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Topic: To provide an overview on the incidence of Acanthamoeba keratitis (AK)., Clinical Relevance: Although being a sight-threatening cause of infectious keratitis, a comprehensive assessment of the incidence of AK is lacking., Methods: Incidence of AK was computed as the number of eyes with AK per health care center, per year (annualized center incidence [ACI]). Two meta-analytical ratios also were calculated: (1) the ratio of eyes with AK to the count of eyes with nonviral microbial keratitis (MK) and (2) the ratio of eyes with AK to the overall population (i.e., the total number of people in a nation or region, as indicated by the authors in each study). Center was defined as the health care facility where the study took place. Actual and projected estimates of the number of eyes with AK in years were calculated multiplying the ratio of eyes with AK to the total population and the corresponding population estimates, sourced from the United Nations Population Prospects., Results: Overall, 105 articles were included, published between 1987 and 2022. The total number of eyes identified was 91 951, with 5660 eyes affected by AK and 86 291 eyes affected by nonviral MK. The median ACI was 1.9 eyes with AK per health care center per year (95% confidence interval [CI], 1.5-2.6 eyes), with no statistically significant differences among continents. The ratio of eyes with AK to the total number of eyes with MK was 1.52% (95% CI, 1.03%-2.22%), whereas the ratio of eyes with AK in relationship to the entire population was estimated at 2.34 eyes per 1 000 000 people (95% CI, 0.98-5.55 per 1 000 000 people). The projected increase in the numbers of eyes with AK indicated an increase of 18.5% (n = 15 355 eyes with AK) in 2053 and 25.5% (n = 16 253 eyes with AK) in 2073, compared with the baseline of 2023 (n = 12 953 eyes with AK)., Discussion: Acanthamoeba keratitis emerged as a relatively low-incident disorder, and no significant differences in terms of its incidence were found among different continents., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The study investigates the impact of the d-lactic acid units content on the crystallinity and crystal structure of commercial poly(lactic acid) (PLA) grades, which are copolymers of poly(l-lactic acid) (PLLA) containing a minor amount of d-units. As the d-units content increases, a detectable decrease in crystallinity was observed along with a simultaneous rise in mobile amorphous fraction (MAF) and a reduction in rigid amorphous fraction (RAF). The percentage of d-units was found not to significantly affect RAF thickness, suggesting that the d-units are not completely excluded from the crystals. The inclusion of d-units as defects in the PLA crystal lattice was confirmed by XRD analysis, which disclosed that the crystal phase gets gradually richer of d-units as the crystallization time evolves. FT-IR analysis proved that the incorporation of d-units in the crystal phase is promoted by the formation of local CH 3 ···O=C interactions, similar to those massively active between PLLA and poly(d-lactic acid) (PDLA) in the stereocomplex. The establishment of these interactions leads to a contraction of the interplanar distances and a decrease in the crystal cell volume with increasing the crystallization time and the d-units percentage. In summary, the study proves that for PLA copolymers containing a d-units percentage at least up to about 8 %, d-units are included in the crystal lattice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures None.

