Association of Herpes simplex infection with significantly increased risk of head and neck cancer: real-world evidence of about 500,000 patients.

BACKGROUND: The role of viral agents in the development of head and neck cancers has remained controversial. While markers of viral origin have been isolated from oral cancer tissues, a causative relationship has yet to be shown. The aim of this study was to evaluate the relationship between head and neck cancers and Herpes simplex virus, one of the most common viral infections of the oral orifice. METHODS: Here, we conducted a retrospective analysis of two age- and gender-matched cohorts extracted from the real-world database TriNetX on March 10th, 2023, each consisting of 249,272 patients with and without Herpes simplex infections (ICD-10: B00). The diagnoses C00-C14 were analyzed, and risk analysis and Kaplan-Meier survival statics were computed. RESULTS: The strongest association was found for lip cancer (ICD-10: C00) with a hazard ratio [HR (CI 95% low-high)] of 3.08 (1.77-5.35). A significant association with HR of 1.17 (1.02-1.34) was found for the entire group of head and neck cancers. Confounders like smoking and alcohol dependence were considered using propensity score matching. CONCLUSION: The surprisingly strong correlation with lip, oral cavity, and pharynx neoplasms sheds new light on supposedly harmless herpes simplex infections, suggesting them as a possible new factor for risk stratification.

Exogenous Estrogen in the Development of Head and Neck Cancer.

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients. Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

Beneficial Effect of Metformin on the Five-Year Survival in about 40,000 Patients with Head and Neck Cancer.

INTRODUCTION: Even in times of new therapy regimes, the overall survival of patients with head and neck cancer remains low. Since the previous studies showed the beneficial effect of metformin medication on the survival of patients with cancer, our objective was to investigate if-and in which way-metformin medication affects the overall survival of patients with head and neck cancer. METHODS: Clinical data pertaining to patients diagnosed with head and neck cancer (International Classification of Diseases 10 codes C00-C14, C31, and C32) were retrospectively retrieved from the TriNetX network (TriNetX, Cambridge, MA, USA). The initial cohort extracted from the network was stratified into two groups: patients on metformin medication (cohort I), and individuals not on metformin medication (cohort II). The matching criteria included age, gender, BMI, type 2 diabetes, and risk factors, such as nicotine and alcohol abuse/dependence. Kaplan-Meier analysis, risk analysis, and the calculation of odds and hazard ratios were conducted. Additionally, the Hemoglobin A1c values were subject to analysis. RESULTS: Following matching, each cohort comprised 20,416 patients. Cohort I exhibited a higher five-year survival rate at 75.3%, in contrast to cohort II, which registered a rate of 69.8%. The odds ratio was 0.79 (95% CI = 0.75-0.83), and the hazard ratio was 0.78 (95% CI = 0.75-0.82). CONCLUSION: Metformin medication may correlate with improved five-year survival rates in patients with head and neck cancer. Since potentially influencing factors such as comorbidities and the initial tumor stage were not available, the results of our retrospectively conducted study must be interpreted with caution.

Cross-sectional analysis comparing prefabricated titanium to individualized hybrid zirconia abutments for cemented zirconia based fixed dental prostheses: a critical concept assessment.

PURPOSE: Despite the differences in material properties and shapes among the different types of prefabricated titanium (pTiA) and individualized hybrid zirconia abutments (ihZiA), the biological and clinical relevance of materials and construction features remains vague. Yet, individualized ihZiA are increasingly implemented into daily routine aiming to satisfy rising expectations. The objective was to compare these two types of abutments in fixed dental prostheses (FDP). METHODS: This cross-sectional study examined 462 implants in 102 patients comparing pTiA (52 patients) to ihZiA (50 patients) for FDP. These different treatment regimens were evaluated in terms of peri-implant health, radiographic bone loss, and oral-health related quality of life (OH-QoL) with special consideration of abutment type and superstructure design. RESULTS: ihZiA showed significantly different design features than prefabricated pTiA, but the annual bone loss in both groups did not. Visible titanium in the esthetic zone negatively impacted OHIP 14 scores. The combination of an emergence angle (EA) of < 30° and a concave emergence profile (EP) as well as gingiva thickness (p = 0.002) at the time of the prosthetic restoration significantly improved the annual peri-implant bone loss, independently of the abutment type. CONCLUSION: ihZiA showed comparable results to pTiA. To optimize the long-term outcome, not just material alone but generating adequate soft tissue thickness, minimizing the EA, and applying a concave EP seem to be the most relevant factors. To improve OH-QoL, particular attention must be paid to the esthetic zone.

