318/82-003-x202301000002-eng.

ABSTRACT

BACKGROUND: Canadian and international research has shown that the COVID-19 pandemic led to changes in health behaviours, including participation in physical activity and screen time.

METHODS: The Canadian Community Health Survey asks Canadian adults (aged 18 to 64 years) and older adults (aged 65 and older) to report the time they spend active by domain: recreation, transportation, and household and/or occupation. Survey respondents are also asked to report their screen time on days they worked and days they did not work. The present analysis compares the physical activity from four cross-sectional samples collected during 2018 (n=50,093), January to mid-March 2020 (n=13,933), September to December 2020 (n=25,661) and January 2021 to February 2022 (n=45,742). Screen time is compared between 2018 and 2021. Sub-annual analyses examine how physical activity and screen time varied within and between years.

RESULTS: The percentage of 18- to 64-year-old women meeting the physical activity recommendation did not change from 2018 (54.3%) to 2021 (55.1%), while a slight decrease was observed among men (63.0% in 2018 to 59.8% in 2021). The percentage of adults aged 65 years and older meeting the recommendation increased from 2018 to 2021 among both men (40.7% to 43.8%) and women (33.4% to 36.9%). Total physical activity decreased by 17.5 minutes per week among 18- to 64-year-old men and increased by 8.4 minutes per week among 18- to 64-year-old women. Men and women aged 65 and older increased their total physical activity by about 30 minutes per week from 2018 to 2021. The percentage of 18- to 64-year-old adults in the lowest screen time category decreased from 53.9% in 2018 to 45.0% in 2021 on work days and from 37.8% in 2018 to 28.0% in 2021 on non-work days. The percentage of adults aged 65 and older in the lowest screen time category decreased from 49.4% in 2018 to 37.8% in 2021 on work days and from 29.4% in 2018 to 21.5% in 2021 on non-work days.

INTERPRETATION: Physical activity among men aged 18 to 64 years decreased from 2018 to 2021, while women of this age group maintained their physical activity. Older adults increased their physical activity from 2018 to 2021. Many Canadian adults shifted from the lowest screen time category (two hours or less per day) to the highest screen time category (four hours or more per day) during the 2020 and 2021 pandemic years. It is unknown whether the short-term impact of the COVID-19 pandemic on physical activity and screen time will persist over time. Ongoing surveillance of the longer-term impacts of the pandemic on the health behaviours of Canadians is important.

PMID:37856572 | DOI:10.25318/82-003-x202301000002-eng

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The ongoing impact of the COVID-19 pandemic on physical activity and screen time among Canadian youth

Health Rep. 2023 Oct 18;34(10):3-12. doi: 10.25318/82-003-x202301000001-eng.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused changes in health behaviours, including participation in physical activity and screen time. The purpose of this paper is to examine trends in physical activity and screen time among Canadian youth from January 2018 to February 2022.

METHODS: The Canadian Community Health Survey asks Canadian youth (aged 12 to 17 years) to report the time they spend active by domain: recreation, transportation, school and household. Survey respondents are also asked to report their screen time on school days and non-school days. The present analysis compares the physical activity from four cross-sectional samples collected during 2018 (January to December; n=3,952), January to March 2020 (n=911), September to December 2020 (n=1,573), and January 2021 to February 2022 (n=3,501). Screen time is compared between 2018 and 2021/2022. Sub-annual descriptive analyses examine how physical activity and screen time varied within and between these years.

RESULTS: Before the COVID-19 pandemic, half of Canadian youth met the physical activity recommendation (2018: 49.6%; January to March 2020: 53.7%). The percentage meeting the recommendation dropped in the first year of the pandemic (September to December 2020: 37.3%) and recovered slightly in 2021 (43.8%). From 2018 to 2021, total physical activity dropped by 8.3 minutes per day (58.1 minutes per week) among girls and by 2.1 minutes per day (14.7 minutes per week) among boys. The percentage of youth meeting the screen time recommendation on school days dropped from 40.7% in 2018 to 29.1% in 2021 and from 21.4% in 2018 to 13.2% in 2021 on non-school days.

INTERPRETATION: The COVID-19 pandemic had a detrimental impact on the physical activity and screen time of youth, in particular among girls. This analysis provides an update on how the pandemic has continued to affect the physical activity and screen habits of youth in 2020, 2021, and early 2022.

PMID:37856571 | DOI:10.25318/82-003-x202301000001-eng

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Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs

J Natl Compr Canc Netw. 2023 Oct;21(10):1039-1049.e10. doi: 10.6004/jnccn.2023.7047.

ABSTRACT

BACKGROUND: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied.

METHODS: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation.

RESULTS: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant “on-treatment” hypertension was not associated with MACE.

CONCLUSIONS: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.

PMID:37856199 | DOI:10.6004/jnccn.2023.7047

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Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer

J Natl Compr Canc Netw. 2023 Oct;21(10):1011-1019.e6. doi: 10.6004/jnccn.2023.7048.

ABSTRACT

BACKGROUND: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer.

METHODS: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups.

RESULTS: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population’s 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results.

CONCLUSIONS: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

PMID:37856198 | DOI:10.6004/jnccn.2023.7048