Subsequent Lesions Research Articles

Theta-burst transcranial magnetic stimulation attenuates chronic ischemic demyelination and vascular cognitive impairment in mice

Vascular cognitive impairment and dementia (VCID) is mainly caused by chronic cerebral hypoperfusion and subsequent white matter lesions. Noninvasive transcranial magnetic stimulation has been utilized in treating various neurological disorders. However, the function of theta-burst transcranial magnetic stimulation on VCID remains to be defined. We utilized 4-week bilateral carotid artery stenosis model of male mice to mimic VCID. Intermittent theta-burst stimulation (iTBS) or consecutive theta-burst stimulation (cTBS) was administered for 14 consecutive days. Through luxol fast blue staining, electron microscopy and immunofluorescence, we found that iTBS, not cTBS, significantly improved demyelination, axonal damage and β-amyloid deposition, without affecting cerebral blood flow in VCID mice. At cellular levels, iTBS rescued the loss of mature oligodendrocytes, promoted precursor cell differentiation, and inhibited pro-inflammatory activation of astrocytes and microglia. Notably, iTBS attenuated cognitive deterioration in both short-term retention and long-term spatial memory of VCID mice as indicated by serial neurobehavioral tests. To explore the molecular involvement of iTBS, mRNA sequencing was carried out. By real-time PCR and combined RNA fluorescence in situ hybridization with immunofluorescence, iTBS was confirmed to increase Rxrg expression specifically in mature oligodendrocytes. Collectively, iTBS could ameliorate vascular cognitive dysfunction, probably via mitigating white matter lesions and neuroinflammation in the corpus callosum. Rxrg signaling in mature oligodendrocytes, which was increased by iTBS, might be a potential target for VCID treatment.

HPV Infection and Prevention in Patients With Immune-Mediated Inflammatory Diseases: A Scoping Review.

Human papillomavirus (HPV) infections are a significant public health concern as they cause various cancers, including those of the cervix, vulva, vagina, anus, penis, and oropharynx, in both women and men. Individuals with immune-mediated inflammatory diseases, particularly systemic lupus erythematosus, have an increased risk of developing persistent HPV infection and subsequent precancerous lesions due to their immunosuppression. Vaccination and screening for precancerous lesions are 2 central management strategies that must be implemented in patients with immune-mediated inflammatory diseases. Although HPV vaccination has been proven to be safe and effective in these patients, coverage remains low and should be encouraged. Screening for cervical cancer should be more widely implemented in this population, as recommended in guidelines for other immunosuppressed patients. Catch-up vaccination, vaginal self-sampling screening for HPV detection, and therapeutic vaccination are new options that should be considered.

Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS.

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2-22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy.

Pulmonary abscess secondary to epididymitis caused by extended spectrum β-lactamase-producing hypervirulent Klebsiella pneumoniae: a case report

BackgroundPulmonary abscesses resulting from epididymitis caused by extended spectrum β-lactamase-producing hypervirulent Klebsiella pneumoniae (ESBL-hvKp) in a nondiabetic patient are extremely uncommon. The infection caused by this disseminated drug-resistant bacteria, which is generally considered an intractable case, poses a potential challenge in clinical practice.Case presentationIn this case report, we present the clinical course of a 71-year-old male patient with epididymitis, who subsequently developed cough and dyspnea following anti-infection treatment. Imaging examinations revealed severe pneumonia and pulmonary abscess. The infection of ESBL-hvKp in the epididymis led to bacteremia and subsequent lung lesions. Due to poor response to anti-infection therapy, the patient required an extended duration of anti-infection treatment and ultimately chosed to discontinue treatment.ConclusionsAcute epididymitis caused by ESBL-hvKP infection can result in the spread of the infection through the bloodstream, leading to severe pneumonia and lung abscess. Given the critical condition of the patient, even with active anti-infection treatment, there is a risk of treatment failure or potentially fatal outcomes.