The risk of osteomyelitis after mandibular fracture is doubled in men versus women: analysis of 300,000 patients.

Postoperative complications following mandibular fracture treatment vary from local wound infections to severe conditions including osteomyelitis and impaired fracture healing. Several risk factors have been associated with the development healing disorders, including fracture localisation, treatment modality and substance abuse. However, limited research on the sex-specific influence of these complications exists. A total of about 300,000 female and male patients with mandibular fractures were examined in two cohorts. After matching for confounders (age, nicotine and alcohol dependence, malnutrition, overweight, anaemia, diabetes, osteoporosis and vitamin D deficiency), two cohorts were compared with propensity-score-matched patients according to outcomes (osteomyelitis, pseudoarthrosis and disruption of the wound) within 1 year after fracture. There were significant differences between female and male patients regarding the occurrence of osteomyelitis (odds ratio [OR] [95% confidence interval]: 0.621 [0.563; 0.686]) and disruption of the wound (OR [95% confidence interval]: 0.703 [0.632; 0.782]). Surprisingly, matching for the expected confounders did not change the results substantially. Sex plays a dominant role in determining the risk stratification for postoperative osteomyelitis and disruption of the wound, after accounting for other potential confounding factors. Additional research is needed to understand the underlying mechanisms and to develop sex-specific strategies to prevent these complications.

Worse prognosis in females with new onset of depression after oral cancer diagnosis: a retrospective case-control study.

Background: Sex-related discrepancies in the prognosis of oral cancer patients have not been clarified. This study aimed to assess survival outcomes and potential prognostic factors in female and male patients with oral cancer. Methods: A retrospective search of the TriNetX network (TriNetX, Cambridge, Massachusetts, USA) was conducted to identify patients diagnosed with oral cancer (International Classification of Diseases (ICD)-10 codes C02-C06), within the past 20 years from the access date April 21, 2023. Patients were categorized according to sex (female vs. male). Following matching for age and risk factors such as nicotine dependence and alcohol abuse, Kaplan-Meier analysis was performed and risk, odds, and hazard ratios were calculated. Outcome variables were five-year disease-free survival (DFS) and overall survival (OS). Additionally, the female and male patient cohort were compared with regard to the novel diagnosis of depression (depressive episode, major depressive disorder, dysthymic disorder) after the tumor diagnosis. Results: A total of 77,348 patients were assessed. After propensity score matching, 26,578 male and 26,578 female patients were included in each group (mean age 63 years). DFS (71.92% in females vs. 68.29% in males; hazard ratio (HR) 0.870; p < 0.001) and OS (77.08% in females vs. 71.74% in males; HR 0.793; p < 0.001) were significantly higher in the female cohort. However, in patients diagnosed with depression after the initial cancer diagnosis (N = 4,824), survival was worse in female patients compared to male patients (82.48% in females vs. 86.10% in males; HR 1.341; p < 0.001). Conclusion: This retrospective case-control study showed that females with oral cancer had a better DFS and OS than males. However, survival in females with a newly diagnosed depression after the oral cancer diagnosis was worse compared to those of male oral cancer patients. Depression may be a relevant prognostic factor that contributes to sex disparities in oral cancer patients.

Comparison of the risk of hospital admission, need for ventilation, sepsis, pneumonitis and death among the recent monkeypox outbreak and historical outbreaks.

BACKGROUND: The course of monkeypox can be severe. Our aim was to retrospectively compare the risk of hospital admission, the need for ventilation, sepsis, pneumonitis and death between the recent outbreak and historical outbreaks. MATERIALS AND METHODS: Cases of monkeypox were retrieved from the TriNetX database and assigned to either cohort I (recent outbreak between May 1st and September 16th, 2022) and cohort II (historical outbreaks before May 1st, 2022). After matching for age distribution, statistical analysis was performed. RESULTS: Of 640 patients with monkeypox 81 subjects per cohort remained after matching (mean age±standard deviation = 36.1±18.3 years). Within 56 days after diagnosis 10 patients per cohort were hospitalized (12.4%) and/or developed sepsis (12.4%). The risk of ventilation and pneumonitis were significantly lower among cohort I compared with cohort II (0 vs. 10 cases; risk difference = 12.4%; p = 0.001; Log-Rank test). No cases of death were recorded. CONCLUSION: Even though monkeypox provides a risk of severe courses, the infection is self-limiting in most cases. Unlike past outbreaks, the risk of ventilation and pneumonitis may be relatively low among recent outbreaks.

