Infection Of Oral Cavity Research Articles

Deep Neck Infections. Review of 111 cases.

<b>Introduction:</b> Deep neck infections (DNI) are potentially life-threatening conditions. The infections are commonly polymicrobial, and develop as a result of oral cavity infections, tonsilitis, laryngitis, trauma, or malignancy. Timely diagnostics and management are essential to prevent severe complications such as airway obstruction, sepsis or mediastinitis. Our study highlights the clinical characteristics of DNI etiology, complications, and treatment outcomes.<b>Aim:</b> This study aimed to provide a structured overview of a cohort of 111 patients with deep neck infection, comprising patient characteristics, etiology, clinical imaging, and complications along with the prognosis according to the used therapeutic strategy.<b>Methods:</b> This is a retrospective analysis of 111 patients who were hospitalized with DNI. We evaluated the demographics, clinical presentation, microbiological findings, and treatment outcomes. Statistical analyses including Pearson's chi-square, Mann-Whitney U test, independent-samples Kruskal-Wallis test and binary logistic regression were used to asses our data.<b>Results:</b> There was a predominance of male patients (62.2%) in our cohort. We found an increased DNI incidence over life in the middle-to-older age groups. The median patient age was 53 for male patients and 55 for female patients. The median hospital stay in our study was 10 days. Odontogenic infections were the leading etiology (37.8%), followed by complications of tonsillitis (23.4%) and phlegmonous laryngitis (12.6%). As many as 38.7% of patients had the following complications: airway obstruction in 25.2%, mediastinitis 10.8%, and sepsis 5.4%. The most commonly used antibiotics were ceftriaxone + metronidazole (28.8%) and amoxiclav (13.5%). The most common bacterium found in swab cultures was Streptococcus constellatus, and complications were more common in patients with a positive culture for <i>Acinetobacter baumannii</i>. Antibacterial resistance was found in 28.8% of the specimens. There was a significant association between antibiotic resistance and complication rates (P<0.05).

Fourier Transform Infrared Spectroscopy Analysis, Antifungal, and Antibacterial Activity of Areca Nut and Red Ginger Combination Extract Against Candida albicans and Staphylococcus aureus

Background: Areca nut (Areca catechu L.) and red ginger (Zingiber officinale Rosc. var. rubrum) are herbal plants that have specific phytochemical compound functional groups that have the potential to be used as antifungal and antibacterial. However, the optimal effect of the combination of the two extracts against oral candidiasis and oral bacterial infections is not yet known with certainty. This study aims to evaluate the effect of the combination of areca nut and red ginger on the development of microbial infection in oral cavity. Methods: Plant extraction is carried out using the maceration method. Functional group test using an FTIR spectrophotometer. The antifungal assay with Candida albicans (C. albicans) ATCC 10231 using well-diffusion technique on sabouraud dextrose agar media. Comparison of concentrations of areca nut: red ginger combination is 80%:20%, 50%:50%, and 20%:80%, respectively. The disc diffusion method was used to determine the antimicrobial activities against Staphylococcus aureus (S. aureus). Data analysis of antifungal assay was carried out using the Kruskall-Wallis test with p<0.05, post-hoc using the Mann-Whitney test, and the antibacterial activity using one-way ANOVA with p<0.05 and post-hoc using LSD test. Results: The areca nut extract confirmed the presence of the phenolic, alcohol, and aromatic benzene compounds. The red ginger contained flavonoid, alkaloid, and aromatic functional groups. The combination of areca nut and red ginger extract with a concentration ratio of 80%:20% had the highest inhibitory activity against C. albicans; 15.13±1.71mm with the positive control being 12.43±1.40 mm. In the antibacterial activity, the combination of 80%:20% areca nut and red ginger extract has an average inhibition zone of 12.43±1.40 mm which is the strongest inhibition ability while the positive control is 11.21±2.62 mm. Conclusion. The combination of areca nut and red ginger extracts contained potential phytochemical compounds that influence the antimicrobial ability. The concentration ratio of 80%:20% of areca nut and red ginger extract has the strongest inhibitory activity against C. albicans and S. aureus.

