Widespread Inflammatory Response Research Articles

Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications due to antiphospholipid antibodies. Catastrophic APS (CAPS), a severe variant, leads to multiorgan failure and is often fatal. Pathogenesis involves antiphospholipid antibodies, particularly anti-beta-2-glycoprotein I (aβ2GPI), which trigger endothelial cell (EC) activation, cytokine release, and a prothrombotic state. Infections, surgeries, and other triggers can precipitate CAPS, leading to widespread microthromboses and systemic inflammatory responses. CAPS predominantly affects younger patients and those with systemic lupus erythematosus (SLE), with a high mortality rate, though recent treatment advances have improved survival. Diagnosing CAPS involves identifying clinical manifestations, including rapid organ involvement and small vessel occlusions, confirmed by histopathology and high antiphospholipid antibody levels. The CAPS registry data indicate that commonly affected organs include kidneys, lungs, central nervous system, and the heart, with a high prevalence of lupus anticoagulant and anticardiolipin antibodies (aCL). Current management strategies focus on therapeutic anticoagulation, immunosuppressive therapies like corticosteroids, and adjunct treatments such as plasmapheresis and intravenous immunoglobulin (IVIG). Early use of glucocorticoids and combination therapy has significantly improved outcomes. In life-threatening cases, especially with microangiopathy, experts recommend performing plasma exchange (PE). Patients with associated autoimmune conditions or refractory cases may receive cyclophosphamide (CY) and rituximab while considering PE for treatment. Maintenance of anticoagulation with an appropriate international normalized ratio (INR) is crucial to prevent recurrence.This article reviews the pathogenesis and epidemiology of CAPS. It also examines the current management strategies, and discusses the challenges and controversies associated with these strategies. It hereafter offers recommendations for future management and outlines directions for further research.

Age, sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients

BackgroundAging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women experience worse neuropathological burden and cognitive decline despite living longer with the disease. Similarly, male 3xTg-AD mice, developed to model Alzheimer’s disease, no longer consistently exhibit standard Alzheimer’s neuropathology yet experience higher rates of mortality - providing a unique opportunity to further elucidate this dichotomy. We hypothesized that sex differences in the biological aging process yield distinct pathological and molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development.MethodsWe aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans (n = 3–8 mice per sex, strain, and age group) and longitudinally assessed neuropathological hallmarks of Alzheimer’s disease, markers of hepatic inflammation, splenic mass and morphology, as well as plasma cytokine levels. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes (DEGs) between 3xTg-AD and B6129 samples and across ages in each sex. We also examined DEGs between clinical Alzheimer’s and control parahippocampal gyrus brain tissue samples from the Mount Sinai Brain Bank study in each sex.Results3xTg-AD females significantly outlived 3xTg-AD males and exhibited progressive Alzheimer’s neuropathology, while 3xTg-AD males demonstrated progressive hepatic inflammation, splenomegaly, circulating inflammatory proteins, and minimal Alzheimer’s neuropathological hallmarks. Instead, 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females. Our clinical investigations revealed that individuals with Alzheimer’s disease develop similar sex-specific alterations in neuronal and immune function. In diseased males of both species, we observed greater upregulation of complement-related gene expression, and lipopolysaccharide was predicted as the top upstream regulator of DEGs.ConclusionsOur data demonstrate that chronic inflammation and complement activation are associated with increased mortality, indicating that age-related changes in immune response contribute to sex differences in Alzheimer’s disease trajectories. We provide evidence that aging and transgene-driven disease progression trigger a widespread inflammatory response in 3xTg-AD males, which mimics the impact of lipopolysaccharide stimulation despite the absence of infection.

Evidence that keratinocyte microvesicle particles carrying Platelet-activating factor mediate the widespread multi-organ damage associated with intoxicated thermal burn injury.

