Signs Of Systemic Inflammation Research Articles

How international guidelines recommend treating children who have severe COVID-19 or risk disease progression.

This study reviewed the current knowledge and guidelines on managing COVID-19 in children and proposed a practical approach to drug treatment. We analysed international guidelines from four prominent scientific bodies on treating COVID-19 in children. These were the UK National Institute for Health and Care Excellence, the American National Institutes of Health, the Infectious Diseases Society of America and the Australian National Clinical Evidence Taskforce COVID-19. Most paediatric patients with COVID-19 only require symptomatic treatment. There was limited evidence on treatment recommendations for children with severe COVID-19 or at risk of disease progression. However, several drugs are available for children and we have summarised the guidelines, in order to provide a concise, practical format for clinicians. All the guidelines agree that nirmatrelvir plus ritonavir or remdesivir can be used as prophylaxis for severe COVID-19 in high-risk patients. Remdesivir can also be used for severe COVID-19 cases. Glucocorticosteroids are recommended, particularly in patients requiring oxygen therapy. Tocilizumab or baricitinib should be reserved for patients with progressive disease and/or signs of systemic inflammation. The guidelines provide useful advice and a degree of consensus on specific drug treatment for children with severe COVID-19 or at risk of progression.

Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. Out of 48,CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

Review of Generalized Pustular Psoriasis: Prevalence, Diagnosis, and Treatment Options

Background: Generalized pustular psoriasis (GPP) is a diagnostic challenge for clinicians and is relatively rare. Prevalence is currently reported to be higher in Asian countries and among female patients; peak age of onset is variable across studies. Objective: This article provides clinicians with an overview of the global prevalence of GPP, common clinical presentation and diagnostic criteria, pathogenesis, and evolving treatment options. Discussion: Clinical presentation is characterized by onset of generalized sterile pustules with erythema, and may include systemic inflammatory signs including fever and lab abnormalities. Diagnostic criteria vary globally. European Rare and Severe Psoriasis Expert Network (ERASPEN) criteria present a clinical diagnosis while Japanese criteria include a biopsy. Advancements in understanding of pathogenesis have uncovered the role of IL-36 as a driver of disease, and this is the target of new treatments including spesolimab, an anti-IL-36 receptor antibody.

STUDY TO DETERMINE THE ASSOCIATION BETWEEN INFLAMMATORY MARKER (C-REACTIVE PROTEIN) AND HBA1C IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objectives: Patients with type 2 diabetes exhibit subclinical inflammation and nearly all signs of systemic inflammation, which characterized by high circulating levels of inflammatory parameters. The present study aimed to assess the levels of the inflammatory markers such as C-reactive protein (CRP) in patients with type 2 diabetes mellitus and to correlate their values with the hemoglobin A1c (HbA1c) levels. Methods: This cross-sectional study was conducted on 78 patients with type 2 diabetes in Patna Medical College and Hospital, Patna. All patients had laboratory investigations including HbA1C and CRP, patients were assessed according to glycemic status, patients with under control of diabetics (HbA1C level was equal to or &lt;6.5%), and patients with poorly-controlled diabetics (HbA1c level was &gt;6.5%). Results: Statistically significant association was observed between CRP levels and level of HbA1c. The CRP level was significantly higher in poorly-controlled diabetic patient than who with well-controlled diabetics (p=0.017). Conclusions: There is positive correlation between the level of glycemic control (HbA1c) and CRP levels; better glycemic control results in significant reduction in the highly sensitive C-reactive protein levels.

