Role of Vimentin and E-cadherin Expression in Premalignant and Malignant Lesions of Oral Cavity.

To determine the role of Vimentin and E-cadherin expression in oral premalignant and malignant lesions. 68 histopathologically confirmed cases of premalignant and malignant oral cavity lesions enrolled. Biopsy specimens were taken from lesion of all cases and subjected to immunohistochemical evaluation of expression of E-cadherin and Vimentin. We examined the relationships between the expression of these markers and specific clinicopathological features were analyzed. Out of 68 cases 28 showed high vimentin expression (3 + and 4 + grade) and 40 showed low vimentin expression (1 + and 2 + grade). 20 cases out of 68 presented with high E-cadherin expression (3 + and 4 +) and rest 48 with low expression (1 + and 2 +) of the same. Smoking and tobacco chewing reflected non-significant association with their expression. In this study all 28 patients (100%) with high vimentin expression had malignant lesions and 17 (60.7%) presented with metastatic lymph nodes Out of 20 patients with high E-cadherin expression 8(40.0%) had malignant lesions and 12 (60.0%) had pre malignant lesions and 4 (20%) showed nodal metastasis. As tumor stage (TNM) progresses, it showed increased vimentin and decreased E-cadherin expression and vice versa. We concluded that increased vimentin and decreased E-cadherin expression in oral cancers are associated with metastasis and disease progression in terms of upstaging of disease. We can use cellular expression of vimentin and E-cadherin for early diagnosis of disease.

Efficacy and Safety of Novel Formulation of Clobetasol Propionate 0.025% Cream in Indian Moderate-to-Severe Psoriasis Patients: Phase-2a, Randomized 3-Arm Study.

INTRODUCTION: Clobetasol propionate (0.05% standard dose formulation), a topical corticosteroid, leads to systemic side-effects like hypothalamic-pituitary-adrenal (HPA) axis suppression at doses as low as 2 g/day. The aim of this study was to evaluate HPA axis suppression, efficacy, and safety of clobetasol propionate (0.025%, formulation 5 and 13) versus currently marketed 0.05% cream in Indian patients with moderate-to-severe psoriasis. METHODS: In this phase 2a investigator-blinded study, patients aged ≥ 18 years with moderate-to-severe psoriasis were randomized 1:1:1 to receive clobetasol propionate 0.025% formulation 5, or 13, or 0.05% cream; twice daily for 28 days. Safety endpoints included adrenocorticotropic hormone (ACTH) test results at day 28 (primary), and local tolerability at each visit (burning/stinging/pruritus, secondary). Efficacy endpoints included Psoriasis Global Assessment (PGA) score. RESULTS: Overall, 88 patients received clobetasol propionate 0.025% formulation 5 and 13 (n = 29 for both) and 0.05% cream (n = 30). At day 28, the proportion of patients with an abnormal ACTH stimulation test (cortisol levels ≤ 18 µg/dl) was numerically lower in 0.025% formulations: 5 (20.7%) and 13 (17.2%) compared with 0.05% cream (30.0%), (p = 0.320). Decrease in burning/stinging /pruritus scores were comparable in all treatment groups and PGA success rates were higher with 0.025% formulations: 5 (38.9%) and 13 (36.8%) compared with 0.05% cream (30.8%). CONCLUSION: Clobetasol propionate 0.025% could be an effective treatment for moderate-to-severe psoriasis compared with 0.05% cream, demonstrating comparable efficacy with a better systemic safety profile. TRIAL REGISTRATION NUMBER: REF/2018/01/016779.

Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study.