Comparison of the 3D-microstructure of human alveolar and fibula bone in microvascular autologous bone transplantation: a synchrotron radiation µ-CT study.

Introduction: Autologous bone transplantation is successfully used in reconstructive surgery of large/critical-sized bone defects, whereby the microvascular free fibula flap is still regarded as the gold standard for the reconstruction of such defects in the head and neck region. Here, we report the morphological and lacunar properties of patient-paired bone samples from eight patients from the jaw (AB; recipient site) and the fibula (FB; donor site) on the micron length-scale using Synchrotron µ-CT. Insights into differences and similarities between these bone structures could offer a better understanding of the underlying mechanism for successful surgical outcomes and might clear the path for optimized, nature-inspired bone scaffold designs. Methods: Spatial vessel-pore arrangements, bone morphology, fluid-simulation derived permeability tensor, osteocyte lacunar density, and lacunar morphology are compared. Results: The orientation of the vessel system indicates a homogenous vessel orientation for AB and FB. The average mineral distance (50%) to the closest vessel boundary is higher in AB than in FB (the mean is 96 µm for AB vs. 76 µm for FB; p = 0.021). Average osteocyte lacunar density is found to be higher in AB than in FB (mean 22,874 mm3 vs. 19,376 mm3 for FB; p = 0.038), which might compensate for the high distance from the mineral to the nearest vessel. No significant differences in lacunar volume are found between paired AB and FB. Discussion: A comparable vessel network and similar distribution of vessel porosity between AB and FB may allow the FB graft to exhibit a high regeneration potential when connected to AB, and this might correlate with a high osteoinductive and osteoconductive potential of FB when connected to AB. Since widely used and potent synthetic bone grafts exist, new insight into the bone structure of well-established autologous bone grafts, such as the free fibula flap, could help to improve the performance of such materials and therefore the design of 3D scaffolds.

Using real-world evidence data and digital monitoring to analyze the hepatotoxic profiles of biologics across more than two million patients.

The real-world evidence data from multiple sources which includes information on patient health status and medical behavior in routine clinical setup can give deeper insights into drugs 'safety and efficacy. The RWE-based analysis in this study revealed a statistically significant link between biologics usage and hepatotoxicity in patients. To the best of our knowledge, this study is the first to conduct a large-scale multi-cohort analysis on the hepatotoxic profiles of biologics. Biologics are among the most prescribed medicines for several chronic inflammatory diseases. These agents target critical pathogenic pathways, but they may also have serious side effects. It is important to analyze whether biologics agents are an added concern or therapeutic opportunity. Real-world evidence (RWE) data were extracted for patients using biologics to monitor the safety and effectiveness of the biologics. All six biologics included in this analysis-are mostly highly prescribed biologics. The aim of the study was to assess the hepatotoxic profiles of subjects using different biologics. We evaluated the safety of current treatment regimens for patients in a large real-world cohort from multiple health care centers. Total number of eligible patients retrieved from the database is 38,112,285. Of these 38 million patients, 2.3 million take biologics. The primary objective was to assess the potential adverse hepatotoxic effects of the six biologics; adalimumab, trastuzumab, prevnar13, pegfilgrastim, interferon-beta1a and insulin glargine across different indications like diabetes mellitus, encounter for immunization, malignant neoplasm of breast, multiple sclerosis, malignant neoplasm of kidney, aplastic anaemias, radiation sickness, Crohn's disease, psoriasis, rheumatoid arthritis, spondylopathies. Data from patients using the six most-used biologics-adalimumab, trastuzumab, prevnar13, pegfilgrastim, interferon-beta1a and insulin glargine were retrieved from a global research network covering 250 million patients' data from 19 countries, and assigned to the cohorts 1 and 2, respectively. The cohorts were propensity score matched for age and sex. After defining the primary outcome as "hepatotoxicity" (endpoint defined as ICD-10 code: K71 (hepatotoxic liver disease), a Kaplan-Meier survival analysis was performed, and risk ratios (RR), odds ratios (OR), and hazard ratios (HR) were determined. A total number of 2,312,655 subjects were eligible who take biologics, and after matching total cohorts accounted for 2,303,445. We have considered the clinical data as a 1:1 matched-study design, using propensity score-matched sub-cohorts to better control for confounding associations that might stem from different distributions of age and gender between the whole dataset and the subset of patients. We discovered evidence supporting the hepatotoxic-causing effect of biologic drugs: (i) all biologics considered together had an OR of 1.9 (95% CI, 1.67-2.35), with (ii) Adalimumab 1.9 (95% CI, 1.72-2.20), Trastuzumab 1.7 (95% CI, 1.2-2.3), Prevnar13 2.3 (95% CI, 2.16-2.60), Pegfilgrastim 2.3 (95% CI, 2.0-2.50), Interferon-Beta1a 1.7 (95% CI, 1.18-2.51), and Insulin glargine 1.9 (95% CI, 1.8-1.99). Our findings indicate that clinicians should consider evaluating hepatic profiles of patients undergoing treatment with biologic drugs and counsel them regarding the risk of developing hepatic injury. Strengths of the study includes a large sample size and robust statistical techniques. Limitations of this study include lack of detailed information regarding clinical severity. Major biologics are associated with hepatotoxicity. We discovered evidence supporting the hepatotoxicity-causing effects of biologics: all biologics considered together had an OR of 1.9 (95% CI, 1.67-2.35).

