Individual Lesions Research Articles

In-phase and opposed-phase Dixon chemical shift imaging for the assessment of skeletal marrow lesions: comparison of measurements from longitudinal sequences to those from axial sequences.

In-phase and opposed-phase chemical shift imaging (CSI) is a useful technique for assessing skeletal lesions. This study determined the frequency of significant differences in measurements obtained from longitudinal (coronal or sagittal) sequences to those obtained from axial sequences. Chemical shift imaging was undertaken in 96 consecutive patients referred from the Musculoskeletal Sarcoma and Spinal Oncology services for assessment of possible bone tumours as part of a standard tumour protocol, which included turbo spin echo and inversion recovery sequences. For spinal lesions, CSI was obtained in the sagittal and axial planes, while for all other sites, it was obtained in the coronal and axial planes. The study included 49 (51.0%) males and 47 (49.0%) females with mean age 42.4 years (range 2-91 years). In 4 cases, 2 individual lesions were assessed, making a total of 100 lesions. Based on typical imaging features (n = 57) or histology (n = 43), 22 lesions (22%) were classified as non-neoplastic, 44 (44%) as benign neoplasms, 6 (6%) as intermediate-grade neoplasms, and 28 (28%) as malignant neoplasms. A significant discrepancy, wherein a lesion was classified as fat-containing (% SI drop >20%-25%) in the longitudinal plane, while in the axial plane it was classified as fat-replacing (% SI drop <20%-25%), or vice versa, occurred in 9%-14% of cases. However, this discrepancy had no appreciable effect on overall diagnostic accuracy, which was calculated at 79% for the longitudinal plane and 75%-80% for the axial plane. Significant differences in CSI measurements occur in 9%-14% of cases based on imaging plane, but with no significant effect on diagnostic accuracy. Radiologists should be aware that CSI measurements in different planes appear to have significant differences in up to 14% of lesions. However, diagnostic accuracy does not seem to be significantly affected.

Cardiac Pulsed Field Ablation Lesion Durability Assessed by Polarization-Sensitive Optical Coherence Reflectometry.

Pulsed field ablation uses electrical fields to cause nonthermal cell death over several hours. Polarization-sensitive optical coherence reflectometry is an optical imaging technique that can detect changes in the tissue ultrastructure in real time, which occurs when muscular tissue is damaged. The objective of this study was to evaluate the ability of a polarization-sensitive optical coherence reflectometry system to predict the development of chronic lesions based on acute changes in tissue birefringence during pulsed field ablation. Superior vena cava isolation was performed in 30 swine using a biphasic, bipolar pulsed field ablation system delivered with a nonirrigated focal tip catheter. Acute changes in tissue birefringence and voltage abatement were analyzed for each individual lesion. A high-resolution electroanatomical map was performed at baseline and 4 to 12 weeks after ablation to locate electrical gaps in the ablated area. A total of 141 lesions were delivered and included in the analysis. Acute electrical isolation based on the electroanatomical map was achieved in 96% of the animals, but chronic isolation was only seen in 14 animals (46%). The mean voltage abatement of lesions that showed recovery was 82.8%±14.6% versus 84.4%±17.4% for those that showed fibrosis (P=0.7). The mean acute reduction in tissue birefringence in points demonstrating fibrosis was 63.8%±11.3% versus 9.1%±0.1% in the points that resulted in electrical gaps. A threshold of acute reduction of birefringence of ≥20% could predict chronic lesion formation with a sensitivity of 96% and a specificity of 83%. Acute tissue birefringence changes assessed with polarization-sensitive optical coherence reflectometry during pulsed field ablation can predict chronic lesion formation and guide the ablation procedure although limited by the tissue thickness.

Updated automated PROMISE assessment: Treatment response evaluation based on PSMA PET/CT.

