Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity ScoreMatched Nationwide Cohort Study

Background@#This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). @*Methods@#We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included.Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. @*Results@#Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74–0.98) and PPI users (OR, 0.62; 95% CI, 0.52–0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52–1.54) or PPI users (OR, 1.22; 95% CI, 0.60–2.51). @*Conclusion@#H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice / 国际口腔科学杂志·英文版

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

Proinflammatory cytokine TNFα promotes HPV-associated oral carcinogenesis by increasing cancer stemness / 国际口腔科学杂志·英文版

High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERT-immortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.

Importance of total radiation dose and overall treatment time in T1 early glottic cancer

Background: In this study, we retrospectively reviewed the treatment outcome of 63 patients with T1 early glottic cancer treated with RT alone to determine the treatment outcome and the prognostic factors affecting local control

Materials and Methods: All patients were treated by 6 MV photons with conventional bilateral fields up to a median dose of 66 Gy in 33 fractions

Results: The 5-year local control rate and overall survival were 77.7% and 93.1%, respectively. The total radiation dose with a cut-off value of 66 Gy was a significant prognostic factor for local control. The 5-year local control rate was 54.5% in patients treated with less than 66 Gy compared to 85.7% in patients treated with 66 Gy or higher dose [p = 0.014]. In subgroup analysis, in patients who received 66 Gy or higher doses, all recurrences developed in whose overall treatment time was 49 days or longer, although the statistical significance was marginal [p = 0.066]

Conclusion: This study showed that a total dose of 66 Gy or higher is required for the treatment of T1 glottic cancer, and delivering the total dose within 49 days seems important for local control

Antimicrobial Effects of Oleanolic Acid, Ursolic Acid, and Sophoraflavanone G against Enterococcus faecalis and Propionibacterium acnes

The aim of this study was to investigate antimicrobial effect of oleanolic acid (OA), ursolic acid (UA), and sophoraflavanone G against Enterococcus faecalis and Propionibacterium acnes, which are the major causative bacteria of endodontic infections. The antimicrobial activity was evaluated by the minimal inhibitory concentration (MIC). The data showed that the OA, UA, and sophoraflavanone G had antimicrobial effect on all the strains use in the study with 16-64 microg/ml, 8-64 microg/ml, and 1-8 microg/ml of MIC values, respectively. These results indicate that OA, UA, and sophoraflavanone G could be useful in the development of antiseptic solution for washing the root canal in endodontic treatments.

Erratum: Antimicrobial Effects of Oleanolic Acid, Ursolic Acid, and Sophoraflavanone G against Enterococcus faecalis and Propionibacterium acnes

We would like to correct the article.

A retrospective comparison of four different procedures for extracting dermoid cyst by laparoscopy / 대한산부인과학회잡지

OBJECTIVES: To compare results of 4 different extraction methods in laparoscopic management of dermoid cyst. STUDY DESIGN: This article is a retrospective, multicenter study for 247 patients with benign dermoid cyst in period of 1995-1998. Dermoid cyst was extracted by Endopouch (99 cases), puncture-irrigation-extraction (69 cases), colpotomy (35 cases), and dermoid cyst as a "pouch bag" (44 cases). RESULTS: We analyzed irrigation amount, operative time, postoperative hospital stay and complications by four different extraction methods. Endopouch extraction method needed less amount of irrigation fluid for cleaning the abdominal cavity and had a shorter postoperative hospital stay (ANOVA, p=0.0001). There were no significant differences in operative times among groups. There were four cases of morbidity in puncture-irrigation-extraction method (6%), three had fever (> 38degrees C) and one intraabdominal abscess. One incisional hernia was noted in "pouch bag" method (2%). CONCLUSIONS: We recommend minimal spillage method for extraction of dermoid and careful irrigation of abdominal cavity to prevent potential risk of chemical peritonitis such as Endopouch, "pouch bag", and colpotomy with the exception of puncture-irrigation-extraction method.

A Study on the Correlation between Categorization of the Individual Exposure Levels to Agent Orange and Serum Dioxin Levels Among the Korean Vietnam Veterans / 예방의학회지

OBJECTIVES: In an epidemiologic study on the health impact of Agent Orange exposure, the valid estimation of exposure level is the most important step. Based on recent studies, we examined the correlation between exposure levels categorized by personal exposure estimates and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD, Dioxin), exploring the possibility of utilizing the exposure level as a surrogate for the estimate of exposure to agent orange. METHODS: During the study period (Jan 1996-Feb 1996), blood specimens of 745 subjects taken randomly among 1,329 persons and kept frozen, were analyzed for 2,3,7,8-TCDD and six other dioxin congeners. The serum dioxin and congeners were measured in 1998 by CDC ,adjusted for serum lipids. We categorized the total exposure scores into five groups based on Agent Orange exposure data collected by interview and military records. Pearson and Spearman's correlation coefficients & multiple regression analysis were used to identify the relationship of the exposure level categorized with serum concentration of 2,3,7,8-TCDD, and six other dioxin congeners. RESULTS: Dioxin and the other congeners, except 1,2,4,6,7,8-HpCDD, showed significant correlations to exposure categories (p<0.005); 2,3,7,8-TCDD and OCDD showed positive correlations, whereas the other congeners did negative. The values of 2,3,7,8-TCDD differed according to exposure category and proportionally increased from the low exposure group to the high, a dose-response relationship, even after other possible confounding variables were adjusted for. In multiple regression analysis, age(beta=0.033), dioxin(beta=0.433), 1,2,3,7,8-PeCDD(beta=0.998), 1,2,3,4,7,8-HxCDD(beta=0.773), 1,2,3,6,7,8-HxCDD(beta=0.255), 1,2,3,7,8,9-HxCDD(beta=3.468), 1,2,3,4,6,7,8-HpCDD(beta=0.109) were found to be significantly related to the total exposure score(p<0.005). CONCLUSION: This study demonstrated that the use of such categorizations as a surrogate measure of agent orange exposure in identifying exposure degrees in a health impact study is valid.

Clinical Trial on the Hypotensive Effect of Arotinolol(S-596) in Essential Hypertension

Arotinolol was administered orally to 31 patients to evaluate is antihypertensive action. After one week of antihypertensive medication, they were given Arotinolol 30mg daily for 4 week. Routine serum chemistries, electrolytes, urinalysis and electrocardiography were studied before and after Arotinolol. Blood pressure measured in sitting, supine and standing position was 175.3+/-5.4/115.7+/-4.0, 168.0+/-5.2/150.0+/-3.8, 154.4+/-8.5/103.4+/-3.2mmHg in control and 143.8+/-2.8/93.3+/-2.8, 144.6+/-5.4/88.1+/-4.3, 139.7+/-4.6/86.8+/-3.4mmHg in Arotinolol treatment group. The differences between both blood pressure were statistically significant(P<0.01). No laboratory test showed significant difference between both period. There were no significant side effects except 2 cases of transient headache and dizziness respectively, and one case of diarrhea. In summary, Arotinolol apears to reduce blood pressure effectively with minimal side effects.