The additive effect of intravitreal dexamethasone combined with bevacizumab in refractory diabetic macular edema.

PURPOSE: To evaluate the short-term structural and visual outcomes and side effects associated with intravitreal dexamethasone (IVD) combined with bevacizumab (IVB) in treating patients with diabetic macular edema (DME) and an inadequate response to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: In this prospective interventional case series, a total of 81 eyes of 81 patients with type 2 diabetes mellitus (T2DM) and refractory DME were included and assigned to one of two groups: I) those receiving three monthly intravitreal injections of combined bevacizumab and dexamethasone (IVB+IVD) and II) those receiving three monthly intravitreal injections of bevacizumab alone (IVB). The primary outcome was the inter-group difference in central macular thickness (CMT); secondary outcomes included best-corrected visual acuity (BCVA), baseline optical coherence tomography (OCT) biomarkers, and intraocular pressure (IOP) one month after the last injection. RESULTS: Reduction in CMT and improvement in BCVA were significantly greater in the IVB+IVD group than the IVB group (109.88±156.25 vs. 43±113.67, respectively, P=0.03; and -0.13±0.23 vs. -0.01±0.17, respectively, P=0.008). Presence of neurosensory retinal detachment (NSD) (P<0.001) and complete inner segment/outer segment junction (IS-OS) disruption (P=0.049) on baseline OCT scans were associated with further CMT reductions in response to IVD. Conversely, identifiable epiretinal membrane (ERM) (P=0.002) and multiple hyperreflective foci (>20) (P=0.049) were associated with smaller reductions in CMT. Vitreomacular traction correlated with worse visual outcomes in the IVB+IVD group (P=0.003). The intergroup IOP difference was not clinically significant. CONCLUSION: In patients with refractory DME, addition of IVD to the standard IVB regimen can improve visual and structural outcomes without increasing the risk of endophthalmitis, IOP rise, or intraocular inflammation. Patients with NSD are more likely to respond well to IVD. The presence of ERM may predict poor treatment response.

Acetazolamide and bevacizumab combination therapy versus bevacizumab monotherapy in macular edema secondary to retinal vein occlusion.

PURPOSE: To determine and compare the efficacy of intravitreal bevacizumab (IVB) and oral acetazolamide (OA) combination therapy versus IVB monotherapy in patients with macular edema secondary to retinal vein occlusion (RVO). METHODS: This randomized clinical trial included 54 eyes of 52 patients with RVO central macular thickness (CMT) of more than 300µm, and best corrected visual acuity (BCVA) between 20/400 and 20/40. Eligible patients were randomly assigned to two groups: (I) IVB and OA (250mg twice daily) combination therapy or (II) IVB monotherapy. Ocular injections were repeated monthly for up to three months; BCVA and CMT were measured monthly. RESULTS: Both regimens resulted in significant reduction in CMT (534±150µm to 352±90µm in the IVB+OA group, P<0.001; and 580±175µm to 362±90µm in the IVB group, P<0.001); neither showed superiority in this regard. Likewise, BCVA showed significant improvement in both groups (0.87±0.56 to 0.53±0.28 LogMAR in the IVB+OA group, P=0.001; and 0.85±0.62 to 0.46±0.4 LogMAR in the IVB group, P<0.001), with no intergroup difference. CONCLUSION: Addition of oral acetazolamide to IVB in eyes with macular edema secondary to RVO may not result in additional short-term benefits regarding functional and anatomical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05290948, registered on March 22, 2022. https://clinicaltrials.gov/ct2/show/NCT05290948.

Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis Patients, Single-Center, Prospective, Open-Label, Single-Arm Clinical Trial, Long-Term Follow-up.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with very limited treatment options. Stem cells have been raised as a new treatment modality for these patients. We have designed a single-center, prospective, open-label, and single arm clinical trial to assess the safety, feasibility, and rather efficacy of administrating allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) in ALS patients. We enrolled 17 patients with confirmed ALS diagnosis with ALS Functional Rating Scale-Revised (ALSFRS-R) ≥24 and predicted forced vital capacity (FVC) ≥40%. Allogeneic Ad-MSCs were transplanted intravenously for all patients. Follow-ups were done at 24 hours, 2, 4, 6, and 12 months after cell infusion by checking adverse events, laboratory tests, and clinically by ALSFRS-R and FVC. Patients were also followed five years later and ALSFRS-R score was recorded in the survived individuals. There was no report of severe adverse events related to cell infusion. Two patients experienced dyspnea and chest pain 36 and 65 days after cell infusion due to pulmonary emboli. The progressive decrease in ALSFRS-R and FVC levels was recorded and three patients died in the first year. During five years follow up, despite a notable decrease in functional scores, 5 patients survived. Intravenous (IV) infusion of allogeneic Ad-MSCs in ALS patients is safe and feasible. The survival rate of the patients is more than IV autologous MSCs (Registration number: IRCT20080728001031N26).

