Lesion Thickness Research Articles

FC24 Zasocitinib (TAK-279), an oral, allosteric, highly selective TYK2 inhibitor, modulates disease-central cytokine pathways that define clinical response in patients with moderate-to-severe plaque psoriasis

Abstract Zasocitinib (TAK-279) demonstrated promising efficacy and was generally well tolerated in a completed Phase 2b study (NCT04999839) in patients with moderate-to-severe plaque psoriasis, with the primary endpoint [75% improvement in psoriasis area and severity (PASI75)] achieved at doses ≥5 mg vs. placebo at Week 12. In an exploratory analysis of this study, associations between zasocitinib treatment, psoriasis/tyrosine kinase 2 (TYK2) biomarkers, and clinical/histological response were investigated. Lesional/non-lesional serum samples and skin biopsies were obtained with consent at Day 1 (pre-dose) and Weeks 4 and 12 from patients receiving zasocitinib (2, 5, 15, and 30 mg) or placebo orally once daily. RT-qPCR, RNA-seq and immunohistochemistry were used to assess changes in lesion keratinocyte proliferation (KRT16 expression), psoriasis/TYK2 biomarkers and lesion gene signatures, and their associations with clinical (PASI75) and histological (plaque resolution) response. Serum samples from 252 patients and biopsy samples from 63 patients were analysed. At Week 12, most clinical responders (n = 21/24, 88%) experienced reductions in KRT16 expression of >87% vs. baseline lesion levels. Pooled analysis showed that, in most histological responders (n = 18/25, 72%), interleukin (IL)17A and IL17F expression reduced by >80% vs. baseline lesion levels. Reductions in lesional type I interferon, IL-12 and IL-23 pathway gene expression were observed at zasocitinib 15 and 30 mg doses compared with baseline levels (P < 0.05). Dose- and time-dependent reductions in serum IL-17A, IL-17C and IL-17F were observed in all zasocitinib groups vs. placebo. In the 15 and 30 mg groups (n = 23), expression of key psoriasis/TYK2 biomarkers (e.g. DEFB4A, IL36G, IL23A) reverted to non-lesional levels at Week 12. Among evaluable PASI90 responders at Week 12 (n = 12), 48/50 of the top upregulated genes in lesions reverted to non-lesional expression levels. In all dose groups, patients had reduced lesional epidermal thickness, CD3+ T-cell counts and CD11c+ myeloid dendritic cell counts with zasocitinib vs. baseline. Zasocitinib treatment did not result in clinically meaningful longitudinal changes in laboratory parameters associated with Janus kinase inhibition. Zasocitinib modulated psoriasis/TYK2 biomarkers were associated with clinical and histological response in patients with moderate-to-severe plaque psoriasis.

Evaluating the Cavitary Lung Lesions on CT Scan of COVID-19 Patients: A Retrospective Study.

It has been shown that cavitary lesions on CT scans of patients with COVID-19 may be related to their clinical symptoms and mortality rate. The study population included patients diagnosed with COVID-19 based on RT-PCR results from throat samples or typical clinical and chest CT scan findings who were hospitalized at Sina Hospital in Tehran in 2020 and underwent chest CT scans. Chest CT scans were examined for the severity of pulmonary opacities and the presence, number, size, wall thickness, and distribution of cavitary lung lesions. Oxygen saturation was lower in patients with cavitary lesions in the initial state and after treatment than those without cavitation, and a statistically significant relationship was observed (p < 0.05). In terms of gender, a significant correlation was observed, and the prevalence of cavitary lesions was higher in men (p < 0.05). Also, the in-hospital mortality rate was higher in patients with cavitary lesions (p < 0.05). Based on our results, the presence of cavitary lung lesions in COVID-19 patients is related to the mortality rate, severity of pulmonary involvement, and patients' gender.

Fovea-Sparing Internal Limiting Membrane (ILM) Peeling and ILM Plug: A Novel Approach for Managing Optic Disc Pit Maculopathy.

