Lesion Area Research Articles

Efficacy of the Novel Formulation of Topical Liothyronine and Liothyronine-insulin in Mild to Moderate Diabetic Foot Ulcer: A Randomized, Triple-blind Clinical Trial.

Diabetic foot ulcer (DFU) is one of the challenging complications of chronic diabetes. The study aimed to investigate whether liothyronine (T3) and liothyronineinsulin (T3/Ins) topical preparations could significantly reduce the healing time of DFU. A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted on patients with mild to moderate DFU, over a lesion area of no greater than 100 cm2. The patients were randomized to receive T3, T3/Ins, or honey cream 10% as the routine of care twice a day. Patients were examined for tissue healing weekly for 4 weeks, or until the total lesion clearance was observed, whichever was earlier. Of 147 patients with DFUs, 78 patients (26 per group) completed the study and were included in the final evaluation. At the time of study termination, all participants in each of the T3 or T3/Ins groups were free of symptoms based on the REEDA score, while about 40% of participants in the control group were detected with each of grades 1, 2, or 3. A significant difference was observed on days 7, 14, and 21 of consumption of topical preparations (p-value < 0.001). The mean time to complete wound closure in the routine care group was about 60.6 days, while it was 15.9 and 16.4 days in T3 and T3/Ins groups, respectively. Within the T3 and T3/Ins groups, significant earlier wound closure was detected at day 28 (p-value < 0.001). T3 or T3/Ins topical preparations are effective for wound healing and acceleration of wound closure in mild to moderate DFUs.

Comparable Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint at a Mean Follow-up of 5 Years

To assess clinical outcomes and return to sport (RTS) rates among patients who undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects. A retrospective review of patients who underwent an OCA or ACI/MACI from 2010 to 2020 was conducted. Patient-reported outcomes collected included visual analog scale for pain/satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and RTS. The percentage of patients that met the patient acceptable symptom state for KOOS was recorded. Logistic regression was used to identify predictors of worse outcomes. A total of 95 patients were included (78% follow-up) with ACI or MACI performed in 55 cases (57.9%) and OCA in 40 (42.1%). A tibial tubercle osteotomy was the most common concomitant procedure for OCA (66%) and ACI/MACI (98%). Overall, KOOS pain was significantly poorer in OCA than ACI/MACI (74.7, 95% confidence interval 68.1-81.1 vs 83.6, 95% confidence interval 81.3, 88.4, P= .012), whereas the remaining KOOS subscores were nonsignificantly different (all P > .05). Overall, RTS rate was 54%, with no significant difference in return between OCA or ACI/MACI (52% vs 58%, P= .738). There were 26 (27%) reoperations and 5 (5%) graft failures in the entire group. Increasing age was associated with lower satisfaction in OCA and poorer outcomes in ACI/MACI, whereas larger lesion area was associated with lower satisfaction and poorer outcomes in ACI/MACI. Clinical and functional outcomes were similar in patients who underwent OCA or ACI/MACI for patellofemoral articular cartilage defects at a mean follow-up of 5 years. Patients who received OCA had a greater proportion of degenerative cartilage lesions and, among those with trochlear lesions, reported greater pain at final follow-up than their ACI/MACI counterparts. Overall, increasing age and a larger lesion size were associated with worse patient-reported outcomes. Level III, retrospective cohort study.

Effects of Different Carbohydrate Content Diet on Gut Microbiota and Aortic Calcification in Diabetic Mice.

Vascular calcification is a major cause of cardiovascular accidents in patients with type 2 diabetes mellitus. This study aimed to investigate the impact of carbohydrates on gut microbiota and aortic calcification in diabetic ApoE-/- mice. The diabetic ApoE-/- mice were randomly divided into 4 groups: ketogenic diet group, low carbohydrate diet group, medium carbohydrate diet group, and high carbohydrate diet group. The mice were fed continuously for 6 months, with blood glucose, blood ketone and body weight monitored monthly. Lipid metabolism indicators and inflammatory factors were detected using ELISA. The intestinal barrier, atherosclerotic lesion areas, and vascular calcifications were analyzed based on their morphology. Gut microbiota was analyzed using 16S rRNA genes. We found that ketogenic diet played some roles improving glucose, lipid metabolism, and inflammation. Ketogenic diet could improve the intestinal barrier to some extent and increase intestinal bacteria. Compared to the other three groups, the relative abundance of genus Allobaculum, species Blautia producta and Clostridium Ramosum in the ketogenic diet group was significantly increased (P <0.05), which has protective effects in diabetic ApoE-/- mice. Ketogenic diet could delay the onset of aortic atherosclerosis, aortic calcification and improve intestinal barrier function in diabetic ApoE-/- mice.

