Modelling the reopen strategy from dynamic zero-COVID in China considering the sequela and reinfection.

Although the dynamic zero-COVID policy has effectively controlled virus spread in China, China has to face challenges in balancing social-economic burdens, vaccine protection, and the management of long COVID symptoms. This study proposed a fine-grained agent-based model to simulate various strategies for transitioning from a dynamic zero-COVID policy with a case study in Shenzhen. The results indicate that a gradual transition, maintaining some restrictions, can mitigate infection outbreaks. However, the severity and duration of epidemics vary based on the strictness of the measures. In contrast, a more direct transition to reopening may lead to rapid herd immunity but necessitate preparedness for potential sequelae and reinfections. Policymakers should assess healthcare capacity for severe cases and potential long-COVID symptoms and determine the most suitable approach tailored to local conditions.

Impact of the COVID-19 pandemic on people in need of care or support: protocol for a SARS-CoV-2 registry.

INTRODUCTION: People in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical and psychosocial impact of the COVID-19 pandemic on people in need of care or support in Bavaria, Germany. To describe the persons' life conditions comprehensively, we assess the perspectives and needs of the respective care teams too. Results will serve as evidence-based source to manage the pandemic and long-term prevention strategies. METHODS AND ANALYSIS: The 'Bavarian ambulatory COVID-19 Monitor' is a multicentre registry including a purposive sample of up to 1000 patient-participants across three study sites in Bavaria. The study group consists of 600 people in need of care with a positive SARS-CoV-2 PCR test. Control group 1 comprises 200 people in need of care with a negative SARS-CoV-2 PCR test, while control group 2 comprises 200 people with a positive SARS-CoV-2 PCR test but are not in need of care. We assess the clinical course of infection, psychosocial aspects and care needs using validated measures. Follow-up is every 6 months for up to 3 years. Additionally, we assess up to 400 people linked to these patient-participants (caregivers, general practitioners (GPs)) for their health and needs. Main analyses are stratified by level of care I-V (I=minor/V=most severe impairment of independence), inpatient/outpatient care setting, sex and age. We use descriptive and inferential statistics to analyse cross-sectional data and changes over time. In qualitative interviews with 60 stakeholders (people in need of care, caregivers, GPs, politicians), we explore interface problems of different functional logics, of everyday and professional perspectives. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Hospital LMU Munich (#20-860) and the study sites (Universities of Wurzburg and Erlangen) approved the protocol. We disseminate the results by peer-reviewed publications, international conferences, governmental reports, etc.

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Tumours of the Oral Cavity and Mobile Tongue.

The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.

Developmental Odontogenic Lesions Associated with the Crown of an Impacted Tooth: A Guide to the Distinct Histologic Features Required for Classification.

Odontogenic cysts are categorized as inflammatory and developmental. Of the developmental odontogenic cysts, the dentigerous cyst is the most common and by definition is attached to the cervical region of an unerupted tooth. The cyst envelops the crown forming a sac. However, there are other developmental cysts, and rarely, odontogenic tumors, that can have a similar clinical and radiographic presentation as dentigerous cyst, including odontogenic keratocyst, orthokeratinized odontogenic cyst and ameloblastoma, unicystic type. Understanding the key histologic differences of these cysts will aid the pathologist to correctly diagnose these lesions, ensuring appropriate clinical management.

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study.

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss' kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons' responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial.

AIMS: Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group. CONCLUSION: Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

Histopathology Feature Mining and Association with Hyperspectral Imaging for the Detection of Squamous Neoplasia.

Hyperspectral imaging (HSI) is a noninvasive optical modality that holds promise for early detection of tongue lesions. Spectral signatures generated by HSI contain important diagnostic information that can be used to predict the disease status of the examined biological tissue. However, the underlying pathophysiology for the spectral difference between normal and neoplastic tissue is not well understood. Here, we propose to leverage digital pathology and predictive modeling to select the most discriminative features from digitized histological images to differentiate tongue neoplasia from normal tissue, and then correlate these discriminative pathological features with corresponding spectral signatures of the neoplasia. We demonstrated the association between the histological features quantifying the architectural features of neoplasia on a microscopic scale, with the spectral signature of the corresponding tissue measured by HSI on a macroscopic level. This study may provide insight into the pathophysiology underlying the hyperspectral dataset.

