Tri-modal <Emphasis Type="Italic">In vivo</Emphasis> Imaging of Pancreatic Islets Transplanted Subcutaneously in Mice

Purpose

Transplantation of pancreatic islets (PIs) is a promising therapeutic approach for type 1 diabetes. The main obstacle for this strategy is that the outcome of islet engraftment depends on the engraftment site. It was our aim to develop a strategy for using non-invasive imaging techniques to assess the location and fate of transplanted PIs longitudinally in vivo.

Procedures

In order to overcome the limitations of individual imaging techniques and cross-validate findings by different modalities, we have combined fluorine magnetic resonance imaging (F-19 MRI), fluorescence imaging (FLI), and bioluminescent imaging (BLI) for studying subcutaneously transplanted PIs and beta cell-like cells (INS-1E cell line) in vivo. We optimized the transduction (using lentiviral vectors) and labeling procedures (using perfluoro crown ether nanoparticles with a fluorescence dye) for PIs and INS-1E cell imaging.

Results

The feasibility of using the proposed imaging methods for PI assessment was demonstrated both in vitro and in vivo. Our data suggested that F-19 MRI is suitable for high-resolution localization of transplanted cells and PIs; FLI is essential for confirmation of contrast localization by histology; and BLI is a reliable method to assess cell viability and survival after transplantation. No significant side effects on cell viability and function have been observed.

Conclusions

The proposed tri-modal imaging platform is a valuable approach for the assessment of engrafted PIs in vivo. It is potentially suitable for comparing different transplantation sites and evaluating novel strategies for improving PI transplantation technique in the future.

     

Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study

Purpose

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most reliable method for the histological diagnosis of pancreatic tumors. Rapid on-site fluorescence-guided histological diagnosis was evaluated by topically applying an enzymatically activatable probe onto the EUS-FNA samples; the probe fluoresces in the presence of γ-glutamyltranspeptidase (GGT).

Procedures

We evaluated GGT expression in pancreatic cancer cell lines in vitro. EUS-FNA was performed in 10 pancreatic tumors. After topical application of the probe, signal intensity was measured using a fluorescence imaging system for 13 min.

Results

GGT was expressed in Panc-1, AsPC-1, and AR42J, but not in KP4 cells. In samples from six cases, several regions of the specimens fluoresced and contained adequate tissue for pathological diagnosis. The remaining four non-fluorescent samples contained very small amounts of carcinoma, normal epithelial cells, or no epithelial cells. The signal intensity at 5 min was 25.5?±?7.7 and 7.7?±?0.5 in fluorescent and non-fluorescent regions, respectively (p?<?0.05).

Conclusions

Application of enzymatically activatable probe onto EUS-FNA samples would be feasible for the rapid evaluation of tissues suitable for histological diagnosis.

     

Comparative Effectiveness of <Emphasis Type="Italic">nab</Emphasis>-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States

Introduction

nab-Paclitaxel plus gemcitabine (nab-P?+?G) and FOLFIRINOX (FFX) are among the most common first-line (1L) therapies for metastatic adenocarcinoma of the pancreas (MPAC), but real-world data on their comparative effectiveness are limited.

Methods

This retrospective cohort study compared the efficacy and safety of 1L nab-P?+?G versus FFX, overall and under specific treatment sequences. Medical records were reviewed by 215 US physicians who provided information on MPAC patients who initiated 1L therapy with nab-P?+?G or FFX between April 1, 2015 and December 31, 2015. Study outcomes were overall survival (OS) and tolerability. OS was compared using Kaplan–Meier curves and adjusted Cox proportional hazards models.

Results

In total, 654 medical records were reviewed, including those of 337 and 317 patients initiated on nab-P?+?G and FFX as 1L MPAC therapy, respectively. nab-P?+?G-initiated patients were older, less likely to have ECOG?≤?1, and had more comorbidities than FFX-initiated patients. Median OS (mOS) was 12.1 and 13.8 months for nab-P?+?G- and FFX-initiated patients, respectively (HR?=?0.99, P?=?0.96). Among patients with ECOG?≤?1, mOS was 14.1 and 13.7 months, respectively (HR?=?1.00, P?=?0.99). Among patients with 1L nab-P?+?G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of 16.3 and 16.6 months, respectively (HR?=?1.04, P?=?0.76). The rates of diarrhea, fatigue, mucositis, and nausea and vomiting were significantly higher in the FFX than nab-P?+?G cohort.

