Persistent Inflammatory Response Research Articles

Study of some immunological signatures and their association with COVID-19 in a sample of recovered Iraqi patients

Since its emergence about two years ago, the novel coronavirus has continued to be a challenge and threat to public health, struck most parts of the world, leaving more than half a billion cases of infection and more than five million deaths. Immune response abnormalities post-infection with SARS-CoV-2 have been reported, and the mechanisms that lead to them are still ambiguous. This study was conducted to evaluate some immunological markers in the serum samples of COVID-19 convalescent patients and investigate the association of these immunological signatures with their age and sex. The serum levels of immunoglobulin G, interleukin-1 beta, and interferon lambda-1 of 75 patients and 50 healthy control group members were measured, with 55 % males and 45 % females participating and ages ranging from 20 to 80 years. The measurement of the immunological signatures was performed using the enzyme-linked immunosorbent assay (ELISA). The result revealed highly significant elevated levels of the serum immunological signatures of the convalescent group in comparison to the control group, with P-values of 0.00001 for each signature. Moreover, age was observed to have an association with an elevated level of the immunological signatures as it increased in the elderly, whereas no association with sex was detected. The findings strongly suggest that COVID-19 infection results in a persistent inflammatory response, which leads to prolonged post-recovery symptoms. Post-COVID-19 syndrome necessitates additional research to clarify its pathophysiology, pathogenesis, and long-term implications.

Phosphorus magnesium fiber regulates macrophage polarization through TRPM7 to accelerate wound healing

Wound healing is a complex process that can be delayed by persistent inflammatory responses after trauma. Many studies have found that in situ application of biomaterials releases metal ions into wounds to promote wound healing, but the underlying mechanism has not been elucidated. Therefore, we developed a novel nanoscale functional material, phosphorus magnesium fiber (PMF), as a wound dressing to explore its association with wound healing. In this study, in vivo wound healing results showed that PMF accelerated wound closure in full-thickness wound animal models, accompanied by collagen deposition and granulation formation. Moreover, PMF accelerated macrophage polarization by regulating TRPM7-ERK1/2 signaling through the long-term release of magnesium ions into the wound, which contributes to enhancing cell proliferation, growth factor production, and synthesis of ECM in the wound bed, ultimately facilitating wound healing. In vitro studies revealed that PMF promoted the polarization of macrophages to the anti-inflammatory M2 phenotype. Meanwhile, PMF up-regulated TRPM7-ERK1/2 expression. In conclusion, our study confirmed the relationship between PMF and macrophage behavior mediated by the TRPM7 channel protein and subsequently investigated the function of PMF in wound healing. This magnesium-based nanofiber material offers an innovative method for treating open wounds and is anticipated to be used as a wound dressing in the field of tissue regeneration.

TSLP and HMGB1: Inflammatory Targets and Potential Biomarkers for Precision Medicine in Asthma and COPD

The airway epithelium, through pattern recognition receptors expressed transmembrane or intracellularly, acts as a first line of defense for the lungs against many environmental triggers. It is involved in the release of alarmin cytokines, which are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Knowledge of the role of epithelial cells in orchestrating the immune response and mediating the clearance of invading pathogens and dead/damaged cells to facilitate resolution of inflammation is necessary to understand how, in many chronic lung diseases, there is a persistent inflammatory response that becomes the basis of underlying pathogenesis. This review will focus on the role of pulmonary epithelial cells and of airway epithelial cell alarmins, in particular thymic stromal lymphopoietin (TSLP) and high mobility group box 1 (HMGB1), as key mediators in driving the inflammation of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), evaluating the similarities and differences. Moreover, emerging concepts regarding the therapeutic role of molecules that act on airway epithelial cell alarmins will be explored for a precision medicine approach in the context of pulmonary diseases, thus allowing the use of these molecules as possible predictive biomarkers of clinical and biological response.

