High Inflammatory State Research Articles

Multi-omics analysis reveals the interplay between pulmonary microbiome and host in immunocompromised patients with sepsis-induced acute lung injury.

Recent research has substantiated the significant role of microbiota in immune regulation, which could influence high inflammatory state and immunocompromise in patients with severe sepsis, as well as provide new opportunities for acute lung injury induced by sepsis diagnosis and treatment. Our study identified some potential critical microbes (Campylobacter concisus and several species of Veillonella), which were correlated with immune-related genes and might be the novel target to regulate immunotherapy in sepsis.

12431 14-year-old Presenting With Thrombocytopenia-Associated Multi-Organ Failure In The Setting Of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome

Abstract Disclosure: N.C. Gunaratne-Breaux: None. D. Deplewski: None. Title: 14-Year-Old Presenting with Thrombocytopenia Associated Multi-Organ Failure in the setting of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome Background: Coagulation complications are rare in hyperglycemia emergencies in children and adolescents. In patients presenting with severe and atypical hyperglycemia emergencies, special considerations need to be made to rule out life-threatening coagulopathy. Clinical Case: A 14-year-old male with history of Type 1 Diabetes presented in severe Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome overlap. Initially had severe hypotension and altered mental status concerning for cerebral edema. Initial venous blood gas showed pH of 6.82, pCO2 17.1, and HCO3 2.8, serum glucose was 1375 mg/dL, serum ketones >7.00 mmol/L, and serum osmolality was 384 mOsm/kg. Once insulin drip was started, glucose, ketones, and serum osmolality improved, but patient continued to be encephalopathic and had worsening tachypnea and desaturations. Patient was eventually intubated. After intubation, patient’s acidosis improved, but patient developed kidney failure (prompting initiation of dialysis), liver injury, decreased cardiac function, and high inflammatory state. A comprehensive multi-specialty team including pediatric intensive care, infectious diseases, rheumatology, neurology, and cardiology were involved in the care. On day three of admission, patient had multiple areas of ischemia on fingertips and ear and clotting of multiple IV and dialysis catheters, prompting a coagulopathy evaluation. Labs showed microcytic anemia (hemoglobin 10.0 g/dL; mean corpuscular volume 75fL), thrombocytopenia (platelet count 17 10e3/uL), coagulopathy (prothrombin time 16.8 sec, INR 1.3, prolonged thrombin time 48.8 sec), and elevated ferritin (507 ng/mL). Given labs and multi-organ involvement, determined by hematology to be Thrombocytopenia Associated Multi-Organ Failure (TAMOF). Patient was started on plasmapheresis and had dramatic improvement – was eventually extubated and returned to neurologic baseline without any notable deficits. Multi-specialty team ruled out all other possible causes of TAMOF; determination that the TAMOF developed secondary to DKA/HHS. Conclusion: Hyperglycemia emergencies can lead to a hyperinflammatory state that can lead to disruption of the coagulation cascade, including disseminated intravascular coagulopathy or thrombotic thrombocytopenia purpura. There have been rare reports of thrombocytopenia associated multi-organ failure provoked by DKA, thought secondary to critical illness mediated low ADAMST13 levels. This is a novel case of TAMOF caused by DKA/HHS overlap syndrome. It is important to screen for coagulopathy in cases of patients with DKA or DKA/HHS who do not show clinical improvement with resolution of ketosis and hyperosmolarity. Presentation: 6/2/2024

Transplantation for immune dysregulatory disorders: current themes and future expectations.

Primary immune regulatory disorders (PIRDs) are an increasing indication for hematopoietic stem cell transplant (HCT) in pediatric patients. Here, we provide an updated overview of HCT for PIRDs, and discuss future avenues for improvement in outcomes. There are now more than 50 described monogenic PIRDs, which impact all aspects of immune tolerance, regulation, and suppression. Disease characteristics are highly variable, and HCT remains the only option for cure. We review advances in targeted therapies for individual PIRDs, which have significantly improved outcomes and the ability to safely bridge to transplant. Additionally, advances in GVHD prevention, graft manipulation, personalized conditioning regimens, and supportive care have all increased survival after HCT. The high inflammatory state increases the risk of nonengraftment, rejection, and autologous reconstitution. Therapy to reduce the inflammatory state may further improve outcomes. In addition, although younger patients with fewer comorbidities have better outcomes, the clinical courses of these diseases may be extremely variable thereby complicating the decision to proceed to HCT. HCT for PIRDs is a growing consideration in cell therapy. Yet, there remain significant gaps in our understanding of which patients this curative therapy could benefit the most. Here, we review the current data supporting HCT for PIRDs as well as areas for future improvement.