Objective: Zonular dialysis (ZD), referred to as the presence of a deficient zonular support for the lenticular capsule, might be the result of several causes and be detected only at the time of cataract surgery. The aim of this study was to evaluate pre-, intra-, and postoperative features of eyes with ZD regardless of the etiology detected during cataract surgery., Methods: A single-centre retrospective observational cohort study was performed at Moorfields Eye Hospital (NHS Foundation Trust, London, U.K.) to identify patients who underwent cataract surgery whose procedure was intraoperatively described as being complicated by ZD between January 1, 2014, and August 22, 2019. Patient characteristics, intraoperative clinical findings, visual and refractive outcomes, and postoperative complications were recorded., Results: ZD was identified intraoperatively in 447 eyes. In most cases (213 of 223; 96.8%), patients underwent a phacoemulsification procedure, not requiring any conversion to intracapsular or extracapsular extraction technique. Intraoperative complications increased to 46.2% (103 of 223), with no significant correlation with ZD width. Capsular tension rings (CTRs) were implanted in 43.4% of patients (97 of 223). The use of CTRs correlated with better postoperative visual and refractive outcomes., Conclusions: ZD is a serious complication of cataract surgery requiring prompt intraoperative diagnosis and proper management. While it tends to worsen cataract surgery outcomes, the implantation of CTRs during the surgical procedure seems to be associated with better postoperative visual and refractive results., (Copyright © 2022 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Morin is a vasorelaxant flavonoid, whose activity is ascribable to Ca V 1.2 channel blockade that, however, is weak as compared to that of clinically used therapeutic agents. A conventional strategy to circumvent this drawback is to synthesize new derivatives differently decorated and, in this context, morin-derivatives able to interact with Ca V 1.2 channels were found by employing the potential of PLATO in target fishing and reverse screening. Three different derivatives (5a-c) were selected as promising tools, synthesized, and investigated in in vitro functional studies using rat aorta rings and rat tail artery myocytes. 5a-c were found more effective vasorelaxant agents than the naturally occurring parent compound and antagonized both electro- and pharmaco-mechanical coupling in an endothelium-independent manner. 5a, the series' most potent, reduced also Ca 2+ mobilization from intracellular store sites. Furthermore, 5a≈5c > 5b inhibited Ba 2+ current through Ca V 1.2 channels. However, compound 5a caused also a concentration-dependent inhibition of K Ca 1.1 channel currents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Geographic variation in health care spending is typically attributed to differences in patient health status and provider practice patterns. While medicolegal considerations (i.e., "defensive medicine") anecdotally impact health care spending, this phenomenon is difficult to measure. The purpose of this study was to explore the association between the medicolegal environment and Medicare costs for diabetes and associated conditions of interest to vascular surgeons. Specifically, we hypothesized that an adverse medicolegal environment is associated with higher per capita Medicare costs for diabetic patients., Methods: Medicare data including the most recent (2018) Medicare Geographic Variation Public Use Files and Chronic Conditions Data Files were linked to National Practitioner Data Bank files from the preceding 5 years (2013-2017), in addition to the US census data and American Medical Association workforce statistics. The state-level medicolegal environment was characterized by K-means clustering across a panel of metrics related to malpractice payment magnitude and prevalence. Per capita Medicare spending for diabetes was compared across 5 distinct medicolegal environments. Costs were standardized and risk-adjusted to account for known geographic variation in health care costs and patient population. Analysis of variance was applied to unadjusted data, followed by multivariate regression modeling. Readmission rates, per capita imaging studies, per capita tests, per capita procedures, and lower extremity amputation rates were compared between the least litigious quintile from the K-means clustering and the 2 most litigious quintiles., Results: The median unadjusted Medicare per capita expenditure on diabetic patients was $15,963 ($14,885-$17,673), ranging from $13,762 (Iowa) to $21,865 (D.C.). A 1.6-fold variation persisted after payment standardization. Cluster analysis based on malpractice-related variables yields 5 distinct medicolegal environments, based on litigation frequency and malpractice payment amounts. Per capita spending on diabetes varied, ranging from $15,799 in states with low payments and infrequent litigation to $18,838 in states with the most adverse medicolegal environment (P < 0.05). After cost standardization and risk adjustment with multiple linear regression, malpractice