Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Biologics in non-infectious uveitis past,present and future

Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.

Non-Infectious Complications of Peritoneal Dialysis in Senegal

Introduction: Senegal has pioneered the implementation of peritoneal dialysis (PD) in West Africa, practicing it since 2004. Non-infectious complications are a significant cause of failure of this technique and the transfer of patients to haemodialysis. The aim of this study was to determine the prevalence and the different types of non-infectious complications in our context. Patients and Methods: This was a 5-year, descriptive, retrospective study of patients on chronic peritoneal dialysis for more than 3 months. Results: During the study period, 75 patients were included. The prevalence of non-infectious complications was 88%, including 45.3% mechanical complications and 76% metabolic complications. Catheter migration was the most common mechanical complication (55.9%), followed by catheter blockage (23.5%). Metabolic complications were dominated by hypoalbuminemia (76.3%). Dyslipidaemia and hypokalaemia affected more than 50% of patients, occurring in 59.3% and 56.9% of cases, respectively. Conclusion: In our study, non-infectious complications related to PD were frequent and varied. They remain a significant cause of technical failure. Mechanical complications are often the cause of permanent transfer to haemodialysis.

Structure and Composition of Non-Infectious Phosphate Calculi Formed in Patients with Low and High Urinary Phosphate Concentrations

Objective: The aim of this paper was to assess the relationships among chemical, phase and structural composition and?etiopathogenic factors of non-infectious phosphate calculi formed in patients with low and high urinary phosphate concentrations, and to characterize the mechanism of their formation related on biochemical results. Material and Methods: Twelve samples of phosphate renal calculi were obtained, 4 from patients with low phosphaturia and 6 from patients with high urinary phosphate concentrations. Their chemical composition was determined qualitatively by energy dispersive X-ray analysis and quantitatively by spectrophotometric and thermal analysis;and their phase composition was determined by Fourier transform infrared transmission spectroscopy and X-ray diffraction. The structure of the calculi was assessed by scanning electron microscopy. Results: Non-infectious phosphate renal calculi of patients with low phosphaturia consist of poorly crystalline carbonate hydroxyapatite, whereas those of patients with high urinary phosphate concentrations consist of poorly crystalline hydroxyapatite with some amount of calcium oxalate crystals. Calculi of patients with high urinary phosphate concentrations are formed at urinary supersaturation with respect to hydroxyapatite and calcium oxalate about 4 times higher than in patients with low phosphaturia. Conclusion: In patients with low phosphaturia, the non-infectious phosphate renal calculi are formed in urine near pH 7 and contain only poorly crystalline carbonate hydroxyapatite. In patients with high urinary phosphate concentrations and hypercalciuria, the calculi are formed in urine near pH 6 and consist of both poorly crystalline hydroxyapatite and some amount of calcium oxalate crystals.

Non-infectious endophthalmitis after vitrectomy

Background Non-infectious endophthalmitis was reported to occur after cataract surgery or intravitreal injections. This study reported a series of patients having non-infectious endophthalmitis after pars plana vitrectomy in the same two operation rooms during the same period to estimate the risk factors for non-infectious endophthalmitis after vitrectomy. Methods Medical records of patients who presented with severe non-infectious endophthalmitis following vitrectomy between May 13 and June 8, 2011, were reviewed. The presenting symptoms and signs were collected, including visual acuity, intraocular pressure, cornea and anterior chamber activity. The treatments and results of microbiology examination were also recorded and analyzed. Results Ten patients were identified with severe non-infectious endophthalmitis, presenting 1 day after pars plana vitrectomy. Three eyes （30%） had previous intraocular surgeries, four （40%） had proliferative diabetic retinopathy, and one （10%） got pars plana vitrectomy combinded with phacoemulsification and intraocular lens implantation. All the patients were initially treated with topical and/or oral steroids. Only two patients had intravenous antibiotics because of the atypical presentation. One eye had paracentesis because of high intraocular pressure and the aqueous sample was sent for microbiological examination. The culture of the aqueous, air in the operation room, the swab from hand of surgeons, infusion fluid, and vitrectomy effluent were all negative for bacteria and fungi. The inflammation regressed rapidly after the initial treatment. Conclusions Intraocular surgery history, poor general health status, longer operation time, and more surgical procedures are the risk factors for non-infectious endophthalmitis after vitrectomy. It responds well to steroids.

Molecular mechanisms implicated in SARS-CoV-2 liver tropism

The coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Hepatic involvement is common in SARS-CoV-2-infected individuals.It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19.In individuals with pre-existing infectious and non-infectious liver disease,who are at a remarkably higher risk of developing severe COVID-19 and death,this pathology is most medically relevant.This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver,systemic inflammation,disrupted coagulation,and the lung.

