Neutrophil Extracellular Traps as a Biomarker in Refractory Non-Type 2 CRSwNP.

PURPOSE: Chronic rhinosinusitis (CRS) is classified into type 2 (T2) and non-T2 inflammation. T2 CRS presents as a severe form, CRS with nasal polyps (CRSwNP), which often occurs with asthma as a comorbidity worldwide. Some cases of non-T2 CRS show nasal polyposis and refractoriness, mainly in Asian countries. However, its mechanism remains elusive. To investigate a biomarker for the refractoriness of non-T2 CRSwNP via RNA sequencing. METHODS: RNA sequencing by using nasal polyps (NPs) and ethmoidal mucosa (EM) from CRS subjects and uncinate tissues from controls was performed, and differentially expressed genes (DEGs) were analyzed (cutoffs: expression change > 2-fold, P < 0.01). Immunofluorescence staining and enzyme-linked immunosorbent assay were performed. RESULTS: We identified DEGs among T2-NP, non-T2-NP, T2-EM, non-T2-EM, and controls (NP vs. controls: 1,877 genes, EM vs. controls: 1,124 genes, T2-NP vs. controls: 1,790 genes, non-T2-NP vs. controls: 2,012 genes, T2-EM vs. controls: 740 genes, non-T2-EM vs. controls: 1,553 genes). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that neutrophil extracellular trap (NET) formation, systemic lupus erythematosus, and the phagosome were enriched in non-T2-NP vs. controls and non-T2-EM vs. controls. Immunofluorescence staining confirmed that NETs were elevated in non-T2-NP. Cytokine analysis demonstrated that NETs were significantly related to the refractoriness in non-T2-NPs. CONCLUSIONS: This study demonstrated DEGs between T2 and non-T2 inflammation. These results suggest that NETs may contribute to the refractoriness in non-T2-NPs and have a promise as a therapeutic strategy for patients with refractory non-T2-NP.

Increasing the Beam Width and Intensity with Refraction Power Effect Using a Combination of Beam Mirrors and Concave Mirrors for Surgical-Fluorescence-Emission-Guided Cancer Monitoring Method.

The primary goal during cancer removal surgery is to completely excise the malignant tumor. Because the color of the tumor and surrounding tissues is very similar, it is difficult to observe with the naked eye, posing a risk of damaging surrounding blood vessels during the tumor removal process. Therefore, fluorescence emission is induced using a fluorescent contrast agent, and color classification is monitored through camera imaging. LEDs must be irradiated to generate the fluorescent emission electromotive force. However, the power and beam width of the LED are insufficient to generate this force effectively, so the beam width and intensity must be increased to irradiate the entire lesion. Additionally, there should be no shaded areas in the beam irradiation range. This paper proposes a method to enhance the beam width and intensity while eliminating shadow areas. A total reflection beam mirror was used to increase beam width and intensity. However, when the beam width increased, a shadow area appeared at the edge, limiting irradiation of the entire lesion. To compensate for this shadow area, a concave lens was combined with the beam mirror, resulting in an increase in beam width and intensity by more than 1.42 times and 18.6 times, respectively. Consequently, the beam width reached 111.8°, and the beam power was 13.6 mW. The proposed method is expected to be useful for observing tumors through the induction of fluorescence emission during cancer removal surgery or for pathological examination in the pathology department.

Optical Methods for Optimizing Fluorescence Imaging Field of View and Image Quality in Surgical Guidance Procedures.

Cancer surgery is aimed at complete tumor resection and accurate lymph node detection. However, numerous blood vessels are distributed within the tumor, and the colors of the tumor, blood vessels, and lymph nodes are similar, making observations with the naked eye difficult. Therefore, tumors, blood vessels, and lymph nodes can be monitored via color classification using an operating microscope to induce fluorescence emission. However, as the beam width of the LED required to induce fluorescence emission is narrow and the power loss of the beam is significant at a certain working distance, there are limitations to inducing fluorescence emission, and light reflection occurs in the observation image, obstructing the view of the observation area. Therefore, the removal of reflected light is essential to avoid missing the diagnosis of the lesion under observation. This paper proposes the use of a beam mirror and polarizing filter to increase the beam width and beam intensity. The refraction and reflection effects of the beam were utilized using the beam mirror, and the rotation angle of the polarizing filter was adjusted to remove light reflection. Consequently, the minimum beam power using the beam mirror was 10.9 mW, the beam width was doubled to 40.2°, and more than 98% of light reflection was removed at 90° and 270°. With light reflection effectively eliminated, clear observation of lesions is possible. This method is expected to be used effectively in surgical, procedural, and diagnostic departments.

Endotype and Phenotype Related Postoperative Effects of Bacterial Lysate in Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. METHODS: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. RESULTS: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. CONCLUSION: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5.

