Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study.

AIMS: To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin. MATERIALS AND METHODS: A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint. RESULTS: AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported. CONCLUSIONS: Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).

Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Optimizing target and diaphragmatic configuration, and dosimetric benefits using continuous positive airway pressure in stereotactic ablative radiotherapy for lung tumors.

PURPOSE: This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. MATERIALS AND METHODS: We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. RESULTS: Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm3 vs. 4.09 cm3; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm3 vs. 22.52 cm3, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. CONCLUSION: This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management.

Outcomes of Hip Arthroplasty in Patients with Preoperative Thrombocytopenia.

Background: Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 × 103/µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty. Methods: Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 × 103/µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 × 103/µL) and non-severe thrombocytopenia (50-149 × 103/µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups. Results: No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110). Conclusions: Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.

Reliability of the 2018 Revised Version of AO/OTA Classification for Femoral Shaft Fractures.

Background: The Arbeitsgemeinschaft für Osteosynthesefragen (AO) and the Orthopaedic Trauma Association (OTA) classification system for diaphyseal fracture has been recently revised to refine and enhance the accuracy of fracture categorization. This study aimed to investigate the interobserver reliability of the new AO/OTA classification and to compare it with the older version in femoral shaft fractures. Methods: We retrospectively analyzed 139 patients (mean age, 43.8 ± 19.5 years; 92 men and 47 women) with femoral shaft fractures who were treated from 2003 to 2017. Four well-trained observers independently classified each fracture following the previous and revised AO/OTA classification system. We calculated the Fleiss kappa for the interobserver reliability. Results: The previous classification showed the kappa value of 0.580 (95% confidence interval [CI], 0.547-0.613), and the revised version showed 0.528 (95% CI, 0.504-0.552). Both the old and the revised versions showed moderate reliability. Conclusions: Our study highlights the moderate interobserver reliability of both the previous and new AO/OTA classification systems for diaphyseal femur fractures. These findings emphasize the importance of standardized systems in clinical decision-making and underscore the need for ongoing education and collaboration to enhance fracture classification.

Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors.

VPS34 is a crucial protein in cells, essential for handling cellular stress through its involvement in autophagy and endocytosis. This protein functions as a Class III phosphatidylinositol 3-kinase, producing phosphatidylinositol 3-phosphate, which is necessary for autophagy and vesicle trafficking. Additionally, VPS34 forms two mutually exclusive complexes, each playing a vital role in autophagy and endocytic sorting. These complexes share common subunits, including VPS15, VPS34, and Beclin 1, with complex I having ATG14 as a specific subunit. Due to its association with various human diseases, regulation of the VPS34 complex I has garnered significant interest, emerging as a potential therapeutic target for drug discovery. Summaries of the structure, function of VPS34 complexes, and developed VPS34 inhibitors have been provided, along with discussions on the regulation mechanism of VPS34, particularly in relation to the initiation complex I of autophagy. This offers valuable insights for treating autophagy-related diseases.

Chronic periodontal disease is related with newly developing hypertension: a nationwide cohort study.

BACKGROUND: Periodontal disease (PD) is a condition that can be treated and managed. This study aimed to determine if chronic PD status is associated with the risk of developing hypertension, utilizing data from the National Health Insurance Database of Korea. METHODS: Participants who received oral health examinations both in 2003 and in 2005-2006 were included. Those with a history of hypertension were excluded. Hypertension was defined as at least one outpatient or inpatient claim diagnosis (primary or secondary) of hypertension (International Classification of Diseases (ICD)-10 codes I10-I11) with prescription for antihypertensive medication or at least one incident of systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg during a health examination. Changes of PD status was determined during two oral examinations. Study participants were divided into 4 groups according to the changes of PD status: PD-free (those consistently free of disease in both exams), PD-recovered (individuals with disease initially but not in the second exam), PD-developed (no disease initially, but present in the second exam), and PD-chronic (disease throughout both exams). The incidence of hypertension after the second oral health examination (index date) was monitored. Participants were observed from the index date until the earliest occurrence of hypertension onset, mortality, or December 2020. RESULTS: The study comprised 706,584 participants: 253,003(35.8%) in the PD-free group, 140,143(19.8%) in the PD-recovered group, 132,397(18.7%) in the PD-developed group, and 181,041(25.6%) in the PD-chronic group. Over a median follow-up duration of 14.3 years, 239,937 (34.0%) cases of hypertension were recorded. The PD-recovered group had a lower risk of hypertension compared to the PD-chronic group, while the PD-developed group had a higher risk of hypertension compared to the PD-free group. CONCLUSION: Chronic PD is associated with an increased risk of developing hypertension. Although the increase in risk is modest, recovery from PD may have beneficial effects in reducing hypertension risk. Further studies are needed to confirm the importance of regular dental examinations and effective management of PD to reduce hypertension risk.