To evaluate the efficacy of fovea-sparing internal limiting membrane (ILM) peeling combined with ILM plug placement in patients with optic disc pit maculopathy (ODP-M). This retrospective study included seven eyes from seven patients diagnosed with ODP-M, treated with fovea-sparing ILM peeling and ILM plug placement. All patients underwent pars plana vitrectomy (PPV), with either SF6 gas or silicone oil used as tamponade. Outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), retinal reattachment, and resolution of retinoschitic lesions (RL). Data were collected at baseline and during follow-ups at 1, 3, 6, and 12 months. The mean age of the study patients was 31 (± 13.14) years, with a marginal male preponderance (M: F = 4:3). All patients achieved complete retinal reattachment, with a significant reduction in CMT from 503.57 (± 154.74) µm preoperatively to 286.29 (± 22.43) µm at 12 months (P=0.02). BCVA improved in 85.7% of patients, from a mean of 0.77 (± 0.19) logMAR to 0.5 (± 0.25) logMAR by 12 months, though this was not statistically significant (P=0.27). Complete resolution of RL was observed in 71.4% of eyes, while 2 eyes showed partial resolution. One patient developed retinal detachment postoperatively, which was successfully managed with additional surgery. Fovea-sparing ILM peeling combined with ILM plug placement resulted in favorable anatomical and functional outcomes for ODP-M patients, with a 100% retinal reattachment rate and significant CMT reduction. This technique offers a viable alternative to conventional approaches, preserving foveal architecture while providing a mechanical barrier to fluid accumulation.

Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.

Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD. AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ. ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade. ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.

Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles.

Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton's jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJ-MSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.

Liquid nitrogen cryotherapy effectively and safely improves response of thick actinic keratoses lesions by 5-aminolevulinic acid-based photodynamic therapy: A randomized, prospective, single-blind trial

BackgroundActinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT). ObjectiveThis study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis. MethodsA total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group (LN-PDT) and control PDT group (C-PDT) with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups. Results3 months after the final treatment, the clearance rates for total AK lesions were 97.4 % (449/461) in the LN-PDT group and 93.4 % (456/488) in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2 % (234/237) for the LN-PDT group and 98.3 % (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5 % (156/160) for the LN-PDT group and 91.9 % (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5 % (58/64) and 78.7 % (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference. ConclusionLiquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes.

Importance of gap evaluation in the ossification of posterior longitudinal ligament lesions using 3-dimensional computed tomography

BACKGROUND CONTEXTEvaluating the gaps within the ossification of the posterior longitudinal ligament (OPLL) lesions, which may contribute to neurological symptoms, using conventional imaging techniques is challenging. OBJECTIVEThis study aimed to investigate the importance of evaluating gaps using 3-dimensional computed tomography (3D-CT) and their association with the occurrence of magnetic resonance imaging (MRI) T2 high intensity in the spinal cord. STUDY DESIGN/SETTINGRetrospective cohort study. PATIENT SAMPLERetrospective analysis of 116 patients diagnosed with cervical OPLL. OUTCOME MEASURESPresence of gaps in OPLL, presence of T2 high intensity in the cervical spinal cord, and OPLL thickness were evaluated. METHODSLateral X-ray, CT, and reconstructed 3D-CT images were reviewed to assess lesion characteristics and the presence of gaps. MRI was used to evaluate the change in spinal cord signal intensity. The relationship among gap presence, lesion morphology, and MRI T2 high intensity in the spinal cord was examined. RESULTSA significant difference in gap detection accuracy was observed between CT and 3D-CT (p=.0054). CT demonstrated false-positive results in the detection of gaps as compared with 3D-CT. The presence of gaps was significantly associated with an increased likelihood of MRI T2 high intensity in the spinal cord (p=.037). Patients with thicker lesions and smaller space available for the spinal cord (SAC) were more likely to exhibit T2 high intensity. Meanwhile, patients with gaps co-occurring with T2 high intensity exhibited significantly thinner lesions (p=.011) and larger SACs (p=.0002). Patients with gaps had a significantly lower JOA scores (p=.0035), which indicates that patient with gaps are likely to exhibit more severe clinical neurological symptoms. CONCLUSION3D-CT showed superiority in accurately identifying gaps within OPLL lesions, while CT demonstrated false-positive results in the detection of gaps. Furthermore, the gap presence was a risk factor for MRI T2 high intensity in the spinal cord, independent of lesion thickness. In addition, gaps are related to more severe clinical symptoms. This study highlighted the importance of evaluating gaps within OPLL lesions using 3D-CT to clarify neurological pathogenesis.

