Evidence Of Systemic Inflammatory Response Research Articles

Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID).

PurposeTo determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV‑2 (Corona Virus Disease 2019 [COVID-19]).MethodsThe study was a multicentric open-label trial of COVID-19 patients who were aged ≥ 18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40 mg bid for 3 days followed by 20 mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed.ResultsA total of 91 patients were screened, and 64 were randomized (mean age70 ± 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; p = 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20–0.89; p = 0.043).ConclusionThe planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19.Supplementary InformationThe online version of this article (10.1007/s00508-020-01805-8) contains supplementary material, which is available to authorized users.

ВЫРАЖЕННОСТЬ СИСТЕМНОГО ВОСПАЛИТЕЛЬНОГО ОТВЕТА У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ, АССОЦИИРОВАННЫМ С ВИЧ-ИНФЕКЦИЕЙ

238 tuberculosis cases with concurrent HIV infection were examined. The age of patients varied from 24 to 57 years old. Men made 189 (79.4%), and women 49 (20.6%). The CD4 count in the examined patients varied from 0 to 1.216 × 10 9 /L. The intensity of systematic inflammatory response was evaluated as per the rates of acute phase reactants: С-reactive protein (СRP), α 1 -antitrypsin (α 1 -АТ), haptoglobin (HG) and fibrinogen (F). It was found out that tuberculosis patients with concurrent HIV infection demonstrated confidently increased levels of C-reactive protein, α 1 -antitrypsin, and haptoglobin, which was the evidence of systemic inflammatory response. However, the increase of fibrinogen level was not typical of tuberculosis patients with concurrent HIV infection. The comparative analysis proved that the intensity of systemic inflammatory response was increasing simultaneously with the severity of the immune deficiency, and the growth of acute phase reactants' level with a parallel reduction of CD4 count was the evidence of the above. C-reactive protein and α 1 -antitrypsin were the most informative markers of systemic inflammatory response intensity in tuberculosis patients with concurrent HIV infection.

Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial

Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class with in vitro activity against clinically important gram-negative, gram-positive aerobic, and facultative bacteria including most of those resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug resistant strains and carbapenem-resistant Enterobacteriaceae, and most anaerobic pathogens. To evaluate the efficacy and safety of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). This was a phase III, randomized, double-blind, multicenter study that evaluated the efficacy and safety of eravacycline in comparison with ertapenem in patients with cIAI requiring surgical or percutaneous intervention. The test-of-cure evaluation was conducted 25 to 31 days after the first dose of the study drug and the follow-up visit was conducted 38 to 50 days after the first dose of the study drug. All patients recruited into this study were hospitalized. Five hundred forty-one patients were recruited for this study; 270 patients were randomized to receive eravacycline, and 271 patients were randomized to receive ertapenem. Patients had to meet all of the following criteria: hospitalized for cIAI requiring intervention; 18 years or older; evidence of systemic inflammatory response; pain caused by cIAI; able to provide informed consent; and diagnosis of cIAI with sonogram or radiographic imaging or visual confirmation. Analyses were done in intent-to-treat and evaluable populations. Patients received eravacycline, 1.0 mg/kg every 12 hours, or ertapenem, 1.0 g every 24 hours, for a minimum of four 24-hour dosing cycles. Clinical outcome assessments were made at the end of treatment, test of cure, and follow-up visits and were classified as clinical cure, clinical failure, or indeterminate/missing. In total, 541 patients were randomly assigned to treatment: 270 in the eravacycline group and 271 in the ertapenem group. The mean ages were 54.9 years and 55.4 years for the eravacycline and ertapenem groups, respectively. Most patients were white (263 of 270 patients [97.4%] in the eravacycline group and 260 of 271 patients [95.9%] in the ertapenem group). For the microbiological intent-to-treat population, the rates of clinical cure at the test-of-cure visit were 86.8% in the eravacycline group and 87.6% in the ertapenem group. The difference in clinical cure rates between the groups was -0.80% (95% CI, -7.1% to 5.5%), meeting the prespecified noninferiority margin and allowing for statistical noninferiority of eravacycline to ertapenem to be declared for this study. Both study drugs were well tolerated. Overall, eravacycline demonstrated noninferiority to ertapenem for the treatment of patients with cIAI. Clinicaltrials.gov Identifier: NCT01844856.

Prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis

Recent research suggested that prophylactic digital cryotherapy (ICE) improved lameness scores, diminished histological changes and early laminar inflammatory signalling in horses following oligofructose administration. In clinical practice, horses at risk for sepsis-associated laminitis receive ICE. Evidence to support this practice is lacking. To determine factors associated with development of laminitis in horses diagnosed with colitis, including ICE. Multicentre retrospective case series. Medical records for horses admitted to 2 university hospitals diagnosed with colitis with evidence of systemic inflammatory response from 2002 to 2012 were reviewed. Horses were excluded if they exhibited signs of laminitis at admission, were ponies, miniature or draught breeds, or <2 years old. Data were analysed using univariate and multivariate logistic regression. Twenty-seven of 130 horses (21%) developed laminitis. Seven of 69 (10%) horses treated with ICE developed laminitis compared with 20/61 (33%) horses that developed laminitis but did not receive ICE. Factors associated with laminitis included site of hospitalisation, admission respiratory rate (↑) and blood L-lactate (↑), and ICE (↓), P<0.05. Horses treated with ICE had 10 times less odds of developing laminitis compared with horses treated without ICE (odds ratio 0.11, 95% confidence limit 0.03-0.44). Sixteen horses (16/130, 12%) were subjected to euthanasia in hospital. Fourteen of these horses had laminitis and 2 did not develop laminitis. Survival for horses with colitis that developed laminitis was 13/27 (48%) compared with survival for horses with colitis that did not develop laminitis, 101/103 (98%). Laminitis occurred in more clinically compromised horses. Use of ICE reduced the incidence of clinical laminitis in the study population suggesting that digital cryotherapy is an effective prophylactic strategy for the prevention of laminitis in horses with colitis.

Assessment of plasma and red cell trace element concentrations, disease severity, and outcome in patients with critical illness

PurposeThe purpose of the study is to examine the value of both plasma and red cell trace element measurements when assessing nutritional status in patients with critical illness. Materials and MethodsA total of 125 patients who were admitted to intensive care unit with evidence of systemic inflammatory response as per Bone's criteria were recruited. Venous blood samples were obtained from all on admission and, in 31 of the 125 patients, on approximately days 4 and 7. Copper, zinc, and selenium concentrations were measured in plasma and erythrocytes and results related to mortality and patient outcome measures. ResultsA total of 125 critically ill patients were recruited; 81 (66%) were male, the median age was 60 (range, 18-100), and the medical/surgical proportion was 55/70 (44%/56%). The median (lower and upper 2.5th percentile) Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and length of stay and mortality were 21 (16-26), 7 (4-9) 3.7 days (1.5-11.1) and 19%, respectively. Plasma zinc and selenium concentrations were significantly lower on admission compared with reference intervals, whereas copper was increased. Normal plasma glutathione peroxidase activity suggested selenium status was adequate on admission; erythrocyte concentrations of glutathione peroxidase and trace elements were normal, suggesting adequate nutritional status 1 to 2 months before admission. Only plasma zinc and selenium were inversely associated with C-reactive protein (rs = −0.266, P = .004, rs = −0.322, P < .001, respectively). Compared with survivors, albumin (P < .001) concentrations were significantly lower in the nonsurvivor group. No significant difference of plasma selenium and zinc between survivors and nonsurvivors was found, although plasma selenium concentrations tended to be lower (P = .04). On multivariate logistic regression analysis of the significant variables, none was independently associated with mortality. ConclusionThe altered plasma concentrations of zinc, selenium, and copper in patients with critical illness were primarily due to the effects of the systemic inflammatory response and do not reliably indicate their status.