Integrated Bio-Electrochemical Approach to Norfloxacin (NFX) Degradation: Efficacy, Degradation Mechanisms, and Toxicological Insights.

Norfloxacin (NFX), a widely used fluoroquinolone antibiotic, poses significant environmental concerns due to its persistence in ecosystems and its potential to foster antibiotic resistance. This study explores the degradation of NFX using a bio-electrochemical system (BES) facilitated by Bacillus subtilis isolated from animal waste sludge. Experimental parameters were optimized to maximize removal efficiency, with the optimal conditions determined as an NFX concentration of 200 mg/L, pH 7, and an applied potential of 1.2 V. The degradation pathway was elucidated through the identification of intermediate products, ultimately leading to the complete mineralization of NFX. To assess the environmental impact of BES-treated water, a series of eco-toxicity assays were conducted. Microbial diversity analysis revealed that soil exposed to BES-treated water maintained a balanced microbial community, contrasting with the disruptions observed in soils exposed to untreated NFX-contaminated water. Phytotoxicity tests, earthworm toxicity assay, and Artemia hatchability & lethality assays further confirmed the reduced toxicity of the BES-treated water. These findings highlight the efficacy of BES in the degradation of NFX, demonstrating its potential as a sustainable strategy for the remediation of antibiotic-contaminated environments and the mitigation of associated ecological risks.

Health risks associated with urinary incontinence among older Korean Americans living in subsidized senior housing.

OBJECTIVES: We examined the association of urinary incontinence (UI) with physical, mental, and social health among older Korean Americans living in subsidized senior housing. DESIGN: Data were obtained from surveys conducted in 2023 with older Korean Americans residing in subsidized senior housing in the Los Angeles area (n = 313). UI was measured using a question about the frequency of involuntary urine loss. Physical, mental, and social health risks were assessed with a single item for self-rated health (fair/poor rating), the Patient Health Questionnaire-9 (probable depression), and the Lubben Social Network Scale-6 (isolation from family and friends). RESULTS: Over half of the sample reported UI, with 46.3% experiencing it infrequently (i.e. seldom) and 10.3% frequently (i.e. sometimes or often). UI was significantly associated with physical and mental health indicators; the odds of reporting fair or poor health and having probable depression were 1.94-7.32 times higher among those with either infrequent or frequent UI compared to those without UI. While family isolation was not associated with UI, the odds of being isolated from friends were 2.85 times greater among those with frequent UI compared to those without UI. CONCLUSION: Our findings confirm the adverse impact of UI on physical and mental health and highlight its unique role in social health. UI-associated social isolation was significant only in relationships with friends, providing new insights into the distinction between isolation from family and friends. These findings enhance our understanding of the health risks associated with UI and inform strategies for health management and promotion within the senior housing context.

Effect of low muscle mass on total mortality related to metabolic disease in chronic kidney disease patients.

Low muscle mass is a risk factor for mortality in patients with chronic kidney disease (CKD). However, it is not clear to what extent low muscle mass contributes to this risk, either independently or in combination with metabolic abnormalities and frailty. This study used data from the National Health and Nutrition Examination Survey 1999-2006 and 2011-2018. Low muscle mass was defined as Appendicular Skeletal Mass Index < 7 kg/m2 in men or < 5.5 kg/m2 in women. The follow-up duration was from the first anthropometric and clinical measurements to death or the last follow-up. This study enrolled 2072 patients with CKD. Low muscle mass was associated with a lower risk of metabolic abnormalities, but was associated with an elevated mortality risk. Conversely, central obesity was associated with a higher likelihood of metabolic abnormalities and frailty, yet showed no significant association with mortality risk. Subsequently conducted mediation analysis indicated that the effect of low muscle mass on mortality was direct, not mediated by frailty and metabolic abnormalities. In spite of the inverse relationship between low muscle mass and metabolic abnormalities, low muscle mass are directly associated with an increased risk of all-cause mortality. Low muscle mass may directly contribute to mortality in patients with CKD, independent of metabolic abnormalities and frailty in these patients.

Behavioral biometric optical tactile sensor for instantaneous decoupling of dynamic touch signals in real time.