Frictional Keratosis, Contact Keratosis and Smokeless Tobacco Keratosis: Features of Reactive White Lesions of the Oral Mucosa.

White lesions of the oral cavity are quite common and can have a variety of etiologies, both benign and malignant. Although the vast majority of publications focus on leukoplakia and other potentially malignant lesions, most oral lesions that appear white are benign. This review will focus exclusively on reactive white oral lesions. Included in the discussion are frictional keratoses, irritant contact stomatitis, and smokeless tobacco keratoses. Leukoedema and hereditary genodermatoses that may enter in the clinical differential diagnoses of frictional keratoses including white sponge nevus and hereditary benign intraepithelial dyskeratosis will be reviewed. Many products can result in contact stomatitis. Dentrifice-related stomatitis, contact reactions to amalgam and cinnamon can cause keratotic lesions. Each of these lesions have microscopic findings that can assist in patient management.

Non-infectious Granulomatous Lesions of the Orofacial Region.

Granulomatous lesions of the orofacial region are a heterogeneous group of disorders characterized by a granulomatous reaction to a variety of stimuli. Infectious agents, foreign material, systemic inflammation and metabolic disorders can all be associated with granulomatous inflammation. In the orofacial region primary causes of granulomatosis include foreign body reaction, delayed hypersensitivity to topical agents and idiopathic orofacial granulomatosis. Secondary causes of granulomas include infectious agents, sarcoid, and Crohn disease. For this review, infectious causes of orofacial granulomatosis (OFG) including bacteria, parasites and fungi will not be discussed.

Data Set for the Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Standardized pathologic reporting for cancers allows for improved communication for patient care and prognostic determination. If used universally, synoptic reporting enhances comparing data globally for scientific leverage. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Multiple different sites within the head and neck may be affected by mucosal melanoma, whose behavior and patient outcome are not equivalent to carcinomas of the corresponding sites. Factors such as Breslow thickness and Clark depth of invasion applied to cutaneous melanomas do not yield any prognostic significance in mucosal sites, and thus are not meaningful. Likewise, margin assessment is unique in head and neck sites. Further, the genetic profile of mucosal melanomas is different from that of most cutaneous tumors. Thus, within the head and neck region, mucosal melanoma is a distinct entity for which a dedicated data set was developed for implementation. The elements that comprise the core (required) and noncore (recommended) elements are discussed.

Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting.

The International Collaboration on Cancer Reporting is a nonprofit organization whose goal is to develop evidence-based, internationally agreed-upon standardized data sets for each cancer site for use throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to the objective of improved patient management and enhanced epidemiologic research. Carcinomas of the oral cavity continue to represent a significant oncologic management burden, especially as changes in alcohol and tobacco use on a global scale contribute to tumor development. Separation of oral cavity carcinomas from oropharyngeal tumors is also important, as management and outcome are quite different when human papillomavirus association is taken into consideration. Topics such as tumor thickness versus depth of invasion, pattern of invasive front, extent and size of perineural invasion, and margin assessment all contribute to accurate classification and staging of tumors. This review focuses on the data set developed for Carcinomas of the Oral Cavity Histopathology Reporting Guide, with discussion of the key elements developed for inclusion.

Prognostic implications of peritumoral vasculature in head and neck cancer.