48 Background: PSMA PETs can track treatment response in patients with prostate cancer. Recent integration of the RECIP framework with PROMISE v2 allows quantitative assessment of PSMA PETs. While useful for assessing differentially responding lesions, manual measurement and tracking is cumbersome and PSA reliance can be misleading. We evaluated an automated AI-enabled platform, aPROMISE, for longitudinal lesion tracking to evaluate treatment response based solely upon tumor volume. Methods: Patients with castration sensitive or resistant disease undergoing 18F-DCFPyL PET/CTs during workup and at ≥3 months after treatment were included. Tracer-avid lesions were identified using the aPROMISE algorithm. Detected lesions were manually approved by an experienced nuclear medicine physician. After lesion identification and approval, the total tumor volume was calculated. The corresponding low-dose CT was auto-segmented, allowing anatomic compartment (prostate/bed, node, bone, or visceral) annotation of 18F-DCFPyL-avid lesions. Baseline and follow-up PETs were deformably co-registered to automatically match individual lesions if they were in the same anatomic compartment, and had overlap &lt;10 mm center-to-center (&lt;50 mm for rib lesions). Unmatched lesions on follow-up PET were noted as new. Response was assessed as CR (no avidity in follow-up), PR (volume decrease ≥30% without new lesions), SD (volume decrease ≥30% with new lesions), or PD (volume increase ≥20% plus new lesions). Volume changes at the total tumor and individual lesion levels were also assessed independent of RECIP imaging criteria. Results: The automated algorithm assigned the correct RECIP classification in 97% of the 67 cases with 14 as CR, 14 as PR, 20 as SD, and 19 as PD. 1027 of the 1686 lesions identified on baseline PET were seen on follow-up. 673 of the 1700 lesions identified on follow-up PET were new. Conclusions: For response assessment using 18F-DCFPyL PET/CT and RECIP imaging criteria, the automated algorithm and manual detection achieved the same clinical classifications. Automated approaches may allow more granular lesion analysis The precision and accuracy this automated process is being validated in prospective clinical studies.

The importance of considering competing risks in recurrence analysis of intracranial meningioma

BackgroundThe risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.MethodsWe surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions.ResultsOf 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions).ConclusionThe importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Ocular surface lesions in clinical grades of Bell's phenomenon.

Bell's phenomenon, also known as the palpebral oculogyric reflex, is a critical reflex that protects the cornea. We developed an innovative, simple, and practical grading scale for Bell's phenomenon that includes the inverse Bell's phenomenon. Using this scale, we investigated the characteristics of Bell's phenomenon among asymptomatic individuals in different age groups and examined the frequency of ocular surface lesions in asymptomatic and symptomatic participants with different grades. In this cross-sectional study, we randomly included 330 eyes of 165 asymptomatic, healthy, White Turkish individuals who attended the outpatient eye clinic, with a male-to-female ratio of 1:1.4, in the control group. These were categorized into four age groups: 4 - 20 years, 21 - 40 years, 41 - 60 years, and > 60 years. Eighty eyes from 40 patients with ocular surface lesions and absence of grade + 2 Bell's phenomenon were included in the symptomatic group. Bell's phenomenon was classified into five grades: grade + 2 (strong positive), grade + 1 (weak positive), grade 0 (no Bell's phenomenon, no eye movement), grade -1 (weak inverse), and grade -2 (strong inverse). We detected higher frequencies of grade + 2, + 1, and 0 in individuals aged 4 - 40, 41 - 60, and > 60 years, respectively. There was a significant difference between age groups in the frequencies of different grades (P < 0.001). Pairwise analysis revealed a significantly lower frequency of grade + 2 in the age group > 60 years compared with the 4 - 20 and 21 - 40 year groups (both P < 0.05). Grade + 2 was the most frequent in both sexes. We detected grade 0 in 27.1% of men and 22.1% of women in the control group, with no significant difference in the frequencies of different grades between sexes (P > 0.05). We observed significant differences between grades with respect to the frequency of ocular surface lesions (P < 0.001). Pairwise analysis revealed a significantly higher frequency of ocular surface lesions in asymptomatic individuals with grade 0 and all four other grades (all P < 0.001). However, the frequency of ocular surface lesions was comparable between sexes (P > 0.05). Of the 40 symptomatic individuals, 28 (70%), 5 (12.5%), 4 (10%), and 3 (7.5%) had grade 0, + 1, -1, and -2, respectively. The number of symptomatic patients was higher in grade 0 (n = 28) than in other grades (grade + 1, -1, and -2: n = 12 patients), and these individuals had a higher frequency of ocular surface lesions (n = 38 lesions) than others (grade + 1, -1, and -2: 7 lesions). Using a simple, practical grading scale for Bell's phenomenon that includes inverse Bell's phenomenon, we observed that inverse Bell's phenomenon is a reflex that may be present in healthy individuals and could have a protective effect on the eye, although not to such a degree as a strong Bell's phenomenon. Our observations imply that bilateral conjunctival calcifications/Vogt's limbal girdle may be associated with grades 0 and + 1 Bell's phenomenon. Further large-scale studies are needed to determine the frequency of Bell's phenomenon in the general population using this innovative, simple, practical grading scale, and to identify the protective or injurious effect of each grade on the ocular surface.