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

BACKGROUND AND HYPOTHESIS: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853, and 39 169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and ≥ 6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. CONCLUSIONS: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Nutritional and physiological responses to dietary phosphorus levels and phytase in pullets and laying hens.

The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13-15 wk, 0.25% during 16-18 wk, and 0.20% during 19-32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.

Impact of Omicron-Variant SARS-CoV-2 Infection on Depression and Anxiety: A Community-Based Study in Korea.

OBJECTIVE: This study seeks to evaluate the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the severity of depression and anxiety in the Korean community during the period dominated by the Omicron variant. METHODS: We used data from the 2022 Daejeon Mental Health Survey, involving data of 985 participants aged 19-69 years. The data collected included SARS-CoV-2 infection experience, days post-infection, and depression and anxiety symptoms evaluated using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder Questionnaire-7, respectively. Additionally, physical health, social activity status, and sociodemographic characteristics such as gender, age, marital status, educational level, and household income were collected. The association between SARS-CoV-2 infection and depression and anxiety were examined. Further analyses explored association between days post- infection and the severity of depression and anxiety. RESULTS: There was no significant correlation between SARS-CoV-2 infection and depression and anxiety in the overall population. Notably, participants under 50 years of age exhibited a transient worsening of depression and anxiety, followed by a decrease in symptoms within 40 days. Participants aged 51 years and older showed no significant change in depression and anxiety. CONCLUSION: This study discerned transient effects of Omicron variant infection on depression and anxiety, particularly in younger individuals. A prospective study encompassing a larger sample size is imperative to investigate the influence of SARS-CoV-2 infection on depression and anxiety.

Assessment of Welfare Problems in Broilers: Focus on Musculoskeletal Problems Associated with Their Rapid Growth.

The growth of the broiler industry has been accompanied with concerns over the environmental and social impacts on intensive production systems, as well as the welfare of the animals themselves. As a result, since the 2000s, there has been growing interest in alternative production systems that improve animal welfare and sustainability. In this context, it is important to prioritize the welfare of broilers in commercial production systems and to use reliable welfare indicators to provide consumers with information about the welfare of the animals they consume. Resource-based measures (RBM) are based on assessing the resources available to the birds in terms of their housing, environment, and management practices, such as stocking density, litter quality, lighting and air quality, etc. Outcome-based measures (OBM), also known as animal-based measures, focus on assessing the actual welfare outcomes for the birds, such as footpad dermatitis, hock burn, contamination or damage to feathers, gait score, mortality, etc. These OBM-based measures are one of the more direct indicators of welfare and can help identify any welfare issues. The present review highlighted the factors that affect animal welfare indicators focused on OBMs which can be used in the commercial broiler farms.

A machine-learning algorithm using claims data to identify patients with homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated ultra-rare disease. We utilized claims data from the Komodo Healthcare Map database to develop a machine-learning model to identify potential HoFH patients. We tokenized patients enrolled in MyRARE (patient support program for those prescribed evinacumab-dgnb in the United States) and linked them with their Komodo claims. A true positive HoFH cohort (n = 331) was formed by including patients from MyRARE and patients with prescriptions for evinacumab-dgnb or lomitapide. The negative cohort (n = 1423) comprised patients with or at risk for cardiovascular disease. We divided the cohort into an 80% training and 20% testing set. Overall, 10,616 candidate features were investigated; 87 were selected due to clinical relevance and importance on prediction performance. Different machine-learning algorithms were explored, with fast interpretable greedy-tree sums selected as the final machine-learning tool. This selection was based on its satisfactory performance and its easily interpretable nature. The model identified four useful features and yielded precision (positive predicted value) of 0.98, recall (sensitivity) of 0.88, area under the receiver operating characteristic curve of 0.98, and accuracy of 0.97. The model performed well in identifying HoFH patients in the testing set, providing a useful tool to facilitate HoFH screening and diagnosis via healthcare claims data.

Improving the hepatitis C virus care cascade with the in-hospital Reflex tEsting ALarm-C (REAL-C) model.

BACKGROUND: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in-hospital Reflex tEsting ALarm-C (REAL-C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. METHODS: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti-HCV between March 2020 and June 2023. Three distinct periods were defined: pre-REAL-C (n = 696), incomplete REAL-C (n = 515) and complete REAL-C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. RESULTS: The rate of HCV RNA testing increased significantly from 51.0% (pre-REAL-C) to 95.6% (complete REAL-C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL-C model. The treatment rate among treatment-eligible patients was 92.4% during the study period. The mean interval from anti-HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti-HCV positivity to direct-acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL-C model. CONCLUSION: The REAL-C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection.