Incidence and visual outcomes of acute endophthalmitis post intravitreal injection of anti-vascular endothelial growth factors in a single referral center.

BACKGROUND: To describe the incidence and factors predicting visual outcome in patients with infectious endophthalmitis following intravitreal anti-VEGF injection. METHODS: Retrospective, single-site, cohort study. Patients with acute endophthalmitis within 6 weeks of intravitreal anti-VEGF injection who were referred to our practice after inciting injection or were injected by us between January 2010 and July 2017 were included. All patients received intravitreal antibiotics with either vitreous/anterior chamber tap (TAP) or pars plana vitrectomy. Visual outcomes pre/post treatment, baseline variables (age, gender, ocular disease) and cultures results were studied. RESULTS: Seventy eyes of 69 patients were included. Presenting VA was the strongest factor associated with final visual outcome after adjusting for other variables including culture status and baseline VA (p = .0002). Cultures were positive in 62.8% of eyes and were associated with worse visual outcome (p = .0087). Growth of Streptococcus or microorganisms other than coagulase negative Staphylococci (CNS) was also associated with worse prognosis, regardless of baseline and presenting VA (p = .0002). The crude incidence of post-injection endophthalmitis was 0.028% in our practice (40 eyes in 143,628 injections) during the study time. No significant difference was found between pre-filled bevacizumab versus ranibizumab or aflibercept drawn from a vial. CONCLUSIONS: In a large, single center, retrospective study, the incidence of acute endophthalmitis post anti-VEGF injection was relatively low. Worse visual acuity at presentation of endophthalmitis and growth of Streptococcus or organisms other than CNS were associated with the worst visual outcomes.

Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress.

Exposures to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) youth have life time exposures to PM2.5 and O3 above standards. We focused on MMC residents ≤30 years and reviewed 134 consecutive autopsies of subjects age 20.03 ± 6.38 y (range 11 months to 30 y), the staging of Htau and ß amyloid, the lifetime cumulative PM2.5 (CPM 2.5) and the impact of the Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD. We also reviewed the results of the Montreal Cognitive Assessment (MoCA) and the brainstem auditory evoked potentials (BAEPs) in clinically healthy young cohorts. Mobile sources, particularly from non-regulated diesel vehicles dominate the MMC pollutant emissions exposing the population to PM2.5 concentrations above WHO and EPA standards. Iron-rich,magnetic, highly oxidative, combustion and friction-derived nanoparticles (CFDNPs) are measured in the brain of every MMC resident. Progressive development of Alzheimer starts in childhood and in 99.25% of 134 consecutive autopsies ≤30 years we can stage the disease and its progression; 66% of ≤30 years urbanites have cognitive impairment and involvement of the brainstem is reflected by auditory central dysfunction in every subject studied. The average age for dementia using MoCA is 20.6 ± 3.4 y. APOE4 vs 3 carriers have 1.26 higher odds of committing suicide. PM2.5 and CFDNPs play a key role in the development of neuroinflammation and neurodegeneration in young urbanites. A serious health crisis is in progress with social, educational, judicial, economic and overall negative health impact for 25 million residents. Understanding the neural circuitry associated with the earliest cognitive and behavioral manifestations of AD is needed. Air pollution control should be prioritised-including the regulation of diesel vehicles- and the first two decades of life ought to be targeted for neuroprotective interventions. Defining paediatric environmental, nutritional, metabolic and genetic risk factor interactions is a multidisciplinary task of paramount importance to prevent Alzheimer's disease. Current and future generations are at risk.

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young.

To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg tests in 575 clinically healthy subjects, age 21.0 ±â€¯5.7 y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3 ±â€¯9.1 y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.

A proposal of an algorithm for the diagnosis and treatment of recurrence or treatment failure of retinopathy of prematurity after anti-VEGF therapy based on a large case series.