BACKGROUND: Itolizumab, a humanized monoclonal antibody to CD6, is a novel therapeutic agent evaluated in chronic plaque psoriasis. OBJECTIVE: We sought to assess the safety and efficacy of itolizumab in moderate to severe chronic plaque psoriasis. METHODS: A total of 225 patients were randomized (2:2:1) to 2 different itolizumab arms (A or B; A = 4-week loading dose of 0.4 mg/kg/wk followed by 1.6 mg/kg every 2 weeks; B = 1.6/mg every 2 weeks) or placebo. At week 12, the placebo arm was switched to 1.6 mg/kg itolizumab every 2 weeks. The primary end point was the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index score at week 12. RESULTS: At week 12, 27.0% in arm A (P = .0172 vs placebo), 36.4% in B (P = .0043 vs placebo), and 2.3% in the placebo arm had at least 75% improvement in Psoriasis Area and Severity Index score. At week 28, the proportion with at least 75% improvement in Psoriasis Area and Severity Index score was comparable: 46.1%, 45.5%, and 41.9% for A, B, and placebo, respectively. In weeks 1 to 12, the incidence of all adverse events was comparable across arms (A, 43%; B, 38%; placebo, 47%) and the incidence of infections was not greater than placebo (11.1%, 8.9%, and 18.6% for A, B, and placebo). LIMITATIONS: No active comparator is a limitation. CONCLUSIONS: Itolizumab is an effective and well-tolerated novel biological therapy in moderate to severe psoriasis.

Overcoming x-ray tube small focal spot output limitations for high-resolution region of interest imaging.

We investigate methods to increase x-ray tube output to enable improved quantum image quality with a higher generalized-NEQ (GNEQ) while maintaining a small focal-spot size for the new high-resolution Micro-angiographic Fluoroscope (MAF) Region of Interest (ROI) imaging system. Rather than using a larger focal spot to increase tube-loading capacity with degraded resolution, we evaluated separately or in combination three methods to increase tube output: 1) reducing the anode angle and lengthening the filament to maintain a constant effective small focal-spot size, 2) using the standard medium focal spot viewed from a direction on the anode side of the field and 3) increasing the frame rate (frames/second) in combination with temporal filter. The GNEQ was compared for the MAF for the small focal-spot at the central axis, and for the medium focal-spot with a higher output on the anode side as well as for the small focal spot with different temporal recursive filtering weights. A net output increase of about 4.0 times could be achieved with a 2-degree anode angle (without the added filtration) and a 4 times longer filament compared to that of the standard 8-degree target. The GNEQ was also increased for the medium focal-spot due to its higher output capacity and for the temporally filtered higher frame rate. Thus higher tube output, while maintaining a small effective focal-spot, should be achievable using one or more of the three methods described with only small modifications of standard x-ray tube geometry.

Evaluation and Comparison of High-Resolution (HR) and High-Light (HL) Phosphors in the Micro-Angiographic Fluoroscope (MAF) using Generalized Linear Systems Analyses (GMTF, GDQE) that include the Effect of Scatter, Magnification and Detector Characteristics.

In this study, we evaluated the imaging characteristics of the high-resolution, high-sensitivity micro-angiographic fluoroscope (MAF) with 35-micron pixel-pitch when used with different commercially-available 300 micron thick phosphors: the high resolution (HR) and high light (HL) from Hamamatsu. The purpose of this evaluation was to see if the HL phosphor with its higher screen efficiency could be replaced with the HR phosphor to achieve improved resolution without an increase in noise resulting from the HR's decreased light-photon yield. We designated the detectors MAF-HR and MAF-HL and compared them with a standard flat panel detector (FPD) (194 micron pixel pitch and 600 micron thick CsI(Tl)). For this comparison, we used the generalized linear-system metrics of GMTF, GNNPS and GDQE which are more realistic measures of total system performance since they include the effect of scattered radiation, focal spot distribution, and geometric un-sharpness. Magnifications (1.05-1.15) and scatter fractions (0.28 and 0.33) characteristic of a standard head phantom were used. The MAF-HR performed significantly better than the MAF-HL at high spatial frequencies. The ratio of GMTF and GDQE of the MAF-HR compared to the MAF-HL at 3(6) cycles/mm was 1.45(2.42) and 1.23(2.89), respectively. Despite significant degradation by inclusion of scatter and object magnification, both MAF-HR and MAF-HL provide superior performance over the FPD at higher spatial frequencies with similar performance up to the FPD's Nyquist frequency of 2.5 cycles/mm. Both substantially higher resolution and improved GDQE can be achieved with the MAF using the HR phosphor instead of the HL phosphor.

Graphical User Interface for a Dual-Module EMCCD X-ray Detector Array.

