Systemic Anti-inflammatory Therapy Research Articles

Effect of Therapeutic Pars Plana Vitrectomy on Total Immunosuppression Load in Patients with Non-Infectious Uveitis

ABSTRACT Purpose The anti-inflammatory effect of therapeutic pars plana vitrectomy (PPV) in the management of posterior segment uveitis is incompletely quantified. In this study, we evaluated the change in total immunosuppression load (TIL) following PPV for the eyes of patients with non-infectious uveitis. Methods Retrospective chart review of patients with non-infectious posterior segment uveitis on continuous anti-inflammatory therapy (systemic corticosteroids ± immunomodulatory therapy [IMT]) ±3 months, who received therapeutic PPV for non-resolving inflammation. The TIL scores were calculated by adding the total daily dose of prednisolone graded on a scale of 0–9, and of the IMT graded between 0 and 3, and calculating the mean values for the pre-operative and post-operative visits, respectively. Results Sixty-five eyes of 65 patients were included. Mean follow-up was 19.1 ± 14.6 months pre-operatively and 9.4 ± 7.1 months post-operatively. Mean TIL scores for the post-operative visits (2.6 ± 1.9) were significantly lower than the pre-operative (4.4 ± 1.7) visits (p < 0.001). Mean logMAR BCVA was four lines better 1 month post-operatively (0.5 ± 0.4) than the immediate pre-operative vision (0.9 ± 0.6, p < 0.001). On multivariate regression analyses, the reduction in mean TIL scores post-operatively was more with longer durations of pre-operative treatment (adjusted risk ratio [aRR] = -0.04, p = 0.04), while the improvement in one-month post-operative BCVA was more if pre-operative vitreous haze was ≥2+ (aRR = −0.25, p = 0.02). Post-operative adverse outcomes included new-onset cystoid macular edema (n = 6), raised intraocular pressure (n = 5), and intra-operative retinal break (n = 1). Eleven (16.9%) patients were off all immunosuppression during the final follow-up. Conclusions Therapeutic PPV allowed control of intraocular inflammation on less intensive systemic anti-inflammatory therapy. Post-operative adverse outcomes observed were manageable.

Adenovirus keratoconjunctivitis after LASIK as a complication of COVID-19 vaccination: a clinical case

During large-scale vaccination against coronavirus infection, studying possible side effects after the introduction of the vaccine is of great practical value. We present a rare clinical case of a complication of COVID-19 vaccine prophylaxis. A 40-year-old female patient was diagnosed with a bilateral adenoviral keratoconjunctivitis complicated by corneal erosion and iritis after a LASIK refractive intervention and a subsequent (after 5 days) immunoprophylaxis with the Gam-COVID-Vac vaccine followed by a displacement of the corneal flap due to involuntary friction of the left eye. The corneal flap was urgently repositioned; its adhesion and stabilization were achieved usinga bandage soft contact lens. The timely local and systemic anti-inflammatory and antiviral therapy allowed achieving a successful visual result (1.0). Ophthalmologists need to remain vigilant about possible adverse effects after immunoprophylaxis on the part of the eye, specifically the conjunctiva and cornea. A timely diagnosis and treatment are important to prevent complications such as persistent corneal opacities that reduce visual acuity, especially in patients who have undergone refractive surgery aimed at achieving the highest possible vision. In our opinion, it is advisable to perform vaccination at least 1 month after the refractive surgery.