Gender characteristics of non-alcoholic fatty liver disease course

Objective. To study the clinical picture, functional indicators of the liver, lipid spectrum, proinflammatory cytokine levels and epithelial dysfunction markers in patients with non-alcoholic fatty liver disease (NAFLD) so as to detect gender differences.&#x0D; Materials and methods. Fifty-two persons with a mean age of 43.0 ± 11.1 years including 17 men (33 %) and 35 women (67 %), who suffered from NAFLD against the background of obesity were examined. The comparison group enclosed 30 practically healthy persons aged 42.3 ± 7.0 years, who had no liver pathology and obesity. The laboratory study included the assessment of functional liver tests, lipid spectrum, proinflammatory cytokine levels and epithelial dysfunction markers.Steatosis of the liver was determined with the method of ultrasonic investigation.&#x0D; Results. In the examined group with NAFLD, there prevailed women (67 %). The structure of complains and concomitant pathology had no marked gender differences. The USI showed the symptoms of liver steatosis in all the patients. Among men and women with NAFLD, normal transaminase levels, cholestasis syndrome, more expressed in men, similar disorders of blood lipid spectrum were registered. The proinflammatory cytokine concentrations in the blood serum of female patients with steatosis were significantly higher than in the comparison group and among males with NAFLD. The disturbance of the endothelial angiogenic function in the form of increased vasculoendothelial growth factor concentration more pronounced in men than in steatosis women was detected (р = 0.031).&#x0D; Conclusions. Among women with NAFLD, slightly expressed cholestasis syndrome, dyslipidemia, signs of systemic inflammation with increased proinflammatory cytokine concentration and disturbance of angiogenic function of endothelium were registered. In men with liver steatosis, there was identified cholestasis syndrome, dyslipidemia, and angiogenic dysfunction of endothelium, more marked than in women.

Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease.

Cardiovascular diseases (CVD) are the leading cause of death globally. Inflammation is an important driver of CVD where tissue damage may lead to the formation of deadly thrombi. Therefore, antithrombotic drugs, such as platelet inhibitors, are crucial for secondary risk prevention in coronary artery disease (CAD) and peripheral artery disease (PAD). For severe forms of the disease, dual-pathway inhibition (DPI) where low-dose aspirin is combined with rivaroxaban has shown improved efficacy in reducing cardiovascular mortality. Given this greater improvement in mortality, and the importance of inflammation in driving atherosclerosis, the potential for off-target inflammation-lowering effects of these drugs was evaluated by looking at the change in immune cell distribution and responsiveness to ex vivo lipopolysaccharide (LPS) stimulation after 3months of DPI in patients with CAD. We observed no changes in whole blood or peripheral blood mononuclear cell (PBMC) immune cell responsiveness to LPS after 3months of DPI. Additionally, we did not observe any changes in the distribution of total white blood cells, monocytes, neutrophils, lymphocytes, or platelets during the study course. Signs of systemic inflammation were studied using Olink proteomics in 33 patients with PAD after 3months of DPI. No changes were observed in any of the inflammatory proteins measured after the treatment period, suggesting that the state of chronic inflammation was not altered in these subjects. Threemonths of DPI does not result in any meaningful change in immune cell responsiveness and distribution in patients with CAD or PAD. ClinicalTrials.gov ID: NCT05210725.

The Clinical Picture of Castleman Disease: A Systemic Review and Meta-Analysis of Almost 2000 Patients