A Randomized Crossover Intervention Study on the Effect a Standardized Maté Extract (Ilex paraguariensis A. St.-Hil.) in Men Predisposed to Cardiovascular Risk.

(1) Background: Due to its richness in chlorogenic acids (CGAs), Maté (Ilex paraguariensis A. St.-Hil.) could be of interest in the prevention of cardiometabolic diseases, however clinical evidence are lacking. This trial aimed to evaluate the impact of maté CGAs, consumed in a daily dose achievable through traditional maté beverages, on parameters related to cardiometabolic risk. (2) Design: Thirty-four male volunteers aged 45-65 years and with at most one criteria of metabolic syndrome, were recruited for a randomized, double-blind, placebo-controlled, and crossover study. The volunteers were assigned to consume an encapsulated dry maté extract for four-weeks, providing 580 mg of caffeoyl quinic acid derivatives (CQAs) daily, or a placebo, with a two weeks washout between intervention periods. Anthropometric variables, blood pressure, plasma glucose, lipids, endothelial, and inflammatory biomarkers were measured in overnight-fasted subjects and after a glucose load. (3) Results: We found no significant effects of treatment on these parameters and the response to the glucose load was also similar between the two interventions. However, a significant decrease in fasting glucose was observed between day 0 and day 28 for the maté group only (-0.57 ± 0.11 mmol/L, p < 0.0002). In subjects with an intermediate to high Framingham risk score, consumption of maté extract induced a 10% increase of high-density lipoprotein (HDL)-c from baseline. In a subgroup representative of the study population, significant decreases in the C-reactive protein (CRP) (-50%) and interleukin-6 (IL-6) (-19%) levels were observed. (4) Conclusions: These clinical observations suggest that maté, naturally rich in CGAs, could improve some cardiometabolic markers in subjects with a higher predisposition to metabolic syndrome, even if that remains to be confirmed in new trials specifically targeting this population.

Cellular and Molecular Mechanisms of Antithrombogenic Plants: A Narrative Review.

Heart attack, stroke, and deep vein thrombosis are among the conditions that alter blood coagulation and are modulated by antithrombogenic drugs. Natural products are an important source of antithrombogenic agents and have been considered remarkable alternatives with greater efficacy and usually with fewer side effects. However, the efficacy and toxicity of many of these plants that are used in traditional medicine must be scientifically tested. Despite a large number of published articles that report that plants or plant-derived components may act as antithrombogenic agents, few studies have investigated the mechanism of action of medicinal plants. This review presents the current knowledge about the major cellular and molecular mechanisms of antithrombogenic plants and their main components. Many well-established mechanisms (e.g., platelet aggregation, coagulation factors, and thrombolysis) are related to the antithrombogenic activity of many natural products. However, the central pathways that are responsible for their activity remain unclear. Further studies are needed to clarify the central role of each of these pathways in the pleiotropic response to these agents.

Evaluation of Th17 associated antigen in Old World Cutaneous Leishmaniasis: A comparative study in acute versus chronic human cutaneous Leishmaniasis using immunohistochemistry.

There are little information about Th17 cells and cutaneous Leishmaniasis (CL), due to an important effect of Th17 cells on immune response, it is worth to explore the role of Th17 on CL. The purpose of this study was to assess Th17 population in patients with acute vs. chronic CL lesions in comparison with skin samples collected from healthy volunteers in an endemic region of Old World CL. A total of 49 patients with clinical manifestations of chronic (n=16) and acute (n=33) CL lesions were recruited. The clinical diagnosis of CL was confirmed by direct smear or PCR. Biopsy specimens from prelesional skin of non-infectious lesions of 30 healthy individuals were used as control. Tissue sections of 3µm thickness were prepared and used for immunohistochemistry (IHC) analysis with primary antibody specific for Th17 associated antigen (CD161). For IHC, Envision+ (DakoCytomation) system was used and developed by using diaminobenzidine (DakoCytomation). The mean age of 33 patients with acute CL and the mean age of 16 patients with chronic CL were accordingly 45.24±16.43 and 33.56±15.87. In acute and chronic CL the mean (±standard deviation) and median (±interquartile range) were accordingly 2.92±2.21, 2.56±2.9 and 2.1±1.99, 1.54±2.81. In healthy controls the mean (±standard deviation) and median (±interquartile range) were 0.72±0.41 and 0.61±0.58 respectively. With pairwise comparison of acute, chronic and control groups, there were significant difference between acute and control (P value < 0.001), chronic and control (P value = 0.043). The results showed that there was an increasing cellular response of Th17 in both acute and chronic CL patients. Th17 was significantly higher in patients with acute and chronic CL lesions in comparison with healthy control group. However, there was no significant difference between acute and chronic infection concerning to Th17 cells.

