Levels Of Acute Phase Reactants Research Articles

Comparison of ankylosing spondylitis patients with and without fibromyalgia syndrome according to the disease activation scores and response to treatment.

Objectives The aim of this study was to investigate the association of fibromyalgia (FM) syndrome with ankylosing spondylitis (AS) and to compare the AS patients with and without FM according to the disease activity, clinical and laboratory findings, and response to treatment. Patients and methods Between September 2016 and September 2020, a total of 511 patients (312 males, 119 females; mean age: 43.0±11.2 years; range, 18 to 77 years) who were diagnosed with AS were retrospectively analyzed. Age, sex, disease duration, disease onset age, and extra-articular findings were recorded. Medical treatments used by the patients for the treatment of AS and FM were noted. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), human leukocyte antigen-B27 (HLA-B27) status, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) with ESR (ASDAS-ESR) and ASDAS-CRP values were recorded. Results The frequency of FM in AS patients was 23.2%. Totally, 75.4% of the FM patients were female. The HLA-B27 positivity, extra-articular involvement frequency, disease duration, and acute phase reactants levels were similar between AS patients with and without FM (p=0.118, p=0.154, p=0.829, p=0.113, and p=0.763, respectively). The AS patients with FM had lower rates of achieving remission or low disease activity, compared to those without FM. The mean of all three disease activity scores between these two groups was also higher in the AS patients with FM (p<0.001). The rate of use of biological therapy was significantly higher in the AS patients with FM than those without FM (p=0.037). Conclusion Since the treatment plan of AS is made based on the disease activity scores, unnecessary biological therapy may be initiated for patients or the biological therapies they use may be switched unnecessarily. Therefore, it should be kept in mind that FM may present with AS in patients who do not respond to treatment clinically, and this may be misinterpreted as treatment unresponsiveness.

Abdominal aortic diameter and cardiovascular status in patients with idiopathic retroperitoneal fibrosis.

Although much debated, an exaggerated inflammatory response to advanced atherosclerosis has been implicated in the pathogenesis of idiopathic retroperitoneal fibrosis (RPF). Clinical presentation, infrarenal abdominal aortic diameter and RPF mass thickness were retrospectively analyzed in 166 patients with idiopathic RPF seen at our referral center between April 1998 and December 2019. Patients were stratified to their infrarenal abdominal aortic diameter at presentation (i.e., non-ectatic [< 25mm]; ectatic [25-29mm]; and aneurysmal [≥ 30mm]) to compare characteristics across groups with an undilated or dilated aorta. Ectatic or aneurysmal aortic dilatation was present in 34% of patients. Most clinical characteristics did not differ across abdominal aortic diameter stratified groups, but RPF mass thickness was greater in patients presenting with aortic aneurysmal dilatation compared to that in patients with an undilated aorta (49.0mm [IQR 34.0-62.0] vs 32.5mm [IQR 25.3-47.8];P < 0.001). A positive linear association was found between aortic diameter on a continuous scale and RPF mass thickness (β0.32 [95% CI 0.34-0.96];P < 0.001). This association remained significant after adjusting for age, sex and acute-phase reactant levels (β0.28 [95% CI 0.15-0.95];P < 0.01). Treatment success across aortic diameter stratified groups did not differ (P = 0.98). Treatment induced RPF mass regression was not associated with an increase in aortic expansion rate (P = 0.44). Aortic dilatation was prevalent among patients. Infrarenal abdominal aortic diameter was independently associated with RPF mass thickness. Findings support the concept that at least in a subset of patients, RPF may be secondary to advanced atherosclerosis.

Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: Cases series

IntroductionCOVID 19 pneumonia can lead to an inappropriate inflammatory response, and can be complicated by acute respiratory distress syndrome, multivisceral failure with a high mortality rate. ObjectiveTo observe the effect of therapeutic plasma exchange on the excessive inflammatory response. Materials and methodsIn this study, we included 7 confirmed cases of COVID-19 in the intensive care unit (ICU) department of the university hospital of Oujda. COVID-19 cases were confirmed by RT PCR (reverse transcription‐polymerase chain) and CT (computerized tomography) imaging according to WHO guidelines. Therapeutic plasma exchange was performed decrease cytokine storm-induced ARDS (Acute respiratory distress syndrome). Inflammation marker assays were performed before and after therapeutic plasma exchange to assess its efficacy. ResultsLevels of inflammatory cytokines (IL-6) and acute phase response proteins, including ferritin and CRP, were elevated before therapeutic plasma exchange.After therapeutic plasma exchange, levels of acute phase reactants, inflammatory mediators, were significantly reduced (p < 0.05). ConclusionOur data suggest that therapeutic plasma exchange reduces the inflammatory response in patients with severe COVID-19 not undergoing mechanical ventilation. Further studies are needed to explore the efficacy of therapeutic plasma exchange in patients with COVID-19.

