ResearchPad - lesions https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel]]> https://www.researchpad.co/article/elastic_article_14730 Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.

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<![CDATA[Prevalence of endosalpingiosis and other benign gynecologic lesions]]> https://www.researchpad.co/article/elastic_article_14492 Endosalpingiosis, traditionally regarded as an incidental pathological finding, was recently reported to have an association with gynecologic malignancies. To determine the prevalence of endosalpingiosis, we evaluated all benign appearing adnexal lesions using the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol, and queried the pathology database for the presence of endosalpingiosis, gynecologic malignancy, endometriosis, Walthard nests, and paratubal cysts. Using the SEE-Fim protocol, the prevalence of endosalpingiosis, endometriosis, Walthard nests, and paratubal cysts were 22%, 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except endometriosis which increased until menopause then decreased dramatically. Among specimens including ovarian tissue, the prevalence of implantation of at least one lesion type was ubiquitous in patients age 51 and older (93%). The clinical significance of endosalpingiosis should be a continued area of research with larger trials assessing prevalence, factors affecting incidence, and association with malignancy. Our findings contribute to elucidating the origin of ectopic lesions and gynecologic disease risk.

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<![CDATA[Early budget impact analysis on magnetic seed localization for non-palpable breast cancer surgery]]> https://www.researchpad.co/article/elastic_article_13866 Current localization techniques used in breast conserving surgery for non-palpable tumors show several disadvantages. Magnetic Seed Localization (MSL) is an innovative localization technique aiming to overcome these disadvantages. This study evaluated the expected budget impact of adopting MSL compared to standard of care.MethodsStandard of care with Wire-Guided Localization (WGL) and Radioactive Seed Localization (RSL) use was compared with a future situation gradually adopting MSL next to RSL or WGL from a Dutch national perspective over 5 years (2017–2022). The intervention costs for WGL, RSL and MSL and the implementation costs for RSL and MSL were evaluated using activity-based costing in eight Dutch hospitals. Based on available list prices the price of the magnetic seed was ranged €100-€500.ResultsThe intervention costs for WGL, RSL and MSL were respectively: €2,617, €2,834 and €2,662 per patient and implementation costs were €2,974 and €26,826 for MSL and RSL respectively. For standard of care the budget impact increased from €14.7m to €16.9m. Inclusion of MSL with a seed price of €100 showed a budget impact of €16.7m. Above a price of €178 the budget impact increased for adoption of MSL, rising to €17.6m when priced at €500.ConclusionMSL could be a cost-efficient localization technique in resecting non-palpable tumors in the Netherlands. The online calculation model can inform adoption decisions internationally. When determining retail price of the magnetic seed, cost-effectiveness should be considered. ]]> <![CDATA[Clustered micronodules as predominant manifestation on CT: A sign of active but indolently evolving pulmonary tuberculosis]]> https://www.researchpad.co/article/N48b20e2f-c3ed-4c3c-a251-c583ed3c8c8a

Objective

To investigate the prevalence, patient characteristics, and natural history of clustered micronodules (CMs) in active pulmonary tuberculosis.

Materials and methods

From January 2013 through July 2018, 833 consecutive patients with bacteriologically or polymerase chain reaction–proven active pulmonary tuberculosis were retrospectively evaluated. CMs were defined as a localized aggregation of multiple dense discrete micronodules, which primarily distributed around small airways distal to the level of the segmental bronchus: small airways surrounded by CMs maintained luminal patency and the CMs might coalesce into a larger nodule. The patients were dichotomized according to whether the predominant computed tomography (CT) abnormalities were CMs. We analyzed radiologic and pathologic findings in patients whose predominant diagnostic CT abnormalities were CMs, along with those of incidental pre-diagnostic CT scans, if available. Chi-square, McNemar, Student t-test and Wilcoxon-signed rank test were performed.

Results

CMs were the predominant CT abnormality in 2.6% of the patients (22/833, 95% CI, 1.8–4.0%) with less sputum smear-positivity (4.8% vs 31.0%; p = .010) and a similar proportion of immunocompromised status (40.9% vs 46.0%; p = .637) than those without having CMs as the predominant CT abnormality. The time interval for minimal radiologic progression was 6.4 months. The extent of CMs increased with disease progression, frequently accompanied by consolidation and small airway wall thickening. Pathologically, smaller CMs were non-caseating granulomas confined to the peribronchiolar interstitium, whereas larger CMs were caseating granulomas involving lung parenchyma. Two of the five patients with a pre-diagnostic CT scan obtained more than 50 months pre-diagnosis showed an incipient stage of CMs, in which they were small peribronchiolar nodules.

