TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis.

Mitochondria are essential for cardiac myocyte function, but damaged mitochondria trigger cardiac myocyte death. Although mitophagy, a lysosomal degradative pathway to remove damaged mitochondria, is robustly active in cardiac myocytes in the unstressed heart, its mechanisms and physiological role remain poorly defined. We discovered a critical role for TRAF2, an innate immunity effector protein with E3 ubiquitin ligase activity, in facilitating physiological cardiac myocyte mitophagy in the adult heart, to prevent inflammation and cell death, and maintain myocardial homeostasis.

Changes in extracellular cytokines in predicting disease severity and final clinical outcome of patients with blunt chest trauma.

BACKGROUND: Chest trauma causes substantial morbidity and mortality and its severity is assessed using clinical diagnosis or scoring systems like Injury severity score (ISS) and thoracic trauma severity score (TTSS). Association of inflammatory cytokines with severity of disease and final clinical outcome is not clearly defined in patients with chest trauma. In this study, we thought to evaluate the inflammatory response in serum and bronchoalveolar lavage fluid (BALF) in chest trauma patients and correlate the level of extracellular cytokines with diseases severity and final outcome. METHODS: A total of 65 patients with blunt chest trauma and 30 healthy controls were enrolled in this prospective observational study. Assessment of inflammatory cytokines such as Interleukin (s) - IL-5, IL-13, IL-2, IL-6, IL-9, IL-1ß, IFN-γ, TNF-α, IL-17A, IL-17F,IL-4, IL-21 and IL-22 was performed in both serum and bronchoalveolar lavage fluid using 13-plex multiplex kit using fluorescence-encoded bead based immunoassays. RESULTS: A significantly higher level of IL-13, IL-2, IL-6, IL-9, IL-1ß, IFN-γ, TNF-α, IL-17A, IL-17F, IL-21 and IL-22 cytokines were observed in patients with blunt chest trauma compared to healthy controls. Level of IL-2, IL-6, IL-1ß and IL-17A was significantly raised in the patients with blunt chest trauma who had a fatal outcome during the hospital stay. An elevated cytokine response of IL-13, IL-4, and IL-21 was noted in the group of patients with high (>5) thoracic trauma severity score. CONCLUSION: Routine monitoring of the inflammatory cytokine level in patients with chest trauma may be used routinely. Longer prospective studies should be encouraged to determine the role of cytokines in patients with chest trauma in predicting the patient final clinical outcome.

Yoga-An Alternative Form of Therapy in Patients with Blunt Chest Trauma: A Randomized Controlled Trial.

BACKGROUND: Yoga as alternative form of therapy has shown positive impact on pulmonary functions, exercise capacity, behavioral changes, and inflammation in non-trauma patients. However, the efficacy of Yoga has not been studied in chest trauma patients. METHODS: This randomized controlled trial was conducted at level-1 Trauma Centre. Isolated chest injury patients were randomized into either standard physiotherapy or Yogatherapy groups. Patients in physiotherapy group received conventional chest physiotherapy and Yogatherapy group received a set of Yogic exercises in addition to conventional chest physiotherapy. Primary outcome measure was changes in pulmonary function tests (PFT) at 4 weeks of discharge. Secondary outcomes were changes in quality of life (QoL), respiratory muscle strength and endurance, chest wall mobility, and levels of cytokines at 4 weeks. Data were analyzed using STATA v14.0. RESULTS: A total of 89 eligible patients were randomized to physiotherapy (n = 46) and Yoga therapy (n = 43) groups. Demographic characteristics were comparable in both the groups. There were statistically significant improvements in PFT in the Yogatherapy group compared with physiotherapy with an increase in Forced vital capacity (p = 0.02) and Forced expiratory volume (p = 0.01) at 4 weeks. In addition, there were significant improvement in physical component of QoL, respiratory muscle endurance (p = 0.003) and axillary cirtometry (p = 0.009) in the Yogatherapy group. However, no statistically significant difference in the trends of cytokine markers seen between the groups. CONCLUSION: Yoga was found to be effective in improving pulmonary functions and QoL in patients with chest trauma. (Trial registered at ctri.nic.in/clinicaltrials/login.php, numberREF/2016/05/011,287).

Predicting Outcomes After Blunt Chest Trauma-Utility of Thoracic Trauma Severity Score, Cytokines (IL-1ß, IL-6, IL-8, IL-10, and TNF-α), and Biomarkers (vWF and CC-16).

