Steroid lifting method during endoscopic submucosal dissection: A novel strategy for stricture prevention.

A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.

The value of routine hemoglobin level evaluation following elective cesarean section: Is it worthwhile?

OBJECTIVE: The aim of this study was to assess the usefulness of routine hemoglobin testing following elective and urgent cesarean section (CS) in patients without primary postpartum hemorrhage (PPH). METHODS: This retrospective cohort study included women who underwent vaginal delivery (VD), elective CS, and urgent CS at Carmel Medical Center from 2015 to 2020. Data were extracted from the obstetric database, excluding deliveries with PPH. Demographic and obstetric variables were recorded. Primary outcomes were the need for packed red blood cell transfusion. RESULTS: A total of 19 446 women were included, with five (0.3%) requiring a blood transfusion in the elective CS group, 27 (0.17%) in the VD group, and eight (0.4%) in the urgent CS group. Urgent CS was associated with a higher risk of blood transfusion, but there was no significant difference between elective CS and VD. Elective CS showed the lowest rates of post-delivery hemoglobin below 7 g/dL 1 (0.1%) compared to VD 16 (0.6%) and urgent CS 13 (0.7%). CONCLUSION: Routine postoperative hemoglobin testing following elective CS in asymptomatic patients without PPH appears unnecessary. This study supports reconsidering routine hemoglobin testing following elective CS, aligning with the goal of optimizing resource utilization while maintaining patient quality.

In steroid-resistant nephrotic syndrome that meets the strict definition, monogenic variants are less common than expected.

BACKGROUND: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics. METHODS: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1-18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy. RESULTS: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)). CONCLUSIONS: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.

Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

Screening of Myelodysplastic Syndromes Using Research Parameters of Complete Blood Count: Automated Detection of Dysplasia.

Myelodysplastic syndromes (MDS) present with polymorphic and non-specific diagnostic features Research parametersfrom hematology analyzers may be useful to discriminate MDS-related cytopenia.Parameters such as Neu X (related to the cytoplasmic complexity) and Neu Y (related to nucleic acid content) show promise to detect dysplasia of MDS and aid to recognize MDS from cytopenias of other etiologies.

Advances in Hematology Analyzers Technology.

The evolution of complete blood count (CBC) methodology from manual calculations to sophisticated high throughput hematology analyzers is the focus of this article. In recent years, hematology testing has greatly benefitted from the combination of various technologies with automated neural networks. In addition to an increasing complexity of the laboratory instrumentation, there is a demand on point of care CBC testing with its benefits and drawbacks. This article highlights exciting advancements of hematology testing from the past to the present and into the future.

A method of impressing flabby ridge.

Flabby ridge remained a challenge in dental clinical practice to obtain an accurate impression for edentulous patients. During the traditional impression making process, the excessive and displaceable soft tissue are usually compressed. In this article, we presented an impression method by using a modified special stock tray, impression compound and polyvinyl siloxane impression materials.•the suitable stock tray was modified with holes about 5 mm diameter in the corresponding area to the crest of the flabby ridge.•the primary impression was made by position the modified tray with the softened compound impression on the edentulous ridge, avoiding the area of the flabby ridge.•the final accurate impression was obtained by using the light body polyvinyl siloxane impression material.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Risk of mortality associated to chronic kidney disease in patients with complete left bundle branch block.

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01-1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63-3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71-3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01-1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41-0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection.

BACKGROUND: Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). METHODS: Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan-Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. RESULTS: Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. CONCLUSIONS: Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

It Is Necessary to Pay Attention to Where the Pcom Originate from the Aneurysm to Treat with FD.