Conclusion

The real-world survival was similar between patients receiving 1L nab-P?+?G or FFX both overall and among patients who received active 2L treatments. In addition, nab-P?+?G was associated with significantly lower rates of common AEs compared with FFX.

Funding

Celgene.

     

A Novel Imaging Biomarker Extracted from Fluorescence Microscopic Imaging of TRA-8/DR5 Oligomers Predicts TRA-8 Therapeutic Efficacy in Breast and Pancreatic Cancer Mouse Models

Purpose

The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in human breast and pancreatic cancer mouse models.

Procedures

Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10⁵ cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (×20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R ²) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R ² value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC₅₀) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models.

Results

Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R ² value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p?<?0.05). The novel imaging biomarker was significantly correlated with either log₁₀(IC₅₀) or %TGI (p?<?0.001).

Conclusion

The imaging biomarker extracted from the cellular distribution pattern of Cy5.5-TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancer patients.

     

Effects of a self-managed home-based walking intervention on psychosocial health outcomes for breast cancer patients receiving chemotherapy: a randomised controlled trial

Purpose

This study evaluated the effectiveness of a self-managed home-based moderate intensity walking intervention on psychosocial health outcomes among breast cancer patients undergoing chemotherapy.

Methods

The randomised controlled trial compared a self-managed, home-based walking intervention to usual care alone among breast cancer patients receiving chemotherapy. Outcome measures included changes in self-report measures of anxiety, depression, fatigue, self-esteem, mood and physical activity. Fifty participants were randomised to either the intervention group (n?=?25), who received 12 weeks of moderate intensity walking, or the control group (n?=?25) mid-way through chemotherapy. Participants in the intervention group were provided with a pedometer and were asked to set goals and keep weekly diaries outlining the duration, intensity and exertion of their walking. Levels of psychosocial functioning and physical activity were assessed pre- and post-intervention in both groups.

Results

The intervention had positive effects on fatigue (F?=?5.77, p?=?0.02), self-esteem (F?=?8.93, p?≤?0.001), mood (F?=?4.73, p?=?0.03) and levels of physical activity (x ²?=?17.15, p?=?0.0011) but not anxiety (F?=?0.90, p?=?0.35) and depression (F?=?0.26, p?=?0.60) as assessed using the HADS. We found an 80 % adherence rate to completing the 12-week intervention and recording weekly logs.

Conclusion

This self-managed, home-based intervention was beneficial for improving psychosocial well-being and levels of physical activity among breast cancer patients treated with chemotherapy.

Trial registration

Current Controlled Trials ISRCTN50709297.

     

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Purpose

During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures

Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.

Results

The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30 % of mice with positive margins. Molecular imaging identified an additional 50 % of residual tumor deposits (p?<?0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.

Conclusions

Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

     

Long-term Efficacy of Safinamide on Parkinson’s Disease Chronic Pain

Introduction

Chronic pain is an important yet overlooked non-motor symptom of Parkinson’s disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms.

Objectives

To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment.

Methods

This is a post hoc analysis of the data from the 2-year study 018, focused on the reduction of concomitant pain treatments and on the scores of pain-related items of the Parkinson’s disease quality of life questionnaire (PDQ-39).

Results

Safinamide, compared with placebo, significantly improved the PDQ-39 items 37 (“painful cramps or spasm,” p?=?0.0074) and 39 (“unpleasantly hot or cold,” p?=?0.0209) and significantly reduced the number of concomitant pain treatments by 26.2% (p?=?0.005). A significantly greater proportion of patients in the safinamide group was not using pain drugs after 2 years of treatment (p?=?0.0478).

Conclusions

The positive effects of safinamide on PD chronic pain were maintained in the long term. Further investigations are desirable to confirm their clinical relevance.

Funding

Zambon SpA.

     

Pancreatic transplants: secretin-stimulated MR pancreatography

Background

Our study was aimed to evaluate the functional status of pancreatic transplants using dynamic MR pancreatography after secretin stimulation.

