Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Japanese Spotted Fever Associated with Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion.

A 58-year-old woman had disseminated intravascular coagulation (DIC) and septic shock caused by Japanese spotted fever (JSF). Following treatment with minocycline, her general condition gradually improved; however, her disorientation persisted. Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type II was diagnosed based on brain magnetic resonance imaging (MRI) showing a hyperintense area in the splenium of the corpus callosum and bilateral cerebral white matter on diffusion-weighted imaging. Thereafter, her consciousness gradually improved, but she continued to experience difficulty concentrating and attention deficits. MERS type II may take longer to improve than type I, and long-term follow-up is required.

A 31-Year-Old Man With Seizures, Brain Lesion, and Lung Nodules.

CASE PRESENTATION: A 31-year-old man was admitted to our hospital with a recent history of generalized seizures. Three months earlier, he started with intermittent hemoptysis. CT scan showed a cavitary lung lesion in the upper segment of the right inferior lobe (RIL). Because of his job as a social worker in a high-risk population, he started treatment for Mycobacterium TB; however, the BAL culture result was negative. At the time of his current admission, he has continued taking rifampicin, isoniazid, pyrazinamide, and levofloxacin. He denied the use of any illicit drugs or alcohol. He had no history of smoking. One year earlier, he visited Southeast Asia, Oceania, and South Africa for several months. He reported a weight loss of 7 kg since then. Except for a recurrent oral candidiasis, he did not have a relevant medical history. His family history was notable for mother with lupus, and brother with sarcoidosis.

Rhino-orbital-cerebral mucormycosis: fungal epidemic in a viral pandemic.

BACKGROUND: Treatment of coronavirus disease 2019 infection can result in immunosuppression. Rhino-orbital-cerebral mucormycosis is a frequent co-infection, even after recovery. METHODS: An ambispective interventional study was conducted of 41 coronavirus patients with rhino-orbital-cerebral mucormycosis at a tertiary care centre from March to May 2021. RESULTS: There were 28 males and 13 females with a mean age of 48.2 years (range, 21-68 years). Twelve had long-standing diabetes mellitus and 28 had been recently diagnosed. Thirty-six had received systemic corticosteroids for coronavirus disease 2019. Nasal signs were present in 95 per cent of patients, ophthalmic symptoms and signs in 87 per cent, palatal necrosis in 46.3 per cent, facial signs in 24.3 per cent, nerve palsies in 60.9 per cent, and intracranial involvement in 21.9 per cent. Treatment with amphotericin B was based on clinical features and co-morbidities. Endonasal debridement was performed in 51.2 per cent of patients, total maxillectomy in 14.6 per cent and orbital exenteration in 9.7 per cent. At the last follow up, 37 patients (90.24 per cent) were on antifungal therapy; 4 (9.75 per cent) did not survive. CONCLUSION: Early detection may improve survival. Follow up of high-risk patients after coronavirus disease 2019 infection is paramount.

Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the "black fungus".

A subset of diabetic COVID-19 patients treated with steroids, oxygen, and/or prolonged intensive care admission develop rhino-orbito-cerebral mucormycosis. Radiologists must have a high index of suspicion for early diagnosis, which prompts immediate institution of antifungal therapy that limits morbidity and mortality. Assessment of disease extent by imaging is crucial for planning surgical debridement. Complete debridement of necrotic tissue improves survival. Imaging features reflect the angioinvasive behaviour of fungal hyphae from the Mucoraceae family, which cause necrotising vasculitis and thrombosis resulting in extensive tissue infarction. Contrast-enhanced magnetic resonance imaging (MRI) is the imaging technique of choice. The classic "black turbinate" on contrast-enhanced imaging represents localised invasive fungal rhinosinusitis (IFRS). A striking radiological feature of disseminated craniofacial disease is non-enhancing devitalised and necrotic soft tissue at the orbits and central skull base. Sinonasal and extrasinonasal non-enhancing lesions in IFRS are secondary to coagulative necrosis induced by fungal elements. Multicompartmental and extrasinonasal tissue infarction is possible without overt bone involvement and caused by the propensity of fungal elements to disseminate from the nasal cavity via perineural and perivascular routes. Fungal vasculitis can result in internal carotid artery occlusion and cerebral infarction. Remnant non-enhancing lesions after surgical debridement portend a poor prognosis. Assessment for the non-enhancing MRI lesion is crucial, as it is a sole independent prognostic factor for IFRS-specific mortality. In this review, we describe common and uncommon imaging presentations of biopsy-proven rhino-orbito-cerebral mucormycosis in a cohort of nearly 40 COVID-19 patients.