Development of a PCSK9-targeted nanoparticle vaccine to effectively decrease the hypercholesterolemia

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) and mediates its internalization and degradation, resulting in an increase in LDL cholesterol levels. Recently, PCSK9 emerged as a therapeutic target for hypercholesterolemia and atherosclerosis. In this study, we develop a PCSK9 nanoparticle (NP) vaccine by covalently conjugating the catalytic domain (aa 153-aa 454, D374Y) of PCSK9 to self-assembled 24-mer ferritin NPs. We demonstrate that the PCSK9 NP vaccine effectively induces interfering antibodies against PCSK9 and reduces serum lipids levels in both a high-fat diet-induced hypercholesterolemia model and an adeno-associated virus-hPCSK9D374Y-induced hypercholesterolemia model. Additionally, the vaccine significantly reduces plaque lesion areas in the aorta and macrophages infiltration in an atherosclerosis mouse model. Furthermore, we discover that the vaccine's efficacy relied on T follicular help cells and LDLR. Overall, these findings suggest that the PCSK9 NP vaccine holds promise as an effective treatment for hypercholesterolemia and atherosclerosis.

Fasciculations detected by muscle ultrasonography in the early stage of amyotrophic lateral sclerosis: An autopsy case

AbstractWe describe an autopsied case of amyotrophic lateral sclerosis, wherein fasciculations were detected by muscle ultrasonography in the early stage. The myotome areas with fasciculations corresponded to areas of severe pathological lesions. Our results demonstrated that these fasciculations indicate excitability and severity of affected lower motor neurons and significantly contribute to diagnosis.

LARP7 overexpression alleviates aortic senescence and atherosclerosis.

Atherosclerosis, characterized by the accumulation of lipid plaques on the inner walls of arteries, is the leading cause of heart attack, stroke and severe ischemic injuries. Senescent cells have been found to accumulate within atherosclerotic lesions and contribute to the progression of atherosclerosis. In our previous study, we discovered that suppressing Larp7 accelerates senescence by inhibiting Sirt1 activity, resulting in increased atherosclerosis in high-fat diet (HFD) fed and ApoE deficient (ApoEKO) mice. However, there has been no direct evidence demonstrating Larp7 per se could attenuate atherosclerosis. To this end, we generated a tetO-controlled and Cre-activated Larp7 gain-of-function mouse. Through RT-PCR and western blotting, we confirmed Larp7 overexpression in the aortas of HFD-fed ApoEKO; Larp7tetO mice. Larp7 overexpression led to increased Sirt1 activity and decreased cellular senescence signals mediated by p53/p65 in the aortas. Additionally, Larp7 overexpression reduced the presence of p16-positive senescent cells in the aortic lesions. Furthermore, Larp7 overexpression resulted in a decrease in pro-inflammatory macrophages and SASP factors. Consequently, Larp7 overexpression led to a reduction in the area of atherosclerotic lesions in HFD-fed ApoEKO; Larp7tetO mice. In summary, our study provides evidence that Larp7 overexpression holds promise as an approach to inhibit cellular senescence and prevent atherosclerosis.

Synergistic effects of intercropping green beans with okra on the bacteria blight disease

Green bean is a widely consumed as vegetable mostly for its nutritional, health and economic values. In Cameroon, the production is hindered by bacterial blight disease cause by Xanthomonas campestris. The aim of this study is to evaluate the synergistic effects of intercropping green bean with okra on bacterial blight disease of green beans. Beans varieties (local green bean, jackpot green bean and dolly green bean) were planted in a field in a Randomized Complete Block Design with six treatments and three replicates in Department of Crop Production Technology of the University of Bamenda research farms. The first, second and third treatments consisted of inter-cropping of dolly green bean, jackpot green beans and local green with okra and fourth, fifth and sixth consisted of mono-cropped of dolly green bean, jackpot green beans and local green beans varieties which serves as the control experiments. Data was collected for disease incidence, disease severity, and number of pods and weight of pods were recorded in all the fields. Pathogenicity assessment was conducted in the green house by inoculating healthy green bean plants with bacterial blight isolate and lesion area measured. Significant variations (P≤0.05) were observed in disease incidence, disease severity and yield. The highest mean disease incident (100 %) severity (64 %)and low number of pods (4.3) were recorded in monocropped fields and the intercropped fields had lowest mean disease incidence(40 %), severity (23 %)and high number of pods (27.3 ).Inter-cropping green beans with okra can be recommended to control bacterial blight disease of green beans varieties.