Descriptive evaluation of a camera-based dairy cattle lameness detection technology

Lameness in dairy cattle is a clinical sign of impaired locomotion, mainly caused by painful foot lesions, compromising the US dairy industry's economic, environmental, and social sustainability goals. Combining technology and on farm data may be a more precise and less labor-intensive lameness detection tool, particularly for early detection. The objective of this observational study was to describe the association between average weekly autonomous camera-based (AUTO) locomotion scores and hoof trimming (HT) data. The AUTO data were collected from 3 farms from April 2022 to March 2023. Historical farm HT data were collected from March 2016 to March 2023 and used to determine cow lesion history and date of HT event. The HT events were categorized as a regular HT (TRIM; n = 2290) or a HT with a lesion recorded (LESION; n = 670). Events with LESION were sub-categorized based on lesion category: digital dermatitis (DD; n = 276), sole ulcer (SU; n = 79), white line disease (WLD; n = 141), and other (n = 174). The data also contained the leg of the LESION, classified as front left (FL; n = 54), front right (FR; n = 146), rear left (RL; n = 281), or rear right (RR; n = 183) leg with 6 events missing the leg. Cows' HT histories were classified as follows: cows with no previous recorded instance of any lesion were classified as TRIM0 (n = 1554). The first instance of any hoof lesion was classified as LESION1 (n = 238). This classification was retained until a subsequent TRIM occurred - recorded as TRIM1 (n = 632). The next unique instance of any lesion following a TRIM1 was classified as LESION2 (n = 86). Any LESION events occurring after LESION1 or LESION2 without a subsequent TRIM were considered a hoof lesion recurrence and classified as LESIONRE1 (n = 164) and LESIONRE2 (n = 22), respectively. TRIM events after LESION2 or LESION2RE (n = 104) or LESION events after LESIONRE1 or LESIONRE2 were classified as LESION_OTHER (n = 160). The AUTO scores from -28 to -1 days prior to the HT event were summarized into weekly scores and included if cows had at least 1 observation per week in the 4 weeks before the event. For all weeks, LESION cows had a higher median AUTO score than TRIM cows. Cows with TRIM0 had the lowest and most consistent median weekly score compared to LESION and other TRIM classifications. Before HT cows with TRIM0 and TRIM1, both had median score increases of 1 across the 4 weeks, while the LESION categories had an increase of 4 to 8. Scores increased with each subsequent LESION event compared to the previous LESION event. Cows with SU lesions had the highest median score across the 4 weeks, WLD had the largest score increase, and DD had the lowest median score and score increase. When grouping a LESION event by leg the hoof lesion was found on, the AUTO scores for four groups displayed comparable median values. Due to the difference between TRIM and LESION events, this technology shows potential for the early detection of hoof lesions.

Retroperitoneal laparoscopic radical nephrectomy in the treatment of renal cancer: a 5-year single-center experience in resource-scare setting

Based on a retrospective hospital-based analysis, this study examines the results of retroperitoneal laparoscopic radical nephrectomy for patients with T1-T2 renal cell carcinoma (RCC) from January 2019 to December 2023. Of the 73 patients, 4.1% had TNM stage II tumors and 95.8% had TNM stage I tumors (53.4% T1a and 42.4% T1b). In terms of frequency, clear cell RCC accounted for 84.9%, with papillary RCC coming in at 9.6% and chromophobe RCC at 4.1%. Following surgery, four patients experienced fevers, one needed a blood transfusion, two had infections, and one had emergency surgery. Lumbar masses and hematuria were absent in all patients. Subsequent metastatic lesions and abnormalities of the renal fossa were not observed on follow-up ultrasounds. 4.1% of the deaths after 25.9 months were due to the disease, and 1.4% were caused by accidents. At one, two, three, and four years, the cumulative survival rates were 100%, 97.2%, and 92.8%, respectively. 48.1 months was the mean postoperative survival period. For RCC stages T1-2, retroperitoneal laparoscopic radical nephrectomy offers significant benefits and comparable results to open surgery.

The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) Project: An Expert Panel Opinion.

Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.

Deciphering the pathogenesis of melanized focal changes in the white skeletal muscle of farmed Atlantic salmon (Salmo salar).