IL-8 Links NF-κB and Wnt/β-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and β-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/β-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/β-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It is pathogenesis complex and includes interaction between genetic and environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play the role of environmental triggers of arthritis in animals and humans. Progress in the understanding of the gut microbiome and RA. has been remarkable in the last decade. In vitro and in vivo experiments revealed that gut dysbiosis could shape the immune system and cause persistent immune inflammatory responses. Furthermore, gut dysbiosis could induce alterations in intestinal permeability, which have been found to predate arthritis onset. In contrast, metabolites derived from the intestinal microbiota have an immunomodulatory and anti-inflammatory effect. However, the precise underlying mechanisms by which gut dysbiosis induces the development of arthritis remain elusive. This review aimed to highlight the mechanisms by which gut dysbiosis could contribute to the pathogenesis of RA. The overall data showed that gut dysbiosis could contribute to RA pathogenesis by multiple pathways, including alterations in gut barrier function, molecular mimicry, gut dysbiosis influences the activation and the differentiation of innate and acquired immune cells, cross-talk between gut microbiota-derived metabolites and immune cells, and alterations in the microenvironment. The relative weight of each of these mechanisms in RA pathogenesis remains uncertain. Recent studies showed a substantial role for gut microbiota-derived metabolites pathway, especially butyrate, in the RA pathogenesis.

Neurocognitive sequelae following COVID-19 infection in older adults with and without pre-infection neurocognitive impairment

In this case report,we describe the clinical characteristics of three older adults aged >65years with cognitive difficulties prior to theirCOVID-19 infection who reported worsening of neurocognitive symptoms in the convalescent COVID-19 phase. Formal neuropsychological testingalong with neuroimaging were included with each patient. These patients described an initial worseningin cognitive functionafter recovering from the acute phase of COVID19. This case reportdescribes variable recoveryof cognitive abilities in the convalescent stage. The direct effectof the viral infection itselfon cognitive function are well documented. We hypothesize that the persistent inflammatory or immune response in the convalescent COVID-19 stage, more commonly referred to as the indirect mechanism, contributes to the clinical syndromeknown as the Post-Acute Sequelae of SARS-CoV-2 (PASC).

Statins change the cytokine profile in Trypanosoma cruzi-infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition.

Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1β, IL-6, and TNF-α to control parasitemia. Although this response contains parasite infection, it causes damage to the heart tissue. Thus, the use of immunomodulators is a rational alternative to CCC. Rho-associated kinase (ROCK) 1 and 2 are RhoA-activated serine/threonine kinases that regulate the actomyosin cytoskeleton. Both ROCKs have been implicated in the polarization of macrophages towards an M1 (pro-inflammatory) phenotype. Statins are FDA-approved lipid-lowering drugs that reduce RhoA signaling by inhibiting geranylgeranyl pyrophosphate (GGPP) synthesis. This work aims to identify the effect of statins on U937 macrophage polarization and cardiac tissue inflammation and its relationship with ROCK activity during T. cruzi infection. PMA-induced, wild-type, GFP-, CA-ROCK1- and CA-ROCK2-expressing U937 macrophages were incubated with atorvastatin, or the inhibitors Y-27632, JSH-23, TAK-242, or C3 exoenzyme incubated with or without T. cruzi trypomastigotes for 30 min to evaluate the activity of ROCK and the M1 and M2 cytokine expression and secretion profiling. Also, ROCK activity was determined in T. cruzi-infected, BALB/c mice hearts. In this study, we demonstrate for the first time in macrophages that incubation with T. cruzi leads to ROCK activation via the TLR4 pathway, which triggers NF-κB activation. Inhibition of ROCKs by Y-27632 prevents NF-κB activation and the expression and secretion of M1 markers, as does treatment with atorvastatin. Furthermore, we show that the effect of atorvastatin on the NF-kB pathway and cytokine secretion is mediated by ROCK. Finally, statin treatment decreased ROCK activation and expression, and the pro-inflammatory cytokine production, promoting anti-inflammatory cytokine expression in chronic chagasic mice hearts. These results suggest that the statin modulation of the inflammatory response due to ROCK inhibition is a potential pharmacological strategy to prevent cardiac inflammation in CCC.