Preoperative Cone Beam Computed Topography Assessment of Maxillary Sinus Variations in Dental Implant Patients.

The study included a cohort of 200 patients recommended for CBCT as part of their preoperative evaluation. The methodology involved detailed CBCT image analysis to identify and document various anatomical variations due to pneumatization, exostosis, hypoplasia, polyps, cysts, foreign bodies, and anthroliths within the maxillary sinus. Pneumatization was the most common variation, present in 77.5% of subjects. Polypoid lesions were found in 17.5% of patients, with a higher prevalence in younger age groups (57.1% in ages 20-35). Cysts and polyps affected 17.5% of subjects, predominantly males (65.7%). Anthroliths were observed in a minimal percentage (2%), and foreign bodies were found in 1.5% of the patients. Positive correlations were observed between the patient's age and both mucosal thickness and polypoid lesions and between the patient's gender and bone thickening (p-values < 0.05). The study concluded that CBCT is essential in the preoperative assessment of the maxillary sinus in dental implant candidates due to its superior imaging capabilities, allowing for the identification of critical anatomical variations and pathologies. This thorough evaluation is imperative to ensure the success of implant placement and to mitigate potential complications. However, further research with larger, more diverse populations is recommended to confirm these findings.

NBI Classification Optimization With Morphological Characteristics in Vocal Fold Leukoplakia.

Objectives: To investigate the pathological contribution of vocal fold leukoplakia (VFL) of type II in narrow-band imaging (NBI) classification and morphological characteristics to improve pathological prediction. Material and Methods: The 59 VFL patients with type II in 2019 Ni classification in NBI were included. The pathological reports were collected and divided following 2005 WHO Blue Book. Low-risk VFL contained non-, mild, moderate dysplasia, high-risk VFL included severe dysplasia. The morphological classification and laryngoscopic scoring system were employed to evaluate leukoplakia for pathological prediction. Results: The pathologies contained 1 case of leukoplakia with non-dysplasia, 12 of mild dysplasia, 15 of moderate dysplasia, 8 of severe dysplasia, and 23 of carcinoma. The 30 smooth VFL contained 1 non-dysplasia, 12 mild dysplasia, 14 moderate dysplasia, 2 severe dysplasia, and 1 carcinoma. The 29 rough cases included 1 moderate dysplasia, 6 severe dysplasia, and 22 carcinomas. Laryngoscopic scoring system revealed irregular texture, large size, and thick lesion as factors in relationship with high-risk leukoplakia in univariate (P = .002, <.001, <.001) and multivariate (P = .025, .002, .016) analysis, irregular texture was the most accurate predictor of high-risk VFL pathology. Conclusions and Significance: The pathologies of VFL with type II in NBI classification were hard to be predicted. Morphological irregular/rough texture contributed to predict high-risk pathology in leukoplakia.

Evaluation of Clobetasol and Tacrolimus Treatments in an Imiquimod-Induced Psoriasis Rat Model.