Mathematical modeling of viral infection and the immune response controlled by the circadian clock.

Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations.

Heart failure — An unexplored risk factor for infective endocarditis after pacemaker implantation

BackgroundWith the widespread use of permanent pacemakers (PPM), and increased mortality associated with pacemaker endocarditis, it is essential to evaluate comorbidities that could potentially increase the risk of infective endocarditis (IE). Heart failure (HF), a common comorbidity, has not been well studied as an independent risk factor for development of IE in individuals with PPM. MethodsThe US National Inpatient Sample database was used to sample individuals with PPM. Patients with concomitant implantable cardioverter defibrillator, acute heart failure, history of endocarditis, intravenous drug use, prosthetic heart valves, or central venous catheter infection were excluded. Propensity matching was performed to match patients with and without HF. Pre- and post-match logistic regression was performed to assess HF as an independent risk factor for IE. A subgroup analysis was performed comparing IE rates between patients with HF with reduced (HFrEF) vs preserved (HFpEF) ejection fraction. ResultsOut of 333,571 patients with PPM included in the study, 121,862 (37 %) had HF. HF patients were older and had a higher prevalence of females. All comorbidities except for dental disease and cancer were more prevalent in the HF group. Patients with HF were 1.30 times more likely to develop IE [OR: 1.30 (1.16–1.47); p < 0.001]. The two cohorts were then matched for age, gender, and 20 comorbidities using a 1:1 propensity score matching algorithm. After matching, HF was still independently associated with increased risk of IE [OR: 1.62 (1.36–1.93); p < 0.001]. In our sub-group analysis, HFrEF and HFpEF patients had similar IE rates. ConclusionIn PPM population, HF was associated with an increased risk of IE compared to those without HF. We hypothesize that HF being a low-flow and high-inflammatory state might have contributed to this increased risk. Larger studies are required to corroborate our findings and evaluate the need for antimicrobial prophylaxis for this population.

Immune landscape of patients with metastatic non-clear cell renal cell carcinoma (nccRCC) treated with atezolizumab plus bevacizumab.

4535 Background: The treatment of metastatic nccRCC remains an area of unmet clinical need. A multicenter phase II trial of atezolizumab/bevacizumab in patients with advanced nccRCC or any RCC type with ≥ 20% sarcomatoid differentiation (NCT02724878) demonstrated clinical activity of these agents, with objective response rates of 50% in patients with sarcomatoid clear-cell RCC (sccRCC) and 26% in patients with nccRCC. We aim to understand the intratumoral and circulating factors that impact immunotherapy response in this population. Methods: We collected blood samples prior to therapy and on-treatment (following 2 cycles of therapy) and quantified levels of plasma soluble factors (cytokines and growth factors) using a fluorescent bead array platform. We used high dimensional flow cytometry on peripheral blood mononuclear cells to analyze the composition and phenotype of peripheral immune cells. Immunohistochemistry and immunofluorescence were performed on available formalin-fixed, paraffin-embedded tumor tissue samples (archival or on-study biopsy) collected prior to the start of therapy. We assessed relationships between biomarkers and outcomes using pairwise Wilcoxon rank-sum test and log-rank tests, and univariate Cox regression models. Results: We collected blood samples from 60 patients with paired tumor samples from 38 patients. Baseline circulating inflammatory cytokines MIP-1b, IL-1, MCP-1, IL-6, and IL-13 were highly correlated with one another, forming an “inflammatory module” that was increased in IMDC-poor risk patients and associated with worse progression-free survival (PFS) (p = 0.028). At baseline, elevated circulating VEGF-A was associated with a lack of response (p=0.03) and worse PFS (p=0.021). Whereas a larger increase in on-treatment levels of circulating VEGF-A was associated with clinical benefit as defined by Braun et al. (Nat Med. 2020) (p=0.01) and improved overall survival (p=0.006). Among peripheral immune cell populations, an on-treatment decrease in circulating PD-L1+ T cells was associated with improved outcomes: reductions in CD4+ PD-L1+ (HR:0.62[0.49-0.91], p=0.016) and CD8+ PD-L1+ T cells (HR:0.59[0.39-0.87], p=0.009) correlated with improved PFS. Within the tumor, a higher percentage of terminally exhausted (PD-1+, TIM-3+ and/or LAG-3+) CD8+ T cells at baseline was associated with worse PFS (p=0.028). Conclusions: Among patients with advanced nccRCC or sccRCC, a baseline high systemic inflammatory state and high circulating VEGF-A are associated with worse outcomes after treatment with atezolizumab and bevacizumab. High levels of intratumor terminally exhausted CD8+ T cells were associated with worse PFS. These results highlight the importance of an integrative approach to explore biomarkers of response in advanced variant histology RCC which may inform future therapeutic approaches.

