Effects of dietary chlorogenic acid on cecal microbiota and metabolites in broilers during lipopolysaccharide-induced immune stress.

Aims: The aim of this study was to investigate the effects of chlorogenic acid (CGA) on the intestinal microorganisms and metabolites in broilers during lipopolysaccharide (LPS)-induced immune stress. Methods: A total of 312 one-day-old Arbor Acres (AA) broilers were randomly allocated to four groups with six replicates per group and 13 broilers per replicate: (1) MS group (injected with saline and fed the basal diet); (2) ML group (injected with 0.5 mg LPS/kg and fed the basal diet); (3) MA group (injected with 0.5 mg LPS/kg and fed the basal diet supplemented with 1,000 mg/kg CGA); and (4) MB group (injected with saline and fed the basal diet supplemented with 1,000 mg/kg CGA). Results: The results showed that the abundance of beneficial bacteria such as Bacteroidetes in the MB group was significantly higher than that in MS group, while the abundance of pathogenic bacteria such as Streptococcaceae was significantly decreased in the MB group. The addition of CGA significantly inhibited the increase of the abundance of harmful bacteria such as Streptococcaceae, Proteobacteria and Pseudomonas caused by LPS stress. The population of butyric acid-producing bacteria such as Lachnospiraceae and Coprococcus and beneficial bacteria such as Coriobacteriaceae in the MA group increased significantly. Non-targeted metabonomic analysis showed that LPS stress significantly upregulated the 12-keto-tetrahydroleukotriene B4, riboflavin and mannitol. Indole-3-acetate, xanthurenic acid, L-formylkynurenine, pyrrole-2-carboxylic acid and L-glutamic acid were significantly down-regulated, indicating that LPS activated inflammation and oxidation in broilers, resulting in intestinal barrier damage. The addition of CGA to the diet of LPS-stimulated broilers significantly decreased 12-keto-tetrahydro-leukotriene B4 and leukotriene F4 in arachidonic acid metabolism and riboflavin and mannitol in ABC transporters, and significantly increased N-acetyl-L-glutamate 5-semialdehyde in the biosynthesis of amino acids and arginine, The presence of pyrrole-2-carboxylic acid in D-amino acid metabolism and the cecal metabolites, indolelactic acid, xanthurenic acid and L-kynurenine, indicated that CGA could reduce the inflammatory response induced by immune stress, enhance intestinal barrier function, and boost antioxidant capacity. Conclusion: We conclude that CGA can have a beneficial effect on broilers by positively altering the balance of intestinal microorganisms and their metabolites to inhibit intestinal inflammation and barrier damage caused by immune stress.

Effects of Aspirin Eugenol Ester on Liver Oxidative Damage and Energy Metabolism in Immune-Stressed Broilers.

The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on liver oxidative damage and energy metabolism in immune-stressed broilers. In total, 312 broilers were divided into 4 groups (saline, LPS, SAEE, and LAEE). Broilers in the saline and LPS groups were fed a basal diet; the SAEE and LAEE groups had an added 0.01% AEE in their diet. Broilers in the LPS and LAEE groups were injected with lipopolysaccharides, while the saline and SAEE groups were injected with saline. Results showed that AEE increased the body weight, average daily gain, and average daily feed intake, as well as decreasing the feed conversion ratio of immune-stressed broilers. AEE protects against oxidative damage in immune-stressed broiler livers by elevating the total antioxidant capacity, superoxide dismutase activity, and glutathione S-transferase alpha 3 (GSTA3) and glutaredoxin 2 (GLRX2) expression, while decreasing malondialdehyde content. AEE lessened inflammation by reducing prostaglandin-F2α production and prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-1beta (IL-1ß) expression. AEE decreased oxidative phosphorylation rates by increasing succinic acid levels and lowering both adenosine diphosphate (ADP) levels and ceroid lipofuscinosis neuronal 5 (CLN5) expression. AEE modulated the metabolism of phenylalanine, tyrosine, lipids, and cholesterol by reducing the phenyllactate and L-arogenate levels, lowering dopachrome tautomerase (DCT) and apolipoprotein A4 (APOA4) expression, and increasing phenylpyruvic acid and dopa decarboxylase (DDC) expression. In summary, AEE can effectively alleviate liver oxidative damage and energy metabolism disorders in immune-stressed broilers.