Thermal burn injuries can result in significant morbidity and mortality. The combination of ethanol intoxication with thermal burn injury results in increased morbidity through an exaggerated inflammatory response involving many organs. Recent studies have linked involvement of the lipid mediator Platelet-activating factor (PAF) in the pathology associated with intoxicated thermal burn injury (ITBI). The present studies tested the roles of PAF and the elevated levels of subcellular microvesicle particles (MVP) generated in response to ITBI in the subsequent multi-organ toxicity. First, thermal burn injury of HaCaT keratinocytes preincubated with ethanol resulted in augmented MVP release, which was blocked by inhibiting the PAF-generating enzyme cytosolic phospholipase A2 and the PAF receptor (PAFR). Second, ITBI of mice resulted in increased pro-inflammatory cytokine production and neutrophilic inflammation in multiple organs which were not present in mice deficient in PAFRs nor the MVP-generating enzyme acid sphingomyelinase (aSMase). Moreover, the increased bacterial translocation from the gut to mesenteric lymph nodes previously reported in murine ITBI was also dependent upon PAFR and aSMase. MVP released from ITBI-treated keratinocytes contained high levels of PAFR agonistic activity. Finally, use of topical aSMase inhibitor imipramine following ITBI attenuated the widespread organ inflammatory response of ITBI, suggesting a potential therapeutic for this condition. These studies provide evidence for PAF-enriched MVP generated in skin, which then act upon the gut PAFR resulting in bacterial translocation as the mechanism for the multi-organ dysfunction associated with ITBI. Inasmuch as aSMase inhibitors are widely available, these studies could result in effective treatments for ITBI.

Application of Machine Learning and its use in determining Sepsis Prediction

Sepsis is a potentially life-threatening and serious condition that occurs when an infection spreads across the body and triggers a widespread inflammatory response. It has a significantly high death rate, especially for patients in the ICU. Early detection and treatment of sepsis is necessary. Machine learning models for sepsis detection can be trained on a variety of data sources, such as electronic health records (EHRs), vital signs, laboratory test results, and demographic information. Exploratory Data analysis was performed using different pre-processing techniques. To classify the disease, the Random Forest Classifier is used, and comparison also performed among various Classifiers like MLP, KNN, etc. Key Words: Sepsis Prediction, Random Forest Classifier, vital signs.

Cord blood-derived biologics lead to robust axonal regeneration in benzalkonium chloride-injured mouse corneas by modulating the Il-17 pathway and neuropeptide Y

BackgroundUmbilical cord blood-derived therapeutics, such as serum (UCS) and platelet-rich plasma (UCPRP), are popular treatment options in clinical trials and can potentially be utilized to address a clinically unmet need caused by preservatives, specifically benzalkonium chloride (BAK), present in ophthalmic formulations. As current clinical interventions for secondary injuries caused by BAK are suboptimal, this study will explore the feasibility of utilizing UCS and UCPRP for cornea treatment and investigate the underlying mechanisms associated with this approach.MethodsMice’s corneas were administered BAK to induce damage. UCS and UCPRP were then utilized to attempt to treat the injuries. Ocular tests were performed on the animals to evaluate recovery, while immunostaining, RNA-seq, and subsequent bioinformatics analysis were conducted to investigate the treatment mechanism.ResultsBAK administration led to widespread inflammatory responses in the cornea. Subsequent treatment with UCS and UCPRP led to the downregulation of immune-related ‘interactions between cytokine receptors’ and ‘IL-17 signaling’ pathways. Although axonal enhancers such as Ngf, Rac2, Robo2, Srgap1, and Rock2 were found to be present in the injured group, robust axonal regeneration was observed only in the UCS and UCPRP treatment groups. Further analysis revealed that, as compared to normal corneas, inflammation was not restored to pre-injury levels post-treatment. Importantly, Neuropeptide Y (Npy) was also involved in regulating immune responses, indicating neuroimmune axis interactions.ConclusionsCord blood-derived therapeutics are feasible options for overcoming the sustained injuries induced by BAK in the cornea. They also have potential applications in areas where axonal regeneration is required.

Advances in nano-based drug delivery systems for the management of cytokine influx-mediated inflammation in lung diseases.

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.

The intersection of coagulation activation and inflammation after injury: What you need to know.

IV, Review article.

Immunological characteristics of CD103+CD8+ Tc cells in the liver of C57BL/6 mouse infected with plasmodium NSM.

CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were sacrificed on 12-16days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8+ Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8+ Tc cells significantly decreased after infection. Compared to that of CD103- CD8+ Tc cells, CD103+ CD8+ Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103+CD8+ Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.

In vitro assessment of inflammatory skin potential of poly(methyl methacrylate) at non-cytotoxic concentrations.

Poly(methyl methacrylate) (PMMA) is considered an attractive substrate material for fabricating wearable skin sensors such as fitness bands and microfluidic devices. Despite its widespread use, inflammatory and allergic responses have been attributed to the use of this material. Therefore, the main objective of this study was to obtain a comprehensive understanding of potential biological effects triggered by PMMA at non-cytotoxic concentrations using in vitro models of NIH3T3 fibroblasts and reconstructed human epidermis (RhE). It was hypothesized that concentrations that do not reduce cell viability are sufficient to activate pathways of inflammatory processes in the skin. The study included cytotoxicity, cell metabolism, cytokine quantification, histopathological, and gene expression analyses. The NIH3T3 cell line was used as a testbed for screening cell toxicity levels associated with the concentration of PMMA with different molecular weights (MWs) (i.e., MW ~5,000 and ~15,000 g/mol). The lower MW of PMMA had a half-maximal inhibitory concentration (IC50 ) value of 5.7 mg/cm2 , indicating greater detrimental effects than the higher MW (IC50 = 14.0 mg/cm2 ). Non-cytotoxic concentrations of 3.0 mg/cm2 for MW ~15,000 g/mol and 0.9 mg/cm2 for MW ~5,000 g/mol) induced negative metabolic changes in NIH3T3 cells. Cell viability was severely reduced to 7% after the exposure to degradation by-products generated after thermal and photodegradation degradation of PMMA. PMMA at non-cytotoxic concentrations still induced overexpression of pro-inflammatory cytokines, chemokines, and growth factors (IL1B, CXCL10, CCL5, IL1R1, IL7, IL17A, VEGFA, FGF2, IFNG, IL15) on the RhE model. The inflammatory response was also supported by histopathological and gene expression analyses of PMMA-treated RhE, indicating tissue damage and gene overexpression. Results suggested that non-cytotoxic concentrations of PMMA (3.0 to 5.6 mg/cm2 for MW ~15,000 g/mol and 0.9 to 2.1 mg/cm2 for MW ~5,000 g/mol) were sufficient to negatively alter NIH3T3 cells metabolism and activate inflammatory events in the RhE skin.

How Can We Predict Disease Severity in Viral Infections?

How Can We Predict Disease Severity in Viral Infections?

Comparison of T Lymphocyte Subsets and Natural Killer Lymphocytes in Moderate Versus Severe COVID-19 Patients.

Severe respiratory involvement that follows a process of immune dysregulation and intense cytokine production remains to be the most dreaded complication of Coronavirus Disease-2019 (COVID-19) infection. The aim of this study was to analyze T lymphocyte subsets and natural killer (NK) lymphocytes in moderate and severe cases of COVID-19 infection and assess their significance in disease severity and prognosis. Twenty moderate cases and 20 severe cases of COVID-19 were studied and compared regarding blood picture, biochemical markers, T lymphocyte population subsets, and NK lymphocytes, which were determined by flow cytometric analysis. On analyzing the flow cytometric data of T lymphocyte cells and their subsets and NK cells in two groups of COVID-19 infection (one group moderate and the other severe cases), some immature NK lymphocyte relative and absolute counts were higher in the severe patients with worse outcome and death, while some mature NK lymphocyte relative and absolute counts were depressed in both groups. Also, interleukin (IL)-6 was significantly higher in severe cases when compared to moderate cases, and there was a positive significant correlation between immature NK lymphocyte relative and absolute counts and IL-6. There was no statistically significant difference between T lymphocyte subsets (T helper and T cytotoxic) with disease severity or outcome. Some immature NK lymphocyte subsets contribute to the widespread inflammatory response that complicates severe cases of COVID-19; therapeutic approaches directed to enhancing NK maturation or drugs that block NK cell inhibitory receptors have a potential role in controlling COVID-19 induced cytokine storm.