Prognostic value of systemic immune inflammation index and geriatric nutrition risk index in early-onset colorectal cancer.

Systemic nutritional and inflammatory markers, which are easy to measure are associated with the progression and prognosis of many cancers. Nevertheless, among the various available indicators, optimal prognostic indicators for patients with early-onset colorectal cancer have not been identified. Therefore, the aim of this study was to identify optimal nutritional and inflammatory markers for early-onset colorectal cancer and examine the relationship between systemic nutritional and inflammatory markers before treatment and survival in patients with early-onset colorectal cancer. We retrospectively collected data from 236 eligible patients with early-onset colorectal cancer. Area under the prognostic curve (AUC) and concordance index (C-index) were used to compare seven systemic nutritional and inflammatory markers to identify the optimal inflammatory immune markers. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of indicators in the total study population and different subgroups. The AUC and C-index showed that the systemic immune inflammation index (SII) and geriatric nutrition risk index (GNRI) had higher prognostic values than other systemic nutritional and inflammatory indicators. Compared with patients in the low SII group, those in the high SII group had lower overall survival (HR, 4.42, 95% CI, 2.36-8.27, p = 0.000). Compared with patients in the high GNRI group, those in the low GNRI group had lower overall survival (HR, 0.33, 95% CI, 0.19-0.56, p = 0.000). SII was negatively associated with GNRI (R = -0.3, p < 0.001), and both were correlated with the tumor stage. SII and GNRI are suitable nutritional and inflammatory factors for predicting OS in patients with early-onset colorectal cancer; high SII and low GNRI were correlated with worse prognoses. Identifying the high inflammatory state and low nutritional state of patients before surgery and conducting active and timely therapeutic interventions could improve patient prognosis.

Influence of cytokines on early death and coagulopathy in newly diagnosed patients with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a better prognosis. But early death (ED) rate remains high. APL patients are simultaneously accompanied by coagulopathy and hyperinflammation at the onset. It is not known what effects cytokines have on ED and coagulopathy in these patients. Therefore, the purposes of this study are to explore the clinical differences between APL and other types of AML, the link between cytokines and coagulopathy in newly diagnosed APL, and their roles in the ED for APL. This study retrospectively collected the information of 496 adult patients with AML (age ≥14 years at admission) newly diagnosed in the First People's Hospital of Yunnan Province between January 2017 to February 2022, including 115 APL patients. The difference of clinical manifestations between two groups [APL and AML (non-APL)] was statistically analyzed. Then, the factors affecting ED in APL patients were screened, and the possible pathways of their influence on ED were further analyzed. The results indicate APL at the onset have a younger age and higher incidence of ED and DIC than other types of AML. Intracranial hemorrhage (ICH), age, and PLT count are found to be independent factors for ED in newly APL, among which ICH is the main cause of ED, accounting for 61.54% (8/13). The levels of cytokines in newly APL are generally higher than that in AML (non-APL), and those in the group of ED for APL were widelymore than the control group. IL-17A and TNF-β are directly related to the ED in newly APL, especially IL-17A, which also affects ICH in these patients. Moreover, the increase of IL-17A and TNF-β cause the prolongation of PT in APL patients, which reflected the exogenous coagulation pathway. However, they have no effect on APTT prolongation and FIB reduction. Thus, it is speculated that IL-17A leads to early cerebral hemorrhage death in newly APL by inducing tissue factor (TF) overexpression to initiate exogenous coagulation and further leading to excessive depletion of clotting factors and prolongation of PT. In conclusion, compared with other types of AML, APL patients have a younger age of onset and high inflammatory state, and are more likely to develop into DIC and die early. Age, and PLT count at diagnosis are independent factors for ED of APL, especially ICH. IL-17A is confirmed to be an independent risk factor for ED and ICH of newly APL. Hence, IL-17A may serve as a predictor of ED in newly diagnosed APL patients, and controlling its expression probably reduce ED in these patients.