Conclusion

Active pulmonary tuberculosis manifested predominantly as CMs in 2.6% of patients, with scarce of acid-fast bacilli smear-positivity and no association with impaired host immunity. CMs indolently progressed, accompanied by consolidation and small airway wall thickening, and originated from small nodules.

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<![CDATA[A new simple brain segmentation method for extracerebral intracranial tumors]]> https://www.researchpad.co/article/Nb837d809-9647-425d-8dfd-2c3174a6dd80

Normal brain segmentation is available via FreeSurfer, Vbm, and Ibaspm software. However, these software packages cannot perform segmentation of the brain for patients with brain tumors. As we know, damage from extracerebral tumors to the brain occurs mainly by way of pushing and compressing while leaving the structure of the brain intact. Three-dimensional (3D) imaging, augmented reality (AR), and virtual reality (VR) technology have begun to be applied in clinical practice. The free medical open-source software 3D Slicer allows us to perform 3D simulations on a computer and requires little user interaction. Moreover, 3D Slicer can integrate with the third-party software mentioned above. The relationship between the tumor and surrounding brain tissue can be judged, but accurate brain segmentation cannot be performed using 3D Slicer. In this study, we combine 3D Slicer and FreeSurfer to provide a novel brain segmentation method for extracerebral tumors. This method can help surgeons identify the “real” relationship between the lesion and adjacent brain tissue before surgery and improve preoperative planning.

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<![CDATA[Iron deficiency anemia, population health and frailty in a modern Portuguese skeletal sample]]> https://www.researchpad.co/article/5c8accd9d5eed0c484990155

Introduction

Portugal underwent significant political, demographic and epidemiological transitions during the 20th century resulting in migration to urban areas with subsequent overcrowding and issues with water sanitation. This study investigates population health during these transitions and interprets results within a framework of recent history and present-day public health information. We investigate skeletal evidence for anemia (cribra orbitalia and porotic hyperostosis) as indicators of stress and frailty–i.e., whether the lesions contribute to susceptibility for disease or increased risk of death.

Methods

The presence and severity of skeletal lesions were compared against known sex and cause of death data to investigate potential heterogeneity in frailty and the relationship between lesions and risk of dying over time. Additionally, we tested for the presence of selective mortality in our data (i.e., whether or not the sample is biased for individuals with higher frailty). Our sample derives from a large, documented, modern Portuguese collection from Lisbon and is the first study of its kind using a documented collection. The collection represents primarily middle-class individuals.

Results and conclusions

Analyses indicated that porotic hyperostosis became more common and severe over time, while cribra orbitalia severity increased over time. Neither process was linked to cause of death. However, there was a significant relationship to sex; males exhibited a higher prevalence and severity of lesions and increased mortality. A Gompertz function showed decreased survivorship in early life but increased survivorship over age 60. Using comorbidities of anemia, we were unable to detect selective mortality–i.e., in our sample, lesions do not represent a sign of poor health or increased frailty and are not significantly linked with a decreased mean age-at-death. However, lesion prevalence and severity do reflect the socioeconomic processes in urban Lisbon during the 1800s and 1900s and the possibility of water-borne parasites as the contributing factor for iron deficiency anemia.

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<![CDATA[Is there a reliable size cut-off for splenic involvement in lymphoma? A [18F]FDG-PET controlled study]]> https://www.researchpad.co/article/5c8c1956d5eed0c484b4d428

Purpose

Aim of present study was to determine whether the currently recommended 13-cm cranio-caudal diameter cut-off on CT for assessment of splenic involvement in lymphoma offers adequate sensitivity and specificity.

Materials and Methods

Patients with histologically proven lymphoma who had undergone [18F]FDG-PET/CT before therapy were included. Cranio-caudal diameters of the spleen were measured on the CT component of PET/CT, and ROC analyses with calculation of respective areas under the curve (AUC) were used to determine cut-off values of cranio-caudal measurements with their respective sensitivities and specificities, using [18F]FDG-PET as the reference standard.

