Comorbidity of periodontitis and herpes in the postcovid period

Improving the diagnosis and provision of dental care for patients with chronic periodontitis in combination with herpetic diseases is an urgent goal of many studies. At the same time, the COVID-19 pandemic, including the course of its post-covid period, has somewhat changed the view of specialists on the diagnosis and treatment of these comorbid diseases. The aim of the study was a metagenomic analysis of the microbiota of patients with periodontitis in combination with herpetic lesions in the postcovid period. Materials and methods. 28 people aged 18—19 years were examined: 8 patients with chronic periodontitis and herpes of the lips in the postcovid period (group I), 9 patients with chronic periodontitis and herpetiform stomatitis in the postcovid period (group II), 11 conditionally healthy young people (group III, comparisons). The biomaterial was selected after professional oral hygiene from periodontal spaces;metagenomic analysis was carried out using a Nanodrop ND-2000 spectrophotometer, "Quant-iT dsDNA HS” analysis kits and "MiSeq” sequencer (Illumina). Results. The structures of microbial communities of 28 samples of the microbiome of periodontal spaces were analyzed, the average length of the resulting sequences was 460 base pairs, an average of 13 974 sequences accounted for the sample, 183 phylotypes belonging to 17 types were identified, of which 46 of the most numerous phylotypes were identified. Relative to the comparison group, the experimental groups showed a tendency to decrease the normal microbiota (Streptococcus, Rothia), an increase in the biodiversity of Shannon and individual representatives of the conditionally pathogenic spectrum (group I — Prevotella, Fusobacterium, Campylobacter, Haemophilus, Selenomonas, Treponema, Tannerella and Filifactor;group II — unclassified TM7-3, Actinomyces, Veillonella, unclassified Gemellaceae, Porphyromonas). Conclusion. The features of the microbiome of the periodontal pocket in comorbid patients with periodontitis and herpes in the postcovid period were revealed, individual representatives of the microbiome were identified, their features were described, which gives grounds for the use of various treatment methods, including using minimally invasive therapy against the background of antiviral agents. © 2023 Clinical Dentistry LLC. All rights reserved.

Chilblain lupus erythematosus associated with systemic lupus erythematosus: A classic diagnosis in a current epidemiological context

Objectives: Chilblain lupus erythematosus (LE) is a rare chronic cutaneous lupus erythematosus (CCLE) characterized by the appearance of violaceous plaques in acral regions most exposed to cold. The isolated form affects middle-aged women, while the familial form manifests in early childhood and is associated with mutations in the TREX1 gene. Result(s): A 13-year-old adolescent, with no relevant family history, was referred in March 2021 for suspected chilblain-like lesions associated with COVID-19 infection. The patient presented with multiple violaceous papules on hands and feet. The lesions were slightly painful. Small hyperkeratotic papules were also observed on finger pads. Physical examination also revealed some aphthae affecting the lips. No other systemic symptoms were reported. A skin biopsy and blood tests were performed due to presumed chilblain LE with probable systemic involvement. Histology revealed basal vacuolar damage and intense perivascular and periadnexal lymphocytic inflammatory dermal infiltrate. Remarkably, mucin was noted among the collagen bundles. Leukopenia and positive ANA antibodies (titre 1:320) were detected. Complement levels were normal. SARS-CoV2 infection was ruled out. Skin lesions disappeared within 1 month under topical corticosteroids. Hydroxychloroquine was afterwards started by Rheumatology without recurrence of skin symptoms until last follow-up. Discussion(s): We present an uncommon case of an adolescent with systemic LE presenting as chilblain LE. Chilblain LE can be accompanied by other discoid CCLE. It can progress to systemic LE in up to 20% of patients, especially when concomitant CCLE is present. This rare presentation of CCLE should be differentiated from typical chilblain and other resembling lesions, such as SARS-CoV2-associated chilblain and acral purpuric lesions (COVID toes). The Mayo Clinic diagnostic criteria can be helpful, particularly in this last SARS-CoV2 outbreak scenario, when the reporting of similar skin lesions has been significant.

LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

Prospects of lassa fever candidate vaccines

Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.

Oral and Dental Needs and Teledentistry Applications in the Elderly: Real-Time Surveillance Using Google Trends

Featured ApplicationThe present cross-sectional analysis aimed to evaluate the level of interest in oral and dental needs and teledentistry applications among the elderly, as well as whether COVID-19 pandemic outbreaks were influenced by real-time surveillance, using Google Trends. As the number of elderly dental patients continues to increase, there is a growing need for specific interventions that address the biological and psychological issues of this population. Teledentistry represents a healthcare delivery system that can overcome these problems, although the oral and dental care provision methods involved are still unknown to most people. Indeed, there is a need to raise awareness of the indications for teledentistry, the available interventions, and the potential benefits for the oral and dental care of elderly patients.Considering the increasing need for oral and dental care in the elderly, teledentistry has been proposed to improve the education of elderly patients in oral health maintenance and risk factor control, identify patients' concerns in advance, facilitate monitoring, and save time and money. The present cross-sectional analysis of Google search data through real-time surveillance with Google Trends aimed to determine Google users' interest in oral and dental needs and teledentistry applications in the elderly, and to compare search volumes before and after the COVID-19 outbreak. Extracted CVS data were qualitatively analyzed. Pearson and Spearman correlation analyses were performed between searches for "elderly” and "teledentistry”, and all the oral and dental needs and teledentistry applications. The Mann–Whitney U test compared search volumes in the 36 months before and after the beginning of the COVID-19 pandemic. Google users' interest in the elderly and related oral and dental needs was diffusely medium–high, while teledentistry and its applications were of lower interest. Interest in teledentistry and its applications was strongly related to interest in the older population, which is consistent with the assumption that older adults represent the population segment that could benefit most from these tools. A positive correlation was also found between searches for "Elderly” and searches for almost all oral and dental needs typical of the geriatric population. Search volumes increased significantly after the outbreak of the COVID-19 pandemic. More information about teledentistry should be disseminated to increase knowledge and awareness, especially among older patients, about its indications, applications, and advantages.

Stress Experienced during the COVID-19 Pandemic, Its Relationship with the Incidence of Recurrent Aphthous Stomatitis (RAS)

The COVID-19 pandemic has affected the lives of people around the world since March 2020. These sudden changes have caused an increase in stress, anxiety, and depression, especially in students who are making adjustments in their academic world. Therefore, this research aims to determine the relationship between the level of stress experienced during the COVID-19 pandemic and the incidence of Recurrent Aphthous Stomatitis (RAS). This research involves an analytic survey with a cross-sectional approach. The populations used were students who are actively learning at the Faculty of Dentistry, University of Sumatra Utara. Sample selection method is by purposive sampling method, where the sample size is determined based on specific characteristics. Inclusion criteria: students with ID numbers in 2017 and 2018 who are willing to sign an informed consent. Determination of a minimum sample size of 130 students. Measurement of research variables was conducted using CPDI questionnaire, and RASDX questionnaire. Data collection is performed online by using Google Forms while data analysis is performed by Chi-square test. In the RASDX test, 27.7% of the students were RAS-positive, 72.3% RAS-negative. There were 32.3% of students who had normal stress levels, 57.7% of students had mild-moderate distress, and 10% of students had severe distress. The major stressors used in this research were;the fear of contracting the virus (36.9%). Chi-square analysis showed p of 0.004, it was concluded that there was a significant relationship between stress during the COVID-19 pandemic and the incidence of RAS in college students. © 2023,Journal of International Dental and Medical Research. All Rights Reserved.

Development of an Integrated Continuous Manufacturing Process for the rVSV-Vectored SARS-CoV-2 Candidate Vaccine.