Clinical characterization of a hypersensitivity mixed bacterial and fungal dermatitis in a translational model of porcine NASH.

The development of animal models of chronic liver disease via diet modification is a promising avenue for translational research but can lead to unexpected side effects that impact model adoption. While these side effects are well characterized in rodent models of nonalcoholic steatohepatitis (NASH), limited knowledge of these effects exists for novel porcine models of NASH. To close this gap, the present study investigates the side effects of diet-based NASH induction in pigs, with a systematic analysis of the pathologic mechanisms underlying dermatitis development and evaluation of treatment approaches. Twelve pigs (10 large domestic pigs, 2 Goettingen minipigs) were fed a methionine- and choline-deficient, high-fat diet for 8 weeks to induce NASH. A retrospective review of each animal's clinical record was performed to identify the side effects of the diet. Following the identification of diet-associated dermatitis, severity was judged by using a novel gradation system that characterized the individual lesions and body regions resulting in a cumulative evaluation. In addition to this clinical assessment, the etiology of the dermatitis was investigated via histopathologic and microbiologic testing. Furthermore, the success of prophylactic and therapeutic treatment approaches was evaluated by considering dermatitis development and clinical course. All study animals demonstrated unexpected side effects of the methionine- and choline-deficient, high fat diet. In addition to marked dermatitis, study pigs showed impaired weight gain and developed steatorrhea and anemia. Based on the skin gradation system, five animals developed severe dermatitis, four animals moderate dermatitis, and three animals mild diet-associated dermatitis. Histological and microbiological evaluation of the affected skin showed signs of a hypersensitivity reaction with secondary infection by bacteria and fungi. The analysis showed that preemptive bathing extended the lesion-free duration by nearly 20 days. Furthermore, bathing in combination with a targeted antibiotic treatment represented a helpful treatment approach for diet-associated dermatitis. The provision of a methionine- and choline-deficient, high fat diet represents an effective approach for inducing NASH liver disease in pigs but predisposes study animals to multiple side effects. These side effects are universal to animals on study but can be adequately managed and do not represent a significant limitation of this model.

Comprehensive biomechanical and anatomical atherosclerotic plaque metrics predict major adverse cardiovascular events: A new tool for clinical decision making

Background and aimsAnatomical imaging alone of coronary atherosclerotic plaques is insufficient to identify risk of future adverse events and guide management of non-culprit lesions. Low endothelial shear stress (ESS) and high plaque structural stress (PSS) are associated with events, but individually their predictive value is insufficient for risk prediction. We determined whether combining multiple complementary, biomechanical and anatomical plaque characteristics improves outcome prediction sufficiently to inform clinical decision-making. MethodsWe examined baseline ESS, ESS gradient (ESSG), PSS, and PSS heterogeneity index (HI), and plaque burden in 22 lesions that developed subsequent events and 64 control lesions that remained quiescent from the PROSPECT study. Results86 fibroatheromas were analysed from 67 patients. Lesions with events showed higher PSS HI (0.32 vs. 0.24, p<0.001), lower local ESS (0.56Pa vs. 0.91Pa, p = 0.007), and higher ESSG (3.82 Pa/mm vs. 1.96 Pa/mm, p = 0.007), while high PSS HI (hazard ratio [HR] 3.9, p = 0.006), high ESSG (HR 3.4, p = 0.007) and plaque burden>70 % (HR 2.6, p = 0.02) were independent outcome predictors in multivariate analysis. Combining low ESS, high ESSG, and high PSS HI gave both high positive predictive value (80 %), which increased further combined with plaque burden>70 %, and negative predictive value (81.6 %). Low ESS, high ESSG, and high PSS HI co-localised spatially within 1 mm in lesions with events, and importantly, this cluster was distant from the minimum lumen area site. ConclusionsCombining complementary biomechanical and anatomical metrics significantly improves risk-stratification of individual coronary lesions. If confirmed from larger prospective studies, our results may inform targeted revascularisation vs. conservative management strategies.