Intermittent hypoxia treatments cause cellular priming in human microglia.

Obstructive sleep apnoea syndrome (OSAS) is a sleep-disordered breathing characterized by nocturnal collapses of the upper airway resulting in cycles of blood oxygen partial pressure oscillations, which lead to tissue and cell damage due to intermittent hypoxia (IH) episodes. Since OSAS-derived IH may lead to cognitive impairment through not fully cleared mechanisms, herein we developed a new in vitro model mimicking IH conditions to shed light on its molecular effects on microglial cells, with particular attention to the inflammatory response. The in vitro model was set-up and validated by measuring the hypoxic state, HIF-1α levels, oxidative stress by ROS production and mitochondrial activity by MTS assay. Then, the mRNA and protein levels of certain inflammatory markers (NF-κB and interleukin 6 (IL-6)) after different IH treatment protocols were investigated. The IH treatments followed by a normoxic period were not able to produce a high inflammatory state in human microglial cells. Nevertheless, microglia appeared to be in a state characterized by increased expression of NF-κB and markers related to a primed phenotype. The microglia exposed to IH cycles and stimulated with exogenous IL-1β resulted in an exaggerated inflammatory response with increased NF-κB and IL-6 expression, suggesting a role for primed microglia in OSAS-driven neuroinflammation.

Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner.

Although the global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, there are currently no specific and highly efficient drugs for COVID-19 available, particularly in severe cases. Recent findings demonstrate that severe COVID-19 disease that requires hospitalization is associated with the hyperactivation of CD4+ and CD8+ T cell subsets. In this study, we aimed to counteract this high inflammatory state by inducing T-cell hyporesponsiveness in a SARS-CoV-2-specific manner using tolerogenic dendritic cells (tolDC). In vitro-activated SARS-CoV-2-specific T cells were isolated and stimulated with SARS-CoV-2 peptide-loaded monocyte-derived tolDC or with SARS-CoV-2 peptide-loaded conventional (conv) DC. We demonstrate a significant decrease in the number of interferon (IFN)-γ spot-forming cells when SARS-CoV-2-specific T cells were stimulated with tolDC as compared to stimulation with convDC. Importantly, this IFN-γ downmodulation in SARS-CoV-2-specific T cells was antigen-specific, since T cells retain their capacity to respond to an unrelated antigen and are not mediated by T cell deletion. Altogether, we have demonstrated that SARS-CoV-2 peptide-pulsed tolDC induces SARS-CoV-2-specific T cell hyporesponsiveness in an antigen-specific manner as compared to stimulation with SARS-CoV-2-specific convDC. These observations underline the clinical potential of tolDC to correct the immunological imbalance in the critically ill.

A single-centre study on predictors and determinants of pubertal delay and growth impairment in Epidermolysis Bullosa.