Prevalence of Maternal Mortality and Clinical Course of Maternal Deaths in COVID-19 Pneumonia-A Cross-Sectional Study.

IntroductionAfter initial studies suggested that pregnant women were not at a higher risk of complications due to COVID‐19 infection. Recent investigations from Sweden and the US have indicated that pregnant and postpartum women are at increased risk of severe complications associated with COVID‐19. This study aims to find out the prevalence of maternal mortality and the clinical course of maternal mortality cases due to COVID-19 pneumonia.MethodologyA cross-sectional study was conducted from May 1st, 2020, to April 30th, 2021, at Postgraduate Institute and YCM Hospital Pimpri Pune (Maharashtra), a dedicated COVID hospital during COVID pandemic. During study period, all pregnant women who were diagnosed to have COVID-19 infection by RT PCR/Rapid Antigen Test were admitted and were enrolled for the study.AimTo audit the maternal mortality due to COVID-19 infection.PrimaryTo estimate the prevalence of maternal mortality due to COVID-19 infection in obstetric patients.SecondaryTo systematically study and analyze the clinical course of infection in mothers who had mortality due to COVID-19 pneumonia. Data collected in standard format regarding Demography, clinical presentation, need for ICU/HDU, CXR findings, laboratory parameters and cases with maternal mortality were studied in detail to fulfill the study objectives.ResultsAmong 871 COVID-19 cases diagnosed during pregnancy, nine patients had maternal mortality due to covid pneumonia. There was no obvious obstetric cause for mortality in these cases. The prevalence of maternal mortality was 0.01 (1.03%). Cases with maternal mortality were mostly in 3rd Trimester (5 of 9 cases) and presented with moderate to severe illness with breathlessness and myalgia in all 9 cases, cough and fever in 7 out of 9 cases, Tachypneoa was noted in all patients. Saturation below 90 in 6 cases and below 94 in 3 cases. Chest X-ray showed bilateral lung affection in all 9 cases. Leukocytosis with raised N:L ratio was predominantly seen, thrombocytopenia noted in 5 cases and elevated levels of acute phase reactants and inflammatory markers such as CRP, S. ferritin, ESR, LDH, D-dimer and S. fibrinogen was observed. None of the study participants received vaccine for COVID-19.ConclusionsCOVID-19 pneumonia is an additional toll for maternal mortality. Obstetric patients in 2nd and 3rd trimester having COVID-19 infection with late presentation to hospital, moderate to severe disease (RR > 30 min), with raised inflammatory markers (N:L ratio, CRP, Ferritin, d-Dimer, etc.) at presentation, having bilateral lung affection are at risk of poor maternal outcome.

Do Redox Balance and Inflammatory Events Take Place in Mild Bronchiectasis? A Hint to Clinical Implications.

We hypothesized that in mild bronchiectasis patients, increased systemic inflammation and redox imbalance may take place and correlate with clinical parameters. In plasma samples from patients with very mild bronchiectasis, inflammatory cells and molecules and redox balance parameters were analyzed. In the patients, lung function and exercise capacity, nutritional status, bacterial colonization, and radiological extension were assessed. Correlations between biological and clinical variables were determined. Compared to healthy controls, levels of acute phase reactants, neutrophils, IgG, IgA, myeloperoxidase, protein oxidation, and GSH increased and lung function and exercise capacity were mildly reduced. GSH levels were even greater in ex-smoker and Pseudomona-colonized patients. Furthermore, radiological extension inversely correlated with airway obstruction and, disease severity, and positively correlated with neutrophil numbers in mild bronchiectasis patients with no nutritional abnormalities. In stable patients with mild bronchiectasis, several important inflammatory and oxidative stress events take place in plasma. These findings suggest that the extension of bronchiectasis probably plays a role in the development of redox imbalance and systemic inflammation in patients with mild bronchiectasis. These results have therapeutic implications in the management of bronchiectasis patients.

Role of serological rapid antibody test in the management of possible COVID-19 cases.