Glycopeptidolipid Defects Leading to Rough Morphotypes of Mycobacterium abscessus Do Not Confer Clinical Antibiotic Resistance.

Mycobacterium abscessus is an emerging pathogen causing severe pulmonary infections. Within chronically infected patients, M. abscessus isolates undergo molecular changes leading to increased virulence and antibiotic resistance. Specifically, mutations in glycopeptidolipid (GPL) synthesis genes, leading to the rough phenotype, are associated with invasive, nonremitting infections and a severe clinical course. It has been unclear whether GPL defects confer antibiotic resistance independently of other molecular changes. We used transposon technology to isolate a rough (GPL-defective; Tn MABS_4099cZeoR) mutant and compare it to a fully isogenic parent strain (ATCC 19977) bearing wild-type zeocin resistance (WTZeoR). Antibiotic susceptibility profiles of Tn_4099cZeoR and WTZeoR were tested and compared using the Sensititre RAPMYCOI antimicrobial susceptibility test plate. MICs were evaluated within clinically relevant values according to the Clinical and Laboratory Standards Institute (CLSI) standards. We found that M. abscessus with rough colony morphotype (Tn_4009c) had comparable antibiotic susceptibility to its smooth isogenic WT counterpart. Small differences (a 1:2 dilution) in MICs were found for imipenem, cefoxitin, and tigecycline, yet those small differences did not change the clinical susceptibility report for these antibiotics, as they fell within the same CLSI cutoffs for resistance. While small alternations in susceptibility to imipenem, cefoxitin, and tigecycline were noted, we conclude that the GPL mutations in M. abscessus did not confer clinically significant antibiotic resistance. Increased antibiotic resistance in the clinical setting may occur in an unrelated and parallel manner to GPL mutations. IMPORTANCE Mycobacterium abscessus chronically infects patients with preexisting lung diseases, leading to progressive deterioration in pulmonary function. The common perception among clinicians is that the rough phenotype is associated with progressive disease and severe clinical course, manifested as a widespread inflammatory response and resistance to antibacterials. However, as clinical isolates accumulate hundreds of mutations over the prolonged course of infection, it is unclear whether the rough phenotype per se is responsible for the antibiotic resistance seen in late-stage infections, or whether the resistance is related to other genetic changes in the bacteria. Previous studies mostly compared rough and smooth clinical isolates. Here, for the first time, we compared WT smooth bacteria to a specific rough, GPL-associated, otherwise-isogenic mutant. We determined that the rough morphotype had essentially identical antibiotic susceptibilities as the parent strain. The mechanistic basis for the antibiotic resistance observed in rough clinical isolates is therefore most probably related to other genetic determinants.

The Effect of Short-term Methylprednisolone on Clinical Outcome and Lung CT Scan in Severe COVID-19: In-hospital and Six Weeks Later Follow-up

Background: The severe coronavirus disease 2019 (COVID-19) induces widespread inflammatory responses that are attempted to be managed by the administration of anti-inflammatory drugs, along with antiviral drugs and respiratory support. This clinical trial study investigated the effect of short-term and low-dose methylprednisolone on the clinical outcome and radiological improvement of admitted patients with severe COVID-19. Methods: In this randomized clinical trial, two strains of patients with severe pneumonia of COVID-19 were evaluated before and after the use of corticosteroids. Inclusion criteria were age over 18 years, definitive case of COVID-19 based on positive reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), and arterial oxygen saturation (SaO2 )<93%; furthermore, at least 7 days and 5 days should be passed since the onset of symptoms and antiviral treatment, respectively. Exclusion criteria were similar to contraindications to the administration of methylprednisolone for short-term injections and pregnancy. Patients received intravenous methylprednisolone succinate (1-1.75 mg/kg/day) for 5 days in addition to treatment based on the World Health Organization (WHO) approved protocol for COVID-19. Finally, demographic characteristics, dyspnea, peripheral oxygen saturation (SpO2), number of lymphocytes, and computed tomography (CT) scan of the patient’s chest before and after taking corticosteroids were evaluated. Results: The average oxygen saturation of patients increased significantly after taking methylprednisolone succinate (P<0.001). Moreover, dyspnea and pulmonary insufficiency in CT scans improved significantly (P<0.001), and among hematological parameters, only lymphocytes increased significantly (P=0.01). Furthermore, methylprednisolone succinate use had no effect on mortality and length of hospitalization. Conclusion: Methylprednisolone succinate use during the treatment period of COVID-19 improves clinical conditions, CT scan findings, and hematological parameters affected by inflammation, but it does not affect the mortality and length of hospitalization of patients.