A simple tool for evaluation of inflammation in psoriasis: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as markers in psoriasis patients and related murine models of psoriasis-like skin disease

Objective parameters to quantify psoriatic inflammation are needed for interdisciplinary patient care, as well as preclinical experimental models. This study evaluates neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in psoriasis patients and five murine models of psoriasis-like skin disease based on topical imiquimod application and overexpression of IL-17A under different promotors. We performed a single-center prospective observational study in a German population, investigating psoriasis patients prior to, 4 weeks, and 16 weeks post begin of systemic anti-inflammatory therapy. Psoriasis area and severity index (PASI), blood count, and C-reactive protein (CRP) levels were attained at each timepoint. Additionally, five murine models of psoriasis-like skin disease involving five distinct experimental procedures differing in time of disease-onset and severity were investigated regarding PLR and NLR. Of 43 recruited psoriasis patients, 34 patients were followed up to 16 weeks. The cohort was 69.77% male, showing a median age of 32.0 years (range 19.0–67.0; IQR 26). The median PASI decreased from 16.35 (8.0–50.0; 10.20) to 1.6 (0–10.3; 2.56) after 16 weeks of systemic therapy. Spearman’s correlation showed statistically significant positive correlation for NLR with PASI (rs = 0.27, p = 0.006), however not for PLR. NLR, but not PLR, was significantly associated with PASI in a multiple linear regression analysis including age, sex, psoriasis arthritis, and smoking. In the murine models of psoriasis-like skin disease, both NLR and PLR were significantly increased in the acute-severe models compared to controls (p < 0.001, p = 0.005, and p = 0.02, respectively), demonstrating gradually less increased values from severe-acute to mild-late-onset psoriatic phenotype. NLR was significantly associated with PASI in psoriatic patients as well as psoriatic phenotype in different murine psoriasis models. Our data warrants investigation of NLR in psoriasis patients and preclinical psoriasis models as an objective biomarker of psoriatic skin inflammation.Key messagesNLR, but not PLR, showed a statistically significant positive correlation with Psoriasis Area and Severity Index (PASI) in our human psoriasis cohort.Both NLR and PLR were significantly increased in murine psoriasis models compared to matched controls, with gradually less increased values from severe-acute to mild-late-onset psoriatic phenotype.NLR may represent an easily available, cheap, and objective parameter to monitor psoriatic inflammation in both clinical patient routine, as well as preclinical experimental murine models.

Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable Long-Acting Insulin in a Rodent Model of Diabetes Eye Disease.

Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize that a combination therapy targeting inflammation and hyperglycemia can prevent diabetic eye diseases. Here, we report a multipronged approach to prevent diabetic cataracts and retinopathy by combining orally bioavailable curcumin-laden double-headed (two molecules of gambogic acid conjugated to terminal carboxyl groups of poly(d,l-lactide-co-glycolide)) nanoparticles and injectable basal insulin. The combination treatment led to a significant delay in the progression of diabetic cataracts and retinopathy, improving liver function and peripheral glucose homeostasis. We found a concurrent reduction in lens aggregate protein, AGEs, and increased mitochondrial ATP production. Importantly, inhibition of Piezo1 protected against hyperglycemia-induced retinal vascular damage suggesting possible involvement of Piezo1 in the regulation of retinal phototransduction. Histologic evaluation of murine small intestines revealed that chronic administration of curcumin-laden double-headed nanoparticles was well tolerated, circumventing the fear of nanoparticle toxicity. These findings establish the potential of anti-inflammatory and anti-hyperglycemic combination therapy for the prevention of diabetic cataracts and retinopathy.

Intravitreal injection versus systematic treatment in patients with uveitis undergoing cataract surgery: a systematic review and meta-analysis.

Cataract surgery in patients with uveitis is challenging, and postoperative inflammation control is crucial for successful outcomes. No consensus exists regarding the optimal method of controlling postoperative inflammation. In this systematic review and meta-analysis, we compared the outcome of intravitreal injection (IVI), including steroid (triamcinolone acetonide) or steroid implant (dexamethasone), with systemic anti-inflammatory therapy (ST), such as systemic steroids with or without immunomodulatory therapy, in patients with uveitis undergoing cataract surgery. We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs), comparative cohort studies, and case-control studies published through May 2021 that compared intraoperative IVI of triamcinolone acetonide or steroid implant with ST with or without immunomodulatory therapy. The following outcomes were evaluated: preoperative best-corrected visual acuity, intraocular pressure, laser flare photometry, central macular thickness and cystoidmacular edema rate. Five studies were selected. Our analysis indicated that compared with ST, IVI treatment may be associated with less anterior chamber inflammation and a lower cystoidmacular edema rate, but the difference in best-corrected visual acuity, intraocular pressure, or central macular thickness was not significant. IVI of steroid or steroid implants might be beneficial in controlling postoperative inflammation for uveitis cataract, especially in patients who cannot tolerate ST. To the best of our knowledge, this is the first meta-analysis to compare the efficacy of intraoperative IVI of steroids with standard-of-care treatment as a prophylaxis for uveitis cataract. However, large-scale RCTs are warranted to compare the IVI of steroid implants and steroids.

