Non-invasive Biopsy Research Articles

Uncovering the potential of CD44v/SYNE1/miR34a axis in salivary fluids of oral cancer patients.

Late-stage diagnosis is one of the major confounders for poor prognosis of patients with oral cancer owing to lack of a biomarker to diagnose this disease at an early stage. Moreover, till date, invasive biopsies are the only option to assess disease occurrence and progression in this malignancy. Thus, this study aims to identify and assess potential salivary markers in OSCC patients in order to open newer avenues in the field of non-invasive biopsies. Bioinformatic-based analysis was performed to identify potential biomarkers that could be assessed in OSCC patients. The expression patterns of CD44v and its genetic and epigenetic modulators were assessed in saliva of OSCC patients, leukoplakia, and controls using real-time and methylation-specific PCR. Statistical analysis was conducted to understand the significance of these markers in terms of their clinical relevance. CD44v/SYNE1/miR34a axis was identified using bioinformatic analysis, and the expression profile of these markers was assessed in saliva of OSCC patients. CD44v6 and CD44v10 demonstrated a significantly increased expression, whereas SYNE1 and miR34a depicted a significantly decreased expression in OSCC patients. Statistical analysis suggested a probable role of CD44v6, SYNE1, and miR34a in early stages of the malignancy, whereas a strong association was observed between CD44v6, CD44v10, and miR34a expression with locoregional aggressiveness and histopathological conditions. Collectively, these findings suggested a plausible role of CD44v/SYNE1/miR34a axis as non-invasive salivary biomarkers to diagnose this disease at an early stage and predict the early onset of metastasis.

A prospective biomarker trial of microbiome, immune, and genomic markers as predictors of radiation response in anal squamous cell carcinoma.

TPS869 Background: Preclinical evidence suggests that the microbiome plays a significant role in carcinogenesis and in response to immunotherapy and chemotherapy, but little is known about the role of the microbiome in response to radiation. Our group previously demonstrated that in patients with cervical squamous cell carcinoma (SCC), radiation response and immune response to radiation are improved with increased rectal microbial diversity. Methods: We are currently enrolling patients with local anal SCC undergoing definitive chemoradiation on a prospective biomarker trial evaluating changes in the gastrointestinal microbiome, immune microenvironment, and whole genome sequencing using a novel, non-invasive swab biopsy technique in addition to serial blood collections. This biopsy technique allows novel evaluation of dynamic changes throughout the course of chemoradiation. Microbiome sequencing is performed using 16s rRNA sequencing. Immune profiling is done using multiparametric flow cytometry for T-cell activation and exhaustion phenotypes and T-cell receptor sequencing. Inclusion criteria are biopsy proven HPV-related SCC of the anus, with no evidence of metastatic disease, and undergoing definitive chemoradiation. Our population is uniquely treated with cisplatin/5-FU based chemotherapy, rather than lymphotoxic mitomycin-C, allowing unique evaluation of immune populations. The primary endpoint of this study is complete tumor response based on pelvic MRI and digital rectal exam at three weeks. Secondary endpoints include FDG-avid diseases at 3 months and disease recurrence. To date we have accrued 10 patients out a planned 30 patient pilot cohort. We expect the remainder of these patients to be accrued by December 2017.

Selection of Implantation Sites for Transplantation of Encapsulated Pancreatic Islets.

Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. To develop a clinically implantable BAP, some key aspects need to be taken into account: encapsulation material, capsule design, and implant site. Among them, the implant site exerts an important influence on the engraftment, stability, and biocompatibility of implanted BAP. Currently, an optimal site for encapsulated islet transplantation may include sufficient capacity to host large graft volumes, portal drainage, ease of access using safe and reproducible procedure, adequate blood/oxygen supply, minimal immune/inflammatory reaction, pliable for noninvasive imaging and biopsy, and potential of local microenvironment manipulation or bioengineering. Varying degrees of success have been confirmed with the utilization of liver or extrahepatic sites in an experimental or preclinical setting. However, the ideal implant site remains to be further engineered or selected for the widespread application of encapsulated islet transplantation.