Thoracic trauma severity score (TTSS) has been used to assess severity and risk of pulmonary complications in patients with chest trauma. The role of cytokines and biomarkers in patients with chest trauma and its association with TTSS is not well elucidated. The aim of the study was to assess the cytokines (IL-1ß, IL-6, IL-8, IL-10, and TNF-α) and biomarkers (vWF, CC-16) in patients of thoracic trauma and correlate it with TTSS and patient's outcome. This was a prospective observational study. Serum and bronchoalveolar lavage fluid samples were collected from chest trauma patients. TTSS was calculated in all patients. Suitable controls for serum and bronchoalveolar lavage (BAL) sample were selected. The outcome parameters included patient discharge or death, duration of hospital, and intensive care unit (ICU) stay. Forty-three patients were included. There was no significant correlation between the measured cytokines and biomarkers and TTSS. The mean TTSS of patients who had a fatal outcome was significantly higher than the patients who recovered. Patients with a high TTSS score had a significant prolonged ICU stay. Patients with a prolonged hospital stay had lower values of CC-16. TTSS is a useful tool to predict severity of chest trauma and prolonged ICU stay. Lower levels of CC-16 in BAL fluid of chest trauma patients were associated with prolonged hospital stay suggestive of its protective role in the airway. Longer prospective studies are required to determine the role of cytokines and biomarkers in patients with thoracic trauma in predicting the patient's outcome.

Pathogen burden & associated antibiogram of Pseudomonas spp. in a tertiary care hospital of India.

Antimicrobial resistance particularly in Gram-negative bacilli is an increasing problem worldwide. Pseudomonas spp. is one the most common Gram-negative bacteria associated with nosocomial infections and therefore, its trend of antimicrobial resistance needs to be studied. The aim of this study was to evaluate the rate of antimicrobial resistance and changes in resistance pattern over a period of five years (2012-2016) in Pseudomonas spp. isolated from trauma patients attending a tertiary care hospital in north India. During the study, a total of 2444 Pseudomonas spp. were isolated from the various clinical sample. The most common species isolated was P. aeruginosa (2331, 95%). The highest level of resistance was observed against levofloxacin (1678, 69%) and the lowest level of resistance was observed against tobramycin (1254, 51%). Irrational and inappropriate use of antibiotics was found to be responsible for multidrug resistance in Pseudomonas spp. Hence, there is an urgent need to emphasize strict antibiotic policy to minimize the misuse of antimicrobials.

A 5-year surveillance on antimicrobial resistance of Acinetobacter isolates at a level-I trauma centre of India.

INTRODUCTION: Acinetobacter spp. has emerged as a major cause of nosocomial outbreaks. Multiple antibiotic resistance is an important problem in Acinetobacter isolates in recent years. The aim of this study was to evaluate the rate of antimicrobial resistance and changes in resistance pattern over a period of 5 years (2012-2016) in Acinetobacter spp. isolated from trauma patients. MATERIALS AND METHODS: Acinetobacter spp. was identified by VITEK 2 and antibiotic susceptibility of isolates was investigated by disc-diffusion method and VITEK 2 automated system. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute guidelines. RESULTS: Out of the total 16,210 isolates obtained throughout the period of 5 years, Acinetobacter spp. accounted for 3744 (28.9%). Out of which, the species which was maximally isolated was Acinetobacter baumannii (98.5%), followed by Acinetobacter lwoffii (1.4%) and Acinetobacter hemolyticus (0.1%). The highest number of clinical isolates of Acinetobacter were recovered from neurosurgical ward (n = 1210), followed by the neurosurgical intensive care unit (ICU) (n = 1000) and surgical ICU (n = 948) and the most common sample of Acinetobacter isolation was from tracheal aspirate (37.1%), followed by wound swab (18.8%). The highest level of resistance was observed against ciprofloxacin (96%), followed by cefepime (95%), ceftazidime (95%), piperacillin (95%), and amikacin (92%). The trend of antibiotic resistance was found to be statistically significant (P < 0.001) for most of the antibiotics being tested such as amikacin and carbapenems. CONCLUSION: The high rate of antibiotic resistance of the Acinetobacter strains indicated that there is an urgent need for controlled antibiotic usage and appliance of hospital infection control measures.

T-helper-17, Regulatory T-helper Cells Related Serum Markers and IL-13 in the Outcome of Polytraumatic Patients with Bacteremia.

BACKGROUND: Bacteremia and sepsis are associated with high mortality, increased hospital stays, and associated costs, especially in trauma patients. Sepsis is a fatal immunological disorder and its pathophysiology is still poorly understood. OBJECTIVE: To ascertain the role of T-helper lymphocyte-related inflammatory serum cytokines in trauma patients with blood culture positive with Gram-negative bacteria. METHODS: Peripheral blood samples (5 ml) were collected from 40 trauma patients on the day of obtaining positive blood culture (i.e., day 0), followed by an appropriate antimicrobial treatment and sample acquisition on day 4 and only once from 40 age-matched healthy controls. Bead-based cytometric analysis was used to quantify extracellular levels of 16 serum cytokines. The cytokine profiles were compared with those in healthy controls and then correlated to clinical outcomes. RESULTS: A total of 40 patients were enrolled during the study period. Of these, 24 patients (60%) were discharged while 16 (40%) had a fatal outcome. Statistically significant elevated levels of serum IL-6, IFN-γ, TNF-α, IL-17A, IL-17F, and IL-4 were observed in septic patients, while lowered IL-13 levels correlated significantly with a favorable outcome. CONCLUSION: Sepsis following trauma elicits a heightened immune response in the body and provokes the production of a diverse array of cytokines that is both pro-inflammatory and anti-inflammatory. However, the unique cytokine profile of septic trauma patients is still not well understood.

