Association between R2CHA2DS2-VASc score and three-vessel coronary artery disease in a large population at high cardiovascular risk.

Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.

S309-CAR-NK cells bind the Omicron variants in vitro and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice.

Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein in vitro. In this study, we further demonstrate that the S309-CAR-NK cells can bind to different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants in vitro. We also show that S309-CAR-NK cells reduce virus loads in the NOD/SCID gamma (NSG) mice expressing the human angiotensin-converting enzyme 2 (hACE2) receptor challenged with SARS-CoV-2 wild-type (strain USA/WA1/2020). Our study demonstrates the potential use of S309-CAR-NK cells for inhibiting infection by SARS-CoV-2 and for the potential treatment of COVID-19 patients unresponsive to otherwise currently available therapeutics. IMPORTANCE: Chimeric antigen receptor (CAR)-NK cells can be "off-the-shelf" products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA/WA1/2020) in the lungs of NOD/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.

Middle meningeal artery embolization reduces recurrence following surgery for septated chronic subdural hematomas.

BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy. SIGNIFICANCE: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.

An expanded RT-PCR melting temperature coding assay to rapidly identify all known SARS-CoV-2 variants and sub-variants of concern.

The continued emergence of vaccine-resistant SARS-CoV-2 variants of concern (VOC) requires specific identification of each VOC as it arises. Here, we report an expanded version of our previously described sloppy molecular beacon (SMB) melting temperature (Tm) signature-based assay for VOCs, now modified to include detection of Delta (B.1.617.2) and Omicron (B.1.1.529) sub-variants. The SMB-VOC assay targets the signature codons 501, 484 and 452 in the SARS-CoV-2 spike protein which we show can specifically detect and differentiate all known VOCs including the Omicron subvariants (BA.1, BA.2, BA.2.12.1, BA.4/BA.5). The limit of detection (LOD) of the assay was 20, 22 and 36 genomic equivalents (GE) per reaction with the Delta, Omicron BA.1 and BA.2 respectively. Clinical validation of the 3-codon assay in the LC480 instrument showed the assay detected 94% (81/86) of the specimens as WT or VOCs and 6% (5/86) of the tests producing indeterminate results compared to sequencing. Sanger sequencing also failed for four samples. None of the specimens were incorrectly identified as WT or as a different VOC by our assay. Thus, excluding specimens with indeterminant results, the assay was 100% sensitive and 100% specific compared to Sanger sequencing for variant identification. This new assay concept can be easily expanded to add newer variants and can serve as a robust diagnostic tool for selecting appropriate monoclonal antibody therapy and rapid VOC surveillance.

12-year follow-up of the first endothelial keratoplasty without Descemet stripping in a 3-month newborn with Congenital Hereditary Endothelial Dystrophy (CHED).

BACKGROUND: Endothelial Keratoplasty (EK) is now considered as the standard treatment for Congenital Hereditary Endothelial Dystrophy (CHED) by many surgeons. We present the 12-year clinical outcome of the youngest operated patient with CHED in which we successfully performed a bilateral EK procedure without removing the recipient endothelium-Descemet complex. CASE PRESENTATION: In November 2010 we performed EK without Descemet Stripping in a 3-month female newborn, thinking that the lower manipulation obtained by leaving the recipient endothelium-Descemet complex could be the key factor for the success of our surgery. Such a particular technique was new in newborns. The surgery was a success, but the long-term visual result was not predictable at that time. We followed the patient at 4 months, and then yearly. At the latest visit in October 2022 the visual, cognitive, and motorial developments were normal, with Best-corrected Distance Visual Acuity of 0.4 LogMAR with - 0.75 D sf + 2.75 D cyl @ 105° in the right eye (RE) and 0.4 LogMAR with + 1.50 D sf + 2.50 D cyl @ 60° in the left eye (LE). The endothelial microscope showed an unexpected healthy endothelium, with a cell count of 2383 cells/mm2 in the RE and of 2547 cells/mm2 in the LE from a starting donor count of 2900 cells/mm2. No secondary procedures were performed during the 12-year follow-up. CONCLUSION: EK without Descemet stripping has proved to be a successful procedure over time in our newborn. The unexpected healthy endothelium suggests a role of the Descemet membrane in CHED.

Detection of Propionic Acids Trapped in Thin Zeolite Layer Using Thermal Desorption Analysis.