Results

In 93 patients, we found a sensitivity of 74.1% and a specificity of 47% for the 13-cm splenic diameter cut-off.

Conclusions

Our results show reasonable, though far from perfect sensitivities and specificities for the currently recommend 13-cm splenic diameter cut-off.

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<![CDATA[Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis]]> https://www.researchpad.co/article/5c8acc39d5eed0c48498f231

Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.

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<![CDATA[Improved visualisation of hepatic metastases in gadoxetate disodium-enhanced MRI: Potential of contrast-optimised (phase-sensitive) inversion recovery imaging]]> https://www.researchpad.co/article/5c897740d5eed0c4847d2834

Background

Detection of metastases can have a significant impact on therapy. Nevertheless, even in gadoxetate disodium-enhanced MR scans, very small hepatic metastases may be difficult to see.

Purpose

To investigate the potential of a contrast-optimised (phase-sensitive) inversion recovery MR sequence in gadoxetate disodium-enhanced scans for detection of hepatic metastases.

Materials and methods

With institutional review board approval and after written informed consent, 40 patients (18 male, 22 female) with suspected or known hepatic metastases were examined on a 1.5 T MR system. A T1-weighted gradient-echo volumetric-interpolated-breath-hold (VIBE) sequence was acquired as part of the standard imaging protocol 20 minutes after administration of gadoxetate disodium. Additionally, an IR sequence was acquired with an inversion time to suppress native signal from metastases. Overall image quality and delineation of lesions were assessed on VIBE as well as on magnitude-reconstructed (MAG) and phase-sensitive IR (PSIR) sequences. Lesion-to-liver contrast (LLC) was compared between VIBE and MAG images.

Results

Overall image quality was high in both VIBE and MAG IR sequences (VIBE 4.275; MAG 4.313), yet significantly lower in PSIR (4.038). Subjective delineation of lesions was higher on MAG and PSIR images compared to VIBE in all size groups with an overall statistically significant difference for VIBE vs. MAG vs. PSIR (p < .001) in the variance analysis. Mean LLC was 0.35±0.01 for VIBE sequences, and 0.73±0.01 for MAG.

Conclusion

Contrast-optimised PSIR seems to improve imaging characteristics of hepatic metastases in gadoxetate disodium-enhanced scans compared to T1 gradient-echo VIBE sequences.

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<![CDATA[Controlling seizure propagation in large-scale brain networks]]> https://www.researchpad.co/article/5c7d95e6d5eed0c484734f24

Information transmission in the human brain is a fundamentally dynamic network process. In partial epilepsy, this process is perturbed and highly synchronous seizures originate in a local network, the so-called epileptogenic zone (EZ), before recruiting other close or distant brain regions. We studied patient-specific brain network models of 15 drug-resistant epilepsy patients with implanted stereotactic electroencephalography (SEEG) electrodes. Each personalized brain model was derived from structural data of magnetic resonance imaging (MRI) and diffusion tensor weighted imaging (DTI), comprising 88 nodes equipped with region specific neural mass models capable of demonstrating a range of epileptiform discharges. Each patient’s virtual brain was further personalized through the integration of the clinically hypothesized EZ. Subsequent simulations and connectivity modulations were performed and uncovered a finite repertoire of seizure propagation patterns. Across patients, we found that (i) patient-specific network connectivity is predictive for the subsequent seizure propagation pattern; (ii) seizure propagation is characterized by a systematic sequence of brain states; (iii) propagation can be controlled by an optimal intervention on the connectivity matrix; (iv) the degree of invasiveness can be significantly reduced via the proposed seizure control as compared to traditional resective surgery. To stop seizures, neurosurgeons typically resect the EZ completely. We showed that stability analysis of the network dynamics, employing structural and dynamical information, estimates reliably the spatiotemporal properties of seizure propagation. This suggests novel less invasive paradigms of surgical interventions to treat and manage partial epilepsy.

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<![CDATA[Combination of colonoscopy and magnetic resonance enterography is more useful for clinical decision making than colonoscopy alone in patients with complicated Crohn's disease]]> https://www.researchpad.co/article/5c76fe3fd5eed0c484e5b78a

Background/aims

The small bowel is affected in more than half of patients with Crohn’s disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy.