Assessment of Patient Referrals with Large Numbers of Non-pedunculated Colorectal Lesions

Background: Large (≥20mm) non-pedunculated colorectal lesions are frequently referred to specialty centers for endoscopic resection. These lesions are technically challenging to resectand associated with substantially greater risk than smaller lesions. Patients with such polypsoften have synchronous lesions. We sought to identify evidence for whether synchronouslesions were sometimes the true basis for referral of large non-pedunculated colorectal polypsfrom community endoscopists to a tertiary center.&#x0D; Methods: We utilized a prospectively collected database of 1356 consecutive referred patients to an expert colonoscopist at our tertiary center between August 2019 and May 2023. We identified patients with ≥30 precancerous lesions resected from the colorectum during their first two colonoscopies at our center. Patients in the database with the same gender, within 3 yearsof age, and with the same location (proximal vs. distal colon) of the index large lesion referred for resection were identified as controls. Groups were compared for the size of index lesion, number of polyps resected by both centers, and size of polyps resected.&#x0D; Results: Among 1356 patients, 49 (3.6%) had ≥30 precancerous lesions resected at our center. Compared to controls, the index lesion was smaller in patients with ≥30 lesions (mean 28.9mmvs 23.3mm). Among patients with ≥30 synchronous polyps, the referring physician resected 10.6% of all synchronous lesions, compared to 47.8% in the control group (p&lt;0.0001). Inpatients with ≥30 lesions, 84% of all synchronous lesions were &lt;10mm, 15% were 10-19mm, and only 1% were &gt;20mm.&#x0D; Conclusion: Our results suggest a subset of patients with large non-pedunculated colorectal precancerous lesions referred to tertiary centers are referred because of the number of lesions present, rather than technical challenges associated with resection of individual lesions. The rationale for these referrals is uncertain. It may lie in the reimbursement system, which only compensates physicians for the first polypectomy.

Dynamics of cell membrane lesions and adaptive conductance under the electrical stress.

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca2+ entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a low 50- to 300-pS conductance, which disappeared instantly once the hyperpolarization was removed. Charging to -240 mV created high-conductance (> 1 nS) pores which persisted for seconds even at zero membrane potential. With incremental hyperpolarization steps, persistent pores often emerged at locations different from those where the short-lived, low-conductance pores or diffuse permeabilization were previously observed. Attempts to polarize membrane beyond the threshold for the formation of persistent pores increased their conductance adaptively, preventing further potential build-up and "clamping" it at a certain limit (-270 ± 6 mV in HEK cells, -284 ± 5 mV in CHO cells, and -243 ± 9 mV in neurons). The data suggest a previously unknown role of electroporative lesions as a protective mechanism against a potentially fatal membrane overcharging and cell disintegration.

Amebicides against Acanthamoeba castellanii: The Impact of Organism Models Used in Amebicide Assays

Acanthamoeba castellanii is a free-living amoeba capable of causing keratitis in humans, with most cases related to contact lens wearers and surgical procedures. In addition, A. castellanii may cause pneumonia, granulomatous encephalitis, and skin lesions in immunocompromised individuals. Considering the lack of adequate treatment for acanthamoebiasis, the aim of this review is to assess relevant original articles that covered the current arsenal of drugs and models of organisms used in the field of experimental A. castellanii infection that have been published within the last 5 years (2018–2023) in journals indexed by the following databases: Electronic Library Online (SciELO), PubMed, Medical Literature Analysis and Retrieval System Online (Medline), Latin American and Caribbean Literature in Health Sciences (Lilacs), Google Academic, and Capes Periodical Portal. Thirty articles were selected, and the main findings showed that the available therapeutics for acanthamoebiasis are still limited and nonspecific, and no innovations have occurred in the last few years. In terms of novel chemotherapeutic advances, the last findings have focused on the activity of natural products (plant-based extracts), nanoemulsions, coated particles, and photodynamic association against A. castellanii, without advancing from the bench to bedside perspective. The choice of a non-representative model system for acanthamoebiasis, as well as the limitations of studies in vivo, impairs the advancement of toxicity analyses. Efforts should be made to expand the model systems used, standardize tests for evaluating anti-A. castellanii drug candidates, and increase and support research groups focusing on the biology of A. castellanii and the pharmacology of acanthamoebiasis.