Volatile organic compounds (VOCs) have recently received considerable attention for the analysis and monitoring of different biochemical processes in biological systems such as humans, plants, and microorganisms. The advantage of using VOCs to gather information about a specific process is that they can be extracted using different types of samples, even at low concentrations. Therefore, VOC levels represent the fingerprints of specific biochemical processes. The aim of this work was to develop a sensor based on a photoionization detector (PID) and a zeolite layer, used as an alternative analytic separation technique for the analysis of VOCs. The identification of VOCs occurred through the evaluation of the emissive profile during the thermal desorption phase, using a stainless-steel chamber for analysis. Emission profiles were evaluated using a double exponential mathematical model, which fit well if compared with the physical system, describing both the evaporation and diffusion processes. The results showed that the zeolite layer was selective for propionic acid molecules if compared to succinic acid molecules, showing linear behavior even at low concentrations. The process to define the optimal adsorption time between the propionic acid molecules was performed in the range of 5 to 60 min, followed by a thermal desorption process at 100 °C. An investigation of the relationship between the evaporation and diffusion rates showed that the maximum concentration of detected propionic acid molecules occurred in 15 min. Other analyses were performed to study how the concentration of VOCs depended on the desorption temperature and the volume of the analysis chamber. For this purpose, tests were performed using three analysis chambers with volumes of 25 × 10-6, 50 × 10-6, and 150 × 10-6 m3 at three different desorption temperatures of 20 °C, 50 °C, and 100 °C, respectively. The results demonstrated that the evaporation rate of the VOCs increased rapidly with an increasing temperature, while the diffusion rate remained almost constant and was characterized by a slow decay time. The diffusion ratio increased when using a chamber with a larger volume. These results highlight the capabilities of this alternative technique for VOC analysis, even for samples with low concentrations. The coupling of a zeolite layer and a PID improves the detection selectivity in portable devices, demonstrating the feasibility of extending its use to a wide range of new applications.

Middle meningeal artery embolization of septated chronic subdural hematomas.

INTRODUCTION: Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence-septated cSDH-remains undetermined. METHODS: From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation. RESULTS: Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59-77) with 20% females. Twenty-eight cSDHs (35%) had septations identified on imaging. Surgical evacuation with burr holes was performed in 45% and craniotomy in 18.8%. Baseline characteristics between no-septations (no-SEP) and septations (SEP) groups were similar except for median age (SEP vs no-SEP, 72.5 vs. 65.5, p = 0.016). The recurrence rate was lower in the SEP group (SEP vs. no-SEP, 3 vs. 16.7%, p = 0.017) with higher odds of response from MMAE for septated lesions even when controlling for evacuation strategy and antithrombotic use (OR = 0.06, CI [0.006-0.536], p = 0.012). MMAE resulted in higher mean absolute thickness reduction (SEP vs. no-SEP, -8.2 vs. -4.8 mm, p = 0.016) with a similar midline shift change. The rate of reoperation did not differ (6.2 vs. 3.1%, p = 0.65). CONCLUSION: MMAE appears to be equal to potentially more effective in preventing the recurrence of cSDH in septated lesions. These findings may aid in patient selection.

From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures.

Background and aim-Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods-Thirty subjects, aged 45-65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results-Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions-The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.

The temporal effects of asymptomatic COVID-19 infection on peri-operative complications in patients receiving total joint arthroplasty.

INTRODUCTION: Recent coronavirus disease 2019 (COVID-19) infection may pose increased risk of post-operative complications after total joint arthroplasty (TJA). Current recommendations suggest waiting four-weeks before elective surgery in asymptomatic patients. The purpose of this study was to propensity-score-match patients who had positive COVID-19-test between (1) 0-2 weeks and (2) 2-4 weeks before TJA with a matching group without COVID-19 history to determine rates of complications at 90-days and 1-year post-operatively. MATERIALS AND METHODS: We queried a national-database for patients who tested positively for COVID-19 within 1-month (n = 1749) before TJA. A propensity-score-match analysis was conducted to limit influence of confounders. They were separated into mutually exclusive asymptomatic cohorts based on time of positive COVID-19-test before TJA: within 2-weeks (n = 1749) and between 2-to-4 weeks (n = 599). Asymptomatic patients were patients with positive test without symptoms of fever, shortness of breath, nausea, vomiting, diarrhea, loss of taste or smell, cough, bronchitis, pneumonia, lung infections, septic shock, and multiple-organ-dysfunction. Complications analyzed: 90-day and 1-year periprosthetic-joint infections (PJIs), surgical-site infections(SSIs), wound complications, cardiac complications, transfusions, and venous thromboembolisms. RESULTS: Asymptomatic patients who have COVID-19 demonstrated increased incidence of PJI in patients who had TJA performed within two weeks from positive test at 90-days compared to patients who did not test positive for COVID-19 (3.0 vs. 1.5%; p = 0.023). Upon totaling all 90-day post-operative complications, no significant difference was found amongst asymptomatic patients who tested positive for COVID-19 for total complications at 90-days (p = 0.936). CONCLUSIONS: Asymptomatic patients who test positive for COVID-19 don't have increased risk for post-operative complications after TJA. However, two-fold increased risk in PJI for patients who tested positive for COVID-19 in first 2-weeks cannot be ignored. These results should be taken into consideration when surgeons consider performing TJA. We recommend asymptomatic patients consider waiting two-weeks before TJA to mitigate risk of PJI. Nevertheless, there's reassurance these patients are not at increased total complication risk.