Methods

A single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of <5. MRE remission was defined as a Magnetic Resonance Index of Activity (MaRIA) score of <50. The time to treatment escalation was assessed by the log-rank test.

Results

Importantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (<10cm), a high MaRIA score still correlated with the need for treatment escalation in stricturing or penetrating disease (P = 0.0306).

Conclusions

The MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.

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<![CDATA[Toxoplasmic retinochoroiditis: The influence of age, number of retinochoroidal lesions and genetic polymorphism for IFN-γ +874 T/A as risk factors for recurrence in a survival analysis]]> https://www.researchpad.co/article/5c6c756dd5eed0c4843cfd80

Purpose

To analyze risk factors for recurrent toxoplasmic retinochoroiditis.

Design

Single center prospective case series.

Population and Methods

A total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects.

Results

One hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01–1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07–2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04–2.14).

Conclusion

The risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence.

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<![CDATA[Liver metastasis and Heng risk are prognostic factors in patients with non-nephrectomized synchronous metastatic renal cell carcinoma treated with systemic therapy]]> https://www.researchpad.co/article/5c76fe33d5eed0c484e5b6ea

Objective

This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy.

Methods

Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7.1%) with previous immunotherapy and 13 (18.6%) with immunotherapy only. The medical records of patients were retrospectively reviewed and analyzed to determine factors of PFS and OS using the Cox proportional hazards model with a statistical significance p-value <0.05.

Results

The median treatment and follow-up periods were 3.9 and 30.9 months, respectively. Disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively. The lung (77.1%) was the most common site of metastasis. Multivariable analysis showed that poor Heng risk (hazard ratio [HR]: 2.37) and liver metastasis (HR: 2.34) were significant prognostic factors for PFS, and female sex (HR: 2.13), poor Heng risk (HR: 3.14), and liver metastasis (HR: 2.78) were significant prognostic factors for OS (p < 0.05). A subset analysis of risk factors among patients without previous history of immunotherapy also showed poor Heng risk (HR 2.92 and HR 4.24 for PFS) and liver metastasis (HR 2.87 and HR 4.81 for OS) as significant factors for both PFS and OS (p<0.05).

Conclusion

Poor Heng risk, sex, and liver metastasis were associated with survival outcomes after first-line systemic therapy in patients with non-nephrectomized synchronous mRCC.

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<![CDATA[Structured reporting of prostate magnetic resonance imaging has the potential to improve interdisciplinary communication]]> https://www.researchpad.co/article/5c75abfdd5eed0c484d07f7d

Background

Effective interdisciplinary communication of imaging findings is vital for patient care, as referring physicians depend on the contained information for the decision-making and subsequent treatment. Traditional radiology reports contain non-structured free text and potentially tangled information in narrative language, which can hamper the information transfer and diminish the clarity of the report. Therefore, this study investigates whether newly developed structured reports (SRs) of prostate magnetic resonance imaging (MRI) can improve interdisciplinary communication, as compared to non-structured reports (NSRs).

Methods

50 NSRs and 50 SRs describing a single prostatic lesion were presented to four urologists with expert level experience in prostate cancer surgery or targeted MRI TRUS fusion biopsy. They were subsequently asked to plot the tumor location in a 2-dimensional prostate diagram and to answer a questionnaire focusing on information on clinically relevant key features as well as the perceived structure of the report. A validated scoring system that distinguishes between “major” and “minor” mistakes was used to evaluate the accuracy of the plotting of the tumor position in the prostate diagram.

Results

The mean total score for accuracy for SRs was significantly higher than for NSRs (28.46 [range 13.33–30.0] vs. 21.75 [range 0.0–30.0], p < 0.01). The overall rates of major mistakes (54% vs. 10%) and minor mistakes (74% vs. 22%) were significantly higher (p < 0.01) for NSRs than for SRs. The rate of radiologist re-consultations was significantly lower (p < 0.01) for SRs than for NSRs (19% vs. 85%). Furthermore, SRs were rated as significantly superior to NSRs in regard to determining the clinical tumor stage (p < 0.01), the quality of the summary (4.4 vs. 2.5; p < 0.01), and overall satisfaction with the report (4.5 vs. 2.3; p < 0.01), and as more valuable for further clinical decision-making and surgical planning (p < 0.01).