claim prevalence (per 100 physicians) remained an independent predictor of states with the highest diabetes mellitus spending (P = 0.022). Moreover, diabetic patients in states with adverse medicolegal environments had more procedures, imaging studies, and readmissions (P < 0.05 for all) but did not have significant differences in amputation rates compared to less litigious states., Conclusions: An adverse medicolegal environment is independently associated with higher health care costs but does not result in improved outcome (i.e. amputation rate) for diabetic Medicare beneficiaries. Across states, a 1% increase in lawsuits/100 physicians was associated with a >10% increase in risk-adjusted standardized per capita costs. These findings demonstrate the potential contribution of "defensive medicine" to variation in health care utilization and spending in a population of interest to vascular surgeons., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sotorasib (Lumakras™) is a first-in-class, non-genotoxic, small molecule inhibitor of KRAS G12C developed as an anticancer therapeutic for treatment of patients that have a high unmet medical need. Anticancer therapeutics are considered out of scope of ICH M7 guidance for control of mutagenic impurities; however, based on ICH S9 Q&A, mutagenicity assessments are needed for impurities that exceed the qualification threshold, consistent with ICH Q3A/B, and non-mutagenic drugs. Here, we carried out hybrid-based mutagenicity assessment of sotorasib drug substance (DS) impurities using in silico quantitative structure-activity relationship (QSAR) modelling and Ames tests (for in silico positive mutagens). We encountered contradictive mutagenicity results for 2 impurities (Beta-Chloride and PAC). PAC was negative initially by QSAR but positive in a GLP full plate Ames test and Beta-Chloride was positive by QSAR, negative in a non-GLP micro-Ames but positive in a GLP full plate Ames assay. Root cause analyses identified and characterized mutagenic contaminants, 3-chloropropionic acid in batches of Beta-Chloride and 3-chloropropionic acid and Chloro-PAC in batches of PAC, used in initial GLP full-plate Ames tests. Significant reduction of these contaminants in re-purified batches resulted in no induction of mutagenicity in follow-up GLP micro-Ames tests. In summary, root-cause analyses led to accurate mutagenicity assessment for sotorasib DS-associated impurities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The outcomes after open repair of thoracoabdominal aneurysms (TAAAs) have been definitively demonstrated to worsen as the TAAA extent increases. However, the effect of TAAA extent on fenestrated/branched endovascular aneurysm repair (F/BEVAR) outcomes is unclear. We investigated the differences in outcomes of F/BEVAR according to the TAAA extent., Methods: We reviewed a single-institution, prospectively maintained database of all F/BEVAR procedures performed in an institutional review board-approved registry and/or physician-sponsored Food and Drug Administration investigational device exemption trial (trial no. G130210). The patients were stratified into two groups: group 1, extensive (extent 1-3) TAAAs; and group 2, nonextensive (juxtarenal, pararenal, and extent 4-5) TAAAs. The perioperative outcomes were compared using the χ 2 test. Kaplan-Meier analysis of 3-year survival, target artery patency, reintervention, type I or III endoleak, and branch instability (type Ic or III endoleak, loss of branch patency, target vessel stenosis >50%) was performed. Cox proportional hazards modeling was used to assess the independent effect of extensive TAAA on 1-year mortality., Results: During the study period, 299 F/BEVAR procedures were performed for 87 extensive TAAAs (29%) and 212 nonextensive TAAAs (71%). Most repairs had used company-manufactured, custom-made devices (n = 241; 81%). Between the two groups, no perioperative differences were observed in myocardial infarction, stroke, acute kidney injury, dialysis, target artery occlusion, access site complication, or type I or III endoleak (P > .05 for all). The incidence of perioperative paraparesis was greater in the extensive TAAA group (8.1% vs 0.5%; P = .001). However, the incidence of long-term paralysis was equivalent (2.3% vs 0.5%; P = .20), with nearly all patients with paraparesis regaining ambulatory function. On Kaplan-Meier analysis, no differences in survival, target artery patency, or freedom from reintervention were observed at 3 years (P > .05 for all). Freedom from type I or III endoleak (P < .01) and freedom from branch instability (P < .01) were significantly worse in the extensive TAAA group. Cox proportional hazards modeling demonstrated that F/BEVAR for extensive TAAA was not associated with 1-year mortality (hazard ratio, 1.71; 95% confidence interval, 0.91-3.52; P = .13)., Conclusions: Unlike open TAAA repair, the F/BEVAR outcomes were similar for extensive and nonextensive TAAAs. The differences in perioperative paraparesis, branch instability, and type I or III endoleak likely resulted from the increasing length of aortic coverage and number of target arteries involved. These findings