Effectiveness of various regimens of systemic anti-inflammatory therapy with glucocorticoids in the development of acute LPS-induced lung damage in the experiment

BACKGROUND: When studying new and effective methods of treating acute respiratory distress syndrome, an immunogenic model of lung injury occupies a special place. To date, the search for the optimal strategy and regimen for the use of glucocorticoids in the development of acute respiratory distress syndromе is relevant.&#x0D; AIM: The article evaluates the effectiveness of various schemes of systemic anti-inflammatory therapy with glucocorticoids in an experimental model of acute LPS-induced lung injury.&#x0D; MATERIALS AND METHODS: The study was conducted on 100 outbred male rats. Acute lung injury was modeled using an experimental model of direct acute lung injury by a single intratracheal injection of lipopolysaccharide (LPS) from the cell wall of the bacterium Salmonella enterica (Sigma-Aldrich) at a dose of LD50 (20 mg/kg). All animals were divided into groups (20 each): 1 intact rats; 2 control group (LPS + saline); 3 LPS + dexamethasone 0.52 mg/kg (small doses); 4 LPS + dexamethasone 1.71 mg/kg (average doses); 5 LPS + dexamethasone 8 mg/kg (high doses). The drugs were administered intraperitoneally once a day for 3 days. Dexamethasone doses were calculated using the interspecies dose transfer method using a factor that takes into account differences in body surface area.&#x0D; RESULTS: It has been established that an experimental model based on the endotracheal administration of S. enterica leads to the development of mortality from pulmonary causes. According to a preclinical study, the systemic use of low doses of dexamethasone (0.52 mg/kg) was found to be better than higher doses (1.71 mg/kg, 8 mg/kg) in the treatment of acute LPS-induced lung injury.

Ocular toxocariasis presenting as leukocoria

An 8-year-old boy presented to Zhongshan Ophthalmic Center (Guangzhou, China) with a 2-month history of leukocoria (white pupil) in the right eye (figure). His visual acuity was reduced to counting fingers in the right eye and was 20/20 in the left eye. Posterior synechiae (iris adhesions to the lens), total cataract, and tractional retinal detachment were noted in the right eye by slit-lamp microscopy and ultrasound (B-mode). His parents recalled that the patient had a long-term habit of playing with their pet dog, but the dog had never been dewormed. Serological testing for toxocariasis showed Toxocara canis-specific IgG in the serum (74·82 units, reference range 0–9) and aqueous humour (58·53 units, reference range 0–3) of the patient. Embryonated eggs and worms of T canis were found in the faeces of the patient's pet dog by microscopic examination after deworming treatment (video). The patient was diagnosed with ocular toxocariasis presenting as leukocoria. He received cataract surgery and systemic anti-inflammatory therapy with oral prednisone (0·5 mg/kg per day for 30 days), but showed no visual improvement at the 6-month follow-up.