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, inflammation, and aberrant differentiation. Imiquimod-induced psoriasis in rodent models has been widely used to study the pathogenesis of the disease and evaluate potential therapeutic interventions. In this study, we investigated the efficacy of two commonly used treatments, Clobetasol and Tacrolimus, in ameliorating psoriatic symptoms in an Imiquimod-induced psoriasis Wistar rat model. Interestingly, rat models are poorly evaluated in the literature despite rats displaying several advantages in evaluating pharmacological substances. Psoriasis-like skin lesions were induced by topical application of Imiquimod cream on shaved dorsal skin for seven consecutive days. Following induction, rats in the treatment groups received either a Clobetasol or Tacrolimus ointment once daily for one week, while the control group did not receive any application. Disease severity was assessed using clinical scoring, histological examination, and measurement of proinflammatory cytokine levels. Both Clobetasol and Tacrolimus treatments significantly reduced psoriatic lesion severity compared to the control group. Clinical scoring revealed a decrease in erythema, scaling, transepidermal water loss, and thickness of skin lesions in both treatment groups with a more marked effect with Clobetasol. Histological analysis demonstrated reduced epidermal hyperplasia in treated animals compared to controls. Furthermore, Clobetasol led to a significant reduction in the expression levels of the interleukin-17 (IL-17a and IL-17f) proinflammatory cytokines in lesioned skin. Overall, our findings demonstrated the therapeutic efficacy of both Clobetasol and, in a modest manner, Tacrolimus in attenuating Imiquimod-induced psoriasis-like symptoms in a rat model. These results support the clinical use of these agents in the management of psoriasis and mitigating psoriatic inflammation. They also provide insights into the use of rats as a relevant species for the Imiquimod-induced psoriasis model.

Diagnostic yield of percutaneous, ultrasound-guided, fine needle aspirates of the gastrointestinal wall: a retrospective analysis of 152 samples.

The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success. Secondary aims included comparing the cytological diagnosis with histopathology, evaluating the utility of concurrent locoregional lymph node cytology and assessing the procedure's complication rate. Gastrointestinal wall cytology from 75 dogs and 70 cats obtained between 2018 and 2023 were reviewed and categorised as successful (resulting in a diagnostic cytology report) and accurate (resulting in the correct diagnosis when compared to histopathology). Unsuccessful fine needle aspirates, not submitted for cytology, were not recorded. Variables recorded included animal signalment, lesion and lymph node's appearance on ultrasound, size, location, number of smears submitted and experience of the ultrasonographer. One hundred and fifty-two reports were analysed. Eighty-eight (58%) were successful: three normal epithelium, 21 inflammatory processes and 64 neoplasms. Variables associated with increased technical success included description of a mass, higher number of slides submitted and thickness of gastrointestinal lesion on ultrasound. Comparison with histopathology, performed for 17 lesions, showed discrepancies in eight, complete agreement in seven and partial in two. Eighty-four loco-regional lymph nodes were sampled, of which, 67 were successful (80%) and 52 brought additional clinical information (supporting GI wall cytology or diagnosing neoplasia not identified on GI wall cytology). No complication strictly attributable to gastrointestinal wall sampling was reported but when possibly related, death of the patient occurred in 2.5% of cases. Ultrasound-guided fine needle aspirate of gastrointestinal wall had moderate accuracy and was unsuccessful in 42% of cases, but technical success increased when sampling mass lesions, thicker intestinal layers and submitting more slides.

High-frequency ultrasound evaluation of morphea: Retrospective analytical study.

To date, there are no accepted outcome measures to monitor morphea, and consensus on specific monitoring criteria for morphea remains elusive. A few studies have assessed the criterion validity of skin ultrasound in morphea. So, in this study, we approach ultrasound findings in morphea lesions. This was a retrospective-analytical study conducted between December 2021 and May 2023. Patients were clinically evaluated at a dermatology outpatient clinic and then referred for high-frequency ultrasound (HF-US) evaluation and were selected to be included in this study. The lesions were confirmed by histopathology as well. Sonographic evaluations were performed on the lesion site and the symmetrical uninvolved other side. Dermal thickness and dermal echogenicities were recorded. Statistical analysis of group differences was performed by using the 2-tailed Student t-test. A p-value of less than 0.05 was considered statistically significant. Forty-one morphea lesions in the inflammatory phase of 27 patients were included in the study. The mean dermal thickness of morphea lesions was 1107.97±414.3 and the mean dermal thickness of the control side was 1094.65±331.06, The difference between these two variables was not statistically significant. The mean dermal density of lesions was 49.13±18.97 and the mean dermal density of the control side was 52.22±25.33. The difference between these two variables was not statistically significant. This study shows that HF-US indicated increasing dermal thickness and reducing the dermal density of the morphea lesions in the inflammatory phase confirmed with the histopathology.