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 μM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fractionin both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 μM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Analysis of the performance of PET/CT using 18F-fluorodeoxyglucose in comparison with other diagnostic methods in drug-resistant epilepsy in children

Background. Epilepsy is one of the most common neurological diseases characterized by a persistent predisposition to epileptic seizures and the neurobiological, cognitive, psychological, and social consequences. In recent decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy that progresses to drug-resistant epilepsy. Currently, surgical treatment is one of the most important ways to treat such epilepsy. Collaboration between multidisciplinary teams and the combination of multiple neuroimaging methods are key to determining the exact localization of the epileptogenic zone. New diagnostic methods are being developed and the number of indications for their use is growing. The purpose of the study was to analyze the scientific literature on the effectiveness of positron emission tomography combined with computed tomography (PET/CT) using 18F-fluorodeoxyglucose compared to other diagnostic methods in drug-resistant epilepsy in children. Materials and methods. A literature search using keywords was conducted in Web of Science, Scopus, PubMed, and Elsevier databases. Results. Surgical treatment of drug-resistant epilepsy in children has become a specialized area in neurosurgery. Surgical removal or disconnection of a part of the brain, in which the epileptogenic zone is suspected, allows for a complete cure or a significant reduction in seizure frequency. It has been shown that a prerequisite for postoperative success is the accurate determination of the epileptogenic zone during a multistage preoperative diagnosis. Among many studies, nuclear medicine technologies play an important role in the presurgical examination of children with drug-resistant epilepsy. In combination with other methods, nuclear medicine helps identify the epileptogenic zone, especially in case of conflicting data, negative magnetic resonance imaging — negative epilepsy, focal cortical dysplasia or extratemporal lobe epilepsy. Single-photon emission CT and PET using functional neuroimaging with nuclear medicine indicators are classical methods and are recommended by neuroimaging specialists. In addition, one of the leading modern methods is PET/CT with 18F-fluorodeoxyglucose. It provides information that might be missed when using anatomical methods such as magnetic resonance imaging, and the area of hypometabolism detected with 18F-fluorodeoxyglucose PET/CT may be larger than the area of anatomical lesion detected on magnetic resonance imaging. Conclusions. For children with drug-resistant epilepsy, PET/CT using 18F-fluorodeoxyglucose is the most optimal method of preoperative diagnosis.

Novel motion correction algorithm improves diagnostic performance of CT fractional flow reserve

ObjectivesThis study aimed to investigate the diagnostic performance of computed tomography (CT) fractional flow reserve (CT-FFR) derived from standard images (STD) and images processed via first-generation (SnapShot Freeze, SSF1) and second-generation (SnapShot Freeze 2, SSF2) motion correction algorithms. Methods151 patients who underwent coronary CT angiography (CCTA) and invasive coronary angiography (ICA)/FFR within 3 months were retrospectively included. CCTA images were reconstructed using an iterative reconstruction technique and then further processed through SSF1 and SSF2 algorithms. All images were divided into three groups: STD, SSF1, and SSF2. Obstructive stenosis was defined as a diameter stenosis of ≥ 50 % in the left main artery or ≥ 70 % in other epicardial vessels. Stenosis with an FFR of ≤ 0.8 or a diameter stenosis of ≥ 90 % (as revealed via ICA) was considered ischemic. In patients with multiple lesions, the lesion with lowest CT-FFR was used for patient-level analysis. ResultsThe overall quality score in SSF2 group (median = 3.67) was markedly higher than that in STD (median = 3) and SSF1 (median = 3) groups (P < 0.001). The best correlation (r = 0.652, P < 0.001) and consistency (mean difference = 0.04) between the CT-FFR and FFR values were observed in the SSF2 group. At the per-lesion level, CT-FFRSSF2 outperformed CT-FFRSSF1 in diagnosing ischemic lesions (area under the curve = 0.887 vs. 0.795, P < 0.001). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. ConclusionThe SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.