Comparison between Conventional Methods and Molecular Diagnosis for Candida albicans and Candida dubliniensis isolated from Cancer Patients Infected with Oral Candidiasis

Abstract Background: Two related pathogenic yeast species, Candida albicans and Candida dubliniensis share many phenotypic and microscopic diagnostic characteristics, in addition to the similarity in the characteristics of diagnosis. Objectives: The present study aimed to diagnose both yeast cells and compare them at the level of the percentage of similarities and differences according to the traditional methods and molecular approaches, which are considered more accurate and sensitive. Materials and Methods: The ability to form germ tubes was conducted for C. albicans and C. dubliniensis. The identification using biochemical tests, VITEK techniques, and molecular techniques was also conducted. Results: The results showed that both pathogenic yeast cells are similar in phenotypic and biochemical diagnosis, whereas the results of molecular diagnosis showed a difference between them, as well as the results of the drug sensitivity test, showed that the two types of yeast cells are sensitive to the antifungal drugs. The current study also showed the diagnosis of new isolates of the two species for the first time, which can be attributed to the occurrence of genetic mutations in them. Conclusion: Both types of pathogenic yeasts that were diagnosed in the current study are the important pathological types prevalent in cancer patients, especially in oral cavity infections, and they are similar to a large extent in terms of phenotypic and diagnostic characteristics.

Oral Complications Due to Medication in Stevens-Johnson Syndrome Patient with Systemic Involvement

Background: Stevens-Johnson Syndrome (SJS) is a drug-induced hypersensitivity reaction involving mucocutaneous with various trigger factors including drugs and herpes simplex virus. Objective: This case report aimed to discuss oral complications due to medication in SJS patients with systemic disease involvement. Case: A 51-year-old man was referred to the Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, at Hasan Sadikin Hospital from the dermatology and venereology department complaining of pain in the oral cavity, especially when eating and drinking two months before, with a history of phenytoin, salbutamol and theophylline therapy. Extraoral examination showed erosive lesions and tended to bleed serosanguinolenta crusts on the lips. Intraoral there were erosive lesions and white plaque on the tongue, buccal mucosa, labial mucosa, and palate, as well as dental caries and calculus. Blood examination showed low hemoglobin, hematocrit, erythrocytes, lymphocytes, monocytes, SGOT, and sodium levels, while HbA1c, random, fasting, and 2 HPP glucose levels were high. Reactive Anti-HSV-1 IgG and rheumatoid factor. KOH examination showed positive spores, hyphae, pseudohypha, and budding cells. The diagnosis was SJS-associated oral lesions with HSV-1 virus infection, oral candidiasis accompanied with diabetes mellitus. For diabetes mellitus treatment, he was referred to the internal medicine department. Case Management: The therapy was 0.9% NaCl for lip compress, acyclovir tablet, nystatin oral suspension, chlorhexidine digluconate 0,12% mouthwash, folic acid, and vitamin B12. Oral lesions were improved significantly after diabetes mellitus was treated. Conclusion: The SJS patient was susceptible to complications in the oral cavity, especially fungal and viral infections due to the received medication.

Prosthetically Guided Reconstruction of Maxilla with Free Fibular Flap as a Secondary Reconstruction in Maxillary Defects Caused by Mucormycosis.

Rhinocerebral mucormycosis (RCM) is devastating disease causing local morbidity as well mortality in some individuals. Many patients have lost their one side or bilateral maxilla and zygomatic bone. Patients survive with such facial deformity and become social cripple. We are proposing technique where existing denture is used as a template and also as temporary prosthesis for plating the fibula in best prosthetical position. Thirty patients were included in the study those fit inclusion criteria. All of them underwent unilateral or bilateral maxillary reconstruction by free microvascular fibular flap for bony as well soft tissue reconstruction. Eight patients have unilateral defect, and 22 had bilateral defects. Out of 30, 1 patient had flap failure due to venous congestion, in all 29 patients flap was well taken. In that patient, we did salvage fibular flap from other lower limb and that was well taken. Other than minor local infection and hyper-granulation tissue formation in oral cavity, we did not have any major complications. This provides best opportunity for prosthetic as well cosmetic rehabilitation. For young and fit patients, this is the best reconstruction option. This approach gives best opportunity for both hard and soft tissue reconstruction and simultaneous dental rehabilitation.