PURPOSE: To provide a diagnostic algorithm of recurrence and treatment failure after intravitreal bevacizumab (IVB) injection for retinopathy of prematurity type 1 (ROP1) and the stepwise therapeutic approach for both conditions. METHODS: Retrospective chart review of all patients diagnosed with ROP1 initially treated with IVB in 6 tertiary referral centers of Toluca and Mexico City from 2005 to 2017. Treatment failure was defined as persistence or progression of neovascularization, elevation of the ridge, worsening of plus disease, or retinal crunch within the first week after treatment. Recurrence was defined as the new appearance of plus disease, an elevated ridge, or pathological new vessels after an initial regression of ROP following treatment. Therapy was observation, switch of anti-VEGF agent, retinal photocoagulation, vitrectomy, or a combination of two or more, depending on the severity of findings. RESULTS: A total of 672 patients who received intravitreal bevacizumab injection for ROP1 treatment were included. Of these, 2.5% (17 patients) failed to treatment, 6.8% (46 patients) developed a recurrence for ROP, and 5.5% (37 patients) carried a misdiagnosis of recurrence and were diagnosed with other than ROP1 after examination. Based on the severity of findings, patients with recurrence or treatment failure were further treated by observation, repeat anti-VEGF intravitreal injection (bevacizumab or other), laser photocoagulation, vitrectomy, or a combination of these. Based on the treatment results, a therapeutic algorithm was created. CONCLUSIONS: Intravitreal injection of anti-VEGFs for the treatment of ROP warrants close follow-up as some of these patients may have treatment failure or recurrence of the disease. It is crucial to differentiate between them to avoid a misdiagnosis and offer the correct treatment. We propose a novel algorithm for the follow-up and treatment approach of ROP1 following initial treatment with IVB. This algorithm offers a summary of our recommendations based on a large case series of ROP1 patients. It is meant to grow and expand as more clinical evidence becomes available.

Cryo-electron tomography analyses of terminal organelle mutants suggest the motility mechanism of Mycoplasma genitalium.

The terminal organelle of Mycoplasma genitalium is responsible for bacterial adhesion, motility and pathogenicity. Localized at the cell tip, it comprises an electron-dense core that is anchored to the cell membrane at its distal end and to the cytoplasm at its proximal end. The surface of the terminal organelle is also covered with adhesion proteins. We performed cellular cryoelectron tomography on deletion mutants of eleven proteins that are implicated in building the terminal organelle, to systematically analyze the ultrastructural effects. These data were correlated with microcinematographies, from which the motility patterns can be quantitatively assessed. We visualized diverse phenotypes, ranging from mild to severe cell adhesion, motility and segregation defects. Based on our observations, we propose a double-spring ratchet model for the motility mechanism that explains our current and previous observations. Our model, which expands and integrates the previously suggested inchworm model, allocates specific functions to each of the essential components of this unique bacterial motility system.

Structural characterization of the NAP; the major adhesion complex of the human pathogen Mycoplasma genitalium.

Mycoplasma genitalium, the causative agent of non-gonococcal urethritis and pelvic inflammatory disease in humans, is a small eubacterium that lacks a peptidoglycan cell wall. On the surface of its plasma membrane is the major surface adhesion complex, known as NAP that is essential for adhesion and gliding motility of the organism. Here, we have performed cryo-electron tomography of intact cells and detergent permeabilized M. genitalium cell aggregates, providing sub-tomogram averages of free and cell-attached NAPs respectively, revealing a tetrameric complex with two-fold rotational (C2) symmetry. Each NAP has two pairs of globular lobes (named α and ß lobes), arranged as a dimer of heterodimers with each lobe connected by a stalk to the cell membrane. The ß lobes are larger than the α lobes by 20%. Classification of NAPs showed that the complex can tilt with respect to the cell membrane. A protein complex containing exclusively the proteins P140 and P110, was purified from M. genitalium and was structurally characterized by negative-stain single particle EM reconstruction. The close structural similarity found between intact NAPs and the isolated P140/P110 complexes, shows that dimers of P140/P110 heterodimers are the only components of the extracellular region of intact NAPs in M. genitalium.

A minimized motile machinery for Mycoplasma genitalium.