Smooth muscle cell-specific deletion of S100A4 modifies smooth muscle cell fate and inflammation in murine atherosclerotic lesions

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF) S100A4, a calcium-binding protein, is crucial in smooth muscle cell (SMC) phenotypic switch, yet its role in atherosclerotic plaque development and SMC plasticity remains unclear. Our previous experiments using an S100A4 neutralizing antibody approach in ApoE-/- atherosclerotic-prone mice showed reduced atherosclerotic burden but did not establish a direct link between the various S100A4-expressing cells and atherosclerosis. Herein, we show that aortic Oil RedO staining in ApoE-/-; S100A4-/- mice subjected to a 12-week high-cholesterol-diet (HCD) revealed reduced lesion areas compared to ApoE-/- mice (Figure 1, from 21.29% of the total aorta in ApoE-/-; S100A4+/+ mice to 13.27% in ApoE-/-; S100A4-/- mice), highlighting a pivotal role for S100A4 in atherosclerotic plaque development. We then used a lineage tracing ApoE-/- mouse model, in which we induced an SMC-specific deletion of S100A4 (SMC-S100A4Δ/Δ). After 12 weeks of HCD, SMC-S100A4Δ/Δ and control mice (SMC-S100A4wt/wt) were sacrificed, and aortas were processed for en face Oil Red O staining, immunohistochemistry, and single-cell RNA sequencing (scRNA-seq). SMC-specific deletion of S100A4 reduced the necrotic core area (from 29.75% of total plaque area in SMC-S100A4wt/wt to 18.23% in SMC-S100A4Δ/Δ mice) without affecting total atherosclerotic plaque size suggesting a more potent impact on plaque composition. ScRNA-seq analysis from SMC-S100A4Δ/Δ and SMC-S100A4wt/wt mice showed that the inflammatory macrophage-like SMC phenotype was highly suppressed in the plaque and associated with increased SMC repair phenotypes as well as a global reduction of myeloid inflammatory cells. SMCs also retained specific contractile SMC markers, namely Acta2 and Myh11 (fold change of 2.285 and 2.492, respectively) hinting towards a more stable fibrous cap. Immunofluorescence staining on aortic roots plaque (Figure 2) confirmed those results with an increase of SMCs (from 11.02% to 16.18%) as well as a-smooth muscle actin (a-SMA, Acta2)-positive SMCs (from 3.25% to 5.1%) in SMC-S100A4 Δ/Δ mice. Furthermore, the Gene Set Enrichment Analysis (GSEA) of scRNAseq data revealed that, in SMC-S100A4Δ/Δ mice, genes related to mitochondrial metabolism and oxidative respiration were highly downregulated in all SMC clusters. We investigated SMC mitochondrial fitness in vitro and showed that S100A4-/- SMCs have an increased basal oxygen consumption rate and an increased proton leak (fold change of 1.37 and 1.96 respectively) suggestive of differences in cellular metabolic adaptability. In conclusion, our research emphasizes the significant role of S100A4 in plaque development, demonstrating how SMC-derived S100A4 knockdown affects plaque evolution, reducing inflammation, and promoting stability likely through influencing SMC phenotypic switch through metabolic pathways.

Comparative analysis of short-term efficacy between robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus.

To investigate the short-term clinical efficacy of robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus (OCLT). This study was divided into two groups: experimental group: robot-assisted retrograde drilling group; control group: arthroscopic microfracture group. A total of 6 OCLT patients who were treated with robot navigation-assisted retrograde drilling and 10 OCLT patients who were treated with arthroscopic microfracture between October 2020 and October 2021 were retrospectively analyzed. There were 11 males and five females, with a mean age of 36 years. The patients were followed up for 6-12 months to compare the changes in the OCLT lesion area by magnetic resonance imaging (MRI), visual analogue scale/score (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) before and after surgery. All 16 patients were followed up for an average of 8 months, and no complications such as joint infection, nerve injury, or active bleeding occurred during the follow-up period. Only one patient suffered discomfort involving transient postoperative pain in the operative area, but did not experience long-term numbness or chronic pain. Postoperative MRI revealed that none of the patients had severe signs of osteonecrosis, osteolysis or cystic changes of the talus, with lesion areas smaller than those before surgery. The difference was statistically significant (P < 0.01). The patients in the experimental group showed a more significant improvement in the last 3 months than in the first 3 months of the follow-up period. At the last follow-up, the VAS score was 3 points in the experimental group and 2.2 points in the control group, and the AOFAS score was 88.6 points in the experimental group and 88 points in the control group, all of which were significantly higher than those before operation, and the differences were statistically significant, but there was no statistically significant difference between the groups. Both robot navigation-assisted retrograde drilling and arthroscopic microfracture for bone marrow stimulation (BMS) to treat OCLT in all patients obtained satisfactory effects in the short term. In addition, the follow-up revealed that with excellent efficacy and few complications, robot navigation-assisted retrograde drilling was safe and minimally invasive, and greatly reduced operative time. Consequently, robot navigation-assisted retrograde drilling for BMS was a safe and effective procedure for the treatment of OCLT.