BackgroundDelayed puberty is a possible complication of Epidermolysis Bullosa (EB), though the actual incidence is still unknown. In chronic illnesses delayed puberty should be correctly managed since, if untreated, can have detrimental effects on adult height attainment, peak bone mass achievement and psychological health.Aims and methodsThis is a single-centre study on pubertal development, growth and bone status in EB. Auxological, densitometric (areal Bone Mineral Density-aBMD Z-score, Bone Mineral Apparent Density-BMAD Z-score, Trabecular Bone Score-TBS and Bone Strain Index-BSI at Lumbar spine) and body composition data (Total Body DXA scans) were collected. Disease severity was defined according to Birmingham Epidermolysis Bullosa Severity (BEBS) score.ResultsTwenty-one patients (12 Recessive Dystrophic EB-RDEB, 3 Dominant Dystrophic EB, 3 Junctional EB-JEB, 2 EB Simplex and one Kindler EB) aged 13 years (females) or 14 years (males) and above were enrolled (age 16.2±2.5 years, M/F 11/10). Short stature was highly prevalent (57%, mean height -2.12±2.05 SDS) with 55% patients with height <-2SD their mid-parental height. 7/21 patients (33%, 6 RDEB and 1 JEB) had delayed puberty with a median BEBS of 50 (range 29 to 63), a height SDS of -2.59 SDS (range -5.95 to -2.22) and a median lumbar BMAD Z-score of -4.0 SDS (range -5.42 to -0.63 SDS). Pubertal status was negatively associated with BEBS, skin involvement, inflammatory state and positively with height SDS and BMI SDS.ConclusionsPubertal delay is highly prevalent in EB, especially in patients with RDEB and JEB, high severity score and inflammatory state. Moreover, pubertal delay worsens growth impairment and bone health. A study on pubertal induction is ongoing to enlighten possible beneficial effects on adult height attainment and peak bone mass accrual.

Sustained Systemic Inflammatory Response Predicts Survival in Patients with Hepatocellular Carcinoma After Hepatic Resection.

Preoperative systematic inflammatory response, represented by neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein-albumin ratio (CAR), has been associated with long-term outcomes in patients with hepatocellular carcinoma (HCC). However, the impact of sustained systematic inflammatory response after resection remains unclear. This study comprised 210 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Preoperative and postoperative NLR, LMR, and CAR were evaluated, and patients were then classified into three groups according to the status of each marker: persistently high inflammatory state (elevated group), preoperatively low inflammatory state (normal group), and preoperatively high but postoperatively low inflammatory state (normalized group). Multivariate Cox proportional hazard models were conducted to assess disease-free and overall survival, adjusting for potential confounders. In multivariate analysis, sex (p=0.002), hepatitis B surface antigen (HBsAg) positivity (p=0.002), serum α-fetoprotein (AFP) level ≥ 20 ng/mL (p<0.001), multiple tumors (p<0.001), microvascular invasion (p=0.003), type of resection (p=0.007), and elevated CAR (hazard ratio [HR] 2.40, 95% confidence interval [CI] 1.55-3.73; p<0.001) were independent and significant predictors of cancer recurrence, while sex (p=0.05), HBsAg positivity (p=0.03), serum AFP level ≥20 ng/mL (p=0.009), multiple tumors (p=0.03), microvascular invasion (p=0.006), and elevated CAR (HR 2.10, 95% CI 1.13-3.91; p=0.02) were independent predictors of overall survival. Sustained elevated CAR may be an independent and significant indicator of poor long-term outcomes in patients with HCC after hepatic resection, suggesting the interplay of the host's inflammatory state and tumor recurrence and progression in HCC.

Periodontal Ligament Stem Cells Reverse the High Glucose Level-Induced Inflammatory State of Macrophages

Periodontal Ligament Stem Cells Reverse the High Glucose Level-Induced Inflammatory State of Macrophages

Effects of Systemic Lupus Erythematosus on Clinical Outcomes and In-Patient Mortality Among Hospitalized Patients With Diverticulitis