BACKGROUNDAlthough the detection of viral particles by reverse transcription polymerase chain reaction (RT-PCR) is the gold standard diagnostic test for coronavirus disease 2019 (COVID-19), the false-negative results constitute a big challenge.AIMTo examine a group of patients diagnosed and treated as possible COVID-19 pneumonia whose multiple nasopharyngeal swab samples were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR but then serological immunoglobulin M/immunoglobulin G (IgM/IgG) antibody against SARS-CoV-2 were detected by rapid antibody test.METHODSEighty possible COVID-19 patients who had at least two negative consecutive COVID-19 RT-PCR test and were subjected to serological rapid antibody test were evaluated in this study.RESULTSThe specific serological total IgM/IgG antibody against SARS-CoV-2 was detected in twenty-two patients. The mean age of this patient group was 63.2± 13.1-years-old with a male/female ratio of 11/11. Cough was the most common symptom (90.9%). The most common presenting chest computed tomography findings were bilateral ground glass opacities (77.2%) and alveolar consolidations (50.1%). The mean duration of time from appearance of first symptoms to hospital admission, to hospital admission, to treatment duration and to serological positivity were 8.6 d, 11.2 d, 7.9 d, and 24 d, respectively. Compared with reference laboratory values, serologically positive patients have shown increased levels of acute phase reactants, such as C-reactive protein, ferritin, and procalcitonin and higher inflammatory markers, such as erythrocyte sedimentation rate, lactate dehydrogenase enzyme, and fibrin end-products, such as D-dimer. A left shift on white blood cell differential was observed with increased neutrophil counts and decreased lymphocytes.CONCLUSIONOur study demonstrated the feasibility of a COVID-19 diagnosis based on rapid antibody test in the cases of patients whose RT-PCR samples were negative. Detection of antibodies against SARS-CoV-2 with rapid antibody test should be included in the diagnostic algorithm in patients with possible COVID-19 pneumonia.

Dynamics of the level of calprotectin in patients with rheumatoid arthritis during rituximab biosimilar (Acellbia “Biocad”) therapy

Objective.To study the relationship between the level of calprotectin (CP) and RA activity, the level of acute phase reactants, proinflammatory cytokines, chemokines and growth factors, to assess its dynamics during rituximab (RTM) biosimilar therapy.Material and methods.20 patients with RA were examined. All patients received 2 intravenous infusions of RTM (Acellbia®) at a dose of 600 mg with an interval of 2 weeks against the background of methotrexate therapy. The level of CP in blood serum was measured by ELISA.Results.Before starting DAS28 (5.6 [4.9–6.8]), SDAI (27.17 [23.08–39.9]) and CDAI (26.6 [22.25–37.0]) corresponded to the high disease activity. A decrease in disease activity was noted after 12 and 24 weeks of therapy: the DAS28 value was 4.28 [3.24–4.75] and 4.14 [3.11–4.66], respectively (p&lt;0.05). Before the start of therapy, patients with RA had a higher CP level compared with healthy donors 9.68 (4.5–21.5) and 2.39 (1.52–4.45) μg/ml, respectively (p&lt;0.05). Against the background of RTM therapy, there was a decrease in the CP level 12 weeks after the first infusion of the drug in the group as a whole by 26.5% from the initial level, among patients with moderate/no effect of therapy – by 32.7% from the initial level.Conclusion.The CP level significantly decreases during therapy and can be used to monitor the effectiveness of therapy. The predictive value of this laboratory parameter requires further study.

Şiddetli COVID-19’lu Ergende Konvalesan (İmmün) Plazmayı İzleyen İntravenöz İmmünoglobülin İnfüzyonu

Coronavirus disease 2019 (COVID-19) pandemic has drawn attention over old immunotherapeutic agents such as convalescent (immune) plasma (CIP). Here, an adolescent with severe COVID-19 case requiring CIP and intravenous immunoglobulin (IVIG) treatments is described. A 17-year-old male patient was brought to the emergency room with complaints of fever, fatigue, and severe cough. Two doses of CIP were infused to the patient because of the increase in persisting fever, dyspnea, and acute phase reactant levels after the third day of routine protocol treatment. IVIG therapy was begun for 2 days at a dose of 1 g/kg/day due to resurgence in acute phase reactants and progressing radiological findings following CIP transfusion. Our patient avoided mechanical ventilation and showed immediate clinical and radiological improvement with CIP transfusion followed by IVIG therapy. Timely initiation of CIP treatment followed by IVIG prevented the disease from worsening and helped to reduce the requirement for mechanical ventilation.