Objective With the expansion of indications of flow diverter (FD) for cerebral aneurysms, FD placement for posterior communicating artery (Pcom) aneurysms has been approved. However, it is controversial whether Pcom aneurysms should be treated with FD or not. In this study, we report the outcome of FD treatment for Pcom aneurysms in Japan. Materials and Methods We retrospectively analyzed 36 patients with 38 aneurysms treated with FD placement for Pcom aneurysms between 2015 and 2021 in our hospital. We divided our cases into complete occlusion (CO) and non-CO groups. And we extracted contributing factors to CO using multivariate analysis. We also compared the complications rate among the three types of FDs. Results CO was obtained in 29 cases (79.3%), and complications were observed in 3 cases (7.9%). Multivariate analysis revealed that the type of Pcom branch from the aneurysmal dome was a significant factor contributing to CO (odds ratio: 0.0052, 95% confidence interval 0.000048-0.584, p = 0.029). In terms of complications, complication rate was significantly higher in the Flow-Redirection Endoluminal Device (FRED) group ( p = 0.0491). Conclusion The outcome for Pcom aneurysms treated by FD was acceptable. When treating, we must pay attention to where Pcom originates. Achieving CO with FD is difficult for aneurysms where the Pcom branches from the dome. Furthermore, when treating Pcom aneurysms with FRED, it is necessary to be careful about thromboembolic complications.

Striving for Excellence: Fabrication of Complete Denture in a Patient With Flabby Ridges Using Specialized Impression Technique.

Tissue growth across the ridges is a typical clinical feature in the mandibular and maxillary arches. This excess tissue is known as flabby ridges. The mobile tissue may be distorted throughout the impression-making process due to the forces applied. The chewing forces will displace the denture if it is not adequately maintained, which will eventually cause the denture to lose its stability, support, and retention. The particular impression technique promoted accurately documenting flabby ridges. Several strategies, including implant therapy, balanced occlusal load distribution, surgical management, and special impression techniques, can be used to treat removable dentures with "flabby ridges." This case study demonstrates the method for constructing a complete denture in a patient with flabby ridges using a specialized impression technique. This impression technique helps to record flabby tissue with minimal displacement, improving the stability, support, and retention of complete dentures.

Ultrasound and diffuse optical tomography-transformer model for assessing pathological complete response to neoadjuvant chemotherapy in breast cancer.

Significance: We evaluate the efficiency of integrating ultrasound (US) and diffuse optical tomography (DOT) images for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. The ultrasound-diffuse optical tomography (USDOT)-Transformer model represents a significant step toward accurate prediction of pCR, which is critical for personalized treatment planning. Aim: We aim to develop and assess the performance of the USDOT-Transformer model, which combines US and DOT images with tumor receptor biomarkers to predict the pCR of breast cancer patients under NAC. Approach: We developed the USDOT-Transformer model using a dual-input transformer to process co-registered US and DOT images along with tumor receptor biomarkers. Our dataset comprised imaging data from 60 patients at multiple time points during their chemotherapy treatment. We used fivefold cross-validation to assess the model's performance, comparing its results against a single modality of US or DOT. Results: The USDOT-Transformer model demonstrated excellent predictive performance, with a mean area under the receiving characteristic curve of 0.96 (95%CI: 0.93 to 0.99) across the fivefold cross-validation. The integration of US and DOT images significantly enhanced the model's ability to predict pCR, outperforming models that relied on a single imaging modality (0.87 for US and 0.82 for DOT). This performance indicates the potential of advanced deep learning techniques and multimodal imaging data for improving the accuracy (ACC) of pCR prediction. Conclusion: The USDOT-Transformer model offers a promising non-invasive approach for predicting pCR to NAC in breast cancer patients. By leveraging the structural and functional information from US and DOT images, the model offers a faster and more reliable tool for personalized treatment planning. Future work will focus on expanding the dataset and refining the model to further improve its accuracy and generalizability.

Occurrence of astrovirus in young racing pigeons and genome characterization of 2 new astrovirus genomes representing 2 new species.

Enteropathies are a serious concern in racing pigeons as they significantly impair performance in races and their training, and viruses are suspected to be one of the main factors. Astroviruses are well-known to be responsible for causing enteric disease in humans and various other animals including birds, although their prevalence and pathogenicity in pigeons is poorly understood. In this study, we investigated 2 groups of young racing pigeons (sick-study group and healthy-control group) to assess the correlation between the number of astrovirus genome copies in cloacal swabs and the occurrence of enteropathy. To determine this, we developed a novel TaqMan quantitative PCR (qPCR) and digital droplet PCR (ddPCR) methods for astrovirus detection and absolute quantitative analysis. We also performed high-throughput sequencing to obtain the complete genome sequences and establish the genetic similarity of the obtained strains to known astroviruses of poultry and other avian species. Two new complete genome sequences of pigeon astroviruses in the Avastrovirus genus were identified, representing 2 new species. These were found most closely related to astroviruses identified in Columbidae species and chickens. They share an average of 75.8% genome-wide pairwise identity and 57.6% and 64.6% capsid protein sequence identity with other unclassified columbid avastrovirus sequences in GenBank. Although the difference in prevalence of astrovirus in the study and control group was found statistically insignificant, there was a significant difference between the number of genome copies in positive samples from both groups. These unambiguous results leave the role of astroviruses as enteropathogenic factors in pigeons still undetermined.