Diagnosis and Management of Idiopathic Persistent Iritis after Cataract Surgery (IPICS)

To investigate the diagnosis and management of patients with idiopathic persistent iritis after cataract surgery (IPICS). Retrospective interventional case series. Patients diagnosed with IPICS were evaluated for demographic and clinical characteristics and immune blood markers. Those with more than 6 months of follow-up were evaluated for treatment efficacy to achieve remission (ie, absence of inflammation for 3 months), with either exclusive slow tapering of topical steroids or the need for systemic immunosuppression. Forty-five patients presented with IPICS. Most were African American (39, 86.7%) or female (33, 77.3%). Antinuclear antibodies were present in 23 (69.9%) of patients. Main complications were steroid dependency (38,84.4%), glaucoma (24,53.5%), and macular edema (11,37.5%). Thirty two patients presented treatment follow up. On these,the proposed treatment strategy achieved remission in 30 (93.8%) of cases in a mean of 6.1 months via tapering of topical steroids in 15 (46.9%) of patients. However, in 17 (53.1%) of cases, adjuvant anti-inflammatory systemic medication was indicated. Meloxicam use was associated with remission in 11 (64.7%) of these patients and, in a minority with persistent iritis, treatment was escalated to methotrexate, which was successful in 4 (100%) of the cases. IPICS is a distinct clinical anterior uveitis most common in African American and female patients, characterized by an unexpected onset of iritis after cataract surgery and high rates of steroid dependency, glaucoma, and macular edema. It is best treated with an initial slow taper of topical steroids; although adjuvant systemic anti-inflammatory therapy may be necessary to obtain remission and avoid complications.

PECULIARITIES OF THE LACRIMAL FLUID CYTOKIN PROFILE IN PATIENTS WITH BACTERIAL KERATITITIS OF THE II DEGREE SEVERETY AND DIABETES MELLITUS

Summary. The aim was to identify the features of the lacrimal fluid cytokine profile in patients with bacterial keratitis of the II degree of severity and type 1 DM in the dynamics of observation.&#x0D; Materials and methods. The lacrimal fluid cytokine profile was analyzed in 6 patients with type 1 DM and bacterial keratitis of the II degree of severity and 6 nondiabetic patients with bacterial keratitis of the II degree of severity on the 1st day, 10-14th day and 24th day of observation. Data from 14 healthy individuals of the appropriate age were used for comparison. II degree of severity of bacterial keratitis was determined according to our proposed scheme at a sum of points 15-21. All patients were treated with instillations of ofloxacin, antiseptics, antioxidants, reparents, artificial tears, mydriatics, systemic anti-inflammatory therapy. The concentration of interleukins (IL)-1β, IL-6 and IL-10 in the lacrimal fluid of the sick and the contralateral eye was determined by quantitative colorimetric enzyme-linked immunosorbent assay using ELISA kits.&#x0D; Results and discussion. In patients with bacterial keratitis of the II degree of severity, both with DM and nondiabetic, within 10-14 days of observation invented the expression of proinflammatory cytokines IL-1β and IL-6 in the lacrimal fluid of the sick eye and anti-inflammatory cytokine IL-10 - in lacrimal fluid of the contralateral eye (p&lt;0.05). In DM patients, a longer expression of IL-1β and IL-6 was detected in the lacrimal fluid of the sick and the contralateral eye, which was observed on the 24th day of the study (p&lt;0.05).&#x0D; Conclusions. There are features of the lacrimal fluid cytokine profile in DM patients with bacterial keratitis of the II severity in the dynamics of observation, namely the longer expression of proinflammatory cytokines IL-1β, IL-6 in the sick and the contralateral eye.

IMMUNOLOGICAL FEATURES OF THE DYNAMICS OF THE I DEGREE SEVERETY BACTERIAL KERATITES DEPENDING ON THE PRESENCE OF DIABETES MELLITUS