Neural Radiance Field-Inspired Depth Map Refinement for Accurate Multi-View Stereo.

In this paper, we propose a method to refine the depth maps obtained by Multi-View Stereo (MVS) through iterative optimization of the Neural Radiance Field (NeRF). MVS accurately estimates the depths on object surfaces, and NeRF accurately estimates the depths at object boundaries. The key ideas of the proposed method are to combine MVS and NeRF to utilize the advantages of both in depth map estimation and to use NeRF for depth map refinement. We also introduce a Huber loss into the NeRF optimization to improve the accuracy of the depth map refinement, where the Huber loss reduces the estimation error in the radiance fields by placing constraints on errors larger than a threshold. Through a set of experiments using the Redwood-3dscan dataset and the DTU dataset, which are public datasets consisting of multi-view images, we demonstrate the effectiveness of the proposed method compared to conventional methods: COLMAP, NeRF, and DS-NeRF.

MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.

Epithelial-mesenchymal transition (EMT) in cancer promotes metastasis and chemotherapy resistance. A subset of triple-negative breast cancer (TNBC) exhibits a mesenchymal gene signature that is associated with poor patient outcomes. We previously identified PTK6 tyrosine kinase as an oncogenic driver of EMT in a subset of TNBC. PTK6 induces EMT by stabilizing SNAIL, a key EMT-initiating transcriptional factor. Inhibition of PTK6 activity reverses mesenchymal features of TNBC cells and suppresses their metastases by promoting SNAIL degradation via a novel mechanism. In the current study, we identify membrane-associated RING-CH2 (MARCH2) as a novel PTK6-regulated E3 ligase that promotes the ubiquitination and degradation of SNAIL protein. The MARCH2 RING domain is critical for SNAIL ubiquitination and subsequent degradation. PTK6 inhibition promotes the interaction of MARCH2 with SNAIL. Overexpression of MARCH2 exhibits tumor suppressive properties and phenocopies the effects of SNAIL downregulation and PTK6 inhibition in TNBC cells, such as inhibition of migration, anoikis resistance, and metastasis. Consistent with this, higher levels of MARCH2 expression in breast and other cancers are associated with better prognosis. We have identified MARCH2 as a novel SNAIL E3 ligase that regulates EMT and metastases of mesenchymal TNBC. SIGNIFICANCE: EMT is a process directly linked to drug resistance and metastasis of cancer cells. We identified MARCH2 as a novel regulator of SNAIL, a key EMT driver, that promotes SNAIL ubiquitination and degradation in TNBC cells. MARCH2 is oncogene regulated and inhibits growth and metastasis of TNBC. These insights could contribute to novel strategies to therapeutically target TNBC.

Human movement avoidance decisions during Coronavirus disease 2019 in Japan.

Understanding host behavioral change in response to epidemics is important to forecast the disease dynamics. To predict the behavioral change relevant to the epidemic situation (e.g., the number of reported cases), we need to know the epidemic situation at the moment of decision, which is difficult to identify from the records of actually performed human mobility. In this study, the largest travel accommodation reservation data covering half of the existed accommodations in Japan was analyzed to observe decision-making timings and how it responded to the changing epidemic situation during Japan's Coronavirus Disease 2019 until February 2023. To this end, we measured mobility avoidance index proposed in Ito et al., 2022 to indicate people's decision of mobility avoidance and quantified it using the time-series of the accommodation booking/cancellation data. We observed matches of the peak dates of the mobility avoidance and the number of reported cases, and mobility avoidance changed proportional to the logarithmic number of reported cases. We also found that the slope of mobility avoidance against the change of the logarithmic number of reported cases were similar among the epidemic waves, while the intercept of that was much reduced as the first epidemic wave passed by. People measure the intensity of epidemic by logarithm of the number of reported cases. The sensitivity of their response is established during the first wave and the people's response became weakened after the first experience, as if the number of reported cases were multiplied by a constant small factor.

A thyroid adenoma in a pubertal male with thyroxine-binding globulin deficiency.