The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, the basic batch mode of manufacturing vectored vaccines does not allow one to cost-effectively meet the global demand for billions of doses per year. To date, the exposure of humans to VSV infection has been limited. Therefore, a recombinant vesicular stomatitis virus (rVSV), which expresses the spike protein of SARS-CoV-2, was selected as the vector. To determine the operating upstream process conditions for the most effective production of an rVSV-SARS-CoV-2 candidate vaccine, a set of critical process parameters was evaluated in an Ambr 250 modular system, whereas in the downstream process, a streamlined process that included DNase treatment, clarification, and a membrane-based anion exchange chromatography was developed. The design of the experiment was performed with the aim to obtain the optimal conditions for the chromatography step. Additionally, a continuous mode manufacturing process integrating upstream and downstream steps was evaluated. rVSV-SARS-CoV-2 was continuously harvested from the perfusion bioreactor and purified by membrane chromatography in three columns that were operated sequentially under a counter-current mode. Compared with the batch mode, the continuous mode of operation had a 2.55-fold increase in space-time yield and a reduction in the processing time by half. The integrated continuous manufacturing process provides a reference for the efficient production of other viral vectored vaccines.

Oro-Facial manifestations of COVID-19 infection in a sample of Iraqi people

Public health officials are gravely concerned about the harm that viral illnesses continue to pose to humanity, various viral outbreaks, including the Middle East Respiratory Syndrome Corona-Virus (MERS-CoV), H1N1 influenza, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and SARS CoV-2 or COVID-19 that struck the globe in December 2019. A wide range of COVID-19 oral symptoms, such as ulceration, blisters, enanthems, hemorrhagic sores and cheilitis. Aim(s): to investigate the prevalence of oral symptoms amongst COVID-19 patients due to the disease's aggressive nature and diverse symptomatology and to assess the impact of oral health conditions on COVID-19 disease severity in a sample of Iraqi people. Material(s) and Method(s): a cross-sectional study was conducted on (200) patients in total, (81) male and (119) female, who were identified as SARS-COV2 patients. Result(s): COVID confirmed patients were involved in the present study with mean age (36.69+/-17.22) years & age range of (16-78) years. at least one of the oral manifestations was present in 72.5% of the patients, while about 27.5% did not experience any oro-facial symptoms. The oral symptom with the highest prevalence was dry mouth 50% followed by gustatory dysfunction 37% then burning mouth sensation 22.5% after that the oral pain 17%;myofacial pain 15.5 %;stomatitis\mucositis 14.5%;the prevalence of aphthous lesions, fissural cheilitis and tongue depapillation were at the same percentage which was 9.5%;then candidiasis 7.5%;the least prevalent oral symptoms was gingival bleeding at percentage of 2.5%. Conclusion(s): COVID-19 has a noticeable effect on oral cavity, there was a correlations between some general and orofacial manifestations of COVID-19.Copyright © 2023, Codon Publications. All rights reserved.

PD13-08 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor-Positive/HER2-Negative Breast Cancer (BC)

Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase I (Topo I) inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Dato-DXd demonstrated compelling single-agent antitumor activity in heavily pretreated patients (pts) with metastatic triple-negative BC (Krop, SABCS 2021). This is the first report of results from the TROPION-PanTumor01 study in pts with unresectable or metastatic hormone receptor- positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-;including HER2-low and HER2-zero) BC. Method(s): TROPION-PanTumor01 (NCT03401385) is a phase 1, multicenter, open-label, 2-part doseescalation/expansion study evaluating Dato-DXd in previously treated pts with solid tumors. Based on previous clinical findings and exposure-response results from pts with NSCLC, Dato-DXd 6 mg/kg IV Q3W is being evaluated in pts with unresectable or metastatic HR+/HER2- BC that progressed on standard therapies. The primary objectives were safety and tolerability. Tumor responses, including ORR (complete response [CR] + partial response [PR]) and DCR (CR + PR + stable disease [SD]), were assessed per RECIST version 1.1 by blinded independent central review. Result(s): As of the April 29, 2022, data cutoff, 41 pts had received Dato-DXd (median follow-up, 10.9 mo [range, 7-13]);9 pts were ongoing. The primary cause of treatment discontinuation was disease progression (63% progressive disease [PD] or clinical progression). Median age was 57 y (range, 33- 75);54% had de novo metastatic disease. Pts were heavily pretreated (Table) with a median of 5 (range, 3-10) prior regimens in the advanced setting;95% had prior CDK4/6i (adjuvant/metastatic). Median time from initial treatment for metastatic disease to the first dose of Dato-DXd was 42.7 mo (range, 10.2-131.1). Treatment-emergent adverse events (TEAEs;all cause) were observed in 98% (any grade) and 41% (grade >=3) of pts. Most common TEAEs (any grade, grade >=3) were stomatitis (80%, 10%), nausea (56%, 0%), fatigue (46%, 2%), and alopecia (37%, 0%). Serious TEAEs were observed in 6 pts (15%);1 pt died due to dyspnea, which was not considered to be treatment related. Dose reductions occurred in 5 pts due to stomatitis (n=3), fatigue (n=2), keratitis (n=1), and decreased appetite (n=1) (>1 AE per pt);14 pts had treatment delayed due to stomatitis (n=8), retinopathy (n=1), dysphagia (n=1), fatigue (n=1), malaise (n=1), COVID-19 (n=1), cellulitis (n=1), urinary tract infection (n=1), decreased lymphocyte count (n=1), and nasal congestion (n=1;>1 AE per pt). Three pts discontinued treatment due to keratitis (n=1) and pneumonitis (n=2);1 case of pneumonitis was adjudicated as grade 2 drug-related interstitial lung disease. The ORR was 29% (11 confirmed PRs;1 pending confirmation), the DCR was 85% (35/41), and the clinical benefit rate (CR + PR + SD >=6 mo) was 41% (17/41). Conclusion(s): Dato-DXd demonstrated a manageable safety profile and encouraging antitumor activity, with high disease control in heavily pretreated pts, the majority having received prior CDK4/6i. Based on these findings, the TROPION-Breast01 (NCT05104866) randomized phase 3 study comparing 2L+ Dato-DXd vs investigator's choice chemotherapy is currently enrolling pts with HR+/HER2- BC.

Clinical and Cytopathological Traits of Herpes Zoster: A Report of Two Cases

Introduction: Varicella zoster virus is a highly infectious alpha-herpesvirus, pathogenic only to humans. The primary infection of varicella zoster virus causes chickenpox, which is contagious and primarily infects children and adolescents in India. Following the primary infection, the virus remains dormant in sensory root ganglia. Activation of the dormant virus in later stages of life causes herpes zoster infection which may vary from subclinical infection to typical zoster, scattered vesicles, zoster sine herpete or disseminated zoster, which depends on the individual's immune status. Case report: In this case series, we present two patients with herpes zoster involving the mandibular branch of the trigeminal nerve. Cytology revealed characteristic features of the infection including nuclear moulding, multinucleated giant cells and ballooning degeneration. Conclusion(s): More recently, patients presenting with herpes zoster have been reported to have sub-clinical Covid-19 infection, suggesting a possibility that herpes zoster might be an indicator for latent Covid-19. Timely detection and treatment of this infection can reduce the risk of post herpetic neuralgia.Copyright © 2022 Sciendo. All rights reserved.