Abstract 12532: Impact of Autoimmune Hepatitis on Mortality and Outcomes of Hospitalized Patients Presenting Non-st-Segment Elevation Myocardial Infarction

Introduction: Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease disease when one’s immune system attacks the liver. Due to the widespread inflammatory response, we sought to evaluate the association between Autoimmune Hepatitis and mortality in patients hospitalized with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). Methods: Patients hospitalized for NSTEMI with and without AutoImmune Hepatitis between 2016 to 2018 were identified from the National Inpatient Sample. The primary outcome was all-cause mortality. The secondary outcomes were; Length of stay, total hospital charge and odds of requiring intra aortic balloon pump. A multivariable logistic regression analysis was used to adjust for in-hospital complications. A p-value of <0.05 was considered significant. Results: There were a total of 949,984 NSTEMI patients. Out of this number, 949,659 patients had NSTEMI without AIH, while 324.9 had NSTEMI with AIH. The mean age for NSTEMI without AIH was 68.2 years while the mean age for NSTEMI with AIH was 68.7 years. The odds of in-patient mortality in NSTEMI without AIH vs NSTEMI with AIH was 3.46% vs 4.62% respectively, (aOR= 1.5 , CI = 0.505 - 4.696, p = 0.76). The length of hospital stay (LOS) in NSTEMI without AIH vs NSTEMI with AIH was 4.58 days vs 4.66 days respectively, (CI = -1.016 - 1.223, P=0.18); and total hospital charges (THC) were $86,631 vs $81,851, ( CI = -23814 - 20432, P = -0.15). The odds of requiring intra aortic balloon pump (IABP) between NSTEMI without AIH vs NSTEMI with AIH was 2.49% vs 1.54% respectively, (aOR = 0.72, CI = 0.101 - 5.177). Conclusions: Patients with AutoImmune Hepatitis in the setting of NSTEMI did not have a difference in mortality or other clinical outcomes when compared with patients without AutoImmune Hepatitis. As with most observational studies, causality may not be confirmed due to potential residual confounding.

Operation "NeuroTeam": rendering the absolute best care for the most deserving patients under the most difficult conditions

The tenets of neurosurgery worldwide, whether in the civilian or military sector, espouse vigilance, the ability to adapt, extreme ownership, and, of course, an innate drive for developing a unique set of technical skills. At a time in history when the complexity of battlefield neurotrauma climaxed coupled with a chronic shortage of military neurosurgeons, modernized solutions were mandated in order to deliver world-class neurological care to our servicemen and servicewomen. Complex blast injuries, as caused by an increased incidence of improvised explosive devices, yielded widespread systemic inflammatory responses with multiorgan damage. In response to these challenges, the "NeuroTeam," originally a unit of two neurosurgeons as deployed during Operation Desert Storm, was redesigned to instead pair a neurosurgeon with a neurointensivist and launched itself during two specialized missions in Operations Iraqi Freedom and Enduring Freedom. Representing a hybridized version of present-day neurocritical care teams, the purpose of this unit was to optimize neurosurgical care by focusing on interdisciplinary collaboration in an Echelon III combat support hospital. The NeuroTeam provided unique workflow capabilities never seen collectively on the battlefield: downrange neurosurgical capability by a board-certified neurological surgeon within 60 minutes from the point of injury paired with a neurocritical care-trained intensivist. This also set the stage for intraoperative telemedicine infrastructure for neurosurgery and optimized the ability to evaluate, triage, and stabilize patients prior to medical evacuation. This novel military partnership ultimately allowed the neurosurgeon to focus on the tenets of the craft and thereby the dynamic needs of the patient first and foremost. Since the success of these missions, the NeuroTeam has evolved into a detachable unit, the "Head and Neck Team," comprising neurosurgeons, otolaryngologists, and ophthalmologists, supported by a postinjury hospital unit, which includes an embedded neurocritical care physician. The creation and evolution of the NeuroTeam, necessitated by a shortage of military neurosurgeons and the dangerous shift in military wartime tactics, best exemplifies multidisciplinary collaboration and military medicine agility. As neurocritical care continues to evolve into a highly complex, distinct specialty, the lessons learned by the NeuroTeam ultimately serve as a reminder for civilian and military physicians alike. Despite the conditions and despite one's professional ego, patients with highly complex morbid neurological disease deserve expert, multidisciplinary management for survival.