PurposeThough there are studies on other autoimmune diseases, the literature is deficient on the associations between systemic lupus erythematosus (SLE) and diverticulitis. This study aims to evaluate the effects of SLE on clinical outcomes and in-patient mortality in patients with diverticulitis.MethodsThe National Inpatient Sample (NIS) database was used to identify adult patients with diverticulitis-related hospitalizations from 2012 to 2014 using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Primary outcomes were mortality, hospital charges, and length of stay (LOS). Secondary outcomes were effects on the complications associated with diverticulitis. Chi-squared tests and independent t-tests were used. Multivariate analysis was performed to assess the primary outcomes after adjusting for confounding variables.ResultsThere were 2,553,320 diverticulitis-related hospitalizations from 2012 to 2014, of which 13,600 patients had SLE. The average LOS was 5.2 days, mortality rate was 0.8%, and total hospital charges per patient were $43,970. SLE was associated with a statistically significant longer LOS and higher hospital costs. SLE was statistically significant for having higher perforation rates but lower rates for morality, abscesses, and fistula formation. Differences in complications such as sepsis, gastrointestinal bleeding, and surgical intervention requirement were non-significant.ConclusionSince SLE causes a high inflammatory state, one would expect higher rates of complications and possibly higher mortality rates in those with concomitant diverticulitis. However, although there was a higher LOS and hospital cost, the mortality rate was lower and only a complication of perforation was found to be higher in SLE patients.

Clinical Outcomes and Inpatient Mortality Among Hospitalized Patients With Concomitant Autoimmune Hepatitis and Systemic Lupus Erythematosus.

BackgroundAutoimmune hepatitis (AIH) is an inflammatory disease of the liver that is characterized by a broad disease spectrum, circulating autoantibodies, and elevated serum globulin levels. Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by a high inflammatory state and is associated with multiorgan system involvement. Despite a well-known association between AIH and other autoimmune diseases, the literature is deficient on the associations between AIH-related outcomes and complications in SLE patients. This study aims to evaluate the effects of SLE on clinical outcomes and inpatient mortality in patients with AIH.MethodThe National Inpatient Sample (NIS) database was used to identify AIH-related hospitalizations from 2012 to 2014 using International Classification of Diseases Ninth Edition Revision (ICD-9) codes. Patients were divided into two groups, those with and without SLE. Primary outcomes were mortality, hospital charges, and length of stay (LOS). Secondary outcomes were complications associated with AIH: cirrhosis, gastrointestinal (GI) bleed, acute liver failure (ALF), cholangitis, pancreatitis, and sepsis. Chi-squared tests for categorical data and independent t-test for continuous data were used to compare outcomes. Multivariate analysis was performed to assess the primary outcomes after adjusting for confounding variables.ResultsThere were 17,050 AIH-related hospitalizations from 2012 to 2014 and 1,115 patients had SLE. In patients with SLE and AIH, 1,035 were female with average age of 48.6. The average LOS was 6.3 days, mortality rate was 1.35%, and total hospital charges were $48,146. SLE was associated with a statistically significant lower mortality rate compared to the control. LOS, hospital cost, and CCI (Charlson Comorbidity Index) were not found to be significantly different. For secondary outcomes, SLE was statistically significant for having higher pancreatitis rates. SLE patients had statistically significant lower cholangitis, and ALF. Differences in complications such as sepsis and GI bleed were non-significant.ConclusionSLE is known to have a high inflammatory state so it was hypothesized that there would be higher rates of complications and a higher mortality rate in those with concomitant AIH. This study showed that the mortality rate was lower in SLE patients with lower rates of complications including ALF and cholangitis. We postulate that SLE patient outcomes are likely affected by the treatment regimen involved with SLE, including corticosteroids. This would provide an immunosuppressive state, limiting the autoreactivity cascade in AIH, in effect leading to better outcomes and a mortality benefit. This study identifies a lower mortality rate and lower complication rates in patients with AIH and SLE overlap as compared to patients with AIH alone and future studies are needed to confirm these associations.

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients.

For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients.Key messages Adenosinergic pathways are modulated on leukocytes from COVID-19 patients.Plasmatic inosine levels are increased in COVID-19 patients.ATP, ADP, AMP, hypoxanthine, and inosine are correlated with coagulation players.The nucleotides and nucleosides are correlated with patients’ clinical features.The P2 receptors and ectoenzymes are correlated with Tissue factor in COVID-19.Supplementary informationThe online version contains supplementary material available at 10.1007/s00109-021-02175-y.