suggest that high-volume centers performing F/BEVAR should expect comparable outcomes for extensive and nonextensive TAAA repair., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC 50 from 2.47 to 5.75 µM) and low cytotoxicity (CC 50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Wound healing represents an urgent need from the clinical point of view. Several diseases result in wound conditions which are difficult to treat, such as in the case of diabetic foot ulcer. Starting from there, the medicinal research has focused on various targets over the years, including GPCRs as new wound healing drug targets. In line with this, GPR120, known to be an attractive target in type 2 diabetes drug discovery, was studied to finalize the development of new wound healing agents. Pinocembrin (HW0) was evaluated as a suitable compound for interacting with GPR120, and was hybridized with fatty acids, which are known endogenous GPR120 ligands, to enhance the wound healing potential and GPR120 interactions. HW0 and its 7-linolenoyl derivative (HW3) were found to be innovative wound healing agents. Immunofluorescence and functional assays suggested that their activity was mediated by GPR120, and docking simulations showed that the compounds could share the same pocket occupied by the known GPR120 agonist, TUG-891., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Quercetin represents one of the most studied dietary flavonoids; it exerts a panel of pharmacological activities particularly on the cardiovascular system. Stimulation of vascular K Ca 1.1 channels contributes to its vasorelaxant activity, which is, however, counteracted in part by its concomitant stimulation of Ca V 1.2 channels. Therefore, several quercetin hybrid derivatives were designed and synthesized to produce a more selective K Ca 1.1 channel stimulator, then assessed both in silico and in vitro. All the derivatives interacted with the K Ca 1.1 channel with similar binding energy values. Among the selected derivatives, 1E was a weak vasodilator, though displaying an interesting Ca V 1.2 channel blocking activity. The lipoyl derivatives 1F and 3F, though showing pharmacological and electrophysiological features similar to those of quercetin, seemed to be more effective as K Ca 1.1 channel stimulators as compared to the parent compound. The strategy pursued demonstrated how different chemical substituents on the quercetin core can change/invert its effect on Ca V 1.2 channels or enhance its K Ca 1.1 channel stimulatory activity, thus opening new avenues for the synthesis of efficacious vasorelaxant quercetin hybrids., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the putative differences in terms of vessel density and flow area between control (CTRL), high-pressure glaucoma (HPG) and normal tension glaucoma (NTG) subjects at macular and peripapillary level. To assess the correlation between Visual Field Index (VFI), the stage of glaucoma, and optical coherence tomography angiography (OCT-A) parameters., Material and Methods: In this pilot, prospective study 46 eyes of 46 glaucomatous patients (19 NTG+27 HPG) and 25 control eyes (CTRL) of 25 subjects were recruited. All patients underwent a complete ophthalmologic examination and visual field testing. A 3×3mm volumetric macular scan (Angio Retina [3.0]) and a 4.5×4.5mm diameter peripapillary scan (Angio Disc [4.5]) were performed in the right eye using RTVue-XR Avanti (Optovue, Inc.) OCT-A., Results: Groups were homogeneous for age (P=0.784) and gender (P=0.623). Among the evaluated optic nerve head (ONH) and macular OCT-A parameters, ONH whole image (P<0.001), inside disc (P=0.021), peripapillary (P<0.001), ONH flow area (P<0.026), macula whole image (P<0.001), fovea (P<0.001), parafovea (P<0.001) showed a significant difference when CTRL group was compared to HPG group at the post hoc test. Similarly, ONH whole image (P<0.001), inside disc (P=0.005), peripapillary (P<0.001), ONH flow area (P<0.026), macula whole image (P<0.001), FOVEA (P<0.001), parafovea (P<0.001) showed a significant difference were CTRL were compared to NTG group. On the contrary, no significant difference was found when NTG and HPG groups were compared. Age was not significantly correlated with any of the OCT-A parameters. The stage of the disease showed a high, significant, correlation with ONH whole image (r=-0.81; P<0.0001), inside disc (r=-0.42; P<0.0001), peripapillary (r=-0.81; P<0.0001), RNFL (r=-0.79; P<0.0001), macula whole image (r=0.56; P<0.0001), fovea (r=-0.78; P<0.0001) and parafovea (r=0.67; P<0.0001). On the contrary, VFI showed a high, significant, correlation with ONH whole image (r=0.77; P<0.0001), inside disc (r=0.39; P=0.0018), peripapillary (r=0.713; P<0.0001), RNFL (r=0.63; P<0.0001), macula whole image (r=-0.39; P=0.0007), fovea (r=0.60; P<0.0001) and parafovea (r=-0.52; P<0.0001)., Conclusions: Our data support the usefulness of the OCT-A in the common clinical practice for diagnosis, staging, evaluating the progression of the disease as well as for better understanding of its pathogenic mechanisms., Competing Interests: Conflicts of interest None., (© 2020 Elsevier B.V. All rights reserved.)