Vestibuloplasty and its impact on the long-term survival and success of dental implants in irradiated and non-irradiated patients after head and neck tumor therapy: a retrospective study.

OBJECTIVES: This study aimed to evaluate the influence of vestibuloplasty on the clinical success and survival of dental implants in head and neck tumor patients. MATERIALS AND METHODS: A retrospective single-center study was conducted. All patients received surgical therapy of a tumor in the head or neck and underwent surgical therapy and, if necessary, radiotherapy/radiochemotherapy. Patients with compromised soft tissue conditions received vestibuloplasty using a split thickness skin graft and an implant-retained splint. Implant survival and success and the influence of vestibuloplasty, gender, radiotherapy, and localizations were evaluated. RESULTS: A total of 247 dental implants in 49 patients (18 women and 31 men; mean age of 63.6 years) were evaluated. During the observation period, 6 implants were lost. The cumulative survival rate was 99.1% after 1 year and 3 years and 93.1% after 5 years for patients without vestibuloplasty, compared to a survival and success rate of 100% after 5 years in patients with vestibuloplasty. Additionally, patients with vestibuloplasty showed significantly lower peri-implant bone resorption rates after 5 years (mesial: p = 0.003; distal: p = 0.001). CONCLUSION: This study demonstrates a high cumulative survival and success rate of dental implants after 5 years in head and neck tumor patients, irrespective of irradiation. Patients with vestibuloplasty showed a significantly higher rate of implant survival and significantly lower peri-implant bone resorption after 5 years. CLINICAL RELEVANCE: Vestibuloplasty should always be considered and applied if required by the anatomical situations to achieve high implant survival/success rates in head and neck tumor patients.

Statin Medication Improves Five-Year Survival Rates in Patients with Head and Neck Cancer: A Retrospective Case-Control Study of about 100,000 Patients.

INTRODUCTION: The overall survival among head and neck cancer patients is still low, even in a time of new therapy regimes. Regarding cancer patients' survival, statin use has already proven to be associated with favorable survival outcomes. Our objective was to investigate the influence of statin medication on the overall survival of head and neck cancer patients. METHODS: Retrospective clinical data of patients diagnosed with head and neck cancer (International Classification of Diseases codes: C00-C14) were retrieved from a real-world evidence database. The initial cohort was divided into patients with statin medication, who were assigned to building cohort I, and subjects without statin medication, who were assigned to cohort II, both matched by age, gender, and risk factors (nicotine and alcohol abuse/dependence). Subsequently, Kaplan-Meier and risk analyses were performed, and odds and hazard ratios were calculated. RESULTS: After matching, each cohort contained 48,626 patients (cohort I = females: 15,409; (31.7%), males 33,212 (68.3%); mean age ± standard deviation (SD) at diagnosis 66.3 ± 11.4 years; cohort II = females: 15,432; (31.7%), males 33,187 (68.2%); mean age ± standard deviation (SD) at diagnosis 66.4 ± 11.5 years). Five-year survival was found to be significantly higher for cohort I, with 75.19%, respectively 70.48% for cohort II. These findings were correlated significantly with a risk of death of 15.9% (cohort I) and 17.2% (cohort II); the odds ratio was 0.91 (95% CI: 0.881-0.942) and the hazard ratio 0.80 (0.777-0.827). CONCLUSIONS: The results indicate that the five-year survival of head and neck cancer patients is significantly improved by statin medication. As this study was conducted retrospectively, our data must be interpreted with caution, especially since other potential influencing factors and the initial tumor stage were not available.