MRSA Enteritis

Purpose: Case:An 83 year old retired dentist presented to the Emergency Room from a nursing facility with a 3 day history of left lower quadrant abdominal crampy non-radiating pain, anorexia and diarrhea. He was hospitalized for a hip fracture complicated by a pneumonia three weeks prior to the presentation. His past medical history was significant for Diabetes Mellitus, Atrial fibrillation, Hypertension and Gout. The patient was on Lipitor, Propranolol, Insulin, Warfarin and Colchicine. On exam, patient was an ill appearing elderly male who was afebrile but tachycardic with an irregular rhythm. The abdominal exam revealed moderate tenderness to palpation in the left lower quadrant without signs of peritonitis. On laboratory data was a leucocytosis of 22,000/ul, a creatinine of 1.3 mg/ml, an INR of 5.7 and urinalysis revealed 8-10 Leucocytes. A CT scan of the abdomen with intravenous contrast was obtained to rule out diverticulitis, which showed a long segment of circumferential mural thickening involving the distal duodenum and proximal jejunum with adjacent stranding. The patient was started on intravenous Metronidazole and Levofloxacin without any improvement by day 4. It was decided to perform an enteroscopy and a colonoscopy as soon as the INR level was acceptable. On day 5, stool cultures grew large numbers of Methicillin Resistant Staphylococcus aureus (MRSA). The patient was started on Vancomycin with complete resolution of pain and diarrhea by day 7 of hospitalization. Discussion: Humans are a natural reservoir of SA. 30-50% of healthy adults are colonized intermittently with the organism. The respiratory tract is the major harbor being involved in up to 15-44% of cases. 5.3% of the patients who are admitted for surgeries and 9% of health care workers have been found to carry MRSA. MRSA enteritis is a very unusual cause of diarrhea which has not been widely studied. Patients present with fever, profuse watery diarrhea and evidence of systemic inflammatory response which may progress to multi-organ failure. The diarrhea typically presents 2-3 days post-operatively and lasts for 5 or more days. Recent surgical operation, antibiotic and/or gastric acid suppressing drugs are usually associated with its occurrence. Post-operative MRSA enteritis can be fatal unless treated with antimicrobial therapy. A Japanese multicentric study assessed the efficacy and safety of Vancomycin in the treatment of MRSA enteritis. 49 patients with diagnosed or strongly suspected MRSA enteritis were given Vancomycin 500 mg four times a day with a 100% clinical response rate. Lately there has been a considerable interest in the specific phenotypic and genotypic characteristic of the organisms causing MRSA enteritis.

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Talc pleurodesis: Evidence of systemic Inflammatory response to small size talc particles

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.

Sepsis associated with central vein catheters in critically III patients: Collignon P, Soni N, Pearson I, et al. Intensive Care Med 14:227, 1988

The purpose of the study is to examine the value of both plasma and red cell trace element measurements when assessing nutritional status in patients with critical illness.A total of 125 patients who were admitted to intensive care unit with evidence of systemic inflammatory response as per Bone's criteria were recruited. Venous blood samples were obtained from all on admission and, in 31 of the 125 patients, on approximately days 4 and 7. Copper, zinc, and selenium concentrations were measured in plasma and erythrocytes and results related to mortality and patient outcome measures.A total of 125 critically ill patients were recruited; 81 (66%) were male, the median age was 60 (range, 18-100), and the medical/surgical proportion was 55/70 (44%/56%). The median (lower and upper 2.5th percentile) Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and length of stay and mortality were 21 (16-26), 7 (4-9) 3.7 days (1.5-11.1) and 19%, respectively. Plasma zinc and selenium concentrations were significantly lower on admission compared with reference intervals, whereas copper was increased. Normal plasma glutathione peroxidase activity suggested selenium status was adequate on admission; erythrocyte concentrations of glutathione peroxidase and trace elements were normal, suggesting adequate nutritional status 1 to 2 months before admission. Only plasma zinc and selenium were inversely associated with C-reactive protein (rs = − 0.266, P = .004, rs = − 0.322, P < .001, respectively). Compared with survivors, albumin (P < .001) concentrations were significantly lower in the nonsurvivor group. No significant difference of plasma selenium and zinc between survivors and nonsurvivors was found, although plasma selenium concentrations tended to be lower (P = .04). On multivariate logistic regression analysis of the significant variables, none was independently associated with mortality.The altered plasma concentrations of zinc, selenium, and copper in patients with critical illness were primarily due to the effects of the systemic inflammatory response and do not reliably indicate their status.