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathological features, including unicentric (UCD), idiopathic multicentric (iMCD) and cases that are associated with the human herpesvirus 8 (HHV8+ MCD). As treatment options for each type of CD vary, it is important to be able to distinguish their clinical presentation from their subtypes and determine the correct diagnosis. To our knowledge, there are no major review articles summarising the clinical features of different CD subtypes. The aim of this study was to describe and compare the clinical presentation of different CD subtypes reported in the literature. Methods: We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following the PRISMA guidelines. Publications were cross-checked by study location, data collection period and investigators to identify duplicated patients. Where a patient may have been included in &amp;gt;1 study, the publication with the fewest patients or least symptom data was excluded. For each subtype of CD within each study, we extracted data on demographics, clinical symptoms and laboratory parameters as stated in the international consensus diagnostic criteria for iMCD. We estimated the mean percentage of patients meeting each diagnostic criterion for each CD subtype using meta-analyses conducted with random-effects logistic regression models. Results: We analysed 32 studies with 1998 patients from 16 countries, including 559 UCD, 1023 iMCD and 416 HHV8+ MCD cases. There was a predominance of males not only in HHV8+ MCD (88.5% males) but also in iMCD (59.1% males). Patients with UCD tended to be younger than patients with iMCD and HHV8+ MCD. Most patients with iMCD (91.8%) and UCD (84.7%) were of Asian ethnicity. Only 58 patients (6.4%) with iMCD were White. In contrast, almost all patients with HHV8+ MCD (93.7%) were White or Black/African American. Many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+ MCD (Table 1). There were no significant differences in laboratory findings between patients with iMCD and HHV8+ MCD. However, compared with patients with HHV8+ MCD, patients with iMCD had significantly lower rates of constitutional symptoms (46.6% vs 98.6%, p=0.038) and splenomegaly (48.2% vs 89.2%, p=0.031). In contrast, renal dysfunction seemed to appear more commonly in iMCD (36.9% vs 17.4%, not statistically significant). Patients with UCD had significantly lower rates of laboratory abnormalities vs those with iMCD and HHV8+ MCD (p&amp;lt;0.05 for all parameters listed in Table 1). Except for cutaneous findings, patients with UCD had significantly lower rates of symptoms than patients with either iMCD or HHV8+ MCD (p&amp;lt;0.05 for all non-cutaneous parameters in Table 1). However, elevated C-reactive protein (CRP), anaemia and hypergammaglobulinaemia occurred in almost 20% of patients with UCD and pulmonary findings were observed in 15.3% of cases. We identified five additional publications including 88 paediatric patients with UCD. Paediatric patients with UCD had more signs of systemic inflammation than adult UCD patients. Elevated CRP was reported in 45.1% (95% CI 20.9-71.8, n=50) of paediatric UCD patients (vs 19.7% of adults [95% CI 11.2-30.9]). Constitutional symptoms were reported in 44.4% (95% CI 21.5-69.2, n=18) of patients - significantly higher than the rate reported in adult patients with UCD (4.5%, 95% CI 1.6-12.3; p=0.0005). Conclusions: This systematic review complements the diagnosis and management guidelines for iMCD and UCD and provides a detailed description of the clinical presentation of HHV8+ MCD. We found several distinct differences between iMCD and HHV8+ MCD, probably reflecting the heterogeneity of the underlying pathomechanisms and/or different comorbidity burdens of these CD subtypes. We confirmed that systemic symptoms may be present in up to 20% of patients with UCD. Whether these cases represent a distinct entity and whether intermediate CD cases require systemic therapy beyond surgery remains to be elucidated.

Clinical burden of invasive Escherichia coli disease among older adult patients treated in hospitals in the United States

BackgroundInvasive extraintestinal pathogenic Escherichia coli disease (IED) can lead to severe outcomes, particularly among older adults. However, the clinical burden of IED in the U.S. has not been well characterized.MethodsIED encounters among patients ≥ 60 years old were identified using the PINC AI™ Healthcare Database (10/01/2015–03/31/2020) by either a positive E. coli culture in blood or another normally sterile body site and ≥ 1 sign of systemic inflammatory response syndrome or signs of sepsis, or a positive E. coli culture in urine with urinary tract infection and signs of sepsis. Medical resource utilization, clinical outcomes, and E. coli isolate characteristics were descriptively reported during the first IED encounter and during the following year (observation period).ResultsOverall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 78.5% with signs of sepsis). Most encounters involved community-onset IED (94.3%) and required hospitalization (96.5%; mean duration: 6.9 days), with 32.4% of patients being admitted to the intensive care unit (mean duration: 3.7 days). Most E. coli isolates were resistant to ≥ 1 antibiotic category (61.7%) and 34.4% were resistant to ≥ 3 antibiotic categories. Following their first IED encounter, 34.8% of patients were transferred to a skilled nursing/intermediate care facility, whereas 6.8% had died. During the observation period, 36.8% of patients were rehospitalized, 2.4% had IED recurrence, and in-hospital death increased to 10.9%.ConclusionsIED is associated with substantial clinical burden at first encounter with considerable long-term consequences. Findings demonstrate the need for increased IED awareness and highlight potential benefits of prevention.

Influence of Nutrition and Physical Activity on Local and Systemic Inflammatory Signs in Experimentally Induced Gingivitis.