The cell wall-less bacterium Mycoplasma genitalium uses specialized adhesins located at the terminal organelle to adhere to host cells and surfaces. The terminal organelle is a polar structure protruding from the cell body that is internally supported by a cytoskeleton and also has an important role in cell motility. We have engineered a M. genitalium null mutant for MG491 protein showing a massive downstream destabilization of proteins involved in the terminal organelle organization. This mutant strain exhibited striking similarities with the previously isolated MG_218 null mutant strain. Upon introduction of an extra copy of MG_318 gene in both strains, the amount of main adhesins P140 and P110 dramatically increased. These strains were characterized by microcinematography, epifluorescence microscopy and cryo-electron microcopy, revealing the presence of motile cells and filaments in the absence of many proteins considered essential for cell adhesion and motility. These results indicate that adhesin complexes play a major role in the motile machinery of M. genitalium and demonstrate that the rod element of the cytoskeleton core is not the molecular motor propelling mycoplasma cells. These strains containing a minimized motile machinery also provide a valuable cell model to investigate the adhesion and gliding properties of this human pathogen.

Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.

BACKGROUND: Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM2.5) and ozone (O3) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. METHODOLOGY: Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. RESULTS: MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. CONCLUSIONS: MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease.

CONSTRUCT AND FACE VALIDITY OF THE EYESI INDIRECT OPHTHALMOSCOPE SIMULATOR.

PURPOSE: To evaluate construct and face validity of the Eyesi Binocular Indirect Ophthalmoscope Simulator. METHODS: The performance of 25 medical students (Group A) was compared with that of 17 ophthalmology and optometry trainees (Group B) on the Eyesi Binocular Indirect Ophthalmoscope Simulator. During the course of a single session, each participant viewed an orientation module followed by an instruction session and a demonstration case, and performed 6 cases of progressively increasing difficulty (4 levels) and a 10-question face validity questionnaire. Outcomes included total score, total examination time, percent retina examined, and duration of eye exposure to light. RESULTS: Group B achieved significantly better total scores than Group A on all difficulty levels (P = 0.02, P = 0.001, P = 0.001, and P = 0.0001, for Levels 1-4, respectively) and had a significantly faster mean duration of examination (8 minutes 58 seconds vs. 5 minutes 21 seconds, P < 0.0001). Medical students reported higher scores in the face validity questionnaire for the simulator experience being helpful at orienting them to true indirect ophthalmology, and that further training on the simulator would improve their skills in the clinic (P = 0.03 for all). CONCLUSION: The Eyesi Binocular Indirect Ophthalmoscope Simulator has significant construct and face validity and shows promise for medical education.

Trans-scleral diode laser cyclophotocoagulation for refractory glaucoma after high-risk penetrating keratoplasty.

To analyze the intraocular pressure reduction, number of anti-glaucoma medications needed, and post-operative complications of trans-scleral diode laser cyclophotocoagulation (DCPC) in patients with high-risk penetrating keratoplasty (PKP) and secondary refractory glaucoma. Prospective interventional, longitudinal, non-comparative series of cases, including 16 eyes of 15 patient's post-PKP on maximal anti-glaucoma medical therapy with intraocular pressures above 22 mmHg. All patients received 18 shots, 360° peri-limbal (avoiding the long posterior ciliary nerves and arteries at 3 and 9 o'clock positions) of trans-scleral DCPC (2000 mW, time: 2.0 s/shot). There was a 55.5 % reduction (total of 14.0 mmHg) of the mean pre-operative IOP (31.5 mmHg) after the first diode laser application (p = 0.0020). Re-treatment was required in 31.2 % of eyes over a mean period of 10.7 months. In these five eyes, the mean pre-operative IOP was 40.4 mmHg, which decreased to 15.0 mmHg post-therapy, and a mean IOP reduction of 25.4 mmHg (p = 0.0218). There was a 51.0 % reduction in the mean number of medications used after the first, and a 57.1 % reduction after a second laser application. The incidence of failure (IOP ≥ 22 mmHg or need of additional medical therapy) from initial intervention to loss of follow-up was 1.3 % per person-month. DCPC effectively reduces the intraocular pressure and the number of anti-glaucoma medications with few complications in patients after high-risk PKP and secondary glaucoma. Only, one-third of the eyes needed a second intervention to control the intraocular pressure. Post-DCPC complications were limited to phthisis bulbi and endothelial dysfunction, one eye each. Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct.