Methods

Thirteen asymptomatic patients previously submitted to isolated pancreas (n = 6) or combined kidney–pancreas (n = 7) transplantation, with enteric-portal pancreatic drainage, underwent MR examination at 1.5 T using a phased-array coil. After the acquisition of axial and coronal T1- and T2-weighted sequences, dynamic MR pancreatography was performed using a coronal breath-hold, thick-slab (40–60 mm), single-shot T2-weighted fast spin-echo sequence. After the intravenous administration of secretin (Secrelux^®, Sanochemia; 1 cU/kg body/weight), a single-slice image acquisition was repeated every 30 s up to 15 min. We estimated the calibre changes of the pancreatic ductal system and the filling of the donor’s duodenum on the basis of pancreatic secretion after secretin stimulation, also evaluated by using a mean signal intensity/time histogram in a chosen region of interest including the transplanted pancreas and the connected small bowel.

Results

All patients well tolerated the examination, and no side effects were reported after secretin administration. In 12/13 cases, a significant increase (more than 1 mm) in the diameter of the mean pancreatic duct was observed after secretin stimulation; in all patients, a noticeable filling of the duodenal graft was demonstrated during dynamic MR pancreatography on both qualitative and quantitative analyses.

Conclusions

Dynamic MR imaging after secretin administration allows non-invasive evaluation of exocrine function of the pancreatic transplants and could be used to differentiate patients with graft rejection from those with normal graft function.

     

Prevalence of restless legs syndrome in migraine patients with and without aura: a cross-sectional,case-controlled study

Background

Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura.

Methods

We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1–8/month), high-frequency (9–14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression.

Results

Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p?=?0.026), though this effect did not persist following adjustment for baseline characteristics (p?=?0.256). The trend was robust in patients whose migraines presented with auras (p _univariate?=?0.002; p _multivariate?=?0.043) but not in those without auras (p _univariate and p _multivariate?>?0.05). Higher anxiety [odds ratio (OR)?=?1.18, p?=?0.019] and sleep disturbance (OR?=?1.17, p?=?0.023) scores were associated with higher RLS prevalence.

Conclusions

Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.

     

Detection of Lymph Node Metastases with SERRS Nanoparticles

Purpose

The accurate detection of lymph node metastases in prostate cancer patients is important to direct treatment decisions. Our goal was to develop an intraoperative imaging approach to distinguish normal from metastasized lymph nodes. We aimed at developing and testing gold-silica surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles that demonstrate high uptake within normal lymphatic tissue and negligible uptake in areas of metastatic replacement.

Procedures

We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancer mouse model using PC-3 cells transduced with mCherry fluorescent protein. Tumor-bearing mice (n?=?6) and non-tumor-bearing control animals (n?=?4) were injected intravenously with 30 fmol/g SERRS nanoparticles. After 16–18 h, the retroperitoneal lymph nodes were scanned in situ and ex vivo with a Raman imaging system and a handheld Raman scanner and data corroborated with fluorescence imaging for mCherry protein expression and histology.

Results

The SERRS nanoparticles demonstrated avid homing to normal lymph nodes, but not to metastasized lymph nodes. In cases where lymph nodes were partially infiltrated by tumor cells, the SERRS signal correctly identified, with sub-millimeter precision, healthy from metastasized components.

Conclusions

This study serves as a first proof-of-principle that SERRS nanoparticles enable high precision and rapid intraoperative discrimination between normal and metastasized lymph nodes.

     

Cerebrolysin for the Treatment of Aneurysmal Subarachnoid Hemorrhage in Adults: A Retrospective Chart Review

Introduction

Cerebrolysin is a neuroprotective drug used in the treatment of acute ischemic stroke. To our knowledge, this drug has never been evaluated in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of Cerebrolysin in patients with aneurysmal SAH.

Methods

Aneurysmal SAH patients who had their aneurysm obliterated at our institution from 2007 to 2016 were retrospectively studied. Patients received Cerebrolysin treatment or standard care only (control group). Subgroup analyses were performed according to Hunt and Hess grade (good grade?≤?2, N?=?216; poor grade?≥?3, N?=?246) and treatment procedure (clip or coil).

Results

In good-grade patients (N?=?216), clinical outcomes and mortality did not differ significantly between the control and Cerebrolysin groups. In poor-grade patients (N?=?246), the mortality rate was significantly lower in the Cerebrolysin group (8.7%) than in the control group (25.4%, p?=?0.006). In patients who received microsurgical clipping (N?=?328), the mortality rate was significantly lower in the Cerebrolysin group (7.3%) than in the control group (18.5%, p?=?0.016).

Conclusion

Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.