NOD1 in the interplay between microbiota and gastrointestinal immune adaptations.

Nucleotide-binding oligomerization domain 1 (NOD1), a pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals, has been linked to inflammatory pathologies. NOD1, which is expressed by immune and non-immune cells, is activated after recognizing microbe-associated molecular patterns (MAMPs). This recognition triggers host defense responses and both immune memory and tolerance can also be achieved during these processes. Since the gut microbiota is currently considered a master regulator of human physiology central in health and disease and the intestine metabolizes a wide range of nutrients, drugs and hormones, it is a fact that dysbiosis can alter tissues and organs homeostasis. These systemic alterations occur in response to gastrointestinal immune adaptations that are not yet fully understood. Even if previous evidence confirms the connection between the microbiota, the immune system and metabolic disorders, much remains to be discovered about the contribution of NOD1 to low-grade inflammatory pathologies such as obesity, diabetes and cardiovascular diseases. This review compiles the most recent findings in this area, while providing a dynamic and practical framework with future approaches for research and clinical applications on targeting NOD1. This knowledge can help to rate the consequences of the disease and to stratify the patients for therapeutic interventions.

[Purple urine bag syndrome (PUBS): about two cases at the Regional University Hospital Center (CHUR) of Ouahigouya]. / Le syndrome de la poche à urines violette: à propos de deux cas au Centre Hospitalier Universitaire Régional (CHUR) de Ouahigouya.

Purple urine bag syndrome (PUBS) is an uncommon complication of urinary tract infection. It mainly affects elderly patients with constipation, chronic urinary catheter and prolonged bed rest. Several bacteria belonging to two different groups, the group converting indoxyl urinary sulphate into indoxyl and the group alkalizing urine by the production of urease, are associated with it. We here report two cases of young patients aged 30 and 16 years, living in Burkina Faso, with uremic encephalopathy associated with severe infection and cloudy urine with purple urine bag. Unlike cases reported in the literature, our cases occurred two and four days after urinary catheterization and in young patients without constipation. Despite early antibiotic therapy, outcome was unfavorable in one patient.

Rhinocerebral mucormycosis secondary to severe acute pancreatitis and diabetic ketoacidosis: a case report.

INTRODUCTION: Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging. CASE PRESENTATION: We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses. CONCLUSIONS: In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.

Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy.

OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats. METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1ß, and IL-6 in the cortex were analyzed. RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats. CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.

Impact of Surgical and Medical Treatment on Survival of Patients with Cerebral Aspergillosis: Systematic Review of the Literature.

OBJECTIVE: Cerebral aspergillosis carries a high mortality. Rapid diagnosis and treatment can increase survival, but symptoms and imaging findings are nonspecific. The literature on cerebral aspergillosis consists mostly of case reports and case series and lacks large-scale review of data. METHODS: We performed a review of the literature using PubMed in March 2019. We recorded the year of publication, age and sex of patients, neurosurgical involvement, the antifungals administered, use of intrathecal antifungals, and the outcome of patients. The relationships among variables were tested using bivariant statics and linear regression. RESULTS: A total of 324 studies met the eligibility criteria, and 198 studies including 248 patients were included. Surgical resection (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.80; P < 0.01) and administration of voriconazole (OR, 0.32; 95% CI, 0.18-0.55; P < 0.001) or itraconazole (OR, 0.36; 95% CI, 0.16-0.72; P < 0.001) were shown to be significantly associated with survival. CONCLUSIONS: Given the significant survival benefits for patients who received voriconazole and surgical intervention, we suggest early antifungal medical treatment and resection.