Determining the optimal distal resection margin in rectal cancer patients by imaging of large pathological sections: An experimental study.

To determine the distal resection margin in sphincter-sparing surgery in patients with low rectal cancer based on imaging of large pathological sections. Patients who underwent sphincter-sparing surgery for ultralow rectal cancer at Guangxi Medical University Cancer Hospital within the period from January 2016 to March 2022 were tracked and observed. The clinical and pathological data of the patients were collected and analyzed. The EVOS fluorescence automatic cell imaging system was used for imaging large pathological sections. Follow-up patient data were acquired mainly by sending the patients letters and contacting them via phone calls, and during outpatient visits. A total of 46 patients (25 males, 21 females) aged 27 to 86 years participated in the present study. Regarding clinical staging, there were 9, 10, 16, and 10 cases with stages I, II, III, and IV low rectal cancer, respectively. The surgical time was 273.82 ± 111.51 minutes, the blood loss was 123.78 ± 150.91 mL, the postoperative exhaust time was 3.67 ± 1.85 days, and the postoperative discharge time was 10.36 ± 5.41 days. There were 8 patients with complications, including 3 cases of pulmonary infection, 2 cases of intestinal obstruction, one case of pleural effusion, and one case of stoma necrosis. The longest and shortest distal resection margins (distances between the cutting edges and the tumor edges) were 3 cm and 1 cm, respectively. The minimum length of the extension areas of the tumor lesions in the 46 images of large pathological sections was 0.1 mm, and the maximum length was 15 mm. Among the tumor lesions, 91.30% (42/46) had an extension area length of ≤5 mm, and 97.83% (45/46) had an extension area length of ≤10 mm. The length of the extension zone was not related to clinical pathological parameters (P > .05). In the vast majority of cases, the distal resection margin was at least 1 cm; thus, "No Evidence of Disease" could have been achieved. Additional high-powered randomized trials are needed to confirm the results of the present study.

Effect of virgin olive oil as spreadable preparation on atherosclerosis compared to dairy butter in Apoe-deficient mice

Olive oil is the main source of lipid energy in the Mediterranean diet and there is strong evidence of its health benefits. The effect of extra virgin olive oil (EVOO) in the form of a preparation of spreadable virgin olive oil (S-VO) on the progression of atheroma plaques was investigated in Apoe-deficient mice, a model of accelerated atherosclerosis. Methods: Two isocaloric Western purified diets containing 20% fat, either as S-VO or as dairy butter, were used to feed 28 males and 16 females of two-month-old Apoe-deficient mice for 12 weeks. S-VO was prepared by blending more than 75% virgin olive oil with other vegetal natural fat to obtain a solid fat. Plasma total cholesterol, triglycerides and HDL cholesterol were measured. Hepatic lipid droplets were analyzed. Areas of atherosclerotic aortic lesions were quantified in cross-sectional images of the proximal aorta and en face analysis of the whole aorta. Results: Total plasma cholesterol was increased in mice on the butter-supplemented diet in both female and male mice compared to S-VO, and the ratio of TC/HDL-cholesterol was significantly lower in S-VO than in the butter diet, although only in males, and no differences in plasma triglycerides were observed. No significant differences in hepatic lipid droplets were observed between diets in either sex. Aortic lesion areas were significantly higher in mice consuming the butter versus the S-VO diet in both sexes. Conclusion: Extra virgin olive oil prepared in spreadable form maintained the delay in atheroma plaque progression compared to butter.