Primena kortikosteroida kod kritično obolelih pacijenata

The use of corticosteroids as immunosuppressants in critically ill patients is a very complex issue. These potent immunomodulators can be used in the treatment of critically ill patients with severe community-acquired pneumonia (SCAP) and/or septic shock. Local and systemic inflammatory responses are increased in SCAP, thus impairing gas exchange. Also, persistent inflammatory response is associated with higher mortality in patients with COVID-19 and non-COVID-19-related ARDS. However, the risk of administering systemic steroids (methylprednisolone, Dexamethasone, hydrocortisone, etc.) to non-responders is evident. In general, the use of corticosteroids in critically ill patients should not be routine (one size fits all approach) but as personalized and individualized as clinically possible (from one size does not fit all to one size fits one).

Pro-inflammatory effects of placebo neurosurgery in rats: age-related features

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, affecting millions of people globally and causing significant disability and mortality. Animal models are the final step in completing preclinical studies and the most appropriate approach for gaining a thorough understanding of disease pathophysiology. Modeling of idiopathic AD and PD in rodents requires stereotactic injections of disease‑triggering substances. The placebo surgery group is an integral component of the design of these experiments in order to diminish study bias as a result of animal stress and non‑specific surgical impact. Inflammation is the most commonly reported non‑specific post‑surgery phenomenon, which can manifest in different ways in animals of different ages used in these experiments. Objective — to compare the long‑term pro‑inflammatory effects of placebo surgery, commonly employed for PD and AD modeling, in rats of different ages. Materials and methods. Adult male Wistar rats aged 4 and 14 months were used in the study. The placebo surgery consisted of a stereotactic unilateral intracerebral infusion of buffer solution. Before the placebo surgery, animals were anaesthetized using ketamine or xylazine administered intraperitoneally. Intact animals of both ages were used as a control. The evaluation of pro‑inflammatory effects of placebo surgery was conducted using biomarkers of local and systemic inflammation: metabolic polarization of phagocytes (microglia, peripheral blood cells), C‑reactive protein (CRP) plasma level, and systemic inflammation indexes calculated from the hemogram study. Results. In young lesioned animals, a pronounced pro‑inflammatory functional shift of microglia and signs of the resolution of systemic inflammation (an anti‑inflammatory skew of circulating phagocyte metabolism as compared to age‑matched intact controls) were observed in the long term after the placebo neurosurgery. In old intact animals, hematological and immunological markers of low‑grade systemic inflammation were observed. In lesioned old rats, residual neuroinflammation along with pronounced systemic inflammatory responses (leukocytosis, substantially increased SIRI and SII values, pro‑inflammatory metabolic shift of peripheral blood phagocytes as compared to age‑matched intact controls) were registered. Conclusions. The effects of placebo neurosurgical manipulations in rats depend on age. Meta‑inflammation inherent to aged rats is aggravated by non‑specific post‑surgery inflammation, leading to pronounced, persistent systemic inflammatory responses.

Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I

Herpes simplex virus-1 (HSV-1) is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis (HSE) with a high mortality rate. Most patients present with changes in neurological and behavioral status, and survivors suffer long-term neurological sequelae. To date, the pathogenesis leading to brain damage is still not well understood. HSV-1 induced encephalitis in the central nervous system (CNS) in animals are usually very diffuse and progressing rapidly, and mostly fatal, making the analysis difficult. Here, we established a mouse model of HSE via intracerebral inoculation of modified version of neural-attenuated strains of HSV-1 (deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region), in which the LMR-αΔpA strain initiated moderate productive infection, leading to strong host immune and inflammatory response characterized by persistent microglia activation. This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage, amyloidosis, Alzheimer's disease, and neurodegeneration, eventually leading to neuronal loss and behavioral changes characterized by hypokinesia. Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled, mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.

Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline.

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I-II) was 1064 pg/mL (142-3738 pg/mL), while, in the group with moderate or severe disease (Stages III-V), it was 1941 pg/mL (529-5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38-0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.