Antibacterial potential of Biduri leaf extract (Calotropis gigantea) against the growth of Streptococcus mutans ATCC 35668 colonies: an experimental laboratory

ABSTRACTIntroduction: Caries is an oral cavity infection that attacks the hard tissue of the teeth. Caries are caused by cariogenic bacteria such as Streptococcus mutans (S.mutans). S.mutans plays a role in the process of biofilm and plaque build up. One alternative ingredient that has antibacterial properties is Biduri leaves (Calotropis gigantea). The research aimed to analyze the antibacterial potential of Biduri leaf extract on the growth of S.mutans colonies. Methods: This type of research is a laboratory experimental research in vitro using the post-test-only control group design method. The antibacterial test used the colony counting method. The extraction process used the maceration method for 1 day with a shaker. The concentrations used were concentrations of 20, 40, and 60%. Control (+) used 0.2% chlorhexidine and control (-) used distilled water. Incubation process was for 24 hours. Counting the growth of S.mutans colonies using a colony counter was carried out by three observers. Data analysis used the Kruskal-Wallis test followed by the Mann-Whitney test. Results: The results showed that there was a significant difference in the growth of S.mutans (p<0.05) after being exposed to Biduri leaf extract at a concentration of 20, 40, and 60%. Conclusion: The Biduri leaf extract has antibacterial potential against S.mutans at concentrations of 20, 40, and 60%, and the best concentration in reducing the growth of S.mutans colonies is the concentration of 60%.KeywordsAntibacterial, Calotropis gigantea, 0.2% chlorhexidine, colony counting, Streptococcus mutans

APPLICATION OF ANTIMICROBIAL NANOPARTICLES OF METALS AND THEIR OXIDES IN IMPROVING DENTAL PROSTHESES

Many nanoparticles of metals and their oxides, including silver, titanium, zinc, copper, zirconium, have antimicrobial properties. These nanoparticles are a promising strategy for the treatment and prevention of oral cavity infections and can be used in various fields of dentistry. The purpose of the work is to present a literature review on the application of applying antimicrobial nanoparticle of metals and their oxides in orthopedic dentistry, in particular, in the improvement of materials for the prosthetics of dentition defects. Literature sources were searched in the PubMed database. Articles for the years 2013–2023 were selected for their involvement in orthodontic dentistry and for the availability of microbiological test data. Recent trends indicate a shift towards enhancing the composition of fundamental materials used in dental prostheses. To mitigate infectious complications, a modification of the base plastic by incorporating nanoparticles with antimicrobial properties is proposed. Silver nanoparticles are widely utilized to modify denture materials and, when combined with polymers or applied as a surface coating on biomaterials, exhibit antimicrobial properties against oral pathogens, along with an anti-biofilm effect. Zinc oxide nanoparticles, recognized for their biocompatibility and non-toxic nature, possess significant biocidal properties effective against a broad spectrum of bacteria and fungi. They demonstrate the ability to inhibit biofilm formation by oral cavity microorganisms, not only on acrylic prostheses but also on surfaces like glass, polystyrene, and silicone. Titanium oxide nanoparticles contribute to reducing microorganism adhesion on various prosthetic materials, including acrylic resins, ceramic glass, and stainless steel. Zirconium oxide nanoparticles, distinct from other metal oxide counterparts, do not compromise the aesthetics of dentures. Simultaneously, they enhance density and reduce polymethylmethacrylate porosity, thereby decreasing candida adhesion and proliferation in the samples. Copper oxide nanoparticles exhibit dose-dependent inhibition of C. albicans and Streptococcus spp. growth, along with biofilm formation, and show cytotoxic effects only at high concentrations. Thus, there are metal and metal oxide nanoparticles that can improve the antimicrobial properties of prosthetic materials for orthopedic dentistry and thus ensure the prevention of infectious complications when using dental prostheses, but for their clinical use, the gap between experiment and practice has yet to be bridged.

Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted the lives of affected patients. However, the involvement of four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E, in oral cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data of seven human oral tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid gland (PG), tongue, gingiva, buccal, periodontium and pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell and scCancer packages were comprehensively used for analysis. We identified specific cell clusters and generated expression profiles of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) in seven oral regions, providing direction for predicting the tropism of four HCoVs for oral tissues, as well as for dental clinical treatment. Based on our analysis, it appears that various SCARFs, including ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, and TMPRSS11A), and FURIN, are expressed at low levels in the oral cavity. Conversely, BSG, CTSB, and CTSL exhibit enrichment in oral tissues. Our study also demonstrates widespread expression of restriction factors, particularly IFITM1-3 and LY6E, in oral cells. Additionally, some replication, assembly, and trafficking factors appear to exhibit broad oral tissues expression patterns. Overall, the oral cavity could potentially serve as a high-risk site for SARS-CoV-2 infection, while displaying a comparatively lower degree of susceptibility towards other HCoVs (including SARS-CoV, MERS-CoV and HCoV-229E). Specifically, MSG, tongue, and gingiva represent potential sites of vulnerability for four HCoVs infection, with the MSG exhibiting a particularly high susceptibility. However, the expression patterns of SCARFs in other oral sites demonstrate relatively intricate and may only be specifically associated with SARS-CoV-2 infection. Our study sheds light on the mechanisms of HCoVs infection in the oral cavity as well as gains insight into the characteristics and distribution of possible HCoVs target cells in oral tissues, providing potential therapeutic targets for HCoVs infection in the oral cavity.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature.