Antibiotics Significantly Decrease the Survival of Head and Neck Carcinoma Patients with Immunotherapy: A Real-World Analysis of More Than 3000 Cases.

OBJECTIVE: The human gut microbiome is strongly influenced by the administration of drugs, namely antibiotics. We hypothesized that the effectiveness of immunotherapy with pembrolizumab in oral squamous cell carcinoma patients is decreased by the administration of antibiotics three months before and after immunotherapy. METHODS: We retrieved data from patients diagnosed with head and neck squamous cell carcinoma (HNSCC) (International Classification of Diseases [ICD]-10 codes C00-C14) and receiving immunotherapy with pembrolizumab from the TriNetX network. Two cohorts were built: patients in cohort I did not receive any antibiotics within three months before or up to three months after immunotherapy, while patients in cohort II were administered antibiotics at least once within three months before or after immunotherapy. To exclude confounders, we matched cohorts 1:1 for age, sex, secondary lymph node metastases, nicotine dependence, the insertion of feeding devices, body mass index (BMI) and severe sepsis. After defining the primary outcome as "death", a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were calculated. RESULTS: A total of 3651 patients were enrolled, and after matching, each cohort consisted of 1362 patients. Among cohorts I and II, 346 and 511 patients were deceased within one year (risk of death = 25.5 and 38.3%, respectively), whereby the risk difference was significant (p = 0.000; log-rank test). The RR was 0.68 (95% confidence interval: 0.60-0.76), OR was 0.57 (0.48-0.67) and HR was 0.58 (0.51-0.67). CONCLUSIONS: Our hypothesis was confirmed: administering antibiotics significantly decreases the drug effectiveness of immunotherapy. We hypothesize that this finding is associated with antibiotic-related changes in the gut microbiome. Prospective clinical studies on the gut microbiome in cancer patients are necessary to understand the complex ecosystem of microbiota during immunotherapy. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.

Increased incidence of adult-onset Still's disease in association with COVID-19 vaccination and SARS-CoV-2 infection.

BACKGROUND: Adult-onset Still's disease (AOSD) is a multi-system, auto-inflammatory disease characterized by fever, arthralgia, typical rash, leukocytosis, sore throat, and liver dysfunction, among other symptoms. Retrospective studies about the frequencies of AOSD have shown that this disease is very rare. However, there has been an increased scientific interest in the last 2 years, as numerous case studies on AOSD have been published. These case studies describe the occurrence of AOSD after SARS-CoV-2 infection and/or COVID-19 vaccination. METHODS: We analyzed the incidence of AOSD to examine a potential association between AOSD and SARS-CoV-2 infection and/or COVID-19 vaccination. The TriNetX dataset consists of 90 million patients. We found 8474 AOSD cases, which we analyzed regarding SARS-CoV-2 infection and/or vaccination status. We also analyzed the cohorts considering demographic data, lab values, co-diagnoses and treatment pathways. RESULTS: We divided the AOSD cases into four cohorts: primary cohort (AOSD), Cov cohort (AOSD + SARS-CoV-2 infection), Vac cohort (AOSD + COVID-19 vaccination) and Vac + Cov cohort (AOSD + COVID-19 vaccination + SARS-CoV-2 infection). For the primary cohort, we found an annual incidence of 0.35 per 100.000. We found an association between AOSD and SARS-CoV-2 infection and/or COVID-19 vaccination. According to the numerical analysis, the incidence of AOSD doubled for the Cov cohort and Vac cohort. Moreover, the incidence of AOSD was 4.82 times higher for Vac + Cov cohort. The lab values for inflammatory markers were increased. Co-diagnoses such as rash, sore throat, and fever appeared in all AOSD cohorts, with the highest occurrences in the AOSD + COVID-19 vaccination + SARS-CoV-2 infection cohort. We identified several lines of treatments, mainly in association with adrenal corticosteroids. CONCLUSIONS: This research supports the assumption of an association between AOSD and SARS-CoV-2 infection and/or COVID-19 vaccination. However, AOSD remains a rare disease and the usage of vaccines to fight the COVID-19 pandemic should not be questioned because of the increased incidence of AOSD.