Hashimoto thyroiditis in Lebanon: Fibrinogen levels increase and redox homeostasis alteration in euthyroid patients and detection of a new SAA1 “ε” isoform (V52-V57)

Hashimoto's thyroiditis (HT), the most common cause of hypothyroidism, is a multifactorial autoimmune condition characterized by elevated levels of anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-Tg), and involving both environmental and genetic factors. This study was designed to evaluate the levels of acute phase reactants and the oxidant/antioxidant status among Lebanese HT patients. It also aims to assess the possible association between selected polymorphisms of three genes, Serum amyloid A1 (SAA1), Interleukin 1 beta (IL1B) and Interleukin 1 receptor antagonist (IL1RN), and the occurrence of the disease. The study included 21 patients diagnosed with HT and 22 healthy controls. Fibrinogen, SAA, mannose binging lectin (MBL), C-reactive protein (CRP) and IL1B levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The lipid peroxidation marker malondialdehyde (MDA) and the antioxidant enzyme catalase were assessed using assay kits. SAA1 (+2995C>T and +3010C>T) and IL1B polymorphisms (g. –511C>T, g. –31T>C and g. +3954C>T) were assessed by polymerase chain reaction (PCR)-digestion. The IL1RN 86 bp variable number of tandem repeats (VNTR) was identified by fragment-size analysis. Fibrinogen levels were significantly higher in HT patients than controls (p < 0.0001), unlike other inflammatory markers which showed comparable levels between both groups. IL1B levels were not detected in plasma of patients and controls. An increase in MDA levels (p < 0.0001) coupled with a decrease in catalase activity (p = 0.034) were observed in the patients' group as compared to controls. No significant association was found between the alleles and genotypes of the studied polymorphisms and the occurrence of the disease. Interestingly, a new SAA1 allele, assigned as “ε”, was observed in two Lebanese HT patients. Our results suggest an ongoing subclinical inflammation and an alteration of the redox homeostasis in HT patients.

Crimean-Congo Hemorrhagic Fever Mimicking Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Diagnostic Challenge