Summary. In patients with diabetes mellitus (DM) there are features of the dynamics of the I degree severity bacterial keratitis, leading to prolongation of the disease and worsening of its consequences.&#x0D; The aim was to identify immunological features of the dynamics of the I degree severity bacterial keratitis depending on the presence of type 1 DM.&#x0D; Materials and methods. The level of interleukins (IL) was analyzed, namely IL-1β, IL-6 and IL-10 in the lacrimal fluid of the sick and the contralateral eye of 6 patients with type 1 DM and the I degree severity bacterial keratitis and 6 nondiabetic patients with I degree severity bacterial keratitis on the 1st day, 10-14th day and 24th day of observation. Data from 14 healthy individuals of the appropriate age were used for comparison. The severity of bacterial keratitis was determined according to our scheme at a total score of ≤ 14. All patients were treated with instillations of ofloxacin, antiseptics, antioxidants, reparents, artificial tears, mydriatics, systemic anti-inflammatory therapy. The level of IL in the lacrimal fluid was determined by quantitative colorimetric enzyme-linked immunosorbent assay using ELISA kits by ANOGEN according to the instructions for use.&#x0D; Results and discussion. In patients with I degree severity bacterial keratitis, both DM and nondiabetic, on the 1st day of observation there was an increase in the level of IL-1β and IL-6 in the lacrimal fluid of the sick eye and IL-10 – of the contralateral eye compared to healthy persons, on the 10th-14th day — increase in the level of IL-1β and IL-6 of the sick and the contralateral eye, as well as IL-10 – of the contralateral eye (p&lt;0.05). On the 24th day in nondiabetic patients with I degree severity bacterial keratitis normalization of interleukin levels in the lacrimal fluid of the sick and the contralateral eye was found, but in DM patients remained elevated levels of IL-1β, IL-6, both in the sick and in the contralateral eye (p&lt;0.05).&#x0D; Conclusions. In DM patients there are immunological features of the dynamics of the I degree severity bacterial keratitis, namely a longer increase in the level of proinflammatory cytokines IL-1β, IL-6 in the lacrimal fluid of the sick and the contralateral eye.

FEATURES OF THE DYNAMICS OF THE II DEGREE OF SEVERETY BACTERIAL KERATITES IN DIABETIC PATIENTS AT DIFFERENT STAGES OF DIABETIC POLYNEYROPATHY

Summary. The neuro-trophic condition of the cornea affects the healing process of corneal defects in patients with keratitis, causing the severity, duration and consequences of the disease.&#x0D; The aim was to identify the features of the dynamics of the II degree of severity bacterial keratitis in patients with diabetes mellitus (DM) at different stages of the severity of diabetic polyneuropathy (DPN).&#x0D; Materials and methods. The results of treatment of 19 patients with bacterial keratitis of the II degree of severity and type 1 DM were analyzed. II degree of severity of bacterial keratitis was determined according to our proposed scheme at a sum of points 15-21. All patients were treated with instillations of the antibiotic ofloxacin, antiseptics, antioxidants, reparants, artificial tears, mydriatics, systemic anti-inflammatory therapy. Patients were divided into two groups according to the severity of DPN: with symptomatic (first group) and stage with impaired DPN (second group). In addition to standard, ophthalmic examination methods included bacteriological examination, fluorescein test, OCT of the anterior segment of the eye, non-contact corneal esthesiometry.&#x0D; Results and discussion. In most patients of the second group, corneal sensitivity and depth of edema of the corneal tissues surrounding the ulcer, the size of the ulcer defect and the depth of corneal infiltration, the degree of pericorneal injection, the depth of the corneal ulcer defect from the 1st, 7th, 10th and 14th days of observation, respectively, were higher than in patients of the first group (p&lt;0,05). The consequence of the disease in patients of the second group was more severe than in patients of the first group.&#x0D; Conclusions. In patients with the stage of impaired DPN, bacterial keratitis is characterized by a longer duration and severity of clinical symptoms, as well as worse consequences of the disease than in patients with symptomatic DPN.

Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis.

Given the lack of head‐to‐head studies of systemic therapies in moderate‐to‐severe atopic dermatitis (AD), network meta‐analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision‐making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short‐term (12–16 weeks) efficacy (Investigator’s Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient‐reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti‐inflammatory therapy). RCTs were analysed in fixed‐effects and random‐effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI‐50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI‐75 and EASI‐90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI‐50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment‐emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45–2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35–2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short‐term RCTs.