Conclusions

Structured reporting of prostate MRI has the potential to improve interdisciplinary communication. Through SRs, expert urologists were able to more accurately assess the exact location of single prostate cancer lesions, which can facilitate surgical planning. Furthermore, structured reporting of prostate MRI leads to a higher satisfaction level of the referring physician.

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<![CDATA[Apolipoprotein B correlates with intra-plaque necrotic core volume in stable coronary artery disease]]> https://www.researchpad.co/article/5c75ac91d5eed0c484d08a4e

Objective

To determine the relationship between plaque composition and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo-B), and Apo-A1 using virtual-histology intravascular ultrasound (VH-IVUS).

Methods

We assessed plaque composition in patients with stable coronary artery disease (SCD) admitted to our hospital for percutaneous coronary intervention (PCI) between November 1, 2012, and March 10, 2015. Before PCI, fibrous (FI), fibrofatty (FF), necrotic core (NC), and dense calcium (DC) regions were evaluated using VH-IVUS, and the contributions of each to the culprit lesion volume were recorded. Plasma LDL-C, HDL-C, Apo-B, and Apo-A1 levels were assessed before PCI. The relationship between the regions on VH-IVUS and plasma lipid levels was assessed. Patients were categorized into low Apo-B (LAB) and high Apo-B (HAB) groups, based on the overall cohort median Apo-B level.

Results

We enrolled 115 patients (median Apo-B, 91 mg/dL, male n = 88) with 57 and 58 patients in the LAB (Apo-B ≤ 90 mg/dL) and HAB (Apo-B ≥ 91 mg/dL) groups, respectively. Vessel, plaque, and %NC volumes were significantly greater in the HAB group than in the LAB group. The %FI, %FF, and %DC volumes were similar in both groups. In all 115 patients, the %NC volume correlated with LDL-C (r = 0.2353, P = 0.0114) and Apo-B (r = 0.2487, P = 0.0074) but not with HDL-C and Apo A-1. The high-sensitivity C-reactive protein level tended to be higher in the HAB group than in the LAB group. Multiple regression analysis showed that being male, Apo-A1, and Apo-B were significant predictors of %NC volume extent.

Conclusions

Elevated Apo-B level was related to the %NC in target coronary artery lesions in SCD patients, suggesting a role of Apo-B as a biomarker of unstable plaque in this population.

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<![CDATA[Histogram analysis of prostate cancer on dynamic contrast-enhanced magnetic resonance imaging: A preliminary study emphasizing on zonal difference]]> https://www.researchpad.co/article/5c6c75d9d5eed0c4843d02ed

Background

This study evaluated the performance of histogram analysis in the time course of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for differentiating cancerous tissues from benign tissues in the prostate.

Methods

We retrospectively analyzed the histograms of DCE-MRI of 30 patients. Histograms within regions of interest(ROI) in the peripheral zone (PZ) and transitional zone (TZ) were separately analyzed. The maximum difference wash-in slope (MWS) and delay phase slope (DPS) were defined for each voxel. Differences in histogram parameters, namely the mean, standard deviation (SD), the coefficient of variation (CV), kurtosis, skewness, interquartile range (IQR), percentile (P10, P25, P75, P90, and P90P10), Range, and modified full width at half-maximum (mFWHM) between cancerous and benign tissues were assessed.

Results

In the TZ, CV for ROIs of 7.5 and 10mm was the only significantly different parameter of the MWS (P = 0.034 and P = 0.004, respectively), whereas many parameters of the DPS (mean, skewness, P10, P25, P50, P75 and P90) differed significantly (P = <0.001–0.016 and area under the curve [AUC] = 0.73–0.822). In the PZ, all parameters of the MWS exhibited significant differences, except kurtosis and skewness in the ROI of 7.5mm(P = <0.001–0.017 and AUC = 0.865–0.898). SD, IQR, mFWHM, P90P10 and Range were also significant differences in the DPS (P = 0.001–0.035).

Conclusion

The histogram analysis of DCE-MRI is a potentially useful approach for differentiating prostate cancer from normal tissues. Different histogram parameters of the MWS and DPS should be applied in the TZ and PZ.