Complete deficiency of thyroxin-binding globulin (TBG-CD) is not commonly associated with clinical symptoms, and little is known about thyroid tumors associated with TBG-CD. We present a case report of an asymptomatic follicular adenoma that spontaneously shrank in a patient with TBG-CD. A previously healthy 13-yr-old male presented with a diffusely swollen thyroid gland. Thyroid function tests revealed low total thyroxin and TBG concentrations, indicating a TBG deficiency. Ultrasonography revealed a mildly swollen thyroid gland with a nodule (14 × 12 × 19 mm) in the left lobe. Genetic analysis of peripheral blood revealed a previously reported SERPINA7 variant, which resulted in complete loss of TBG function. The nodule was identified as a follicular adenoma using fine-needle aspiration. Subsequently, the adenoma shrank without treatment. This pubertal case suggests that careful observation with ultrasonography is warranted for follicular adenoma in patients with TBG deficiency and that treatment may not be required.

Kidney R2* Mapping for Noninvasive Evaluation of Iron Overload in Paroxysmal Nocturnal Hemoglobinuria.

PURPOSE: The kidney iron deposition can cause kidney damage and renal insufficiency in paroxysmal nocturnal hemoglobinuria (PNH) patients. Assessment of iron deposition in the kidney is essential for the early diagnosis of renal damage in PNH patients. The purpose of this study was to evaluate kidney R2* (T2* reciprocals) values in PNH patients using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ). METHODS: Two radiologists measured the R2* values of the renal cortex in 14 PNH patients and 13 healthy volunteers using IDEAL-IQ. Lactate dehydrogenase (LDH), a reliable marker of intravascular hemolysis, was also measured in all participants. RESULTS: The kidney R2* values were significantly higher in PNH patients compared with those in healthy volunteers (P < 0.001). High inter-operator reproducibility of the measurements was also acquired using IDEAL-IQ. LDH levels were also significantly higher in PNH patients compared with those in healthy volunteers (P < 0.001). Kidney R2* values strongly correlated with LDH levels in PNH patients. CONCLUSION: IDEAL-IQ has a possibility of becoming a useful method for the noninvasive evaluation of renal iron overload in PNH patients.

Dual-sgRNA CRISPRa System for Enhanced MK-7 Production and Salmonella Infection Mitigation in Bacillus subtilis natto Applied to Caco-2 Cells.

This study optimized the menaquinone-7 (MK-7) synthetic pathways in Bacillus subtilis (B. subtilis) natto NB205, a strain that originated from natto, to enhance its MK-7 production. Utilizing mutation breeding, we developed NBMK308, a mutant strain that demonstrated a significant 117.23% increase in MK-7 production. A comprehensive transcriptome analysis identified two key genes, ispA and ispE, as being critical in MK-7 synthesis. The dual-sgRNA CRISPRa system was utilized to achieve precise regulation of ispA and ispE in the newly engineered strain, A3E3. This strategic modulation resulted in a significant enhancement of MK-7 production, achieving increases of 20.02% and 201.41% compared to traditional overexpression systems and the original strain NB205, respectively. Furthermore, the fermentation supernatant from A3E3 notably inhibited Salmonella invasion in Caco-2 cells, showcasing its potential for combating such infections. The safety of the dual-sgRNA CRISPRa system was confirmed through cell assays. The utilization of the dual-sgRNA CRISPRa system in this study was crucial for the precise regulation of key genes in MK-7 synthesis, leading to a remarkable increase in production and demonstrating additional therapeutic potential in inhibiting pathogenic infections. This approach effectively combined the advantages of microbial fermentation and biotechnology, addressing health and nutritional challenges.

Determination of Capillary Blood TSH and Free Thyroxine Levels Using Digital Immunoassay.

Background: The remote performance of thyroid function blood tests is complicated because it requires blood collection. Objective: To compare TSH and free thyroxine (FT4) levels between capillary and venous blood and assess the adequacy of measuring each value in capillary blood. Methods: This prospective intervention study was conducted at Ito Hospital and was based on the clinical research method. The participants were 5 healthy female volunteers and 50 patients (41 females and 9 males) between the ages of 23 and 81 years. To measure TSH and FT4 levels in capillary and venous blood, a digital immunoassay (d-IA) method capable of measuring trace samples was used. Chemiluminescence measurements were used as controls. Values obtained for each assay system were compared using Spearman's correlation analysis. Capillary blood was collected using an autologous device (TAP II; not approved in Japan). Results: Capillary plasma volume obtained using TAP II was 125 µL or more in 26 cases, 25 µL to 124 µL in 24 cases, and less than 25 µL in 5 cases. Strong correlations were noted in the TSH and FT4 levels between capillary and venous blood, with correlation coefficients of rs = 0.99 and rs = 0.97, respectively. Conclusion: Capillary TSH and FT4 levels strongly correlate with venous blood values. Trace samples can be used in high-precision d-IA methods. These results may promote telemedicine in assessing thyroid function.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

An Evaluation of the Efficacy of Machine Learning in Predicting Thyrotoxicosis and Hypothyroidism: A Comparative Assessment of Biochemical Test Parameters Used in Different Health Checkups.