Human genital papilloma virus infection is the most prevalent sexually transmitted infection in the world. It is estimated that more than 75% of sexually active women contract this infection in their lifetime. In 80% of young women, there is the clearance of the virus within 18-24 months. In developed countries, oral squamous cell carcinoma (OSCC) is now the most frequent human papilloma virus (HPV)-related cancer, having surpassed cervical cancer, and it is predicted that by 2030 most squamous cell carcinomas will be the HPV-related rather than non-HPV-related form. However, there are currently no screening programs for oral cavity infection. While the natural history of HPV infection in the cervix is well known, in the oropharynx, it is not entirely clear. Furthermore, the prevalence of HPV in the oropharynx is unknown. Published studies have found wide-ranging prevalence estimates of 2.6% to 50%. There are also conflicting results regarding the percentage of women presenting the same type of HPV at two mucosal sites, ranging from 0 to 60%. Additionally, the question arises as to whether oral infection can develop from genital HPV infection, through oral and genital contact or by self-inoculation, or whether it should be considered an independent event. However, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. Therefore, this literature review aims to evaluate whether there is evidence of a connection between oral and cervical HPV, while also endorsing the usefulness of the screening of oral infection in patients with high-risk cervical HPV as a means of facilitating the diagnosis and early management of HPV-related oral lesions. Finally, this review emphasizes the recommendation for the use of the HPV vaccines in primary prevention in the male and female population as the most effective means of successfully counteracting the increasing incidence of OSCC to date.

From the Oral Cavity to the Spine: Prevalence of Oral Cavity Infections in Patients with Pyogenic Spinal Infection.

Background incidence of pyogenic spinal infections has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this patient cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection, and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection has proven to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Gender Difference in DNA Damage Induced by the Environmental Carcinogen Dibenzo[def,p]chrysene Individually and in Combination with Mouse Papillomavirus Infection in the Mouse Oral Cavity.

Tobacco smoking and human papillomavirus infection are established etiological agents in the development of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in men than women. To provide biochemical basis for sex differences, we tested the hypothesis that carcinogen treatment using dibenzo[def,p]chrysene, which is an environmental pollutant and tobacco smoke constituent, in the absence or presence of the mouse papillomavirus infection results in significantly higher levels of DNA damage in the oral cavity in male than in female mice. However, the results of the present investigation do not support our hypothesis since we found that females were more susceptible to carcinogen-induced covalent DNA damage than males independent of the viral infection. Since DNA damage represents only a single-step in the carcinogenesis process, additional factors may contribute to sex differences in humans.

До питання діагностики актиномікозу ротової порожнини

Aim: Discussion of the possibilities of diagnosing actinomycosis of the oral cavity. Materals and meshods. After the clinical examination, laboratory tests were carried out, which included histological and microbiological studies affected tissue of the tongue Results. Cytological and pathohistological examination revealed no signs of the oncological process. However, specific changes in the tissue characteristic of actinomycosis. According to the results of a microbiological study, S.pyogenes was detected in the amount of 104 CFU/ml and Candida albicans in the amount of 105/ml. The growth of colonies typical for actinomycetes was found on the mineral medium. Microscopic examination of the biomass from the colonies confirmed that the isolated culture belonged to Actinomyces. Conclusion. The diagnosis of actinomycosis remains a difficult issue and requires, first of all, the exclusion of an oncological process. The use of pathogistological research, which is the «gold standard» for the diagnosis of actinomycosis, makes it possible to solve the problem. However, in doubtful cases, the percentage of which can be significant, microbiological diagnosis is also important.The decision regarding treatment was made taking into account all factors. In our clinical case, the causative agent of the infectious process turned out to be a presumably low-virulence strain of Actinomyces israelii in association with streptococcus,Antimicrobial therapy was directed to the treatment of both actinomycosis and antistreptococcal treatment. The use of ceftriaxone and penicillin drugs was effective. Fluconazole was also prescribed to prevent candidiasis. Key words: tongue, oral cavity infections, actinomycosis, microbiological diagnosis.