Comparative Study of New Biomarkers in Iraqi DM2 with and without Complications.

Recent research indicates that persistent inflammatory responses may contribute to the rise of diabetic nephropathy (DN) and diabetic cardiovascular disease (DCVD) in type 2 diabetes mellitus patients (DM2). Numerous molecules associated with inflammation and angiogenesis have been implicated in the development and progression of DN and DCVD, respectively. The subjects were separated into five groups: healthy controls (n= 25), type 2 diabetes mellitus patients (n= 30), type 2 diabetes mellitus patients with nephropathy DN (n= 30), and type 2 diabetes mellitus patients with cardiovascular disease DCVD (n= 30). The blood levels of irisin, IL-8, HbA1C, urea, and creatinine were determined. In current study there was high significant increased irisin levels (p< 0.001) in DN patients than other groups and a high significant decreased IL-8 level in DCVD. Serum IL-8 and irisin levels may serve as early indicators of DM2 problems (DN, DCVD).

Impact of Frozen and Conventional Elephant Trunk on Aortic New-Onset Thrombus and Inflammatory Response.

(1) Aim: The primary endpoint of this study was to evaluate the impact of frozen elephant trunk (FET) and conventional elephant trunk (CET) on aortic mural thrombus. The secondary endpoint was to investigate the incidence of persistent inflammatory response (IR) in the form of post-implantation syndrome (PIS) or persistent fever without infection focus after FET and CET, respectively, as well as the risk factors associated with its occurrence. (2) Methods: A single-center, retrospective, observational study of 57 consecutive patients treated with FET and CET between April 2015 and June 2020 was performed. Demographics, procedural data, perioperative laboratory exams as well as vital parameters were recorded. Pre- and postoperative computer tomography angiography (CTA) scans were analyzed with a dedicated software. IR was defined as the presence of continuous fever (>38°, lasting > 24 h) and leukocytosis (white blood cell count > 12 × 1000/µL) developing after surgery in the absence of an infection focus. (3) Results: Fifty-seven consecutive patients (mean age 58.4 ± 12.6 years, 36.8% females) treated with FET (66.6%) or CET (33.3%) for acute aortic dissection (56.1%), post-dissection-aneurysm (19.2%) or aortic aneurysm (24.5%) were included. The median thrombus volume on CTA preoperatively was 10.1 cm3 (range 2–408 cm3). After surgery, the median new-onset mural thrombus was 9.7 cm3 (range 0.2–376 cm3). Nineteen (33.3%) patients developed IR; patients with IR were significantly younger (p = 0.027), less frequently of female gender (p = 0.003) and more frequently affected from acute dissection (p = 0.002) and stayed in the intensive care unit (ICU) significantly longer (p = 0.033) than those without IR. Postoperatively, the volume of new-onset thrombus was significantly greater in the IR group (84.4 vs. 3.2 cm3, p < 0.001). (4) Conclusions: In the context of CET and FET, the persistent inflammatory response occurred in 33.3% of the patients with persistent fever without infection focus. IR was associated with a higher volume of new-onset thrombus and significantly prolonged ICU stay. Further studies to investigate these observations are needed.

Immune dysregulation and RNA N6-methyladenosine modification in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by the host immune dysregulation to infection. It is a highly heterogeneous syndrome with complex pathophysiological mechanisms. The host immune response to sepsis can be divided into hyper-inflammatory and immune-suppressive phases which could exist simultaneously. In the initial stage, systemic immune response is activated after exposure to pathogens. Both innate and adaptive immune cells undergo epigenomic, transcriptomic, and functional reprogramming, resulting in systemic and persistent inflammatory responses. Following the hyper-inflammatory phase, the body is in a state of continuous immunosuppression, which is related to immune cell apoptosis, metabolic failure, and epigenetic reprogramming. Immunosuppression leads to increased susceptibility to secondary infections in patients with sepsis. RNA N6-Methyladenosine (m6A) has been recognized as an indispensable epitranscriptomic modification involved in both physiological and pathological processes. Recent studies suggest that m6A could reprogram both innate and adaptive immune cells through posttranscriptional regulation of RNA metabolism. Dysregulated m6A modifications contribute to the pathogenesis of immune-related diseases. In this review, we summarize immune cell changes and the potential role of m6A modification in sepsis. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.

Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma.

Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.

Therapeutic ultrasound ameliorates hyperalgesia and edema on CFA-induced persistent inflammatory response in mice

BackgroundThe present study investigated the effects of pulsed and continuous ultrasound (USP and USC) in edema and hyperalgesia after chronic inflammatory process induced by Complete Freund's Adjuvant-CFA and analyzing the relationship of the application frequency of ultrasound, in pro- and anti-inflammatory cytokine production. MethodsForty-five animals were divided into 9 groups; all animals from groups 2 to 9 were subjected to a persistent inflammation model induced by CFA in mice. We report the effects and the underlying action mechanisms of USP and USC in the animals which were irradiated two, three or five times a week on the left hind paw. The analyses performed in this study were: evaluation of hind paw edema through the plethysmometer, evaluation of thermal hyperalgesia through withdrawal test using a water container at 44.5°C (± 0.5°C), and the plantar region of the left paw which was removed for analysis of cytokines. ResultsOur results showed that USP and USC consistently reduced paw edema, and pulsed ultrasound showed a higher significant effect than the continuous mode. Moreover, groups with irradiation frequency of five times a week presented an inhibition of the edema, and groups with frequency of three or two times a week reduced mainly hyperalgesia, in comparison with the control group. The beneficial effects of the US then seem to be associated with upregulation of anti- and pro-inflammatory mediators, such as IL-10 and IL-6, respectively. ConclusionThis study provided evidence that ultrasound constitutes an important non-pharmacological intervention for the management of inflammatory and pain states.

CT Characteristics of Acute Pancreatitis with Preexisting Fatty Liver and Its Impact on Pancreatitis Severity and Persistent Systemic Inflammatory Response Syndrome.

PurposeTo study the CT characteristics of acute pancreatitis (AP) associated with preexisting fatty liver (FL) and the impact of preexisting FL on the severity of AP and persistent systemic inflammatory response syndrome (SIRS).Patients and MethodsA total of 189 patients with AP were divided into AP with and without preexisting FL. The CT features, clinical characteristics, severity of AP, and presence of persistent SIRS between the two groups were compared. Univariate and multivariate analyses were performed to determine the risk factors for predicting SIRS. The diagnostic performances of the risk factors were evaluated by receiver operating characteristic (ROC) curve analysis.ResultsAmong the 189 patients, 49.7% (94/189) had preexisting FL. On CT, AP patients with preexisting FL were more likely to develop necrosis (23.4% vs 10.5%, p=0.021), local complications (45.7% vs 29.5%, p=0.025) and persistent SIRS (59.6% vs 27.4%, p<0.001). Multivariate analysis showed that preexisting FL (OR=2.863, 95% CI: 1.264–6.486, p=0.012), APACHE II≥6 (OR=1.334, 95% CI: 1.117–1.594, p=0.002), and MCTSI ≥4 (OR=1.489, 95% CI: 1.046–2.119, p=0.027) could be independent risk factors for persistent SIRS. The areas under the ROC curve of preexisting FL, APACHE II, and MCISI in diagnosing AP patients with persistent SIRS were 0.664, 0.703, and 0.783, respectively.ConclusionPatients with preexisting FL were more likely to develop necrosis and local complications on CT and present more severe AP and persistent SIRS. Preexisting FL can be an independent risk factor in predicting the presence of persistent SIRS in patients with AP.