Factors associated with inflamm-aging in institutionalized older people

The increase in inflammatory cytokines associated with a reduction in the bioavailability of zinc has been used as a marker for inflammation. Despite the high inflammatory state found in institutionalized older individuals, few studies have proposed verifying the factors associated with this condition in this population. To verify the factors associated with inflamm-aging in institutionalized older people. A total of 178 older people (≥ 60 years old) living in nursing homes in Natal/RN were included in the study. Cluster analysis was used to identify three groups according to their inflammatory state. Analysis anthropometric, biochemical, sociodemographic, and health-related variables was carried out. In sequence, an ordinal logistic regression was performed for a confidence level of 95% in those variables with p < 0.20 in the bivariate analysis. IL-6, TNF-α, zinc, low-density lipids (LDL), high-density lipids (HDL), and triglycerides were associated with inflamm-aging. The increase of 1 unit of measurement of LDL, HDL, and triglycerides increased the chance of inflammation-aging by 1.5%, 4.1%, and 0.9%, respectively, while the oldest old (≥ 80 years old) had an 84.9% chance of presenting inflamm-aging in relation to non-long-lived older people (< 80 years). The association between biochemical markers and inflamm-aging demonstrates a relationship between endothelial injury and the inflammatory state. In addition, the presence of a greater amount of fat in the blood may present a higher relative risk of death.

Hypertriglyceridemia in Critically Ill Patients With SARS-CoV-2 Infection.

Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

Perioperative management of a patient undergoing resection of interleukin-6 producing pheochromocytoma

BackgroundPheochromocytomas produce hormones, cytokines, and catecholamines. We report perioperative anesthetic management of a rare interleukin-6 (IL-6)-producing pheochromocytoma.Case presentationA 32-year-old female was scheduled for laparoscopic adrenalectomy for pheochromocytoma. She had a sustained high fever with elevated serum noradrenaline and IL-6 levels. The persistent high inflammatory state, followed by anemia, malnutrition, and coagulopathy, led us to prepone her date of surgery. During general anesthesia, alpha-blockers allowed hemodynamic fluctuations to be controlled. During surgery, simultaneous increases in noradrenaline and IL-6 levels were observed, which rapidly declined after tumor removal. Her postoperative course was uneventful, without pulmonary edema caused by cytokine storms.ConclusionsThe conventional pheochromocytoma strategy allowed surgical removal of an IL-6-producing pheochromocytoma under general anesthesia. However, management of high inflammatory states that induce anemia and coagulopathy is necessary.

Epidemiological, demographic, laboratory, clinical management, and outcome data of symptomatic bradyarrhythmia in COVID-19 patients

BackgroundCardiovascular manifestations are an important cause of mortality and morbidity in COVID-19 infections. Conduction system abnormality in the form of symptomatic bradyarrhythmia is underreported in the literature. AimTo evaluate epidemiological, demographic, laboratory, clinical management, and outcome data of symptomatic bradyarrhythmia in COVID-19 patients. MethodsThis was a retrospective, observational study including all the adult patients (>18 years) who were diagnosed with COVID-19 infection and had complete heart block (CHB) or symptomatic high-grade Atrio-Ventricular (AV) block requiring a temporary pacemaker insertion (TPI). Epidemiological, demographic, laboratory, clinical management, and outcome data were extracted from all the enrolled patients and studied for the primary clinical composite endpoint of all-cause death. ResultsThe study population included 15 patients, including 14 patients with CHB and 1 patient with 2:1 AV block. Syncope was the most common presentation. The clinical endpoint in the form of death was seen in 5 patients (33.3%), 3 patients reverted to sinus rhythm, and 7 patients required permanent pacemaker implantation. The markers of inflammation were raised in all patients; however trend toward more inflammation was seen in patients reaching the primary clinical endpoint. 3 out of 7 patients with narrow QRS rhythm reverted to normal sinus rhythm, while all 8 patients with broad complex QRS either died or required a permanent pacemaker insertion. ConclusionSymptomatic bradyarrhythmia is associated with a high inflammatory state, and high mortality in COVID-19 infection and a transient conduction block in patients with narrow QRS rhythm may suggest local subclinical myocardial inflammation.