High-frequency ultrasonography: one of the modern imaging diagnostic methods in dermatology. Authors' own experience and review.

High-frequency ultrasonography (HFUS) has emerged as a non-invasive and cost-effective diagnostic tool for evaluating the outcomes of dermatological therapeutic procedures. This manuscript presents a comprehensive collection of sonographic images depicting cutaneous lesions associated with various dermatoses, including verruca vulgaris, epidermoid cyst, maculopapular cutaneous mastocytosis and lichen sclerosus et atrophicus. Drawing from an extensive review of the existing literature and supported by empirical observations, the study highlights key sonographic attributes observable in both normal and pathological skin variants. It has been demonstrated that individual skin lesions exhibit distinct characteristics on HFUS. Furthermore, ultrasonographic examination has proven to be valuable for the objective assessment of disease severity. Additionally, the study contributes to a deeper understanding of HFUS as a valuable tool in dermatological diagnostics.

Study on mid-term outcomes of atherectomy for patients with femoral popliteal artery lesions with different Global Limb Anatomic Staging System grades.

To investigate the mid-term efficacy and patency rate of TurboHawk peripheral plaque excision system in the treatment of femoral popliteal artery lesions with different Global Limb Anatomic Staging System (GLASS) grades. The clinical data of 141 patients with femoral popliteal arteriosclerosis obliterans who were treated with TurboHawk from January 2018 to July 2022 in our institution were retrospectively analyzed. There were 109 male patients and 32 female patients. Recordings were made of the patient's symptoms of limb ischemia, technical success rate, primary patency rate of target vessels, ankle brachial index (ABI), GLASS grades, postoperative complications, and a statistical analysis with the patient's preoperative treatment was conducted. All patients had improved limb ischemia symptoms to varying degrees after surgery, with a technical success rate of 100% (femoral artery puncture and superficial femoral artery recanalization) without bleeding, hematoma, pseudoaneurysm, arteriovenous fistula or other complications. The follow-up period was 1-24 months, during which the severity of claudication, resting pain, and toe ulcers significantly improved. The primary patency rate of the target vessel was 98.58% (139/141), and the ABI significantly increased on the second day, three months, and six months after surgery compared to before surgery. No major adverse events were found during follow-up. The patency rates at 1, 6, 12 and 24 months after intervention were 100%, 80%, 75% and 60% respectively. The mid-term efficacy and patency rate of TurboHawk in the treatment of femoral popliteal artery lesions with GLASS I patients have the best mid-term prognosis, the highest mid-term survival rate, and the highest vascular patency. The plaque removal system has proven to be an effective treatment for individual localized chronic total occlusion lesions. Additionally, the TurboHawk system provides a safe and minimally invasive treatment alternative for superficial femoral artery conditions, achieving significant therapeutic results within a brief period.

Imaging in immunotherapy for tumor diseases

Immunotherapeutic agents and in particular immune checkpoint inhibitors (ICI) have opened up extensive new therapeutic possibilities in oncology over the last decade. For numerous entities these substances have improved the clinical outcome, sometimes as monotherapy but also in combination with cytostatic or targeted treatment. In routine clinical practice the type of radiological response often differs from what is seen under cytostatic treatment: amixed response of individual lesions is more frequently observed and occasionally also aresponse after an initial progress (so-called pseudoprogression). Furthermore, there is adiverse spectrum of toxicity in the form of immune-related adverse events (irAE), which is observed in large temporal variability to the application. Therefore, early detection and rapid side effect management are essential.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers. Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase. PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Intrahepatic splenosis: Contrast enhanced ultrasound and magnetic resonance imaging findings.