Objective This study assessed the efficacy of machine learning in predicting thyrotoxicosis and hypothyroidism [thyroid-stimulating hormone (TSH) >10.0 mIU/L] by leveraging age and sex as variables and integrating biochemical test parameters used by the Japan Society of Health Evaluation and Promotion (JHEP) and the Japan Society of Ningen Dock (JND). Subjects and Methods Our study included 20,653 untreated patients with Graves' disease, 3,435 untreated patients with painless thyroiditis, 4,266 healthy individuals, and 18,937 untreated patients with Hashimoto's thyroiditis. Machine learning was conducted using Prediction One on three distinct datasets: the Ito dataset (age, sex, and 30 blood tests and biochemical test data), the JHEP dataset (age, sex, and TP, T-Bil, AST, ALT, γGTP, ALP, CRE, UA, and T-Cho test data), and the JND dataset (age, sex, and AST, ALT, γGTP, CRE, and UA test data). Results The results for distinguishing thyrotoxicosis patients from the healthy control group showed that the JHEP dataset yielded substantial discriminative capacity with an area under the curve (AUC) of 0.966, sensitivity of 92.2%, specificity of 89.1%, and accuracy of 91.7%. The JND dataset displayed similar robustness, with an AUC of 0.948, sensitivity of 92.0%, specificity of 81.3%, and accuracy of 90.4%. Differentiating hypothyroid patients from the healthy control group yielded similarly robust performances, with the JHEP dataset yielding AUC, sensitivity, specificity, and accuracy values of 0.864, 84.2%, 72.1%, and 77.4%, respectively, and the JND dataset yielding values of 0.840, 83.2%, 67.2%, and 74.3%, respectively. Conclusions Machine learning is a potent screening tool for thyrotoxicosis and hypothyroidism.

Impact of the quality of resected thyroid cancer tissue sample on next-generation sequencing testing.

Activating rearranged during transfection (RET) proto-oncogene alterations can be identified using next-generation sequencing (NGS) of tumor DNA/RNA. We assessed factors associated with NGS (Oncomine Dx Target Test [ODxTT]) success for resected thyroid cancer (TC) specimens, including sample age, processing conditions, and DNA/RNA quality. TC samples were from three Japanese hospitals, with sample age <1-<10 years, fixative 10%/15% neutralized buffered formalin (NBF), and fixation time ≤48 h/>48 h-≤72 h. NGS success rate was defined as the percentage of samples returning validated NGS results (RET fusion-positive/negative [RNA] or RET mutation-positive/negative [DNA], detected using ODxTT). DNA/RNA quality was assessed with indexes based on electrophoresis (DNA/RNA integrity number, DV200 ) and quantitative polymerase chain reaction (DNA/RNA integrity score [ddCq/ΔCq]). NGS success rate (N = 202) was 90%/93% (DNA/RNA) overall, 98%-100% (DNA and RNA) for samples <3 years old, and 91% (DNA and RNA) for samples ≥3-<5 years old fixed in 10% NBF for ≤48 h. Multivariate logistic regression analysis identified ddCq and ΔCq as significant predictors of DNA and RNA NGS success rates, respectively. Quality assessment of nucleic acid extracted from archival tissue samples is important for achieving high NGS success rates in clinical practice, especially for samples ≥3 years old.

Pose Estimation of Ultrasound Probe Using CNN and RNN with Image Reconstruction Loss.

It is necessary to estimate the pose of the probe with high accuracy to reconstruct 3D ultrasound (US) images only from US image sequences scanned by a 1D-array probe. We propose the probe pose estimation method using Convolutional Neural Network (CNN) with training by image reconstruction loss. To calculate the image reconstruction loss, we use the image reconstruction network which consists of an encoder that extracts features from the two US images and a decoder that reconstructs the intermediate US image between the two images. CNN is trained to minimize the image reconstruction loss between the ground-truth image and the reconstructed image. Through experiments, we demonstrate that the proposed method exhibits efficient performance compared with the conventional methods.