Altering the intestinal microbiota for therapeutic benefit in uveitis

An intestinal dysbiosis is connected to a number of inflammatory diseases through various mechanisms relating to its effect on immune cell function and differentiation.This is a review of the literature summarizing our current understanding of intestinal microbial contributions to non-infectious uveitis and strategies to target the intestinal microbiome to treat uveitis.Several groups have demonstrated an intestinal dysbiosis associated with certain types of non-infectious uveitis.Additionally,approaches to treat uveitis by modifying the intestinal microbiota,such as oral antibiotics or administration of oral short chain fatty acids(SCFAs),which are intestinal bacterial metabolites produced by fermentation of dietary fiber,can successfully treat uveitis in mouse models.This reduction in severity of ocular inflammation occurs via the following mechanisms:enhancement of regulatory T cells,decreasing intestinal permeability,and/or affecting T cell trafficking between the intestines and the spleen.Other strategies that are directed at the intestinal microbiota that might be effective to treat uveitis include dietary changes,probiotics,or fecal microbial transplantation.The commensal gut bacteria are influential in systemic and intestinal mucosal immunity and thus contribute to the development of extraintestinal inflammation like uveitis.Targeting the intestinal microbiome thus has the potential to be a successful strategy to treat non-infectious uveitis.

Research progress of autophagy in acute lung injury induced by multiple factors

Autophagy is a highly conserved catabolic process, involving the degradation of cellular components, including damaged organelles, denatured proteins and various pathogens. It is a defense and stress mechanism for maintaining cell and tissue homeostasis. More and more evidences show that autophagy is closely related to many diseases. Acute lung injury is caused by intrapulmonary or extrapulmonary factors, with hypoxia and low lung compliance as the main manifestations. At present, its pathogenesis is not clear. It is known that the imbalance of inflammatory response and oxidative stress mechanism are the important mechanisms of its occurrence. The inflammatory response caused by acute lung injury has been reported to involve a series of changes in autophagy expression. Autophagy may be protective or harmful in acute lung injury. This article will summarize the respective roles of autophagy in acute lung injury caused by infectious factors (such as pathogen infection, lipopolysaccharide, sepsis) and non-infectious factors (acute pancreatitis, chlorine poisoning), so as to provide new ideas and strategies for better prevention of acute lung injury.

Biologic response modifiers in retinal vasculitis

Intraocular inflammation is an important cause of blindness both in the developing and developed world. Corticosteroids play a pivotal role in the treatment of intraocular inflammation. Lately, therapy by immuno-suppression has taken the center stage for patients with severe intraocular infammation. However, the side effects of immunosuppressive drugs are oncogenic, in-fectious, and hematological. Recently, biologic response modifiers specifically targeting suppression of the im-mune effector responses have revolutionized the treat-ment of intraocular infammation. Anti-tumour necrosis factor agents are etanercept, infiximab, and adalimum-ab. Newer drugs include certolizumab and golimumab. Infiximab has been found to be superior to corticoste-roids in treating retinal vasculitis. Anti-interlenkin thera-pies include rituximab, daclizumab, anakinra, tocilizum-ab and secukinumab. Rituximab has been proven to be quite effective. Other biologics used are interferons and abatacept. However, there are several limitations and side effects associated with their use.

Human-driven global nutrient imbalances increase risks to health

Human-induced inputs of nitrogen(N)and phosphorus(P)into the biosphere have reached unprecedented levels,particularly N,leading to an escalating global anthropogenic N:P ratio.This ratio has emerged as a significant driver of environmental change,impacting organisms,ecosystems,and global food security.However,the implications of this ratio for human health have been largely overlooked and remain uncertain.This article aims to fill this knowledge gap by exploring the potential effects of N:P ratios on both non-infectious and infectious diseases.Preliminary data emphasize the importance of investigating the influence of N:P ratios on human health,suggesting a potential role in the rise of non-infectious diseases,such as cancer,as well as the proliferation of infectious diseases,including Zika and malaria.These findings highlight the urgent need for increased attention from the scientific community and policymakers regarding the complex impacts of the human-induced biospheric N:P ratio.It is crucial to investigate and understand the underlying mechanisms and drivers behind these effects.Furthermore,there is significant potential for improving human health through the manipulation of N:P ratios and the availability of N and P.This applies not only to medical treatments but also to innovative fertilizer management strategies.These avenues present promising opportunities to address the challenges associated with human health in an ever-changing world.