Odontogenic orbital cellulitis: literature review

Introduction: Odontogenic origin is a rare cause (1.3–5%) of cases of orbital cellulitis, but it can lead to very important morbidity such as blindness or thrombosis of the cavernous sinus. It is therefore important to know how to recognize it. Methods: A literature review was performed. The parameters analyzed included age, sex, ethnicity, clinical presentation, imaging to determine orbital involvement, etiology, microbiology, treatment (medical and/or surgical), and final outcome of each case. Chandler's classification was used to classify the different types of cellulitis. Results: Thirty-five cases of odontogenic orbital cellulitis have been described in literature from 1980 to 2022. In 42.9% of cases, the cellulitis corresponded to an intra-orbital abscess (Chandler stage IV). Thrombosis of the cavernous sinus (stage V) was detected in 5.7% of cases. Periorbital edema (100%), ocular or facial pain (82.9%) and limitation of eye movements (82.9%) were the three most common ophthalmological signs. The anamnesis revealed an element pointing to a dental origin in 97.1% of the cases, the two most frequent being a dental avulsion (20%) or an endodontic treatment (14.3%), in days or weeks preceding the onset of symptoms. Imaging was performed on admission in 94.3% of cases. Regarding the most frequently encountered germs, commensal streptococcus of the oral cavity or anaerobic bacteria were found in 25.7% of cases, and coagulase-negative staphylococcus in 22.9% of cases. In 94.3% of cases, broad-spectrum intravenous antibiotic therapy was initiated as soon as the diagnosis was made. The common feature was the use of metronidazole in 51.4% of cases, combined with a third-generation cephalosporin (11.4%) or amoxicillin-clavulanic acid (8.6%). Orbital drainage was necessary in 71.4% of cases to allow resolution of symptoms, associated with drainage of the maxillary sinus in 45.7% of cases. Finally, the treatment allowed a recovery without sequelae in 80% of cases. Discussion: In case of suspected orbital cellulitis, imaging is crucial to confirm the diagnosis, the type of cellulitis and plan the appropriate surgical treatment. The first step of treatment will be the quick start of a broad spectrum intravenous antibiotic therapy, targeting aerobic and anaerobic bacteria. However, it seems imperative to associate a surgical treatment consisting in a first step of an oral drainage and an elimination of the oral infectious source, as well as an orbital drainage whose approach will have been determined by the imaging. Conclusion: Orbital cellulitis is a rare complication of oral cavity infections, but it must be recognized and treated in time to avoid serious morbidity. An early medical and surgical treatment will usually allow good results and a healing process without sequelae.

A Preliminary Evaluation of the Antibacterial Activity of Lemon Fruit Juice, Mondia whitei Ethanolic Extract, and Their Combination Against Streptococcus mutans.

Dental caries has gained momentum as one of the main public healthcare concerns worldwide. Although the occurrence of dental caries in Uganda is on the rise, little attention has been paid to promoting oral healthcare in the country. Thus, this study aimed to evaluate the citrus lemon extracts, and Mondia whitei root bark ethanolic extract as candidate alternative therapeutic agents for streptococcus mutans, the causative agent of dental caries. In this study, the citrus lemon juice, pulp citrus lemon juice, and Mondia whitei ethanolic extract were screened for phytochemicals. Furthermore, the anti-Streptococcus mutans activity of the citrus lemon juice, citrus lemon pulp juice, and Mondia whitei ethanolic extract was determined by the agar well diffusion method while the minimum inhibitory concentration and minimum bactericidal concentration were determined by serial broth dilution. Phytochemical screening revealed the presence of alkaloids, flavonoids, terpenoids, and tannins in the Mondia whitei ethanolic extract and citrus lemon juices, while glycosides were only detected in lemon extracts. The zones of inhibition of Mondia whitei ethanolic extract, citrus lemon juice, citrus lemon pulp juice, and the cocktail were 13.67 ± 0.33 mm, 18.67 ± 0.33 mm, 18.33 ± 0.67 mm, and 18.00 ± 0.58 mm, respectively. The citrus lemon juice and citrus lemon pulp juice exhibited significantly lower MIC of 0.195 mg/mL, and 0.391mg/mL, respectively. The efficacy of the extract/juices increased with an increase in the concentration. The study findings revealed that Mondia whitei ethanolic extract and lemon extracts have potent antibacterial activity against streptococcus mutans, the main causative agent of dental caries; thus, can be further explored to formulate a herbal concoction for the prevention and treatment of oral cavity infections in resources-limited low-income communities.

Safety and Efficacy Results from the Phase I Study of a Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory Mantle Cell Lymphoma

Background: Relapsed/Refractory (R/R) mantle cell Lymphoma (MCL) has poor long-term survival compared with other B-cell malignancies. As a result, there is an urgent need for safe and effective treatments, particularly for patients who have progressed on covalent (c) Bruton tyrosine kinase inhibitors (BTKis) therapy. LP-168 is a highly selective, next-generation BTKi with a unique dual binding mode: covalent binding to wild-type BTK and reversible binding to mutated BTK. Pre-clinical data has demonstrated that LP-168 is highly potent in inhibiting C481 mutated BTK. Here, we report the safety and efficacy of LP-168 monotherapy in the R/R MCL patients as part of an ongoing phase 1 study (NCT04993690) in B-cell malignancies. Methods: This is a Phase 1 first-in-human multicenter open-label study of LP-168 enrolling Chinese patients with B cell Non-Hodgkin Lymphoma (NHL) who have progressed after at least 1 or 2 prior treatments. The study has two parts: Phase 1a: “3+3” dose escalation and Phase 1b: dose expansion in disease-specific cohorts (e.g. R/R MCL, R/R MZL, etc.). Results: Between 10 August 2021 and 31 May 2023, 33 R/R MCL patients who received at least one dose were enrolled and received LP-168 100mg (n=8), 150mg (n=24), and 200mg (n=1) QD, respectively. Baseline characteristics are summarized in Table 1. The median age was 58 (range, 32-79) years old; 27 (81.8%) were male. 15 (45.5%) subjects had intermediate to high risk disease per MCL International Prognostic Index (MIPI). Median lines of prior therapies were 2 (range, 1-11) with 24.2% refractory to the last prior treatment. All patients have received rituximab or a rituximab-containing regimen. 19 (57.6%) subjects have received at least a cBTKi or cBTKi-containing regimen. The most common treatment emergent adverse events (TEAEs) (occurring in ≥20% subjects) were platelet count decreased (30.3%), neutropenia and anemia (27.3% each) and COVID-19 (24.2%), most of which were Grade 1. Grade 3 or more TEAEs were seen in 9 (27.3%) subjects. Serious AE (SAE) (lung infection, oral cavity infection and lymphocytosis, all Grade 3) occurred in 3 (9.1%) subjects. Dose interruptions due to AE occurred in 7 patients (21.2%)，but no AE has led to dose adjustment, drug discontinuation or death. Of 31 efficacy evaluable subjects with median follow up of 5.5 months (range: 2.0-22.5), 24 (77.4%) achieved response including 12 (38.7%) complete metabolic response or complete response (CMR/CR). In addition, 5 (71.4%) out of 7 subjects with blastoid/ pleomorphic variant MCL achieved response (2 CMR/CR, 3 PMR/PR). More importantly, of 17 subjects who had prior cBTKi exposure, 12 (70.6%) responded to LP-168 and 6 (35.3%) achieved CMR. LP-168 also showed efficacy in 2 subjects who have received ≥ 2 cBTKi treatments. Another 2 subjects responded to LP-168 even after disease progression on a cBTKi and a BTK degrader. 5 subjects have achieved progression-free survival (PFS) more than 1 year and are still on treatment (Figure 1). Conclusion: In this Phase 1 trial, the novel BTK inhibitor LP-168 demonstrated a high CR rate and durable response in heavily pre-treated R/R MCL including blastoid/pleomorphic variant with favorable safety. Moreover, LP-168 could effectively overcome the acquired resistance to prior cBTKi. Based on the safety, PK and preliminary efficacy data from the Phase 1 study so far, we have determined the recommended phase 2 dose (RP2D) for MCL as 150 mg QD. A phase 2 trial of LP-168 in R/R MCL is currently ongoing (NCT05716087).

A Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma: Safety and Efficacy Results from a Phase 1 Study

Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKis) have improved clinical outcomes and revolutionized the treatment landscape of several B cell Non-Hodgkin Lymphoma (B-NHL), including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). However, cBTKi intolerance and resistance remain the main causes of treatment failure. LP-168 is a highly selective, next-generation BTKi with high bioavailability and potency. It can act as a cBTKi which irreversibly inhibits wildtype BTK while can overcome the resistance of cBTKi by non-covalent binding and reversible inhibition of C481 mutated BTK. In this abstract are the results from a Phase 1 trial (NCT04993690) that evaluates the safety and efficacy of LP-168 monotherapy in Chinese patients with relapsed/refractory (R/R) B-NHL. Methods: This multicenter Phase 1 study contains a “3+3” dose escalation part (Phase 1a) followed by a dose expansion part (Phase 1b). Subjects with R/R B-NHL are eligible to receive LP-168 once daily treatment until disease progression or unacceptable toxicity. This study was designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of LP-168. The efficacy assessment was based on Lugano 2014, 2018 International Workshop on CLL (iwCLL) and the 6 th International Workshop for WM response criteria. Results: Between 10 August 2021 and 31 May 2023, 68 subjects (33 MCL, 14 diffuse large B cell lymphoma [DLBCL], 15 marginal zone lymphoma [MZL], 3 CLL/SLL, 2 follicular lymphoma [FL] and 1 primary mediastinal large B cell lymphoma [PMBCL]) were enrolled. Cohorts of 100 mg (N=13) 150 mg (N=40) and 200 mg (N=15) taken QD were treated respectively. The median age was 59.2 (range, 32-79) years old; 22 (64.7%) were male. The median number of prior therapies was 2 (range, 1-10) and 25 (36.8%) subjects had received at least a cBTKi-containing regimen. The median follow-up was 4.5 (0.3-21.3) months with 46 subjects remaining on treatment. No dose-limiting toxicities (DLTs) were observed during dose escalation from 100mg QD, 150mg QD to 200mg QD, and the maximum tolerated dose (MTD) was not reached. The most common treatment-emergent adverse events (TEAEs) occurring in ≥20% subjects included neutropenia, platelet count decreased and anemia, most of which were Grade 1 or 2 (as detailed in Table 1). ≥Grade 3 treatment related adverse events (TRAEs, including possibly related, probably related and definitely related) included neutropenia (7.4%), lung infection (2.9%), lymphopenia, leukocytosis, lymphocytosis and oral cavity infection (1.5% each). 9 (13.2%) subjects experienced Serious Adverse Event (SAE). Serious adverse reactions included lung infection, oral cavity infection and lymphocytosis. No major bleeding, hypertension, or atrial fibrillation was observed in this study. Dose reduction occurred in only 1 subject due to AE (immune-mediated pancreatitis, unlikely related). No TEAE led to drug discontinuation. 1 subject experienced Grade 5 lung infection (not related to LP-168). Of 60 efficacy-evaluable subjects, overall response rate (ORR) was 65.0%. In particular, ORR in R/R MCL (N=31) was 77.4% with a CR of 38.7%, non-GCB DLBCL (N=10) had an ORR of 70.0% with a CR of 40.0% and MZL (N=11) had an ORR of 72.7% with a CR of 9.1% (Figure 1). LP-168 steady state plasma exposure increases dose-dependently with limited accumulation at 100 to 200 mg. Plasma concentration peaks at approximately 2 to 3 hours at fasted state, the average terminal half-life was 15.1 hours, supporting once daily dosing. Conclusion: The current results of the Phase 1 study showed that LP-168 was well tolerated at 100-200 mg QD with favorable PK profile and has demonstrated encouraging efficacy in multiple B-cell malignancies, including those who had progressed on prior cBTKi.

Clinical manifestation and microbial profiling of recurrent MDR microorganisms associated with head and neck infection- a retrospective study