The importance of early-stage blood pressure control in thyroid cancer patients treated with lenvatinib from the perspective of dose intensity.

PURPOSE: Lenvatinib (LEN) is a multikinase inhibitor that strongly inhibits tyrosine kinase receptors, especially VEGFR-2, which can cause hypertension, as well as strong tumor shrinkage. Though control of any side effects (SEs) is important for maintaining dose intensity (DI), hypertension is particularly important, because blood pressure (BP) can change quickly and respond to LEN administration and withdrawal, and it can be controlled with antihypertensive medications. Focusing on the early phase of treatment, the effect of BP 8 weeks after LEN initiation (BP8w) on DI at 8 weeks (DI8w) was investigated. METHODS: The subjects were 85 thyroid cancer patients who started LEN at 24 mg/day and continued for ≥8 weeks. The BP at the start of LEN (BPbase), BP8w grade, and DI8w were examined. RESULTS: Median (range) systolic BP changed significantly from BPbase of 117 (84-167) mmHg to BP8w of 134 (103-168) mmHg (p<0.001). Antihypertensive treatment at baseline, systolic BPbase, and male sex were related to higher DI8w on multivariate analysis. The median DI8w of the 23 patients who required dose modification due to hypertension was 20.2 mg/day (n=6) in grade 1, 15.8 mg/day (n=13) in grade 2, and 14.5 mg/day (n=4) in grade 3, showing a trend toward lower DI8w as the grade level increased. CONCLUSION: LEN can increase BP by 20 mmHg at 8 weeks even with intensive antihypertensive management. Baseline antihypertensive treatment and BPbase can affect DI8w. A higher DI8w may be achieved by aiming for a low 8-week BP with more intensive antihypertensive therapy after LEN initiation.

Role of the degree of vascular invasion in predicting prognosis of follicular thyroid carcinoma.

OBJECTIVE: The present study investigated the prognostic factors for follicular thyroid carcinoma (FTC) with the incorporation of the histologic subtype and degree of vascular invasion (VI). PATIENTS: The records of 474 patients with FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were reviewed in this retrospective cohort study. The Cox proportional hazard model was used to determine factors associated with disease-free survival (DFS) and distant metastasis-free survival. RESULTS: Of the 474 patients, 140 (30%) had minimally invasive follicular thyroid carcinoma (MI-FTC), 260 (55%) had encapsulated angio-invasive follicular thyroid carcinoma (EA-FTC), and 74 (16%) had widely invasive follicular thyroid carcinoma (WI-FTC). Among the 428 patients with M0 FTC, the 10-year DFS rates of patients with MI-FTC (n = 133), EA-FTC (n = 247), and WI-FTC (n = 48) were 97.3%, 84.2%, and 69.9% (p < 0.001), respectively. A multivariate analysis identified age ≥ 55 years (hazard ration [HR], 2.204; 95% confidence interval [CI], 1.223-3.969; p = 0.009), histologic subtype (HR, 2.068; 95% CI, 1.064-4.021, p = 0.032), number VI of ≥ 2 (HR, 6.814; 95% CI, 3.157-14.710, p < 0.001), and tumor size > 40 mm (HR, 2.014; 95% CI, 1.089-3.727, p = 0.026) as independent negative prognostic factors for DFS. CONCLUSIONS: Our study results may enable us to stratify the prognosis of FTC more accurately by combining the histologic subtype with the degree of VI ≥ 2, age ≥ 55 years, and tumor size > 40 mm.

PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies.