Mingjing granule inhibits the subretinal fibrovascular membrane of two-stage laser-induced neovascular age-related macular degeneration in rats.

The study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism. The nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial-choroid-sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR. The current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone. Combining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.

A scoring system for stratifying the risk of postoperative bone metastases in colorectal cancer

BackgroundSurveillance recommendations for postoperative high-risk colorectal bone metastases patients remain in a gray area of guidelines. We aimed to develop a risk stratification system to select ideal candidates for follow-up of colorectal bone metastases status. MethodsPostoperative colorectal cancer patients were included to develop a risk-scoring system to predict bone metastases. Risk scores were calculated based on the predictive factors for bone metastases, which were identified using the Cox proportional hazard regression model. Kaplan–Meier curves visualize the differences between risk groups. ResultsEight risk factors (age, lymph node metastasis, pathologic tumor deposit, KRAS mutation status, suspicious retroperitoneal lymph node metastasis, lung metastasis status, largest thickness of colorectal cancer lesion, largest short diameter of lymph node) were predictors of colorectal bone metastases and incorporated into the risk scoring system, and the patients were categorized into 2 risk groups. In the low-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 2.4%, 4.6%, and 3.7%, respectively, whereas in the high-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 15.6%, 29.9%, and 44.4%, respectively. The risk scoring system exhibited a C-index of 0.706, 0.795, and 0.841 in 1, 3, and 5 years, respectively. The Kaplan–Meier curve demonstrates that the incidence of colorectal bone metastases was higher in the high-risk group than in the low-risk group (50.5% vs 11.4%, P < .001). ConclusionThis risk-scoring system may be valuable in predicting colorectal bone metastases in colorectal cancer patients, and we suggest that colorectal bone metastases status surveillance be added in the high-risk group.

One-year longitudinal changes of peripheral CD4+ T-lymphocyte counts, gut microbiome, and plaque vulnerability after an acute coronary syndrome

BackgroundLongitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. MethodsOver one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. ResultsAt admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. ConclusionsPatients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

Differential efficacy of SV-BR-1-GM in inducing intracranial metastasis regression.

e13119 Background: Breast cancer metastasis to the central nervous system (CNS) and intracranial area often leads to severe morbidity and mortality. While systemic treatments manage systemic tumors, their impact on CNS/intracranial metastases is limited. Cell based therapies like SV-BR-1-GM may overcome this limitation. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. We report its efficacy on CNS tumor regression. Methods: Post-hoc analysis of a subset of all advanced MBC patients with CNS/intracranial metastases from previous phase 1, 2, and an ongoing randomized phase 2, trials (n=7 subjects) of SV-BR-1-GM. Bria-IMT monotherapy (intradermal SV-BR-1-GM + cyclophosphamide 300 mg/m2, +interferon-alpha) was administered q3wks to 2 subjects; an immune checkpoint inhibitor (ICI) was administered with each cycle in the combination setting (n=5). Results: There were 7 patients with intracranial metastases at baseline of whom 5 had intracranial tumor responses. Of the 5 responders, median pt age = 66 (range 58-70), median prior lines = 5.5 (3-13), and median time from initial diagnosis = 7.5 years (3-10). 4/5 pts had ≥1 HLA class match with SV-BR-1-GM. 3 were HR + and 1 HER2 +. Pt A002 (ER+/PR+, HER2-) received 6/6 planned cycles, achieving an 83% reduction in breast lesions; after 3 months off therapy, imaging revealed multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles there was marked regression in both brain and breast lesions. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles of SV-BR-1-GM and observed a 60% reduction (5mm -&gt; 2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe. Pt 06-005 (ER+/PR-, HER2 1+) demonstrated a 56% (9mm -&gt; 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI. After 2 additional cycles of SV-BR-1-GM + ICI and 1 cycle of SV-BR-1-GM (ICI skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -&gt; 0m). Pt06-007’s (ER-/PR-, HER2 1+) CNS lesions showed a median reduction of 49% compared to baseline after 3 cycles. Pt 11-018 (ER+/PR-, HER2 +) showed standard progression (SD) at initial restaging; 14% increase in sum of diameters of intracranial metastasis. Subsequent imaging, after 3 cycles, showed significant orbital tumor reduction along with reported improvement in eye pain. Conclusions: This post-hoc analysis demonstrated promising efficacy of the Bria-IMT regimen either alone or in combination with ICIs in CNS/intracranial metastasis. The CNS/intracranial regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will further evaluate the efficacy of the Bria-IMT regimen in patients with CNS/intracranial metastasis. Clinical trial information: NCT03328026 .