Противовоспалительная cистемная фармакотерапия пародонтита (обзор литературы)

Проведен поиск в базах данных Scopus, Web of Science, MedLine, The Cochrane Library. Заболевания пародонта — основная причина потери зубов. Пародонтит — воспалительное заболевание, которое вызывается специфической микрофлорой и приводит к прогрессирующему разрушению связочного аппарата зуба и альвеолярной кости. Это сопровождается образованием рецессии десны, формированием пародонтальных карманов как отдельно, так и обоюдно. Пародонтит отмечается у 9–85 % детей, 70–90 % подростков, более чем у половины взрослых людей. Активация воспаления в пародонте неразрывно связана с системными процессами в организме, сопровождающимися воспалительным ответом, и потому пародонтит является сопутствующим фактором при ишемической болезни сердца и цереброваскулярных заболеваниях/ишемическом инсульте, негативно влияет на пищеварительную, сердечно-сосудистую, эндокринную и другие системы организма. Неконтролируемый воспалительный ответ организма в условиях микробной биопленки, которая плотно прилегает к поверхности зуба, приводит к разрушению тканей пародонта, потере костной ткани. Если острое воспаление своевременно стихает, предотвращая деструкцию, но не происходит полного восстановления гомеостаза тканей, это приводит к повреждениям, вызванным нейтрофилами, и хроническому воспалению. Системная противо-воспалительная терапия с использованием неселективных нестероидных противовоспалительных лекарственных средств является важным направлением терапии пародонтита, что обеспечивает снижение интенсивности воспаления, минимизирует разрушение тканей пародонта, ограничивает ресурс питательных веществ для патогенных микроорганизмов, предупреждает резорбцию альвеолярной кости. Для профилактики гастропатии целесообразно в комплексе терапии применять синтетический аналог простагландина E2 мизопростол. Менеджмент взаимодействия лекарственных средств целесообразно проводить в случае назначения нестероидных противовоспалительных лекарственных средств пациенту, который принимает производные сульфонилмочевины, варфарин, антигипертензивные лекарственные средства и др.

Update on Surgical Interventions In Management Of Dry Eyes

Dry eye disease (DED) is an inflammatory disease with tear film instability and hyperosmolarity. It is also a common symptom encountered in a general ophthalmology practice. The DED symptoms range from mild, moderate to severe. The Rapid Diagnosis with non-invasive techniques are possible in the out-patient clinic itself. The management includes medical and surgical, which depends on the patients' objective symptoms, subjective complaints, and the severity of the disease. Medical treatment includes preservative-free tear substitutes, oral secretagogues, topical, and systemic anti-inflammatory therapy. The surgical modalities are the treatment options in very severe disease. The severity of the disease at the time of presentation, lifestyle modifications, compliance with the treatment is associated with a better prognosis. This review provides an update with a practical approach to surgical interventions of DED with emphasis on treatment for specific disease subtype and severity of the condition.

FEATURES OF THE DYNAMICS OF THE I DEGREE OF SEVERETY BACTERIAL KERATITES IN DIABETIC PATIENTS

Summary. Diabetes mellitus (DM) is a risk factor for severe bacterial keratitis, which often leads to complications.&#x0D; The aim was to identify the features of the dynamics of the I degree of severity bacterial keratitis in diabetic patients.&#x0D; Materials and methods. The results of treatment of 15 patients with type 1 DM and bacterial keratitis of the I degree of severity (main group) and 20 patients with bacterial keratitis of the I degree of severity without DM (control group) were analyzed. The severity of bacterial keratitis was determined according to our proposed scheme with a total score of ≤ 14. All patients were treated with instillations of ofloxacin, antiseptics, antioxidants, reparents, artificial tears, mydriatics, systemic anti-inflammatory therapy. In addition to standard, ophthalmic examination methods included bacteriological examination, fluorescein test, OCT of the anterior segment of the eye, non-contact corneal esthesiometry.&#x0D; Results and discussion. In diabetic patients with bacterial keratitis of the I degree of severity the degree of inflammatory reaction in the anterior chamber of the eye and the average threshold of corneal sensitivity at all airflow temperatures at the first visit exceeded the indicators of controls (p&lt;0.05). The degree of the average corneal sensitivity threshold decrease throughout the observation, the degree of pericorneal injection, the size of the corneal ulcer, the depth of corneal infiltration from the 3rd day of observation, the depth of corneal ulcer and corneal edema from the 7th day exceeded indicators of controls (p&lt;0.05).&#x0D; Conclusions. Diabetic patients have features of the dynamics of the I degree of severity bacterial keratitis, which lead to prolongation of the disease and worsening of its consequences.