Real-world evidence for beneficial effects of dipyrone in 4,278 patients with pulmonary hypertension - Analysis of the risk of ventilation, hospitalization, and agranulocytosis.

INTRODUCTION: Dipyrone has been used as an analgesic for a century, but recently was proposed as a novel therapeutic strategy for the prevention and therapy of pulmonary hypertension (PH). The aim of this study was to analyze whether the risk for ventilation procedures and hospitalization was lower among patients with PH who used dipyrone compared to subjects who did not use dipyrone. MATERIALS AND METHODS: Initially, patients with PH were retrieved from the TriNetX database, whereby subjects who used dipyrone were assigned to cohort I, and cohort II was formed by those individuals who did not use dipyrone. Both cohorts were matched for several variables. The outcomes were requirement for ventilation procedures and hospital admission, whereby the time window to record events was 5 years after diagnosis of PH. Subsequently, risk analysis was carried out, and risk ratio (RR) and odds ratio (OR) were calculated. In addition, the risk of agranulocytosis was determined for both cohorts. RESULTS: Out of 741,875 individuals diagnosed with PH 4,282 and 737,593 patients were assigned to the cohorts I and II. After matching, each cohort accounted for 4,278 individuals. Among the cohorts I and II 10 and 187 individuals required ventilation procedures. The according risks of 0.2% vs. 4.4% were significantly different (p < 0.0001; Log-Rank test). RR and OR were 0.053 and 0.051. Within the cohorts I and II 10 and 1,195 subjects required hospital admission. The risks of hospitalization of 0,4% vs. 27.9% differed significantly (p < 0.0001). RR and OR were 0.016 and 0.012. Among the cohorts I and II 47 and 66 individuals were diagnosed with agranulocytosis, whereby no significance was found (p > 0.05). CONCLUSIONS: The risk for ventilation measures and hospitalization among patients with PH was found to be significantly lower when dipyrone was used. Even though the underlying mechanisms remain unknown to date, they are supposedly mediated by an active metabolite of dipyrone. The obtained results appear to be promising for patients suffering from PH. Hence, the present study may encourage further research.

A retrospective case-control study for the comparison of 5-year survival rates: the role of adjuvant and neoadjuvant chemotherapy in craniofacial bone sarcoma in adults.

Background: The impact of adjuvant or neoadjuvant chemotherapy in the treatment of craniofacial bone sarcomas has not been clarified. This study aimed to assess whether survival outcomes differed between patients who underwent adjuvant or neoadjuvant chemotherapy. Methods: A retrospective search for adult patients diagnosed with malignant neoplasms of the craniofacial bones (International Classification of Diseases 10 codes C41.0-C41.1), within the past 20 years from the access date 28 April 2022, was conducted using the TriNetX network (TriNetX, Cambridge, MA, USA). Cohort I included patients who underwent adjuvant chemotherapy and cohort II included patients with neoadjuvant chemotherapy. A refined search for individuals that received common chemotherapeutic agents, such as methotrexate, doxorubicin, cisplatin, and/or ifosfamide, was conducted and patients were assigned to cohort A (adjuvant chemotherapy) and cohort B (neoadjuvant chemotherapy). Following matching for age and sex, Kaplan-Meier analysis was performed, and risk ratio, odds ratio (OR), and hazard ratio were calculated. Results: Patients were assigned to two cohorts, with 181 patients each after matching. In cohorts I and II, 55 and 41 patients died, respectively. No significant differences were found between the two cohorts regarding the 5-year survival probability (I: 59.87% versus II: 68.45%; p = 0.076; log-rank test), or the risk of dying (I: 0.304 versus II: 0.227; risk difference: 0.077; p = 0.096). The risk analysis before matching for age and sex showed a significant survival benefit in cohort II (OR: 1.586; p = 0.0295; risk difference: 0.093). After a refined query to identify patients treated with methotrexate, doxorubicin, cisplatin, and/or ifosfamide, the two cohorts included 47 patients, respectively. In cohort A (adjuvant chemotherapy), 19 patients died, whereas 12 patients died in cohort B (neoadjuvant chemotherapy) within 5 years after diagnosis. Further analysis indicated a greater survival in cohort B, but the survival probability between the cohorts did not differ significantly (A: 43.55% versus B: 54.49%; p = 0.171). Conclusion: The use of neoadjuvant chemotherapy may improve survival rates in patients with surgically treated craniofacial bone sarcomas. Due to the retrospective nature of this study, randomized controlled studies are required to derive treatment recommendations.

