The term "classic invasive lobular carcinoma" of the breast defines breast malignancies of vastly different nature.

PURPOSE: To describe in detail the special features of a previously unappreciated "classic invasive lobular carcinoma" which is confined to the terminal ductal lobular units (TDLUs) and differs considerably from the extensive classic invasive lobular carcinoma, and to suggest specific terminology. METHOD: All invasive breast cancer cases without associated microcalcifications diagnosed in our Institution with the histopathologic diagnosis of classic invasive lobular carcinoma during the years 1996-2019 (n = 560) formed the basis of this study. The cases were prospectively classified according to their imaging biomarkers (mammographic features) and followed up to Dec 31, 2021, to determine long-term patient outcome. An additional 2600 invasive breast cancer cases (diagnosed other than invasive lobular carcinoma) without associated microcalcifications served as a reference group. Detailed histopathologic analysis used large format (10x8 cm) thin section technique and staining methods including hematoxylin-eosin (H&E), E-cadherin, cytokeratin CK 5/6, a transmembrane glycoprotein (CD44) and anti-actin or anti-smooth muscle myosin heavy chain. RESULTS: The imaging biomarkers differentiated two separate disease subgroups, having the same histopathologic diagnosis, classic invasive lobular carcinoma. One of these has the imaging biomarker of extensive architectural distortion with no central tumour mass, occupies the extralobular mesenchyme and has a long-term survival of 56%. The other subgroup forms stellate or circular non-calcified tumour masses usually smaller than 20 mm, which appear to arise in the intralobular mesenchyme, and has a significantly better long-term survival of 84%. CONCLUSIONS: There is a striking difference between the subgross histopathology and the mammographic appearance (imaging biomarkers) of two breast malignancies having the same histopathologic diagnosis, "classic invasive lobular carcinoma". The large difference in the long-term outcome of these two tumour types is even more striking. Using the same specific term, "classic invasive lobular carcinoma", to describe these two separate entities can adversely affect management decisions.

Factors affecting infection control measures performed by dental workers.

Background/purpose: An understanding of self-protection related factors is important for dental infection control. This study aimed to investigate factors associated with personal self-protection in infection control among dental care workers. Materials and methods: A cross-sectional survey with self-report questionnaire was conducted between Jan and Dec, 2018.275 dentists and 298 dental assistants were enrolled from randomly selected dental care settings. Results: Compliance with wearing hair caps, facial masks, and hand washing is not as high as oral masks and gloves (over 90%). For dentists, the level of clinical setting (aOR = 3.1, P < 0.001) and the correct use of disinfectants for impression materials (aOR = 2.0, P < 0.05) were associated with hair cap wearing. Gender (aOR = 0.15, P < 0.05) and correct use of indicator during sterilization (aOR = 2.9, P < 0.05) were associated with facial mask wearing. The correct use of indicator during sterilization (aOR = 2.4, P < 0.05) and disinfection for impression materials (aOR = 2.2, P < 0.05) were associated with hand washing. For dental assistants, longer work experience (aOR = 1.05, P < 0.05), working days (aOR = 1.82, P < 0.05), the correct use of disinfectants for impression materials (aOR = 2.4, P < 0.001), and the frequent use of gloves (aOR = 8.0, P < 0.05) were associated with facial mask wearing. The surface disinfection of working tables (aOR = 2.8, P < 0.001) and the frequent changing of gloves (aOR = 5.96, P < 0.05) were associated with hand washing. Conclusion: Gender, the length of work practice, and correct techniques for sterilization use were identified as major factors associated with compliance with self-protection in infection control among dental care workers.

The challenging imaging and histopathologic features of diffusely infiltrating breast cancer.

PURPOSE: Clinical, imaging and outcome observations indicate that diffusely infiltrating breast cancer, presenting as a large region of architectural distortion on the mammogram and conventionally termed classic infiltrating lobular carcinoma of diffuse type, represents a very unusual breast malignancy. This article aims to draw attention to the complex clinical, imaging, and large format thin and thick section histopathologic features of this malignancy, which challenges our current diagnostic and therapeutic management practices. METHODS: Prospectively collected data from the randomized controlled trial (1977-85) and from the subsequent, ongoing population-based mammography service screening (1985-2019) with more than four decades of follow up in Dalarna County, Sweden provided the database for investigating this breast cancer subtype. Large format thick (subgross) and thin section histopathologic images of breast cancers diagnosed as "diffusely infiltrating lobular carcinoma of the breast" were correlated with their mammographic tumour features (imaging biomarkers) and the long-term patient outcome. RESULTS: This malignancy does not have a distinct tumour mass or focal skin retraction at clinical breast examination; instead, it causes an indistinct "thickening" and eventually shrinks the entire breast. A dominant feature is extensive architectural distortion on the mammograms caused by an excessive amount of cancer-associated connective tissue. Unlike other invasive breast malignancies, this subtype forms concave contours with the surrounding adipose connective tissue, a feature that makes it difficult to detect on mammograms. Women with this diffusely infiltrating breast malignancy have a 60% long-term survival. Its long-term patient outcome is surprisingly poor compared to that expected from its relatively favourable immunohistochemical biomarkers, including a low proliferation index and remains unaffected by adjuvant therapy. CONCLUSIONS: The unusual clinical, histopathologic and imaging features of this diffusely infiltrating breast cancer subtype are consistent with a site of origin quite different from that of other breast cancers. Additionally, the immunohistochemical biomarkers are deceptive and unreliable because they indicate a cancer with favourable prognostic features predictive of a good long-term outcome. The low proliferation index is usually indicative of a breast cancer with a good prognosis, but in this subtype the prognosis is poor. If we are to improve the dismal outcome of this malignancy, it will be necessary to clarify its true site of origin, which will be a prerequisite for gaining a better understanding why current management efforts often fail and why the fatality rate is so unfortunately high. Breast radiologists should be watchful for the development of subtle signs of architectural distortion at mammography. Large format histopathologic technique enables adequate correlation of the imaging and histopathologic findings.