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation

Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor’s PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1β, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.

Results of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Inflammatory Choroidal Neovascularization.

Purpose:To report the visual outcomes of intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) in inflammatory choroidal neovascularization (iCNV).Methods:A retrospective study of 43 eyes of 38 patients with active choroidal neovascularization (CNV) related to ocular inflammatory disease, treated with IVT injections of anti-VEGF (bevacizumab, ranibizumab, or aflibercept), with or without associated systemic anti-inflammatory therapy, at Fattouma Bourguiba University Hospital, Monastir, Tunisia (24 eyes of 23 patients) and at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (19 eyes of 15 patients) from January 1, 2013, to December 31, 2018.Results:The mean age was 35.5 ± 16.4 years. The sex ratio male:female was 0.27. Seventeen eyes (39.5%) of 17 patients (44.7%) had only anti-VEGF injections, and 26 eyes (60.5%) of 21 patients (45.3%) had anti-VEGF injections and associated systemic anti-inflammatory therapy. Bevacizumab was injected in 36 eyes (83.7%), ranibizumab in six eyes (14%), and aflibercept in one eye (2.3%). Mean follow-up was 20.3 ± 19.2 months (range, 6–106 months). Mean visual acuity improved from 0.8 ± 0.37 logMAR (approximate Snellen equivalent 20/125) to 0.51 ± 0.42 logMAR (approximate Snellen equivalent 20/63) (P < 0.001). Mean central macular thickness on optical coherence tomography decreased from 403.7 ± 121.9 to 293.7 ± 82.8 μm (P < 0.001). Mean gain of vision was 2.9 ± 3.1 lines. The mean number of injections was 2.5. Twenty eyes (46.5%) received a single injection. There were no side effects related to the IVT injections of anti-VEGF.Conclusions:CNV is a sight-threatening complication of uveitis. IVT anti-VEGF seems to be an effective and safe treatment for iCNV when inflammation is controlled.

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation.

Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)-coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA2-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles (n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) (n = 8) and untreated controls (n = 8). PLGA-GA2-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA2 nanoparticles for systemic drug delivery across ocular barriers.

A multistage combined approach to promote diabetic wound healing in COVID‐19 era

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet‐rich plasma (PRP), and other advanced moist wound dressing have been proposed. During Coronavirus disease 2019 (COVID‐19) pandemic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non‐healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the postoperative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti‐inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis.

Examining the pathogenesis and therapeutic strategy of keloids from the perspective of systemic inflammation

Keloid is a disease that is difficult to cure and has a high recurrence rate. In the past, research on keloid focused on keloid cells themselves and the therapeutic strategy limited to local treatment, whereas the role of systemic factors in the process of occurrence and development of disease was usually neglected. Based on the literature reports and clinical evidence, we propose that the pro-inflammatory constitution of keloid patients can serve as a systemic factor to interact with local factors such as skin lesion, and thus leads to the initiation and development of keloid. The classical theory about close relationship between visceral malfunctions and skin diseases described in traditional Chinese medicine has provided supporting evidence. Therefore, we suggest that systemic anti-inflammatory therapy should be included in the design of future keloid therapeutic strategies and be verified by the clinical trials. Additionally, the therapeutic strategies of traditional Chinese medicine including anti-dampness, detoxing and heating removing can also be employed as a part of systemic treatment of keloids.