To the Editors: Crimean-Congo hemorrhagic fever (CCHF), which is endemic in our country, is a zoonotic disease characterized by fever and hemorrhage that may be severe and even fatal. The primary transmission route to humans is tick bite; however, other forms of transmission are also reported including direct contact with blood or other bodily fluids of infected animals, nosocomial and vertical transmission.1 The clinical diagnosis of CCHF is difficult to establish because symptoms are nonspecific in the prehemorrhagic phase of the disease and laboratory findings are similar to other childhood infectious diseases.1,2 Here, we report two cases with fever, elevated inflammatory markers, and multisystem organ involvement initially considered as multisystem inflammatory syndrome in children (MIS-C), but subsequently diagnosed with CCHF—highlighting the diagnostic challenge in distinguishing MIS-C from other infectious diseases. To our knowledge, no CCHF cases misdiagnosed as MIS-C have been reported to date. Case 1 A 9-year-old boy was referred to our clinic with a preliminary diagnosis of MIS-C because of persisting fever, abdominal pain, conjunctivitis and increasing levels of acute phase reactants despite intravenous antibiotic treatment. His mother had been diagnosed with coronavirus disease-2019 (COVID-19) 2 months prior to admission. On admission, he had tachycardia (130 beats/min), conjunctivitis and maculopapular rash. His laboratory examination revealed lymphocytopenia, thrombocytopenia and elevated levels of liver function tests, troponin, pro-brain natriuretic peptide (pro-BNP) and inflammatory markers including procalcitonin (Table 1). Although all MIS-C criteria were met, CCHF diagnosis was also suspected, despite lack of tick bite, since the patient had progressively decreasing platelet count, and had a history of living in an endemic area and his family was engaged in animal husbandry. Polymerase chain reaction (PCR) test for CCHF was positive, and the patient was treated and discharged without any complications. TABLE 1. - Clinical and Laboratory Findings of Patients Case 1 Case 2 Demographics Age, years 9 15 Gender Male Male Presenting symptoms Fever (duration) Yes (4 days) Yes (3 days) Abdominal pain Yes Yes Vomiting Yes Yes Diarrhea Yes Yes Headache No Yes Nonpurulent conjunctivitis Yes Yes Rash Maculopapular rash Malar rash Admission laboratory findings White blood cell count (×103/µL) 3.49 2.33 Absolute lymphocyte count (/µL) 730 460 Absolute neutrophil count (/µL) 2630 1410 Hemoglobin (g/dL) 14.3 15 Platelet count (/μL) 43,000 130,000 Ferritin (normal range: 6–40 ng/mL) 20,880 1940 D-dimer (normal range: 0–550 ng/mL) 18,100 2150 CRP (normal range: 0–4 mg/L) 78 37 LDH (normal range:140–260 IU/L) 787 455 Albumin level (g/dL) 2.9 4.6 AST/ALT (U/L) 120/115 98/68 Procalcitonin (< 0.5 ng/mL) 8 Not performed Troponin (< 0.05 ng/mL) 0.08 0.03 Pro-BNP (< 71 pg/mL) 160 Not performed Imaging results Abdominal ultrasound Normal Hepatosplenomegaly Echocardiogram Mitral regurgitation Normal Organ system involvement Cardiovascular ✓ No Respiratory No No Gastrointestinal ✓ ✓ Hematologic ✓ ✓ Renal No No Neurologic No No Dermatologic ✓ ✓ SARS-CoV-2 RT-PCR Negative Negative SARS-CoV-2 antibody Negative Negative History of COVID-19 exposure Yes Yes CCHF-related characteristics History of tick bite No No History of close contact with animals Yes Yes CCHF PCR Positive Positive Treatment Ribavirin Ribavirin ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BNP, brain natriuretic peptide; CCHF, Crimean-Congo hemorrhagic fever; COVID-19, coronavirus disease 19; CRP, C-reactive protein; LDH, lactate dehydrogenase; MIS-C, multisystem inflammatory syndrome; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory system coronavirus 2. Case 2 A 15-year-old boy was referred to our hospital with a preliminary diagnosis of MIS-C because of having fever, conjunctivitis, gastrointestinal symptoms, elevated inflammatory markers and history of exposure to his father who had documented COVID-19 infection three months ago. On admission, he had fever, bilateral conjunctivitis, and malar rash. Laboratory analysis revealed lymphocytopenia and thrombocytopenia in addition to elevated inflammatory markers (Table 1). Detailed questioning revealed that he had a history of close contact with animals; however, history of tick bite was not present. On the following days, his fever persisted and platelet count continued to decrease. CCHF PCR was positive and he was treated successfully. To conclude, similar to MIS-C, clinical manifestations of CCHF include fever, headache, myalgia, rash, conjunctivitis, abdominal pain, nausea, vomiting and diarrhea.1,3 Detailed patient history and differential diagnosis are important to avoid unnecessary treatment and protect healthcare providers since infection control measures are essential in CCHF. Our two cases highlight that CCHF should be ruled out when evaluating possible MIS-C, even in the absence of tick bite history, especially in patients with progressive decline in platelet count, those living in endemic areas, and those with a history of close contact with animals.

Changing aetiology of paediatric septic arthritis.

The management of septic arthritis in children requires the prompt administration of antibiotic therapy and the identification of the causative pathogen. In the past, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae type b were considered the main causative agents of the disease, but a substantial fraction of presumptive joint infections remained unconfirmed by conventional bacteriologic cultures. In the last two decades, our knowledge of the aetiology of paediatric infectious arthritis has substantially changed as the result of the implementation of vaccination programmes against H. influenzae type b and pneumococci, and by the use of improved detection methods. In 1988, the inoculation of synovial fluid aspirates into blood culture vials revealed that Kingella kingae, a commensal member of the oropharyngeal microbiota, was the prime aetiology of skeletal system infections in children aged 6-48 months. The clinical presentation of K. kingae arthritis is subtle, and the disease is frequently missed by classic clinical and laboratory diagnostic criteria. Many children are afebrile, the acute phase reactants levels and the white blood cell counts in the blood and synovial fluid specimens are frequently normal, requiring a high clinical acumen. Increasing use of sensitive molecular methods in recent years, and particularly nucleic acid amplification tests that target K. kingae-specific genes, has further improved the detection of this elusive pathogen, demonstrated that it is responsible for 30-93% of all cases of septic arthritis below 4 years of age and reduced the fraction of culture-negative infections.