Genomics and taxonomy of the glyphosate-degrading, copper-tolerant rhizospheric bacterium Achromobacter insolitus LCu2.

A rhizosphere strain, Achromobacter insolitus LCu2, was isolated from alfalfa (Medicago sativa L.) roots. It was able to degrade of 50% glyphosate as the sole phosphorus source, and was found resistant to 10 mM copper (II) chloride, and 5 mM glyphosate-copper complexes. Inoculation of alfalfa seedlings and potato microplants with strain LCu2 promoted plant growth by 30-50%. In inoculated plants, the toxicity of the glyphosate-copper complexes to alfalfa seedlings was decreased, as compared with the noninoculated controls. The genome of A. insolitus LCu2 consisted of one circular chromosome (6,428,890 bp) and encoded 5843 protein genes and 76 RNA genes. Polyphasic taxonomic analysis showed that A. insolitus LCu2 was closely related to A. insolitus DSM23807T on the basis of the average nucleotide identity of the genomes of 22 type strains and the multilocus sequence analysis. Genome analysis revealed genes putatively responsible for (1) plant growth promotion (osmolyte, siderophore, and 1-aminocyclopropane-1-carboxylate deaminase biosynthesis and auxin metabolism); (2) degradation of organophosphonates (glyphosate oxidoreductase and multiple phn clusters responsible for the transport, regulation and C-P lyase cleavage of phosphonates); and (3) tolerance to copper and other heavy metals, effected by the CopAB-CueO system, responsible for the oxidation of copper (I) in the periplasm, and by the efflux Cus system. The putative catabolic pathways involved in the breakdown of phosphonates are predicted. A. insolitus LCu2 is promising in the production of crops and the remediation of soils contaminated with organophosphonates and heavy metals.

Efficacy and prognosis of HER2-Low and HER2-Zero in triple-negative breast cancer after neoadjuvant chemotherapy.

Mounting evidence showed that HER2-Low breast cancer patients could benefit from the novel anti-HER2 antibody-drug conjugates (ADCs) treatment, which pointed the way towards better therapy for HER2-Low patients. The purpose of this study was to describe the clinicopathological features, along with chemotherapeutic effects and survival outcomes of HER2-Low and HER2-Zero in TNBC who received neoadjuvant chemotherapy (NACT). We retrospectively evaluated 638 triple-negative breast cancer patients who were treated with neoadjuvant chemotherapy between August 2014 and August 2022. Pathologic complete response (pCR) and survival outcomes were analyzed in HER2-Low cohort, HER2-Zero cohort and the overall patients, respectively. In the entire cohort, 342 (53.6%) patients were HER2-Low and 296 (46.4%) patients were HER2-Zero. No significant difference was found between HER2-Low and HER2-Zero patients based on all the clinical-pathological characteristics. 143 cases (22.4%) achieved pCR after NACT in the overall TNBC patients. The pCR rate of the HER2-Low patients and the HER2-Zero patients was 21.3% and 23.6%, respectively, exhibiting no statistical difference (p = 0.487). The survival of pCR group after NACT significantly improved compared to non-pCR group either in HER2-Low patients or in HER2-Zero patients. Although we found that patients with HER2-Low had longer DFS than patients with HER2-Zero, there was no considerable difference (p = 0.068). However, HER2-Low patients had a dramatically longer OS than HER2-Zero patients (p = 0.012). The data from present study confirmed the clinical importance of HER2-Low expression in TNBC. Further effort is needed to determine whether HER2-Low could be a more favorable prognostic marker for individual treatment.

TP53 signature predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: Observational and confirmational study using prospective study cohorts.

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group.