Although numerous studies have been published investigating the relationship between various dietary components and inflammatory periodontal disease, it has not yet been possible to clearly distinguish between periodontally healthy and unhealthy diets. This clinical study aimed to assess the association of specific food ingredients and physical activity on local and systemic inflammatory signs in experimentally induced gingivitis. Thirty-nine non-smoking periodontally healthy volunteers (mean age 23.2 ± 3.8 years) refrained from oral hygiene in the right maxilla for 21 days to induce an experimental gingivitis. Clinical examination (baseline and day 21) included plaque index, bleeding on probing (BOP), gingival crevicular fluid volume and high sensitive C-reactive protein levels (blood sample). Accompanying the intervention, volunteers documented with validated questionnaires their physical activity converted into metabolic equivalent (MET) and their nutrition converted into the dietary inflammatory index (DII). Significantly lower BOP (p = 0.039) was found for subjects with a more anti-inflammatory DII than for those with a more pro-inflammatory DII; higher MET values were correlated with lower BOP at day 21 (correlation coefficient -0.36). The results show an influence of nutrition and physical activity on periodontal inflammation signs. The DII may be a suitable parameter to verify the relationship between nutrition and inflammatory periodontal diseases.

Laparoscopic Cholecystectomy in Acute Calculous Cholecystitis: A Secondary Center Experience.

Background Laparoscopic cholecystectomy (LC) has increasingly been accepted as the procedure of choice for the treatment of acute cholecystitis (AC). However, the timing of this procedure in the management of AC remains controversial. Hence this study was conducted to assess the feasibility of early laparoscopic cholecystectomy in acute cholecystitis. Materials and methods Patients who presented with symptoms of acute cholecystitis such as pain and tenderness in the right upper quadrant, systemic signs of inflammation, and positive ultrasound findings according to Tokyo guidelines were included for evaluation. Group 1 includes patients presented within 24 hours of the onset of symptoms whereas those presented between 25 and 72 hours of the onset of symptoms belonged to Group 2. All patients were taken up for early LC after assessment. Intraoperative and postoperative complications were analysed. Results Out of 120 patients, 37 belonged to Group 1 (30.83%) and 83 belonged to Group 2 (69.17%). There was a significant difference between the study groups in terms of certain demographic, laboratory findings and duration of surgery. None of the patients in Group 1 developed postoperative complications, whereas one patient in Group 2 had a bile leak on postoperative Day 2. Group 2 had a higher conversion rate to open procedure (p = 0.059). The mean duration of hospital stay for patients in Groups 1 and 2 were 3 and 3.3 days, respectively. Conclusion Laparoscopic cholecystectomy is safeand feasible with minimal conversion rates in patients presenting with early symptoms of AC. With the availability of good visualisation, optics, instruments and energy sources, good outcomes can be achieved.

Inflammatory hallmarks in 6-OHDA- and LPS-induced Parkinson's disease in rats

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting more than 1% of aged people. PD, which was previously identified as movement disorder, now is recognized as a multi-factorial systemic disease with important pathogenetic and pathophysiological role of inflammation. Reproducing local and systemic inflammation, which is inherent in PD, in animal models is essential for maximizing the translation of their potential to the clinic, as well as for developing putative anti-inflammatory neuroprotective agents. This study was aimed to compare activation patterns of microglia/macrophage population and systemic inflammation indices in rats with 6-Hydroxydopamine (6-OHDA)- and Lipopolysaccharide (LPS)-induced PD. Metabolic and phenotypic characteristics of microglia/macrophage population were examined by flow cytometry, systemic inflammatory markers were calculated using hematological parameters in 6-OHDA- and LPS-lesioned Wistar rats 29 days after the surgery.Microglia/macrophages from rats in both models exhibited pro-inflammatory metabolic shift. Nevertheless, in LPS-lesioned animals, highly increased proportion of CD80/86+ cells in microglia/macrophage population was registered alongside increased values of systemic inflammatory indices: neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio and systemic immune inflammation index (SII). There was significant positive correlation between the count of CD80/86+ cells and systemic inflammatory indices in these animals. Microglia/macrophages from 6-OHDA-lesioned rats were characterized by the increased fraction of CD206+ cells alongside decreased proportion of CD80/86+ cells. No signs of systemic inflammation were observed. Negative correlation between quantitation characteristics of CD80/86+ cells and values of systemic inflammatory indices was registered. Collectively, our data show that LPS-PD model unlike 6-OHDA-PD replicates crosstalk between local and systemic inflammatory responses, which is inherent in PD pathogenesis and pathophysiology.