Post-COVID Cutaneous Manifestations: A Retrospective Study at a Tertiary Care Centre

Introduction: COVID-19 disease is caused by SARS COV-2 virus. Though it primarily affects the lower respiratory tract, reports have indicated that specific cutaneous manifestations are associated with COVID-19. Objective(s): To evaluate the persistent dermatologic long term sequelae of SARS-CoV-2 infection, among recovered COVID-19 infected patients. Method(s): Baseline data were retrospectively collected from patient's medical records from the department of dermatology over 1 year (January 2021-January 2022), at a designated tertiary care centre. The demographic data, severity of COVID disease, and pre-existing cutaneous and systemic co-morbidities were noted. Dermatologic, hair and nail manifestations were recorded. The results were statistically analyzed. Result(s): Record of total 972 patients were analyzed in our study, with 432 males and 340 females. Out of these, 88 cases (9.05%) had skin manifestations, of which 35 (39.77%) were male, and 53 (60.22%) were females. About 50% of cases experienced long term skin diseases after 6 months of the recovery. The majority, 47 (53.4%) of patients with skin manifestations, were in the age group of 30-50 years, followed by 31 (35.22 %) of patients in the 50 years age and above group. Urticaria and Pruritus were the most common manifestations 26 (29.5%), followed by telogen effluvium 24 (27.7%), herpes zoster 16(18.1%), pityriasis rosea, acneform eruptions, acral erythema, irritant contact dermatitis, palmar keratoderma, aphthous ulcer with lip crackling, eruptive pseudo angiomatosis, aquagenic keratoderma, and others. Conclusion(s): Prevalence of cutaneous, hair and nail manifestations among COVID-19 patients was 88 (9.05%) in our study. More extensive research is required to establish our knowledge on the relation between skin and COVID-19.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Effect of SARS CoV-2 Infection on Periodontal Tissue: A Systematic Review

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection in human respiratory cells. The first spread of this disease first occurred in Wuhan, China, in December 2019, and on March 11, 2020, the World Health Organization declared the spread of the infection as a global pandemic. People who are infected experience mild to moderate clinical symptoms which are characterized by an increase in T cell, CD8, and IgM/IgG levels. The occurrence of severe clinical symptoms reflects an excessive and uncontrolled increase in the secretion of pro-inflammatory cytokines, which impacts the systemic condition and periodontal tissues of affected patients. Objective(s): The aim of this study is to describe the impact of SARS CoV-2 infection on periodontal tissues. Method(s): In this study, we searched the NCBI, PubMed, Google Scholar, and Research Gate databases. The keywords used were "coronavirus disease" o"COVID-19" or "SARS-CoV-2" with "oral manifestations" and "periodontal," and we screened the articles using the PRISMA flow diagram. Result(s): Patients with COVID-19 present with a variety of systemic symptoms, as well as manifestations in the periodontal tissues, especially in the gingival area. Conclusion(s): SARS CoV-2 infection can impact periodontal tissues in the form of necrotizing ulcerative gingivitis, aphthous stomatitis, gingivahyperpigmentation, edema and erythema, lichen planus, and aphthous-like ulcers.Copyright © 2023 Karyadi et al.

A Review: Zinc as an Antivirus Alternative Treatment for Herpes Simplex Virus Infection

This study aimed to review zinc's effectiveness as an antivirus in treating herpes simplex virus infection. The authors use international journals published from 2000-2022, and use search engines such as Google Scholar, PubMed, and Science Direct with the keywords "zinc and herpes simplex virus". The herpes simplex virus that often causes symptoms in humans are HSV type 1 and type 2. The lesions appear as vesicles which then rupture into ulcers. Zinc is one of the most abundant nutrients or metals in the human body besides iron. Studies about the effects of zinc on HSV have shown that it has the function of inhibiting the viral life cycle. HSV attaches to the host cells to replicate and synthesize new viral proteins. Zinc can inhibit this process by depositing on the surface of the virion and inactivating the enzymatic function which is required for the attachment to the host cell, disrupting the surface glycoprotein of the viral membrane so it could not adhere and carry out the next life cycle, it can also inhibit the function of DNA polymerase that works for viral replication in the host cell. This article showed that zinc has effectiveness as an antivirus against the herpes simplex virus, therefore, patients infected with HSV can be treated with zinc as an alternative to an antivirus drug.Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

Treatment of HER2-positive (HER2+) hormonereceptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant

Background: HER2+ mBC remains incurable, with a need for new HER2-directed therapies and regimens, including chemotherapy-free options. Zanidatamab (zani) is a novel HER2-targeted bispecific antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of antitumor activity, including complement-dependent cytotoxicity. A CDK4/6 inhibitor combined with endocrine therapy is an approved treatment for HER2-negative/HR+ mBC and this combination has also demonstrated encouraging antitumor activity when paired with HER2-targeted therapy(ies) in HER2+/HR+ mBC. Here, we report results from ZWI-ZW25-202 (NCT04224272), an ongoing singlearm phase 2 study of zani combined with palbociclib (palbo) and fulvestrant (fulv) in pts with HER2+/HR+ mBC. Method(s): Eligibility requirements include: HER2+/HR+ unresectable, locally advanced BC or mBC;ECOG PS of 0 or 1;prior treatment with trastuzumab, pertuzumab and T DM1 (additional prior HER2-targeting agents are permitted);and no prior treatment with CDK4/6 inhibitors. Part 1 of the study evaluated the safety and tolerability of the zani/palbo/fulv combination and determined the recommended doses for use in Part 2, where the antitumor activity of the combination is being evaluated. Endpoints include safety outcomes, progression-free survival at 6 months (PFS6), confirmed objective response rate (cORR) per RECIST v1.1;disease control rate (DCR=complete response [CR] plus partial response [PR] plus stable disease [SD]);duration of response (DOR);PFS;and overall survival. Result(s): As of 24 Feb 2022, 34 pts (33 HER2+/HR+ per central analysis) with a median age of 52 (range 36-77) have been treated. In the metastatic setting, pts had received a median (range) of 4 (1-10) prior systemic regimens, including 3 (1-8) different prior HER2 targeted therapies, and 1 (0-4) endocrine therapy. Seven pts (20%) had prior T DXd treatment and 7 pts had prior fulv treatment. All pts received zani (20 mg/kg Q2W) and standard doses of palbo and fulv. Eighteen pts (53%) remained on treatment;median duration of zani treatment was 6.9 mo (range 0.5- 16.3). A dose-limiting toxicity (DLT) of neutropenia occurred in 1 of 7 DLT-evaluable pts in Part 1. Among all pts (n=34), the most common (>20%) treatment (zani, palbo and/or fulv)-related adverse events (TRAEs) were diarrhea (74%), neutrophil count decreased/neutropenia (62%), stomatitis (41%), asthenia (26%), nausea (24%), and anemia (21%). Grade (Gr) >=3 TRAEs in 2 or more pts included neutrophil count decreased/neutropenia (50%), anemia (6%), diarrhea (6%), and thrombocytopenia (6%). AEs of special interest were all Gr <=2 and included 4 pts with cardiac events (LVEF decrease of >=10% from baseline) and 1 pt with infusion-related reaction. There were no treatment-related serious AEs. Palbo was discontinued for 1 pt due to an AE (AST increase);no pt discontinued zani treatment as a result of AEs. Two deaths occurred: 1 due to disease progression and 1 due to an unrelated AE of pneumonia caused by COVID-19. In 29 pts with measurable disease, the cORR was 34.5% (95% CI: 17.9, 54.3), all responses were cPRs, of which 1 is pending CR confirmation. DOR ranged from 2.3 to 14.9+ mo, with 8 confirmed responses ongoing, and the DCR was 93.1% (95% CI: 77.2, 99.2). Interim median PFS was 11.3 mo (range 0.03-16.7;95% CI: 5.6, not estimable). PFS6 analysis is planned following the completion of enrollment. Conclusion(s): Zani in combination with palbo and fulv shows encouraging antitumor activity with durable responses in heavily pretreated pts and a manageable safety profile. This regimen has the potential to be a chemotherapy-free treatment option in pts with HER2+/HR+ mBC. Enrollment in the study is continuing.