BACKGROUND: There is conflicting evidence regarding the role of peritumoral lymphatic vessel density (LVD) and blood microvessel density (MVD) in the metastasis and prognosis of head and neck squamous cell carcinoma (HNSCC). Existing studies are limited to one or two head and neck subsites and/or small sample sizes. A larger study incorporating multiple sub-sites is needed to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis. METHODS: Tissue samples from 200 HNSCC cases were stained simultaneously using immunohistochemistry (IHC) for markers of peritumoral LVD (lymphatic vessel marker D240) and MVD (blood vessel marker CD31). Of the stained slides, 166 and 167 were evaluable for LVD and MVD, respectively. The results were then correlated with clinicopathologic features and patient outcomes. RESULTS: Patients with metastatic disease were more likely to have high peritumoral MVD. Through multivariable analyses, MVD was not significantly related to DFS and OS, while low LVD was related to higher risk of disease progression and poor survival. CONCLUSIONS: Peritumoral MVD was found to be positively associated with metastasis, while LVD was found to be inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC.

Oral epithelial dysplasia, atypical verrucous lesions and oral potentially malignant disorders: focus on histopathology.

The term oral potentially malignant disorders (OPMDs) describes a recognizable group of mucosal diseases that have a risk of progressing to squamous cell carcinoma. Oral leukoplakia, the most common OPMD, has a 1% prevalence and reported malignant transformation rates of 2% to 5%. Other OPMDs include erythroplakia, erythroleukoplakia, submucous fibrosis, lesions of reverse smokers, and inherited genetic disorders, such as Fanconi anemia. The histopathologic assessment of OPMDs is an area of subjectivity, and oral epithelial dysplasia (OED) is fraught with both interrater variability and intrarater variability. Both architectural and cytologic changes are utilized when developing criteria for grading OED. However, the concept of atypical verrucous lesions, particularly as it pertains to proliferative verrucous leukoplakia, suffers from lack of histopathologic diagnostic criteria. Histopathologic mimics of OPMDs, including reactive/regenerative epithelium, frictional keratosis, and infection, can result in patient mismanagement. This review will focus specifically on the histologic features of OED, including human papillomavirus-associated dysplasia, as well as the histologic features of atypical verrucous keratoses/hyperplasia, particularly those that arise in the setting of proliferative verrucous leukoplakia along with OPMD mimics.

Detection and delineation of squamous neoplasia with hyperspectral imaging in a mouse model of tongue carcinogenesis.

Hyperspectral imaging (HSI) holds the potential for the noninvasive detection of cancers. Oral cancers are often diagnosed at a late stage when treatment is less effective and the mortality and morbidity rates are high. Early detection of oral cancer is, therefore, crucial in order to improve the clinical outcomes. To investigate the potential of HSI as a noninvasive diagnostic tool, an animal study was designed to acquire hyperspectral images of in vivo and ex vivo mouse tongues from a chemically induced tongue carcinogenesis model. A variety of machine-learning algorithms, including discriminant analysis, ensemble learning, and support vector machines, were evaluated for tongue neoplasia detection using HSI and were validated by the reconstructed pathological gold-standard maps. The diagnostic performance of HSI, autofluorescence imaging, and fluorescence imaging were compared in this study. Color-coded prediction maps were generated to display the predicted location and distribution of premalignant and malignant lesions. This study suggests that hyperspectral imaging combined with machine-learning techniques can provide a noninvasive tool for the quantitative detection and delineation of squamous neoplasia.

Elastic particle deformation in rectangular channel flow as a measure of particle stiffness.

In this study, we experimentally observed and characterized soft elastic particle deformation in confined flow in a microchannel with a rectangular cross-section. Hydrogel microparticles of pNIPAM were produced using two different concentrations of crosslinker. This resulted in particles with two different shear moduli of 13.3 ± 5.5 Pa and 32.5 ± 15.7 Pa and compressive moduli of 66 ± 10 Pa and 79 ± 15 Pa, respectively, as measured by capillary micromechanics. Under flow, the particle shapes transitioned from circular to egg, triangular, arrowhead, and ultimately parachute shaped with increasing shear rate. The shape changes were reversible, and deformed particles relaxed back to circular/spherical in the absence of flow. The thresholds for each shape transition were quantified using a non-dimensional radius of curvature at the tip, particle deformation, circularity, and the depth of the concave dimple at the trailing edge. Several of the observed shapes were distinct from those previously reported in the literature for vesicles and capsules; the elastic particles had a narrower leading tip and a lower circularity. Due to variations in the shear moduli between particles within a batch of particles, each flow rate corresponded to a small but finite range of capillary number (Ca) and resulted in a series of shapes. By arranging the images on a plot of Ca versus circularity, a direct correlation was developed between shape and Ca and thus between particle deformation and shear modulus. As the shape was very sensitive to differences in shear modulus, particle deformation in confined flow may allow for better differentiation of microparticle shear modulus than other methods.