The enhanced recovery after surgery (ERAS) protocol in elderly patients with acute cholecystitis: A retrospective study.

Enhanced recovery after surgery (ERAS) protocol is a perioperative management theory aimed at reducing the injury of surgical patients and accelerating postoperative recovery. It has been widely recognized and applied in elective surgery. This study aimed to evaluate the clinical value of the ERAS protocol during the perioperative period of laparoscopic cholecystectomy in elderly patients with acute cholecystitis. This study aimed to evaluate the clinical value of the ERAS protocol during the perioperative period of laparoscopic cholecystectomy in elderly patients with acute cholecystitis. We collected medical data from 126 elderly patients with acute cholecystitis from October 2018 to August 2021. Among the 126 patients, 70 were included in the ERAS group and 56 in the traditional group. We analyzed the clinical data and postoperative indicators of the 2 groups. No significant differences were observed regarding the general characteristics of the 2 groups (P > .05). The ERAS group had significantly earlier time to first flatus, time to first ambulation, and time to solid intake, compared with the traditional group (P < .001); additionally, the ERAS group had significantly shorter stay and gentler feeling of postoperative pain (P < .001). Furthermore, the ERAS group had significant incidences of lower postoperative lung (P = .029) and abdominal cavity infection (P = .025) compared to the traditional group. No significant difference was observed regarding the incidences of other postoperative complications between the 2 groups (P > .05). The ERAS protocol helps reduce elderly patients' stress reactions and accelerate postoperative recovery. Thus, it is effective and beneficial to implement the ERAS protocol during the perioperative period of elderly patients with acute cholecystitis.

Case of granulomatosis with polyangiitis: optimal possibilities for rapid diagnosis in a multidisciplinary hospital

Introduction. One of the distinguishing features of systemic vasculitis is their manifestation under the guise of a lesion of one or another organ system, which is often multi-organ in nature with signs of systemic inflammation. The latter is interpreted primarily as part of an infectious or paraneoplastic process, which causes a delay in the diagnosis.The aim of the study was to present the diversity of the clinical picture in vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), the speed and large volume of diagnostic measures with the effective cooperation of therapeutic and surgical specialists, radiologists on the way to verifying granulomatosis with polyangiitis in a young woman.Materials and methods. Patient K., 46 y. o., was hospitalized in the Otolaryngology Department of the N.I. Pirogov City Clinical Hospital No. 1 of the Moscow Health Department with complaints of hearing loss, pain and stuffiness in the left ear, unproductive cough, hoarseness and fever up to 38.5 °C. According to the radiography (RG) of the chest organs, right-sided pneumonia was detected. Conducted antibiotic therapy without effect. As part of the differential diagnostic search, the following nosologies were excluded: infective endocarditis, sepsis, tuberculosis, primary multiple or central lung cancer complicated by paracancer pneumonia, metastatic lesion, infectious, brucellosis spondylodiscitis.Results. In the blood test, attention was drawn to a decrease in the level of hemoglobin to 111 g / l, an increase in the rate of erythrocyte sedimentation to 45 mm / h and the level of C-reactive protein to 142 mg / l, microhematuria according to the general urine analysis. Instrumental research methods – RG of 16.02.22, MSCT of the chest organs on 17.02.22, 27.02.22, 10.03.22 showed progressive bilateral focal pneumonia with a focus of consolidation in the middle lobe, EchoCG, ultrasound of the abdominal cavity and small pelvis, RG of the temporal bone, bronchoscopy with bronchoalveolar lavage and microscopic analysis, for atypia and bacteriological culture. A gynecological examination and a smear from the cervical canal for microscopic analysis were performed, atypical cells, consulted by a phthisiatrician (no data for tuberculosis), consulted three times by a thoracic surgeon (exclusion of volumetric formation of the middle lobe of the right lung). Given the history and clinical presentation (female gender, young age, bilateral otitis media, hoarseness, and destructive nature of pneumonia), granulomatosis with polyangiitis was suspected, and tests for ANCA were prescribed. A transthoracic biopsy of the right lung was performed. A rheumatologist prescribed induction pulse therapy with corticosteroids, and after serological and histological confirmation (antibodies to Proteinase-3 Anti-PR3 &gt; 200 IU / ml, productive pneumonitis, granulomas without signs of tuberculosis), immunosuppressive therapy with cyclophosphamide. Against the background of pathogenetic treatment, a pronounced clinical and laboratory effect was noted.Conclusion. In this clinical situation, the simultaneous involvement of specialists of various profiles, the performance of a large number of laboratory and instrumental studies in dynamics, the absence of delay in histological verification made it possible to quickly exclude common diseases in the population and suspect systemic vasculitis, establishing a correct diagnosis within 5 weeks of the hospitalization period.

