Inflammation In Severe Patients Research Articles

Analysis of risk factors for pulmonary tuberculosis with persistent severe inflammation: An observational study.

Introduction:Patients with pulmonary tuberculosis (TB) sometimes show persistent severe inflammation for more than 1 month, even if TB treatment is effective. Although this inflammation can be improved through continuous antituberculous therapy, the risk factors for persistent inflammation remain unclear. Therefore, we sought to study the characteristics of patients with persistent severe inflammation.Materials and methods:We retrospectively analyzed 147 hospitalized adult patients with C-reactive protein (CRP) levels of 5 mg/dL or more on admission to Fukujuji Hospital from April 2019 to March 2021. The patients were divided into 2 groups: 40 patients (27.2%) had CRP levels of 5 mg/dL or more at 4 weeks after admission (persistent inflammation group), and 107 patients (72.8%) had CRP levels that fell below 5 mg/dL within 4 weeks of admission (improved inflammation group).Results:The median CRP level on admission in the persistent inflammation group was 10.8 mg/dL (interquartile range 9.1–14.5), which was higher than that in the improved inflammation group (median 8.2 mg/dL [6.5–12.1], P = .002). Patients in the persistent inflammation group had a higher prevalence of large cavities, defined as cavities ≥4 cm in diameter, on chest computed tomography (CT) (n = 20 [50.0%] vs n = 12 [11.2%], P < .001).Discussion and conclusions:This study showed that 27.2% of patients who had high or moderate inflammation on admission did not achieve low CRP levels within 4 weeks after admission. Risk factors for persistent severe inflammation in patients with TB were presence of a large cavity (cavity diameter ≥4 cm) on chest CT and a high CRP level on admission. Therefore, in a patient with a large cavity on chest CT and/or CRP ≥9.0 mg/dL on admission, long-term inflammation may occur despite antituberculous therapy if other diseases are ruled out.

CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.

Reduced BDCA3+ dendritic cells in nasal mucosa induce severe inflammation in patients with allergic rhinitis and chronic rhinosinusitis

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a crucial role in T helper (Th) cell differentiation. DCs of human airway comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs), of which the cDCs lineage consists of cDC type 1 (cDC1) and cDC type 2 (cDC2). These DCs subsets differ in ontogeny and functional properties in immune response. Thus, we aimed to evaluate the expression of different dendritic cell subsets in nasal mucosa of patients with allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Nasal polyp tissues or ethmoid mucosa from patients undergoing endoscopic sinus surgery or septoplasty were collected. The expression of DCs was investigated by flow cytometry via surface markers including BDCA-1 (CD1c) for cDC1, BDCA-3 (CD141) for cDC2, and BDCA-2 (CD303) for pDC. In subjects with AR, BDCA-3+cDC levels significantly decreased in patients with accompanying CRS, more reduced in eosinophilic CRS (ECRS) than in non-eosinophilic CRS (NECRS), compared to non-CRS patients. In subjects with CRS, the expression of BDCA-3+cDC decreased in patients with accompanying AR; more reduced in multiple allergens sensitization. Consequently, the IF result showed CD4+ CD25+ Foxp3+ regulatory T cell expression was significantly decreased in CRS patients with AR compared to those without AR. Furthermore, the level of BDCA-3+cDC was also inversely related with preoperative CT scores, serum eosinophils and IgE levels. We suggest that BDCA-3+cDC may play an essential role in immunoregulation and induction of clinical tolerance. Reduced frequency of BDCA-3+cDC followed by impaired Treg expression in CRS patients with AR might reflect the mechanism of severe inflammation in patients of CRS combined with AR.

Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) μmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) μmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) μmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

A case of panuveitis with hypopyon due to presumed ocular leishmaniasis in a HIV patient.

BackgroundPost-kala-azar dermal leishmaniasis is a well-known immunologic cutaneous reaction. There are few case reports of ocular leishmaniasis. It is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. Ocular leishmaniasis panuveitis can present with severe inflammation in patients with highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome.FindingsA case of a 40-year-old man, human immunodeficiency virus (HIV) positive on HAART, with a presumed diagnosis of ocular leishmaniasis, is presented. He had a past history of visceral leishmaniasis and was referred to the uveitis service with rapidly worsening panuveitis and counting fingers vision in both eyes. On empirical anti-leishmania therapy and systemic steroids, the visual acuity of the left eye improved to 6/9 but remained poor in the right eye. Based on the medical history, improvement with therapy and the exclusion of other common infections, a presumed diagnosis of ocular leishmaniasis-related panuveitis was made.ConclusionsA major immune reaction against lingering parasites may play a key role in the pathogenesis of this sight-threatening and rapidly progressive condition. Both the infection and the immune reaction should be treated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12348-014-0021-0) contains supplementary material, which is available to authorized users.