Co-testing for detection of high-grade cervical intraepithelial neoplasia and cancer compared with cytology alone: a meta-analysis of randomized controlled trials.

BACKGROUND: Human papillomavirus (HPV) DNA testing combined with cytology has been recommended as a primary cervical cancer screening strategy. METHODS: PubMed/MEDLINE, Embase, the Cochrane Library and the NIH trial registry were searched for randomized controlled trials comparing co-testing with cytology alone for the detection of high-grade CIN lesions and cancers. Of 1156 articles identified, four met inclusion criteria. The performance of co-testing and cytology alone was compared at baseline screening, second round screening and overall. Cumulative meta-analysis, Begg's test, Egger's test and sensitivity analysis were performed. RESULTS: At baseline, co-testing was associated with a significantly higher detection rate of CIN 2+ [risk ratio (RR) = 1.41, 95% confidence interval (CI): 1.12, 1.76] and a non-significantly higher CIN 3+ detection rate (RR = 1.15, 95% CI: 0.99, 1.33). At second round screening, co-testing was associated with significantly lower detection rates of both CIN 2+ and CIN 3+ (RR = 0.77, 95% CI: 0.63, 0.93; RR = 0·68, 95% CI: 0.55, 0.85). The overall detection rate did not differ between co-testing and cytology alone for CIN 2+ (RR: 1·19, 95% CI: 0.99, 1.46) or CIN3+ (RR: 0.99, 95% CI: 0.87, 1.14). CONCLUSION: Co-testing increases the detection of CIN2+ lesions at baseline and significantly decreases the detection rates of CIN2+ or CIN3+ lesions at subsequent screening compared with cytology alone.

Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility.

Cranberry supplements are commonly used to prevent urinary tract infections (UTIs). However, their usefulness is uncertain in pregnant women. We aimed to comprehensively summarize the current knowledge on cranberry supplements' efficacy and acceptability during pregnancy in addition to the outcomes measurement methods and studies' feasibility. To achieve it, we searched PubMed, PMC, and Europe PMC databases plus screened citations followed by critical appraisal of included eligible English-written primary studies that (1) focused on pregnant women supplemented with any cranberry supplements; (2) provided data on cranberry supplements' efficacy, acceptability, outcomes measurement methods, and studies' feasibility; (3) included human subjects; and (4) published worldwide. Two randomized clinical trials (RCTs) and one nested cohort study, including 1156 pregnant women in total, contributed to our analysis. A tendency toward UTI reduction was demonstrated, although the results' validity was impacted by significant juice-induced gastrointestinal intolerance (23%; 44 of 188 subjects). Changing the form of supplementation from cranberry juice to capsules reduced the issue, causing side effects in one of 49 subjects (2%). Nevertheless, both RCTs still experienced significant recruitment and retention problems, which were at 33% and 59% on average, respectively. Newly acquired safety data on 919 more subjects suggests no increased risks of all malformations, vaginal bleeding, and neonatal complications. Investigating cranberry capsules' efficacy as a non-antibacterial option for UTI prevention in pregnant women has become a feasible and important direction with the current advancement in understanding cranberry supplements' actions, recommended doses plus regimens, and their safety in the population. We reviewed the challenges and discovered knowledge gaps and the implementation strategies for future studies.

Correction: Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility.

[This corrects the article DOI: 10.7759/cureus.46738.].

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates.

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programs, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG binding and neutralizing antibodies against several SARS-CoV-2 variants, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2.

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Clinical characteristics of a large cohort of patients with scleritis and episcleritis.