Comparative study of lesions obtained with radiofrequency between irrigated ablation catheter with flexible tip and non-irrigated catheter in ex vivo porcine heart slices

Abstract Background Lesion formation through radiofrequency (RF) is related to various parameters, including power, contact force, duration of energy delivery and temperature. Notably, the characteristics of the lesions differ when comparing irrigated to non-irrigated catheters. Non-irrigated catheter lesions present a larger surface area and shallower depth, while irrigated catheters induce deeper lesions with higher volumes. Particularly, flexible-tip open-irrigated catheter exhibit unique irrigation characteristics and the resulting lesions may show a reduced surface area but extend deeper into the tissue. Main drawbacks of using non-irrigated catheter are the risk of clot formation and of steam pops, both possibly avoidable with an irrigated catheter. Purpose The aim of the study was to demonstrate that flexible-tip open-irrigated catheter generate lesions with a smaller surface area and deeper extension when compared to non-irrigated catheter. Methods An ex vivo model consisting of porcine heart slices in a warmed saline chamber was used. A flexible-tip open-irrigated ablation catheter and a non-irrigated catheter were positioned with a stable tissue contact weight ranging from 10 to 20 g of force in perpendicular position. RF was delivered at powers of 20, 30 and 40 Watt for 60s. Lesion dimensions were analyzed. The occurrence of steam pop was registered. Results The ablations were conducted using flexible-tip open-irrigated (n=55) and non-irrigated (n=39) catheters in a power-control mode. Superficial length and width of lesions were greater with the non-irrigated catheter than with the irrigated catheter, irrespective of the power delivered (superficial length: p=0,0001 at 20W, p=0,002 at 30 W and p=0,0001 at 40 W; superficial width: p=0,001 at 20 W, p=0,019 at 30 W and p=0,003 at 40 W). When computing superficial areas, lesions performed with the non-irrigated catheter were significantly wider, regardless of the power delivered (p=0,001 at 20 W, p=0,005 at 30 W and p=0,001 at 40 W). The irrigated catheter determined significantly greater values of lesion maximum depth at high power delivery (40 W, p=0.007). No steam pop was observed using the irrigated ablation catheter, while 12 steam pops occurred with the non-irrigated catheter. Conclusions This study highlights that RF ablation using flexible-tip open-irrigated catheter has the potential to generate smaller lesion areas when compared to a non-irrigated tip. Furthermore, it may contribute to decrease steam pops, even with escalating power output. This irrigated catheter might be a preferable choice when precision is crucial, particularly in determining superficial area of lesions. Specifically, it might be advantageous for procedure as atrioventricular nodal reentry tachycardia (AVNRT) ablation, minimizing the risk of iatrogenic conduction disturbance related to RF delivery in the region of the compact AV node, located superficially at a millimeter distance from the ablation site.Experiment setting, lesion measurementsLesion superficial area