Abstract 1667: A pilot study correlating baseline plasma levels of adenosine 2A receptor (A2aR) with acute phase reactants in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors

Abstract Background: Acute-phase reactants, such as C-reactive protein (CRP) and IL-6, can modulate immune suppression within the tumor microenvironment (TME) and thus potentially result in inferior outcomes to immune checkpoint inhibitors (ICIs). Immunosuppression within the TME is also be mediated by tumoral adenosine production, via hypoxia-induced exonuclease activity of CD39 and CD73 and adenosine 2a receptor (A2aR) signaling. We sought to evaluate whether plasma levels of A2aR correlate with the acute phase reactants (CRP and IL-6) in advanced NSCLC patients treated with ICIs. Methods: Between December 2016 and April 2019, we enrolled 18 patients with advanced NSCLC treated with single-agent ICIs or in combination with chemotherapy. We isolated plasma samples from patients before ICI initiation and again after each treatment. Plasma concentrations of A2aR and IL-6 were measured using ELISA. The baseline level of CRP was obtained from peripheral blood at ICI initiation (± 3 days). Previous studies correlating CRP and cancer outcomes defined a C-reactive protein (CRP) cutoff of 10 mg/L to define normal (CRP-N) and high CRP (CRP-H) levels. We assessed the relationship between CRP, IL-6, and A2aR plasma levels. Statistical analyses were performed using the Mann-Whitney test and linear regression analysis. Results: At the initiation of ICI, the median age of the cohort was 63. Two patients had stage III disease and 16 patients had stage IV disease. Four had squamous cell carcinoma, and 14 had non-squamous cell carcinoma. Six patients were treated with concomitant chemotherapy (pembrolizumab with carboplatin and pemetrexed). Patients received a median of 4 ICI cycles (range: 1-8 cycles) in our study. In the cohort, the median baseline levels of CRP, IL-6, and A2aR were 16.9 mg/L, 5.1 pg/mL, and 3.6 ng/mL, respectively. A positive correlation was present between baseline CRP levels and IL-6 plasma levels (R=0.76; p=0.003). Seven patients were CRP-N, and 11 patients were CRP-H. CRP-H patients had a greater median baseline level of A2aR (6.0 ng/mL vs. 1.3 ng/mL; p=0.01). Likewise, patients with baseline IL-6 levels greater than 5 pg/mL had a higher median baseline level of A2aR (6.0 ng/mL vs. 1.3 ng/mL; p=0.02). Conclusions: In a small, heterogeneous cohort of advanced NSCLC patients treated with ICIs, we demonstrate that elevated baseline levels of acute-phase reactants (CRP and IL-6) potentially act as an indirect surrogate for high plasma A2aR levels. Validation from larger studies is required to understand the biomarker implications of these findings in determining outcomes to ICIs. J.D.M. and A.R.N contributed equally to this work. Citation Format: Justin D. McCallen, Abdul R. Naqash, Mona A. Marie, Nitika Sharma, Mahvish Muzaffar, Paul R. Walker, Li Yang. A pilot study correlating baseline plasma levels of adenosine 2A receptor (A2aR) with acute phase reactants in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1667.

Implementation of an Enhanced Recovery After Surgery (ERAS) protocol for acute complicated and uncomplicated appendicitis.

Enhanced Recovery After Surgery (ERAS) protocols are well-documented logistic programs in elective surgery but it is still uncertain whether ERAS can benefit emergency patients, because of significant challenges facing its application to emergency surgery. The aim of this study was to evaluate the implementation of an ERAS protocol for patients with acute appendicitis (AA), both complicated and uncomplicated. A prospective observational study was performed at two university hospitals in Spain, between January 2012 and December 2019. Inclusion criteria were patients with diagnosis of AA, undergoing appendectomy following an ERAS protocol of perioperative care. The different items of the ERAS protocol were recorded and their implementation was separately evaluated. Analyzed variables also included postoperative complications, hospital stay and readmission rate. Levels of acute phase reactants were assessed as predictors of implementation for the ERAS protocol. Eight hundred fifty patients were included; 498 males (58.5%) and 302 females (41.5%), with a mean age of 34.95 ± 17years. The implementation of all the items of the protocol was achieved in 770 patients (90.6%), 86.8% of patients with complicated AA and 93.1% of patients with uncomplicated AA (p = 0.02). Higher preoperative C-reactive protein (CRP) levels were significantly associated with the impossibility of implementing all the items of the ERAS protocol (p < 0.001), establishing a cut-off point at CRP = 13.5mg/dl. The implementation of ERAS protocols is safe and feasible in patients with AA. Although the implementation rate of all the items is lower in patients with complicated AA, it can be completed in 86.8% of these patients. CRP levels over 13.5mg/dl are predictors of difficulties in the implementation of all the items of ERAS protocols.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Resolution of large vessel stenosis in giant cell arteritis (GCA) by tocilizumab