Pegfilgrastim-induced vasculitis of the subclavian and basilar artery complicated by subarachnoid hemorrhage in a breast cancer patient: a case report and review of the literature

BackgroundPegfilgrastim (PEG) is a sustained-duration pegylated form of filgrastim, a granulocyte-colony stimulating factor agent that is widely used as prophylaxis against febrile neutropenia during chemotherapy. We report the case of a breast cancer patient who developed PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) and review the relevant literature.Case presentationA 48-year-old woman had undergone surgery for breast cancer and was receiving docetaxel and cyclophosphamide as adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); on day 4 of treatment, PEG had been administered. On day 14, she was admitted to hospital with fever, general malaise, and neck pain, and her C-reactive protein level was found to be high (12.65 mg/dL). Although infection was initially suspected, antimicrobial treatment was ineffective and other laboratory test results were negative for this. Contrast-enhanced computed tomography on day 22 showed thickened vessel walls in the left subclavian artery, the origin of the common carotid artery, and the thoracoabdominal aorta. On day 26, magnetic resonance imaging of the head to investigate possible causes of headache showed signs consistent with SAH, and magnetic resonance angiography images showed irregularity in the basilar artery wall; the findings of both studies were considered to be due to PEG-induced vasculitis. Once treatment with prednisolone 40 mg/day had started, the wall thickening and irregularity improved.ConclusionAlthough an uncommon adverse effect, vasculitis affecting vessels of various sizes may be caused by PEG. To the best of our knowledge, this report is the first to describe a case of G-CSF-induced vasculitis complicated by SAH. In cases of persistent high fever and elevated inflammatory response after PEG administration and in the absence of infection, clinicians should consider the possibility of drug-induced vasculitis.

Sulfonated Thermoresponsive Injectable Gel for Sequential Release of Therapeutic Proteins to Protect Cardiac Function after Myocardial Infarction.

Myocardial infarction causes cardiomyocyte death and persistent inflammatory responses, which generate adverse pathological remodeling. Delivering therapeutic proteins from injectable materials in a controlled-release manner may present an effective biomedical approach for treating this disease. A thermoresponsive injectable gel composed of chitosan, conjugated with poly(N-isopropylacrylamide) and sulfonate groups, was developed for spatiotemporal protein delivery to protect cardiac function after myocardial infarction. The thermoresponsive gel delivered vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and platelet-derived growth factor (PDGF) in a sequential and sustained manner in vitro. An acute myocardial infarction mouse model was used to evaluate polymer biocompatibility and to determine therapeutic effects from the delivery system on cardiac function. Immunohistochemistry showed biocompatibility of the hydrogel, while the controlled delivery of the proteins reduced macrophage infiltration and increased vascularization. Echocardiography showed an improvement in ejection fraction and fractional shortening after injecting the thermal gel and proteins. A factorial design of experimental study was implemented to optimize the delivery system for the best combination and doses of proteins for further increasing stable vascularization and reducing inflammation using a subcutaneous injection mouse model. The results showed that VEGF, IL-10, and FGF-2 demonstrated significant contributions toward promoting long-term vascularization, while PDGF's effect was minimal.

Frontal fibrosing alopecia: A review of disease pathogenesis.

Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia that mostly affects postmenopausal women and causes frontotemporal hairline regression and eyebrow loss. Although the incidence of FFA has increased worldwide over the last decade, its etiology and pathology are still unclear. We cover the latest findings on its pathophysiology, including immunomodulation, neurogenic inflammation, and genetic regulation, to provide more alternatives for current clinical treatment. A persistent inflammatory response and immune privilege (IP) collapse develop and lead to epithelial hair follicle stem cells (eHFSCs) destruction and epithelial-mesenchymal transition (EMT) in the bulge area, which is the key process in FFA pathogenesis. Eventually, fibrous tissue replaces normal epithelial tissue and fills the entire hair follicle (HF). In addition, some familial reports and genome-wide association studies suggest a genetic susceptibility or epigenetic mechanism for the onset of FFA. The incidence of FFA increases sharply in postmenopausal women, and many FFA patients also suffer from female pattern hair loss in clinical observation, which suggests a potential association between FFA and steroid hormones. Sun exposure and topical allergens may also be triggers of FFA, but this conjecture has not been proven. More evidence and cohort studies are needed to help us understand the pathogenesis of this disease.