     

CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy

Purpose

The objectives of this retrospective study were to describe the characteristics and topography of pancreatic ductal adenocarcinoma and its early local recurrence after pancreaticoduodenectomy and identify predictive factors of local early recurrence by imaging computed tomography (CT).

Methods

The institutional review board approved the study and did require additional informed consent for reviewing the patients’ medical records and images. Patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma, a preoperative CT scan, and adequate postoperative CT were included. After postoperative imaging, correlations among clinical and histological characteristics and preoperative imaging were evaluated.

Results

Among the 123 patients who underwent pancreaticoduodenectomy, 48 patients had sufficient follow-up imaging and were included in this study. A total of 33 patients experienced local early recurrence (Group 1), and 15 exhibited no local recurrence (Group 2). Local recurrence consisted of two types of anomalies: tissue nodules on surgical clips (94 %) and peri-arterial encasement (82 %). On preoperative imaging, the tumor diameter (p = 0.02) and the presence of a venous borderline resectable tumor (p < 0.0001) were predictive of local recurrence.

Conclusions

Tissue nodules on surgical clips and arterial encasement characterize early local recurrence, and nodules and encasement should not be considered common post-operative infiltration. The role of the radiologist is essential to assess the predictive factors of recurrence and to identify early local recurrence.

     

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B,D and its Impact on Small Airway Function: A Randomized Controlled Trial

Introduction

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.

Methods

Eligible participants (n?=?170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.

Results

After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41?±?3.56 and 11.08?±?3.05, p?<?0.0001). The changes of CAT (p?=?0.028) and mMRC scores (p?=?0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF₂₅% pred) was significantly improved after 3 months (4.84?±?8.73%, p?<?0.0001) and 6 months (6.21?±?8.65%, p?<?0.0001). There was a significant difference in small airway function tests (MEF₅₀% pred, MEF₂₅% pred, and MMEF% pred) between the two groups after 6 month of treatment (p?=?0.003, p?<?0.0001, and p?=?0.021, respectively).

Conclusions

Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

     

<Emphasis Type="Italic">L</Emphasis><Subscript><Emphasis Type="Italic">p</Emphasis></Subscript> Regularization for Bioluminescence Tomography Based on the Split Bregman Method

Purpose

Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L _p regularization with the Split Bregman method.

Procedures

The diffusion equation was used as the forward model. Then, we defined the objective function of L _p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method.

Results

The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions.

Conclusions

The Split Bregman iteration method is able to minimize the L _p regularization problem and achieve fast and accurate reconstruction in BLT.

     

Quantitative [<Superscript>18</Superscript>F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer

Purpose

Evaluation of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer.

Procedures

Mice with BT474, HER2+ tumors, were imaged with [¹⁸F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.

Results

[¹⁸F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P?<?0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P?<?0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r ² ?=?0.85).

Conclusions

[¹⁸F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.

     

Multimodal Genetic Approach for Molecular Imaging of Vasculature in a Mouse Model of Melanoma

Purpose

In this study, we evaluated a genetic approach for in vivo multimodal molecular imaging of vasculature in a mouse model of melanoma.

Procedures

We used a novel transgenic mouse, Ts-Biotag, that genetically biotinylates vascular endothelial cells. After inoculating these mice with B16 melanoma cells, we selectively targeted endothelial cells with (strept)avidinated contrast agents to achieve multimodal contrast enhancement of Tie2-expressing blood vessels during tumor progression.

Results

This genetic targeting system provided selective labeling of tumor vasculature and showed in vivo binding of avidinated probes with high specificity and sensitivity using microscopy, near infrared, ultrasound, and magnetic resonance imaging. We further demonstrated the feasibility of conducting longitudinal three-dimensional (3D) targeted imaging studies to dynamically assess changes in vascular Tie2 from early to advanced tumor stages.

Conclusions

Our results validated the Ts-Biotag mouse as a multimodal targeted imaging system with the potential to provide spatio-temporal information about dynamic changes in vasculature during tumor progression.

     

Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells

Purpose

Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells.

Procedures

We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR).

Results

The sensor activity showed an inverse relationship with mitochondrial function (R ²?=??0.975, p?=?0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry.

Conclusions

Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.