Abstract Introduction: Progressive large vessel involvements including stenosis are commonly associated with giant cell arteritis (GCA). Glucocorticoids (GCs) are the mainstay of therapy for GCA stenosis, however, adverse effects including cardiovascular events are frequent. Patients concerns: We describe an 87-years old male patient with a medical history of diabetes mellitus and old cerebral infarction who presented with right temporal headache. Diagnosis: Color duplex sonography revealed the thickening of arterial wall and halo sign in the affected temporal arteries. In laboratory data, the elevated levels of acute phase reactants, including C-reactive protein and serum amyloid A were noted. Temporal artery biopsied specimens showed the lymphocytic infiltration and granulomatous inflammation within the arterial media, which are typical findings associated with GCA. Intervention: The patient was treated with subcutaneous injections of tocilizumab (TCZ, 162 mg) once weekly. Initially, glucocorticoids were withheld since the patient was diabetic and had a history of cerebral infarction. However, low dose prednisolone was combined with the reduced doses of TCZ (162 mg biweekly) injections due to the TCZ-related leukopenia. Outcomes: This treatment strategy resulted in the improvement of the patient's temporal headache and normalized levels of C-reactive protein and serum amyloid A. Follow-up imaging by color duplex sonography revealed the resolution of the temporal artery stenosis after 5 months of TCZ treatment. Conclusions: Patients with GCA often require long duration of steroid therapy and commonly suffer steroid-related complications. TCZ monotherapy, could induce early resolution of progressive vascular inflammation and stenosis in untreated GCA cases.

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

ObjectiveTo investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment.MethodsParticipants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies....

Von Willebrand Factor, Factor VIII, and Other Acute Phase Reactants as Biomarkers of Inflammation and Endothelial Dysfunction in Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGvHD) is an immune mediated late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Discovery of adequate biomarkers could identify high-risk patients and provide an effective pre-emptive intervention or early modification of therapeutic strategy, thus reducing prevalence and severity of the disease among long-term survivors of alloHSCT. Inflammation, endothelial injury, and endothelial dysfunction are involved in cGvHD development. Altered levels of acute phase reactants have shown a strong correlation with the activity of several immune mediated disorders and are routinely used in clinical practice. Since elevated von Willebrand factor (VWF) and factor VIII (FVIII) levels have been described as acute phase reactants that may indicate endothelial dysfunction and inflammation in different settings, including chronic autoimmune diseases, they could serve as potential candidate biomarkers of cGvHD. In this review we focused on reported data regarding VWF and FVIII as well as other markers of inflammation and endothelial dysfunction, evaluating their potential role in cGvHD.

High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients.

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00018-021-03808-8.

Apoptosis-induced T-cell lymphopenia is related to COVID-19 severity.

Increased levels of acute-phase reactants and lymphopenia are predictors of disease severity in coronavirus disease 2019 (COVID-19). This study aimed to investigate the role of apoptosis in the etiology of lymphopenia in patients with COVID-19. This multicentered, prospective, and case-control study was conducted with polymerase chain reaction(+) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and an age-gender-matched control group. Samples were taken at the time of diagnosis and analyzed via flow cytometry within 24 h. The participants' demographic data and initial laboratory tests were also recorded. In total, 33 patients with COVID-19 (mean age = 45.4 ± 17.2) and 25 controls (mean age = 43.4 ± 17.4) participated in the study. All patients were identified as having mild (16), moderate (5), or severe (12) disease severity. Both early and late apoptotic cells in B and T lymphocytes were increased in all patients with COVID-19 (p < .05). Early apoptotic (EA) B and T lymphocytes were also higher in severe cases compared to mild cases (p = .026). There was no significant difference between lymphopenia and apoptosis in patients with COVID-19. However, patients with lymphopenia (n = 14) and severe COVID-19 (p = .013) had increased EA T lymphocytes. This study's results show that B and T lymphocytes' apoptosis increases in patients with COVID-19. In addition, enhanced T lymphocyte apoptosis is associated with disease severity in lymphopenic patients with COVID-19.

Factors associated with radiographic progression in patients with Takayasu's arteritis.

To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.