To evaluate the contrast enhanced ultrasound (CEUS) and contrast enhanced magnetic resonance imaging (CEMRI) features of intrahepatic splenosis (IHS). Five patients (three males and two females, median age, 44 years; range,32-73 years) with seven IHSs were retrieved from the database of our hospital from March 2012 to October 2021. All IHSs were confirmed histologically by surgery. The CEUS and CEMRI characteristics of individual lesion were fully analyzed. All IHS patients were asymptomatic and four out of five patients had history of splenectomy. On CEUS, all IHSs were hyperenhancement in arterial phase. 71.4% (5/7) of IHSs manifested overall filling within few seconds, the other two lesions showed centripetal filling. Subcapsular vascular hyperenhancement and feeding artery was seen in 28.6% (2/7) and 42.9% (3/7) of IHSs, respectively. During portal venous phase, IHSs presented hyperenhancement (2/7) or isoenhancement (5/7). Moreover, rim-like hypoenhanced area was uniquely observed surrounding 85.7% (6/7) of IHSs. In late phase, seven IHSs remained continuous hyper- or isoenhancement. On CEMRI, five IHSs showed mosaic hyperintense in early arterial phase, the other two lesions showed homogeneous hyperintense. In portal venous phase, all IHSs revealed continuous hyper- (71.4%, 5/7) or iso-intense (28.6%, 2/7). During late phase, one IHS (14.3%, 1/7) became hypointense, the other lesions remained hyper- or isointense. Diagnosis of IHS can be based on typical CEUS and CEMRI features in patients with history of splenectomy.

Phytocompounds from Phyllanthus acidus (L.) Skeels in the management of Monkeypox Virus infections

Monkeypox is a communicable disease similar to smallpox, primarily occurring in African countries. However, recently it has spread to countries outside Africa and may arise as the next threat after COVID-pandemic. The causative organism, i.e. Monkeypox Virus (MPV) spreads from one individual to another primarily through inhalation of respiratory droplets or through contact with skin lesions of infected individuals. No known drugs are available specifically for MPV. Due to its similarity with smallpox, treatment of monkeypox is being attempted through the administration of the smallpox vaccine. Therefore, we evaluated the efficacy of the plant Phyllanthus acidus against MPV since it is traditionally used in the treatment of chickenpox and smallpox. Through functional annotation, PASS prediction and Network pharmacology analysis, the effectiveness of these chosen P. acidus-derived phytocompounds against MPV was confirmed. Target prediction of the phytocompounds identified in GC-MS analysis of the plant extract showed them to be associated with 76 human proteins. The compounds also show good binding affinity with selected viral proteins: DNA polymerase (DNApol), Putative Virulence Factor (vPVF) and Cytokine Binding Protein. Prediction of Activity Spectra for Substances (PASS) and functional annotation of the target proteins further support their antiviral nature through interaction with these proteins. The compounds were found to modulate pathways related to symptoms of viral infection and this may help in maintaining homeostasis. Our study demonstrates antiviral activity as well as the therapeutic potential of the plant against MPV infection.Communicated by Ramaswamy H. Sarma

Validating the association of Oxford classification and renal function deterioration among Taiwanese individuals with Immunoglobulin A nephropathy

Validation of the Oxford classification (MEST and MEST-C) for Immunoglobulin A nephropathy (IgAN) in the Taiwanese population is lacking. Our study aimed to validate this classification and assess individual lesion impact. We conducted a retrospective cohort study at Taichung Veterans General Hospital, Taiwan (Jan 2011–Jul 2023). Composite renal outcomes were evaluated using clinical conditions and estimated glomerular filtration rate (eGFR). We used Kaplan–Meier, univariable/multivariable logistic regression and ROC curves. Subgroup analysis considered eGFR < or ≥ 30.0 ml/min/1.73 m2. In 366 renal biopsies, serum creatinine was 1.34 mg/dl, eGFR 53.8 ml/min/1.73 m2, urine protein–creatinine ratio 1159 mg/g. T1/T2 lesions had lowest baseline eGFR (39.6/11.5 ml/min/1.73 m2), correlating with poorest renal survival (median survival 54.7/34.4 months). Univariable analysis linked all individual variables to worse renal outcomes. Multivariable analysis (MEST/MEST-C) showed only T1/T2 linked to worse outcomes. T score had highest predictive power (AUC 0.728, sensitivity 60.2%, specificity 83.6%), with MEST having high AUC (0.758). No extra predictive power was seen transitioning MEST to MEST-C. Subgroup analysis (eGFR < 30.0 ml/min/1.73 m2) associated C1 with improved renal outcomes (odds ratio 0.14, 95% CI 0.03–0.65). T lesion correlated with worse outcomes across subgroups. The T lesion consistently correlated with worse renal outcomes across all groups and baseline statuses. Integrating the C lesion into the transition from MEST to MEST-C did not enhance predictive power. Importantly, the C1 lesion was linked to improved renal outcomes in the eGFR < 30.0 ml/min/1.73 m2 subgroup, likely due to treatment effects.