Albuminuria improves R2CHA2DS2-VASc score in predicting mortality in high cardiovascular risk population.

BACKGROUND AND AIMS: The CHA2DS2-VASc score estimates the risk of cardioembolism in patients with atrial fibrillation (AF). It also predicts vascular events and death in different clinical settings, even in the absence of AF. The R2CHA2DS2-VASc score, obtained by adding the glomerular filtration rate to CHA2DS2-VASc, shows a higher prediction ability for new events and all-cause mortality. The present study aims to assess whether the addition of albuminuria to R2CHA2DS2-VASc score further improves its discrimination ability in predicting all-cause mortality in a sample of high cardiovascular risk population. METHODS AND RESULTS: Prospective, monocentric, observational study, evaluating a subset of 737 subjects consecutively undergoing to coronary angiography at Coronary Unit of Scientific Institute "Casa Sollievo della Sofferenza" from June 2016 to December 2018. The presence of albuminuria was significantly associated with all-cause mortality (p < 0.0001). Any one-point increase of Alb-R2CHA2DS2-VASc score increased mortality of about 1.5-fold (adjusted HR 1.49; 95%CI: 1.37-1.63; p < 0.0001). Considering tertiles of Alb-R2CHA2DS2-VASc, the third tertile showed a 9.5-fold increased risk of mortality (HR 9.52; 95% CI: 5.15-17.60, p < 0.001). Comparing the two scores, the Alb-R2CHA2DS2-VASc score (C-statistic = 0.751; 95%CI: 0.69-0.81) outperformed the R2-CHA2DS2-VASc score (C-statistic = 0.736; 95%CI: 0.68-0.961) in predicting mortality (delta C-statistic = 0.015; 95%CI: 0.001-0.029). The better prediction ability of the Alb-R2CHA2DS2-VASc score was also proven by an IDI of 0.024 (p < 0.0001) and a relative IDI of 24.11% (p < 0.0001), with an NRI = 0.608 (p < 0.00001). CONCLUSIONS: The addition of albuminuria to R2CHA2DS2-VASc significantly and independently predicts the risk of all-cause mortality in a sample of high CV risk patients. Moreover, Alb-R2CHA2DS2-VASc outperforms R2CHA2DS2-VASc.

Oral Epithelial Cells Expressing Low or Undetectable Levels of Human Angiotensin-Converting Enzyme 2 Are Susceptible to SARS-CoV-2 Virus Infection In Vitro.

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics.

Acuity and Quality of Vision in Eyes with Epithelial Basement Membrane Dystrophy after Regular Pseudophakia.

PURPOSE: This retrospective case-control study was conducted to quantitatively and qualitatively assess the visual impairment in eyes with Epithelial Basement Membrane Dystrophy (EBMD) after regular cataract surgery. METHODS: EBMD pseudophakic eyes were compared with matched pseudophakic eyes free from surface disorders. At least 3 weeks after surgery we evaluated uncorrected and best-corrected distance visual acuity (UDVA and CDVA), objective aberrometry, Point Spread Function (PSF), Modulation Transfer Function (MTF), and patient complaints. RESULTS: Twenty-five EBMD eyes and 25 control eyes (13 patients per group) were included. Nine patients per group had a monofocal IOL, and four patients had a trifocal IOL. All the EBMD patients complained of postoperative blurred vision with ocular discomfort; intensive use of lubricants induced subjective improvement only in eyes with monofocal IOLs. Postoperative mean UDVA was 0.19 ± 0.16 LogMAR in the EBMD eyes and 0.11 ± 0.04 LogMAR in the control group (p = 0.016). Mean CDVA was 0.18 ± 0.15 LogMAR in the EBMD eyes and 0.06 ± 0.04 LogMAR in the control eyes (p = 0.001). The PSF curve width was significantly worse in the EBMD group (p < 0.001). The MTF cut-off value was lower in the EBMD group than in the control group (p < 0.001). CONCLUSION: After cataract removal, eyes with EBMD had significantly lower UDVA and CDVA than controls. All the aberrometric parameters were significantly worse in EBMD cases. EBMD patients complained about their postoperative visual outcome, while control patients did not.

Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms.

Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required. Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM). Results: MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001). Conclusions: Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.

Refractive Outcome and 5-Year Capsulotomy Rate of Hydrophobic and Hydrophilic IOLs with Similar Optical Design: A Contralateral Study.