In the last few years, the possible link between obstructive sleep apnea (OSAS) and glaucoma, has attracted the interest of many scientists, especially in those forms of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG), in which a progression of the disease occurs, even though intraocular pressure (IOP) is in the range of normality. The increased prevalence of POAG or NTG in patients affected by OSAS, and vice versa, has stimulated interest in the pathogenetic mechanisms that could trigger these two diseases. Hypoxia generated by apnea/hypopnea cycles has been identified as the main cause of many changes in the vascular and neurological systems, which alter the functioning not only of the optic nerve, but also of the whole organism. However, many other factors could be involved, like mechanical factors, obesity, hormonal imbalance and other sleep disorders. Furthermore, the demonstration of typical glaucomatous or glaucoma-like changes in the anatomy or function of the optic nerve and retinal nerve fiber layer by sensitive specific and diagnostic methods, such as perimetry, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and electrophysiological exams keeps interest high for this field of study. For this reason, further investigations, hopefully a source of stronger scientific evidences, are needed., (© 2020 Elsevier B.V. All rights reserved.)

Background: glaucoma is the leading cause of irreversible blindness all over the world. The degree of visual field loss accounts for the severity of the disease and represents the main clinical outcome of treatment for patients affected by glaucoma. The α2 agonists, like brimonidine, emerged in the 1960s as topical ophthalmologic treatment. Their neuroprotective mechanism in glaucoma is still debated, ranging from effect on extracellular glutamate, to ocular hypotension and blood flow., Objectives: this systematic review and meta-analysis aims at assessing the efficacy of brimonidine on visual field deterioration during glaucoma through the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) approach. Databases consulted: the literature search has been performed on PubMed, MEDLINE, ClinicalTrials.gov and Scopus up to June 10th, 2020. Study eligibility criteria, participants, and interventions: clinical trials assessing the effects of brimonidine on visual field in patients with glaucoma. Study appraisal: the eligibility of the studies has been assessed by two independent authors and the selection has followed the PRISMA flow diagram. The retrieved results have been subjected to risk of bias evaluation., Results: the search of literature has retrieved 418 papers, among which 5 are eligible for inclusion in the qualitative analysis. All the studies present high heterogeneity, therefore meta-analysis has not been possible. The results obtained suggest that brimonidine improves visual field, but the design of the clinical trials rises some concerns in terms of risk of bias., Conclusions: the evidence of neuroprotective effect of brimonidine is inconclusive and needs stronger support. Large double-blind randomized clinical trials are necessary to strengthen this evidence., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© 2020 Elsevier B.V. All rights reserved.)

Background: Fenestrated endovascular aneurysm repair (FEVAR) allows endovascular treatment of thoracoabdominal and juxtarenal aneurysms previously outside the indications of use for standard devices. However, because of considerable device costs and increased procedure time, FEVAR is thought to result in financial losses for medical centers and physicians. We hypothesized that surgeon leadership in the coding, billing, and contractual negotiations for FEVAR procedures will increase medical center contribution margin (CM) and physician reimbursement., Methods: At the UMass Memorial Center for Complex Aortic Disease, a vascular surgeon with experience in medical finances is supported to manage the billing and coding of FEVAR procedures for medical center and physician reimbursement. A comprehensive financial analysis was performed for all FEVAR procedures (2011-2015), independent of insurance status, patient presentation, or type of device used. Medical center CM (actual reimbursement minus direct costs) was determined for each index FEVAR procedure and for all related subsequent procedures, inpatient or outpatient, 3 months before and 1 year subsequent to the index FEVAR procedure. Medical center CM for outpatient clinic visits, radiology examinations, vascular laboratory studies, and cardiology and pulmonary evaluations related to FEVAR were also determined. Surgeon reimbursement for index FEVAR procedure, related adjunct procedures, and assistant surgeon reimbursement were also calculated. All financial analyses were performed and adjudicated by the UMass Department of Finance., Results: The index hospitalization for 63 FEVAR procedures incurred $2,776,726 of direct costs and generated $3,027,887 in reimbursement, resulting in a positive CM of $251,160. Subsequent related hospital procedures (n = 26) generated a CM of $144,473. Outpatient clinic visits, radiologic examinations, and vascular laboratory studies generated an additional CM of $96,888. Direct cost analysis revealed that grafts accounted for the largest proportion of costs (55%), followed by supplies (12%), bed (12%), and operating room (10%). Total medical center CM for all