Awareness Among Dentists Regarding Oral Manifestations Of Post Covid 19 Disease: An Observational Crossectional Study In Central India

Background: It is very important to increase awareness and understanding of oral manifestations of post COVID-19 disease among dentists which can happen by continuing education and training for dentists to recognize and manage oral manifestations of post COVID-19 disease. Aims & objectives: The aim of this is to aware dentists regarding oral manifestation of covid 19 disease. The objectives of study were to assess the level of awareness, understanding and factors influencing awareness among dentists regarding oral manifestations of post COVID-19 disease. Evaluate the of oral manifestations of post COVID-19 among dentists in central India. Methodology: A cross-sectional, questionnaire-based study was carried out among COVID-19 recovered patients. A sample of 100 subjects, diagnosed as mild and moderate cases of COVID-19 disease were selected based on inclusion and exclusion criteria. A well-structured questionnaire composed of total 21 Closed ended questions was send to sunjects. Result(s): The study comprised an almost equal number of male (54%) and female (48%) participants and among them, 47% belong to the health professional group. A total of 56% of subjects were aged above 35 years and 47% below 35 years. Xerostomia, frequent aphthous ulcers, swallowing difficulty, and burning mouth were the most frequently encountered symptoms in study subjects during the disease and post recovery. Conclusion(s): In the present study, dentists were found to have good knowledge toward novel corona virus disease with optimum preparedness level for dental practice modification. Dental fraternity is further advised to follow the standard guidelines overcoming this pandemic.Copyright © 2022 Authors. All rights reserved.

Vulvar Aphthous Ulcers in Children with COVID-19: A case series

Background: Vulvar aphthous ulcers are defined by acute onset of painful genital lesions that are associated with viral illness. They classically present in non-sexually active girls and are diagnosed once other more common cause of genital ulcerations, including STIs or autoimmune bullous diseases, have been excluded. Previous reports of vulvar aphthous ulcers associated with COVID-19 have described treatment of the symptoms with either local or systemic corticosteroids. This case series illustrates the ability to manage these patients conservatively resulting in complete and spontaneous resolution of the ulcers. Case: Four females, ages ranging from 10 to 21, presented to the emergency department for vulvar pain. Each patient was diagnosed with vulvar aphthous ulcers based on physical examination. All four patients were diagnosed with COVID-19 with rapid antigen testing. With directed counseling, each patient and their family were instructed on a regimen of acetaminophen, sitz baths, and voiding in the bath. Topical analgesics such as lidocaine gel were not administered and steroids were not prescribed. All four patients were able to manage their symptoms at home and did not require admission to the hospital. All patients experienced spontaneous and complete restoration of anatomy in 1-2 weeks. Comments: The novel coronavirus pandemic caused by SARS-CoV02 has resulted in considerable morbidity and mortality. While immunocompromised hosts are more susceptible to complications of COVID-19, patients with intact immune systems may also experience distressing viral related symptoms. The pathogenesis of these ulcers has been hypothesized to be a result of non-specific inflammatory response to a viral systemic illness resulting in blistering of the mucosal genital surfaces It has been proposed that the ulcers are secondary to a cytokine storm that occurs in SARS-CoV-2 infections. Elevated cytokines, including TNF-alpha, result in neutrophil chemotaxis to mucosal tissue and subsequent ulceration of the tissue. Previous case studies discussing vulvar aphthous ulcers associated with COVID-19 all required hospitalization for pain control and/or urinary retention and treatment with steroids. Hospitalization can be a traumatic experience for both child and adolescent patients as well as their family. The added isolation and precautions required for treating COVID positive patients can have a further psychological impact. Through directive counseling, all patients in our case series were able to avoid hospitalization and supportive care of the genital lesions in the outpatient setting was sufficient.Copyright © 2023

Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.