Analysis of the Risk of Oral Squamous Cell Carcinoma in Patients with and without Recurrent Aphthous Stomatitis: A Retrospective Evaluation of Real-World Data of about 150,000 Patients.

Background: Recurrent aphthous stomatitis (RAS) is found among the most frequent diseases of the oral cavity. It is characterized by repeated formation of painful ulcers. The question has risen if due to potential tumor-promoting inflammation and sustaining proliferative signaling RAS may contribute to oral cancer. Accordingly, the aim of the study was to assess if an association of RAS and the development oral squamous cell carcinoma (OSCC) could be found in a larger cohort. As recurrent aphthous stomatitis is not classified as an oral potentially malignant disorder, it was assumed that the risk of OSCC did not differ between patients with (cohort I) and without RAS (cohort II). Methods: Retrospective clinical data of patients diagnosed with and without RAS (International Classification of Diseases (ICD)-10 code K12) within the past 20 years and a body mass index of 19−30 kg/m2 were retrieved from the TriNetX database to gain initial cohort 0. Subjects suffering from RAS were assigned to cohort I, whereby cohort II was obtained from the remaining individuals, and by matching for age, gender, as well as (history of) nicotine and alcohol dependence. After defining the primary outcome as "OSCC" (ICD-10 codes C00-C14), a Kaplan−Meier analysis was performed, and risk and odds ratios were calculated. Results: Of a total of 24,550,479 individuals in cohort 0, 72,845 subjects were each assigned to cohort I (females: 44,031 (60.44%); males: 28,814 (39.56%); mean current age (±standard deviation) = 35.51 ± 23.55 years) and II (females: 44,032 (60.45%); males: 28,813 (39.55%); mean current age (±standard deviation) = 35.51 ± 23.56 years). Among the cohorts I and II, 470 and 135 patients were diagnosed with OSCC within five years. The according risk of developing oral cancer was 0.65% and 0.18%, whereby the risk difference of 0.47% was highly significant (p < 0.0001; Log-Rank test). The RR and OR were calculated as 3.48 (95% confidence interval (CI) lower: 2.88 and upper: 4.21) and 3.50 (95% CI lower: 2.89 and upper: 4.24). Conclusions: Among the patients suffering from RAS, a significantly augmented risk of developing OSCC was found. However, it has to be emphasized that the recent literature does not provide any confirmatory evidence that supports the retrieved results. Furthermore, the findings need to be interpreted cautiously due to specific limitations that come along with the applied methods. It should thus far only be concluded that further research is necessary to evaluate hypotheses that may be retrieved from the obtained results. Despite this controversy, oral ulcers suspicious of OSCC should undergo biopsy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary.

Influence of sex on survival rates of HPV-positive oropharyngeal cancers.

The role of human papillomavirus (HPV) status for the prognosis of oropharyngeal cancers (OPCs) is discussed controversially. Here, we present an analysis of 144,969 head and neck cancer cases (ICD-10 codes: C00-C13) with a sub-cohort of 62,775 tumor cases of the oropharynx (C01, C09, and C10). To this end, de-identified data from electronic health records of about 60 healthcare organizations from 30 different countries were used. Odds ratios, hazard ratios (HRs), and Kaplan-Meier analyses were used to compare outcomes between different cancer entities of neoplasms of the base of the tongue (C01), of tonsils (C09), and of the oropharynx (C10) of women and men with and without HPV infection. To avoid the bias from different age distributions, the cohorts were balanced using propensity score matching. The 5-year survival rate for HPV-positive patients is somewhat better than that for HPV-negative patients, but for age- and sex-balanced cohorts, there remains no significant advantage for HPV-positive patients [HR, 1.126 (0.897-1.413)]. Looking at the different entities and HPV status for age-matched male and female patients separately, HPV is a significantly positive prognostic factor for female patients in some entities, whereas for male patients, it is only a positive prognostic factor for malignant neoplasms of oropharynx (C10) [HR, 1.077 (0.602-1.926)].