FEVAR services was $492,521. Average surgeon reimbursements per FEVAR from 2011 to 2015 increased from $1601 to $2480 while the surgeon payment denial rate declined from 50% to 0%. Surgeon-led negotiations with the Centers for Medicare & Medicaid Services during 2015 resulted in a 27% increase in physician reimbursement for the remainder of 2015 ($2480 vs $3068/case) and a 91% increase in reimbursement from 2011 ($1601 vs $3068). Assistant surgeon reimbursement also increased ($266 vs $764). Concomitant FEVAR-related procedures generated an additional $27,347 in surgeon reimbursement., Conclusions: Physician leadership in the coding, billing, and contractual negotiations for FEVAR results in a positive medical center CM and increased physician reimbursement., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Repeated percutaneous interventions on failing arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) for hemodialysis are common, but the outcomes are largely unknown. We sought to determine the results of the second percutaneous intervention on failing AVGs and AVFs and to identify factors associated with loss of patency., Methods: For the purpose of this study, the second percutaneous intervention was identified as the index procedure. We reviewed the second percutaneous interventions on failing AVFs and AVGs at a single institution between 2007 and 2013. Patient comorbidities, graft or fistula configuration, lesion characteristics, and procedural characteristics of the intervention performed were analyzed with respect to technical success, primary patency, primary assisted patency, and secondary patency. Patency was defined per Society for Vascular Surgery recommended reporting standards and was determined from the time of the index procedure. Cox proportional hazards multivariable modeling was performed to identify independent determinants of loss of patency., Results: Among 91 patients, 96 second-time percutaneous interventions were performed on 52 AVFs and 44 AVGs. Patients included 56% men and 44% women with a mean age of 64 ± 17 years. The lesions intervened on were primarily located along the accessed portion of the outflow in AVFs and within the length of the graft and at the venous anastomosis in AVGs. Transluminal angioplasty alone was performed in 82 procedures (85%), and uncovered or covered stents were placed in 15 procedures (16%). Pharmacomechanical thrombectomy was performed in 32 patients (34%) and was more commonly performed in AVGs compared with AVFs (53% vs 17%; P = .0002). Technical success was achieved in 90 procedures (97%; n = 92). One-year primary patency, assisted primary patency, and secondary patency rates were 35%, 86%, and 86%, respectively. One-year primary patency did not differ between AVFs and AVGs, but secondary patency was lower for AVG in comparison to AVF (P = .04). On multivariable analysis, only the need for pharmacomechanical thrombectomy significantly predicted failure of primary patency (hazard ratio, 2.6; 95% confidence interval, 1.6-4.3). The presence of an AVG rather than an AVF independently predicted failure of secondary patency (hazard ratio, 2.9; 95% confidence interval, 1.0-8.2)., Conclusions: The second percutaneous interventions on AVFs and AVGs are associated with excellent technical success but poor primary patency. The need for pharmacomechanical thrombectomy predicts the need for additional percutaneous intervention to maintain patency. With additional interventions, acceptable secondary patency out to 5 years can be achieved, although AVGs have inferior secondary patency to AVFs. To develop optimal practice management algorithms, the effectiveness of repeated percutaneous interventions for failing AVGs and AVFs vs creation of a new access should be further investigated., (Copyright © 2016. Published by Elsevier Inc.)

Penetrating corneal transplant (PKP) surgery has been performed for centuries as the procedure of choice to restore vision in cases of advanced corneal disease. However, the last two decades have seen the introduction of lamellar corneal surgery (deep anterior lamellar keratoplasty, DALK; Descemet stripping-automated endothelial keratoplasty, DSAEK; and Descemet membrane endothelial keratoplasty, DMEK) which has shown several advantages over PKP and has rapidly gained popularity, given its benefits. Glaucoma after corneal graft surgery is an important cause of visual loss and graft failure. The main risk factors for developing glaucoma after any type of corneal graft are steroid-related intraocular hypertension and pre-existing glaucoma. The incidence of glaucoma after corneal graft surgery varies according to the specific risk factors and the type of corneal graft performed. One major advantage of modern layer selective lamellar keratoplasty is the reduced risk of glaucoma compared with PKP. This reduced glaucoma risk after corneal lamellar graft surgery is mainly due to the less destructive surgical nature of the lamellar procedures and also the reduced use of postoperative steroid treatment. Glaucoma can complicate not only corneal transplantation but has also been observed following other anterior segment procedures from laser refractive surgery to keratoprosthesis. The aim of this chapter is to describe the incidence, etiology, and management of glaucoma after corneal transplant and some common corneal surgical procedures., (© 2015 Elsevier B.V. All rights reserved.)