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<![CDATA[Early-stage serrated adenocarcinomas are divided into several molecularly distinct subtypes]]> https://www.researchpad.co/article/5c76fdead5eed0c484e5b080

Serrated adenocarcinoma (SAC) is considered the end stage of the serrated neoplasia pathway. Although SAC prognosis is not widely recognized, the serrated pathway-associated subtype consistently exhibits unfavorable prognosis in genetic studies. Herein, we classified molecularly distinct subtypes of serrated adenocarcinomas and clarified their associated clinicopathological characteristics and genetic changes. We examined 38 early-stage colorectal SACs. Of these, 24 were classified into three molecularly distinct groups by colon cancer subtyping (CCS). The clinicopathological characteristics, Ki 67 labeling index (LI), and SAC epithelial serration were assessed. The DNA from carcinomas and normal tissue/adenoma was extracted by laser microdissection and sequenced by next-generation sequencing, and mutation numbers and patterns of a 15-oncogene panel were determined. The CCS groups included CCS1 (CDX2+, HTR2B-, FRMD6-, ZEB1-, and microsatellite instable-low [MSI-L]/microsatellite stable [MSS]; 14 cases), CCS2 (microsatellite instable-high [MSI-H], 5 cases), and CCS3 (CDX2-, HTR2B+, FRMD6+, ZEB1+, and MSI-L/MSS; 5 cases). Invasive cancer was significantly more frequent in CCS3 than in CCS1 (5/5 versus 3/14, respectively). Ki67 LI and epithelial serration were higher in CCS3 than in CCS1 (83.0 ± 5.8 versus 65.4 ± 4.0 and 5/5 versus 3/14, respectively; p = 0.031 and 0.0048). CCS2 showed the highest mutation number, whereas KRAS and BRAF mutation numbers were higher in CCS3 than in CCS1. Early-stage SACs were classified into three molecularly distinct subtypes with different clinicopathological and genetic characteristics.

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<![CDATA[Resolution invariant wavelet features of melanoma studied by SVM classifiers]]> https://www.researchpad.co/article/5c648cd2d5eed0c484c81893

This article refers to the Computer Aided Diagnosis of the melanoma skin cancer. We derive wavelet-based features of melanoma from the dermoscopic images of pigmental skin lesions and apply binary C-SVM classifiers to discriminate malignant melanoma from dysplastic nevus. The aim of this research is to select the most efficient model of the SVM classifier for various image resolutions and to search for the best resolution-invariant wavelet bases. We show AUC as a function of the wavelet number and SVM kernels optimized by the Bayesian search for two independent data sets. Our results are compatible with the previous experiments to discriminate melanoma in dermoscopy images with ensembling and feed-forward neural networks.

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<![CDATA[Very severe tungiasis in Amerindians in the Amazon lowland of Colombia: A case series]]> https://www.researchpad.co/article/5c65dce5d5eed0c484dec4b0

Background

Tungiasis is a parasitic skin disease caused by penetrating female sand fleas. By nature, tungiasis is a self-limiting infection. However, in endemic settings re-infection is the rule and parasite load gradually accumulates over time. Intensity of infection and degree of morbidity are closely related.

Methodology/principal findings

This case series describes the medical history, the clinical pathology, the socio-economic and the environmental characteristics of very severe tungiasis in five patients living in traditional Amerindian communities in the Amazon lowland of Colombia. Patients had between 400 and 1,300 penetrated sand fleas. The feet were predominantly affected, but clusters of embedded sand fleas also occurred at the ankles, the knees, the elbows, the hands, the fingers and around the anus. The patients were partially or totally immobile. Patients 1 and 3 were cachectic, patient 2 presented severe malnutrition. Patient 3 needed a blood transfusion due to severe anemia. All patients showed a characteristic pattern of pre-existing medical conditions and culture-dependent behavior facilitating continuous re-infection. In all cases intradomiciliary transmission was very likely.

Conclusion/significance

Although completely ignored in the literature, very severe tungiasis occurs in settings where patients do not have access to health care and are stricken in a web of pre-existing illness, poverty and neglect. If not treated, very severe tungiasis may end in a fatal disease course.

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<![CDATA[Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum]]> https://www.researchpad.co/article/5c58d665d5eed0c484031d84

Background

Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy.

Methodology/findings

We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL.

Conclusions

Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.

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