Decoupling dynamic touch signals in the optical tactile sensors is highly desired for behavioral tactile applications yet challenging because typical optical sensors mostly measure only static normal force and use imprecise multi-image averaging for dynamic force sensing. Here, we report a highly sensitive upconversion nanocrystals-based behavioral biometric optical tactile sensor that instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. By mimicking the sensory architecture of human skin, the unique luminescence signal obtained is axisymmetric for static normal forces and non-axisymmetric for dynamic shear forces. Our sensor demonstrates high spatio-temporal screening of small objects and recognizes fingerprints for authentication with high spatial-temporal resolution. Using a dynamic force discrimination machine learning framework, we realized a Braille-to-Speech translation system and a next-generation dynamic biometric recognition system for handwriting.

Radiofrequency ablation with sine and square electrical waveforms to enhance ablation range.

Radiofrequency ablation (RFA) is a local treatment modality for primary liver cancers. Although various input parameters of the RF generator have been adjusted to improve the ablation ranges, the limited ablation ranges remain an obstacle to RFA. This study aimed to compare the ablation ranges and efficacy of sine and square electrical waveforms in a mouse tumor model. An RF generator with an adjustable electrical waveform was developed, and its ablation range in the porcine liver was compared. For all RF parameters, the square electrical waveform ablation range was greater than that of the sine electrical waveform (all p < 0.001) in the porcine liver. The 45 BALB/c nude mice were used to evaluate the efficacy of the two electrical waveforms after the RFA. The mean tumor volume in the square group was significantly lower than that in the sine group (p < 0.001), indicating a higher survival rate (60%). The cellular coagulative necrosis, inflammatory cell infiltration, heat shock proteins, cellular necrosis, and tumor necrosis were significantly greater in square electrical waveform than in sine electrical waveform (all; p < 0.05). RFA with square electrical waveforms has therapeutic potential for tumor management with an enhanced ablation range.

Motile bacteria crossing liquid-liquid interfaces of an aqueous isotropic-nematic coexistence phase.

In nature, bacteria often swim in complex fluids, but our understanding of the interactions between bacteria and complex surroundings is still evolving. In this work, rod-like Bacillus subtilis swims in a quasi-2D environment with aqueous liquid-liquid interfaces, i.e., the isotropic-nematic coexistence phase of an aqueous chromonic liquid crystal. Focusing on the bacteria motion near and at the liquid-liquid interfaces, we collect and quantify bacterial trajectories ranging across the isotropic to the nematic phase. Despite its small magnitude, the interfacial tension of the order of 10 µN m-1 at the isotropic-nematic interface justifies our observations that bacteria swimming more perpendicular to the interface have a higher probability of crossing the interface. Our force-balance model, considering the interfacial tension, further predicts how the length and speed of the bacteria affect their crossing behaviors. Investigating how a phase change affects bacterial motion, we also find, as soon as the bacteria cross the interface and enter the nematic phase, they wiggle less, but faster, and that this occurs as the flagellar bundles aggregate within the nematic phase. Given the ubiquity of multi-phases in biological environments, our findings will help to understand active transport across various phases.

Innovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.

Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.

Anti-aminoacyl-tRNA synthetase-interacting multifunctional protein-1 antibody improves airway inflammation in mice with house dust mite induced asthma.

Background: Several biologics have been developed and used to treat severe asthma. However, commercialized biologics have limitations in treating T2-low asthma because their main target is the T2 inflammation marker. Therefore, there is an unmet need for treating T2-low severe asthma. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is an auxiliary protein in the mammalian multi-aminoacyl-tRNA synthetase complex. AIMP1 also acts as a cytokine and induces the secretion of proinflammatory cytokines. Since anti-AIMP1 has been shown to reduce interleukin (IL)-6, tumor necrosis factor-α, and IL-17A levels in a mouse model, it could be effective in the treatment of T2-low severe asthma. Methods: Wild-type BALB/c mice were sensitized and challenged with intranasal inoculation of a crude HDM extract. Atliximab, a chimeric AIMP1 antibody, was administered once (20 µg, 40 µg, 100 µg) on Day 14. We evaluated airway hyperresponsiveness (AHR), performed cellular analyses of the bronchoalveolar lavage fluid (BALF), measured inflammatory cytokine levels, and examined peribronchial histological features. Results: Atliximab reduced AIMP1 levels in asthmatic mice in a dose-dependent manner. AHR and Inflammatory cells such as neutrophils and eosinophils in the BALF decreased in asthmatic mice treated with atliximab. The levels of IL-6, IL-13, and transforming growth factor-ß (TGF-ß) in the lung tissue decreased in asthmatic mice treated with a high dose of atliximab (100 µg). Atliximab also reduced goblet cell hyperplasia and peribronchial fibrosis. Conclusions: Atliximab improved asthmatic airway inflammation including neutrophilic inflammation in HDM-induced asthma mice. These data suggest that anti-AIMP1 plays an important role in the treatment of severe T2-low asthma.

Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study.

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

Skin Improvement Effects of Ultrasound-Enzyme-Treated Collagen Peptide Extracts from Flatfish (Paralichthys olivaceus) Skin in an In Vitro Model.

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.

The Disease-Modifying Effects of a Single Intra-Articular Corticosteroid Injection during the Freezing Phase of Frozen Shoulder in an Animal Model.

Although frequently prescribed for frozen shoulder, it is not known if corticosteroid injections improve the course of frozen shoulder. This study aimed to assess the disease-modifying effects of an intra-articular corticosteroid administration at the freezing phase of frozen shoulder. Twenty-four Sprague-Dawley rats were divided into four groups. Their unilateral shoulders were immobilized for the first 3 days in all groups, followed by an intra-articular corticosteroid injection in Group A, an injection and the cessation of immobilization in Group B, no further intervention in Group C, and the cessation of immobilization in Group D. All rats were sacrificed in Week 3 of study, at which point the passive shoulder abduction angles were measured and the axillary recess tissues were retrieved for histological and Western blot analyses. The passive shoulder abduction angles at the time of sacrifice were 138° ± 8° (Group A), 146° ± 5° (Group B), 95° ± 11° (Group C), 132° ± 8° (Group D), and 158° ± 2° (Control). The histological assessments and Western blots showed greater fibrosis and inflammation in the groups that did not receive the corticosteroid injection (Groups C and D) compared to the corticosteroid-injected groups (Groups A and B). These findings demonstrate the anti-inflammatory and disease-modifying effects of corticosteroid injections during the freezing phase of frozen shoulder in an animal model.

Omission of axillary surgery in cN0, postmenopausal ER-positive/HER2-negative breast cancer patients undergoing breast-conserving treatment.

Background: Previous clinical trials have diminished the significance of lymph node (LN) metastasis and axillary surgery in breast cancer, particularly in cN0, postmenopausal estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patients undergoing breast-conserving treatment (BCT). We assessed the replacement of axillary surgery with preoperative imaging modalities by analyzing the proportion of high nodal burden (HNB) patients with ≥3 LN metastases in these patients. Methods: We retrospectively identified 333 cN0, postmenopausal ER-positive/HER2-negative breast cancer patients who underwent BCT in two hospitals between January 2003 and December 2017. The proportion of LN metastasis patients and the number of metastatic LN were investigated. Risk factors of LN metastasis were analyzed and recurrence-free survival (RFS) was compared. Results: Axillary surgery confirmed LN metastasis in 81 (24.3%) of the cN0 patients. The clinical tumor size (cT) and age were factors associated with LN metastasis [cT: odds ratio (OR), 2.92, 95% confidence interval (CI): 1.69-5.05, P<0.001; age: OR, 0.33, 95% CI: 0.11-0.99, P=0.048]. However, HNB patients with ≥3 LN metastases were 15 (4.5%) of all the patients. There was statistically significant difference in the incidence of HNB between patients with cT1 tumors (3.6%) and those with cT2 tumors (7.4%) (P<0.001). Conclusions: In cN0, postmenopausal ER-positive/HER2-negative patients who underwent BCT, patients with cT1 tumors had lower rate of LN metastasis, and there were fewer instances of HNB. Therefore, in these patients, omission of axillary surgery including SLNB can be carefully considered.

Comparison of Franseen and novel tricore needles for endoscopic ultrasound-guided fine-needle biopsy in a porcine liver model.

Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P < 0.001) and better ultrasound visibility (168.97 vs. 125.04, P = 0.004). The Tricore needle also achieved faster specimen acquisition time (48.94 vs. 59.90 s, P = 0.038), larger total specimen area (6.67 vs. 4.68 mm2, P = 0.049), fewer fragments (23.94 vs. 31.94, P = 0.190), lager fragment area (0.28 vs. 0.15 mm2, P < 0.001), and more the number of complete portal tracts (15.44 vs. 9.33, P = 0.017) compared to the Franseen needle. The newly designed Tricore needle showed enhanced procedural performance and specimen quantity and quality compared to commercially available Franseen needle. Although further clinical studies are required, the Tricore needle may represent a favorable option for endoscopic ultrasound-guided fine-needle biopsy procedures.