Evaluating correlates of protection for mix-match vaccine against COVID-19 VOCs with potential of evading immunity.

BACKGROUND: In the face of rapid emerging variants of concern (VOCs) with potential of evading immunity from Beta to Omicron and uneven distribution of different vaccine brands, a mix-match strategy has been considered to enhance immunity. However, whether increasing immunogenicity using such a mix-match can lead to high clinical efficacy, particularly when facing Omicron pandemic, still remains elusive without using the traditional phase 3 trial. The aim of this study is to demonstrate how to evaluate correlates of protection (CoP) of the mix-match vaccination. METHODS: Data on neutralizing antibody (NtAb) titers and clinical efficacy against Wuhan or D614G strains of homologous ChAdOx1 nCov-19 or mRNA-1273 and heterologous vaccination were extracted from previous studies for demonstration. The reductions in NtAb titers of homologous vaccination against Beta, Delta, and Omicron variants were obtained from literatures. A Bayesian inversion method was used to derive CoP from homologous to mix-match vaccine. Findings The predicted efficacy of ChAdOx1 nCov-19 and mRNA-1273 for Wuhan or D614G strains was 93 % (89 %-97 %). Given 8 âˆ¼ 11-fold, 2 âˆ¼ 5.5-fold, and 32.5 âˆ¼ 36-fold reduction of NtAb for Beta, Delta, and Omicron variants compared with D614G, the corresponding predictive efficacy of the mix-match ranged from 75.63 % to 73.87 %, 84.87 % to 81.25 %, and 0.067 % to 0.059 %, respectively. Interpretations While ChAdOx1 nCov-19 and mRNA-1273 used for demonstrating how to timely evaluate CoP for the mix-match vaccine still provides clinical efficacy against Beta and Delta VOCs but it appears ineffective for Omicron variants, which highlights the urgent need for next generation vaccine against Omicron variant.

Review of epidemic, containment strategies, clinical management, and economic evaluation of COVID-19 pandemic.

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

Risk Prediction of Prostate Cancer with Single Nucleotide Polymorphisms and Prostate Specific Antigen.

PURPOSE: Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information. MATERIALS AND METHODS: We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above. RESULTS: The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined. CONCLUSIONS: Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.

Association Between Colorectal Cancer Mortality and Gradient Fecal Hemoglobin Concentration in Colonoscopy Noncompliers.

Background: To what extent the risk for colorectal cancer (CRC) death among noncompliers of colonoscopy is elevated following positive fecal immunological testing and whether the elevated risk varies with the fecal hemoglobin concentration (f-Hb) and location of CRC have not been researched. Methods: We used data on 59 389 individuals (4.0%) among 1 489 937 Taiwanese screenees age 50 to 69 years with f-Hb 20 µg hemoglobin or more per gram of feces from 2004 to 2009. They were classified into 41 995 who received colonoscopy and 10 778 who received no confirmatory examination; the latter was categorized into three risk groups according to f-Hb (20-49, 50-99, and 100+). Mortality from CRC as the primary end point was monitored until December 31, 2012. Results: A 1.64-fold (95% confidence interval [CI] = 1.32 to 2.04) increased risk for CRC death for the noncolonoscopy group as opposed to the colonoscopy group adjusting for differences in baseline characteristics. A gradient relationship was noted between cumulative mortality and age- and sex-adjusted f-Hb categories with 1.31-fold (95% CI = 1.04 to 1.71), 2.21-fold (95% CI = 1.55 to 3.34), and 2.53-fold (95% CI = 1.95 to 3.43) increased risk, respectively, for the 20-49, 50-99, and 100+ risk groups in the noncolonoscopy group compared with the colonoscopy group. The noncolonoscopy group led to a statistically significant 1.75-fold increased risk (95% CI = 1.35 to 2.33) for CRC of the distal colon but a statistically nonsignificant 1.11-fold increased risk (95% CI = 0.70 to 1.75) for the proximal colon, compared with the colonoscopy group. When the comparator was limited to subjects whose colonoscopy was completed to the cecum, the statistically significantly elevated risk for CRC mortality was seen for both distal and proximal colon in the noncolonoscopy group. Conclusions: After a positive fecal immunochemical test, colonoscopy can reduce by about half the number of deaths from CRC. Among colonoscopy noncompliers, higher f-Hb is associated with an increased risk of mortality from CRC in a dose-response manner.