The complexation of heptakis(6-deoxy-6-thio)cyclomaltoheptaose to gold nanoparticles prepared by using the Metal Vapour Synthesis (MVS) led to water soluble gold nanoaggregates, thermally stable at 25°C. The role of gold concentration in the MVS-derived starting solution as well as of the cyclodextrin to gold molar ratio on the size of cyclodextrin-capped gold nanoparticles were investigated. The ability of cyclodextrin bonded to gold nanoparticles to include deoxycytidine was also probed in comparison with that of 1-thio-β-D-glucose sodium salt., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Aims: Increased epithelial cell proliferation may be detected in diverticular disease, but antibiotics have failed in reducing it. We assess therefore the effect of mesalazine on epithelial cell proliferation in diverticular disease., Methods: A prospective study was conducted on 20 consecutive patients with a new endoscopic diagnosis of symptomatic uncomplicated diverticular disease. The patients were treated with mesalazine 1.6 mg/day for 1 year. The Ki-67 antigen index of the whole crypt and in the upper third was separately evaluated before and after starting the treatment., Results: Cell proliferation index was higher in diverticular disease patients than healthy controls both in the whole crypt (median 6.7%, range 2-9% vs. median 1.6%, range 1-3%, p=0.001) and in the upper third of the crypt (median 6.8%, range 2-8% vs. median 1.8%, range 1-3%, p=0.001). Cell proliferation decreased throughout the follow-up. In the whole crypt it was 6.7% at entry and 3.8% at the end of treatment (p<0.005), whereas it was 6.8% at entry and 2.9% at the end of treatment in the upper third of the crypt (p<0.005)., Conclusions: We found mesalazine effective in reducing the colonic cell proliferation in long-term treatment for colonic diverticular disease.

The simultaneous quantitative assay of 1,4-dihydropyridine calcium antagonist manidipine and its main photodegradation by-product has been defined by using a multivariate calibration on UV spectra based on a classical least squares regression. Optimization of the procedure was achieved by means of a calibration model using suitable wavelength ranges singled out from a fractionation scheme thereat defined. Recovery values of 99 and 96% for the drug and the by-product, respectively, were found either in appropriately prepared mixtures and commercial formulations. Quantification limit for the photoproduct concentration was estimated as 1.0% for the reference samples.

Glucocorticoid (GC)-induced apoptosis is a well-recognized physiologic regulator of murine T-cell number and function. We have analyzed its mechanisms in human mature T cells, which have been thought to be insensitive until recently. Peripheral blood T cells showed sensitivity to GC-induced apoptosis soon after the proliferative response to a mitogenic stimulation, and were also sensitive to spontaneous (ie, growth factor deprivation-dependent) apoptosis. CD8+ T cells were more sensitive to both forms than CD4+ T cells. Acquisition of sensitivity to GC-induced apoptosis was not associated with any change in number or affinity of GC receptors. Both spontaneous and GC-induced apoptosis were increased by the macromolecular synthesis inhibitors, cycloheximide (CHX) and puromycin. A positive correlation between the degree of protein synthesis inhibition and the extent of apoptosis was observed. Interleukin-2 (IL-2) IL-4, and IL-10 protected (IL-2 > IL-10 > IL-4) T cells from both forms of apoptosis in a dose-dependent manner. Our data suggest that spontaneous and GC-induced apoptosis regulate the human mature T-cell repertoire by acting early after the immune response and differentially affecting T-cell subsets.