Bioperformance of chitosan/fluoride-doped diopside nanocomposite coatings deposited on medical stainless steel.

This work focuses on the structure, bioactivity, corrosion, and biocompatibility characteristics of chitosan-matrix composites reinforced with various amounts of fluoride-doped diopside nanoparticles (at 20, 40, 60, and 80 wt%) deposited on stainless steel 316 L. Bioactivity studies reveal that the presence of the nanoparticles in the coatings induces apatite-forming ability to the surfaces. Based on electrochemical impedance spectroscopy and polarization experiments, the in vitro corrosion resistance of the substrate was enhanced by increasing the level of the nanoparticles in the coating. The sample containing 60% of the nanoparticles presented the highest osteoblast-like MG63 cell viability, in comparison to the other prepared and even control samples. Also, the cell attachment on the surfaces was improved with increasing the amount of the nanoparticles in the coatings. It is eventually concluded that the application of chitosan/fluoride-doped diopside nanocomposite coatings improves the bioperformance of metallic implants.

Differentiating Atypical Hemangiomas and Metastatic Vertebral Lesions: The Role of T1-Weighted Dynamic Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: Vertebral hemangiomas are benign vascular lesions that are almost always incidentally found in the spine. Their classic typical hyperintense appearance on T1- and T2-weighted MR images is diagnostic. Unfortunately, not all hemangiomas have the typical appearance, and they can mimic metastases on routine MR imaging. These are generally referred to as atypical hemangiomas and can result in misdiagnosis and ultimately additional imaging, biopsy, and unnecessary costs. Our objective was to assess the utility of dynamic contrast-enhanced MR imaging perfusion in distinguishing vertebral atypical hemangiomas and malignant vertebral metastases. We hypothesized that permeability and vascular density will be increased in metastases compared with atypical hemangiomas. MATERIALS AND METHODS: Consecutive patients from 2011 to 2015 with confirmed diagnoses of atypical hemangiomas and spinal metastases from breast and lung carcinomas with available dynamic contrast-enhanced MR imaging were analyzed. Time-intensity curves were qualitatively compared among the groups. Perfusion parameters, plasma volume, and permeability constant were quantified using an extended Tofts 2-compartment pharmacokinetic model. Statistical significance was tested using the Mann-Whitney U test. RESULTS: Qualitative inspection of dynamic contrast-enhanced MR imaging time-intensity curves demonstrated differences in signal intensity and morphology between metastases and atypical hemangiomas. Quantitative analysis of plasma volume and permeability constant perfusion parameters showed significantly higher values in metastatic lesions compared with atypical hemangiomas (P < .001). CONCLUSIONS: Our data demonstrate that plasma volume and permeability constant perfusion parameters and qualitative inspection of contrast-enhancement curves can be used to differentiate atypical hemangiomas from vertebral metastatic lesions. This work highlights the benefits of adding perfusion maps to conventional sequences to improve diagnostic accuracy.

Variation in bacterial endosymbionts associated with the date palm hopper, Ommatissus lybicus populations.

The date palm hopper, Ommatissus lybicus, is a key pest of the date palm, which is expected to be comprised of many allopatric populations. The current study was carried out to determine bacterial endosymbiont diversity in the different populations of this pest. Ten date palm hopper populations were collected from the main date palm growing regions in Iran and an additional four samples from Pakistan, Oman, Egypt and Tunisia for detection of primary and secondary endosymbionts using polymerase chain reaction (PCR) assay with their specific primers. The PCR products were directly sequenced and edited using SeqMan software. The consensus sequences were subjected to a BLAST similarity search. The results revealed the presence of 'Candidatus Sulcia muelleri' (primary endosymbiont) and Wolbachia, Arsenophonus and Enterobacter (secondary endosymbionts) in all populations. This assay failed to detect 'Candidatus Nasuia deltocephalinicola' and Serratia in these populations. 'Ca. S. muelleri' exhibited a 100% infection frequency in populations and Wolbachia, Arsenophonus and Enterobacter demonstrated 100, 93.04 and 97.39% infection frequencies, respectively. The infection rate of Arsenophonus and Enterobacter ranged from 75 to 100% and 62.5 to 100%, respectively, in different populations of the insect. The results demonstrated multiple infections by 'Ca. Sulcia muelleri', Wolbachia, Arsenophonus and Enterobacter in the populations and may suggest significant roles for these endosymbionts on date palm hopper population fitness. This study provides an insight to endosymbiont variation in the date palm hopper populations; however, further investigation is needed to examine how these endosymbionts may affect host fitness.