Characteristics and management of patients undergoing emergency surgery for diabetic foot attack.

Diabetic foot attack (DFA) is considered one of the worst manifestations of diabetic foot. It is necessary to act quickly to prevent amputation and save the patient's life. The aim of this study is to reveal the characteristic features of DFAs and be a guide to healthcare professionals to manage and refer these patients. Sixty-five patients with DFAs were analyzed retrospectively. Demographics were collected. All patients' ınfectious dis-eases Society of America/International Working Group on the Diabetic Foot (IDSA/IWDGF) stages, site ıschemia neuropathy, bacterial ınfection and depth (SINBAD) and laboratory risk ındicator for necrotizing fasciitis (LRINEC) scores were calculated. According to these measurements, patients were categorized and statistical results were obtained. We found that patients who underwent emergency surgery due to DFA applied to an average of two hospitals before applying to our facility and the median acceptance time since the beginning of the first complaint was 9 days. All patients were IDSA/IWDGF stages three and four. Most of the patients had SINBAD scores between four and six. 60% of the patients were at high risk for necrotizing fasciitis according to the LRINEC score. 58.2% of patients had periferic arterial stenosis and the amputation rate was 69.2%. 21.3% of the patients were followed in the intensive care unit, and our patients' mortality rate was 4.2%. DFA is an emergency surgical condition that requires high clinical suspicion. If not diagnosed and treated with emergency surgery, it has a high mortality and amputation rate. High white blood cell count in patients, local and systemic signs of inflammation, presence of subcutaneous emphysema in the lower extremities on a direct X-ray radiography, and high blood sugar should be considered as warning signs for DFA. Emergency surgical intervention should be performed on these patients, and if the patient is not in a suitable center for emergency surgery, they should be rapidly referred to a center with experienced clinicians.

Diagnostic Inexperience of Takayasu Arteritis in Pediatric Neurology: A Case Report and Mini-Review of the Literature

Takayasu arteritis (TA) is a chronic inflammatory vasculitis involving the aorta and its main branches. It usually starts with systemic inflammatory signs after ten years of age. Neurological symptoms seen depend on aneurysmatic, stenotic and thromboembolic events in the affected vessels. It is rarely seen in childhood and presentation with epileptic seizure is extremely rare in infantile age. In this case report, a 22-month-old child who was admitted with epileptic seizure and had a large infarction in the area matching the right middle cerebral artery (MCA) watershed. Symptoms and imaging findings due to infarction developed hours after epileptic seizure. First, low molecular weight heparin treatment was started. Following the development of multiple aneurysmatic-stenotic lesions in the left brachial artery and profunda branch, diagnosed as TA. It was added to oral steroid and azathioprine. Resistant seizures were controlled with levetiracetam and valproic acid in the poststroke period. Multidisciplinary follow-up is ongoing with anticoagulant, antiepileptic and immunosuppressive treatments. TA rarely occurs in the infantile period with acute neurological symptoms such as epileptic seizure and stroke. It is important to make diagnosis early in order to reduce the neurological comorbidities that may occur in the long term.