Head and neck infection (HNI) can lead to life-threatening complications, including death. The purpose of this study is to look at the entire clinico-demographic profile of patients with HNI as well as the microbiologic profile of recurring bacterial infection cases with a variety of symptoms. A retrospective cross-sectional study was conducted on 1080 HNI patients in a tertiary care hospital in Bhubaneswar, Odisha, India, from January 2018 to December 2022. Of the 1080 cases, 771 (71.39%) were males, 309 (28.61%) were females, and 603 (55.83%) were from rural areas reporting to a tertiary care hospital. 62% of the cases were between the ages of 31 and 60. Neck abscesses account for 570 (52.78%) of all cases, with parotid abscesses accounting for 233 (21.57%), peritonsillar abscesses accounting for 170 (15.74%), otitis media 32 (2.96%), and oral cavity infection accounting for 26 (2.41%). In 854 (79.07%) cases, the etiology was odontogenic, followed by sinus in 188 (17.41%) and otogenic in 38 (3.52%). The most common presenting features were neck swelling in 537 (49.72%) cases and face swelling in 238 (22.04%) cases, followed by jaw pain in 26 (2.41%) cases and others. Patients were hospitalized for an average of 11.824.38 days. Treatment and recurrence had a strong significant relationship (p 0.001). Microbiologic investigation of recurrent patients revealed 12 microorganisms, including bacteria and fungus, mainly multidrug-resistant in given ascending order Staphylococcus aureus (26.74%), Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Candida albicans (4.65%), Aspergillus fumigatus, A. flavus, A. niger, C. tropicalis, C. glabrata, C. krusei. Apart from colistin, almost all antibiotics were highly resistant to gram-negative bacteria, whereas against S. aureus, benzylpenicillin, and oxacillin showed 100% resistance, followed by erythromycin (91.3%), levofloxacin (86.96%), and ciprofloxacin (82.61%). This exploratory study would aid in determining the HNI burden and epidemiology, as well as their treatment status.

Zanthoxylum acanthopodium: Microscopic, Chemical Characteristic, and anti- Enterococcus faecalis Effectivity of Fruit and Leaves Ethanol Extract

Oral and dental problems caused by microbial infections are one of the global health problems which reduce the quality of life for those affected. Enterococcus faecalis is a gram-positive bacterium, linked to oral cavity infections, which are usually managed by chlorhexidine as an oral antiseptic. However, there is a concern related to the occurrence of its resistance. Zanthoxylum acanthopodium has been reported to have antimicrobial activity, but its activity against E. faecalis has not yet been known. This research aims to observe microscopic characteristics by scanning electron microscopic, determining total flavonoid content, and identifying anti-E. faecalis effectiveness of fruit and leaf of Z. acanthopodium ethanol extract. Microscopic evaluation confirmed the presence of the epicarp and mesocarp in fruits, meanwhile three different forms of calcium oxalate existed in its leaf. Further evaluation showed that fruit ethanol extract (flavonoid content of 20.84 mg EQ/g) did not exhibit activity against E. faecalis. However, leaf ethanol extract (flavonoid content of 131.73 mg EQ/g) showed activity against E. faecalis with a coefficient value of 0.4 relative to chlorhexidine. This study demonstrated for the first time, antimicrobial effectiveness of Z. Acanthopodium leaves ethanol extract against E. faecalis.

Evaluation of the Antimicrobial Activity of Licorice (Glycyrrhiza glabra) Plant Against Representative Oral pathogens

Introduction: Oral health is important for general health because, without proper oral hygiene, bacteria can reach levels that might lead to oral infections. Pathogens' resistance to traditional antibiotic products available on the market represents a point of common interest to the scientific community throughout the world and has led to a pressing need to develop new and innovative antimicrobial agents, and among the potential sources of new agents, plants have represented a good alternative. This research is looking at the biological activities of the licorice (Glycyrrhiza glabra) plant as an antimicrobial agent for oral infections. Method: The antimicrobial activities of various extract fractions prepared from methanol, chloroform, and cyclohexane were evaluated against selected oral pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candia albicans, using the agar-well diffusion method. Results: The results indicated that methanolic extract had antimicrobial activity against the selected isolates, with a zone of inhibition equal to 23mm for S. aureus, 14mm for E. coli, 15mm for P. aeruginosa, and 22mm for C. albicans. Regarding sensitivity, the results showed that S. aureus and C. albicans were the most sensitive isolates toward the tested licorice extracts. The results also showed that licorice extract in chloroform and cyclohexane had no activity against the tested isolates of Gram-negative bacteria. Conclusion: In conclusion, our study provides further evidence of the antimicrobial activity of G. glabra, especially against the selected isolates, and encourages the use of this plant in a suitable dosage form to treat the oral cavity infection that could possibly be caused by the tested microbes.

Cervical Necrotizing Fasciitis Caused by Oral Cavity Infection: A Case Report Considering Therapeutic Approach and its Morphofunctional Implications

Cervical Necrotizing Fasciitis Caused by Oral Cavity Infection: A Case Report Considering Therapeutic Approach and its Morphofunctional Implications