#2615 Altered peroxidasin expression pattern in IgA nephropathy

Abstract Background and Aims PXDN is a multifunctional heme peroxidase responsible for the crosslinking of type IV collagen protomers at basement membranes, playing a crucial role in the extracellular matrix dynamics. In renal pathophysiology, increased PXDN expression has been associated with pro-fibrotic and pro-carcinogenic mechanisms and we have shown that PXDN is expressed throughout all kidney compartments since the early stages of nephrogenesis. However, the role of PXDN in kidney health and disease remains largely unknown. In this work we performed a comparative analysis of PXDN expression between renal biopsy samples from IgA nephropathy (IgAN) patients and healthy kidney biopsy samples. IgAN was the selected CKD model due to its straightforward diagnosis by standard protocols for histopathological evaluation of kidney biopsies, and to the fact that the renal outcomes are consistently associated with several key pathologic features, including tubular atrophy and interstitial fibrosis. Correlations between PXDN expression and IgAN disease and kidney function parameters as well as with ECM proteins were also explored. Method Fluorescence immunohistochemistry for PXDN was performed in biopsy samples from IgAN patients (n = 20) and in biopsies from healthy kidney donors (n = 7). Proximal tubules were assessed by anti-CD15 fluorescent staining. Collagen III (COLIII) deposition was investigated in IgAN samples (n = 7) by immunofluorescence. Brightfield images were manually segmented into glomeruli, proximal and distal tubules, and interstitium, using QuPath software, and the fluorescence intensity measurements were obtained with ImageJ/Fiji. Results Results showed that, in comparison with healthy kidney samples, PXDN is significantly decreased in proximal and distal tubules of IgAN patients (P &amp;lt; 0.001 and P &amp;lt; 0.05, respectively) whereas it is increased in IgAN interstitium (P &amp;lt; 0.001). When IgAN samples were stratified by the presence or absence of chronic lesions (glomerular sclerosis and interstitial fibrosis) we observed that in the proximal tubules, PXDN is decreased even in areas without lesions while in the distal tubules the expression is compromised only in the lesioned areas. In the interstitium, PXDN shows a tendency of increase from healthy tissue to IgAN in areas without and with tubulointerstitial fibrosis, presenting a significant increase in the lesioned areas (P &amp;lt; 0.001). Concerning ECM deposition, results showed a significant correlation between the expression of PXDN and COLIII in sclerotic glomeruli (R = 0.8214; P = 0.0341) and in the tubulointerstitial fibrotic areas (R = 0.93; P = 0.0067). Moreover, although no differences were observed in the glomerular expression of PXDN between healthy and IgAN samples, when considering eGFR, a significant increase of PXDN was observed in both non-lesioned and sclerotic glomeruli from IgAN patients with eGFR bellow 60 ml/min/1,73 m2. In the interstitium, the expression of PXDN was also increased in tubulointerstitial fibrotic areas of IgAN patients with eGFR bellow 60 ml/min/1,73 m2, in comparison with the same areas in patients with higher eGFR values. Conclusions Overall, our study shows a differential expression of PXDN in IgAN, with loss in the tubular region that relates with the state of interstitial fibrosis, and gain in the glomerular and interstitial region where it correlates with COLIII compartment-specific deposition and with kidney function as assessed by eGFR. These data support, for the first time, the enrollment of PXDN in the topographic mechanism of IgA-mediated kidney lesion that deserves further investigations. Given that sclerosis and fibrosis are a common pathogenic mechanism of CKD, irrespective of the underlying etiology, we postulate that PXDN may serve as a novel therapeutic target for this disease.

Topical 5-Fluorouracil 0.5% as primary treatment for Ocular Surface Squamous Neoplasia.

To evaluate the efficacy of topical treatment with 5-Fluorouracil (5-FU) 0.5% in cases of Ocular Surface Squamous Neoplasia (OSSN), and to assess the tolerance of patients undergoing treatment. Patients with clinical diagnosis of OSSN referred to the Ocular Oncology division from the Federal University of Sao Paulo, Brazil, were recruited for the current study. Patients were treated with topical 5-FU 0.5% using a regimen of 4 times daily for 10 days, followed by a 3-week drug holiday, continued up to 3 cycles before an alternative treatment. Lesions were evaluated at baseline and throughout treatment. Treatment adherence was assessed using the Morisky Medication Adherence scale. Any adverse events along the treatment were noted. A total of 30 eyes of 30 patients adherent to the treatment were included in the study. Among the total cases treated with 5-FU 0.5%, 24 patients achieved therapeutic success after a mean treatment duration of 21.71 ± 7.77 days, representing a success rate of 80.00% (95% CI: 60.75-91.18%). For each 1 mm2 increase in the lesion area, the odds of treatment success decrease by 6% (OR: 0.94; 95%CI: 0.88-0.99; p = 0.033). Only mild adverse events such as ocular discomfort, ocular burning and tearing were observed along the treatment in 8 patients. Topical 5-FU 0.5% is an effective therapeutic option in the treatment of OSSN, with an 80% therapeutic success rate, showing good tolerability. The size of the lesion was identified as a factor influencing treatment success, therefore it should be taken into consideration when defining treatment approaches.

Detection of mild cognitive impairment based on attention mechanism and parallel dilated convolution

Mild cognitive impairment (MCI) is a precursor to neurodegenerative diseases such as Alzheimer’s disease, and an early diagnosis and intervention can delay its progression. However, the brain MRI images of MCI patients have small changes and blurry shapes. At the same time, MRI contains a large amount of redundant information, which leads to the poor performance of current MCI detection methods based on deep learning. This article proposes an MCI detection method that integrates the attention mechanism and parallel dilated convolution. By introducing an attention mechanism, it highlights the relevant information of the lesion area in the image, suppresses irrelevant areas, eliminates redundant information in MRI images, and improves the ability to mine detailed information. Parallel dilated convolution is used to obtain a larger receptive field without downsampling, thereby enhancing the ability to acquire contextual information and improving the accuracy of small target classification while maintaining detailed information on large-scale feature maps. Experimental results on the public dataset ADNI show that the detection accuracy of the method on MCI reaches 81.63%, which is approximately 6.8% higher than the basic model. The method is expected to be used in clinical practice in the future to provide earlier intervention and treatment for MCI patients, thereby improving their quality of life.