Melanized focal changes (MFCs) in the fillet of farmed Atlantic salmon is a major quality concern. The changes are thought to initially appear as acute red focal changes (RFCs) that progress into chronic MFCs. Recent findings have indicated that hypoxia may be important in their development, possibly leading to necrosis affecting not only myocytes but also adipocytes. Thus, the aim of this study was to investigate possible hypoxic conditions in RFCs and the subsequent inflammatory responses and lesions in the adipose tissue in RFCs and MFCs. A collection of RFCs, MFCs and control muscle samples from several groups of farmed salmon was studied. Using immunohistochemistry, we found induction of the hypoxia-inducible factor 1 pathway in RFCs. Histological investigations of RFCs and MFCs revealed different stages of fat necrosis, including necrotic adipocytes, a myospherulosis-like reaction and the formation of pseudocystic spaces. Accumulations of foamy macrophages were detected in MFCs, indicating degradation and phagocytosis of lipids. Using insitu hybridization, we showed the presence of tyrosinase- and tyrosinase-related protein-1-expressing amelanotic cells in RFCs, which in turn became melanized in MFCs. In conclusion, we propose a sequence of events leading to the formation of MFCs, highlighting the pivotal role of adiposity, hypoxia and fat necrosis.

Healing of periapical lesion by non-surgical endodontic therapy: A case series

Trauma to the anterior teeth can lead to pulp necrosis and subsequent periapical lesions. Most of the cases remain undetected unless found in an IOPAR, the tooth gets discoloured or gets secondarily infected. In such cases, non-surgical endodontic therapy can be done as the first line of management with regular follow up. Surgical approach is indicated only if the non- surgical approach becomes a failure. A series of two cases with large periapical lesion following trauma to the maxillary anteriors were treated with multivisit non –surgical endodontic therapy. Inter-appointment dressings were given. Patients were recalled for evaluation of healing. Six months follow up radiographs showed healing of the lesion with significant increase in the radiopacity suggestive of bony healing. For the treatment of periapical lesions, non-surgical endodontic therapy should be considered as first line treatment option as it proves to be a more conservative approach.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Hemodynamic coupling between a primary atherosclerotic plaque and subsequent secondary lesions

Atherosclerosis is one of the most common diseases of the arterial tree, especially in the coronary arteries. Stenoses exceeding 50% area reduction are shown to alternate the downstream coronary flow, and hemodynamics will lead to further atherogenesis. Clinical evidence also confirms that vascular stenoses are not stagnant since they are usually associated with downstream lesions. In this study, it is hypothesized that the formation of secondary plaques, or aneurysms downstream of a primary stenosis, compensates for the abnormal ranges of hemodynamic forces caused by the primary stenosis. An experimental setup captured the hemodynamics of non-Newtonian blood flow in three-dimensional (3D) printed phantoms of coronary arteries with various sequences of lesions. Then, based on the collected data, in silico models of these lesions were simulated using computational fluid dynamics. For the proposed cases, time-averaged wall shear stress, velocity profile, oscillatory shear index, and relative residence time were extracted at the plaque side and the plaque front walls and compared to the reference model with only the primary plaque. The secondary plaque postulated the abnormal hemodynamic conditions to its downstream, which implies endothelial activation and onset of further pathologic events. However, the secondary aneurysm restored flow conditions to normal after its distal shoulder, preventing more damage to the endothelium. Examined angiograms of patients with developed atherosclerotic lesions unveiled that a sequence of plaques is formed over time, and most interestingly, the series stopped after the formation of an aneurysm.

Influence of cervical treatment methods on subsequent vaginal lesions: A study of HPV-related neoplasia.

The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key precancerous conditions in women. This study investigates the influence of different cervical treatment methods on the rate of subsequent vaginal neoplasia. It also considers age and menopausal status as risk factors for higher-grade VaIN and the role of persistent HPV infections in the development of new VaIN cases post-treatment. The cohort consisted of 275 female patients treated for CIN, with a follow-up period of six months including HPV and ThinPrep cytologic test (TCT) testing. The evaluated treatments included laser therapy, cervical conization, loop electrosurgical excision procedure (LEEP), and radical hysterectomy. Statistical analysis was performed using SPSS 26.0 to determine treatment efficacy, the impact of age and menopausal status, and the relationship between HPV clearance and VaIN outcomes. Radical hysterectomy was linked with a higher recurrence of VaIN. Additionally, patients over 50 years old and those who were postmenopausal were significantly more likely to develop more severe VaIN and persistent HPV infections. Persistence of HPV after treatment was linked to a higher incidence of new VaIN cases. High-risk HPV significantly increased the recurrence of VaIN, with no significant link found between TCT results and VaIN severity. Therefore, selecting appropriate cervical lesion treatment, considering the patient's age and menopausal status, and managing HPV infections are essential in preventing and managing the risk and progression of VaIN. Radical hysterectomy showed a distinct increase in VaIN incidence, emphasizing the need for individualized clinical assessments.

Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer.

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.

Sulfuric Acid Ingestion: May the Severity of the Metabolic Acidosis be Considered as a Predictive Sign of Late Damage to the Gastrointestinal Tract?

Caustic substances ingestion results in a complex syndrome. The patient characteristics and severity of injury are important prognostic predictors. The monitoring of clinical changes and the multidisciplinary approach are necessary to prevent death in the early stages of the poisoning. The case report describes the suicide of a woman by ingestion of a large amount of 15% sulfuric acid for suicidal purposes (15-20 ml). The initial conditions were stable, and no changes were found on a CT scan. However, the main sign was a severe metabolic acidosis. After 7 hours, haematemesis and oedema of the larynx appeared, and oro-tracheal intubation and ICU admission were necessary. Consequent progressive haemodynamic deterioration with persistent severe metabolic acidosis, increasing lactates and septic shock appeared. A new CT scan with contrast was performed 22 hours later detecting diffuse perforations and liquid in pleurae and abdomen. A pleural sample showed necrotic liquid. The death was 24 hours after ingestion and no surgical treatment was performed because of the diffuse lesions to the thoracoabdominal districts. Early detection of gastroenteric lesions and the monitoring of clinical changes are mandatory to avoid the death of the patient. Gastroenteric perforations require an immediate radiological evaluation and surgical treatment. The clinical case report states the severity of prognosis was related to high doses of sulfuric acid ingestion. The immediate metabolic acidosis is related to quick subsequent severe systemic pathological lesions of the gastrointestinal tract. The severity of absorption metabolic acidosis, consequently, may be an early and prognostic sign of the late chest and abdominal lesions. Severity of metabolic acidosis after sulfuric acid ingestion may anticipate late damage to the gastrointestinal tract.

Adaptive mask-based brain extraction method for head CT images.

Brain extraction is an important prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion identification, localization, and segmentation. To address the problem that the current traditional image segmentation methods are fast in extraction but poor in robustness, while the Full Convolutional Neural Network (FCN) is robust and accurate but relatively slow in extraction, this paper proposes an adaptive mask-based brain extraction method, namely AMBBEM, to achieve brain extraction better. The method first uses threshold segmentation, median filtering, and closed operations for segmentation, generates a mask for the first time, then combines the ResNet50 model, region growing algorithm, and image properties analysis to further segment the mask, and finally complete brain extraction by multiplying the original image and the mask. The algorithm was tested on 22 test sets containing different lesions, and the results showed MPA = 0.9963, MIoU = 0.9924, and MBF = 0.9914, which were equivalent to the extraction effect of the Deeplabv3+ model. However, the method can complete brain extraction of approximately 6.16 head CT images in 1 second, much faster than Deeplabv3+, U-net, and SegNet models. In summary, this method can achieve accurate brain extraction from head CT images more quickly, creating good conditions for subsequent brain volume measurement and feature extraction of intracranial lesions.

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.

Decreased Lung Metastasis in Triple Negative Breast Cancer Following Locally Delivered Supratherapeutic Paclitaxel-Loaded Polyglycerol Carbonate Nanoparticle Therapy.

Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, current treatments are insufficient for treating or preventing metastatic disease. Herein, we describe supratherapeutic paclitaxel-loaded nanoparticles (81 wt % paclitaxel) to treat the primary tumor and reduce the risk of subsequent metastatic lesions in the lungs. Primary tumor volume and lung metastasis are reduced by day 30, compared to the paclitaxel clinical standard treatment. The ultrahigh levels of paclitaxel afford an immunotherapeutic effect, increasing natural killer cell activation and decreasing NETosis in the lung, which limits the formation of metastatic lesions.

Pancoronary plaque characteristics in STEMI patients with rapid plaque progression: An optical coherence tomography study

BackgroundNon-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level. Methods and resultsFrom January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old. ConclusionsSTEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.