OBJECTIVE: To evaluate the demographic characteristics, clinical features, ocular complications, and disease associations of patients with scleritis and episcleritis; as well as to delineate the risk factors for decreased vision in patients with scleritis. DESIGN: Retrospective case series. PARTICIPANTS: Five hundred patients with scleritis and 85 patients with episcleritis. METHODS: The electronic health records of 500 patients with scleritis and 85 patients with episcleritis seen at 2 tertiary referral centers were reviewed and their clinical features were studied. MAIN OUTCOME MEASURES: Clinical features (pain, scleral inflammation), ocular complications (decrease in vision, anterior uveitis, peripheral ulcerative keratitis, ocular hypertension), and disease associations. RESULTS: In a series of 585 patients, 500 patients had scleritis (85.5%) and 85 patients had episcleritis (14.2%). Ocular complications were more frequent overall in patients with scleritis versus in those with episcleritis (45.0% vs. 19.0%), including decrease in vision (15.8% vs. 2.3%), anterior uveitis (26.4% vs. 16.5%), peripheral ulcerative keratitis (7.4% vs. 0%), and ocular hypertension (14.2% vs. 3.5%; P<0.0001 for each). Disease association was observed in 35.8% of patients with scleritis versus 27.1% of episcleritis patients, including connective tissue or vasculitic diseases in 24.8% versus 15.3%, respectively. Scleritis preceded systemic disease diagnosis in 38.7% of patients. Ocular complications (90.0%) and disease association (80.0%) occurred most often in patients with necrotizing scleritis (P<0.0001 for each). Risk factors for decrease in vision in patients with scleritis included necrotizing scleritis (odds ratio [OR], 6.63; P<0.001), posterior scleritis (OR, 2.33; P = 0.042), degree of scleral inflammation of more than 2+ (range, 0-4+; OR, 3.60; P<0.001), anterior uveitis (OR, 1.78; P = 0.033), ocular hypertension (OR, 3.19; P<0.001), and associated disease (OR, 2.66; P<0.001), mainly infectious (OR, 4.44; P<0.001). CONCLUSIONS: Scleritis is associated more often with ocular complications than episcleritis, and necrotizing scleritis is the type of scleritis most often associated with ocular complications and disease association. Risk factors for decrease in vision in patients with scleritis include necrotizing scleritis, posterior scleritis, scleral inflammation of more than 2+, anterior uveitis, ocular hypertension, and associated infectious disease. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Scleritis therapy.

OBJECTIVE: To delineate factors associated with a successful response to treatment in patients with various manifestations of scleritis. DESIGN: Retrospective case series. PARTICIPANTS: A total of 392 patients with noninfectious anterior scleritis. METHODS: We reviewed the electronic health records of 392 patients with noninfectious anterior scleritis seen at 2 tertiary referral centers and studied the factors associated with successful treatment. MAIN OUTCOME MEASURES: Patient characteristics (age, sex); ocular disease characteristics (laterality, type of scleritis, degree of scleral inflammation, ocular complications, delay in presentation, and follow-up period), systemic disease association (associated disease, potentially lethal associated disease); and anti-inflammatory and immunosuppressive medications were studied in patients with scleritis. Successful treatment response to nonsteroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (SAIDs), immunosuppressive therapy drugs (immunomodulatory therapy [IMT]), or biologic response modifiers (BRMs) was assessed. RESULTS: Treatment of 392 patients with noninfectious anterior scleritis included NSAIDs in 144 (36.7%), SAIDs in 29 (7.4%), IMT in 149 (38.0%), BRMs in 56 (14.3%), and none (N = 14). Successful response to treatment with NSAIDs was associated with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation (≤ 2+) (odds ratio [OR] = 2.89, P < 0.001) and with idiopathic diffuse or nodular scleritis without ocular complications (OR = 3.13, P < 0.001). Successful treatment with SAIDs was associated with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation (>2+) (OR = 4.70, P = 0.001). Successful treatment with IMT was associated with diffuse or nodular scleritis with associated systemic disease (OR = 1.57, P = 0.047), mainly potentially lethal (OR = 17.41, P=0.007), and necrotizing scleritis (OR = 4.73, P = 0.026). Successful treatment with BRMs was associated with diffuse or nodular scleritis with associated systemic disease (OR = 3.15, P < 0.001). This study did not require institutional review board approval because the information does not contain any subject identifiers. CONCLUSIONS: Patients with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation or without ocular complications may respond to NSAIDs. Patients with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation may respond to SAIDs. Patients with diffuse or nodular scleritis with associated systemic disease may respond to IMT or BRMs. Patients with necrotizing scleritis may respond to IMT, mainly alkylating agents. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinical features and presentation of infectious scleritis from herpes viruses: a report of 35 cases.