A new Graphical User Interface (GUI) was developed using Laboratory Virtual Instrumentation Engineering Workbench (LabVIEW) for a high-resolution, high-sensitivity Solid State X-ray Image Intensifier (SSXII), which is a new x-ray detector for radiographic and fluoroscopic imaging, consisting of an array of Electron-Multiplying CCDs (EMCCDs) each having a variable on-chip electron-multiplication gain of up to 2000× to reduce the effect of readout noise. To enlarge the field-of-view (FOV), each EMCCD sensor is coupled to an x-ray phosphor through a fiberoptic taper. Two EMCCD camera modules are used in our prototype to form a computer-controlled array; however, larger arrays are under development. The new GUI provides patient registration, EMCCD module control, image acquisition, and patient image review. Images from the array are stitched into a 2k×1k pixel image that can be acquired and saved at a rate of 17 Hz (faster with pixel binning). When reviewing the patient's data, the operator can select images from the patient's directory tree listed by the GUI and cycle through the images using a slider bar. Commonly used camera parameters including exposure time, trigger mode, and individual EMCCD gain can be easily adjusted using the GUI. The GUI is designed to accommodate expansion of the EMCCD array to even larger FOVs with more modules. The high-resolution, high-sensitivity EMCCD modular-array SSXII imager with the new user-friendly GUI should enable angiographers and interventionalists to visualize smaller vessels and endovascular devices, helping them to make more accurate diagnoses and to perform more precise image-guided interventions.

Generalized two-dimensional (2D) linear system analysis metrics (GMTF, GDQE) for digital radiography systems including the effect of focal spot, magnification, scatter, and detector characteristics.

The MTF, NNPS, and DQE are standard linear system metrics used to characterize intrinsic detector performance. To evaluate total system performance for actual clinical conditions, generalized linear system metrics (GMTF, GNNPS and GDQE) that include the effect of the focal spot distribution, scattered radiation, and geometric unsharpness are more meaningful and appropriate. In this study, a two-dimensional (2D) generalized linear system analysis was carried out for a standard flat panel detector (FPD) (194-micron pixel pitch and 600-micron thick CsI) and a newly-developed, high-resolution, micro-angiographic fluoroscope (MAF) (35-micron pixel pitch and 300-micron thick CsI). Realistic clinical parameters and x-ray spectra were used. The 2D detector MTFs were calculated using the new Noise Response method and slanted edge method and 2D focal spot distribution measurements were done using a pin-hole assembly. The scatter fraction, generated for a uniform head equivalent phantom, was measured and the scatter MTF was simulated with a theoretical model. Different magnifications and scatter fractions were used to estimate the 2D GMTF, GNNPS and GDQE for both detectors. Results show spatial non-isotropy for the 2D generalized metrics which provide a quantitative description of the performance of the complete imaging system for both detectors. This generalized analysis demonstrated that the MAF and FPD have similar capabilities at lower spatial frequencies, but that the MAF has superior performance over the FPD at higher frequencies even when considering focal spot blurring and scatter. This 2D generalized performance analysis is a valuable tool to evaluate total system capabilities and to enable optimized design for specific imaging tasks.

Near-infrared phosphorescent polymeric nanomicelles: efficient optical probes for tumor imaging and detection.

We report a formulation of near-infrared (near-IR) phosphorescent polymeric nanomicelles and their use for in vivo high-contrast optical imaging, targeting, and detection of tumors in small animals. Near-IR phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin (Pt(TPNP)) were found to maintain their near-IR phosphorescence properties when encapsulated into phospholipid nanomicelles. The prepared phosphorescent micelles are of approximately 100 nm size and are highly stable in aqueous suspensions. A large spectral separation between the Pt(TPNP) absorption, with a peak at approximately 700 nm, and its phosphorescence emission, with a peak at approximately 900 nm, allows a dramatic decrease in the level of background autofluorescence and scattered excitation light in the near-IR spectral range, where the signal from the phosphorescent probe is observed. In vivo animal imaging with subcutaneously xenografted tumor-bearing mice has resulted in high contrast optical images, indicating highly specific accumulation of the phosphorescent micelles into tumors. Using optical imaging with near-IR phosphorescent nanomicelles, detection of smaller, visually undetectable tumors has also been demonstrated.