Tunable, Ultrafast Fiber-Laser between 1.15 μm and 1.35 μm for Harmonic Generation Microscopy in Human Skin

We demonstrate a fiber-optic ultrafast tunable source for harmonic generation microscopy (HGM) in human skin. The source is based on a 31-MHz Er-fiber laser followed by self-phase modulation enabled spectral selection (SESS). The resulting pulses are tunable between 1.15 and 1.35 μm with up to >10-nJ pulse energy and ∼100-fs pulse duration. We employ this source to drive a scanning microscope for HGM imaging of ex vivo human skin. A systematic investigation on imaging depth versus excitation wavelength reveals that excitation wavelengths in the 1.15–1.25 μm range exhibit low optical attenuation within the tissue and allows larger imaging depth for HGM in human skin. HGM driven by fiber-based SESS sources constitutes an enabling tool for noninvasive virtual skin biopsy in clinical applications.

Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer

Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLC patients. CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform; Rarecells) from 106 NSCLC patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor cells and WBCs. CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥1 PD-L1-positive CTCs and 11 patients (15%) showed ≥1% PD-L1-positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity = 100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥1% PD-L1-positive immune infiltrates in tumor tissue and 39 patients (53%) showed ≥1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells (progression-free and overall survival), similar to the effects of PD-L1 expression in matched-patient tumors. These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.

The role of noninvasive tests and liver biopsy in the diagnosis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of significant alcohol consumption (<40 g/week). The essential metabolic trait is insulin resistance, which is why NAFLD is associated with obesity, diabetes mellitus (DM), hyperlipidemia.Approximately one-quarter of adults with NAFLD present nonalcoholic steatohepatitis (NASH) leading to progressive hepatic fibrosis and finally cirrhosis and hepatocellular carcinoma.If liver biopsy (LB) has traditionally been NAFLD’s gold standard, over the past 15 years, its use has undergone an important transformation.In this review, the role of noninvasive tests (serological markers, imaging techniques) in the NAFLD evaluation is analyzed, starting from the low adherence of patients for LB, the complications of the technique, and the increased cost.LB is the only investigation that distinguishes between simple steatosis and NASH.However, in the medical practice, LB has gained lesser value; it is worth mentioning that NASH represents a small proportion compared to NAFLD. For this reason, most patients only show biopsy steatosis, which has a good prognosis. In addition, judging by the appearance of inflammation markers and fibrosis in the diagnosis technique, the use of LB has become increasingly rare in the definition of NASH.

Aberrant SEPT9 methylation in plasma cell-free DNA of CRC patients

Colorectal cancer (CRC) is one of the most common cancers worldwide. CRC develops from precancerous polyps in the colon or rectum and is preventable by an early diagnosis and with the removal of precursor lesions. Numerous genetics and epigenetic alterations transform benign polyps to malignant tumors by affecting different pathways. Over the past decade, increasing evidence represent the utility of cell-free DNA as a ‘liquid biopsy’ to supplement non-invasive biopsies for genetic and epigenetic characterization and monitoring of solid cancers. One of the epigenetic biomarkers that has gained more attention in CRC is aberrant DNA methylation of Septin 9 gene. In this study we try to evaluate the methylation of Septin 9 gene status in the cfDNA of the plasma in colorectal cancer patients. Plasma cell-free DNA samples were extracted from 30 patients with background of tumors or polyps and 30 samples from healthy individuals. Septin 9 methylation analysis was performed by using the bisulfite specific high resolution melting analysis. The result showed a sensitivity and specificity of 10% and 53.33%, respectively. In conclusion, our results demonstrated that Septin 9 DNA methylation in plasma determined by THP and BSP-HRM had not have sufficient accuracy.

Non-Invasive Prostate Cancer Characterization with Diffusion-Weighted MRI: Insight from In silico Studies of a Transgenic Mouse Model.