Early detection of white matter hyperintensities using SHIVA-WMH detector.

White matter hyperintensities (WMHs) are well-established markers of cerebral small vessel disease, and are associated with an increased risk of stroke, dementia, and mortality. Although their prevalence increases with age, small and punctate WMHs have been reported with surprisingly high frequency even in young, neurologically asymptomatic adults. However, most automated methods to segment WMH published to date are not optimized for detecting small and sparse WMH. Here we present the SHIVA-WMH tool, a deep-learning (DL)-based automatic WMH segmentation tool that has been trained with manual segmentations of WMH in a wide range of WMH severity. We show that it is able to detect WMH with high efficiency in subjects with only small punctate WMH as well as in subjects with large WMHs (i.e., with confluency) in evaluation datasets from three distinct databases: magnetic resonance imaging-Share consisting of young university students, MICCAI 2017 WMH challenge dataset consisting of older patients from memory clinics, and UK Biobank with community-dwelling middle-aged and older adults. Across these three cohorts with a wide-ranging WMH load, our tool achieved voxel-level and individual lesion cluster-level Dice scores of 0.66 and 0.71, respectively, which were higher than for three reference tools tested: the lesion prediction algorithm implemented in the lesion segmentation toolbox (LPA: Schmidt), PGS tool, a DL-based algorithm and the current winner of the MICCAI 2017 WMH challenge (Park et al.), and HyperMapper tool (Mojiri Forooshani et al.), another DL-based method with high reported performance in subjects with mild WMH burden. Our tool is publicly and openly available to the research community to facilitate investigations of WMH across a wide range of severity in other cohorts, and to contribute to our understanding of the emergence and progression of WMH.

The course of arterial hypertension in patients with type 2 diabetes after surgical treatment of carotid artery stenotic lesions

Background. Arterial hypertension (AH) is the cause of 70–75 % of strokes. Atherosclerotic lesion of the carotid artery (CA) is a classic example of a vascular lesion in individuals with hypertension. The risk of stroke increases twice when hypertension and diabetes are combined. Carotid endarterectomy (CA), which has both a curative and preventive nature, is the main method of surgical treatment of CA stenoses. The purpose was to study the course of blood pressure in patients with type 2 diabetes and without it after CE. Materials and methods. 138 patients with arterial hypertension and CA stenosis were selected for the purpose of CE under local anesthesia. Patients were divided into two groups: 68 patients with type 2 diabetes (group I) and 70 patients without diabetes (group II). The median age of patients in group I was 64 [50–71] years, group II — 63.5 [47–68] years. Daily blood pressure monitoring (BPD) was performed 2 days before surgery (1 examination), 5–7 days after surgery (2 examinations) and 3–6 months after CE (3 examinations). The average indicators of systolic blood pressure (SBP) and diastolic blood pressure (DBP) per day, day, and night were evaluated; average pulse blood pressure (BP); variability of SBP and DBP per day, day, night. Results. Before the operation, group I, in contrast to group II, recorded significantly higher indicators: SATdb (p = 0.02), SATd (p = 0.03), SATn (p = 0.01), DBTn (p &lt; 0, 05), PAT (p = 0.03), varDATdb (p = 0.03), varSATd (p = 0.03), varDATn (p = 0.04). During the second examination in group II, significantly more significant dynamics of DMAT indicators were noted: SATdb (p = 0.002), SATd (p = 0.02), DAPdb (p = 0.002), DAPd (p = 0.01), DAPn (p = 0.03), varSATn (p &lt; 0.04), varDATn (p &lt; 0.05), varSATdb (p = 0.0002), varDATdb (p = 0.0001). The dynamics of PAT and midnight SAT were insignificant. 3 months after KE, all mean values of SBP and DBP, as well as PAT, decreased significantly in patients of group II. The expressiveness of changes in SBP indicators during the day, day and night, as well as indicators of SBP variability in group II was more significant. During the third examination, the proportion of patients with a "dipper" circadian rhythm increased in the two groups (p &lt; 0.05). In group II, the proportion of patients with an unfavorable type of daily profile "over-dipper" significantly decreased (p &lt; 0.001), which did not occur in group I. Conclusions. Surgical treatment of carotid stenoses in patients with and without type 2 diabetes is associated with a decrease in blood pressure in the early postoperative period and is observed for several months after the operation.