     

Prospective,Randomized, Single Masked,Parallel Study Exploring the Effects of a Preservative-Free Ophthalmic Solution Containing Hyaluronic Acid 0.4% and Taurine 0.5% on the Ocular Surface of Glaucoma Patients Under Multiple Long-Term Topical Hypotensive Therapy

Introduction

To compare the effects of a preservative-free (PF) ophthalmic solution containing hyaluronic acid (HA) 0.4% and taurine (TAU) 0.5% with those of a PF ophthalmic solution containing HA 0.2% on ocular surface signs, symptoms, and morphological parameters in glaucoma patients under multiple long-term topical hypotensive therapy.

Methods

Eligible patients underwent evaluation of ocular surface parameters by ocular surface disease index (OSDI) and glaucoma symptom scale (GSS) questionnaires, breakup time test (BUT), Schirmer I test, corneal and conjunctival staining (Oxford scale), and conjunctival in vivo confocal microscopy (Heidelberg Retina Tomograph 3, Heidelberg Engineering GmbH, Heidelberg, Germany). After the baseline visit, patients were randomized to use a PF ophthalmic solution containing HA 0.4% and TAU 0.5%, QID, in both eyes (group 1) or to use a PF ophthalmic solution containing HA 0.2%, QID (group 2) in addition to the ongoing preserved hypotensive treatment. Follow-up visits were scheduled at 30 and 90 days.

Results

Thirty-nine eyes of 39 glaucoma patients were included in the study. At baseline, results of study tests of both groups were similar. After 90 days in group 1 the BUT (p?=?0.01), the Oxford score (p?=?0.03), the conjunctival goblet cells (CGC) density (p?=?0.0005) ,and the two questionnaires score significantly improved (OSDI, p?=?0.003; GSS, p?=?0.003) compared to baseline values, while in group 2 all these parameters did not differ from baseline (BUT, p?=?0.39; Oxford score, p?=?0.54; CGC density, p?=?0.33, OSDI p?=?0.65, GSS, p?=?0.25). The BUT and the CGC density were statistically different between groups both at 30 and 90 days (p?=?0.04 and p?=?0.04, respectively). The Schirmer I test did not statistically change after 90 days in both groups.

Conclusions

The PF ophthalmic solution with HA 0.4% and TAU 0.5% seems to improve CGC density and reduce signs and symptoms of dry eye in glaucoma patients under long-term multiple preserved hypotensive therapy.

Trial registration

ClinicalTrials.gov identifier, NCT03480295.

     

Dynamic changes in injured myocardium,very early after acute myocardial infarction,quantified using T1 mapping cardiovascular magnetic resonance

Background

It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI.

Methods

A first group (n?=?31) underwent 3 acute 3?T CMR scans (time-point (TP) <?3?h, 24?h and 6?days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n?=?17) had a single scan at 24?h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.

Results

The mean T1 relaxation time value within the AAR of the first group was reduced after 24?h (P?<?0.001 for TP1 vs.TP2) and subsequently increased at 6?days (P?=?0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P?=?1.0) but was between TP2 &TP3 (P?=?0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42?±?15% vs. 39?±?15%, P?=?0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.

Conclusion

The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

     

Validation trial for efficacy of ultrasonographic measurement method to predict ascitic volume using virtual ultrasonography

Purpose

The aim of this study was to clarify whether ultrasound quantitative methods were positively correlated with volume of ascites evaluated by whole abdominopelvic CT.

Methods

Sixty-eight patients with cirrhotic ascites were retrospectively analyzed. First, to confirm that virtual ultrasonography (VUS) is an alternative method to conventional ultrasound, 22 patients underwent both conventional ultrasonography and VUS. Second, the efficacy of US quantitative methods (3-point method, 4-point method, 5-point method, and Matsumoto’s method) was confirmed by VUS in 68 patients. We assessed whether the ascites volume predicted by VUS corresponded with that calculated by 3D-CT. Of the 68 patients, 23 patients were analyzed before and after administration of tolvaptan.

Results

The predictive volumes calculated by VUS were remarkably relative to those yielded by conventional US. Correlations between exact volume and those measured by VUS were significantly high (3-point method: r?=?0.882, p?<?0.001; 4-point method: r?=?0.797, p?<?0.001; 5-point method: r?=?0.836, p?<?0.001; Matsumoto’s method: r?=?0.453, p?<?0.001). Correlations between decreasing volume on 3D-CT and that measured by VUS were also significantly high in patients with administration of tolvaptan.

Conclusion

Ascites volume measured by ultrasound was effective, especially the 3-point and 5-point methods. It was useful to assess the efficacy of diuretics in cirrhotic patients.