Diffusion-weighted magnetic resonance imaging (DWI) enables non-invasive, quantitative staging of prostate cancer via measurement of the apparent diffusion coefficient (ADC) of water within tissues. In cancer, more advanced disease is often characterized by higher cellular density (cellularity), which is generally accepted to correspond to a lower measured ADC. A quantitative relationship between tissue structure and in vivo measurements of ADC has yet to be determined for prostate cancer. In this study, we establish a theoretical framework for relating ADC measurements with tissue cellularity and the proportion of space occupied by prostate lumina, both of which are estimated through automatic image processing of whole-slide digital histology samples taken from a cohort of six healthy mice and nine transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. We demonstrate that a significant inverse relationship exists between ADC and tissue cellularity that is well characterized by our model, and that a decrease of the luminal space within the prostate is associated with a decrease in ADC and more aggressive tumor subtype. The parameters estimated from our model in this mouse cohort predict the diffusion coefficient of water within the prostate-tissue to be 2.18 × 10−3 mm2/s (95% CI: 1.90, 2.55). This value is significantly lower than the diffusion coefficient of free water at body temperature suggesting that the presence of organelles and macromolecules within tissues can drastically hinder the random motion of water molecules within prostate tissue. We validate the assumptions made by our model using novel in silico analysis of whole-slide histology to provide the simulated ADC (sADC); this is demonstrated to have a significant positive correlation with in vivo measured ADC (r2 = 0.55) in our mouse population. The estimation of the structural properties of prostate tissue is vital for predicting and staging cancer aggressiveness, but prostate tissue biopsies are painful, invasive, and are prone to complications such as sepsis. The developments made in this study provide the possibility of estimating the structural properties of prostate tissue via non-invasive virtual biopsies from MRI, minimizing the need for multiple tissue biopsies and allowing sequential measurements to be made for prostate cancer monitoring.

An overview of methods to mitigate artifacts in optical coherence tomography imaging of the skin.

Optical coherence tomography (OCT) of skin delivers three-dimensional images of tissue microstructures. Although OCT imaging offers a promising high-resolution modality, OCT images suffer from some artifacts that lead to misinterpretation of tissue structures. Therefore, an overview of methods to mitigate artifacts in OCT imaging of the skin is of paramount importance. Speckle, intensity decay, and blurring are three major artifacts in OCT images. Speckle is due to the low coherent light source used in the configuration of OCT. Intensity decay is a deterioration of light with respect to depth, and blurring is the consequence of deficiencies of optical components. Two speckle reduction methods (one based on artificial neural network and one based on spatial compounding), an attenuation compensation algorithm (based on Beer-Lambert law) and a deblurring procedure (using deconvolution), are described. Moreover, optical properties extraction algorithm based on extended Huygens-Fresnel (EHF) principle to obtain some additional information from OCT images are discussed. In this short overview, we summarize some of the image enhancement algorithms for OCT images which address the abovementioned artifacts. The results showed a significant improvement in the visibility of the clinically relevant features in the images. The quality improvement was evaluated using several numerical assessment measures. Clinical dermatologists benefit from using these image enhancement algorithms to improve OCT diagnosis and essentially function as a noninvasive optical biopsy.

Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy

Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions. In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015. Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided. Biopsy sensitivity and specificity with vs without PLA data. Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P < .001) with PLA data. The noninvasive PLA enables dermatologists to significantly improve biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.

Is there a practical role for a virtual bone biopsy using high‐resolution imaging of bone in patients with chronic kidney disease?

Renal osteodystrophy (ROD) refers to alterations in bone turnover, mineralisation, mass and microarchitecture in patients with chronic kidney disease (CKD) and represents the skeletal component of 'CKD-mineral and bone disorder'. Changes in bone structure lead to impaired bone quality, compromised bone strength and increased susceptibility to fractures with associated significant morbidity, mortality and financial cost. Diagnosis and management of ROD is hindered by the inadequacy of currently available diagnostic methods to interpret the complex pathophysiology. Bone biopsy, the perceived gold standard test to assess ROD, is invasive and suboptimal for disease screening and management in routine clinical practice. High-resolution imaging, such as high-resolution peripheral quantitative computed tomography and high-resolution magnetic resonance imaging provide accurate non-invasive quantification of bone microarchitecture and facilitate assessment of mechanical competence of bone, correlating with skeletal fragility. We discuss the potential for these imaging techniques in patients with CKD to provide quantification and assessment of bone structure and strength. When used in conjunction with serum biomarkers, these investigative tools may provide a non-invasive diagnostic virtual bone biopsy.

AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions

This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”.The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers).Moreover, we critically report on the diagnostic role of non-invasive biomarkers, imaging techniques and liver biopsy, which remains the reference standard for diagnosing the disease, but cannot be proposed to all patients with suspected NAFLD.Finally, the management of NAFLD is also reviewed, by highlighting the lifestyle changes and the pharmacological options, with a focus on the innovative drugs.We conclude that the results of ongoing studies are eagerly expected to lead to introduce into the clinical arena new diagnostic and prognostic biomarkers, prevention and surveillance strategies as well as to new drugs for a tailored approach to the management of NAFLD in the individual patient.

OA12.05 Noninvasive CT-Based Image Biopsy System (iBiopsy) for Early Stage Lung Adenocarcinoma

CT screening programs frequently detect early stage lung adenocarcinoma. Recent studies show that distinct subtypes of lung adenocarcinoma are associated with different prognosis and suggest that treatment should be tailored to histological subtypes as identified in the new WHO Lung Tumor Classification. To develop this personalized approach, it is important to have reliable tools to diagnose tumors before treatment, preferably non-invasively through image analysis. We have developed a CT-image analysis system (iBiopsy) that uses computerized deep learning and artificial intelligence. To validate the accuracy of a noninvasive CT-based image biopsy system (iBiopsy) in differentiating early stage lung adenocarcinoma subtypes of atypical adenomatous hyperplasia (AAH), adenocaricnoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). We retrospectively identified 365 eligible patients from Zhongshan Hopsital Fudan University, diagnosed with AAH, AIS, MIA or IAC by surgical pathological diagnosis. The last high definition CT scan prior to the surgery of the lesion was analyzed using the iBiopsy system, blinded to pathological result. Based on a pulmonary nodule image feature set (PNIFS) in combination with classified pattern models, such as R-SVM, all the pulmonary nodules were classified into four groups. For diagnosis efficacy, area under the curve (AUC) of Precision-Recall score (PRS), receiver operating characteristic (ROC) of a classification model were calculated in each group. 365 patients were included in the analysis. The classification recognition rate of the PNIFS was 80.03%. The average value of PRS is 0.92, the mean of ROC is 0.95, and it is more than 0.80 for the cross validation value. iBiopsy system allows the non-invasive imaged based stratification of pulmonary adenocarcinoma nodules into four groups, from AAH to IAC. Our result suggest that iBiopsy system could ultimate facilitate the diagnosis and precision management of pulmonary nodules.

Latent Class Analysis of Noninvasive Methods and Liver Biopsy in Chronic Hepatitis C: An Approach without a Gold Standard.

Aims To evaluate the applicability of the Latent Class Analysis (LCA) and accuracy of transient elastography (TE), aspartate-to-platelet-ratio-index (APRI), enhanced liver fibrosis (ELF), and liver biopsy (LB) for liver fibrosis assessment in a model without a gold standard. Methods Significant fibrosis was defined as TE ≥ 7.1 kPa, APRI ≥ 1.5, ELF ≥ 9.37, or LB METAVIR F ≥ 2. Cirrhosis was defined as TE ≥ 12.5 kPa, APRI ≥ 2.0, ELF ≥ 10.31, or LB as METAVIR F = 4. Results 117 patients with chronic hepatitis C were included. In the LCA, for significant fibrosis the sensitivities and specificities (95% CI) were 0.92 (0.86–0.98) and 0.79 (0.72–0.86) for TE; 0.47 (0.40–0.54) and 0.99 (0.95–1.00) for APRI; 0.81 (0.74–0.88) and 0.78 (0.71–0.85) for ELF; and 0.86 (0.68–1.00) and 0.91 (0.79–1.00) for LB. For cirrhosis, the sensitivities and specificities were 0.92 (0.76–1.00) and 0.94 (0.91–0.97) for TE; 0.57 (0.37–0.77) and 0.97 (0.93–1.00) for APRI; 0.94 (0.84–1.00) and 0.88 (0.82–0.94) for ELF; and 0.30 (0.12–0.48) and 1.00 for LB. Conclusion LCA was useful to evaluate accuracy of methods for liver fibrosis staging. Sensitivities and specificities of noninvasive methods were increased in LCA compared to the use of LB as the gold standard.