Comorbid Condition Induced by Lichenoid Tuberculosis of the Skin and Lichen Planus. Significance of a Multidisciplinary Approach to Timely Diagnosis and Treatment

In Ukraine, all cases tuberculosis (TB) of the skin are classified as «extrapulmonary TB», which complicates the accurate determination of disease prevalence. Clinical cases of skin TB require a multi­disciplinary approach for diagnosis, particularly for differential diagnosis from chronic dermatoses with similar morphological skin lesions and for treatment. Objective — to conduct a differential diagnosis and determine the presence of comorbid pathology in a patient exhibiting clinical manifestations typical of both lichenoid tuberculosis of the skin and lichen planus. This involves utilising a suite of modern diagnostic procedures, including pathohistological analysis and Doppler laser flowmetry. Materials and methods. We observed a patient, B., born in 2005, who presented with skin lesions characteristic of both lichenoid TB of the skin and lichen planus. According to the patient's history, the duration of the disease was 4 years. Using laser Doppler flowmetry with a Vingmed SD-100 flowmeter (Medata, Sweden), we measured microcirculation and its standard deviation, coefficient of variation and maximum amplitude of slow, fast and pulse oscillations in the affected areas and visually unchanged skin (3—4 cm from the rash elements). Pathohistological examinations were also conducted in the areas of efflorescence. Results and discussion. Considering the clinical examination data, results of comprehensive laboratory and pathohistological research, and indicators of laser Doppler flowmetry in the areas of skin lesions, a comorbid condition caused by lichenoid TB of the skin and lichen planus was diagnosed. The patient was referred to a phthisiologist at his place of residence for comprehensive specific treatment with antitubercu­lar drugs. The patient was also recommended to undergo dermatological monitoring to assess the effectiveness of the pathogenetic therapy prescribed for lichen planus. Conclusions. The variety of clinical forms of skin TB and a number of chronic dermatoses, particularly lichen planus, as well as the similarity in the clinical picture of morphological elements of the skin rash in these diseases, necessitate a multidisciplinary approach and the execution of a complex of clinical, specialised laboratory, pathohistological and modern diagnostic instrumental studies. These enable timely differential diagnosis of skin lesions, including comorbid conditions, and the prescription of rational comprehensive therapy. The use of laser Doppler flowmetry to determine the state of dermal blood circulation in the affected skin areas is an important additional diagnostic test in the differential diagnosis of some chronic dermatoses or in determining a comorbid state.

Quantitative radiomics analysis of imaging features in adults and children Mycoplasma pneumonia.

This study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs. In a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p < 0.05) were selected. After segmenting the lesion area on the CT image as the region of interest, 1,904 radiomic features were extracted. Then, Pearson correlation analysis (PCC) and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features. Based on the selected features, multivariable logistic regression analysis was used to establish the clinical model, CT image model, radiomic model, and combined model. The predictive performance of each model was evaluated using ROC curves, AUC, sensitivity, specificity, accuracy, and precision. The AUC between each model was compared using the Delong test. Importantly, the radiomics features and quantitative and qualitative CT image features were analyzed using Pearson correlation analysis and analysis of variance, respectively. For the individual model, the radiomics model, which was built using 45 selected features, achieved the highest AUCs in the training set, validation set, and external test set, which were 0.995 (0.992, 0.998), 0.952 (0.921, 0.978), and 0.969 (0.953, 0.982), respectively. In all models, the combined model achieved the highest AUCs, which were 0.996 (0.993, 0.998), 0.972 (0.942, 0.995), and 0.986 (0.976, 0.993) in the training set, validation set, and test set, respectively. In addition, we selected 11 radiomics features and CT image features with a correlation coefficient r greater than 0.35. The combined model has good diagnostic performance for differentiating between adults and children with mycoplasmal pneumonia, and different CT imaging signs are quantitatively represented by radiomics.