Generation and characterization of monodisperse deformable alginate and pNIPAM microparticles with a wide range of shear moduli.

Monodisperse particles of varying size, shape, and deformability were produced using two microfluidic strategies. For both strategies, monodisperse emulsion droplets of a crosslinkable solution were generated via flow-focusing. Subsequently, droplets were crosslinked either on chip or in an external bath. On-chip gelation resulted in spherical particles; varying the degree of crosslinking varied the deformability systematically. The optimized flow-focusing device design separated the production of monodisperse aqueous alginate droplets and the on-chip introduction of crosslinking ions. Two features were then adapted to target softer particles: the dispersed phase design and the polymer choice. The alternative design used a sheathed dispersed phase, with the polymer solution surrounding an unreactive viscous core, which generated alginate particles with a softer core. Poly(N-isopropylacrylamide) (pNIPAM) allowed access to a broad range of moduli. The resulting spherical particles were characterized using capillary micromechanics to determine the shear (G) and compressive (K) moduli. Particles with G = 0.013 kPa to 26 kPa and K = 0.221 kPa to 34.9 kPa were obtained; the softest particles are an order of magnitude softer than those previously reported. The second approach, based on earlier work by Hu et al., produced axisymmetric, non-spherical particles with fore-aft asymmetry. Alginate drops were again formed in a flow-focusing device but were crosslinked off-chip in an external gelation bath. By changing the bath viscosity, crosslinker concentration, and outlet height, the falling droplets deformed differently during gelation, resulting in a variety of shapes, such as teardrop, mushroom, and bowl shapes.

Evaluation and comparison of two microfluidic size separation strategies for vesicle suspensions.

Two size-based separation strategies are evaluated for suspensions consisting of giant unilamellar vesicles with a broad, continuous distribution of diameters. Microfluidic devices were designed to separate an initial suspension into larger and smaller particles via either filtration or inertial focusing. These separation mechanisms were tested with suspensions of vesicles and suspensions of rigid spheres separately to illustrate the effect of deformability on separation ability. We define several separation metrics to assess the separation ability and to enable comparison between separation strategies. The filtration device significantly reduced the polydispersity of the separated vesicle fractions relative to the starting suspension and displayed an ability to separate vesicle suspensions at high throughputs. The device that utilized inertial focusing exhibited adequate polydispersity reduction and performed best with diluted vesicle suspensions. The inertial device had fewer issues with debris and trapped air, leading to short device preparation times and indicating a potential for continuous separation operation.

Update from the 4th Edition of the World Health Organization of Head and Neck Tumours: Tumours of the Oral Cavity and Mobile Tongue.

There have been several additions and deletions in Chapter 4 on Tumours of the oral cavity and mobile tongue in the 2017 fourth edition of the World Health Organization Classification of Tumours of the Head and Neck. This chapter excludes the oropharynx, which now is a stand-alone chapter acknowledging the uniqueness of the oropharynx from the oral cavity. New entries in Chapter 4 include rhabdomyoma, haemangioma, schwannoma, neurofibroma and myofibroblastic sarcoma in the section titled Soft tissue and neural tumours. Discussion of salivary gland entities have been reduced and includes mucoepidermoid carcinoma and pleomorphic adenoma as the other salivary gland types are discussed elsewhere. In the Haematolymphoid tumours section, like the salivary gland section, only tumors that commonly present in the oral cavity are discussed in Chapter 4. Excluded entities in the updated classification include papillary hyperplasia, median rhomboid glossitis, keratoacanthoma, focal oral mucinosis, and secondary tumors. This article will summarize the changes in the new classification since the 2005 edition focusing on selected entities that have had significant changes along with new entries.