The proliferative responses to phytohemagglutinin (PHA) and to OKT3 monoclonal antibody of various human thymocyte subsets were studied. Unfractionated thymocytes are very poorly responsive cells, as assessed by both PHA and OKT3 stimulation. The mitogen responsiveness is confined to the T3-enriched (T3+) subset, the T6-positive (T6+) cells being almost completely devoid of proliferative capacity. The addition of exogenous IL-2 increases the proliferative responses to PHA and OKT3 of both unfractionated and T3+ thymocytes. This implies that the endogenous IL-2 production by thymocytes is inadequate to fully support the intrinsic proliferative capacity of these cells. Even in the presence of an optimal amount of IL-2, T3+ thymocytes exhibit proliferative responses of lower magnitude as compared to those of peripheral T counterpart (PBT). These observations indicate that the maturative level attained by the T3+ subpopulation within the thymus is considerably inferior to that of T3+ fully immunocompetent peripheral T lymphocytes. Macrophages are activated to produce IL-1 following the stimulation by OKT3-pulsed T lymphocytes. T3+ thymocytes are markedly less efficient than PBT in inducing IL-1 secretion. These data suggest that T3+ lymphocytes within the thymus are relatively immature in terms of cooperative capacities with accessory cells. In conclusion, T3+ cells constituting the more mature intrathymic pool do not reach a complete functional differentiation as compared with the T3+ peripheral counterpart.

The proliferative responses of human peripheral blood mononuclear cells (PBL) and thymocytes to OKT3 monoclonal antibody have been investigated. The PBL response to OKT3 was maximal after 72 hr while that of thymocytes was inappreciable at all times measured. Unlike phytohemagglutinin, OKT3 was unable to elicit the mitogenesis of adherent cell-depleted T cells in spite of the presence of exogenously added Interleukin 1 and/or Interleukin 2. The addition of autologous or heterologous adherent cells restored the OKT3 mitogenic response of peripheral purified T cells but not of thymocyte cultures. The adherent cell population that was able to sustain the OKT3-elicited T-cell mitogenesis was constituted by Ia-, Fc receptor-positive cells. These data suggest that the adherent cell-T cell interaction is mediated via the Fc portion of the OKT3 molecule. Furthermore, unlike peripheral T cells, T3-positive thymocytes, which represent the more mature. PHA-responsive subset within the thymus, are unable to cooperate with accessory cells when pulsed with OKT3 monoclonal antibody.

In this paper we studied the effect of cyclosporin A (CyA) on interleukin 1 (IL-1) and interleukin 2 (IL-2) production and on IL-2 receptor expression by human peripheral blood lymphocytes induced to proliferate following OKT3 monoclonal antibody stimulation. CyA inhibited T-cell proliferation in a dose-dependent manner and its effect was inversely correlated with the entity of the mitogenic signal. The drug reduced not only IL-2 synthesis but also IL-1 production. CyA was also found to be able to inhibit the expression of IL-2 receptors on T cells. By supplementing with IL-1 and/or IL-2 the cultures carried out in the presence of CyA, it became evident that the inhibition of IL-2 production mainly depended on the CyA-induced reduction of IL-1 synthesis. Thus the IL-2 production by "resting" T cells had to be considered as an IL-1-dependent event. In addition it was found that the presence of IL-1 constituted a crucial requirement for the induction and the positive modulation of IL-2 receptor expression. Although IL-2 could play a role in facilitating the expression of IL-2 receptors, its effectiveness to do so depended on the presence of IL-1. In conclusion, CyA is to be considered not only as a potent immunodepressive drug but also as a valuable tool for the study of T-cell activation and proliferation.

The addition of L-652,731 and L-653,150, two synthetic PAF-specific receptor antagonists, to 72 hour cultures of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear leukocytes (PBML) caused a dose-dependent inhibition of (3H)-thymidine incorporation into T-cells (IC50: 25 microM and 3.2 microM, respectively). This inhibition was not reversed by exogenous interleukin (IL)-1 and IL-2. PAF receptor antagonists did not affect the expression of IL-2 receptors (TAC-antigen) on T-cells. Exogenous PAF which by itself had no significant effect on PHA-stimulated PBML proliferation, only partially reversed the inhibition of proliferation caused by PAF receptor antagonists. These results may suggest the involvement of endogenously produced PAF in the regulation of immune reactions.