Acute hyperglycaemia and inflammation in patients with ST segment elevation myocardial infarction

Acute hyperglycaemia in patients with acute coronary syndromes (ACS) is associated with increased cardiovascular (CV) risk among both diabetic and non-diabetic patients although the mechanisms underlying this association are not clearly understood. Acute hyperglycaemia in patients with ACS may be associated with increased systemic inflammation. Leukocytes are the major cellular mediators of inflammation and their elevated count is associated with higher CV event rate in ACS patients. Thus, it is possible that there is a relationship between acute hyperglycaemia and high leukocyte count and concomitant presence of these two conditions may contribute to increased CV risk among patients with ST segment elevation myocardial infarction (STEMI). To investigate the relationship between acute hyperglycaemia and high leukocyte count and to evaluate its association with outcomes in patients with STEMI. Glucose level and leukocyte count on admission were measured in 246 patients with STEMI admitted in 2004- -2007 to the First Department of Cardiology and Hypertension at the University Hospital in Cracow who were treated with an early invasive management strategy. Patients were divided into two groups, with acute hyperglycaemia (glycaemia on admission ≥ 7.8 mmol/L) and with normoglycaemia (glycaemia on admission < 7.8 mmol/L). Leukocyte count was defined as high when it was greater than or equal to the median in the overall study group. Acute hyperglycaemia was noted in 136 (55.3%) patients. Median leukocyte count on admission in the overall study group was 10.8 × 103/mm3 (interquartile range: 8.5-13.0). Significantly higher in-hospital mortality (11.8% vs. 1.8%, p = 0.0029) and higher rates of cardiogenic shock (10.3% vs. 0.9%, p = 0.0022), Killip class > 1 heart failure (HF; 44.1% vs. 20.0%, p < 0.0001), atrial fibrillation (11.0% vs. 3.6%, p = 0.0308), ventricular fibrillation (5.9% vs. 0.9%, p = 0.0389), repeated percutaneous coronary angioplasty (5.2% vs. 0.0%, p = 0.0158), the primary endpoint defined as death and/or cardiogenic shock (16.9% vs. 1.8%, p = 0.0001), and the secondary endpoint defined as atrial fibrillation and/or second or third degree atrioventricular block and/or HF and/or stroke/transient ischaemic attack (53.7% vs. 23.6%, p < 0.0001) were noted in the acute hyperglycaemia group in comparison with the normoglycaemic group. Adverse events were associated with high leukocyte count in all patients and in both diabetic and non-diabetic subgroups. Mean leukocyte count was higher in patients who died (13.3 ± 4.01 vs. 11.0 ± 3.56 [103/mm3], p = 0.0115; 14.2 ± 1.59 vs. 10.8 ± 3.18 [103/mm3], p = 0.0210; and 13.5 ± 4.79 vs. 11.1 ± 3.72 [103/mm3], p = 0.0363 in the overall study group, diabetics and non-- diabetics, respectively), in patients with cardiogenic shock (14.0 ± 4.56 vs. 11.0 ± 3.52 [103/mm3], p = 0.0019; and 15.4 ± 4.93 vs. 11.0 ± 3.66 [103/mm3], p = 0.0007 in the overall study group and non-diabetics, respectively), and in patients with HF (12.1 ± 3.78 vs. 10.8 ± 3.51 [103/mm3], p = 0.0083; and 12.1 ± 3.39 vs. 10.3 ± 2.90 [103/mm3], p = 0.0159 in the overall study group and diabetics, respectively) as compared to patients without respective adverse events. Glucose level on admission correlated positively with the on-admission leukocyte count. This correlation was statistically significant in the overall study group (r = 0.25, p < 0.0001), in diabetics (r = 0.27, p = 0.021), and in non-diabetics (r = 0.35, p < 0.0001). Patients with both acute hyperglycaemia and the leukocyte count greater than or equal to the median in the overall study group had a higher in-hospital risk of death and/or cardiogenic shock (odds ratio 17.6, 95% CI 1.9-165.3, p = 0.0122). Acute hyperglycaemia is associated with worse in-hospital outcomes in patients with STEMI. More severe inflammation (defined as leukocyte count on admission) is noted in STEMI patients with adverse events. A significant positive correlation can be seen between glucose level and leukocyte count on admission, and concomitant presence of both acute hyperglycaemia and more severe inflammation in patients with STEMI was found to be an independent predictor of poor in-hospital outcomes.