Selection of Biopsy Site for Patients with Systematic Amyloidosis.

Objective To evaluate the sensitivities of various biopsy methods for the diagnosis of systematic amyloidosis (SA). Methods The clinical data and biopsy results of 194 SA patients who were treated in Peking Union Medical College Hospital from January 2009 to June 2015 were retrospectively analyzed. Results The highest sensitivity was achieved by biopsy of affected organs,with renal biopsy 97.4%,heart biopsy 95.0% and liver biopsy 87.5%. Among non-invasive biopsy methods,tongue biopsy was found to be 75% sensitive,followed by gingiva biopsy at 57%,abdominal fat pad aspiration at 57%,rectum biopsy at 16%,and bone marrow examination at 8%. Combination of tongue and abdominal fat pad biopsy yielded a detection rate of 93.1%. Conclusions Biopsy of the involved organ has the highest sensitivity. However,combination of multiple non-invasive biopsy methods may has sensitivity comparable to organ biopsy and is safer and more convenient.

High Protein Dietary Intervention Improves Body Mass Index (BMI) and Reduces the NAFLD Fibrosis Score (NFS) in Veterans with Obesity

Introduction: In 2014, approximately 78% of veterans were either overweight or obese. Obesity is a leading cause of non-alcoholic fatty liver disease (NAFLD), which progresses to cirrhosis requiring liver transplantation. Efforts to improve NAFLD include exercise and dietary interventions. We showed in animal models of obesity that a high protein diet results in significant reduction in BMI and hepatic fat. Additionally we found that in a Western-diet induced rat model that switching to a high protein diet induced changes in the cecal microbiota favoring Akkermansia which may be responsible for these effects. Thus, similar to these animal models, we hypothesized a high protein diet would decrease hepatic steatosis in humans. Objectives: To evaluate the effects of a high protein diet on body weight, body composition and liver steatosis in obese human subjects. Methods: This is prospective trial conducted at a single site and approved by the VA IRB. The inclusion criteria were obese men and women aged ≥30 years with a BMI of 27-40 kg/m2 that were randomized to at least 3 months of a high protein diet (HPD= 1 gm protein/lb lean body mass) compared to a standard Western diet. The NAFLD Fibrosis Score (Angulo Hepatology 2007): -1.675+ 0.037 x age [yrs] + 0.094 x BMI +1.13 impaired fasting glucose or diabetes (yes=1; no=0) + 0.99 x AST/ALT ratio - 0.013 x PLT count - 0.66 x Albumin level [g/dl]. As defined, a score < -1.455 suggested absence of significant fibrosis (F0-F2); -1.455 to 0.675 suggested indeterminate fibrosis; and a score of > 0.675 suggested advanced fibrosis (F3-F4). Results: Twenty-seven subjects met inclusion criteria with a mean follow-up of 8 months. In total, 16/27 (55%) and 14/27 (52%) patients had decreased BMI and NFS, respectively, from baseline compared to post-HPD time points. The average baseline BMI was 34.7 kg/m2 as compared to post-HPD BMI of 33.9 kg/m2, indicating a mean change of -0.8kg/m2 in BMI with HPD. Of the 16 subjects who lost weight on the high protein diet, the average change in NAFLD Fibrosis Score was -0.41, indicating improvement in hepatic fibrosis. Conclusions: A high protein diet for 3 months results in weight loss in overweight and obese veterans with improvement in the NAFLD Fibrosis Score, suggesting potential reversibility of NAFLD. Further confirmation with non-invasive imaging or tissue biopsies is warranted.

Hepatology Clinical.

Hepatology Clinical.

Efficacy and safety of permethrin 5% topical gel vs. placebo for rosacea: a double-blind randomized controlled clinical trial.