33977 Successful management of disseminated and disfiguring silicone granulomatosis and associated autoimmune syndrome induced by adjuvants (ASIA) as a complication of illicit filler use

Silicone granulomatosis, both in locally destructive and disseminated forms, is an uncommon but devastating complication of illicit filler use seen most frequently in cosmetic body augmentation cases. In its most severe form, a widespread systemic inflammatory response may be triggered by the immune system’s reactivity to the illicit substance(s), often with pronounced clinical signs and symptoms. This inflammatory autoimmune syndrome induced by adjuvants has been colloquially termed ASIA in recent literature. Management of silicone granulomatosis and associated ASIA is challenging and often unsuccessful due to the pervasive intercalation of the illicit substance into local tissues and resulting persistent overstimulation of the host immune system. In this report, we present a case of severely disfiguring, disseminated silicone granulomatosis and associated ASIA as a complication of illicit filler use which was successfully managed with systemic immunomodulatory therapy.

The effects of preoperative supplementation with a combination of beta\u2010hydroxy\u2010beta\u2010methylbutyrate, arginine, and glutamine on inflammatory and hematological markers of patients with heart surgery: a randomized controlled trial

BackgroundCardiac surgery is associated with a widespread inflammatory response, by an additional release of free radicals. Due to the importance of these patient’s nutritional status, the present study was designed to evaluate the effectiveness of supplementation with a combination of glutamine, β-hydroxy-β-methylbutyrate (HMB) and arginine in patients undergoing to the heart surgery.MethodsThe experiment was performed in 1 month (30 days) before cardiac surgery. patients were asked to take 2 sachets of Heallagen® (a combination of 7 g l-arginine, 7 g l-glutamine, and 1.5 g daily HMB) or placebo with identical appearance and taste (maltodextrin) with 120 cc of water. Clinical and biochemical factors were evaluated in the baseline and end of the study.ResultsTotally, 60 preoperative patients (30 interventions and 30 placeboes) with a mean age of 53.13 ± 14.35 years participated in the study. Subjects in Heallagen® group had a lower serum levels of interleukin-6 (P = 0.023), erythrocyte sedimentation rate (P < 0.01), high sensitivity C-reactive protein (P < 0.01), and lymphocyte number (P = 0.007) compared to the placebo, at end of the study.ConclusionIn the patients undergoing heart surgery, Heallagen® significantly improved some of the inflammatory factors and hematological parameters. These results need to be confirmed in a larger trial.Trial registration: The protocol of the study was registered in the IRCT.ir with registration no. IRCT20120913010826N31 at 13/10/2020.

COVID-19 patients with obesity at risk for worse outcomes despite younger age and fewer inflammatory derangements.