Gene Correction of DNMT3A:R882H in Primary Human AML Demonstrates That This Mutation Is Not Required for Disease Maintenance, but Is Associated with Increased Leukemia Stem Cell Frequency

Introduction: The genetic landscape of AML comprises numerous genetic alterations contributing to disease initiation and progression. Among these lesions, frequently occurring missense variants in DNMT3A:R882 are typically found as pre-leukemic events. An important and understudied question in leukemia pathogenesis is whether individual mutations are required for disease initiation, maintenance of established disease, or both. This is particularly the case with pre-leukemic mutations that affect the epigenome, as such mutations might be required to provide the epigenetic background necessary for disease initiation, but may no longer be required for disease maintenance. Here, we dissect the contribution of DNMT3A mutations to leukemic initiation and maintenance by gene correction in primary patient AML specimens. Methods: To functionally interrogate the contribution of DNMT3A mutations in human AML pathogenesis, we generated a novel CRISPR/Cas9-mediated toolset to selectively and specifically revert DNMT3A:R882 missense variants back to wildtype, or re-introduce the original mutation as a control, directly in both primary pre-leukemic HSCs (pHSCs) and primary leukemic blasts from 7 patient samples, leaving the remaining mutations and underlying germline background intact. Gene-corrected or re-mutated cells were subjected to functional assays both in vitro and in vivo. Results: We demonstrate that correction of DNMT3A mutations is feasible, achieving 5-40% gene editing both in purified pHSCs and leukemic blasts (n=7 patient samples). Using this approach, we first establish that DNMT3A mutations confer increased stemness in human pHSCs, with increasing serial replating capacity (mean increase re-mutated vs. corrected 5.53-fold, p&amp;lt;0.05). Surprisingly however, correction of DNMT3A mutations in leukemic blasts led to no immediate functional consequences. Specifically, primary patient leukemic blasts corrected for DNMT3A mutations retained the ability to engraft leukemia in NSGS mice and showed no difference in human chimerism or immunophenotype compared to re-mutated control from 5/5 primary patient samples. Importantly, limiting dilution transplantation assays (LDA) with two cases revealed no impact of DNMT3A mutations on leukemia-initiating cell (LIC) frequency in primary recipients, highlighting that DNMT3A mutations have no immediate effect on disease maintenance. We then performed whole-genome bisulfite sequencing and RNA-sequencing on leukemic blasts isolated from engrafted mice 4 months after DNMT3A correction or re-mutation. Global methylation levels between corrected and re-mutated cells were within the variance in either of these groups, and gene expression profiles were similarly driven by patient. However, paired analysis of each patient sample revealed that DNMT3A correction led to a consistent loss of stem cell expression signatures, suggesting influence of DNMT3A mutations on leukemia stem cell programs. Thus, we interrogated the effect of DNMT3A mutations on LSCs by performing secondary transplantations with two cases. In LDA assays, we observed a significant decrease in LIC frequency in the corrected leukemic blasts compared to re-mutated controls, indicating that correction of DNMT3A mutations induces a reduction in leukemia stem cell frequency, but does not completely abrogate leukemogenic potential. Conclusion: In summary, our work demonstrates a novel CRISPR/Cas9 approach to dissect the contribution of individual somatic lesions in human leukemia. The precise correction of single lesions while leaving co-occurring mutations intact allows us to perform controlled, functional genetic experiments on primary human AML. Here, we employ this approach to dissect the contribution of DNMT3A mutations to leukemia initiation and maintenance. We find that DNMT3A mutations impart increased stemness on human pHSCs, consistent with a key role in leukemia initiation. However, in primary patient blasts, we find that DNMT3A mutations are not required for leukemia maintenance. Strikingly, DNMT3A mutations in established leukemia were found to increase leukemia stem cell frequency. This approach will now allow for a detailed evaluation of differential methylation in mean and entropy and can be extended to other mutations of interest, extending our toolkit to unravel human AML biology directly in primary cancer specimens.