BACKGROUND: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost. METHODS: Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n = 11) or placebo (n = 3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3 months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9 months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses. RESULTS: EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4 + T-cell responses in greater than 80% of recipients, and CD8 + T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected. CONCLUSIONS: This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications. CLINICALTRIALS: gov: NCT02654080.

Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine.

The ongoing pandemic of coronavirus (CoV) disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome CoV 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single-dose, fast-acting vesicular stomatitis virus (VSV)-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (i.m.) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (i.n.) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to results for control animals. While both i.m. and i.n. vaccination induced neutralizing antibody titers, only i.m. vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of i.m. vaccinated animals only. Overall, the data demonstrate that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study. IMPORTANCE The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola virus (EBOV) vaccine was approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use against the deadly disease. Here, we demonstrate the protective efficacy of a VSV-EBOV-based COVID-19 vaccine against challenge in nonhuman primates (NHPs). When a single dose of the VSV-SARS2-EBOV vaccine was administered intramuscularly (i.m.), the NHPs were protected from COVID-19 within 10 days. In contrast, if the vaccine was administered intranasally, there was no benefit from the vaccine and the NHPs developed pneumonia. The i.m. vaccinated NHPs quickly developed antigen-specific IgG, including neutralizing antibodies. Transcriptional analysis highlighted the development of protective innate and adaptive immune responses in the i.m. vaccination group only.

An Unusual case of epstein-barr virus hepatitis mistaken for multisystem inflammatory syndrome in children

Case Report: As COVID-19 infections became more common, children began presenting with multisystem inflammatory syndrome (MIS-C). It can be difficult to distinguish rare presentations of common diseases from MIS-C, especially when there has been a close contact with COVID-19. Epstein-Barr virus (EBV) is a universally common infection with 90% of individuals showing serological signs of past infection. Both MIS-C and EBV can present with similar signs and symptoms. Our case aims to remind the reader to keep in mind uncommon presentations of common viral infections which may mimic MIS-C. Case Presentation: A previously healthy 5-year-old girl presented with persistent fevers for 12 days, associated with stomatitis, vomiting, and diarrhea. Physical exam was significant for a moderately ill-appearance, small (<1 cm) left posterior cervical lymphadenopathy, and soft palate and buccal oral ulcers. Initial labs (see Table) revealed leukocytosis with reactive lymphocytes and cholestatic hepatitis with mild coagulopathy. Although she had no respiratory symptoms, CT chest revealed left upper lobe pneumonia. Abdominal ultrasound showed diffuse hepatosplenomegaly, gallbladder wall thickening, and enlarged epigastric lymph nodes. Echocardiogram showed normal systolic function and coronary arteries without dilation. Extensive viral and bacterial nasal swab and serologic testing, including for SARS-CoV-2 antibodies, was negative. On Day 2, her Monospot was positive, along with EBV viral capsid antigen IgM and IgG with the absence of EBV nuclear antigen IgG. In addition, serum PCR was positive for EBV. Management and Outcome: Due to persistent fevers on Day 3 of broad-spectrum antibiotics, coupled with a close contact with active COVID infection, she was treated with the MIS-C protocol of intravenous immunoglobulin G (IVIG), prednisone, and aspirin. Within a day of IVIG, she improved clinically and fever resolved. By discharge on Day 8, her lab values had begun to normalize. Discussion(s): EBV is known to present in children with typical infective mononucleosis symptoms such as fever, sore throat, and lymphadenopathy. However, these can be lacking which makes the diagnosis challenging. Although hepatitis is a common sequalae of EBV, EBV induced pneumonitis and stomatitis are rare, especially in immunocompetent individuals. While our patient improved after treatment with IVIG, suggesting MIS-C, we still attribute her illness to EBV, as IVIG has been shown to provide antiviral and anti-inflammatory benefit in EBV infections. This case highlights the challenge of recognizing and overtreating rare presentations of common viral infections in the face of an emerging disease such as MIS-C. Significant Laboratory Values [Table presented] Copyright © 2023 Southern Society for Clinical Investigation.