BackgroundCoronavirus disease 2019 (COVID-19) is a viral pulmonary infection that can progress to cytokine storm syndrome because of widespread dysregulated inflammatory response. Many patients at risk for severe COVID-19 manifestation have been identified as those with preexisting conditions of pulmonary origin, as well as conditions that impair appropriate immune response, such as obesity.ObjectivesThe aim of this study is to describe the manifestation, clinical course, and inflammatory biomarker milieu of COVID-19 in patients with obesity.SettingUniversity Hospital Philadelphia, Pennsylvania.MethodsIn this retrospective cohort study, 600 patients who were positive for COVID-19 were stratified by World Health Organization (WHO) obesity class and their presenting symptoms, disease biomarkers, demographics, and outcomes (intubation rate, intensive care unit [ICU] admission, length of stay [LOS], and mortality) were investigated.ResultsAge was inversely related to obesity class; patients of obesity class III presented 12.9 years younger than patients of normal weight (P < .0001). Initial ferritin lab values were negatively correlated with increasing obesity class (P = .0192). Normal or near-normal lymphocyte profile was noted in patients with obesity compared with patients without obesity (P = .0017). Patients with obesity had an increased rate of ICU admission (P = .0215) and increased length of stay (P = .0004), but no differences in intubation rate (P = .3705) or mortality (P = .2486).ConclusionPatients with obesity were more likely to present to the hospital at a younger age, with reduced levels of COVID-19 related biomarker disturbances, and increased LOS and ICU admission rates, although were not at increased risk for mortality.

Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low- and Middle-Income Countries (LMICs).

Currently, the coronavirus disease 2019 (COVID-19) is the priority of the global health agenda. Since the first case was reported in Wuhan, China, this infection has continued to spread and has been considered as a pandemic by the World Health Organization (WHO) within 3 months of its outbreak. Several studies have been done to better understand the pathogenesis and clinical aspects of the disease. It appears that COVID-19 affects almost all body organs due to the direct effect of the virus and its induced widespread inflammatory response. This multi-systemic aspect of the disease has to be inculcated in COVID-19 management by health providers to improve patient outcomes. This strategy could help curb the burden of the disease especially in low- and middle-income countries (LMICs) like most African countries where the pandemic is at an “embryonic” stage.

Potential Use of Cellular Stromal Vascular Fraction In Post-COVID-19 Pulmonary Injury and Adult Respiratory Distress Syndrome

A coronavirus (nCoV-2) has caused a worldwide pandemic, beginning in Wuhan, China. Patient’s acquiring viral infection (COVID-19) which is often featured by elevation of temperature (&gt;100.3 F°), cough, severe fatigue, and a variety of symptoms mimicking the flu and pneumonias. This gradually may extend to a progressive and serious respiratory failure with associated ARDS-like status and severe pneumonias with residual scarring of the interstitial areas of the lung alveoli, resulting in acute life-threatening, and permanent compromised gas exchange. Those that survive with controlled ventilation (low tidal volumes), medical induced coma, and prone positioning, are often left with reduction in pulmonary function abilities. This paper reviews some pertinent knowledge and advances in understanding of the pulmonary injuries and long-term damage of the COVID-19 patients, and reports a study to ameliorate such damage with use of cSVF for those who successfully recover.&#x0D; There now exists technology to perform sophisticated analytics (Functional Respiratory Imaging, FRI) developed by Fluidda (Belgium, EU) which provides great detail and information, including the ability to help triage the infected patients early to help assist in prediction of ventilation and ICU needs. In addition, author’s experience with use in Chronic Obstructive Pulmonary Disease (COPD) and Fibrotic Lung Diseases, the ability to evaluate effectiveness of use of cellular Stromal Vascular Fraction (cSVF) following intravascular deployment of isolated and concentrated cSVF. The hypothesis is that reduction of the widespread pulmonary inflammatory and immune responses which destroy much of the gas exchange abilities in the acute and residual damage which appears to create a long-term problem in the surviving patient population. Fluidda imaging analytics, coupled with standard pulmonary function studies, are effective at predictive studies which may prove of great help in anticipating which patient group is at most risk in the earlier infections to require ICU and potential ventilation needs.&#x0D; Use of Stromal Vascular Fraction Cells (cSVF) are known to help mitigate damage from severe inflammatory disorders, provide immunomodulation, and promote repair and regenerative effects. The ease of access, simple ability to obtain significant numbers of viable cell elements, and the deployment via intravascular route has proven safe and efficacious in other forms of lung disease, including fibrotic lung disorders.&#x0D; This paper reviews many of the current issues facing the severely infected Post-COVID-19 patient’s lung compromise, and a therapeutic option which clearly shows promise to reverse some residual damage of the lung and gas exchange functions.&#x0D;