Early diagnosis of melanoma: a randomized trial assessing the impact of the transmission of photographs taken with a smartphone from the general practitioner to the dermatologist on the time to dermatological consultation

BackgroundDifficulty obtaining a dermatological consultation is an obstacle to the early diagnosis of melanoma. On the one hand, patients survival depends on the lesion thickness at the time of diagnosis. On the other hand, dermatologists treat many patients with benign lesions. Optimizing patient care pathways is a major concern. The aim of the present study was to assess whether the e-mail transmission of photographs of suspected melanoma lesions between general practitioners (GPs) and dermatologists reduces the time to dermatological consultation for patients whose suspicious skin lesions ultimately require resection.MethodsWe conducted a cluster-randomized controlled study in primary care involving 51 French GPs between April 2017 and August 2019. A total of 250 patients referred to a dermatologist for a suspected melanoma lesion were included GPs were randomized to either the smartphone arm or the usual care arm. In the smartphone arm, the GPs referred patients to the dermatologist by sending 2 photographs of the suspicious lesion using their smartphone. The dermatologist then had to set up an appointment at an appropriate time. In the usual care arm, GPs referred patients to a dermatologist according to their usual practice. The primary outcome was the time to dermatological consultation for patients whose lesion ultimately required resection.Results57 GPs volunteered were randomized (27 to the smartphone arm, and 30 to the usual care arm). A total of 125 patients were included in each arm (mean age: 49.8 years; 53% women) and followed 8 months. Twenty-three dermatologists participated in the study. The time to dermatological consultation for patients whose suspicious skin lesion required resection was 56.5 days in the smartphone arm and 63.7 days in the usual care arm (mean adjusted time reduction: -18.5 days, 95% CI [-74.1;23.5], p = .53).ConclusionsThe e-mail transmission of photographs from GPs to dermatologists did not improve the dermatological management of patients whose suspicious skin lesions ultimately required resection. Further research is needed to validate quality criteria that might be useful for tele-expertise in dermatology.Trial RegistrationRegistered on ClinicalTrials.gov under reference number NCT03137511 (May 2, 2017).

Diagnostic Accuracy of Ultrasound Guided Percutaneous Pleural Needle Biopsy for Malignant Pleural Mesothelioma.