Sonication versus the conventional method for evaluation of the dental microbiome: a prospective pilot study.

OBJECTIVES: To investigate sonication as a new tool in microbiological probing of dental infections. METHODS: Comparison of a standard probing method: intraoperative swab, with sonication, and vortex of the removed tooth, was performed on 20 carious destructed teeth. Illumina high throughput sequencing of the 16S-rRNA-gene was used for assessing the microbial composition. Antibiotic susceptibility has been assigned based on known resistances of each detected species. Probing procedures were compared using Bland-Altmann-Test, and antibiotic susceptibility using the Friedmann-Test and alpha-adjusted post-hoc-analysis. RESULTS: In total, 60 samples were analysed: 20 intraoperative swabs, 20 vortex fluids, and 20 sonication fluids. Sonication fluid yielded the highest number of bacterial sequencing reads in all three procedures. Comparing the operational taxonomic units (OTUs) of the identified bacteria, significantly more OTUs were found in sonication fluid samples. Phylum and order abundances varied between the three procedures. Significantly more Actinomycetales have been found in sonication fluid samples compared to swab samples. The assigned resistance rates for the identified bacteria (1.79-31.23%) showed no differences between the tested probing procedures. The lowest resistance rates were found for amoxicillin + clavulanate (3.95%) and levofloxacin (3.40%), with the highest in amoxicillin (30.21%) and clindamycin (21.88%). CONCLUSIONS: By using sonication on extracted teeth, it is possible to get a more comprehensive image of the residing microbial flora compared to the standard procedure. If sonication is not available, vortexing is a potential alternative. In immunocompromised patients, especially when actinomycosis is suspected, sonication should be considered for a more detailed microbiological evaluation of the potential disease-causing microbiome. Due to the high rates of antibiotic resistance, a more targeted antibiotic therapy is favourable. Levofloxacin should be considered as a first-line alternative to amoxicillin + clavulanate in patients with an allergy to penicillin.

Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy.

Purpose: Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants. Patients and Methods: One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN® (medication support system) and individual recommendations for 34 drug classes were generated. Results: In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented. Conclusion: Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug-drug-gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.

Comparison of five-year survival rates among patients with oral squamous cell carcinoma with and without association with syphilis: a retrospective case-control study.

BACKGROUND: Syphilis is an infectious disease that is at least discussed to be premalignant. This potential, combined with its general pathological impact, raises the question if syphilis increases mortality in oral cancer patients. The aim of the study was to assess if the five-year survival rates among patients suffering from oral squamous cell carcinoma (OSCC) with (cohort I) and without association with syphilis (cohort II) differ. METHODS: Retrospective clinical data of patients diagnosed with OSCC (International Classification of Diseases [ICD]-10 codes C01-06) within the past 20 years from the access date September 25, 2021 were retrieved from the TriNetX network (TriNetX, Cambridge, Massachusetts, USA) to gain initial cohort 0. Subjects also diagnosed with syphilis (ICD-10 codes A51-53) were assigned to cohort I. Cohort II was comprised of the remaining individuals of cohort 0 by creating a group with the same number of patients as cohort I, and by matching for age and gender. Subsequently, Kaplan-Meier analysis and Cox proportional hazards regression were performed, and risk, odds and hazard ratios were calculated. RESULTS: Of a total of 73,736 patients in cohort 0, 199 individuals were each assigned to cohort I and II. During the five-year period after tumor diagnosis, 39 and 30 patients in cohort I and II died. The five-year survival probabilities did not significantly differ between the cohorts (I vs. II = 74.19% vs. 75.01%; p = 0.52; Log-Rank test), nor the risk of dying (I vs. II = 19.6% vs. 15.08%; risk difference = 4.52%; p = 0.23). The calculated risk, odds and hazard ratios were 1.3 (95% confidence interval [CI] = 0.84; 2.00), 1.37 (95% CI = 0.81; 2.31) and 1.17 (95% CI = 0.73; 1.88), respectively. CONCLUSIONS: The obtained results indicate that the survival rate of individuals with OSCC might not be negatively influenced if syphilis is present/associated. However, the results need to be interpreted cautiously due to limitations related to the retrospective approach, especially as data on the tumor staging were not accessible. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.