Clinico-microbiological profile of healthcare associated pneumonia in critically ill patients at level-I trauma centre of India.

INTRODUCTION: Device-associated infections constitute the majority of health-care infections in Intensive Care Units (ICUs). Trauma patients are more prone to acquire such infections; ventilator-associated pneumonia (VAP) being the most common Health care associated infections (HAI) in ICU has serious implications such as increased morbidity, prolonged hospital stay, and mortality. This study aims to compare the clinicomicrobiological profile of VAP and non-VAP trauma patients at Level I trauma center. MATERIALS AND METHODS: A 4-year retrospective study of prospectively maintained database was conducted at Level 1 trauma center from January 2013 to December 2016. The patients were classified into two groups named VAP and non-VAP patients. VAP patients were defined according to the criteria of the Centers for Disease Control and Prevention. The data were compiled and analyzed. Statistical data were analyzed using SPSS version 21 software. RESULTS: During the study period, 134 (13%) cases of VAP and 909 (87%) non-VAP cases were observed in our study. The total number of ventilator days for VAP patients was 5128 days, which ranged from 2 to 82 days (median 42 days). The length of hospital stay in non-VAP category ranged from 1 to 390 days (median 195.5 days). Inhospital mortality was observed in 62 (46%) patients with VAP. Three hundred and eighteen (35%) non-VAP patients had also had a fatal outcome. Gram-negative organisms, most commonly Acinetobacter spp. (13, 21%), were reported in the fatal VAP patients. CONCLUSION AND DISCUSSION: Higher rate of mortality was observed in patients with VAP in comparison to non-VAP patients, both being on mechanical ventilation. Early recognition of VAP, implementation of proper VAP preventive bundle strategies, and stringent infection control practices are essential mandates to prevent VAP.

Prevalence, etiology, and antibiotic resistance profiles of bacterial bloodstream infections in a tertiary care hospital in Northern India: A 4-year study.

INTRODUCTION: Bloodstream infections (BSIs) can lead to life-threatening sepsis and are globally associated with high morbidity and mortality. Although BSIs require immediate antimicrobial treatment, their prevalence, etiology, and antimicrobial susceptibilities differ from one country to other. There is a dearth of such data from India. Here, we report the 4-year etiologic data on BSI in trauma patients admitted to a tertiary care referral hospital in New Delhi, India. MATERIALS AND METHODS: A retrospective study was conducted at the trauma center between January 2013 and December 2016. The routine microbiological data on bacterial BSI were recorded and determined retrospectively from the laboratory records. Antimicrobial susceptibility profiles were statistically analyzed. RESULTS: A total of 2017 bacterial strains isolated from blood culture samples were included for microbiological analysis. During the study, the median age of the patients varied from 30 to 35 years, with the percentage of females in the study population varying from 17% to 19%. The predominant pathogens were Gram-negative bacteria, with Acinetobacter species, followed by Klebsiella species being the most commonly isolated organisms throughout the 4 years of study. Among Gram-positive isolates, Staphylococcus species were the leading pathogens (11%-15%). CONCLUSIONS: A detailed analysis of prevalence, etiology of BSIs in India and its resistance profile is crucial for appropriate antibiotic use, clinical management, and formulation of antibiotic policies and preventive measures.

Pattern of antimicrobial resistance of Gram-negative bacilli in surgical site infections in in-patients and out-patients at an apex trauma Center: 2013-2016.

INTRODUCTION: Antimicrobial resistance is an increasing problem worldwide especially among the surgical site infections (SSIs). SSI is becoming more serious due to hospital-acquired infections/nosocomial infections, which further leads to the overuse of broad-spectrum antibiotics. To investigate the antimicrobial resistance patterns among Gram-negative bacteria in SSI in in- and out-patients the present study was designed. METHODOLOGY: During the 4 years (January 2013-December 2016), the antimicrobial resistant pattern was studied in the admitted patients and in the patients who were followed up to the outpatients department (OPD) after discharge. Antimicrobial resistance pattern testing was done by the disk diffusion method on Mueller-Hinton agar and by E-test for ten antibiotics according to The Clinical and Laboratory Standards Institute guidelines for Gram-negative bacilli. RESULTS: A total of 2,447 strains were isolated from the studied population on over the period of 4 years. Of 2447, 1996 (81%) were isolated from patients who had SSI during the hospital stay, and 451 (18%) were from patients who attended the OPD after discharge. In the outpatients, who followed up in the OPD for the SSI, Escherichia coli (148), and Pseudomonas aeruginosa (93), whereas in the patients who develop SSI during their hospital stay, Acinetobacter baumannii (622), E. coli (424), and Klebsiella pneumoniae (315) were found to be common. A very high resistance pattern was observed in both the studied groups; however, a higher resistance pattern was seen in in-patients as compared to outpatients. CONCLUSION: In our study, we have reported resistance pattern in Gram-negative bacteria isolated from the patients who were came for the follow as well as in the inpatients. For the outpatients, it can be concluded that it could be a community-acquired infection which is also an alarming condition for our society.