Background/Objectives: Ultrasound (US) has been progressively spreading as the most useful technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. Malignant pleural mesothelioma (MPM) represents the most common malignant pleural tumour. Thoracoscopy represents the gold standard for diagnosis, although conditions hampering such diagnostic approach often coexist. The Objective was to determine whether ultrasound-guided percutaneous needle biopsy (US-PPNB) has a high diagnostic accuracy and represents a safe option for diagnosis of MPM. Methods: US-PPNB of pleural lesions suspected for MPM in patients admitted from January 2021 to June 2023 have been retrospectively analyzed. An 18-gauge semi-automatic spring-loaded biopsy system (Medax Velox 2®) was used by experienced pneumologists. The obtained specimens were histologically evaluated and defined as adequate or non-adequate for diagnosis according to whether the material was considered appropriate or not for immunohistochemistry (IHC) analysis. The primary objective of the study was the diagnostic yield for a tissue diagnosis. Results: US-PPNB was diagnostic of MPM in 15 out of 18 patients (sensitivity: 83.39%; specificity: 100%; PPV: 100%). Three patients with non-adequate US-PPNB underwent thoracoscopy for diagnosis. We found significant differences in terms of mean pleural lesion thickness between patients with adequate and not-adequate biopsy (15.4 mm (SD: 9.19 mm) and 3.77 mm (SD: 0.60 mm), p < 0.0010. In addition, a significant positive correlation has been observed between diagnostic accuracy and FDG-PET avidity value. Conclusions: US-PPNB performed by a pneumologist represents a valid procedure with a high diagnostic yield and accuracy for the diagnosis of MPM, and may be considered as an alternative option in patients who are not suitable for thoracoscopy.

RECENT ADVANCES IN NANOTECHNOLOGY - BASED DRUG DELIVERY SYSTEMS FOR DELIVERY OF PHYTOCONSTITUENTS WITH SPECIAL EMPHASIS ON PSORIASIS MANAGEMENT

Psoriasis is an inflammatory, autoimmune disorder characterized by thick and silvery lesions of the skin. Beyond its physical dimension, this disease has a significant adverse effect on quality of life and represents a huge social health burden. Based on symptoms, psoriasis may be characterized from mild to severe. A range of therapeutic agents are available to treat the disease, but none is able to provide permanent cure of the disease. The most commonly used medicines for treatment of psoriasis include anti-inflammatory drugs, steroids, biological and immunosuppressants. Though these drugs cure the disease to an extent, they are associated with many contra-indicative manifestations. Hence, an alternative system of medicine could be an excellent approach in the management of this disease, and numerous studies proved that bio-actives derived from natural sources have potential anti-psoriatic activity. Further, the therapeutic actions of these natural products can be enhanced by incorporating them in nano-formulations. The present era of medicine is focusing on implementation of natural product based nanotechnology to overcome the drawbacks of conventional treatment. This review primarily aims to focus on the recent advances in the field of natural product based nanomedicines for the effective management of psoriasis.

Evaluation of the safety and efficacy of the novel Mycoplasma gallisepticum vaccine, Vaxsafe MG304, after spray-vaccination of 1-day-old specific pathogen-free chicks

Mycoplasma gallisepticum causes chronic respiratory disease in poultry. A novel vaccine, Vaxsafe MG304 (the ts-304 strain), has greater protective efficacy in chickens than the Vaxsafe MG (strain ts-11) vaccine when delivered by eye drop at 3 weeks of age. Applying this vaccine in the hatchery to 1-day-old birds, using mass administration methods, would improve animal welfare and reduce labour costs associated with handling individual birds. This study assessed the protection provided by vaccination with Vaxsafe MG304 after administration to 1-day-old chicks. Chicks were administered a single dose of the vaccine to assess the efficacy of either a high dose (107.0 colour changing units, CCU) or a low dose (105.7 CCU) after eye drop or spray (in water or gel) administration against experimental challenge with virulent M. gallisepticum strain Ap3AS at 7 weeks of age. The vaccine was able to colonise the palatine cleft of chicks after vaccination by eye drop (at both doses) or by spray (in water or gel) (at the high dose). The high dose of vaccine, when delivered by eye drop or spray, was shown to be safe and induced a serological response and protective immunity (as measured by tracheal mucosal thickness and air sac lesion scores) against challenge. Vaccination of 1-day-old chicks with Vaxsafe MG304 by eye drop induced protective immunity equivalent to vaccination at 3 weeks of age. Vaxsafe MG304 was also protective when applied by both coarse- and gel spray methods at the higher dose and is therefore a suitable live attenuated vaccine for use in 1-day-old chicks.