Expression of protein arginine methyltransferase 5 (PRMT5) is highly positively correlated to DNA damage repair (DDR) and DNA replication pathway genes in many types of cancer cells, including ovarian and breast cancer. In the current study, we investigated whether pharmacologic inhibition of PRMT5 downregulates DDR/DNA replication pathway genes and sensitizes cancer cells to chemotherapy and PARP inhibition. Potent and selective PRMT5 inhibitors significantly downregulate expression of multiple DDR and DNA replication genes in cancer cells. Mechanistically, PRMT5 inhibition reduces the presence of PRMT5 and H4R3me2s on promoter regions of DDR genes such as BRCA1/2, RAD51, and ATM. PRMT5 inhibition also promotes global alternative splicing changes. Our data suggest that PRMT5 inhibition regulates expression of FANCA, PNKP, and ATM by promoting exon skipping and intron retention. Combining C220 or PRT543 with olaparib or chemotherapeutic agents such as cisplatin demonstrates a potent synergistic interaction in breast and ovarian cancer cells in vitro. Moreover, combination of PRT543 with olaparib effectively inhibits the growth of patient-derived breast and ovarian cancer xenografts. Furthermore, PRT543 treatment significantly inhibits growth of olaparib-resistant tumors in vivo. These studies reveal a novel mechanism of PRMT5 inhibition and suggest beneficial combinatorial effects with other therapies, particularly in patients with tumors that are resistant to therapies dependent on DNA damage as their mechanism of action. SIGNIFICANCE: Patients with advanced cancers frequently develop resistance to chemotherapy or PARP inhibitors mainly due to circumvention and/or restoration of the inactivated DDR pathway genes. We demonstrate that inhibition of PRMT5 significantly downregulates a broad range of the DDR and DNA replication pathway genes. PRMT5 inhibitors combined with chemotherapy or PARP inhibitors demonstrate synergistic suppression of cancer cell proliferation and growth in breast and ovarian tumor models, including PARP inhibitor-resistant tumors.

Current Situation and Problems in Diagnosis of Early Chronic Pancreatitis.

OBJECTIVES: The Japan Pancreas Society introduced the concept of early chronic pancreatitis (ECP) in 2009, but its epidemiology remains unclear. This study investigated challenges in ECP diagnosis. METHODS: Early chronic pancreatitis was diagnosed in 4 cohorts between April 2019 and November 2021 using the Clinical Diagnostic Criteria for Chronic Pancreatitis 2019. These cohorts included patients with abdominal/back pain, abnormal pancreatic enzyme levels, ECP suspected due to other reasons, and those who underwent endoscopic ultrasonography for other diseases. RESULTS: A total of 2502 cases were analyzed and 150 (40 alcoholic and 110 nonalcoholic) cases with ECP findings on endoscopic ultrasonography were included. Early chronic pancreatitis was confirmed in 14 cases (9%), including 9 (22.5%) alcoholic and 5 (4.5%) nonalcoholic cases. Early chronic pancreatitis was confirmed in 15%, 0%, 2.2%, and 0.13% cases in the 4 cohorts, respectively. Early chronic pancreatitis was confirmed in 10 (48%) of the 21 (14%) cases with pancreatic pain. CONCLUSIONS: Early chronic pancreatitis diagnostic rate was low, particularly in nonalcoholic cases, but was slightly higher in cases with pancreatic pain. The diagnostic rate was highest in the abdominal/back pain group. Further studies are required to establish appropriate diagnostic criteria for ECP.

Clinical classification of recurrent laryngeal nerve palsy.

Background: The application of intraoperative neurophysiological monitoring (IONM) has been accepted to avoid injury of a recurrent laryngeal nerve (RLN). Loss of the neuromonitoring signal indicates nerve injury and is subdivided into segmental type and global type nerve paralysis. This study aimed to determine the course of vocal cord function recovery after definitive loss of signal (LOS) types. Methods: This retrospective study included 1,442 patients (with 2,752 nerves at risk) who had thyroidectomies between January 2018 and December 2021. Preoperative and postoperative vocal cord functions were evaluated by laryngoscopic examination. Results: LOS occurred in 168 of 1,442 (11.7%) patients and 171 of 2,748 (6.2%) nerves at risk during surgery. Of LOS nerves of benign tumors, 74.2% showed global type. In cancer cases, segmental paralysis was more common, accounting for 51.3% of LOS nerves. Of nerves with segmental LOS in cancer patients, 55.3% needed partial layer resection for RLN invasion. Intraoperative recovery was seen in 9 of 62 nerves (14.5%) with segmental LOS and 32 of 109 (29.4%) nerves with global type LOS. The vocal cord palsy rate on postoperative days (PODs) 2-3 was lower after global type nerve paralysis (63.6%) than after segmental loss (84.9%). At 6 months postoperatively, the rate of vocal cord paralysis in benign tumors was not significantly different between segmental type and global type (P=0.586). However, cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively (rate of nerve palsy: segmental 40.0% vs. global 3.4%) (P<0.001). Conclusions: The intraoperative recovery rate and early nerve recovery rate are significantly higher for patients with global LOS than for patients with segmental LOS. Cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively.

Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.