Progress in the Application of Nanoparticles and Graphene as Drug Carriers and on the Diagnosis of Brain Infections.

The blood-brain barrier (BBB) is the protective sheath around the brain that protects the sensitive microenvironments of the brain. However, certain pathogens, viruses, and bacteria disrupt the endothelial barrier and cause infection and hence inflammation in meninges. Macromolecular therapeutics are unable to cross the tight junctions, thereby limiting their bioavailability in the brain. Recently, nanotechnology has brought a revolution in the field of drug delivery in brain infections. The nanostructures have high targeting accuracy and specificity to the receptors in the case of active targeting, which have made them the ideal cargoes to permeate across the BBB. In addition, nanomaterials with biomimetic functions have been introduced to efficiently cross the BBB to be engulfed by the pathogens. This review focuses on the nanotechnology-based drug delivery approaches for exploration in brain infections, including meningitis. Viruses, bacteria, fungi, or, rarely, protozoa or parasites may be the cause of brain infections. Moreover, inflammation of the meninges, called meningitis, is presently diagnosed using laboratory and imaging tests. Despite attempts to improve diagnostic instruments for brain infections and meningitis, due to its complicated and multidimensional nature and lack of successful diagnosis, meningitis appears almost untreatable. Potential for overcoming the difficulties and limitations related to conventional diagnostics has been shown by nanoparticles (NPs). Nanomedicine now offers new methods and perspectives to improve our knowledge of meningitis and can potentially give meningitis patients new hope. Here, we review traditional diagnosis tools and key nanoparticles (Au-NPs, graphene, carbon nanotubes (CNTs), QDs, etc.) for early diagnosis of brain infections and meningitis.

The gut microbiota-brain axis in behaviour and brain disorders.

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the 'gut-brain axis'. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host-microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health.

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology.

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1ß and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

Prognosis of Patients with Sepsis and Non-Hepatic Hyperammonemia: A Cohort Study.

BACKGROUND Hyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear. MATERIAL AND METHODS Information about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality. RESULTS A total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis. CONCLUSIONS Higher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

Probiotics Exert Protective Effect against Sepsis-Induced Cognitive Impairment by Reversing Gut Microbiota Abnormalities.

Recent evidence has revealed that probiotics could affect neurodevelopment and cognitive function via regulating gut microbiota. However, the role of probiotics in sepsis-associated encephalopathy (SAE) remained unclear. This study was conducted to assess the effects and therapeutic mechanisms of probiotic Clostridium butyricum (Cb) against SAE in mice. The SAE model mouse was induced by cecal ligation and puncture (CLP) and was given by intragastric administration with Cb for 1 month. A series of behavioral tests, including neurological severity score, tail suspension test, and elevated maze test, were used to assess cognitive impairment. Nissl staining and Fluoro-Jade C (FJC) staining were used to assess neuronal injury. Microglia activation, the release of neuroinflammatory cytokines, and the levels of ionized calcium-binding adapter molecule 1 (Iba-1) and brain-derived neurotrophic factor (BDNF) in the brain were determined. The compositions of the gut microbiota were detected by 16S rRNA sequencing. Our results revealed that Cb significantly attenuated cognitive impairment and neuronal damage. Moreover, Cb significantly inhibited excessive activation of microglia, decreased Iba-1 level, and increased BDNF level in the SAE mice. In addition, Cb improved gut microbiota dysbiosis of SAE mice. These findings revealed that Cb exerted anti-inflammatory effects and improved cognitive impairment in SAE mice, and their neuroprotective mechanisms might be mediated by regulating gut microbiota.