Rosacea is a chronic, multifactorial, dermatological condition. Increased density of Demodex folliculorum mites in the skin of rosacea patients suggests a possible role for these mites in the pathophysiology of rosacea. To evaluate the effects of permethrin 5% topical gel vs. placebo on Demodex density (Dd) and clinical presentations of rosacea patients, and also to further refine the quantitative assessment of Dd in the non-invasive standard skin surface biopsy (SSSB). Twenty patients with bilateral papulopustular rosacea and ≥5 mites/cm2 were enrolled in the study. Participants and physicians were blinded to the group assignments. Each patient applied permethrin on one side and placebo on the other side of the face twice daily for 12 weeks. SSSB and photography and Rosacea Clinical Scorecard of the National Rosacea Society were used to assess the patients at the baseline, 2nd, 5th, 8th, and 12th weeks for both sides of the face. Causality and severity of adverse drug reactions (ADRs) were assessed by WHO Scale and Hartwig Scale, respectively. Dd was not significantly different between the two groups at the baseline. In both groups, Dd significantly decreased after 12 weeks compared to the baseline. At the end of the 12th week, the Dd in the permethrin group was significantly lower than the placebo group. Severity of the clinical presentations decreased in both groups at the end of week 12 in comparison to the baseline, particularly in the permethrin group. ADRs were all mild and in most cases unlikely related to permethrin. Permethrin 5% gel can significantly reduce the Dd and severity of presentations in rosacea patients and can be a safe and effective option in the management of this chronic disorder. This new SSSB technique offers an easy, quick, inexpensive, and non-invasive sampling method proper for quantitative assessment of Dd.

Commentary on ‘Ultrasonography of Skin Changes in Legs with Chronic Venous Disease’

The paper by Dr. Caggiati 3 has opened a new path in this area as it provides a way to objectively evaluate the skin and subcutaneous tissue with ultrasound in patients with CVD. The ultrasound findings were impressive and in accord with previous histological descriptions. In patients with C2 with an apparently normal skin some may have ultrasonographic changes related to more advanced disease. It was suggested that such findings may separate patients with cosmetic issues from those having medical problems. This finding is valuable as it can affect the decision on treating such patients. In patients with edema and skin damage (C3eC6) the changes observed were more severe and affected most areas studied. Such findings may provide a sharper discrimination between the different CVD classes and better characterize the effects of CVD on skin and subcutaneous tissues. In our center, although we have not studied this prospectively, we have similar findings to those reported in the current paper. Dr. Caggiati also demonstrated that some of these changes detected by ultrasound can be reversed by the application of compression. This is very important, as treatment of reflux or obstruction, or both, can be studied in a more objective way. I believe that the “non-invasive ultrasound biopsy” proposed in this study can shed a different light on patients with CVD but also on other conditions such as the different clinical stages of patients with peripheral arterial disease. Furthermore, it may identify patients that are more likely to respond to the application of different types of treatment. This study was cross sectional and thus it is not known how accurately improvement or worsening of CVD can be determined. Also, the sample size was small and did not allow precise definitions in the different C classes, as the spectrum of presentation and skin changes is wide. For example, we have observed micro-edema in early CVD, extreme fibrotic changes in patients with C4b, and in a few patients dense acoustic shadowing from calcification or ossification of the subcutaneous tissues. The data from this study need to be reproduced by others and validated in a bigger prospective cohort. Ideally, the ultrasound data should be correlated with histological changes. Furthermore, it is very important that the effects of different types of treatment are evaluated in prospective longitudinal studies. In this way, the impact of these ultrasound observations can add another dimension to their clinical importance and also on monitoring the patient status.The current findings in this paper warrant further studies to better evaluate and understand the changes that occur in patients with CVD.

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation.

Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). The research included 70 patients (the average age of 49.3±10.2years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80%, specificity-83% and diagnostic accuracy-82%. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50% correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6%, sensitivity-60% and diagnostic accuracy-74.5%. For only LGE specificity was 16%, sensitivity-90% and diagnostic accuracy-28%. The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.