INTRODUCTION: To compare the short-term visual and aberrometric outcomes and the long-term capsulotomy incidence in a cohort of patients receiving IOLs with similar structural profile but with a hydrophobic matrix in one eye (PHOB group) and a hydrophilic matrix in the other one (PHIL group). METHODS: In this retrospective, contralateral study, 26 patients sequentially undergoing phacoemulsification were implanted as mentioned above. Refraction and aberrometry were evaluated 6 months after surgery. For the quality of vision, the Hartmann-Shack optical aberration, Double-Pass Modulation Transfer Function (MTF), contrast sensitivity, and dysphotopsia results were compared. Capsulotomy was ascertained and dated by medical chart revision or phone call. RESULTS: All the considered quantitative and qualitative visual parameters tested statistically comparable between PHIL and PHOB group. After 5 years, four patients (16.7%) in the PHOB group and five patients (20.8%) in the PHIL group underwent a Nd:YAG posterior capsulotomy (P > 0.5). CONCLUSION: In this contralateral comparative study, the hydrophobic and hydrophilic matrix of the IOL similarly influenced the visual and aberrometric outcomes. Also the long-term laser capsulotomy incidence did not statistically differ between groups. The posterior IOL profile, rather than matrix hydrophilia, could consistently influence the posterior capsule opacification.

Asymptomatic carotid artery stenosis: a summary of current state of evidence for revascularization and emerging high-risk features.

Carotid artery stenosis is a leading cause of ischemic stroke. While management of symptomatic carotid stenosis is well established, the optimal approach in asymptomatic carotid artery stenosis (aCAS) remains controversial. The rapid evolution of medical therapies within the time frame of existing landmark aCAS surgical revascularization trials has rendered their findings outdated. In this review, we sought to summarize the controversies in the management of aCAS by providing the most up-to-date medical and surgical evidence. Subsequently, we compile the evidence surrounding high-risk clinical and imaging features that might identify higher-risk lesions. With this, we aim to provide a practical framework for a precision medicine approach to the management of aCAS.

Middle Meningeal Artery Embolization for Chronic Subdural Hematomas With Concurrent Antithrombotics.

BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment. OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma. METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in CSDH thickness, and midline shift. RESULTS: Fifty-seven patients met inclusion criteria. The median age was 66 years (IQR 58-76) with 21.1% females. Sixty-six embolizations were performed. The median length to follow-up was 20 days (IQR 14-44). Nineteen patients (33.3%) had rapid reinitiation of antithrombotics (5 antiplatelet, 11 anticoagulation, and 3 both). Baseline characteristics between the no antithrombotic (no-AT) and the AT groups were similar. The recurrence rate was higher in the AT group (no-AT vs AT, 9.3 vs 30.4%, P = .03). Mean absolute reduction in CSDH thickness and midline shift was similar between groups. Rate of reoperation did not differ (4.7 vs 8.7%, P = .61). CONCLUSION: Rapid reinitiation of AT after MMA embolization for CSDH leads to higher rates of recurrence with similar rates of reoperation. Care must be taken when initiating antithrombotics after treatment of CSDH with MMA embolization.

One-dioptre toric IOL versus spherical IOL in eyes with low preoperative corneal astigmatism.

PURPOSE: To investigate the advantages/disadvantages of a 1.0 D toric IOL vs spherical IOL after regular phacoemulsification in eyes with preoperative astigmatism ≤ 1 D. METHODS: Retrospective comparative series involving pseudophakic eyes with preoperative topographic astigmatism ≤ 1.0 D implanted either with monofocal 1.0 D Toric IOL (T-group), or with spherical IOL (S-group). The postoperative refractive astigmatism (PRA, i.e. surgically induced + corneal) was the main outcome; also considered in the analyses were the uncorrected and best-corrected distance visual acuity (VA). The data were referred to the last postoperative follow-up visit, 2 to 4 months after surgery. RESULTS: A total of 60 eyes were included: 30 in the T-group and 30 in the S-group, matched for patient's age, laterality, and axial length. Before surgery, the mean corneal astigmatism was 0.62 ± 0.39 D in the T-group and 0.54 ± 0.33 D in the S-group (p = 0.4). In the S-group, PRA was 0.73 ± 0.37 D, higher than the corresponding preoperative corneal astigmatism (p = 0.040). In the T-group, PRA was 0.58 ± 0.31 D; the variation was not statistically significant. Uncorrected VA was significantly better in the T-group vs the S-group (p = 0.007), and the best-corrected VA was comparable in the two groups. CONCLUSION: The present study indicated that in eyes with very low preoperative astigmatism, 1.0 D toric IOLs were able to limit the increase of the PRA instead of those observed with the spherical IOLs. This could support the better uncorrected VA recorded in the T-group.