PURPOSE: To describe clinical features and presentation of infectious scleritis resulting from herpes viruses. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-five patients out of 500 with scleritis. METHODS: We reviewed the electronic health records of 500 patients with scleritis, 35 of whom were diagnosed with herpes virus infection, seen at 2 tertiary referral centers. We studied the clinical features and ocular complications of this subset of patient with scleritis. MAIN OUTCOME MEASURES: Correlation between classification, severity, and symptoms (i.e., pain) and diagnosis of herpetic-associated scleritis. Vision loss, presence of associated uveitis, keratitis, glaucoma, or systemic disease were documented over the follow-up period. Other outcome measures included epidemiologic data: age, gender, laterality, visual acuity, duration of symptoms, and underlying systemic or ocular diseases. RESULTS: Of 500 patients with scleritis, 47 (9.4%) had an underlying infectious cause. Thirty-five (74.4%) of these were diagnosed with herpes virus infection, 5 (10.6%) with tuberculosis, and the remaining 7 (14.8%) with other infectious disease. Patients with herpes-associated scleritis were analyzed as a group and then compared with those with idiopathic scleritis. Most patients with herpetic scleritis presented with acute (85.7%) and unilateral (80%) scleral inflammation. Pain was moderate or severe in 68.6% of the patients. The most common type of scleritis was diffuse anterior in 80% (n = 28), followed by nodular anterior 11.4% (n = 4), and necrotizing in 8.6% (n = 3). Necrotizing anterior scleritis was more commonly seen in patients with herpetic scleritis versus patients with idiopathic disease (8.6% vs 1.2%; P<0.05). Unilaterality was also more common in herpetic scleritis (80%) than in idiopathic disease (56.7%; P<0.05). Vision loss was significantly greater in herpetic than idiopathic scleritis (34.3% vs 11.5%; P<0.001). CONCLUSIONS: The association between scleritis and infectious disease may be higher than previously reported by other series. Herpes viruses account for 7% of all scleritis cases and its diagnosis may be challenging when there is not a classically diagnostic clinical picture. We present the observed clinical features of herpetic scleritis and describe the clinical differences at presentation between patients with idiopathic scleritis and those with herpes infection.

Exposure to severe urban air pollution influences cognitive outcomes, brain volume and systemic inflammation in clinically healthy children.

Exposure to severe air pollution produces neuroinflammation and structural brain alterations in children. We tested whether patterns of brain growth, cognitive deficits and white matter hyperintensities (WMH) are associated with exposures to severe air pollution. Baseline and 1 year follow-up measurements of global and regional brain MRI volumes, cognitive abilities (Wechsler Intelligence Scale for Children-Revised, WISC-R), and serum inflammatory mediators were collected in 20 Mexico City (MC) children (10 with white matter hyperintensities, WMH(+), and 10 without, WMH(-)) and 10 matched controls (CTL) from a low polluted city. There were significant differences in white matter volumes between CTL and MC children - both WMH(+) and WMH(-) - in right parietal and bilateral temporal areas. Both WMH(-) and WMH(+) MC children showed progressive deficits, compared to CTL children, on the WISC-R Vocabulary and Digit Span subtests. The cognitive deficits in highly exposed children match the localization of the volumetric differences detected over the 1 year follow-up, since the deficits observed are consistent with impairment of parietal and temporal lobe functions. Regardless of the presence of prefrontal WMH, Mexico City children performed more poorly across a variety of cognitive tests, compared to CTL children, thus WMH(+) is likely only partially identifying underlying white matter pathology. Together these findings reveal that exposure to air pollution may perturb the trajectory of cerebral development and result in cognitive deficits during childhood.