396 The potential role of periostin in psoriasis

Chronic plaque-type psoriasis is an inflammatory skin disease, where alterations can be found at the dermal-epidermal junction (DEJ) of the non-lesional (NL) skin and signs of systemic inflammation can also be detected. Periostin is also located at the DEJ, besides periostin is known to play a role in inflammatory and wound healing processes. Thus, we aimed to investigate the potential role of periostin in the pathogenesis of psoriasis. Serum and skin samples were collected from untreated and systemically treated (ST) psoriatic patients (PS) and from healthy (H) volunteers.

High Plasma Levels of Activated Factor VII-Antithrombin Complex Point to Increased Tissue Factor Expression in Patients with SARS-CoV-2 Pneumonia: A Potential Link with COVID-19 Prothrombotic Diathesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.

Familial Hemophagocytic Lymphohistiocytosis (Type 2) with solitary neurological presentation due to PRF1 gene mutation

Familial hemophagocytic lymphohistiocytosis (FHLH) clinically manifest with fever, hepatosplenomegaly, pancytopenia, hyperferritenemia, hypofibrinogenemia and/or neurological signs. We report a case of solitary neurological presentation and absence of systemic signs of inflammation which was initially thought to be genetic leukodystrophy but latter turn out to be FHLH type 2 due to mutation in PRF1 gene. Pediatricians should keep FHLH as a differential diagnosis in a patient with solitary neurological presentation due to neuroinflammation even if no signs of systemic inflammation or abnormal laboratory parameters.

Delirium: Fallout of Neuro-Behcet’s Disease – A Case Report

Here, we present a case of an elderly male with hypertension and diabetes, who presented to ER with delirium, ataxia, and slurring of speech associated with altered psychomotor behaviour, also features such as anorexia, painful erythematous patches over extremities, tender knee, and ankle joints were conspicuous at presentation. A brain scan on admission revealed multiple lacunar cerebellar infarcts, whereas routine blood investigations did not reveal anything substantial contributions to the cause of presenting symptoms, including negative serology for ANA, DS-DNA, HAL-B51, and anticardiolipin antibodies, done to rule in, presence of systemic autoimmune causes for the gamut of clinical features at presentation. Contemplation over past and associated clinical features, such as ocular ailment, recurrent aphthous ulcers, dermatological lesions (erythema nodosum and peudofolliculitis), and past MRI showing lesions in the thalamus and pons (diencephalon predilection) a diagnosis of Behcet’s disease (BD) was considered based on ‘International Study Group Diagnostic Criteria for BD’. More so in the event of no better explanation for the neurological involvement, in a diagnosed case of BD, presenting delirium was considered to be the fallout of Neuro-Behcet’s Disease (NBD). The Patient responded to steroids and was discharged on a combination of tapering doses of steroids with Azathioprine. Emphasising the fact that the central nervous system affection in a case presenting with signs of systemic inflammation, autoimmune vasculitis as a cause of neurological involvement should be considered, as this is critical for deciding onto the course of treatment. NBD being secondary to systemic vasculitis as compared to atherosclerotic vascular affection seen in regular stroke, require steroids and immunomodulators rather than antiplatelets and anticoagulants.

A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression

Immune-checkpoint blockade (ICB) therapy has changed the clinical outcome of many types of aggressive tumors, but there still remain many cancer patients that do not respond to these treatments. There is an unmet need to develop a feasible clinical therapeutic platform to increase the rate of response to ICB. Here we use a previously described clinically tested aptamer (AS1411) conjugated with SMG1 RNAi (AS1411-SMG1 aptamer-linked siRNA chimeras [AsiCs]) to inhibit the nonsense-mediated RNA decay pathway inducing tumor inflammation and improving response to ICB. The aptamer AS1411 shows binding to numerous mouse and human tumor cell lines tested. AS1411 induces tumor cytotoxicity in long incubation times, which allows for the use of the aptamer as a carrier to target the RNAi inhibition to the tumor. The AS1411-SMG1 AsiCs induce a strong antitumor response in local and systemic treatment in different types of tumors. Finally, AS1411-SMG1 AsiCs are well tolerated with no detected side effects.